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Cancer
Principles & Practice of Oncology
REVIEW
4th Edition
Editors
Ramaswamy Govindan, MD
Professor
Department of Medicine
Division of Oncology
Alvin J. Siteman Cancer Center at Washington University School of Medicine
St. Louis, Missouri
Daniel Morgensztern, MD
Associate Professor
Department of Medicine
Division of Oncology
Alvin J. Siteman Cancer Center at
Washington University School of Medicine
St. Louis, Missouri
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4th edition
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TO OUR CONTRIBUTORS
CONTRIBUTORS
Douglas R. Adkins, MD
Professor
Internal Medicine–Medical Oncology
Washington University School of Medicine
St. Louis, Missouri
George Ansstas, MD
Assistant Professor
Department of Medicine
Division of Oncology
Washington University School of Medicine
St. Louis, Missouri
Pasquale W. Benedetto, MD
Leonard M. Miller Professor of Medicine
Department of Medicine
University of Miami
Professor of Medicine
Medicine/Division of Hematology–Oncology
University of Miami Sylvester Cancer Center
Miami, Florida
Hak Choy, MD
Professor and Chairman
Nancy B. and Jake L. Hamon Distinguished Chair in Therapeutic Oncology Research
Department of Radiation Oncology
UT Southwestern Medical Center
Dallas, Texas
Amanda F. Cashen, MD
Associate Professor
Department of Medicine
Division of Oncology
Washington University School of Medicine
St. Louis, Missouri
Siddhartha Devarakonda, MD
Clinical Fellow
Division of Hematology/Oncology
Washington University School of Medicine
St. Louis, Missouri
Laura Divine, MD
Clinical Fellow
Department of Obstetrics and Gynecology
Division of Gynecology
Washington University School of Medicine
Barnes-Jewish Hospital
St. Louis, Missouri
Lingling Du, MD
Clinical Fellow
Department of Medicine
Division of Medical Oncology
Washington University School of Medicine
St. Louis, Missouri
Vinicius Ernani, MD
Clinical Fellow
Department of Hematology and Medical Oncology
Emory University School of Medicine
Atlanta, Georgia
Shirish M. Gadgeel, MD
Professor
Department of Oncology
Karmanos Cancer Institute
Wayne State University
Detroit, Michigan
Sarah B. Goldberg, MD, MPH
Assistant Professor
Department of Medicine (Medical Oncology)
Yale School of Medicine
New Haven, Connecticut
Hassan Hatoum, MD
Assistant Professor
Department of Internal Medicine
University of Oklahoma
Health Science Center/Stephenson Cancer Center
Oklahoma City, Oklahoma
Brian Hess, MD
Clinical Fellow
Hematology/Oncology
Washington University School of Medicine
St. Louis, Missouri
Renuka Iyer, MD
Associate Professor of Oncology
Department of Internal Medicine
Co-Director Liver and Pancreas Tumor Center
Roswell Park Cancer Institute
Buffalo, New York
Jesse Keller, MD
Clinical Fellow
Department of Hematology & Oncology
Washington University School of Medicine
St. Louis, Missouri
Robert A. Kratzke, MD
John Skoglund Chair of Lung Cancer Research
Department of Medicine
University of Minnesota Medical School
Minneapolis, Minnesota
Loren Michel, MD
Associate Professor of Medicine
Internal Medicine–Medical Oncology
Washington University School of Medicine
St. Louis, Missouri
Daniel Morgensztern, MD
Associate Professor
Department of Medicine
Division of Oncology
Alvin J. Siteman Cancer Center
Washington University School of Medicine
St. Louis, Missouri
David G. Mutch, MD
Vice Chairman of Gynecology
Obstetrics and Gynecology
Washington University School of Medicine
St. Louis, Missouri
Russell Pachynski, MD
Assistant Professor
Department of Medicine
Oncology Division
Medical Oncology Section
Washington University School of Medicine
St. Louis, Missouri
Dilan Patel, MD
Resident
Department of Medicine
Washington University School of Medicine
Barnes-Jewish Hospital
St. Louis, Missouri
Matthew A. Powell, MD
Associate Professor
Obstetrics and Gynecology
Washington University School of Medicine
St. Louis, Missouri
Suresh S. Ramalingam, MD
Assistant Dean for Cancer Research
Professor
Emory University School of Medicine
Deputy Director
Director of Medical Oncology
Hematology and Medical Oncology
Winship Cancer Institute
Atlanta, Georgia
Thomas Regenbogen, MD
Clinical Fellow
Department of Medicine
Washington University School of Medicine
St. Louis, Missouri
Rizwan Romee, MD
Assistant Professor of Medicine
Medicine/Oncology
Washington University School of Medicine
St. Louis, Missouri
George R. Simon, MD
Professor
Department of Thoracic/Head and Neck Medical Oncology
Division of Cancer Medicine
Chief
Section of Experimental Therapeutics
The University of Texas MD Anderson Cancer Center
Houston, Texas
Thomas E. Stinchcombe, MD
Associate Professor
Division of Hematology/ Oncology
University of North Carolina
Chapel Hill, North Carolina
Keith Stockerl-Goldstein, MD
Associate Professor of Medicine
Medicine/Oncology
Washington University School of Medicine
St. Louis, Missouri
Benjamin R. Tan, MD
Assistant Professor of Medicine
Department of Medicine
Division of Oncology
Washington University School of Medicine
St. Louis, Missouri
Viralkumar Vaghani
School of Biomedical Informatics
University of Texas Health Science Center
Houston, Texas
Nina Wagner-Johnston, MD
Associate Professor of Oncology
John Hopkins Medicine
Director of Lymphoma Drug Development
Johns Hopkins University
Baltimore, Maryland
We are pleased to publish the fourth edition of the companion review book for DeVita,
Hellman, and Rosenberg’s Cancer: Principles and Practice of Oncology, 10th edition (PPO). While
these review books are often seen as study aids for last-minute cramming for the board
examinations, we hope this book will enable readers to learn key points from each chapter of
the PPO textbook. Each chapter in the review book corresponds to one or more chapters in
the main textbook just as they were in the first three editions. We hope you find this book
useful and informative. Please do not hesitate to contact us with comments, criticisms, and
suggestions.
Ramaswamy Govindan, MD
Daniel Morgensztern, MD
PREFACE TO PREVIOUS EDITION
The past decade has witnessed numerous advances in cancer therapy. Even since the
publication of the previous edition of Cancer: Principles and Practice of Oncology (PPO), or
simply known as the “DeVita book,” several new drugs have been approved for cancer
therapy. Cancer Genome Sequencing projects are going ahead full steam. Molecular
mechanisms that underline the course of several cancer types and responses to specific
therapies are understood better than before. This companion review book, now in its third
edition, is an attempt to cull out the key learning pointsfrom the massive tome of “the DeVita
book” that captures all these advances in a timely manner. While these review books are
often seen as “study-aids” for last minute cramming for the board examinations, we hope this
book would serve to highlight key points from each chapter of PPO. Each chapter in the
review book corresponds to one or more chapters in the main textbook just as they were in
the first two editions. We hope you find this book useful and informative. Please do not
hesitate to contact me with comments, criticisms, and suggestions. You can reach me by
email at rgovinda@dom.wustl.edu.
Ramaswamy Govindan
ACKNOWLEDGMENTS
At the outset, I want to thank the contributors for their diligence, time, and patience.
My special thanks to Dr. Daniel Morgensztern for his hard work, dedication, and commitment
to make this project successful. I want to thank Julie Goolsby and Emilie Moyer from Wolters
Kluwer for their support.
Needless to say, these projects take a sizeable amount of time away from the family. I will
always be grateful to my wife Prabha and my two children, Ashwin and Akshay.
Ramaswamy Govindan
I would like to thank my mentor Ramaswamy Govindan for the opportunity to participate as
a co-editor on the fourth edition of the PPO review, the contributors for their excellent
chapters, and Julie Goolsby and Emilie Moyer from Wolters Kluwer for their constant
support. I am also very grateful to my parents Silvia and Felipe, my lovely wife Marcela and
my three delightful children Alan, David, and Michael.
Daniel Morgensztern
CONTENTS
3. Epidemiology of Cancer
Thomas E. Stinchcombe
4. Etiology of Cancer
Shirish M. Gadgeel
5. Cancer Screening
Megan E. Wren
6. Cancer Prevention
Lingling Du, Richard Chen, Daniel Morgensztern, and Rebecca Aft
7. Genetic Counseling
Jennifer Ivanovich
26. Sarcomas
Brian A. Van Tine and Angela C. Hirbe
28. Lymphomas
Nina Wagner-Johnston and Dilan Patel
Index
1 Molecular Biology of Cancer • Part 1
Robert A. Kratzke
QUESTIONS
Each of the numbered items below is followed by lettered answers. Select the ONE lettered answer
that is BEST in each case unless instructed otherwise.
Question 1.1 Completion of the Human Genome Project has revealed that human cells have
a repertoire of genes of which approximate number?
A. 2,500 genes
B. 25,000 genes
C. 250,000 genes
D. 2,500,000 genes
Question 1.2 One of the reasons to use cancer cell culture experiments in preclinical studies
of cancers is:
A. Allows evaluation of cancer cell interaction with the tumor microenvironment.
B. Cell cultures are amenable to easily manipulated experimental techniques.
C. Adaptation of cancer cells to growth in culture corresponds exactly to cancer cell
growth in vivo.
D. Allows evaluation of cancer cell interaction with the native immune system.
Question 1.3 Which of the following is TRUE with regard to genetic mutations in cancer?
A. Gain-of-function mutations (oncogenes) are generally dominant at the cellular level.
B. Loss-of-functions mutations (tumor suppressor genes) are generally recessive at the
cellular level.
C. Ninety percent of germ line mutations in familial cancer syndromes are in tumor
suppressor genes.
D. All of the above.
Question 1.4 Which of the following proteins has inhibitory activity in the cell cycle?
A. Cyclin D1
B. E2F
C. p16INK4a
D. Cyclin-dependent kinase 4
Question 1.6 Which of the following prevents successful invasion and metastasis ?
A. Senescence
B. Angiogenesis
C. Evasion of apoptosis
D. Self-sufficiency in growth signals
Question 1.7 Which of the following best describes the term “protooncogene”?
A. A normal cellular gene that has been transduced by a retrovirus that is then mutated
following viral replication.
B. A homologue of a known oncogenic element identified in prehistoric specimens.
C. A transforming viral gene that can cause malignant transformation in fibroblasts in
vitro.
D. The first oncogene discovered to be associated with human cancer.
E. A viral oncogene that, following infection, is the direct causative agent of human
cancer.
Question 1.8 The DNA damage checkpoints are located in which phase of the cell cycle?
A. G1/S
B. S/G2
C. M
D. All of the above
Question 1.10 Which of the following statements about miRNAs is/are TRUE?
A. Consist of RNA 19 to 24 nucleotides in length
B. Cannot be evaluated in array format as part of clinical studies
C. Alters gene expression and protein translation
D. A and C
Question 1.12 Which one of the following statement is CORRECT with regard to molecular
profiling using gene arrays and proteomics?
A. Gene arrays can predict protein–protein interactions.
B. Protein levels and protein function do not correspond directly with gene transcript
levels.
C. Polymerase chain reaction can be used to amplify biopsy material for use in gene
arrays, whereas no signal amplification technology is standard in protein arrays.
D. All of the above
E. B and C
Question 1.16 The presence of mutations in p53 has been associated with which of the
following properties on cells:
A. Loss of the G2 checkpoint following treatment with DNA-damaging agents
B. Enhanced capacity to undergo apoptosis following exposure to radiation
C. Increased capacity for DNA amplification
D. A and C
Question 1.17 Which of the following is an example of gene amplification found in cancer?
A. N-myc amplification in neuroblastoma
B. C-myc amplification in small cell lung cancer
C. Her2/neu amplification in breast cancer
D. All of the above
Question 1.18 Which of the following is TRUE regarding microsatellite instability in colon
cancer?
A. Approximately 15% of patients with hereditary nonpolyposis coli have mutations in
MLH1 or MSH2.
B. There is potential resistance to 5-fluorouracil.
C. It has a less favorable prognosis.
D. Evidence is in favor of it occurring only late in sporadic colon cancer cases.
Question 1.19 Which of the following is TRUE about excision repair mechanisms?
A. Increased expression of ERCC1 in non–small-cell lung cancer is associated with response
to cisplatin.
B. There are two nucleotide excision repair (NER) pathways.
C. Base excision repair is involved in response to damage from chemicals and radiographs.
D. B and C.
Question 1.20 ATR/CHK1 signaling is associated with all of the following statements,
A. Bone marrow failure
B. Predisposition to squamous cell carcinoma
C. Predisposition to acute leukemia
D. All of the above
Question 1.21 Which of the following syndromes are associated with abnormalities in the
double-strand repair?
A. Xeroderma pigmentosum
B. Fanconi anemia
C. Lynch syndrome
D. Bloom syndrome
Question 1.22 Decreased expression of Aurora B kinase could lead to the following:
A. Inability for sister chromatids to separate before anaphase
B. Rapid cell division
C. Aneuploidy
D. Increased disassembly of kinetochore proteins
Question 1.27 All of the following is/are evidence for senescence as a tumor suppressor
mechanism, EXCEPT:
A. Several “tumor suppressor” proteins that are involved in senescence pathways (e.g.,
p16INK4a) are mutated in familial cancer syndromes.
B. Mice and humans with impaired p16INK4a and p53 function develop normally other
than an age-dependent decrease in cancer and decreased susceptibility to cancer in
response to carcinogen exposure.
C. Reestablishment of p53 activity in sarcoma and hepatocellular carcinoma has led to
cessation of tumor growth.
D. Growth arrest in lung epithelium has been demonstrated in response to oncogenic
events.
E. A, C, and D.
Question 1.28 Which of the following is/are potential therapeutic strategy (ies) to promote
apoptosis in cancer cells?
A. Inhibition of p16INK4a activity
B. Inhibition of p16INK4a activity via activation of DNA methyltransferases
C. Activation of MDM2
D. Promotion of p16INK4a-p53 interactions
Question 1.30 Telomerase-null mice are associated with which of the following?
A. Decreased sensitivity to radiation
B. Decreased sensitivity to chemotherapy that induces double-strand breaks (DSBs)
C. Decreased genomic stability in the presence of p53 deficiency
D. Decreased rate of spontaneous malignancy
Question 1.32 Which of the following is TRUE about receptor tyrosine kinases?
A. They are always monomeric.
B. Activation always requires tyrosine phosphorylation in all classes.
C. Different types of ligands can activate the same class of receptors.
D. Different types of ligands induce the same receptor conformational changes on binding.
Corresponding chapters in Cancer: Principles & Practice of Oncology, Tenth Edition: 1 (The Cancer Genome), 2 (Hallmarks of
Cancer: An Organizing Principle for Cancer Medicine), and 3 (Molecular Methods in Cancer).
2 Molecular Biology of Cancer • Part 2
Viralkumar Vaghani and George R. Simon
QUESTIONS
Each of the numbered items below is followed by lettered answers. Select the ONE lettered answer
that is BEST in each case unless instructed otherwise.
Question 2.2 The cyclin responsible for facilitating the progress of the cell into and through
mitosis is:
A. Cyclin A
B. Cyclin B
C. Cyclin D
D. Cyclin E
Question 2.3 Which of the following are means of regulating cyclin-dependent kinases
(CDKs)?
A. Positive regulatory acetylation
B. Negative regulatory phosphorylation
C. CDK inhibitors
D. B and C
E. A and C
Question 2.4 Which of the following is necessary for the G1/S-phase transition?
A. Cyclin B-CDK1 complex accumulation
B. Cyclins E and A accumulation
C. Dephosphorylation of T14 and Y15
D. CDK1 activation along with binding of CDC20 to anaphase promoting
complex/cyclosome (APC/C)
Question 2.8 Of the genes listed below, select the gene that is involved in both cell-cycle
regulation and DNA repair?
A. TP53
B. NBS1
C. PTTG1
D. CHK2
Question 2.10 Genes that encode negative regulators of growth and proliferation are:
A. Protooncogenes
B. Oncogenes
C. S-phase genes
D. Tumor suppressor genes
Question 2.11 Select the syndrome that is associated with a mutation in the gene encoding
Nbs1, leading to microcephaly and a strong predisposition to lymphoid malignancies?
A. Nijmegen disease
B. Von Hippel–Lindau (VHL) syndrome
C. Familial malignant melanoma syndrome
D. Li–Fraumeni syndrome
Question 2.12 Type I cell death is also known as:
A. Autophagy
B. Apoptosis
C. Necrosis
D. Autolysis
Question 2.13 Which of the following proteins serve as are ligands for the death receptor
pathway?
A. TNFα
B. Fas
C. Noxa
D. A and C
E. A and B
Question 2.15 RAF is inhibited by which of these therapeutic agents that induce apoptosis?
A. Sorafenib
B. Imatinib mesylate
C. Bortezomib
D. Taxanes
Question 2.16 Bcl-2 small molecule inhibitors like ABT-737 induce apoptosis by:
A. Binding to the BH3-binding pocket.
B. Inhibiting tyrosine kinase activity of Bcr/Abl restoring Bim function.
C. Stimulating Bim expression
D. Blocking proteasome degradation of Bim
Question 2.27 VEGF is inducible by many factors, of which the most important may be:
A. H1F1α
B. TSP-1
C. pVHL
D. p53
Question 2.30 Which of the following is/are potential toxicity(ies) of antiangiogenic agents?
A. Hypertension
B. Aplastic anemia
C. Arteriothrombotic event
D. A and B
E. A and C
Question 2.31 Which of the following factors is/are associated with risk of metastasis?
A. Tumor grade
B. Depth of invasion beyond normal cellular compartments
C. Lymphovascular invasion
D. All of the above
Question 2.32 The percentage of tumor cells that can give rise to metastases is?
A. <0.01%
B. 1%
C. 20%
D. >80%
Question 2.33 Genes that can mediate tumorigenic functions and secondarily serve
metastatic-specific functions either in a general way or with particular organ selectivity is
best known as:
A. Tumorigenic genes
B. Metastasis progression genes
C. Metastasis virulence genes
D. Protooncogenes
Question 2.34 Cells that mediate the breakdown of the basement membrane allowing for
tumor invasion are known as:
A. Carcinoma-associated fibroblasts
B. Pericyte-derived fibroblast
C. Tumor-associated macrophages (TAMs)
D. Dendritic cells
Question 2.35 Cellular loss of this molecule leads to decreased cellular attachment and
enhanced tumor invasion/motility:
A. E-cadherin
B. β-Catenin
C. α-Tubulin
D. Ankyrin
Question 2.36 The following are the selective pressures experienced by circulating tumor
cells (CTCs)
A. Shear stress
B. Nitric oxide
C. Nutrient deprivation
D. A, B, and C
Question 2.37 Which of the following molecules are known to assist in the extravasation of
CTCs?
A. Ezrin
B. VEGF
C. CXCL12
D. CXCR4
E. All of the above
Question 2.38 Osteoblastic bone metastases are characteristic of which type of cancer?
A. Breast
B. Prostate
C. Lung
D. Renal cell
Question 2.39 Which of the following cancers rarely metastasize to the liver?
A. Colon cancer
B. Breast cancer
C. Prostate cancer
D. Melanoma
Question 2.40 The stochastic model of tumor heterogeneity is best described as:
A. Every cell has equal potential to initiate and sustain tumor growth, but most cells do
not proliferate extensively because of the low cumulative probability of permissive
events.
B. Cancer stem cells (CSCs) are biologically distinct from the bulk cell population, which
does not possess tumor-initiating activity.
C. Tumors are heterogeneous secondary to random, acquired mutations.
D. Tumors are pressured into heterogeneity by variable pressures applied to the tumor.
Question 2.41 The hierarchy model of tumor heterogeneity is best described as:
A. Every cell has equal potential to initiate and sustain tumor growth, but most cells do
not proliferate extensively because of the low cumulative probability of permissive
events.
B. CSCs are biologically distinct from the bulk cell population, which does not possess
tumor-initiating activity.
C. Tumors are heterogeneous secondary to random, acquired mutations.
D. Tumors are pressured into heterogeneity by variable pressures applied to the tumor.
Question 2.42 The drug vemurafenib (PLX4032) targets which gene in the MAPK/ERK
pathway?
A. RAS
B. BRAF
C. BIM
D. ERK
Question 2.43 Which of the following agents targets tumor metabolic pathways?
A. Pemetrexed
B. 5 FU
C. Temsirolimus
D. All of the above
ANSWERS
Corresponding Chapters in Cancer: Principles & Practice of Oncology, Tenth Edition: 1 (The Cancer Genome), 2 (Hallmarks of
Cancer: An Organizing Principle for Cancer Medicine), and 3 (Molecular Methods in Cancer).
3 Epidemiology of Cancer
Thomas E. Stinchcombe
QUESTIONS
Each of the numbered items below is followed by lettered answers. Select the ONE lettered answer
that is BEST in each case unless instructed otherwise.
Question 3.3 Confounding factors and interaction (also known as effect modification) are
common in epidemiologic studies. Which of the following statements is TRUE in regards to
confounding and interaction?
A. Confounder is not associated with exposure
B. Confounder is associated with the disease and dependent on the exposure
C. Confounder may be an intermediate step between exposure and disease
D. Confounder is not a true relationship and interaction is true relationship between an
exposure and disease
Question 3.4 Statistical methods are required to evaluate the role of chance, and a usual way
to estimate chance is to calculate the upper and lower limits of a 95% confidence interval
around a point estimate for relative risk. Which of the following are TRUE related to the use
and interpretation of confidence intervals? (Select two correct responses)
A. If the confidence interval does not include 1, the observed association is statistically
significant. If the confidence includes 1, then the observed relationship is not
statistically significant
B. The width of the confidence interval is directly related to the number of participates in
a study or sample size
C. The choice of 95% confidence interval is commonly used, but the upper and lower
limits of the interval (e.g., 90% or 99%) can certainly be calculated and interpreted
accordingly
D. All of the above
Question 3.5 Dr. Bush wishes to study the relationship between diet soda consumption and
the development of gastric cancer. He selects the cases of gastric cancer detected over the
last 15 years, and then to obtain his controls he selects for patients who referred to the
gastroenterology clinic. This is as an example of:
A. Information bias
B. Selection bias
C. Misclassification bias
D. All of the above
Question 3.6 For which of the following analytical studies is the group the unit of analysis?
A. Ecologic
B. Cross-sectional
C. Cohort
D. Case-control
Question 3.9 The discontinuation of the routine use hormone replacement therapy following
the publication of the Women’s Health Initiative study is thought to contribute to the
declining rate of which of these cancers
A. Breast cancer
B. Lung cancer
C. Colorectal cancer
D. Stomach cancer
Question 3.10 Which of the following is TRUE about the Surveillance, Epidemiology, and
End Results (SEER) Program?
A. It covers approximately 10% of the US population
B. Staging, treatment and outcome assessment is highly standardized
C. It provides the most precise measure of long-term trends in cancer incidence
D. All of the above
ANSWERS
Corresponding chapters in Cancer: Principles & Practice of Oncology, Tenth edition: 11 (Epidemiologic Methods) and 12
(Trends in United States Cancer Mortality).
4 Etiology of Cancer
Shirish M. Gadgeel
QUESTIONS
Each of the numbered items below is followed by lettered answers. Select the ONE lettered answer
that is BEST in each case unless instructed otherwise.
Question 4.1 Which of the following statements regarding the relationship between
cigarette smoking and lung cancer are CORRECT? (Select two correct responses)
A. The duration of smoking is a strong risk factor for developing lung cancer in smokers.
B. Smoking is only associated with a risk of developing squamous cell lung cancer and not
adenocarcinoma of the lung.
C. The risk of developing lung cancer in ex-smokers drops to the level of never smokers 2
years after smoking cessation.
D. The risk of developing lung cancer increases with the number of cigarettes smoked.
Question 4.2 Which of the following statements regarding the role of specific tobacco
products and tobacco related carcinogens in the development of cancer are CORRECT?
A. Polycyclic aromatic hydrocarbons in cigarette smoke are major causative factors for
development of lung cancer.
B. Nicotine is an important carcinogen in the causation of laryngeal cancer.
C. Cigarettes with lower tar yields are associated with reduced risk of diseases from
cigarette smoking.
D. Smokeless tobacco products don’t contain high amounts of carcinogens.
Question 4.3 Which of the following is TRUE regarding cigarette smoking causing cancer?
A. DNA adducts caused by carcinogens in cigarette smoke are responsible for mutations
that can eventually cause cancer.
B. Nicotine can reduce apoptosis and promote angiogenesis.
C. Compounds that promote inflammation may play a role in cancer development
D. All of the above.
Question 4.8 Data on markers of inflammation and prognosis of cancer patients shows
A. Glasgow Prognostic Score (GPS) is based on absolute white cell count, neutrophil to
lymphocyte ratio, and platelet count.
B. Glasgow Prognostic Score predicts for higher risk of death in prostate cancer patients.
C. In a study of renal cancer patients, inflammatory markers did not correlate with overall
survival.
D. Elevated C reactive protein levels are associated with higher disease free survival in
breast cancer patients.
Question 4.12 Cellular response to correct and prevent damage from ionizing radiation (IR)
is characterized by
A. DNA damage induced by IR can be repaired by mechanisms such as homologous
recombination repair pathway and nonhomologous end joining pathway.
B. If the DNA is damaged by IR, there are no mechanisms in place to prevent cells with
DNA damage from entering into critical phases of cell cycle.
C. All cells in the body are equally sensitive to radiation-induced cell killing.
D. IR-induces cell death through apoptosis alone.
Question 4.15 Alcohol consumption and risk of cancer (Select two correct responses)
A. Alcohol is not a carcinogen since it only induces cancer indirectly by causing
inflammation.
B. Types of alcoholic drinks can influence the risk of cancer.
C. Mechanisms of inducing cancers include direct damage to cells, modulation of DNA
methylation, and causing DNA adducts.
D. Alcohol can increase the risk of breast cancer.
Question 4.16 Which statement is CORRECT concerning dietary influence on risk of cancer
A. Dietary fat intake is an important contributor to breast cancer incidence.
B. Cancer risk is more related to the types of foods consumed than the total caloric intake.
C. Data supports a link between consumption of fat-containing animal products and
incidence of prostate cancer.
D. A higher intake of vegetable fat was associated with greater risk of breast cancer in
premenopausal women.
Question 4.17 Fruit and vegetable consumption and risk of cancer are characterized by
A. There is an inverse relationship between consumption of fruits and vegetables and risk
of colon cancer.
B. An inverse relationship between intake of fruits and vegetables and risk of estrogen
receptor negative breast cancer has been shown by the Nurse’s Health Study.
C. Consumption of fruit and vegetables reduces total cancer incidence.
D. None of the above.
Question 4.18 Data on the influence of specific nutrients and risk of cancer shows
A. Individuals with higher 25 (OH) D levels have a lower risk of colorectal cancer.
B. Higher intake of beta carotene reduces the risk of lung cancer.
C. In the Selenium and Vitamin E Cancer Prevention Trial (SELECT) trial selenium was
found to protect from development of prostate cancer.
D. High intake of calcium protects development of prostate cancer.
Question 4.19 Obesity and physical activity as risk factors for breast cancer is characterized
by
A. Low level of physical activity is a risk factor for breast cancer in postmenopausal
women but not premenopausal women.
B. Obesity is associated with reduced risk of breast cancer in postmenopausal women.
C. Obesity is associated with reduced risk of breast cancer in premenopausal women.
D. None of the above.
Question 4.20 Obesity and physical activity are associated with following cancers:
A. Obesity but not low physical activity is associated with risk of colon cancer.
B. Obesity is not a risk factor for endometrial cancer.
C. Higher lifetime physical activity is associated with lower risk for pancreatic cancer.
D. Obesity lowers the risk of gallbladder cancer.
ANSWERS
QUESTIONS
Each of the numbered items below is followed by lettered answers. Select the ONE lettered answer
that is BEST in each case unless instructed otherwise.
Question 5.1 Studies of screening for cancer are subject to several types of bias. If screening
detects a cancer earlier (before it becomes symptomatic), but treatment has no effect on the
course of the disease, then the subject will seem to live longer than if he/she had presented
symptomatically (i.e., the cancer is known for a longer period of time, but the time of death
is not altered). This type of bias is known as
A. Lead-time bias.
B. Length bias.
C. Selection bias.
D. Overdiagnosis bias.
Question 5.2 In planning a prostate cancer screening program you are concerned that a
prostate specific antigen (PSA) threshold of 4 ng/mL has a sensitivity of just 24% for the
diagnosis of prostate cancer. You can anticipate that lowering the PSA threshold to 2.5
ng/mL threshold will
A. Decrease the positive predictive value (PPV).
B. Decrease the rate of true-positive results.
C. Decrease the sensitivity.
D. Increase the positive predictive value (PPV).
E. Increase the specificity.
Question 5.3 In the PLCO Cancer Screening Trial men were randomized to receive annual
PSA testing for 6 years or usual care. At the conclusion of the 13 year follow-up period it was
found that there was a high rate of PSA testing among men randomized to the control arm.
This “drop-in” had what effect on the results?
A. Increased the positive predictive value (PPV) of the PSA test.
B. Increased the relative risk reduction (RRR) of the screening arm as compared with the
control arm.
C. Reduced the sensitivity of the PSA test.
D. Reduced the statistical power of the study to detect differences in outcome between the
two arms.
Question 5.4 The U.S. Preventive Services Task Force (USPSTF)
A. Is composed of government employees with limited clinical experience.
B. Formulates recommendations based on expert opinion more than on evidence based
medicine.
C. Weighs benefits and harms of screening tests in the context of cost effectiveness.
D. Weighs benefits and harms of screening tests without considering cost effectiveness.
Question 5.5 A new screening test for ovarian cancer was developed. It was tested in a
tertiary care academic medical center in a group of women with breast cancer (BRCA)
mutations and was found to have a sensitivity of 70%, specificity of 90%, and positive
predictive value (PPV) of 10%. If a woman in the study population is found to have a
positive (abnormal) test result, how would you interpret it?
A. There is a 30% chance that this represents a false-positive result.
B. There is a 10% chance that this represents a false-positive result.
C. There is a 9 in 10 chance that this represents a false-positive result.
D. You can be 90% sure that your patient has the disease.
Question 5.6 If the use of this test (from Question 5.5) is expanded to the general
population, it is expected that
A. The test sensitivity will be lower.
B. The test specificity will be lower.
C. The PPV will be lower.
D. The test specificity will be higher.
Question 5.7 In analyzing a randomized controlled trial of a screening test which is the best
indicator of effectiveness?
A. Absolute reduction in mortality
B. Evidence of stage shift
C. Increased 5-year survival
D. Relative reduction in mortality
Question 5.8 Which statement regarding screening for breast cancer is TRUE?
A. The monthly breast self-examination (BSE) is a crucial component of breast cancer
screening programs.
B. The BSE has been shown to be ineffective for breast cancer screening.
C. Increasing the interval of mammographic screening from 1 year to 2 years results in a
halving of the mortality benefit.
D. Mammography has a higher positive predictive value (PPV) for women aged 40 to 49
as compared with women aged 50 to 59.
Question 5.9 The American Cancer Society (ACS) recommends annual screening
mammography and MRI starting at age 30 for women at high risk for breast cancer including
which of the following? (Select two correct responses)
A. Women with a history of fibrocystic breast disease
B. Women with a history of mantle radiation for Hodgkin disease
C. Women with a known BRCA mutation
D. Women with increased mammographic breast density
Question 5.10 A 19-year-old woman presents for a health maintenance visit. She has been
sexually active for 4 years and has had one episode of chlamydia. What is the recommended
approach to cervical cancer screening for her?
A. Begin annual screening with cervical cytology (Pap smear) plus HPV cotesting.
B. Begin annual screening with cervical cytology alone.
C. No cervical cancer screening at this time; start screening at age 21 with cervical
cytology alone.
D. No cervical cancer screening at this time; start screening at age 21 with cervical
cytology and HPV cotesting every 3 years.
Question 5.11 A 40-year-old woman had her first screening mammogram and was noted to
have increased mammographic breast density. Current evidence suggests that the best
recommendation for future breast cancer screening would be
A. Annual mammography alone.
B. Annual mammography + annual MRI.
C. Annual mammography + monthly breast self-examination (BSE).
D. Annual mammography + monthly breast self-examination (BSE) + annual MRI.
Question 5.12 The United States Preventive Services Task Force (USPSTF), the American
College of Obstetricians and Gynecologists (ACOG), and the American College of Physicians
(ACP) agree on which one of the following recommendations for ovarian cancer screening in
women ages 20 to 65 years without oophorectomy?
A. Annual pelvic examination for all women
B. Annual serum CA-125 measurement
C. No population-based screening is recommended
D. Transvaginal ultrasound every 5 years
E. Two-stage screening: annual CA-125, then transvaginal ultrasound if elevated or rising
CA-125
Question 5.13 A 44-year-old woman had a total hysterectomy for fibroids and menorrhagia.
What is the recommended approach to cervical cancer screening for her?
A. Cervical cytology testing should be discontinued.
B. Cervical cytology testing should be performed annually indefinitely.
C. Cervical cytology testing should be performed every 1 to 3 years until age 65 years.
D. Cervical cytology testing plus HPV cotesting should be performed every 5 years until
age 65 years.
Question 5.14 In the Mayo Lung Project randomized controlled trial more than 9,200 male
smokers were randomized to intensive screening (sputum cytology and CXR every 4 months
for 6 years) or a control group (same tests performed annually). After nearly 20 years of
follow-up there were more lung cancers diagnosed in the intensive screening arm versus the
control arm (585 vs. 500) but the intensive screening arm did not show improvement in lung-
cancer mortality (4.4 lung cancer deaths per 1,000 person-years in the intensively screened
arm vs. 3.9 per 1,000 person-years in the control arm). This is best explained by
A. Lead-time bias.
B. Overdiagnosis.
C. Selection bias.
D. Stage shift
Question 5.15 Based on the results of the National Lung Screening Trial (NLST) several
organizations recommended consideration of lung cancer screening with low-dose
computerized tomography (LDCT) for patients who would have qualified for the trial.
Eligible patients had to have which two of the following criteria? (Select two correct
responses)
A. Age less than 60 years
B. At least a 30 pack-year smoking history
C. At least a 50 pack-year smoking history
D. Current smoker
E. Relatively good health
Question 5.16 Which of the following statements regarding prostate cancer screening is
TRUE?
A. Intensity of prostate cancer screening has been shown to correlate with the degree of
mortality benefit.
B. Prostate cancer screening and therapy are associated with significant harms.
C. PSA levels are unaffected by benign prostate diseases.
D. Routine annual PSA testing is recommended for all men ages 55 to 74 years.
Question 5.18 More frequent screening for colorectal cancer (CRC) is recommended in
certain high risk individuals. Which two of the following groups need to have screening
increased to colonoscopy every 5 years starting by age 40? (Select two correct responses)
A. First-degree relative with CRC or adenomatous polyp at age ≥60 years
B. One first-degree relative with CRC or adenomatous polyps diagnosed at age <60 years
C. One second-degree relative with colorectal cancer
D. Two or more first-degree relatives with CRC
E. Two second-degree relatives with CRC
Question 5.19 Which of the following CRC screening tests can directly prevent colorectal
cancer?
A. CT colonography (“virtual colonoscopy”)
B. Double-contrast barium enema
C. Fecal immunochemical testing (FIT)
D. High-sensitivity fecal occult blood testing (FOBT)
E. Optical colonoscopy (endoscopy)
ANSWERS
Corresponding chapter in Cancer: Principles & Practice of Oncology, Tenth edition: 34 (Cancer Screening).
6 Cancer Prevention
Lingling Du, Richard Chen, Daniel Morgensztern, and Rebecca Aft
QUESTIONS
Each of the numbered items below is followed by lettered answers. Select the ONE lettered answer
that is BEST in each case unless instructed otherwise.
Question 6.1 Which of the following statements regarding nicotine replacement therapy
(NRT) is TRUE?
A. NRT increases the odds of quitting smoking compared to placebo.
B. NRT is associated with increased risk of carcinogenesis in the general population.
C. a and b
D. None of the above
Question 6.3 Varenicline (Chantix) is associated with which of the following side effects?
A. Hypertension
B. Anorexia
C. Suicidal ideation
D. Elevated liver enzymes
Question 6.6 In clinical trials, systemic retinoids and beta carotene were shown to reduce
cancer incidence in this group of high-risk individuals
A. Skin cancer in patients with xeroderma pigmentosum
B. Lung cancer in heavy smokers
C. Cervical cancer in patients with cervical dysplasia
D. Colorectal cancer in patients with adenoma
Question 6.7 Which of the following was associated with selenium supplementation in
randomized clinical trials?
A. Decreased risk of squamous cell skin cancer
B. Reduced incidence of prostate cancer
C. Increased incidence of nonmelanoma skin cancer
D. Increased risk of prostate cancer
Question 6.8 Which of the following statements is/are TRUE regarding calcium and vitamin
D?
A. Calcium reduces the risk of recurrent colorectal adenoma.
B. The combination of vitamin D and calcium decreased the risk of developing colon
cancer in postmenopausal women in the Women’s Health Initiative (WHI) trial.
C. The combination of vitamin D and calcium reduced the risk of breast cancer in
postmenopausal women in the WHI trial.
D. High serum level of vitamin D is associated with decreased risk of pancreatic cancer.
Question 6.9 Which of the statements is/are TRUE regarding nonsteroidal anti-inflammatory
drugs (NSAIDs) in the prevention of colorectal cancer?
A. Chemopreventive effects of low-dose aspirin on colorectal cancer development were
demonstrated in clinical trials, and its overall benefits outweigh the risks in adults at
average risks of developing colorectal cancer.
B. High-dose sulindac prevents the development of new polyps, although it does not cause
the regression of established polyps.
C. In randomized trials, both rofecoxib and celecoxib were shown to reduce the risk of
metachronous colorectal adenomas and colorectal cancer.
D. Considering the risks associated with these agents, screening strategy alone is
recommended in average-risk adults.
Question 6.10 Which of the statement is TRUE regarding tamoxifen and raloxifene?
A. Tamoxifen reduces the risk of ER-negative breast cancer.
B. Raloxifene reduces breast cancer-specific mortality rates.
C. Tamoxifen is more effective than raloxifene in reducing breast cancer incidence.
D. Both tamoxifen and raloxifene decrease the risk of in situ breast neoplasms.
Question 6.11 The risk of which of the following toxicities is increased in patients treated
with raloxifene?
A. Endometrial cancer
B. Vertebral fracture
C. Stroke
D. Coronary artery heart disease
Question 6.12 Which of the following statement is TRUE regarding the role of 5-alpha-
steroid reductase inhibitors in preventing prostate cancer?
A. Finasteride does not reduce the incidence of prostate cancer.
B. Patients treated with finasteride or dutasteride who develop prostate cancer are more
likely to have tumors of a high Gleason score compared to patients treated with
placebo.
C. Finasteride decreases the survival after prostate cancer diagnosis compared to placebo.
D. Dutasteride increases the risk of prostate cancer.
Question 6.15 Which of the following is TRUE regarding diet-derived natural products?
A. There have been no large prospective trials demonstrating the efficacy of natural
products in reducing cancer risk.
B. Berry formulations reduce esophageal dysplasia and oral leukoplakia in phase II studies.
C. Both a and b.
D. None of the above.
Question 6.16 Helicobacter pylori infection is associated with increased risk of which of the
following?
A. Esophageal adenocarcinoma
B. Gastric cardia carcinoma
C. Esophageal squamous cell carcinoma
D. Intestinal-type gastric adenocarcinoma
Question 6.18 In patients with medullary thyroid carcinoma (MTC), which of the following
preoperative basal calcitonin levels is an indication for ipsilateral central and lateral neck
dissection?
A. 15 to 20 pg/mL
B. 20 to 50 pg/mL
C. 50 to 200 pg/mL
D. 200 to 500 pg/mL
Question 6.19 What is TRUE regarding the risk of endometrial cancer for patients with
Lynch syndrome?
A. The risk for women with Lynch syndrome varies from 20% to 60% and is higher than
development of ovarian cancer.
B. Clinically, these cancers are frequently poorly differentiated, present at an advanced
stage, and associated with poor prognosis.
C. Risk reducing hysterectomy should be performed shortly after menarche.
D. Estrogen replacement is contraindicated in women with Lynch syndrome undergoing
bilateral salpingo-oophorectomy.
Question 6.20 What is the best treatment of a patient with FAP presenting with
approximately 300 colorectal polyps and 15 rectal adenomas?
A. Observation
B. Total proctocolectomy with permanent ileostomy (TPC)
C. Proctocolectomy with ileal pouch-anal anastomosis (IPAA)
D. Total colectomy with ileorectal anastomosis (IRA)
Question 6.21 Which of the following malignancies are associated with germ line mutations
in the RET protooncogene?
A. Multiple endocrine neoplasia (MEN) 2A
B. MEN 2B
C. Sporadic medullary thyroid carcinoma
D. All the above
ANSWERS
Corresponding Chapters in Cancer: Principles & Practice of Oncology, Tenth Edition: 31 (Tobacco Use and the Cancer Patient),
32 (Role of Surgery in Cancer Prevention), and 33 (Cancer Risk Reducing Agents).
7 Genetic Counseling
Jennifer Ivanovich
QUESTIONS
Each of the numbered items below is followed by lettered answers. Select the ONE lettered answer
that is BEST in each case unless instructed otherwise.
Refer to the following pedigree for Questions 7.1 to 7.4.
Question 7.1 The family depicted has Lynch syndrome (previously referred to as the
hereditary nonpolyposis colon cancer [HNPCC]) syndrome. This syndrome is characterized by
a high risk to develop colon and endometrial cancer and an increased risk to develop various
other tumor types. Before her death, individual III-2 had genetic testing of the MLH1 and
MSH2 genes, and an MSH2 gene mutation was identified. Specifically, the mutation is c.942
+ 3A > T. MLH1 and MSH2 gene mutations account for 80% to 90% of families with
HNPCC. Individual II-1, depicted with the arrow, has not been diagnosed with cancer. He has
undergone frequent colonoscopy screening. He has also had genetic testing and was found to
carry the family MSH2 gene mutation. The finding that individual II-1 has not been diagnosed
with cancer can be explained by which of the following concepts?
A. Genetic testing laboratory error
B. Clinical variability
C. Genetic heterogeneity
D. Reduced penetrance
Question 7.2 Assuming individual II-3 has the family MSH2 gene mutation, what is the
calculated probability Diane (individual IV-1) has inherited the MSH2 gene mutation?
A. 0%
B. 12.5%
C. 25%
D. 50%
Question 7.3 Diane (individual IV-1) is 24 years of age. She approaches her primary care
physician about her medical management, given her family history of the Lynch syndrome.
She has a healthy body weight and does not smoke. Both her paternal grandmother (II-3) and
her father (III-6) refuse to have genetic testing. In addition to her annual Pap smear, which of
the following cancer screening is most appropriate for Diane?
A. Colonoscopy screening to begin at 50 years of age
B. Sigmoidoscopy screening to begin by 25 years of age
C. Colonoscopy screening to begin by 25 years of age
D. Colonoscopy and mammography screening to begin by 25 years of age
Question 7.4 Diane (individual IV-1) decides to pursue genetic testing to aid in her medical
management. She states that her father will not undergo genetic testing. What specific
genetic test should be ordered?
A. Full sequencing of the MSH2 gene
B. Full sequencing of the MSH2 and MLH1 genes
C. Mutation specific analysis of the MSH2 gene
D. Deletion analysis using multiplex ligation-dependent probe amplification
Question 7.5 Which of the following factors suggest that a family may have hereditary
cancer?
A. Young age at diagnosis
B. Bilateral cancer in an affected family member
C. Multiple affected generations
D. All of the above
Refer to the following pedigree for Questions 7.6 to 7.8.
Olivia is a 38-year-old healthy woman who presents to her primary care physician
concerned about her family history of cancer. She has no chronic health concerns. Both
her mother’s and father’s family are of Ashkenazi Jewish ancestry. Olivia pursues an
evaluation with a clinical geneticist for assessment and genetic testing.
Question 7.6 The clinical geneticist diagnoses the family with which cancer predisposition
syndrome?
A. HNPCC syndrome
B. Hereditary breast cancer 1 (BRCA1) syndrome
C. Li–Fraumeni syndrome
D. Hereditary BRCA2 syndrome
E. None of the above
Question 7.7 Genetic testing is recommended to begin with which family member(s)?
A. Olivia, III-2
B. Olivia’s oldest sibling, individual III-4
C. Olivia and her two siblings should be tested at the same time
D. Olivia’s maternal first cousin, individual III-1
Question 7.9 Jennifer is a 38-year-old woman who was diagnosed with stage IIA ductal
carcinoma at 30 years of age. She undergoes direct genetic testing of the BRCA1 and BRCA2
genes and is found to have a BRCA2 gene variant. Specifically the variant is Q713L (2366A >
T), which results in the substitution of leucine for glutamine at amino acid 713 of the BRCA2
protein. The functional significance is unknown. Jennifer’s sister, Angela, is 40 years of age
and has no personal history of cancer. Which is the most appropriate genetic testing approach
for Angela?
A. Genetic testing is recommended for Angela because it will clarify her breast cancer risk.
B. Genetic testing is not recommended for Angela because it will not clarify her breast
cancer risk.
C. Genetic testing is recommended for Angela because it will help clarify Jennifer’s genetic
test results.
D. A and C.
Question 7.10 Which of the following statements regarding people with a BRCA1 or BRCA2
gene mutation are TRUE?
A. The majority of BRCA1 gene mutation carriers who develop breast cancer develop
estrogen receptor–positive breast tumors, and BRCA2 gene mutation carriers most often
develop estrogen receptor–negative breast tumors.
B. BRCA1 and BRCA2 gene mutation carriers have an increased risk to develop pancreatic
cancer.
C. BRCA2 gene mutations are associated with an increased risk for follicular thyroid cancer
D. Prophylactic bilateral mastectomy decreases the risk of breast cancer by more than 90%
among women with a BRCA1 or BRCA2 gene mutation.
Refer to the following pedigree for Questions 7.11 and 7.12.
Question 7.11 Pauline, the family proband as designated by the arrow, is a healthy 36-year-
old woman who presents to her gynecologist concerned about her breast cancer risk. She
requests genetic testing. No other family member has undergone genetic testing. The
gynecologist orders BRCA1 and BRCA2 gene testing. No mutation is identified. Which of the
following statements is the CORRECT interpretation of Pauline’s testing?
A. Pauline’s test result is a true negative.
B. Pauline’s test result is a variant of uncertain significance.
C. Pauline’s test result is uninformative.
D. Pauline’s test result is positive.
Question 7.13 Which of the following malignancies does NOT have a significant increase in
incidence among people with Lynch syndrome?
A. Colon cancer
B. Cervical cancer
C. Ovarian cancer
D. Endometrial cancer
Question 7.14 A 28-year-old woman with bilateral ductal cancer presents to the medical
oncologist for assessment and treatment. Her medical history is notable for intussusception at
6 years of age. On her physical examination, the medicine resident notices small blue/black
hyperpigmented macules on her lips, buccal mucosa, and fingertips. What is her diagnosis?
A. Hereditary BRCA1 syndrome
B. Hereditary BRCA2 syndrome
C. Li–Fraumeni syndrome
D. Peutz–Jeghers syndrome
E. Cowden syndrome
ANSWERS
Corresponding Chapter in Cancer: Principles & Practice of Oncology, Tenth Edition: 35 (Genetic Counseling).
8 Principles of Radiation Oncology
Hak Choy and Aaron Laine
QUESTIONS
Each of the numbered items below is followed by lettered answers. Select the ONE lettered answer
that is BEST in each case unless instructed otherwise.
Question 8.1 Which of the following describes the specific pathways for the repair of
double-stranded DNA breaks?
A. The repair may be by homologous recombination (HR) or nonhomologous end-joining
(NHEJ) pathway.
B. The HR repair pathway functions by degrading the single strand at each side of the
break and then annealing the two ends.
C. The NHEJ pathway functions by replicating the missing genetic information from the
homologous DNA template.
D. NHEJ is a minor component of mechanism for repair of double-stranded DNA breaks in
mammalian cells.
Question 8.2 Which of the following is TRUE about ionizing events in tissues caused by x-
rays?
A. Radiation dose describes the quantity of energy deposited.
B. The direct effect of radiation is primarily due to injury to cellular membranes.
C. The relative biological effectiveness (RBE) describes the ratio of doses required to give
the same amount of killing under normoxic and hypoxic conditions.
D. Indirect action of ionizing radiation where hydroxyl radicals damage target tissues is
commonly seen.
Question 8.3 Which of the following statements describes the DNA damage/repair process
associated with ionizing radiation?
A. Single-stranded breaks of the DNA are thought to represent the lethal event.
B. All of the radiation-induced, double-stranded breaks are rejoined in cells within 2 hours.
C. In mammalian cells, choice of repair can be biased by phase of the cell cycle and by
abundance of repetitive DNA.
D. Nonhomologous end-joining (NHEJ) is effective in rejoining DNA double-strand break
because it is an error free process.
Question 8.4 Which of the following statements describes the dose-related cellular response
to radiation?
A. In mammalian cells, there is generally a linear and quadratic relationship between the
cell killing and the dose given.
B. The term “D0” describes the quasi-threshold dose, defining the width of the shoulder
C. Densely ionizing radiation leads to an extended shoulder on the survival curve.
D. In general, postirradiation conditions that accelerate the cell division are the ones most
favorable to repair of potentially lethal damage.
Question 8.5 Which of the following statements is TRUE regarding independent events (4
R’s) that occur during fractionated radiotherapy?
A. Repopulation refers to spontaneous repopulation and induced cell proliferation or
recruitment of cells after irradiation.
B. Repair explains the linear portion of the radiation survival curve showing that cells can
repair some of the radiation damage.
C. Redistribution explains migration of cells away from an irradiation source.
D. Reoxygenation describes the decrease of tumor oxygen levels during fractionated
radiation.
Question 8.6 Which of the following acute effects are related to radiation-induced cell
death?
A. Cystitis
B. Esophagitis
C. Dermatitis
D. Proctitis
E. All of the above
Question 8.8 Which of the following best describes the modern linear accelerator?
A. A modern linear accelerator (LINAC) can deliver energies up to 1 MeV.
B. Generate Bremsstrahlung x-rays by bombarding a target with high-energy electrons
C. Primarily uses 60Cobalt which is always “on” and must be kept in a shielded position
until the beam is needed for treatment.
D. The focal point of the gantry’s rotation is called the field edge.
Question 8.9 Which of the following statements describes the role of oxygen in radiation
effects?
A. A greater dose of radiation is required for cell killing in an oxic condition compared
with a hypoxic condition.
B. A randomized trial showed that epoetin b improved survival in patients with head and
neck cancer.
C. Oxygen need not be present at the time of irradiation for oxygen enhancement of
radiotherapy to occur.
D. Hyperbaric oxygen often shows a dramatic increase in curability with standard
fractionated radiotherapy.
E. The oxygen enhancement ratio (OER) has more relevance on the exponential portion of
the cell survival curve.
Question 8.10 Which of the following best describes the concept of altered fractionation?
A. Accelerated fractionation does not reduce the overall treatment time.
B. Hyperfractionation refers to a radiotherapy schedule that uses multiple daily treatments
more than 6 hours apart with reduced fraction size and increased number of fractions.
C. Standard fractionation is commonly defined as 3 to 5 Gy/day
D. The goal of accelerated fractionation is to complete radiation before accelerated
reoxygenation occurs
Question 8.11 Which of the following statements regarding interaction of chemotherapy and
radiation therapy is TRUE?
A. Rationale for combining radiation therapy with radiosensitizing chemotherapy is
primarily to confer an additive effect.
B. Gemcitabine is a potent radiosensitizer and special consideration is not required when
administered with radiation for treatment of lung and head and neck cancers.
C. Paclitaxel radiosensitizing effect to due to G1 cell-cycle arrest
D. Mechanism of radiosensitization by cisplatin may be due to its ability to inhibit DNA
repair of radiation induced DNA double-strand breaks.
Question 8.13 Which of the following statements best describes the tissue effects from
radiation?
A. Early or acute effects typically occur within months after irradiation.
B. Large α/β> ratio has a small “shoulder” in the low-dose portion.
C. The frequencies of late effects depend strongly on radiation fraction size.
D. Typical human tumors and early-responding normal tissues have a small α/β ratio.
Question 8.14 Which of the following statements describes of the interaction of x-rays with
biologic material?
A. In modern treatment with greater than 4 MeV photons, photoelectric effect dominates
the interaction.
B. In Compton scattering, an incoming x-ray transfers all its energy to an inner orbit
electron, which is ejected from the atom. A photon is produced as an outer shell
electron fills the vacant hole.
C. In photoelectric effect, energy from the x-ray is both absorbed and scattered. The
photon emerges with reduced energy and a change in direction.
D. In pair production, an electron and a positron are produced.
Question 8.15 Which of the following statements describes the depth dose characteristics of
radiation?
A. Higher-energy photons deposit more dose to the skin surface.
B. For a given energy, electrons generally penetrate deeper in tissue compared with
photons.
C. Electron beams deposit less dose to the skin surface as the incident electron energy
increases.
D. Depth of maximum dose increases as the energy of the incident beam increases.
Question 8.17 Which of the following can be a subacute toxicity from radiation therapy?
A. Pneumonitis
B. Myelitis.
C. Brain necrosis.
D. B and C.
Question 8.18 Which of the following best describes the treatment planning process?
A. At the time of image acquisition for planning, tumor motion caused by respiration must
be determined.
B. Immobilization is not important because it does not add to accuracy.
C. Three-dimensional dose distribution in each patient is easily measured.
D. Intensity-modulated radiation therapy (IMRT) cannot control the shaping of the dose
distribution.
Question 8.19 Which of the following is TRUE regarding charged particle beams?
A. Charged particle beam therapy includes photon-based therapy.
B. Protons have shown to confer a definite clinical benefit over photon-based therapies for
most clinical cancer applications.
C. Ability of charged particles to stop at a given depth gives it a potential advantage for
treatment of tumors in close proximity to critical structures.
D. Charged particle therapy is relatively inexpensive in terms of the cost involved with
production and operation of such facility.
ANSWERS
Corresponding chapter in Cancer: Principles & Practice of Oncology, Tenth Edition: 13 (Essentials of Radiation Therapy).
9 Systemic Therapy for Cancer
Sara K. Butler and Leigh M. Boehmer
QUESTIONS
Each of the numbered items below is followed by lettered answers. Select the ONE lettered answer
that is BEST in each case, unless instructed otherwise.
Question 9.2 A 35-year-old female is currently being treated with pazopanib (CYP3A4
substrate). She is admitted for seizure management and the consult team recommends
initiation of phenytoin. What effect may concurrent administration have on pazopanib
concentrations?
A. Decrease pazopanib concentration
B. Increase pazopanib concentration
C. No change in pazopanib concentration
D. None, if the pazopanib is taken with food
Question 9.3 Which of the following scenarios best identifies a prognostic marker?
A. KRAS mutation testing in setting of colon cancer
B. Dihydropyrimidine dehydrogenase (DPD) deficiency in the setting of 5-FU therapy
C. MMR protein expression deficiency in setting of colon cancer
D. UGT1A1*28 polymorphism in setting of irinotecan therapy
Question 9.4 HG is a 55-year-old patient with BRAF mutation positive, metastatic melanoma
on vemurafenib therapy. Despite an initial dramatic response, his disease relapsed after
roughly 6 month of treatment. Which of the following explanations describes the most likely
mechanism of resistance?
A. KRAS mutation
B. MEK mutation
C. T790M mutation
D. T315I mutation
Question 9.5 Which of the following medication:pharmacogenomic assay pairs are correctly
matched (select two correct responses)?
A. 6-mercaptopurine:thiopurine methyltransferase (TPMT) activity
B. Tamoxifen:uridine diphosphate glucuronosyltransferase (UGT) 1A1 activity
C. 5-fluorouracil:dihydropyrimidine dehydrogenase (DPD) activity
D. Afatinib:anaplastic lymphoma kinase (ALK) gene rearrangement
Question 9.7 RT is a 50-year-old female with progressive disease following two cycles of
carboplatin and paclitaxel for advanced ovarian cancer. Based on our current understanding,
which of the following mechanisms may best explain platinum-resistant tumor cells (select
two correct responses)?
A. Decreased damage tolerance
B. Reduced cellular accumulation
C. Inactivation of autophagy
D. Intracellular detoxification
Question 9.8 PL is a-65 year-old patient with newly diagnosed metastatic non–small cell
lung adenocarcinoma scheduled to begin treatment with cisplatin and pemetrexed in 1 week.
Which of the following medications should be started today to help minimize hematologic
toxicities with pemetrexed?
A. Vitamin B6 and Vitamin B12
B. Folic acid and dexamethasone
C. Folinic acid and Vitamin B6
D. Vitamin B12 and folic acid
Question 9.11 Which of the following kinase inhibitors were originally developed as a direct
inhibitor of a mutated/amplified tyrosine kinase (select two correct responses)?
A. Imatinib for the treatment of GIST
B. Erlotinib for the treatment of non–small cell lung cancer
C. Lapatinib for the treatment of HER2-positive breast cancer
D. Vandetanib in the treatment of medullary thyroid cancer
Question 9.12 Which of the following is a CORRECT statement regarding the role of VEGF
inhibition in the treatment of kidney cancer?
A. VEGF inhibitors like pazopanib or sunitinib are effective in the treatment of kidney
cancer due to known kinase mutations in VEGF.
B. The mechanism in which mTOR inhibitors are effective in the treatment of kidney
cancer is solely based on the antiproliferative impact against endothelial cells resulting
in anti-angiogensis.
C. The increase activation of the hypoxia inducible factor (HIF) pathway results in
activation of downstream target genes such as VEGF.
D. Inhibition of VEGF via bevacizumab has resulted in greater disease response than
inhibition of VEGF via multikinase inhibitors such as sunitinib or sorafenib.
Question 9.13 LB is a 63-year-old patient with newly diagnosed metastatic melanoma. His
tumor was sent for mutational analysis and was found to be BRAF V600E mutation positive.
Which of the following is a CORRECT statement regarding treatment of his tumor?
A. Due to sorafenib’s inhibition of RAF, it can be used as initial therapy.
B. BRAF inhibition is the most important part of his therapy and treatment with a MEK
inhibitor should not be considered.
C. BRAF inhibitors are only approved in the second-line setting and LB should be initiated
on either cytotoxic chemotherapy or immunotherapy with ipilimumab.
D. High serum levels of BRAF inhibitors are important to allow for achieving adequate
pathway inhibition.
Question 9.15 PM is an 82-year-old male with newly diagnosed multiple myeloma who
presents for discussion of management of his disease. Past medical history is significant for
diabetes, peripheral neuropathy, hyperthyroidism, and hypertension. Which of the following
would be the most appropriate management of his cancer?
A. Bortezomib 1.3 mg/m2 subcutaneously on days 1, 4, 8, and 11 and dexamethasone.
B. Carfilzomib 20 mg/m2 IV on days 1, 2, 8, 9, 15, and 16 and dexamethasone.
C. Bortezomib 1.3 mg/m2 IV on days 1, 4, 8 and 11 and dexamethasone.
D. Carfilzomib 27 mg/m2 IV on days 1, 2, 8, 9, 15, and 16 and dexamethasone.
Question 9.16 Poly (ADP-ribose) polymerase (PARP) signals the presence of DNA damage
and facilitates DNA repair. Which of the following is a role for PARP inhibition? (Select two
correct responses).
A. Chemopotentiation
B. Serine/threonine kinase inhibition
C. Synthetic lethality with BRCA 1/2 mutations
D. Increased hypoxia-inducible factor-1 function
Question 9.18 SB is a patient with metastatic prostate cancer who presents to the clinic with
hypokalemia and peripheral edema. He recently started on abiraterone 1,000 mg po daily
after disease progression on docetaxel. Which of the following would be the most appropriate
treatment options?
A. Switch the patient to enzalutamide therapy.
B. Decrease the dose of abiraterone to 750 mg po daily.
C. Initiate prednisone 5 mg po twice daily.
D. Initiate spironolactone 50 mg po daily.
Question 9.20 TB is a 72-year-old male with progressive CLL who is about to initiate
therapy with ofatumumab. Which of the following are considered advantages to ofatumumab
over rituximab therapy?
A. Ofatumumab induces more antibody-dependent cell-mediated toxicity (ADCC) than
rituximab.
B. Ofatumumab causes more complement activation than rituximab.
C. Ofatumumab is a humanized monoclonal antibody whereas rituximab is chimeric.
D. Ofatumumab demonstrated about an 80% response rate in treatment refractory disease.
ANSWERS
Corresponding chapters in Cancer: Principles & Practice of Oncology, Tenth Edition: 15 (Pharmacokinetics and
Pharmacodynamics), 16 (Pharmacogenomics), 17 (Alkylating Agents), 18 (Platinum Analogs), 19 (Antimetabolites), 20
(Topoisomerase-Interacting Agents), 21 (Antimicrotubule Agents), 22 (Kinase Inhibitors as Anticancer Drugs), 23 (Histone
Deacetylase Inhibitors and Demethylating Agents), 24 (Proteasome Inhibitors), 25 (Poly[ADP-Ribose] Polymerase Inhibitors),
26 (Miscellaneous Chemotherapeutic Agents), 27 (Hormonal Agents) and 28(Antiangiogenesis Agents), 29 (Monoclonal
Antibodies).
10 Principles of Immunotherapy
Sarah B. Goldberg
QUESTIONS
Each of the numbered items below is followed by lettered answers. Select the ONE lettered answer
that is BEST in each case unless instructed otherwise.
Question 10.1 Which of the following types of immunity is most responsible for the host
response to tumor development?
A. Humoral immunity
B. B-cell–mediated immunity
C. T-cell–mediated immunity
D. Antibody-mediated immunity
Question 10.2 Currently, what is the proposed mechanism for using immunotherapy to
destroy cancer cells?
A. Develop antibodies to target growth factors on cancer cells
B. Increase levels of immune lymphocytes
C. Develop antibodies to directly destroy the cancer cells
D. Increase levels of antigen-presenting cells
Question 10.3 A 55-year-old woman with metastatic melanoma enters a clinical trial with a
cancer vaccine. Approximately 4 weeks after starting treatment she develops abdominal pain
and watery diarrhea. Which of the following is the most likely diagnosis and the etiology?
A. Autoimmune colitis from activation of T cells against antigen found in cells lining the
gastrointestinal tract
B. Autoimmune colitis from antibody production targeting antigen found in cells lining the
gastrointestinal tract
C. Infectious colitis from immunosuppression due to aberrant T-cell production
D. Infectious colitis from contamination of the vaccine product with a virus capable of
infecting the gastrointestinal tract
Question 10.4 Expression of the Epstein–Barr virus (EBV) latent gene EBNA is seen in which
of the following cancers?
A. Nasopharyngeal carcinoma
B. Burkitt lymphoma
C. T-cell lymphoma
D. All of the above
Question 10.5 A 20-year-old sexually active woman inquires about the role of the human
papilloma virus (HPV) vaccine in relation to cervical cancer. Which of the following
statements regarding the HPV vaccine is CORRECT?
A. It prevents the development of cervical cancer in all patients
B. It induces regression of cervical cancer tumors
C. It prevents infection with HPV 16 and 18
D. It prevents the development of cervical cancer in patients infected with HPV 16 and 18
Question 10.8 A 48-year-old man presents with hematuria, and CT imaging reveals a 5-cm
kidney mass. Imaging of his chest shows multiple small bilateral lung nodules consistent with
metastatic renal cell cancer. He is asymptomatic and in otherwise good health. You discuss
treatment options with him including the use of IL-2 therapy. Which of the following
statements is TRUE regarding the use of IL-2 in this situation?
A. IL-2 is very well-tolerated with minimal side effects in the majority of patients
B. IL-2 is FDA-approved for multiple cancer types given the excellent outcomes, including
kidney cancer, melanoma, and lung cancer.
C. The chance of tumor regression with the use of IL-2 in kidney cancer is approximately
75%.
D. Although tumor response is seen in approximately 20% of patients with kidney cancer
treated with IL-2, some patients can have durable benefit without tumor progression for
several years.
Question 10.11 The purpose of checkpoint molecules such as CTLA-4 and PD-1 are to:
A. Enhance the immune response against infectious agents by activating T cells.
B. Enhance the immune response against cancer by activating T cells.
C. Protect normal tissues against autoimmunity by inhibiting T cells.
D. Protect normal tissues from tumorigenesis by stimulating the immune system.
Question 10.12 A 67-year-old man presents with abdominal pain and weight loss and is
found to have multiple liver masses and diffuse lymphadenopathy. Biopsy of a liver lesion
confirms metastatic melanoma. He is otherwise healthy with no other significant medical
problems. Which of the following is accurate regarding the use of immunotherapeutic agents
in metastatic melanoma?
A. Nivolumab is an inhibitor of the checkpoint molecule CTLA-4, and its use can result in
significant tumor regression
B. Nivolumab often results in autoimmune toxicity while ipilimumab is rarely associated
with side effects
C. Both nivolumab and ipilimumab can result in durable tumor regression
D. The combination of nivolumab and ipilimumab does not appear to result in additional
toxicity than either agent alone
Question 10.13 Which of the following has been associated with death in trials of nivolumab
for lung cancer?
A. Neutropenia
B. Pneumonitis
C. Hepatitis
D. Hypophysitis
Question 10.17 Which of the following is CORRECT regarding adoptive cell therapy?
A. Adoptive cell therapy is only effective if the lymphocytes are genetically modified prior
to infusing them into the patient.
B. Both nonviral- and viral-based gene delivery platforms have been used to genetically
modify cells for use in adoptive cell therapy
C. Targeting antigens that are expressed only on tumor cells and not on normal tissue can
decrease the toxicity associated with on-target, off-tumor effects of the lymphocytes
D. B and C only
Question 10.18 Which of the following indicates the potential utility of anti-CD19 CAR T
cells?
A. They have been used in many types of solid tumors because of the high prevalence of
CD19 on solid tumor cells.
B. Because they are found on almost all malignant B cells, they have been tested in
patients with hematologic malignancies.
C. Toxicity associated with this therapy is typically long term due to graft-versus-host
disease.
D. B and C only
ANSWERS
Corresponding chapter in Cancer: Principles & Practice of Oncology, Tenth edition: 14 (Cancer Immunotherapy).
11 Assessment of Clinical Responses
Vinicius Ernani and Suresh S. Ramalingam
QUESTIONS
Each of the numbered items below is followed by lettered answers. Select the ONE lettered answer
that is BEST in each case unless instructed otherwise.
Question 11.2 In children with lymphoblastic leukemia, folic acid was observed to:
A. Cause disease proliferation.
B. Cause disease regression.
C. Have no effect.
D. Improve survival.
Question 11.4 In patients with advanced or metastatic disease, which of the following has
curative potential with primary induction chemotherapy?
A. Germ cell cancer
B. Non–small cell lung cancer
C. Gastric cancer
D. Colorectal cancer
Question 11.5 The goals of therapy in incurable, advanced, metastatic disease include:
A. Obtain a complete response
B. Palliate tumor-related symptoms
C. Deliver higher doses of chemotherapy
D. Never offer therapy
Question 11.6 Neoadjuvant chemotherapy can be utilized in which of the following cancers?
A. Burkitt lymphoma
B. Hodgkin lymphoma
C. Multiple Myeloma
D. Lung cancer
Question 11.7 Which of the following is TRUE regarding the purpose of administering
adjuvant chemotherapy?
A. To increase quality of life.
B. To reduce local and distant recurrence.
C. To use as primary therapy instead of surgery.
D. To use as primary therapy instead of radiation.
Question 11.8 Which of the following play essential role in activating apoptosis?
A. Bcl-2
B. NF-κB
C. Caspases
D. Bcl-xL
Question 11.9 The most important indicator of the effectiveness of chemotherapy is:
A. Achievement of a minor response.
B. Achievement of a partial response.
C. Achievement of a complete response.
D. Achievement of stable disease.
Question 11.10 According to RECIST criteria 1.1, a partial response is defined as:
A. At least a 30% reduction in measurable tumor mass.
B. At least a 10% reduction in measurable tumor mass.
C. Improvement in quality of life.
D. Improvement in survival.
Question 11.12 In early-stage colon cancer treated with adjuvant chemotherapy, the
majority of relapses occur:
A. Within the first 5 years.
B. Within the first 3 years.
C. Within the first 2 years.
D. Within the first year.
Question 11.14 Which of the following is the most common genetic change associated with
development of resistance to tyrosine kinase inhibitors (TKI) in patients with epidermal
growth factor receptor (EGFR) mutation?
A. T790M mutation
B. PTEN overexpression
C. D761Y mutation
D. MET gene mutation
Question 11.15 Which of the following is TRUE regarding intention to treat (ITT) analysis?
A. Increases the risk of bias
B. Should not be used in a randomized control trial
C. Small effect on overall survival and progression-free survival
D. All patients randomized to a group will be analyzed
Question 11.16 In patients with colorectal cancer the genetic change associated with
resistance to cetuximab is:
A. BRAF mutation.
B. Wild-type KRAS.
C. EGFR-TK mutation.
D. NFκB activation.
Question 11.17 Dose-dense chemotherapy was developed after the observation that:
A. The growth of cells is significantly lower in the early part of the growth curve.
B. The log cell kill is higher in smaller volume tumors, resulting in more rapid growth
between chemotherapy cycles.
C. Growth between chemotherapy cycles is halted.
D. More frequent administration of chemotherapy led to less toxicity.
Question 11.18 In most cases, normal bone marrow and gastrointestinal (GI) precursor cells
are able to counteract the effects of cytotoxic chemotherapy because:
A. They are not exposed to the chemotherapeutic agent.
B. They have intact mechanisms for apoptosis and cell-cycle arrest.
C. They have rapid turnover.
D. They possess resistance mechanisms.
Question 11.19 Which of the following is TRUE concerning p53?
A. It is a targetable mutation for therapy
B. It is a potent inducer of apoptosis.
C. It causes S-phase arrest in the cell cycle.
D. It can decrease the activity of cytotoxic chemotherapy.
Question 11.20 The final stage of the programmed-cell death pathway is mediated by:
A. Bcl-2.
B. p53.
C. Tumor necrosis factor.
D. Caspase cascade.
Question 11.27 Which of the following is TRUE regarding the use of time to progression as
an end point in clinical trials?
A. Uses a smaller sample size when compared with using overall survival as an end point.
B. Not confounded by subsequent therapies.
C. The study can be completed in a shorter amount of time.
D. All of the above.
ANSWERS
Corresponding chapter in Cancer: Principles & Practice of Oncology, Tenth Edition: 30 (Assessment of Clinical Response).
12 Design and Analysis of Clinical Trials
Ling Chen and Kathryn Trinkaus
QUESTIONS
Each of the numbered items below is followed by lettered answers. Select the ONE lettered answer
that is BEST in each case unless instructed otherwise.
Question 12.2 Phase I trials of cytotoxic agents are designed to determine a dose that is
appropriate for use in phase II trials. Which of the following statements is TRUE about phase
I trials?
A. Phase I trials involve the first use of a drug, device, or procedure in humans in a new
disease setting or a new combination of therapies.
B. Patients for phase I trials are usually not chosen on the basis of their likelihood of
having a favorable response to the experimental treatment.
C. Phase I trials do not require statistical justification because the sample sizes are usually
small.
D. A and B.
Question 12.3 Which of the following regarding the conventional 3 + 3 phase I designs is
TRUE?
A. Participants are often those with end-stage disease who have many treatment options.
B. Such studies are usually performed by starting with a high dose.
C. Cohorts of three to six patients are treated at each dose level, and the initial dose is
chosen to cause little or no toxicity.
D. The optimal dose recommended for phase I is chosen using a dose-toxicity curve
generated from a statistical model fitted to the full data.
Question 12.4 Traditional phase I trials are designed to determine a dose that is appropriate
for use in phase II trials. Which of the following statement on traditional phase I trials is
TRUE?
A. Many patients may receive subtherapeutic doses and it does not allow for dose
escalation in the individual patient.
B. All phase I trials are completed in a short time period.
C. Dose escalation in the individual patient is allowed.
D. Phase I trial provides substantial information regarding cumulative toxicity from the
study drug
Question 12.5 A drug, device, or other treatment may be considered for phase II testing
when:
A. The maximum tolerable dose is known but there is genuine doubt about efficacy and
patients with the condition of interest and a likely favorable outcome can be recruited
as study participants.
B. A standard treatment exists for comparison.
C. Accrual is rapid enough to allow recruitment of 20 to 30 patients.
D. An appropriate control group can be recruited at the same time as the experimental
group.
Question 12.6 which of the following statements regarding phase II trials is CORRECT?
A. Phase II trials are traditionally performed in patients with a wide variety of tumor
types.
B. Two-stage designs allow for early elimination of ineffective drugs.
C. Patient eligibility should not be restricted by biomarker testing.
D. Phase II trials cannot help develop predictive biomarker assays for the study drug.
Question 12.7 Phase II trials of a single agent are designed to determine whether the
experimental drug has any antitumor activity against a given type of tumor and the
antitumor effect is often measured as an objective response based on tumor shrinkage.
However, such a trial is NOT appropriate for the question of patient welfare because:
A. The welfare of patients with cancer is often measured by survival or symptom control,
but there is no necessary relationship between such beneficial end points and tumor
response.
B. Survival is inherently a comparative end point that should be assessed in a
prognostically comparable set of patients.
C. Comparing the survival times of responders and nonresponders is not a valid means of
showing a treatment is beneficial to patients because responders may have more
favorable prognostic factors than nonresponders.
D. All of the above.
Question 12.8 Patients in a phase II trial are often recruited in a two-stage manner that
allows early stopping if the null hypothesis is unlikely to be rejected, thus saving patients
from unnecessary exposure to inactive agents. Which of the following is TRUE of a two-stage
design?
A. The optimal two-stage design minimizes the average sample size and thus optimizes the
protection of patients given an inactive agent.
B. Simon two-stage designs are often applied in phase II trials on molecularly targeted
drugs and therapeutic cancer vaccines.
C. If both stages are completed, the minimax design usually enrolls more patients
compared with the optimal design.
D. Simon two-stage designs are often used in phase II trials comparing treatment groups to
an internal control group to draw conclusions about survival.
Question 12.9 Unlike cytotoxic agents that work by killing tumor cells, cytostatic agents
work via biologic effects that modify the environment of tumor growth; that is, inhibition of
a molecular target. Which of the following is TRUE regarding early-phase trials of cytostatic
agents such as molecularly targeted drugs and cancer therapeutic vaccines?
A. Phase I trials on cytostatic agents are often designed to identify maximum tolerated
dose.
B. Heavily treated patients with end-stage disease greatly benefit from a cancer vaccine.
C. The response rate based on tumor shrinkage is the best primary end point measuring
treatment efficacy in phase II trials on cytostatic agents.
D. Because of the nature of low toxicity profiles in cytostatic agents, factorial designs and
randomized studies have appealing features and are used to evaluate multiple drugs in a
single trial.
Question 12.10 Which of the following best describes Simon phase 2.5 design on
molecularly targeted drugs and cancer therapeutic vaccines?
A. The design compares progression-free survival times of the same patient from the
current trial with his/her previous trial.
B. The design first treats all eligible patients with two to four courses of the experimental
drugs. Patients are then evaluated, and the experimental drug is either continued or
discontinued, depending on their response to the initial treatment.
C. The design is similar to a phase III trial except that it allows a relatively large type I
(false positive) error and aims to identify a relatively large difference, thus requiring
fewer patients.
D. The design will compare time to progression of patients in the study with a
prospectively identified and prognostically comparable historical control.
Question 12.14 Which of the following is TRUE of power and hypothesis testing in clinical
trials?
A. Statistical power mainly depends on the anticipated size of treatment effect. Trials
designed to detect a large effect will demand small sample sizes.
B. Statistical power is also heavily influenced by the prespecified type I error (probability
of erroneously claiming a “positive” result), and a two-sided type I error of 0.05 has
been widely accepted, especially in phase III trials.
C. Confidence intervals do not provide information about the size and direction of
treatment effect, and it is less informative than significance testing.
D. Because data from small randomized trials can be pooled for meta-analysis, the
calculation of sample size for a randomized clinical trial is no longer critical.
Question 12.15 Which of the following is TRUE for therapeutic equivalence (or
noninferiority) trials?
A. Therapeutic equivalence trials are designed to test similarity, as measured by a clinical
end point, between the experimental drugs and the standard treatment.
B. Because it is impossible to prove equivalence in true sense, in practice therapeutic
equivalence will be accepted if the difference in efficacy is larger than or smaller than a
prespecified amount δ.
C. The traditional superiority trials can be used to prove equivalence
D. A trial designed to demonstrate therapeutic equivalence requires fewer patients because
it usually allows a relatively large type I error.
Question 12.17 Which one of the following describing the pros and cons of Bayesian
methods in planning clinical trials is TRUE?
A. In the traditional statistical (frequentist) methods, the treatment effect is regarded as a
fixed but unknown parameter, and the likelihood of the parameter is described using a
probability derived from observed frequencies in a defined distribution. In contrast, a
Bayesian statistical method assumes that the treatment effect itself is a random quantity
drawn from a prior distribution.
B. Bayesian methods are more widely applied in planning phase III trials than phase I or
phase II trials.
C. Bayes’ theorem can be considered as a substitute for randomization.
D. Bayesian clinical trials require fewer patients than frequentist trials.
Question 12.18 The intention-to-treat analysis is considered the primary analysis of data
from a clinical trial. Which of the following describes an intention-to-treat analysis?
A. An ineligible patient is not included in an intention-to-treat analysis because the study
treatment is not appropriate for that patient.
B. All patients who give consent and are randomized are included in the intention-to-treat
analysis in the study arm to which they were randomized.
C. Data from patients who are ineligible or who die or withdraw from the study before
completion should be analyzed separately from data from eligible patients who
complete the trial.
D. Lack of compliance can distort the results from patients who fail to complete the trial,
so these data should be dropped from an intention-to-treat analysis.
Question 12.19 An interim analysis is any assessment of data performed during patient
enrollment or follow-up period of a trial. Which of the following is TRUE for planning
clinical trials with interim analyses?
A. Multiple looks at outcome data over the course of a trial will alter type I and II errors.
Unless they are included in the design, multiple looks will cause the operating
characteristics of the trial to deviate from the planned values.
B. Interim outcome information is generally available to participating physicians and study
leaders.
C. The method of stochastic curtailment is designed to calculate conditional power (the
projected probability of rejecting the null hypothesis at the end of study), conditional
on the accumulated information, and to stop the trial if the conditional power is small
(e.g., 0.2). In such a “futility” analysis, the number of interim analyses does not need to
be fixed in advance.
D. A data-safety committee is usually put in charge of the interpretation of interim
analyses. The committee also includes the study leaders to notify the patients and
medical community in a timely manner.
Question 12.20 One of the most important features that make survival data different from
other kinds of data is the presence of censoring. That is, the actual survival times for some
patients cannot be observed during the study. Which of the following is TRUE for the analysis
of survival data?
A. The usual statistical methods are appropriate for analyzing survival data.
B. Two methods are most frequently used for the estimation of survival curves. The life
table method requires relatively large sample size, and the Kaplan–Meier product limit
method is appropriate for any sample size.
C. Traditional summary statistics, such as means and standard deviations, can provide a
sufficient summary for survival data without censoring.
D. The statistical power of clinical trials using survival as a primary end point will be
mainly determined by the total number of patients rather than the actual number of
events including death or tumor progression.
Corresponding chapter in Cancer: Principles & Practice of Oncology, Tenth edition: 36 (Design and Analysis of Clinical Trials).
13 Cancer of the Head and Neck
Douglas R. Adkins, Jessica C. Ley and Loren Michel
QUESTIONS
Each of the numbered items below is followed by lettered answers. Select the ONE lettered answer
that is BEST in each case unless instructed otherwise.
Question 13.1 A 65-year-old man with a 40 pack-year history of smoking presented with
hoarseness and a neck mass. The patient did not aspirate and had not lost weight. The patient
was found to have T4N2cM0 squamous cell carcinoma (SCC) of the glottic larynx. T4
classification was based on limited cortical erosion of the thyroid cartilage. A total
laryngectomy and bilateral neck dissections followed by adjuvant radiation therapy was
recommended by the otolaryngologist. However, the patient preferred a chance to preserve
the larynx. Which treatment approach offers the best chance to preserve the patient’s larynx
and prevent disease recurrence?
A. Radiation therapy alone
B. Induction chemotherapy followed by radiation therapy
C. Concurrent chemotherapy and radiation therapy
D. Chemotherapy alone
Question 13.2 Which of the following statements about the epidermal growth factor
receptor (EGFR) in head and neck SCC (HNSCC) is TRUE?
A. Randomized trials demonstrated that oral tyrosine kinase inhibitors (TKI) of EGFR such
as erlotinib and monoclonal antibody inhibitors of EGFR such as cetuximab resulted in
similar tumor control.
B. Activating EGFR mutations are frequent in HNSCC.
C. The EGFR inhibitor cetuximab improved overall survival when added to definitive
radiation therapy or to palliative platin-based chemotherapy in HNSCC.
D. High EGFR expression is associated with sensitivity to radiation therapy.
Question 13.3 Which of the following are risk factors for HNSCC?
A. Tobacco use
B. Alcohol use
C. Fanconi anemia
D. All of the above
Question 13.4 Which of the following characteristics are typical features of human
papilloma virus (HPV)-related HNSCC?
A. Most patients have limited or no smoking history and most have primary tumors that
involve the oropharynx (base of tongue or palatine tonsils).
B. Survival outcomes are substantially better than in patients with smoking-associated
HNSCC.
C. The role of the HPV in subsites other than the oropharynx is not clear.
D. All of the above.
Question 13.5 A 56-year-old man presented to his primary care physician with a 3-month
history of right ear pain and two masses on the right side of his neck. On examination, he
was found to have a 3-cm right palatine tonsil mass and two enlarged lymph nodes under the
upper part of the right sternocleidomastoid muscle. One lymph node was 2 cm, and the other
was 1 cm in diameter. A fine-needle aspiration (FNA) of one of the neck lymph nodes was
performed and it was consistent with p16+ SCC. Neck and chest computed tomography (CT)
showed no additional lymphadenopathy or distant metastasis. What is the stage of his
disease?
A. Stage II
B. Stage III
C. Stage IVA
D. Stage IVC
Question 13.8 A 66-year-old man presented to his otolaryngologist with a 4-cm left floor of
mouth SCC. A 3-cm left neck node was felt on examination. CT of the neck also showed that
the primary tumor invaded into the mandible. There was no evidence of distant metastasis on
CT of the chest. What is the most appropriate initial therapy for this patient?
A. Surgery
B. Radiation therapy
C. Concurrent chemotherapy and radiation therapy
D. Chemotherapy
Question 13.11 Which of the following statements about the treatment of laryngeal SCC is
TRUE?
A. Radiation therapy alone resulted in worse overall survival compared with concurrent
chemotherapy and radiation therapy in patients with locally advanced laryngeal SCC.
B. Concurrent chemotherapy and radiation therapy resulted in better local tumor control
and laryngeal preservation rate than radiation therapy alone for locally advanced SCC
of the larynx.
C. A total laryngectomy is required for the treatment of locally advanced SCC of the
larynx.
D. Large-volume laryngeal SCC is defined as tumor that extends more than 1 cm onto the
base of tongue and/or extension through the thyroid cartilage into adjacent soft tissue
and is best treated with nonsurgical therapy.
Question 13.12 True or False: There is an overall survival benefit with adjuvant
chemotherapy given after resection of a SCC of the larynx.
A. True
B. False
Question 13.13 Which of the following statements are TRUE? (Select two correct responses)
A. The three subtypes of nasopharyngeal carcinoma are World Health Organization (WHO)
type I keratinizing SCC; WHO type II nonkeratinizing SCC; and WHO type III
undifferentiated carcinoma or lymphoepithelioma. Type III nasopharyngeal SCC is due
to EBV infection and has a much better prognosis than Type I nasopharyngeal SCC.
B. Nasopharyngeal carcinoma is usually treated with chemotherapy and radiation.
C. Common presenting symptoms of nasopharyngeal carcinomas include hoarseness,
painful lower neck mass, and weight loss.
D. The majority of nasopharyngeal carcinomas present with distant metastatic disease.
Question 13.14 A 56-year-old woman presented to her primary care physician with left-
sided facial swelling and facial drooping. The patient had weakness of the lower portion of
her face and a palpable left parotid mass. A biopsy was performed and showed high-grade
mucoepidermoid carcinoma. There were no palpable neck lymph nodes. What is the best
treatment for this patient?
A. Radiation alone
B. Concurrent chemotherapy and radiation therapy
C. Surgery alone
D. Surgery followed by adjuvant radiation therapy
Question 13.15 Which of the following statements is TRUE about locally advanced HNSCC?
(Select two correct responses)
A. The most common long-term complication of radiation therapy is xerostomia.
B. Once the patient is able to receive nutrition via a G-tube, there is no benefit from
having the patient continue to swallow during radiation therapy.
C. Intensity-modulated radiation therapy (IMRT) decreases the risk of xerostomia.
D. The severity of the acute side effects of radiation therapy is similar when chemotherapy
is given concurrently.
Question 13.16 Which of the following statements are TRUE regarding second primary
cancers in patients with HNSCC?
A. Patients with HPV-related oropharyngeal SCC have a similar risk of second primary
cancers as do patients with smoking-induced HNSCC.
B. Patients with resected HNSCC who quit smoking have a lower risk of second primary
cancers than those who continue to smoke.
C. Treatment with α-tocopherol decreases the incidence of second primary cancers.
D. Treatment with isotretinoin decreases the incidence of second primary cancers.
Question 13.17 Which of the following statements regarding induction chemotherapy in the
treatment of HNSCC is TRUE?
A. Treatment with concurrent chemotherapy and radiation therapy resulted in improved
overall survival compared to induction chemotherapy followed by radiation therapy for
locally advanced laryngeal SCC.
B. Addition of docetaxel to cisplatin and 5FU was associated with similar overall survival
when compared to cisplatin and 5FU in patients with locally advanced HNSCC
subsequently treated with radiation therapy alone or concurrent carboplatin and
radiation therapy.
C. Induction chemotherapy may facilitate organ preservation in patients with locally
advanced laryngeal or hypopharyngeal SCC.
D. Induction chemotherapy followed by concurrent cisplatin and radiation therapy results
in improved overall survival compared to concurrent cisplatin and radiation therapy.
Question 13.18 A 35-year-old nonsmoking female with a history of chronic oral lichen
planus presented with a painful right oral tongue lesion measuring 2.5 cm. Biopsy revealed
well-differentiated SCC. Ultrasound revealed that the oral tongue lesion was 0.6 cm thick. CT
showed no abnormal neck nodes. The lesion was widely excised and a right selective neck
dissection (SND) was performed. Pathology revealed a 2.6 cm SCC, negative surgical
margins, no perineural or lymphovascular invasion, and all 15 lymph nodes without SCC. The
pathologic stage was II (T2N0M0). The most appropriate next therapy is:
A. Postoperative adjuvant radiation therapy.
B. Postoperative adjuvant concurrent chemotherapy and radiation therapy.
C. Close monitoring.
D. Left selective neck dissection.
Question 13.19 A 58-year-old male with stage IVA SCC of the larynx was treated with
concurrent chemotherapy and radiation therapy 12 months ago. On routine surveillance CT,
multiple new bilateral pulmonary nodules were noted. A biopsy of one of the pulmonary
nodules showed SCC consistent with metastases from the laryngeal cancer. The patient has an
ECOG performance status of 0 and has no serious comorbidities. What is the most effective
treatment for this patient’s cancer?
A. Weekly administration of cetuximab
B. Weekly paclitaxel
C. Carboplatin, docetaxel, and cetuximab with peg-filgrastim
D. Carboplatin, 5FU, and cetuximab
Question 13.20 A 65-year-old male presented with a large hard palate mass. Biopsy showed
a salivary ductal adenocarcinoma. The mass was completely excised and pathology revealed a
4 cm tumor with positive surgical margins. Postoperative adjuvant radiation therapy was
given. Nine months later, a surveillance CT showed several pulmonary nodules. A biopsy of
one of the pulmonary nodules showed metastatic salivary ductal adenocarcinoma. The patient
was referred to medical oncology for management. The most appropriate next step in the
management of this patient is:
A. Weekly cetuximab.
B. Platin, 5FU, and cetuximab.
C. Taxane.
D. Perform immunohistochemistry stain for the androgen receptor.
ANSWERS
Corresponding chapters in Cancer: Principles & Practice of Oncology, Tenth Edition: 37 (Molecular Biology of Head and Neck
Cancers), 38 (Cancer of the Head and Neck), and 39 (Rehabilitation after Treatment of Head and Neck Cancer).
14 Lung Cancer and Mesothelioma
Siddhartha Devarakonda and Saiama N. Waqar
QUESTIONS
Each of the numbered items below is followed by lettered answers. Select the ONE lettered response
that is BEST in each case.
Question 14.2 Sequencing the lung adenocarcinoma of a 54-year-old man with a 60 pack-
year smoking history is likely to reveal which of the following features?
A. EML4-ALK translocation
B. An excess of C>T transitions
C. Co-mutation of TP53 and RB1
D. An excess of G>T transversions
Question 14.3 A 55-year-old man with a 30 pack-year history of smoking, presents to the
emergency room with shortness of breath. Chest radiograph demonstrates a right upper lobe
opacity. Computed tomography (CT) scan reveals a 3.5-cm spiculated mass in the peripheral
right upper lobe, which is suspicious for malignancy, without any hilar or mediastinal
lymphadenopathy. What is the next best step in management?
A. Bronchoscopy and biopsy of the mass
B. CT-guided biopsy of the mass
C. Brain MRI
D. Refer to thoracic surgeon for resection.
Question 14.4 A 65-year-old man with a 40 pack-year history of smoking, presents to the
emergency room with shortness of breath. Chest radiograph demonstrates a left lower lobe
mass and left pleural effusion. CT reveals a 3-cm left lower lobe mass, left hilar fullness, and
a moderate left pleural effusion. Biopsy of the mass and thoracentesis are both positive for
adenocarcinoma. Staging studies do not reveal any distant metastases. Which of the following
is the next best step in his management?
A. Referral to a thoracic surgeon
B. Radiation to the chest
C. Concurrent chemotherapy and radiation
D. Platinum-based doublet therapy
Question 14.5 A 66-year-old man, with a 30 pack-year history of smoking, presents to your
office for consultation regarding chemotherapy options for metastatic non–small cell lung
cancer (NSCLC), squamous histology. He has no significant medical problems and the
performance status (PS) is 1. Laboratory studies reveal normal blood counts, liver enzymes,
and kidney function. Which of the following treatment regimens would you recommend?
A. Cisplatin and pemetrexed
B. Carboplatin, paclitaxel, and bevacizumab
C. Carboplatin and paclitaxel
D. Carboplatin and erlotinib
Question 14.6 A 55-year-old Asian woman, who is a never smoker, completed four cycles of
front-line carboplatin and paclitaxel, for metastatic NSCLC. Imaging studies done after
completion of therapy show stable disease. She is very active and has continued to work as a
nurse throughout her treatment. Her PS is 0 and she has tolerated the treatment well, other
than grade I neuropathy. Her tumor EGFR status is wild type. She wants “the best treatment
possible” and desires further treatment. What would you recommend?
A. Treatment break, erlotinib at the time of disease progression
B. Stopping carboplatin, continuing paclitaxel till disease progression
C. Continuing carboplatin and paclitaxel for four additional cycles
D. Pemetrexed maintenance therapy
Question 14.7 A 58-year-old man, with a 40 pack-year history of smoking is referred to you
by a radiation oncologist for management of limited-stage SCLC. What treatment would you
recommend?
A. Cisplatin and etoposide chemotherapy
B. Cisplatin and etoposide chemotherapy with concurrent thoracic radiation
C. Cisplatin and etoposide chemotherapy, followed by PCI if response to chemotherapy
D. Cisplatin and etoposide chemotherapy with concurrent thoracic radiation, followed by
PCI if response to treatment
Question 14.8 Which of the following statement(s) is/are CORRECT regarding the role of
adjuvant chemotherapy after resection for NSCLC?
A. Adjuvant chemotherapy benefits patients with stage IA disease.
B. Adjuvant chemotherapy benefits patients with node-positive disease.
C. Adjuvant chemotherapy may benefit patients with stage IB disease, who have primary
tumors less than 4 cm in size.
D. All of the above.
Question 14.10 Which of the following statement is TRUE regarding first-line therapy with
EGFR tyrosine kinase inhibitors (TKIs) in patients with EGFR-mutated lung adenocarcinoma?
A. Response rates with TKIs are similar to that achieved with chemotherapy, although they
are more durable.
B. TKIs have consistently shown superior overall survival compared to chemotherapy.
C. TKIs when combined with chemotherapy yield better outcomes than treatment with
either modality alone.
D. TKIs show better response rates and progression-free survival compared to
chemotherapy.
Question 14.11 A 60-year-old man with a 45 pack-year history of smoking, presents with
chest pain. Chest x-ray reveals a right upper lobe mass. CT scan of the chest demonstrates a
4-cm right upper lobe lung mass, with right hilar and multiple ipsilateral enlarged
mediastinal lymph nodes. Bronchoscopy and biopsy of the mass reveals NSCLC. PET scan
demonstrates increased FDG-uptake in the lung mass, right hilar and mediastinal lymph
nodes, but no other site of metastatic disease. CT of the abdomen and brain MRI are
unremarkable. Mediastinoscopy and biopsy reveals NSCLC. His cancer is staged as T2aN2M0,
stage IIIA NSCLC. His PS is 1 and he is otherwise in good health. Which of the following is
the best management for this patient?
A. Definitive radiation to the chest
B. Radiation to the chest, followed by platinum-based chemotherapy
C. Concurrent radiation to the chest and platinum-based chemotherapy
D. Platinum-based chemotherapy
Question 14.12 When treating a patient with metastatic ALK rearranged adenocarcinoma of
the lung, disease progression was noted after 9 months of treatment with crizotinib. Which of
the following is/are valid treatment option(s) for this patient?
A. Treatment with a second-generation ALK inhibitor such a ceritinib
B. Treatment with chemotherapy
C. Treatment with local ablative techniques for oligo-progression
D. All of the above
Question 14.13 A 45-year-old Asian woman, who is a never smoker, presents to your office
for consultation regarding systemic therapy for metastatic adenocarcinoma of the lung. Her
tumor has an activating EGFR mutation. Which of the following is a valid first-line treatment
option for this patient?
A. Cetuximab
B. Afatinib
C. Necitumumab
D. Crizotinib
Question 14.14 A 65-year-old Caucasian man, who is a never smoker, presents to your office
for consultation regarding therapy for metastatic adenocarcinoma of the lung. Genotyping of
his tumor revealed a gene fusion involving ROS1. The patient is interested in knowing more
about this alteration and if he would qualify for treatment with any of the currently approved
TKIs. Which of the following response is CORRECT?
A. While ROS1 alterations are seen in nearly 15% of adenocarcinomas, but there are no
TKIs known to be active in this setting
B. ROS1 rearrangements are seen in 5% of adenocarcinomas, and these tumors respond
well to treatment with erlotinib.
C. ROS1 rearrangements are seen in nearly 2% of adenocarcinomas, and these tumors
respond well to treatment with crizotinib.
D. ROS1 rearrangements are seen in 15% of all adenocarcinomas, and these tumors can
respond to crizotinib.
Question 14.15 A 65-year-old man, who is a former smoker presents for consultation
regarding management of unresectable stage IIIB adenocarcinoma of the lung. He has a PS of
0 and adequate blood counts, hepatic, and renal function. Which of the following would you
recommend?
A. Concurrent definitive cisplatin and etoposide therapy, no consolidation therapy, no PCI
B. Concurrent definitive cisplatin and etoposide therapy, consolidation docetaxel therapy,
no PCI
C. Concurrent definitive cisplatin and etoposide therapy, consolidation gefitinib therapy,
no PCI
D. Concurrent definitive cisplatin and etoposide therapy, consolidation gefitinib therapy,
followed by PCI
Question 14.17 Which of the following is a characteristic genomic feature of small cell lung
cancer?
A. Recurrent alterations in EGFR and ALK
B. Recurrent alterations in TP53 and RB1
C. Recurrent mutations in DDR2
D. Recurrent KRAS mutations.
Question 14.18 A 45-year-old male was diagnosed with stage II adenocarcinoma of the right
lung. Staging revealed ipsilateral hilar lymph-node involvement and no distant metastatic
disease. Patient underwent a sleeve resection of the tumor and his postoperative recovery
was uneventful. Which is the next preferred step in the management of his disease?
A. No further treatment, observation only.
B. Adjuvant chemotherapy with a doublet containing cisplatin
C. Adjuvant chemotherapy with a doublet containing carboplatin
D. Prophylactic cranial irradiation
Question 14.19 What is the most common histologic subtype of malignant mesotheliomas?
A. Epithelial
B. Sarcomatoid
C. Poorly differentiated
D. Biphasic
Question 14.23 Frequent alteration of which of the following novel tumor suppressor genes
is seen in mesothelioma?
A. RBL1
B. APC
C. RB1
D. BAP1
Question 14.25 A 60-year-old man was recently diagnosed with metastatic pleural
mesothelioma. Assuming that this patient has no other significant comorbidities, which of the
following chemotherapy regimens would be most preferable in the first-line setting?
A. Cisplatin and gemcitabine
B. Carboplatin and gemcitabine
C. Single agent pemetrexed
D. Cisplatin and pemetrexed
ANSWERS
Corresponding chapters in Cancer: Principles & Practice of Oncology, Tenth Edition: 40 (Molecular Biology of Lung Cancer), 41
(Non–Small Cell Lung Cancer), 42 (Small Cell and Neuroendocrine Tumors of the Lung), and 114 (Benign and Malignant
Mesothelioma).
15 Neoplasms of the Mediastinum
Gregory P. Kalemkerian
QUESTIONS
Each of the numbered items below is followed by lettered answers. Select the ONE lettered answer
that is BEST in each case unless instructed otherwise.
Question 15.1 A 46-year-old woman presents with dull anterior chest pain. She is a lifelong
nonsmoker. Her medical history is significant for Hashimoto thyroiditis, for which she has
been taking levothyroxine for 1 year. Examination is unremarkable. Chest radiograph reveals
clear lung fields with a retrosternal density. Computed tomography (CT) scan shows a 4-cm,
smooth, anterior mediastinal mass. Laboratory studies show normal blood counts, blood
chemistry, lactate dehydrogenase (LDH), α-fetoprotein (AFP), and β-human chorionic
gonadotropin (β-hCG). What is the most likely diagnosis?
A. Small cell lung cancer (SCLC)
B. Thymoma
C. Pericardial cyst
D. Nonseminomatous germ cell tumor (NSGCT)
Question 15.3 Which of the following statements regarding myasthenia gravis are TRUE?
(Select three correct responses).
A. Myasthenia gravis occurs in 30% to 50% of people with thymoma.
B. Ocular symptoms are the most common initial manifestation of myasthenia gravis.
C. Myasthenia gravis is caused by autoantibodies against presynaptic muscarinic
acetylcholine receptors.
D. Thymoma is diagnosed in 15% of people with myasthenia gravis.
Question 15.4 A 32-year-old man presents with an anterior mediastinal mass that was
identified incidentally on a chest radiograph done as part of an employment examination. He
is asymptomatic and a lifelong nonsmoker, with no significant medical history. Examination
is unremarkable. CT scan shows a 4-cm, smooth, lobulated, anterior mediastinal mass without
local invasion. Resection of the mass reveals an encapsulated, lymphocyte-rich thymoma
(World Health Organization [WHO] type B1) with no capsular invasion. He recovers from
surgery without complications. What is the most appropriate next step in the management of
this patient?
A. Clinical surveillance
B. Adjuvant radiotherapy alone
C. Adjuvant chemotherapy alone
D. Adjuvant chemotherapy plus radiotherapy
Question 15.5 Which of the following are the most appropriate systemic therapy options for
the treatment of advanced, stage IV thymoma? (Select two correct responses)
A. Gemcitabine and docetaxel
B. Cyclophosphamide, doxorubicin, and cisplatin
C. Cisplatin plus etoposide
D. Carboplatin plus paclitaxel
Question 15.6 Which of the following paraneoplastic syndromes are associated with
thymoma? Select all that apply.
A. Myasthenia gravis and pure red cell aplasia
B. Subacute cerebellar degeneration and gynecomastia
C. Polymyositis and hypothyroidism
D. Opsoclonus/myoclonus syndrome and Pel–Ebstein fever
Question 15.7 Which of the following molecularly targeted therapies has meaningful clinical
activity in advanced thymoma?
A. Octreotide, a somatostatin analog
B. Erlotinib, an EGFR inhibitor
C. Imatinib, a c-kit inhibitor
D. Sorafenib, a multitargeted kinase inhibitor
Question 15.8 A previously healthy 51-year-old man presents with facial and bilateral upper
extremity edema that has progressed over the past 2 weeks. Examination reveals moderate
facial, cervical, and bilateral upper extremity edema and prominent anterior chest wall
vasculature. He is tachycardic, but his heart sounds are regular and his lungs are clear. There
is no lower extremity edema. CT scan of the chest shows a large anterior mediastinal mass
encasing and narrowing the superior vena cava, and invading the pericardium and upper lobe
of the left lung. There are numerous dilated, intrathoracic collateral vessels. An experienced
thoracic surgeon deems that the lesion is primarily unresectable. Mediastinotomy with biopsy
of the mass reveals well-differentiated thymic carcinoma (WHO type B3). PET scan shows the
large FDG-avid mediastinal mass with no evidence of metastatic disease. What is the most
appropriate management of this patient?
A. Palliative radiotherapy followed by chemotherapy
B. Definitive radiotherapy with concurrent chemotherapy
C. Neoadjuvant chemotherapy followed by surgical resection and postoperative
radiotherapy
D. Palliative chemotherapy alone
Question 15.9 Which of the following histologic subtypes is associated with a more
favorable outcome in patients with thymic carcinoma?
A. Clear cell carcinoma
B. Well-differentiated squamous cell carcinoma
C. Sarcomatoid differentiation
D. Small cell carcinoma
Question 15.10 Thymic carcinoid is associated with which genetic predisposition syndrome?
A. Multiple endocrine neoplasia type 1 (MEN 1)
B. Louis–Bar syndrome
C. Li–Fraumeni syndrome
D. Cowden syndrome
Question 15.11 A 21-year-old man presents with anterior chest pain and cough. Physical
examination is unremarkable and his performance status is excellent. Chest radiography
shows widening of the superior mediastinum. CT scan shows a 6-cm anterior mediastinal
mass encasing the trachea and great vessels and three 1-cm pulmonary nodules. CT scan of
the abdomen and pelvis and a testicular ultrasound examination are normal. Laboratory
studies reveal normal blood counts and blood chemistry, LDH of 880 IU/L (normal, 120 to
240 IU/L), AFP of 1,800 ng/mL (normal, <8 ng/mL), and β-hCG of 1.2 mIU/mL (normal,
<5 mIU/mL). What is the most likely diagnosis?
A. Hodgkin lymphoma
B. Benign teratoma
C. Nonseminomatous germ cell tumor (NSGCT)
D. Seminoma
Question 15.12 Which of the following statements is TRUE regarding mediastinal germ cell
tumors?
A. The incidence of malignant mediastinal germ cell tumors is the same in men and
women.
B. Seminoma is the most common mediastinal germ cell tumor.
C. An elevated serum AFP in a patient with biopsy-proven seminoma indicates the
presence of a nonseminomatous component.
D. Mediastinal NSGCTs are associated with better overall survival than testicular NSGCTs.
Question 15.13 A 33-year-old woman presents with a cough and dyspnea on moderate
exertion. Physical examination shows an anxious woman with a pulse of 110 beats/min, a
respiratory rate of 24 breaths/min, and mild stridor. Lungs are otherwise clear to
auscultation, and heart sounds are regular. Chest radiography shows a large anterior
mediastinal mass with narrowing of the midtrachea. CT scan shows a 10-cm, heterogeneous,
anterior mediastinal mass with foci of dense calcification that compresses the trachea and
narrows, but does not obstruct, the superior vena cava. Laboratory studies reveal normal
blood counts, blood chemistry, LDH, carcinoembryonic antigen (CEA), AFP, and β-hCG. She
undergoes complete resection of the mass. Pathologic evaluation reveals a multicystic mass
with foci of mature gland formation, respiratory epithelium, cartilage, and bone. There is no
invasion into adjacent structures, and surgical margins are negative. What is the most
appropriate management of this patient?
A. Clinical surveillance
B. Adjuvant radiotherapy
C. Cisplatin plus etoposide × 4 cycles
D. Doxorubicin plus ifosfamide × 6 cycles
Question 15.14 A 23-year-old man presents with hoarseness, cough, and anterior chest pain.
He has a 10 pack-year smoking history. Physical examination is normal. Chest radiography
shows a large left mediastinal mass and clear lung fields. CT scan of the chest shows a 5-cm
irregular left paratracheal mass. Serum CEA, β-hCG, and AFP are normal. Left
mediastinotomy with biopsy of the anterior mediastinal mass reveals a poorly differentiated
malignant neoplasm that is immunohistochemically negative for leukocyte common antigen,
vimentin, S100, TTF1 and chromogranin, but positive for low–molecular-weight cytokeratin.
Genetic studies reveal no B- or T-cell rearrangements, and karyotypic analysis shows
aneuploidy and isochromosome 12p. Which of the following is the most appropriate therapy
for this patient?
A. Cisplatin plus etoposide
B. Cisplatin, etoposide, and bleomycin (BEP)
C. Concurrent chemotherapy and radiation therapy
D. Cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)
Question 15.15 A previously healthy 28-year-old man presents with fatigue and vague chest
discomfort. A chest radiograph shows a widened mediastinum, and a CT scan confirms a 9-cm
anterior mediastinal mass with focal hemorrhage that fills the substernal space and invades
into the upper lobe of the left lung. Laboratory studies show LDH of 850 IU/L (normal, 120
to 240 IU/L), AFP of 8,700 ng/mL (normal, <8 ng/mL), and β-hCG of 220 mIU/mL (normal,
<5 mIU/mL). Biopsy confirms embryonal carcinoma with elements of choriocarcinoma.
After four cycles of cisplatin, etoposide, and bleomycin (BEP), a CT scan shows marked
shrinkage of the mediastinal mass, now 3 cm in maximal diameter. One month after
completion of therapy, LDH is 150 IU/L, AFP is 5 ng/mL, and β-hCG is 2.4 mIU/mL. Which
of the following is the most appropriate management of this patient?
A. Clinical surveillance
B. Cisplatin, ifosfamide, and vinblastine (VIP)
C. Two additional cycles of cisplatin, etoposide, and bleomycin (BEP)
D. Resection of the residual mediastinal mass
Question 15.16 A 22-year-old man has a retrosternal mass identified on a chest radiograph
done during his enlistment into military service. He is an asymptomatic nonsmoker with no
significant medical history. CT scan shows a 2.5-cm smooth anterior mediastinal mass
without local invasion. Serum LDH, β-hCG, and AFP are normal. Testicular ultrasound is
normal. He refuses primary surgical resection. A percutaneous core biopsy shows pure
seminoma. Which of the following is the most appropriate management of this patient?
A. Surgical resection
B. Radiotherapy
C. Cisplatin, etoposide, and bleomycin (BEP)
D. Cisplatin plus etoposide followed by surgical resection
Question 15.17 Mediastinal nonseminomatous germ cell tumors are associated with which
of the following? (Select two correct responses)
A. Myasthenia gravis
B. Acute megakaryocytic leukemia
C. Klinefelter syndrome
D. Thymic carcinoid
Question 15.18 A 30-year-old man presents with chest tightness and shortness of breath. A
chest radiograph shows a large mediastinal mass. CT scan shows a 9-cm, lobulated, anterior
mediastinal mass invading the left lung and the pericardium with a small pericardial effusion,
a 3-cm right paratracheal lymph node, and a 5-cm subcarinal lymph node. Echocardiogram
shows no tamponade. Serum LDH is 440 IU/L (normal, 120 to 240 IU/L), but AFP and β-hCG
are normal. Testicular ultrasound is normal. Bronchoscopic core biopsy of the subcarinal mass
reveals seminoma. Which of the following is the most appropriate initial management of this
patient?
A. Carboplatin plus etoposide
B. Radiotherapy
C. Surgical resection
D. Cisplatin plus etoposide
Question 15.19 A previously healthy 45-year-old man presents with hoarseness and vague
chest discomfort. A chest radiograph shows a widened mediastinum, and a CT scan confirms a
large anterior mediastinal mass encasing the trachea and abutting the superior vena cava, left
pleura, and superior pericardium. Serum AFP is normal, but β-hCG is 10 mIU/mL (normal,
<5 mIU/mL). Biopsy shows seminoma. He is treated with cisplatin, etoposide, and
bleomycin (BEP). CT scan after treatment shows marked shrinkage of the mediastinal mass,
now 2 cm in maximal diameter. β-hCG is 1.2 mIU/mL. Which of the following is the most
appropriate management of this patient?
A. Clinical surveillance
B. Cisplatin, ifosfamide, and vinblastine (VIP)
C. Resection of the residual mediastinal mass
D. Involved-field radiotherapy
Question 15.20 Which of the following is TRUE for mediastinal germ cell tumors according
to the International Germ Cell Consensus Classification (IGCCC)?
A. All pure mediastinal seminomas are good risk
B. All mediastinal nonseminomatous germ cell tumors are poor risk
C. Pure mediastinal seminomas with nonpulmonary visceral metastases are poor risk
D. Mediastinal nonseminomatous germ cell tumors without visceral metastases are
intermediate risk
ANSWERS
Corresponding chapter in Cancer: Principles & Practice of Oncology, Tenth Edition: 43 (Neoplasms of the Mediastinum).
16 Esophagus and Stomach Cancer
Hassan Hatoum and Renuka Iyer
QUESTIONS
Each of the numbered items below is followed by lettered answers. Select the ONE lettered answer
that is BEST in each case unless instructed otherwise.
Question 16.1 Which of the following statements about the incidence of esophageal cancer
is TRUE?
A. Esophageal cancer is relatively uncommon in the United States, and the lifetime risk of
being diagnosed with the disease is less than 1%.
B. Incidence rates among white men continue to increase and now exceed 8 per 100,000
person-years, and reflect the marked increase in the incidence of adenocarcinoma of the
esophagus of more than 400% in the past 2 decades.
C. Although the incidence of adenocarcinoma in white women (2 per 100,000) is lower
than that in white men, rates of adenocarcinoma have increased in women by more
than 300% during the past 20 years.
D. Only A and B
E. All of the above
Question 16.2 Which of the following statements are TRUE? (Select two correct responses)
A. Blood group B has been associated with gastric cancers.
B. Most of the patients with Helicobacter pylori infection will develop gastric cancer.
C. Epstein–Barr virus infection has been noted in a certain type of gastric carcinoma.
D. WHO classifies H. pylori infection as class I carcinogen.
Question 16.3 Which of the following are risk factors for development of esophageal
adenocarcinoma? (Select two correct responses)
A. Gastroesophageal reflux disease
B. Low BMI
C. Barrett esophagus
D. H. Pylori infection
Question 16.4 Which of the following is TRUE for cancer of the esophagus?
A. Adenocarcinoma has a better outcome compared to squamous cell carcinoma of the
esophagus.
B. HER2+ overexpression is an adverse prognostic factor similar to breast cancer.
C. The incidence of esophageal cancer is higher in African-American compared to
Caucasian men.
D. The lifetime risk of being diagnosed with esophageal cancer is 1%.
Question 16.5 Which of the following statement(s) about the molecular biology of
esophageal cancer is/are TRUE?
A. EGFR overexpression correlates with poor prognosis including poor response to
chemotherapy.
B. Presence of p53 point mutation correlates with response to induction chemotherapy and
predicts survival after esophagectomy.
C. Reduced expression of E-cadherin correlates with progression from Barrett esophagus to
dysplasia and finally to adenocarcinoma.
D. All of above
Question 16.6 Which of the following is TRUE about Barrett esophagus with high-grade
dysplasia?
A. Esophageal cancer incidence per year is 30%.
B. Esophagectomy is the only available treatment option.
C. Endoscopic mucosal resection can be used as a therapeutic option in this case.
D. Surveillance with annual endoscopy
Question 16.8 A 48-year-old man with a long-standing history of GERD presented to the
clinic with dysphagia and weight loss. The patient had EGD with biopsies that showed a
friable circumferential lesion in the lower part of the esophagus. EUS revealed a cT3 lesion
with one regional lymph node. CT and PET scan for evaluation did not show any distant sites
of metastasis. Initial treatment with preoperative chemoradiation using weekly carboplatin
and paclitaxel was suggested for the patient. Which of the following is TRUE for this
treatment modality?
A. The rate of pathologic complete response is 5%.
B. Chemoradiation followed by surgery can be used only for localized esophageal
adenocarcinoma but not squamous cell carcinoma.
C. Chemoradiation followed by surgery improves PFS but not OS compared to surgery
alone.
D. Chemoradiation followed by surgery improves both PFS and OS compared to surgery
alone.
Question 16.9 A 54-year-old male has a 10-year history of untreated GERD. He presents to
his primary care physician with melena. The patient underwent EGD which revealed a mass
in the GEJ junction that is biopsy proven to be adenocarcinoma. EUS and PET-CT scan
showed a mass that is abutting the diaphragm, but no evidence of distant metastasis. The
patient has no comorbid conditions and has very good performance status. What of the
following responses are TRUE about using perioperative chemotherapy ECF? (Select two
correct responses)
A. The lesion is not resectable and hence only chemotherapy should be offered.
B. There was a 6-month improvement in progression-free survival, a 4-month
improvement in median survival.
C. There was 25% pathologic complete response seen.
D. The use of ECF in this setting did not increase the rate of curative resection though it
improves survival.
Question 16.10 A 49-year-old female with a long-standard history of GERD presents to her
gastroenterologist with worsening abdominal pain, weight loss, and heart burn. EGD with
biopsy shows a tumor in the lower third of the esophagus. Biopsy reveals high-grade
adenocarcinoma. EUS shows cT3 and one paraesophageal lymph node. CT scan and PET scan
done for staging shows multiple liver lesions consistent with metastasis. The patient has no
comorbidities and her performance status is 0. Which of the following is the most appropriate
next step?
A. Chemotherapy with cisplatin and 5FU
B. Docetaxel, cisplatin, and 5FU
C. Epirubicin, cisplatin, and 5FU
D. Check for HER2 overexpression on the esophageal tumor tissue
Question 16.11 In the question above, HER2 was overexpressed on the tumor tissue. Which
treatment do you offer?
A. Chemotherapy
B. Chemotherapy plus cetuximab
C. Chemotherapy plus trastuzumab
D. Supportive care
Question 16.12 Which of the following cases would be sent for genetic testing? (Select two
correct responses)
A. A patient with gastric cancer histopathologically confirmed as diffuse and older than 50
years with a first-degree relative with stomach cancer at the age of 55.
B. A patient with diffuse gastric cancer, who has an uncle with stomach cancer diagnosed
at the age of 45 years with an aunt with lobular breast cancer.
C. A 37-year-old man diagnosed with diffuse gastric cancer, and no family history of
gastric cancer.
D. A 62-year-old male smoker diagnosed with gastric cancer and history of nasopharyngeal
cancer.
Question 16.13 Which of the following syndrome is usually associated with intestinal type
of gastric cancer?
A. Lynch syndrome
B. Li–Fraumeni syndrome
C. Familial adenomatous polyposis syndrome
D. Peutz–Jeghers syndrome
Question 16.14 Which of the following gene mutations is associated with the highest gastric
cancer risks?
A. BRCA1/2
B. P53
C. CDH1
D. APC
Question 16.15 A 22-year-old woman is diagnosed with metastatic gastric cancer, with
diffuse involvement of the stomach and linitis plastica. Her father died of the same cancer at
an age of 42 years. Her mother is concerned about familial gastric cancer and is asking for
information about hereditary gastric cancer and appropriate screening for her other children.
Which of the following would be the most appropriate recommendation to this family?
A. Hereditary gastric cancer is rare and unlikely. She may just have some environmental
exposures or DNA mismatch repair gene mutations that cannot be screened for.
B. She may very well have hereditary early onset diffuse gastric cancer, but no
surveillance or workup is recommended because this has yet to be confirmed in larger
studies.
C. E-cadherin mutation testing should be considered here, and, in fact, prophylactic
gastrectomy should be considered strongly for her siblings if a germline E-cadherin
mutation is confirmed and mucosal abnormality can be documented by endoscopic
examination of the stomach.
D. E-cadherin mutation testing should be considered, and, in fact, prophylactic
gastrectomy should be considered strongly for her siblings if a germline E-cadherin
mutation is confirmed even if no mucosal abnormalities are seen by endoscopic
examination of the stomach.
Question 16.16 Which of the following is TRUE about the use of diagnostic modalities in
patients with gastric cancer?
A. PET scan is less useful in assessing metastasis of signet cell subtype.
B. The accuracy rate of CT scan for staging of advanced gastric cancer was 96%.
C. There is no role for laparoscopy if staging CT scan was negative.
D. Brain MRI should be routinely done as part of the initial work up.
Question 16.17 A 48-year-old male who was diagnosed with adenocarcinoma of the stomach
underwent partial gastrectomy. PET-CT prior to surgery shows no evidence of distant
disease. He had 1 of 18 lymph nodes removed involved with cancer. Margins were negative
for cancer. The pathologic stage is IIB (T3 N1 tumor). He was referred to you to discuss
adjuvant treatment options. He has an ECOG performance status of 1. What is the best
treatment modality?
A. Chemotherapy with Carboplatin and Paclitaxel
B. There is no evidence for benefit from adjuvant treatment in this case.
C. 5FU and leucovorin, followed by 45 Gy in 25 fractions plus concurrent 5FU and
leucovorin.
D. Check for HER2 over expression and if positive, treat with cisplatin/5FU plus
trastuzumab.
Question 16.18 A 48-year-old gentleman presents to the clinic with abdominal pain and
weight loss. CT scan of the abdomen and pelvis showed diffuse gastric wall thickening as
well as liver lesions suspicious for metastasis. CT-guided biopsy of one of the lesions
confirmed metastatic adenocarcinoma of the stomach. HER2 was not overexpressed on the
tumor tissue. Which of the following are TRUE regarding combination chemotherapy for the
treatment of metastatic gastric cancer? (Select two correct responses)
A. Cisplatin is superior to oxaliplatin with a better OS.
B. 5FU is superior to capecitabine with better OS.
C. Oxaliplatin is noninferior to cisplatin in terms of OS.
D. Capecitabine is noninferior to 5FU in terms of OS.
Question 16.19 57-year-old man presented to your clinic for a second opinion on treatment
of metastatic HER2 negative gastric cancer. The patient has received first-line treatment with
epirubicin/cisplatin/5FU. On his last evaluation, his CT scan of the chest, abdomen, and
pelvis showed progression of the disease in the lungs and liver. The patient remains
asymptomatic except for fatigue. His weight is stable and his performance status is 1. Blood
work included CBC that showed mild anemia and his chemistry panel including liver function
test and bilirubin was normal. Which of the following is the best recommendation for this
patient?
A. Refer to hospice
B. Erlotinib single agent
C. Ramucirumab single agent
D. Trastuzumab/cisplatin/capecitabine
Corresponding chapters in Cancer: Principles & Practice of Oncology, Tenth Edition: 44 (Molecular Biology of the Esophagus
and Stomach), 45 (Cancer of the Esophagus), 46 (Cancer of the Stomach), and 47 (Genetic Testing in Stomach Cancer).
17 Pancreatic and Hepatobiliary Cancer
Thomas Regenbogen and Andrea Wang-Gillam
QUESTIONS
Each of the numbered items below is followed by lettered answers. Select the ONE lettered answer
that is BEST in each case unless instructed otherwise.
Question 17.1 Which of the following factors are associated with an increased risk of
pancreatic cancer?
A. Cigarette smoke
B. Chronic pancreatitis
C. Prior cholecystectomy
D. African-American ethnicity
E. All of the above
Question 17.2 Which of the following statements regarding pancreatic cancer is TRUE?
A. At diagnosis, 31% have evidence of distant metastases.
B. Pancreatic cancer decreases in incidence later in life.
C. Activation of the KRAS oncogene plus inactivation of tumor suppressor genes (TP53,
DPC4, p16, and BRCA2) are associated with the development of pancreatic cancer.
D. Pancreatic intraepithelial neoplasms (PanINs) are intraductal proliferative epithelial
lesions that will not progress to pancreatic cancer.
E. Patients with advanced pancreatic cancer will have high levels of CA 19-9 if they are
Lewis antigen-a or -b negative.
Question 17.3 A 56-year-old man is evaluated for a 1-month history of gradually worsening
painless jaundice and a 10-lb weight loss. Computed tomography (CT) scan of the abdomen
and pelvis revealed a 3.3-cm pancreatic head mass adjacent to the superior mesenteric vein
with no intervening fat plane and encasing both the superior mesenteric vein and artery. The
common bile duct was dilated and the pancreatic body and tail were atrophied with dilatation
of the pancreatic duct. Portal lymphadenopathy measuring 2 cm was present. The patient
underwent endoscopic retrograde cholangiopancreatography and a biliary stent was placed.
Biopsy tissue of the mass was consistent with moderately differentiated pancreatic
adenocarcinoma. What stage is this patient’s cancer per the TNM staging system?
A. Stage I
B. Stage II
C. Stage III
D. Stage IV
Question 17.4 A 67-year-old woman presents to her local emergency department with a 2-
month history of right upper quadrant pain, jaundice, and 20-lb weight loss. CT of the
abdomen with contrast reveals a 2.5-cm, ill-defined soft tissue density within the head of the
pancreas and mild celiac axis, porta hepatis, and portacaval adenopathy, with the largest
being within the celiac axis region measuring 2.0 × 1.8 cm. Following admission endoscopic
retrograde cholangiopancreatography with biliary stent placement and biopsy is done.
Pathology reports poorly differentiated adenocarcinoma. What test should be ordered at this
point to help establish her stage?
A. Multiphase multidetector helical computerized tomography
B. Magnetic resonance imaging
C. Ultrasonography
D. Serum CA 19-9 measurement
E. Endoscopic ultrasonography
Question 17.5 A 71-year-old woman undergoes Whipple resection for a T3N1M0 pancreatic
adenocarcinoma. Postoperative recovery was uneventful, and she starts adjuvant therapy 7
weeks later with gemcitabine given intravenously weekly for 3 weeks, followed by a 1-week
break. In a follow-up visit after her first cycle, she reports a 5-lb weight loss, nausea,
decreased appetite, and diarrhea with floating stools. What should be done next?
A. Increase pancreatic enzyme supplementation
B. Admit the patient for small bowel obstruction
C. Hold chemotherapy for 1 week and follow up on symptoms
D. CT scan of the chest, abdomen, and pelvis to rule out metastatic disease
Question 17.6 Which of the following statements regarding adjuvant therapy of pancreatic
adenocarcinoma is TRUE?
A. In RTOG 9704 administering gemcitabine before and after adjuvant 5-FU based CRT for
resected pancreatic head adenocarcinoma demonstrated a trend toward improved
median OS compared with 5-FU before and after 5-FU CRT.
B. CONKO-001 demonstrated gemcitabine when compared with observation improves
disease free survival but not overall survival.
C. GITSG 9173 clearly showed no benefit with 5-FU based chemoradiation followed by
chemotherapy compared with observation.
D. ESPAC-1 showed that those who received CRT did better than those treated with
chemotherapy alone.
Question 17.8 A 52-year-old woman is evaluated for chronic right upper quadrant
abdominal pain and is diagnosed with pancreatic adenocarcinoma with metastasis to the
liver. She is distraught and wants to do everything possible to prolong her life. Which of the
following regimens has been shown to prolong overall survival compared with gemcitabine
alone?
A. Gemcitabine and oxaliplatin
B. Gemcitabine and capecitabine
C. Gemcitabine and nab-paclitaxel
D. Gemcitabine, cisplatin, and bevacizumab
E. Gemcitabine and cetuximab
Question 17.9 A 45-year-old man with unintentional weight loss is diagnosed with
metastatic adenocarcinoma of the pancreas. Which of the following chemotherapy regimens
would be appropriate first-line treatment choice in this otherwise healthy patient with normal
organ function?
A. Gemcitabine
B. FOLFIRINOX (5FU, leucovorin, irinotecan, and oxaliplatin)
C. 5FU with radiation
D. FOLFOX (5FU + leucovorin + oxaliplatin)
Question 17.10 Mutation of which tumor suppressor gene is most frequently associated with
familial pancreatic cancer?
A. BRCA2
B. PALB2
C. KRAS
D. TP53
Question 17.11 Which one of the following statements regarding risk factors for pancreatic
cancer is CORRECT?
A. People with blood types A, B, and AB are more likely than type O to develop pancreatic
cancer.
B. Testing for KRAS mutations in the pancreatic juice of patients is an effective screening
test for pancreatic cancer.
C. Patients with hereditary nonpolyposis colorectal cancer syndrome do not have an
increased risk for pancreatic cancer.
D. Hereditary pancreatitis is not a significant risk factor for pancreatic cancer.
Question 17.12 A 65-year-old male diagnosed with metastatic pancreatic cancer received
treatment with single-agent gemcitabine. He now has disease progression and is interested in
pursuing further systemic therapy. Which one of the following should be offered as a second-
line treatment choice?
A. OFF (oxaliplatin, 5FU, and leucovorin)
B. Erlotinib
C. Paclitaxel
D. Supportive care alone
Question 17.13 Which of the following is/are TRUE about pancreatic cancer?
A. Most pancreatic cancers have mutations in KRAS, TP53, SMAD4, p16/CDKN2A.
B. Telomere shortening is the earliest and prevalent genetic change identified in the
precursor lesions.
C. Underexpression of TGF-β is observed in some pancreatic cancers.
D. p16-mediated CDK inhibition is a protective mechanism against pancreatic cancer.
E. All of the above.
Question 17.14 A 52-year-old man is found to have mildly abnormal liver function and an
elevated serum α-fetoprotein (AFP). Workup reveals prior hepatitis B viral (HBV) infection.
Ultrasound reveals a 4-cm lesion in the left hepatic lobe, and a computed tomography (CT)
scan reveals no evidence of metastatic disease or vascular involvement. MRI demonstrates
features consistent with hepatocellular carcinoma (HCC). The patient undergoes partial
hepatectomy, surgical margins are clear. The pathology report confirms the diagnosis of
HCC. Which of the following approaches should be followed?
A. Adjuvant sorafenib
B. Combination chemotherapy that is doxorubicin based
C. Adjuvant external beam radiation to surgical bed
D. Routine surveillance
Question 17.15 Which of the following criteria help(s) guide selection of patients with HCC
appropriate for potential liver transplantation?
A. Patients with solitary tumors ≤5 cm, or patients with multifocal disease with ≤3
tumor nodules each ≤3 cm in size
B. Patients with Child–Pugh B or C cirrhosis
C. Tumors without evidence of macrovascular invasion and distant metastasis
D. All of the above
Question 17.16 Which of the following statements about staging systems for hepatocellular
carcinoma is TRUE?
A. The Okuda system takes into account several clinical features that include tumor size
(>50% of liver), ascites (positive or negative), hypoalbuminemia (<3 g/dL), and
hyperbilirubinemia (>3 mg/dL).
B. The Cancer of the Liver Italian Program system uses hepatic tumor morphology and
extent of liver replacement, Child–Pugh score, portal vein thrombosis, and serum AFP
levels.
C. The Barcelona Clinic Liver Cancer scoring system combines assessment of tumor stage,
liver function, and patient symptoms with a treatment algorithm and has been shown to
correlate well with patient outcomes.
D. All of the above.
Question 17.18 An increased risk of developing HCC is associated with which of the
following?
A. Wilson disease
B. Hereditary tyrosinemia
C. Porphyria cutanea tarda
D. Primary biliary cirrhosis
E. All of the above
Question 17.19 Which of the following statements about screening and prevention is
CORRECT?
A. The advent of vaccination for hepatitis B is unlikely to reduce HCC in endemic areas.
B. A combination of AFP and ultrasound screening is used in high-risk populations.
C. Aggressive screening programs for HCC have been shown to improve survival.
D. Detection of HCC, through surveillance of patients awaiting liver transplantation, does
not increase priority for orthotopic liver transplantation.
Question 17.21 A 66-year-old man is noted to have painless jaundice on a routine follow-up
at his primary care physician’s office. Workup reveals a mass causing biliary obstruction at
the hilum. Endoscopic retrograde cholangiopancreatography confirms a high-grade stricture
predominantly involving the left hepatic duct; however, brushings reveal atypical cells and
no malignancy. He is seen at a tertiary care center and offered surgical management, an en
bloc resection of the left hepatic lobe and extrahepatic bile duct, and a complete periportal
lymphadenectomy. Which of the following statements about management/natural history of
hilar cholangiocarcinoma is/are TRUE?
A. Surgical resection is associated with an operative mortality rate of 30%.
B. Recurrences occur most commonly at the bed of resection, followed by retroperitoneal
lymph nodes. Distant metastases occur in one-third of cases.
C. Less than 10% of patients have resectable cancer at the time of diagnosis.
D. All of the above.
Question 17.22 A 70-year-old man presents with 16-lb weight loss and persistent right upper
quadrant pain. CT scan reveals a gall bladder stone and thickening of the anterior wall of the
gall bladder. He undergoes a laparoscopic cholecystectomy. Pathology reveals a moderately
differentiated 2-cm gallbladder adenocarcinoma invading the perimuscular connective tissue.
Margins of resection are negative for tumor. Based on the available information, what is the
stage of this cancer?
A. Stage IA
B. Stage IB
C. Stage II
D. Stage IIIA
Question 17.23 The patient in Question 17.22 recovers from surgery and seeks a second
opinion at a tertiary care center 5 weeks after his cholecystectomy. A CT scan 2 weeks after
surgery shows mild periportal fullness. What is the most appropriate next step in
management?
A. Perform en bloc resection of the gallbladder, resection of segments IVb and V of the
liver, and regional lymph node dissection.
B. No further therapy is warranted; surveillance with CT scans and laboratories done every
3 months.
C. He requires a second laparotomy to assess the extent of remaining disease to guide
further therapy.
D. Perform ultrasound-guided biopsy of the periportal nodes; if positive, then
fluoropyrimidine-based chemoradiation is indicated.
Question 17.24 Which one of the following statements about adjuvant therapy for biliary
cancers is TRUE?
A. Based on retrospective data it appears patients may benefit from adjuvant
chemotherapy.
B. Adjuvant radiation is superior to chemotherapy alone.
C. Adjuvant therapy can improve overall survival for patients with R0 resections.
D. Fluoropyrimidine-based chemoradiation is standard because it is superior to radiation
alone.
Question 17.29 Which of the following statement(s) regarding hepatitis C infection is/are
CORRECT?
A. Sixty percent to 80% HCV infections become chronic in contrast to 10% HBV infections.
B. HBV genome integrates into hepatocyte DNA while HCV genome does not.
C. The average interval from HCV infection to HCC is 30 years in contrast to 40 to 50
years for HBV infection.
D. All of the above.
Question 17.30 A 45-year-old man with a history of alcoholic cirrhosis was found by
screening ultrasound to have two new lesions in hepatic segments 7 and 3, measuring 3 cm
and 2 cm, respectively. MRI findings were consistent with hepatocellular carcinoma. He has
been abstinent from alcohol use for the past 2 years. His total bilirubin is 1.5 mg/dL, serum
albumin 3 g/dL and INR is 1.6. He does not have ascites or encephalopathy. There is no
evidence of metastatic disease and he is referred for orthotopic liver transplantation
evaluation. He is deemed to be an acceptable candidate. While waiting for a donor organ,
what should be done next?
A. Refer to interventional radiology for ablative therapy
B. Sorafenib to prevent disease progression while waiting for donor organ
C. Cisplatin, IFNα-2b, doxorubicin, and 5FU as neoadjuvant therapy
D. Observation
Question 17.31 A 45-year-old woman presents with painless jaundice and weight loss. Her
total bilirubin is 17.6 mg/dL, alkaline phosphatase is 568 units/L and alanine transaminase
(ALT) is 138 units/L. Viral hepatitis serology is negative. CT chest abdomen and pelvis with
contrast is performed and reveals an ill-defined, infiltrative, hypoattenuating lesion at the
hepatic hilum with marked intrahepatic biliary ductal dilatation. MRI of the liver
characterizes the lesion as compatible with cholangiocarcinoma centered in the hepatic hilum
extending to the confluence of the left medial and lateral hepatic ducts, involving the cystic
duct, proximal extrahepatic duct, and abutting the undersurface of the portal vein and right
hepatic artery. ERCP is performed with common bile duct stenting. Pathology reports
atypical epithelial cells in the brushing. Hepatobiliary surgery is consulted and determines
that her tumor is unresectable and she is not a liver transplant candidate due to psychosocial
issues. What is the next step in management once hyperbilirubinemia resolves?
A. FOLFOX
B. Gemcitabine and cisplatin
C. External beam radiation therapy with concurrent 5FU
D. Palliative care alone including routine stent exchange
Question 17.32 Which of the following individuals would meet criteria to have surveillance
for HCC?
A. A 28-year-old African woman who is a hepatitis B carrier.
B. A 47-year-old Indian woman who is hepatitis B carrier and has a brother with HCC.
C. A 62-year-old Hispanic male with alcoholic cirrhosis.
D. A 42-year-old Chinese man who is a hepatitis B carrier.
E. All of the above
Question 17.33 A 52-year-old man is admitted to the hospital due to new onset of
symptomatic ascites and jaundice. He is an alcoholic and has no history of medical care prior
to this encounter. He is mildly encephalopathic. Serum total bilirubin is 5.6 mg/dL and INR is
2.1. He is diagnosed with unresectable metastatic hepatocellular carcinoma and alcoholic
cirrhosis after an extensive work up. The patient’s family arrives and would like to discuss
treatment options. Your recommendation will be:
A. Gemcitabine and oxaliplatin.
B. Sorafenib.
C. Sunitinib.
D. Hospice or supportive care alone
ANSWERS
Corresponding chapters in Cancer: Principles & Practice of Oncology, Tenth Edition: 48 (Molecular Biology of Pancreas
Cancer), 49 (Cancer of the Pancreas), 51 (Molecular Biology of Liver Cancer), 52 (Cancer of the Liver), and 53 (Cancer of the
Biliary Tree).
18 Small Bowel Cancers and Gastrointestinal Stromal
Tumors (GIST)
Benjamin R. Tan, Jr.
QUESTIONS
Each of the numbered items below is followed by lettered answers. Select the BEST answer(s).
Question 18.1 A 60-year-old previously healthy woman noted abdominal distension and
discomfort for 6 months, associated with nausea and vomiting. Computed tomography (CT)
scan shows a 20 × 25-cm abdominal mass, and exploratory laparotomy demonstrated a
pedunculated mass arising from the stomach. No other metastases were found. A partial
gastrectomy was done, and pathology revealed a gastrointestinal stromal tumor (GIST) which
strongly stains for CD117 and CD34. Sixty mitoses were seen per 50 high-power field (HPF).
Which of the following is TRUE regarding GISTs?
A. The most common mutation associated with GIST involves the inactivation of a tumor
suppressor gene.
B. Both tumor size and mitotic index predict response to imatinib therapy.
C. Gastric GISTs are associated with relatively worse outcomes compared with small
intestinal GISTs.
D. Patients with metastatic GIST tumors harboring exon 9 mutations have a better
prognosis and response to imatinib compared with those with exon 11 mutation.
E. None of the above.
Question 18.2 After the patient in Question 18.1 has recovered from surgery, what would
you recommend for this patient on the basis of current data?
A. Observation with serial scans
B. Imatinib 400 mg per os (PO) daily for 1 year
C. Imatinib 400 mg PO daily for at least 3 years
D. Sunitinib 50 mg 4 weeks on/2 weeks off therapy for 5 years
Question 18.3 A 52-year-old woman with metastatic gastric GIST had an initial complete
response to daily imatinib 400 mg with resolution of her hepatic and peritoneal metastases
after 6 months of therapy. Imatinib was continued for 18 months when her CT scan showed
recurrent hepatic lesions. Imatinib was increased to 800 mg daily. However, subsequent scans
revealed progressive disease. You recommend starting sunitinib for this patient. Which of the
following statements are TRUE? (Select two correct responses)
A. Acquired resistance to imatinib therapy may be associated with the development of
secondary KIT or PDGFRA mutations.
B. Sunitinib therapy for patients with imatinib-resistant GIST improved progression-free
survival compared with placebo.
C. Patients with GIST harboring exon 11 mutation have a higher response to sunitinib than
those with exon 9 mutation.
D. Patients with the wild-type GIST are resistant to both imatinib and sunitinib therapy.
Question 18.4 The patient in Question 18.3 started sunitinib 50 mg daily for 28 days
followed by a 2-week break. After two cycles, repeated CT scans showed a decrease in the
measurable lesions. In addition to hypopigmentation of her hair, she also noted progressive
generalized fatigue. Patient denies any dyspnea on exertion, diarrhea, or pedal edema.
Physical examination reveals an erythematous rash in the hands, clear lungs, no cardiac
gallops or rubs, and no focal neurologic deficits. Pertinent laboratory tests are as follows:
White blood cell 5.6 × 103 cells/μL
Hemoglobin 11.8 g/dL
Sodium 145 mmol/L
Potassium 4.5 mmol/L
Creatinine 0.8 mg/dL
Total bilirubin 0.5 mg/dL
Alkaline phosphatase 118 μ/L
What would you order next?
A. Magnesium level
B. Magnetic resonance imaging of the brain
C. Thyroid function tests
D. 25-Hydroxycholecalciferol level
Question 18.5 After 6 months of sunitinib therapy, the patient in Question 18.4 was noted to
have progression of her liver and omental lesions. Her Karnofsky performance status is 90%
and hematologic, renal, and hepatic functions are all adequate. She is interested in further
therapy. What would be your best recommendation?
A. No further therapy and proceed with hospice because there is no standard therapy after
second-line sunitinib.
B. Sorafenib
C. Regorafenib
D. Bevacizumab
Question 18.6 Familial and genetic syndromes associated with GIST are: (Select two correct
responses)
A. Cowden syndrome
B. Li–Fraumeni syndrome
C. Carney triad
D. Neurofibromatosis
Question 18.7 What is the most common type of small bowel malignancy?
A. Adenocarcinoma
B. Lymphoma
C. Carcinoid
D. Schwannoma
Question 18.8 Which of the following are characteristic of primary intestinal mucosal-
associated lymphoid tissue (MALT) lymphoma? (Select two correct responses)
A. Association with Hashimoto thyroiditis
B. The majority of patients present with stages I and II
C. Most common in women
D. Associated with the translocation t(11;14)
Question 18.9 A 50-year-old male presented with bloating, and tarry stools. Upper
endoscopy revealed a mass in the third portion of the duodenum, with the biopsy showing
moderately differentiated adenocarcinoma. Resection demonstrated three periduodenal
lymph nodes involved with carcinoma. CT scan showed no distant metastases. Which of the
following statements regarding small bowel adenocarcinoma is TRUE?
A. The duodenum is the most common location for adenocarcinoma.
B. Jejunal and ileal tumors are associated with worse outcomes compared to duodenal
adenocarcinoma.
C. Stage III small bowel adenocarcinoma is associated with a 63% survival.
D. Adjuvant therapy with irinotecan, 5-fluorouracil, and leucovorin is standard for stage III
duodenal adenocarcinoma.
Question 18.11 The risk for progressive disease for a patient with small intestinal GIST
measuring less than 2 cm with more than five mitoses/50 hpf is:
A. 0%
B. 4.3%
C. 24%
D. 50%
E. 85%
Question 18.12 A 20-year-old student presented to the emergency department with a 2-day
history of right lower abdominal pain associated with fever. His abdomen was slightly
distended with diffuse tenderness but without guarding or rebound tenderness. Rectal
examination showed no masses and was negative for occult blood. Complete blood count
showed a slightly elevated white blood cell at 11,000. CT scan showed a mass in the terminal
ileum with no evidence of free peritoneal air. Colonoscopy revealed a terminal ileum mass,
the biopsy of which showed sheets of monotonous round nucleated cells with abundant
basophilic cytoplasm with numerous macrophages. Ki-67 index was 100%. What is your
diagnosis?
A. MALT lymphoma
B. Burkitt lymphoma
C. Peripheral T-cell lymphoma
D. Medullary carcinoma of the small intestine
ANSWERS
Corresponding chapters in Cancer: Principles & Practice of Oncology, Tenth Edition: 54 (Cancer of the Small Bowel) and 55
(Gastrointestinal Stromal Tumor).
19 Colorectal and Anal Cancers
Ashley Morton and Benjamin R. Tan, Jr.
QUESTIONS
Each of the numbered items below is followed by lettered answers. Select the ONE lettered answer
that is BEST in each case unless instructed otherwise.
Question 19.1 A 30-year-old multigravid woman presents with a large abdominal mass
associated with abdominal pain. She underwent a total proctocolectomy for colon cancer
secondary to familial adenomatous polyposis (FAP) 4 years ago followed by adjuvant
chemotherapy for node-positive disease. A recent esophagogastric endoscopy revealed only a
tubulovillous adenoma in the duodenum but the computed tomography (CT) scan revealed a
10-cm mass filling the pelvis. Biopsy showed desmoid tumor. A TRUE statement regarding
desmoid tumors is:
A. Desmoid tumors represent the second most common cause of death for patients with
FAP.
B. Desmoid tumors are uniformly aggressive and locally invasive.
C. Adjuvant radiation is recommended.
D. Adjuvant chemotherapy is recommended.
Question 19.2 A 55-year-old woman underwent a right hemicolectomy for a cecal mass, 15
years ago. Four years later, she was found to have a hepatic flexure adenocarcinoma and a
total colectomy was performed. Four years ago, she presented with postmenopausal bleeding
and was found to have endometrial adenocarcinoma. She also had multiple skin malignancies,
including sebaceous adenomas and keratoacanthomas. One year ago, she underwent a
Whipple procedure for a duodenal adenocarcinoma invading into the pancreas. She has three
siblings and a paternal uncle with colorectal cancer all diagnosed in their late 30s. What is
the most probable primary genetic explanation for her inherited colorectal cancer syndrome?
A. Chromosomal instability characterized by the deletion or mutation of a tumor
suppressor gene
B. Chromosomal instability characterized by activation of an oncogene
C. Microsatellite instability (MSI) caused by germline mutations in a DNA mismatch repair
(MMR) gene
D. MSI caused by epigenetic changes associated with hypermethylation in CpG islands
Question 19.3 Other than genetic counseling, which test would you order to confirm the
diagnosis in the patient in Question 19.2?
A. TP53 mutation and loss of heterozygosity of chromosome 18q
B. APC mutation, including the I1307K allele
C. MSI testing and methylation of CpG islands
D. MSI test and MMR gene mutation including MLH1, MSH2, and MSH6
Question 19.4 The patient in Question 19.3 had a positive test result. What screening tests
and surveillance program would you recommend to her three daughters aged 24, 22, and 20
years?
A. Colonoscopy now and repeat every 1 to 2 years and transvaginal ultrasound for her
daughters starting at age 30 to 35 years
B. Colonoscopy for all and transvaginal ultrasound for her daughters starting at age 30 to
35 years
C. Colonoscopy now and repeat every 1 to 2 years with transvaginal ultrasound at age 30
to 35 years only for her children confirmed to have the same genetic mutation as the
patient; colonoscopy at age 40 to 50 years for those with no mutation
D. Colonoscopy and transvaginal ultrasound at age 30 to 35 years only for those confirmed
with the same mutation as the patient; colonoscopy at age 40 to 50 years for those with
no mutation
Question 19.5 Which gene is associated with hereditary nonpolyposis colorectal cancer
(HNPCC)?
A. APC
B. MYH
C. STK11
D. MSH2
Question 19.6 A 65-year-old woman presented with intermittent constipation and diarrhea
associated with abdominal cramping. A colonoscopy revealed a near-obstructing mass and
biopsy showed a villoglandular polyp. She underwent an exploratory laparotomy and
resection of a 5 × 5-cm circumferential necrotic and fungating mass. Pathology revealed a
moderately differentiated adenocarcinoma invading into the pericolonic fat with 2 of 30
positive lymph nodes. Margins were negative. CT scan showed no evidence of metastatic
disease. After recovery from her surgery, based on current evidence, you would recommend:
A. 5FU with leucovorin × 6 months
B. Capecitabine × 6 months
C. Irinotecan with 5FU (FOLFIRI) × 6 months
D. Oxaliplatin with 5FU (FOLFOX) × 6 months
E. Oxaliplatin with 5FU (FOLFOX) and bevacizumab × 6 months
Question 19.7 One week after the first dose of chemotherapy, the patient in Question 19.6
developed a fever of 102°F associated with chills. She also developed diarrhea, mucositis,
confusion, and ataxia. Repeat complete blood count showed a white blood cell count of 0.5 ×
103 cells/μL with an absolute neutrophil count of 100, hemoglobin of 11.7 g/dL, and platelet
count of 42,000. Which one of the following pharmacogenetic conditions would best explain
her clinical course?
A. The patient is homozygous for the thymidylate synthase (TYMS) *3/*3 polymorphism.
B. The patient is homozygous for UGT1A1*28 polymorphism.
C. The patient is heterozygous for the IVS14 + 1 G>A DPYD*2A mutation.
D. The patient is heterozygous for the ERCC2 Lys751Gln polymorphism.
Question 19.8 A 62-year-old engineer was diagnosed with metastatic cecal adenocarcinoma
to the lung and liver. He was initially treated with oxaliplatin plus infusional 5FU (FOLFOX6)
and bevacizumab. After four cycles (2 months), his CT scan showed progressive disease. You
discussed irinotecan 180 mg/m2 every 2 weeks plus weekly cetuximab based on the results of
the EPIC study. A test for UGT1A1 polymorphism was done, and results revealed him to be
homozygous for UGT1A1*28/*28. Which of the following statements is/are TRUE?
A. Patients homozygous for the UGT1A1*28 polymorphism glucuronidate SN38 more
efficiently than those with the wild-type *1 genotype.
B. Patients homozygous for the UGT1A1 *28 polymorphism glucuronidate SN38 less
efficiently than those with the wild-type *1 genotype.
C. Patients homozygous for UGT1A1*28 polymorphism are at greater risk for severe
neutropenia with irinotecan compared with those with the wild-type *1 genotype.
D. A and C are true.
E. B and C are true.
Question 19.9 A 52-year-old teacher presents with a 2-month history of rectal bleeding. A
rectal examination revealed a palpable nonobstructing mass 5 cm from the anal verge.
Subsequent colonoscopy confirmed a friable, tethered mass biopsy that showed moderately
differentiated adenocarcinoma. Transrectal ultrasound revealed a T3N1 cancer. CT scans of
the chest, abdomen, and pelvis revealed no metastatic sites. Which of the following treatment
strategies would you recommend?
A. Total mesorectal excision (TME) alone
B. TME followed by chemotherapy
C. TME followed by chemoradiation
D. Neoadjuvant 5FU-based chemoradiation followed by TME and adjuvant chemotherapy
Question 19.10 Which of the following appropriately staged patients with rectal cancer
would be the best candidate for transanal excision?
A. A 48-year-old woman with a 2.5-cm T1 moderately differentiated rectal
adenocarcinoma 4 cm from the anal verge.
B. A 65-year-old man with a 4.5-cm T2 well-differentiated circumferential rectal mass 6 cm
from the anal verge.
C. A 30-year-old man with a 2-cm well-differentiated T1 mucinous adenocarcinoma 12 cm
from the anal verge.
D. A 52-year-old woman with a 3-cm well-differentiated T1N1 adenocarcinoma 5 cm from
the anal verge.
E. None of the above.
Question 19.11 For the patient you have selected for transanal resection in Question 19.10,
pathologic review of the excised specimen showed no lymphovascular invasion and all
margins were negative. Which of the following options would you recommend?
A. No further therapy
B. Short-course (25 Gy/5 fractions) radiation
C. Intracavitary radiation
D. Adjuvant chemotherapy without radiation
E. Adjuvant chemotherapy with radiation
Question 19.12 Which of the following are TRUE statements regarding MYH-associated
polyposis? (Select two correct responses)
A. Inheritance is autosomal dominant.
B. Clinical features of MYH-related polyposis may be similar to FAP.
C. The MYH gene is a base-excision repair gene.
D. A deficiency in MYH leads to accumulation of germline mutations in the APC gene.
Question 19.13 A 49-year-old woman noted rectal bleeding for 2 months. She denied any
pain, diarrhea, constipation, or weight loss. A colonoscopy was done that revealed a 2-cm
low-lying mass 1 cm from the anal verge. A transrectal ultrasound revealed no lymph nodes.
Biopsy showed basaloid squamous cell carcinoma. CT scans of the abdomen and pelvis did
not reveal any metastatic disease. The BEST curative treatment option for this patient is:
A. APR
B. Short-course (25 Gy/5 fractions) radiation followed by APR
C. Neoadjuvant chemoradiation with 5FU followed by APR
D. Chemoradiation alone with 5FU and mitomycin
Question 19.14 A 58-year-old man presented with a 6-month history of anorexia, fatigue,
and a vague right-sided abdominal discomfort. His physical examination was unremarkable
except for mild pallor. Initial laboratory test revealed a hemoglobin level of 10.7 g/dL with a
mean corpuscular volume of 73. He also had mildly elevated alkaline phosphatase and
hepatic transaminases. Colonoscopy revealed a nonobstructing transverse colon mass. Biopsy
demonstrated moderately differentiated adenocarcinoma. CT scan revealed a 3-cm lesion in
the left lobe of the liver and two other lesions measuring 1.5 to 2 cm in the right lobe of the
liver. Positron emission tomography revealed uptake in the transverse colon and all three
known hepatic lesions. Among the following options, what would be the best option for this
patient based on current studies?
A. Curative-intent resection of the transverse colon primary and all three hepatic lesions
followed by active surveillance
B. Palliative-intent front-line chemotherapy with bevacizumab for metastatic colon cancer
until progression, followed by palliative second-line chemotherapy
C. Curative-intent resection of the transverse colon primary and all three hepatic lesions
with perioperative chemotherapy
D. Curative-intent resection of the transverse colon primary and all three hepatic lesions
with radiotherapy
Question 19.15 Which genetic change is associated with resistance to treatment with
cetuximab?
A. KRAS mutation
B. EGFR over expression
C. KRAS wild type
D. MLH1 inactivation
Question 19.16 A 54-year-old woman has completed six cycles of first-line therapy for
metastatic KRAS codon 12 mutated colon cancer with FOLFOX and bevacizumab, and was
shown to have stable disease on restaging scans. Her CEA has also decreased from 135 ng/mL
at initial diagnosis to 4.5 ng/mL. She is asking about taking a break from chemotherapy
altogether for the next few months given the stable disease. When considering observation
versus maintenance chemotherapy in metastatic colorectal cancer, you inform her that:
A. There is no benefit in maintenance therapy with capecitabine and bevacizumab and
observation is preferred.
B. She should switch to FOLFIRI–panitumumab given no response noted on imaging.
C. Maintenance therapy with capecitabine and bevacizumab will lengthen the time to
progression and is preferred
D. She needs to complete a total of 12 cycles of oxaliplatin-based regimen before she can
consider observation.
Question 19.17 Common clinical characteristics for BRAF V600E colorectal tumors include
all of the following: (Select two correct responses)
A. Male
B. Right-sided tumors
C. Low-grade features
D. MSI-H
Question 19.18 High-risk features for stage II colon cancers include which TWO of the
following characteristics?
A. T4 perforated tumor
B. Moderately differentiated
C. Sampling of 0/8 lymph nodes
D. No lymphovascular invasion
ANSWERS
Corresponding chapters in Cancer: Principles & Practice of Oncology, Tenth Edition: 56 (Molecular Biology of Colorectal
Cancer), 57 (Cancer of the Colon), 60 (Cancer of the Rectum), and 61 (Cancer of the Anal Region).
20 Prostate, Bladder, and Kidney Cancer
Russell K. Pachynski
QUESTIONS
Each of the numbered items below is followed by lettered answers. Select the ONE lettered answer
that is BEST in each case unless instructed otherwise.
Question 20.1 Activating mutations in which of the following genes is seen in patients with
hereditary papillary renal cell carcinoma?
A. VHL
B. MET
C. FLCN
D. SDHB
Question 20.2 A 56-year-old moderately obese woman with a medical history of chronic
hypertension well controlled on a thiazide diuretic presents to the emergency department
with a 1-day history of abdominal pain, diarrhea, nausea, and fever. General physical
examination is significant only for some mild abdominal tenderness; negative stool guaiac; a
white blood cell count of 14.2/μL; hemoglobin of 14.5 g/dL; a normal platelet count; normal
electrolytes, amylase, lipase, and transaminases; and a creatinine of 0.9 mg/dL. Workup
includes an abdominal computed tomography (CT) scan, which is remarkable for a 1.5-cm
enhancing left renal mass in the left lower pole that is interpreted by the radiologist as a
“probable renal cell carcinoma” without evidence of other metastases. The patient undergoes
a laparoscopic partial nephrectomy. There are no postoperative complications, and she is
back to work 3 weeks later. Postoperative creatinine is 1.3 and pathology reveals a 2.5-cm
renal cell carcinoma, granular cell type, that is confined to the renal parenchyma. No lymph
nodes were recovered. The next appropriate step is:
A. Open retroperitoneal lymph node dissection.
B. Adjuvant sunitinib.
C. Adjuvant local radiotherapy.
D. Submission of pathology specimen for second review.
Question 20.3 A 55-year-old woman undergoes partial nephrectomy for clear cell carcinoma
of the kidney, Fuhrman grade IV. The patient does well for 10 years, at which time she
develops a pathologic intratrochanteric fracture of her left hip. CT scanning of the chest,
abdomen, pelvis, and brain and bone scan reveals no other sites of disease. The most
appropriate next step is:
A. Radiation alone.
B. High-dose interleukin-2 alone.
C. Orthopedic resection of the tumor with reconstruction followed by radiation.
D. Temsirolimus.
Questions 20.4–5 A 76-year-old man with chronic obstructive pulmonary disorder and
diabetes mellitus presents with back pain and confusion. Workup reveals extensive metastatic
disease in the lungs, bones, and liver and a 6-cm tumor in the kidney. There is no evidence of
cord compression. Laboratory studies reveal a calcium level of 11.5 mg/dL, lactate
dehydrogenase (LDH) of 600, and a creatinine level of 2.0 mg/dL. After hydration and
zoledronate, his calcium normalizes, hemoglobin is 9.5, creatinine decreases to 1.7, and
Eastern Cooperative Oncology Group performance status is 2.
Question 20.4 Based on MSKCC risk factors, this patient would be considered:
A. No risk.
B. Low risk.
C. Intermediate risk.
D. Poor risk.
Question 20.6 A 25-year-old Caucasian man without a medical history presents with
hematuria. Workup reveals bilateral renal cysts, at least one of them suspicious for
malignancy. Family history is significant for a pheochromocytoma in his father and a
pancreatic islet cell tumor and early death from kidney cancer in a paternal aunt. The most
likely familial cancer syndrome is:
A. Von Hippel–Lindau disease.
B. Birt–Hogg–Dubé syndrome.
C. Hereditary papillary renal cancer.
D. Hereditary leiomyomatosis and renal cancer.
Question 20.7 Which of the following associated with loss of VHL function is most likely to
lead to tumor angiogenesis?
A. Modulation of NF-kB activity and downregulation of JUNB
B. Increase in matrix metalloproteinases
C. Increase in hypoxia inducible factor (HIF)
D. Destabilization of microtubule formation
Question 20.8 Inactivation or alteration in which of the following tumor suppressor genes is
implicated in the pathogenesis of invasive bladder cancer?
A. TP53
B. RB1
C. PTEN
D. All of the above
Question 20.9 A patient with hematuria is taken to the operating room, where an
examination under general anesthesia reveals a mobile bladder. Resection of the papillary
lesion reveals grade III urothelial papillary carcinoma, and multiple biopsies of the
erythematous areas of the bladder all reveal diffuse carcinoma in situ. Muscle is present in
the pathologic specimens, and there is no evidence for invasive tumor. The appropriate
therapy is:
A. Intravesical Bacillus Calmette–Guérin (BCG) vaccine.
B. Intravesical cyclophosphamide.
C. Radiation.
D. Cystectomy.
Question 20.10 The patient receives definitive treatment, as well as with a follow-up
maintenance program; however, 4 months after initiating the maintenance BCG program, the
urologist notes multiple recurrent papillary lesions. Repeat biopsy reveals urothelial cancer
invasive into muscle. CT scans of the chest, abdomen, and pelvis are unremarkable,
creatinine remains normal at 1.2 mg/dL, and his performance status is excellent. Appropriate
initial therapy at this point is:
A. Reinduction with intravesical BCG.
B. Intravesical chemotherapy with mitomycin-C.
C. Partial cystectomy.
D. Cisplatin-based multiagent chemotherapy.
Question 20.11 Which of the following is the most common molecular abnormality seen in
patients with prostate cancer?
A. KRAS mutation
B. BRAF mutation
C. p53 mutation
D. Chromosomal translocations involving TMPRSS2
Question 20.12 Which of the following are risk factors for cancer of the male urethra?
A. HPV-16
B. Chronic irritation
C. Infection
D. Caucasian race
Question 20.13 Which of the following statements about radical cystectomy is most
CORRECT?
A. An orthotopic neobladder is less effective in women than in men.
B. An abdominal wall diversion will require a urostomy bag.
C. An orthotopic neobladder will require the patient to be willing and able to perform self-
catheterization.
D. Metabolic acidosis is not a significant problem with continent diversions.
Question 20.14 Which of the following statements about combined radiation and
chemotherapy is most CORRECT?
A. Toxicity profile and tolerability of combined radiation and chemotherapy are
significantly better than that of radical cystectomy.
B. Long-term cancer outcome is similar to cystectomy.
C. It is preferred over cystectomy because of her cardiac history.
D. It will obviate the need for cystectomy.
Question 20.16 Which of the following genes is most commonly found to be abnormally
altered in invasive (≥T2) urothelial carcinoma of the bladder?
A. ERBB2
B. TP53
C. MDM2
D. FGFR3
Question 20.17 A 71-year-old man without significant medical history presents with
hematuria and flank pain. CT scan reveals a mass at the pelvic–ureteral junction with
associated hydronephrosis, but no associated lymphadenopathy. Cystoscopy and ureteroscopy
reveal an obstructing mass at the pelvic–ureteral junction, and cytology is diagnostic for
urothelial cancer. Which of the following is the most appropriate therapy?
A. Open nephroureterectomy and bladder cuff resection
B. Open radical nephrectomy with retroperitoneal lymph node dissection
C. Laparoscopic radical nephrectomy without retroperitoneal lymph node dissection
D. Definitive radiation and combined chemotherapy
Question 20.18 A 51-year-old man with a strong family history of prostate cancer, a normal
digital rectal examination, no significant comorbid medical problems, and a PSA of 2.9 seeks
advice on prostate cancer prevention. He is sexually active in a monogamous relationship and
denies any urinary or rectal symptoms. Which is the most likely to reduce his risk of
developing prostate cancer?
A. Reducing his alcohol intake.
B. Taking supplemental high dose vitamin E.
C. Avoiding high fat intake, reducing his BMI (avoiding obesity), and increasing his
physical activity.
D. Increasing his calcium/vitamin D intake.
Question 20.19 The most CORRECT statement about this case is:
A. Biopsy should be discussed because the PSA increase is >0.75 ng/ mL/year.
B. Biopsy should not be discussed because PSA is normal for his age.
C. Biopsy should not be discussed because his expected survival makes treatment not
worthwhile, even if prostate cancer is discovered.
D. Biopsy should be discussed because the PSA is >4 ng/mL.
E. The free-to-total PSA ratio will determine the need for biopsy.
Question 20.20 Biopsy reveals Gleason 8 prostate cancer in six of six cores. CT scan of the
abdomen and pelvis and bone scan are unremarkable. The most appropriate therapy is:
A. Radical retropubic prostatectomy.
B. Three-dimensional conformal radiotherapy with concomitant androgen ablation.
C. Interstitial radiotherapy with 125I.
D. All of the above.
Question 20.21 After discussion with a radiation oncologist and a urologist, the patient
elects to undergo combined androgen ablation and external beam radiation therapy. The
androgen ablation is administered before the radiation therapy and continued for 3 months
thereafter. Radiotherapy is complicated only by a mild diarrhea that resolves once the
radiation therapy is complete. The PSA nadirs at 1.2 ng/mL; however, 9 months after his last
dose of the luteinizing hormone–releasing hormone (LHRH) agonist, the PSA increases to 2.4
ng/mL and then to 3.6 ng/mL 1 month later. Testosterone level is normal at 350 ng/mL. The
most appropriate next therapeutic and/or diagnostic maneuver is:
A. Perform MRI of the pelvis to assess for local recurrence.
B. Reinitiate androgen ablation.
C. Refer the patient to a urologist for salvage prostatectomy.
D. Initiate docetaxel-based chemotherapy.
Question 20.22 The patient is treated with an LHRH agonist along with the antiandrogen
bicalutamide. PSA declines to 0.8 ng/mL, but after 10 months, the PSA begins to slowly
increase to a value of 3.7. He continues to feel well and has minimal urinary symptoms, no
bone pain, and no weight loss. The most appropriate therapy at this point is:
A. Docetaxel-based chemotherapy.
B. Discontinuing the antiandrogen bicalutamide.
C. Hospice care.
D. Radionuclide therapy with strontium-98 (Metastron).
Question 20.23 Infestation with which of the following parasites is a risk factor for
developing bladder cancer?
A. Clonorchis sinensis
B. Opisthorchis viverrini
C. Schistosoma haematobium
D. None of the above
Question 24–25 A 51-year-old black male executive with no medical history undergoes a
routine PSA screening evaluation and is found to have a PSA of 5.5 ng/mL. Biopsy reveals a
Gleason 3 + 3 prostate cancer in two of six biopsy cores. After discussion with a radiation
oncologist and urologist, he elects to receive treatment with a radical retropubic
prostatectomy.
Question 20.24 Which of the following statements about the surgery is TRUE?
A. Robotic laparoscopic prostatectomy is associated with a lower incidence of impotence
than open retropubic prostatectomy.
B. The incidence of impotence under the assumption that a bilateral nerve sparing
procedure can be performed is <10%.
C. Problems with incontinence persist in approximately 20% of patients.
D. Surgical experience has only a minimal impact on the positive margin rate.
Question 20.25 Surgical pathology confirms a Gleason score 6 tumor in both lobes of the
prostate. There is a focal surgical positive margin. There is no evidence of seminal vesicle or
lymph node invasion. His postoperative PSA is undetectable, and he has good continence. The
most appropriate next step is:
A. Adjuvant radiotherapy.
B. Repeat surgical exploration with possible reexcision of the prostatic bed.
C. Pelvic CT scan.
D. Prostascint scan.
Question 20.26 The patient maintains an undetectable PSA until 8 years later (at the age of
59 years), recurrent biochemical disease is noted. After appropriate discussion, androgen
ablation with an LHRH agonist alone is initiated, and the PSA once again becomes
undetectable. The patient maintains an undetectable PSA while on androgen ablation for 3
years, when he develops sudden midback pain after lifting his grandson. There are no
associated neurologic signs or symptoms. Bone scan shows marked uptake at the T8 vertebra
and PSA remains undetectable. The most appropriate therapeutic or diagnostic maneuver is:
A. Immediate radiotherapy to T8.
B. Therapy with ketoconazole, 400 mg three times daily with hydrocortisone replacement.
C. Spinal MRI to rule out cord compression.
D. Bone densitometry to assess for osteoporosis.
Question 20.27 A 75-year-old man with diabetes, hypertension, and coronary artery disease
who is receiving atorvastatin, glyburide, and an angiotensin-converting enzyme inhibitor is
under surveillance after external beam radiotherapy for a Gleason 3 + 3 prostate cancer that
was diagnosed and treated 10 years earlier when he was found to have a PSA of 4.3 on
routine screening. His PSA level, which had been 0.2 ng/mL, has increased to 0.3, 0.35, and
then 0.40 over the period of 18 months. The most appropriate therapy at this time is:
A. Androgen ablation with an LHRH agonist.
B. Continued active surveillance.
C. High-intensity focused ultrasound to his prostate.
D. High-dose (150 mg) bicalutamide.
Question 20.28 A 65-year-old man has been receiving combined androgen ablation with
leuprolide and bicalutamide for 4 years for biochemical recurrence after radical
prostatectomy. His PSA has increased from an undetectable nadir to 1.1 ng/mL on serial
measurement over the period of 6 months. The PSA then continues to increase 2 months later
to 2.5, with serum testosterone of 10 ng/mL. Bone scan and CT of the abdomen/pelvis do not
reveal any metastatic disease, and he remains asymptomatic. The most appropriate therapy
option is:
A. Continue current treatment regimen and active surveillance.
B. Docetaxel-based chemotherapy.
C. Start enzalutamide.
D. Discontinue bicalutamide.
Question 20.29 Which of the following has the highest risk of developing prostate cancer?
A. A 60-year-old Caucasian male with no family history of cancer.
B. A 60-year-old African-American male with a father with prostate cancer.
C. A 40-year-old Asian male.
D. A 40-year-old obese Caucasian male.
Question 20.30 Genetic alterations in which of the following is most common in prostate
adenocarcinoma?
A. NRIP1
B. FOXA1
C. PTEN
D. CDK2
Question 20.31 Which of the following statements about the androgen receptor is most
CORRECT?
A. The majority of its activity in prostate cancer is due to its cytoplasmic effects.
B. Upregulation of androgen receptor expression has been linked to prostate cancer
development.
C. Castration leads to complete inactivation of all androgen receptor-mediated pathways.
D. Castrate-resistant prostate cancer (CRPC) is associated with upregulation of androgen
receptor expression.
Question 20.32 A 63-year-old uncircumcised man without any significant medical history
presents to his physician with an inability to retract the foreskin. Examination reveals
phimosis, with an underlying painless ulcerated mass of 1 × 2 cm. A 2.5-cm hard node is
palpated in the left inguinal region. Biopsy of the penile lesion reveals squamous cell cancer.
In addition to wide surgical resection of the primary lesion, other appropriate therapeutic
and/or diagnostic maneuvers at this time include:
A. Four-week course of a broad-spectrum antibiotic.
B. Left inguinal lymph node dissection.
C. Bilateral inguinal radiotherapy.
D. Taxane-based chemotherapy.
ANSWERS
Corresponding chapters in Cancer: Principles & Practice of Oncology, Tenth Edition: 62 (Molecular Biology of Kidney Cancer),
63 (Cancer of the Kidney), 64 (Molecular Biology of Bladder Cancer), 65 (Cancer of the Bladder, Ureter, and Renal Pelvis), 66
(Genetic Testing in Urinary Tract Cancers), 67 (Molecular Biology of Prostate Cancer), and 68 (Cancer of the Prostate).
21 Testicular Cancer
Pasquale Benedetto
QUESTIONS
Each of the numbered items below is followed by lettered answers. Select the ONE lettered answer
that is BEST in each case unless instructed otherwise.
Question 21.1 A 24-year-old man has, for the past week, experienced dyspnea on climbing
two flights of stairs. In the ED arterial blood gas on room air demonstrates PO2 66 mm Hg,
PCO2 34 mm Hg, and pH 7.42. On examination he is in no acute distress at rest. Lungs are
clear to auscultation, there is a no organomegaly but a firm enlargement of the right testis.
Chest x-ray reveals multiple bilateral pulmonary nodules. Pathology from the orchiectomy
specimen demonstrates embryonal carcinoma. hCG level is 1,024 mIU/mL, alpha-fetoprotein
(AFP) is 248 ng/mL. While in the hospital he develops headaches and a CAT scan of his brain
shows multiple small hemispheral metastases. Which of the following is the most appropriate
next step in management?
A. Begin whole brain radiotherapy, and after its completion in 2 weeks, start
chemotherapy.
B. Begin chemotherapy immediately.
C. Begin whole brain radiotherapy and whole lung radiotherapy to be followed in 3 weeks
by chemotherapy.
D. Begin concomitant whole brain radiotherapy and chemotherapy.
E. Use CCNU in high dose because it will cross the blood brain barrier and thus be
effective against both lung and brain metastases.
Question 21.2 23-year-old male presents to his physician with a 3-week history of back pain.
Physical examination demonstrates a 3-cm hard mass in the left testis and an easily palpable
mass is noted in the left upper quadrant. Chest x-ray is negative. Abdominal imaging reveals
a 10-cm retroperitoneal mass only. AFP is within normal limits, beta-hCG is 3,000 mIU/mL.
Which one of the following statements is most accurate?
A. Initial diagnostic procedure should include percutaneous biopsy of the testis.
B. Histology is likely to be nonseminomatous germ cell cancer.
C. The patient should undergo debulking retroperitoneal lymphadenectomy.
D. The probability of cure with combination chemotherapy is approximately 60%.
E. The patient should receive radiation therapy to the abdomen.
Question 21.3 A 30-year-old man has multiple pulmonary lesions detected at the time of
diagnosis of an embryonal carcinoma of the right testis. After orchiectomy and three cycles of
BEP chemotherapy, chest x-ray demonstrates a persistent 2-cm nodule in the right mid lung
field; the other lesions have disappeared. Computed tomography confirms this finding; the
mediastinum and retroperitoneum appear normal. The serum level of beta-human chorionic
gonadotropin, previously elevated, is now undetectable. The most appropriate management
of this patient is:
A. Needle biopsy of the nodule
B. Surgical resection of the nodule
C. Continuation of chemotherapy, without bleomycin
D. Radiotherapy to the residual nodule
E. Obtain PET scan
Question 21.4 A 26-year-old man presents with cough and a left testicular mass. Work-up
reveals multiple retroperitoneal lymph nodes and several lung nodules. Serum hCG is 80
mIU/mL, AFP is normal. Pathologic diagnosis of the testicular mass is pure seminoma. What
is the best management decision?
A. Two cycles of BEP (bleomycin, etoposide, cisplatin)
B. Three cycles of BEP
C. Four cycles of BEP
D. Three cycles of EP
Question 21.5 A 28-year-old man with a history of Klinefelter syndrome presents to his
physician with a complaint of cough and hoarseness of 3 months duration. A chest x-ray
reveals a widened mediastinum. CT confirms the presence of an 8-cm superior mediastinal
mass, Serum AFP is 1,500 ng/mL, beta-hCG 20,000 mIU/mL. A diagnosis of germ cell tumor
of mediastinal origin is made. Which is the most appropriate next step in management?
A. Surgical resection of the mass
B. Three cycles of BEP
C. Four cycles of BEP
D. Radiation therapy
E. Testicular ultrasound
Question 21.6 A 23-year-old male presents with painless enlargement of the testis and
cough. Ultrasound reveals an intratesticular mass. CT scan of the chest, abdomen, and pelvis
reveals multiple retroperitoneal nodes, liver metastases, and multiple pulmonary nodules,
AFP is 16,000 ng/mL, beta-hCG is 200 mIU/mL. At the start of the third cycle of BEP, the
patient is asymptomatic. AFP has decreased to 200, beta-hCG is undetectable. What is the
next step in management?
A. Complete four cycles of BEP
B. Change treatment to salvage therapy with TIP
C. Repeat CT scans for assessment of disease response
D. Consider tandem high-dose therapy with stem cell rescue
E. Obtain PET scan
Question 21.7 A 29-year-old male presents to his physician with left supraclavicular
adenopathy. Examination reveals a hard left testicle. Further workup includes CT imaging,
which demonstrates a 7-cm retroperitoneal mass without parenchymal pulmonary nodules.
AFP is 16,534 ng/mL, beta-hCG 333 mIU/mL. Pathology of the orchiectomy specimen
confirms a mixed germ cell tumor with elements of seminoma, embryonal carcinoma, and
yolk sac tumor. At the completion of the fourth cycle of chemotherapy, repeat CAT scans
reveal a large residual retroperitoneal mass with both solid and cystic components. Tumor
markers have normalized. The patient undergoes retroperitoneal exploration and removal of
the large mass. Pathology reveals mature teratoma. Three years after surgery, the AFP is
now elevated to 33.5. Serial assays confirm increase to 243.6. Repeat scans reveal only a new
retroperitoneal density at the site of previous disease. What is the next best step in the
management of this patient?
A. Initiate salvage chemotherapy with ifosfamide-based chemotherapy
B. Refer for resection of the abdominal mass
C. Prepare for high-dose chemotherapy and stem cell rescue.
D. Any of the above
Question 21.8 A 26-year-old man presents with cough and a left testicular mass. Work-up
reveals a palpable abdominal mass and several lung nodules, Serum AFP is 11,000 ng/mL,
beta-hCG is 450 mIU/mL. Pathologic diagnosis of the testicular mass is pure seminoma. What
is the next best step in the optimal management of this patient?
A. Two cycles of BEP
B. Three cycles of BEP
C. Four cycles of BEP
D. Three cycles of EP
Question 21.9 A 32-year-old man previously treated for testicular cancer 3 years ago with
four cycles of BEP now presents with pancytopenia. Evaluation reveals acute myelogenous
leukemia (AML). What is the likely chromosome abnormality associated with this leukemia?
A. 47XXY
B. t(9:22)
C. 5q-
D. 13q deletion
E. 11q23 translocation
Question 21.10 A 24-year-old man presents with a left testicular mass and undergoes a
radical orchiectomy. Pathologic evaluation of the resected specimen reveals embryonal
carcinoma with vascular invasion. The preoperative level of human chorionic gonadotropin
(hCG) is 950 mIU/mL. The AFP level is within normal limits. CT imaging demonstrates no
evidence of metastatic disease. The marker normalizes postsurgery, but 3 months later on
surveillance the hCG is elevated to 110 mIU/mL, confirmed on repeat. Repeat imaging
demonstrates no pulmonary, liver, or retroperitoneal abnormalities. Which one of the
following would you advise?
A. Four cycles of BEP (bleomycin, etoposide, and cisplatin)
B. Three cycles of BEP
C. Three cycles of etoposide and cisplatin
D. Radiation therapy to the abdomen
E. Observation
Question 21.11 A 27-year-old man is hospitalized with respiratory symptoms. His physical
examination is noncontributory. Plane x-ray of the chest shows several 2-cm nodular
pulmonary lesions bilaterally and a large mediastinal mass. A computed tomographic (CT)
scan of the chest, abdomen, and pelvis confirms a large anterior mediastinal mass and
pulmonary nodules. Fine-needle biopsy of the lung reveals anaplastic carcinoma.
Laboratory studies reveal:
Question 21.12 Risk factors for germ cell tumors includes which one(s) of the following?
(Select three correct responses)
A. Cryptorchidism
B. Intratubular germ cell neoplasia (ITGCN)
C. Father with history of testicular cancer
D. Turcot syndrome
Question 21.13 Germ cell tumors may express which of the following immunohistochemical
proteins? (Select four correct responses)
A. Cytokeratin
B. Placental alkaline phosphatase (PLAP)
C. CD 20
D. CD 30
E. CD 10
F. OCT3/4
Question 21.14 For patients with clinical stage I testis cancer which factor(s) predict for risk
of recurrence after orchiectomy? (Select two correct responses)
A. Presence of lymphovascular invasion and embryonal carcinoma histology
B. Presence of choriocarcinoma as an element in mixed germ cell tumors
C. Seminoma ≥4 cm
D. Degree of elevation of the preorchiectomy markers
E. Seminoma with presence of syncytiotrophoblasts
Question 21.15 Adjuvant chemotherapy for patients with pathologic stage II disease after
RPLND is recommended for patients with:
A. Three positive lymph nodes.
B. Extranodal extension of tumor.
C. Pure embryonal carcinoma histology.
D. Microscopic disease with no lymph node greater than 2 cm.
Question 21.16 According to the International Germ Cell Consensus Classification, which
patient vignette is consistent with poor risk seminoma?
A. Multiple pulmonary metastases with hCG 10,000
B. Disseminated disease with a solitary brain metastasis
C. Multiple liver metastases associated with enlarged retroperitoneal nodes
D. None of the above
Question 21.17 Which of the following is a TRUE statement regarding hCG in germ cell
tumors?
A. The presence of elevated hCG is indicative of nonseminomatous histology
B. The half-life of hCG is 5 to 7 days
C. Very high levels of hCG can produce symptoms of hyperthyroidism
D. Very high levels of hCG are common in patients with disseminated yolk sac tumor
Question 21.18 Which one of the following statements is TRUE regarding NSGCT in first
relapse?
A. Such patients are incurable with standard-dose chemotherapy.
B. EP chemotherapy can be repeated if the patient achieved a complete remission with
first-line BEP therapy.
C. High-dose chemotherapy and autologous stem cell rescue should be considered in the
treatment paradigm.
D. Three cycles of ifosfamide-based chemotherapy should be administered.
Question 21.20 A 55-year-old male patient presents to his physician because of scrotal
swelling. An ultrasound demonstrates an intratesticular mass. What is the most likely
histology of the lesion?
A. Leydig cell tumor
B. Liposarcoma of the spermatic cord
C. Large B-cell lymphoma
D. Granulosa cell tumor
E. Metastatic carcinoma
ANSWERS
Corresponding chapter in Cancer: Principles & Practice of Oncology, Tenth Edition: 70 (Cancer of the Testis).
22 Vulvar, Vaginal, Uterine, and Cervical Cancer
Matthew A. Powell and Laura Divine
QUESTIONS
Each of the numbered items below is followed by lettered answers. Select the ONE lettered answer
that is BEST in each case unless instructed otherwise.
Question 22.1 Which of the following feature is most characteristic of type I endometrial
cancers?
A. Most of these cancers have serous or clear cell histology.
B. Risk factors include unopposed estrogen, anovulation, and obesity.
C. They are rarely (less than 5% of cases) associated with microsatellite instability.
D. The precursor lesion is preneoplastic atrophic endometrium.
Question 22.2 Type II endometrial cancers have which of the following features?
A. The precursor lesion is atypical hyperplasia.
B. The majority of tumors are slow growing.
C. These cancers are unrelated to estrogen exposure.
D. All of the above.
Question 22.3 Genetic changes commonly seen in type I endometrial cancers include:
A. KRAS mutation
B. PTEN mutation
C. β-Catenin mutation
D. All of the above
Question 22.4 Which of the following genetic change(s) is/are most characteristic of type II
endometrial cancers (select three correct answers)?
A. Microsatellite instability (MSI)
B. HER2/neu amplification
C. BCL2 overexpression
D. p53 mutations
Question 22.5 Risk factors for endometrial cancer include: (Select two correct responses)
A. Increasing age.
B. Black race.
C. Family history of endometrial cancer.
D. Combination oral contraceptives (contain estrogen and progestogen).
Question 22.6 The majority of cervical, vaginal, and vulvar cancers appear to have a
common cause, which is:
A. Increased exposure to exogenous estrogen.
B. Chronic bacterial and parasitic infections.
C. Multiple prior herpes simplex virus (HSV) infections.
D. Human papillomavirus (HPV) infection with high-risk types.
Question 22.7 In patients with gestational trophoblastic disease (GTD) with a complete
mole, molecular features include which of the following?
A. Mutations in p53.
B. Most are diploid with duplication of a haploid maternal genome.
C. Predominance of maternal chromosomes is common.
D. Several genes, including CMYC, ERBB2, CFMS, and BCL2, have been implicated in the
pathogenesis of complete moles.
Question 22.8 A 39-year-old married woman is seeing you in the office after recently having
a cervical biopsy that demonstrated cervical cancer. She has no prior medical problems other
than anemia and one prior uncomplicated child birth. You tell her which of the following
epidemiologic factors are TRUE?
A. During the past 80 years, death rates from cervical cancer have decreased primarily
because of improved treatment of STDs such as gonorrhea, chlamydia, and syphillis.
B. Delayed childbearing is associated with an increased risk of cervical cancer.
C. HSV is thought to be the causative agent for the majority of patients.
D. The incidence of cervical cancer is 30% and 100% higher in Black and Hispanic women,
respectively, compared with Whites in the United States.
Question 22.9 The patient asks about prevention and treatment of HPV infections, and you
advise her:
A. The viral infections are rare.
B. Treatments for HPV infections with antiviral therapy are effective if taken within 4 days
of exposure.
C. HPV vaccines have been approved by the Food and Drug Administration (FDA) to help
prevent infection from the most common HPV types.
D. She should receive the HPV vaccine now to help treat her cancer.
Question 22.10 You counsel her about HPV and human immunodeficiency virus (HIV). After
extensive discussion, you decide to proceed with testing for HIV with which of the following
justifications? (Select three correct responses)
A. HIV immunosuppression is correlated with an increased risk of cervical HPV infections.
B. Patients with HIV appear to have a faster rate of progression to high-grade dysplasia
(cervical intraepithelial neoplasia [CIN]).
C. Antiretroviral therapy to manage HIV has demonstrated direct activity against HPV.
D. Cervical cancers in HIV-positive women may be more aggressive than in HIV-negative
women.
Question 22.11 She has done extensive reading about cervical cancer and asks you about
factors that are associated with metastatic disease. You advise her that the following are
associated with extracervical disease:
A. Tumor size and histologic subtype
B. Presence of microinvasion and lymphovascular space invasion
C. Depth of invasion and presence of microinvasion
D. Presence of lymphovascular space invasion and history of pelvic surgery
Question 22.12 If her initial biopsy returned with invasive squamous cell carcinoma with 2
mm of invasion and no lymphovascular space involvement (LVSI), you recommend:
A. Simple hysterectomy.
B. Radiation therapy with possible chemotherapy.
C. Chemotherapy with cisplatin 40 mg/m2 weekly for six cycles.
D. Cervical conization.
Question 22.13 The patient has a 3-cm visible tumor found on her cervix that is biopsied
and is frankly invasive squamous cell carcinoma. She has several questions regarding staging
of her cancer. You advise the following:
A. If enlarged lymph nodes are seen on her computed tomography (CT) scan, her cancer
would be staged appropriately as at least stage III.
B. Staging for cervical cancer is clinical, involving pelvic examination.
C. If hydronephrosis is demonstrated on her CT scan, her cancer would be staged
appropriately as at least stage II.
D. Positron emission tomography (PET) scanning is used in staging to determine nodal
involvement.
Question 22.14 The patient’s 3-cm visible tumor appears confined to the cervix and is staged
as IB1. Which of the following therapies is most appropriate?
A. Radiation and chemotherapy with weekly cisplatin dosed at 40 mg/m2
B. Simple hysterectomy with removal of fallopian tubes and ovaries
C. Radiation therapy or radical hysterectomy with lymphadenectomy
D. Brachytherapy radiation with a dose of 75 Gy
Question 22.15 A 40-year-old woman is diagnosed with invasive cervical cancer. She has a
5-cm cervical tumor with parametrial involvement, and evidence of hydronephrosis on
imaging. Her cancer is stage IIIB. You elect to treat her with combined chemotherapy and
radiation. Which of the following applies to the treatment of locoregionally advanced
cervical cancer?
A. Randomized trials involving patients with locally advanced cervical cancer have failed
to demonstrate a benefit of chemotherapy in addition to standard radiation therapy.
B. Carboplatin appears to be the most appropriate agent to combine with radiation therapy
for cervical cancer and this should be followed by hysterectomy.
C. Paclitaxel with cisplatin is an acceptable regimen to combine with radiation therapy and
has demonstrated improved survival.
D. Weekly cisplatin with radiation therapy appears as active as other regimen with
manageable toxicity.
Question 22.16 After receiving definitive concurrent chemoradiotherapy for her stage IIIB
cervical cancer, the patient develops a recurrence in the cervix, 18 months from the
completion of therapy. Imaging studies suggest no extrapelvic disease. You recommend the
following:
A. Referral back to the radiation oncologist for consideration of further radiation
B. Chemotherapy with combined cisplatin and topotecan
C. Chemotherapy with combined cisplatin and paclitaxel
D. Referral for consideration of further surgery
Question 22.17 A 67-year-old woman presents for evaluation of a cancer found in the
vagina. Before any examination or evaluation, you review with her that which of the
following are TRUE? (Select two correct responses)
A. Prior in utero exposure to the synthetic estrogen diethylstilbestrol (DES) places a
woman at an increased risk for development of vaginal clear cell adenocarcinoma.
B. Most cancers found in the vagina are actually metastases or direct extensions from other
gynecologic tumors.
C. Vaginal squamous cell carcinoma is thought to be unrelated to the HPV.
D. Staging for primary vaginal cancers includes surgical exploration.
Question 22.18 The patient is found to have had a prior hysterectomy for mild dysplasia.
Her apparent primary vaginal cancer extends to the subvaginal tissues and is appropriately
staged as a stage II cancer. You recommend:
A. Referral for total radical vaginectomy
B. Chemotherapy with a cisplatin-based regimen
C. Referral for radiation therapy
D. Local excision followed by close observation
Question 22.19 Which of the following statement(s) applies to invasive vulvar cancer?
(Select two correct responses)
A. There are three distinct types of invasive squamous vulvar cancer.
B. HPV-associated vulvar cancer tends to occur in younger women (age <55 years) and is
associated with prior cervical precancerous abnormalities.
C. Melanoma of the vulva is caused by exposure to HPV.
D. Non–HPV-associated invasive squamous vulvar cancer is associated with lichen
sclerosis.
Question 22.20 A 55-year-old patient with a history of abnormal Pap smears presents for
evaluation of a 3-cm vulvar mass. The mass is located 1 cm lateral to the clitoris on the right
and has an ulcerated appearance. She states she noticed it 2 years ago and has tried many
different ointments to help control the itching and irritation. This was recently biopsied to
reveal invasive squamous cell carcinoma. What treatment would you recommend?
A. Neoadjuvant chemoradiation followed by local resection
B. Concurrent chemoradiation
C. Radical vulvectomy with bilateral inguinal lymphadenectomy
D. Local resection followed by radiation and/or chemotherapy
Question 22.21 Which of the following histologic feature(s) is/are most significant in
predicting the outcome for a patient with vulvar cancer? (Select two correct responses)
A. Presence of lymphovascular invasion
B. Tumor grade
C. Depth of invasion and tumor diameter
D. Presence and number of positive lymph nodes
Question 22.22 The final pathology reveals a 3.3-cm invasive squamous cell carcinoma with
2 involved (positive) lymph nodes larger than 1.0 cm, without extracapsular spread, in the
right inguinal/femoral lymph node dissection out of 12 removed. The contralateral node
dissection was negative. Margins around the primary tumor were negative and greater than 1
cm. Her appropriate International Federation of Gynecology and Obstetrics (FIGO) and TNM
stage are:
A. II and T2N2M0.
B. IIIA and T3N1M0.
C. IIIB and T2N1M0.
D. IVA and T2N1M0.
Question 22.23 The most appropriate therapy for this patient after she recovers from
surgery is:
A. Close observation.
B. Chemotherapy with cisplatin plus 5FU.
C. Referral for consideration of radiation therapy.
D. Exploration with dissection of the pelvic lymph nodes.
Question 22.24 Unfortunately, despite the use of adjuvant therapy, this patient’s cancer
recurs locally on the vulva with a 2-cm lesion. Which of the following would you advise?
A. Repeat resection
B. Chemotherapy with bleomycin
C. Best supportive care
D. Chemotherapy with cisplatin plus 5FU
Question 22.25 A 62-year-old woman has been diagnosed with a uterine corpus (body)
cancer. You have not received her records for review, but she is seen in your office for
consultation and asks many general questions. Which of the following would you tell her?
A. Approximately 90% of these cancers arise from the endometrial lining and are typically
managed with hysterectomy and staging.
B. Most of these cancers are caused by exogenous estrogen use.
C. Uterine sarcomas are more common than endometrial cancers and represent
approximately 90% of corpus cancers.
D. Endometrial cancer typically presents at late stage with patients having abnormal
uterine bleeding.
Question 22.26 This patient’s records arrive in the office, and the pathology verifies the
diagnosis of a grade 2 endometrioid-type endometrial cancer from an office endometrial
biopsy. She asks what has caused her cancer to develop. Which of the following are
considered to be independent risk factors for the development of endometrial cancer? (Select
three correct responses)
A. Obesity
B. Diabetes mellitus
C. Premature ovarian failure with early menopause
D. Presence of an estrogen-producing tumor
Question 22.27 For this patient with an office biopsy demonstrating grade 2 endometrioid
endometrial cancer who is of apparent good heath with no other medical comorbidities, you
recommend:
A. Further evaluation with CT scan and PET scan to evaluate for metastatic disease.
B. A formal dilation and curettage (D&C) to obtain a more accurate pathologic diagnosis.
C. Hysterectomy with removal of the tubes and ovaries with consideration of pelvic and
para-aortic lymphadenectomy.
D. Referral for radiation therapy with possible chemoradiation.
Question 22.28 During the patient’s initial visit, she reports that her mother was diagnosed
with endometrial cancer at age 42, her maternal aunt with colon cancer at age 51, and her
sister with endometrial cancer at age 38. You are concerned her cancer may be hereditary.
You advise that:
A. She undergoes colon assessment if she is not up to date with age-appropriate screening
and considers counseling and possible testing for hereditary nonpolyposis colorectal
cancer (Lynch II syndrome).
B. She undergo breast MRI and be tested for BRCA1 and BRCA2.
C. Colon and endometrial cancers are common, and no further evaluation is necessary at
this time.
D. The maternal side of her family very likely has familial adenomatous polyposis and
should be further evaluated.
Question 22.29 The patient undergoes hysterectomy with full staging, including pelvic
washing for cytology, removal of both tubes and ovaries as well as pelvic and para-aortic
lymph nodes. She is noted to have cancer involving three pelvic lymph nodes, but not the
para-aortic lymph nodes. Her stage is designated:
A. IIIB.
B. IIIC1.
C. IIIC2.
D. IVA.
Question 22.30 For this patient with three positive pelvic lymph nodes and a grade 2
endometrioid endometrial cancer, you recognize adjuvant therapy is controversial but
ultimately recommend:
A. Hormone therapy with a progestational agent
B. Referral for pelvic radiation therapy
C. Chemotherapy with combined paclitaxel, cisplatin, and doxorubicin
D. Combination of radiation and chemotherapy
Question 22.31 The most active (improved disease-free and overall survival) chemotherapy
regimen as determined in randomized clinical trials in women with advanced or recurrent
endometrial cancer with measurable disease is:
A. Doxorubicin plus paclitaxel
B. Cisplatin/doxorubicin
C. Cisplatin/doxorubicin/paclitaxel
D. Ifosfamide plus paclitaxel
Question 22.32 A 17-year-old female patient presents to your office with pelvic ultrasound
suggesting intrauterine gestational trophoblastic neoplasia (GTN). The most common of the
distinct clinicopathologic entities of GTN is:
A. Complete hydatidiform mole.
B. Partial hydatidiform mole.
C. Choriocarcinoma.
D. Placental site trophoblastic tumor.
Question 22.33 This patient has a beta-human chorionic gonadotropin (hCG) of 122,300 and
undergoes therapy with a suction D&C. Final pathology confirms the diagnosis of complete
hydatidiform mole. The patient is followed with the following:
A. CT scan every 3 months.
B. Ultrasound of the pelvis every 3 months.
C. Pelvic examination with Pap smear every 6 weeks.
D. Beta-hCG weekly.
Question 22.34 After a complete metastatic workup, the patient is determined to have low-
risk disease. You recommend the following chemotherapy:
A. Etoposide
B. Vincristine
C. Methotrexate
D. Cyclophosphamide
ANSWERS
Corresponding chapters in Cancer: Principles & Practice of Oncology, Tenth Edition: 71 (Molecular Biology of Gynecologic
Cancers), 72 (Cancer of the Cervix, Vagina, and Vulva), 73 (Cancers of the Uterine Body), 74 (Genetic Testing in Uterine
Cancer), and 75 (Gestational Trophoblastic Neoplasms).
23 Ovarian Cancers
David G. Mutch
QUESTIONS
Each of the numbered items below is followed by lettered answers. Select the ONE lettered answer
that is BEST in each case unless instructed otherwise.
Question 23.2 A 35-year-old woman presents to you for recommendations regarding therapy
of her newly diagnosed mucinous ovarian cancer. This was a 5-cm, grade 1, left-sided mass
that was incidentally found at the time of surgery for endometriosis as part of an infertility
workup. The ovary was removed, and the operative note states that there was no evidence of
tumor on the external surface of the ovary or elsewhere in the abdomen, but full surgical
staging was not performed. A postoperative computed tomography (CT) scan of the abdomen
and the pelvis is unremarkable, and CA-125 is within normal limits. Pelvic examination is
unremarkable. The patient would like to have children but does not want to compromise her
survival. You should advise her that:
A. She is unlikely to have any residual cancer or a recurrence, and further surgery or
chemotherapy is not needed.
B. She should have a positron emission tomography (PET) scan, and if there is no uptake,
she does not need further surgery or chemotherapy.
C. Because her CT scan and CA-125 are normal, she is unlikely to have any residual
disease, and further surgery is not needed. However, because the mucinous subtype of
ovarian cancer has a very poor prognosis, she will require three to six cycles of
carboplatin/paclitaxel chemotherapy.
D. She should have complete surgical staging, if possible, via laparoscopy, with the option
of preserving her uterus and contralateral ovary if there is no further evidence of
tumor, which is associated with a >90% chance of 5-year survival and does not require
chemotherapy.
E. She should have complete surgical staging, including TAH/BSO. If no further disease is
found, she will need only three cycles of carboplatin/paclitaxel chemotherapy, but if
there is disease outside the ovary, she will need six cycles.
Question 23.3 In what aspect of ovarian cancer management is CA-125 most useful?
A. Screening
B. Diagnosis
C. Monitoring treatment
D. Equally useful in all of the above
Question 23.4 Which of the following increases the risk of a woman developing ovarian
cancer?
A. Use of oral contraceptives for >5 consecutive years
B. Nulliparity
C. Breastfeeding
D. Tubal ligation
Question 23.5 A 50-year-old woman presents with a pelvic mass. She is found to have a
tumor of low malignant potential. With TAH/BSO and staging, there is no gross disease but
the washings were positive on final pathology and there was one positive lymph node,
making her disease stage IIIC. What is the most appropriate therapy postoperatively?
A. Intraperitoneal cisplatin and intravenous (IV) taxane
B. IV platinum and a taxane
C. Hormonal therapy with tamoxifen or an aromatase inhibitor
D. No further therapy
Question 23.6 A 50-year-old woman was diagnosed with stage III ovarian cancer and
underwent primary resection followed by chemotherapy. She is asymptomatic but has an
elevated CA-125. Imaging studies do not identify recurrent disease. Which of the following is
the best treatment option?
A. Hormonal therapy
B. Platinum-based chemotherapy
C. Single-agent doxorubicin
D. Single-agent paclitaxel
Question 23.7 Which of the following is/are a founder BRCA mutation(s) associated with
individuals of Ashkenazi descent?
A. 185delAG
B. 5382insC
C. 617delT
D. All of the above
Question 23.8 What percentage decrease in the incidence of ovarian cancer is associated
with oral contraceptive use for more than 5 years?
A. 5%
B. 10%
C. 20%
D. 50%
E. 80%
Question 23.9 A 25-year-old woman has her left ovary removed because of an ovarian mass.
The final pathology shows that this is a moderately differentiated papillary serous cancer.
There was no other evidence of disease in the abdominal cavity. What is the likelihood that
this patient has a positive pelvic or para-aortic lymph node metastasis?
A. 5%
B. 15%
C. 30%
D. 50%
Question 23.10 A 55-year-old woman who has just achieved a complete clinical remission
(normal CT scan, pelvic examination, and CA-125) after six cycles of chemotherapy for stage
IIIC optimally debulked serous ovarian cancer presents to you for a second opinion regarding
her prognosis and treatment options at this point. She is in excellent general health and
tolerated chemotherapy well except for some numbness in her fingers and toes, which caused
her treating oncologist to switch her treatment from paclitaxel/carboplatin to
docetaxel/carboplatin after cycle three. You should advise her that:
A. The risk of eventual relapse for an optimally debulked patient with a complete clinical
remission is approximately 30%. No therapy is proven to be of any further survival
benefit at this point.
B. She should have second-look surgery. If residual disease is found, she should have four
to six cycles of intraperitoneal platinum-based therapy because this can improve
survival in patients with platinum-sensitive, minimal residual disease.
C. She should have a PET scan. If residual disease is found, she should have four to six
cycles of a non–cross-resistant drug, such as topotecan.
D. Her risk of eventual relapse is approximately 70%. She should be offered consolidation
therapy with paclitaxel 175 mg/m2 every 3 weeks for 12 months with the expectation
of a 30% improvement in survival.
E. Her risk of relapse is approximately 70%. No therapy is proven to be of any survival
benefit at this point.
Question 23.11 Which of the following statement(s) is/are TRUE about granulosa cell
tumors of the ovary?
A. They usually occur in premenopausal women
B. They are usually stage III/IV
C. Survival of patients with stage I disease is generally good, but they may relapse later
D. Survival of patients with stage III/IV disease is poor, and they should consider
chemotherapy
E. They may be associated with endometrial cancer
F. C, D, and E
Question 23.12 Which of the following statements is TRUE about germ cell tumors of the
ovary?
A. They occur more often in younger women.
B. They are usually stage III/IV.
C. Appropriate therapy includes TAH/BSO/full surgical staging and chemotherapy
regimens similar to those used in male testicular cancer.
D. Survival of patients with stage III/IV disease is poor.
E. The chemotherapy will usually result in infertility.
Question 23.13 A 51-year-old woman presents to you for recommendations regarding the
treatment of her recurrent ovarian cancer. She was optimally debulked for stage IIIC serous
ovarian carcinoma and completed six cycles of carboplatin/paclitaxel 36 months ago with a
clinical complete remission. She now has recurrent ascites, which is histologically positive for
tumor compatible with her original primary. CT scan shows peritoneal carcinomatosis and a
pelvic mass. You should advise her that:
A. Prognosis of recurrent ovarian cancer is poor. She may achieve short-term benefit from
chemotherapy although hospice is a reasonable option.
B. Tamoxifen has a 40% chance of response.
C. She has a very high likelihood of disease shrinkage and symptom palliation with further
platinum-based chemotherapy.
D. She has a chance of cure with autologous stem cell transplant.
E. Liver metastases and liver failure will probably be her ultimate cause of death.
Question 23.14 A 45-year-old woman has undergone surgical resection followed by adjuvant
chemotherapy for her stage IIIC ovarian cancer. She is now in complete remission and is
interested in further treatment to reduce the risk of recurrent disease. Which of the following
would you recommend?
A. Maintenance treatment with single-agent paclitaxel for 12 months
B. Clinical surveillance
C. Maintenance treatment with single-agent topotecan
D. Maintenance treatment with bevacizumab
Question 23.16 A 53-year-old patient presents with ascites, omental caking, and peritoneal
nodularity. Her ovaries are normal. She undergoes surgery and all gross tumors are removed.
The final diagnosis is papillary serous primary peritoneal cancer. How should this patient be
treated?
A. As if she had a standard ovarian cancer
B. As if she had a peritoneal mesothelioma
C. As if she had breast cancer
D. As a germ cell cancer
ANSWERS
Corresponding chapters in Cancer: Principles & Practice of Oncology, Tenth Edition: 76 (Ovarian Cancer, Fallopian Tube
Carcinoma, and Peritoneal Carcinoma) and 77 (Genetic Testing in Ovarian Cancer).
24 Breast Cancer
Foluso C. Ademuyiwa, Ron Bose, and Cynthia X. Ma
QUESTIONS
Each of the numbered items below is followed by lettered answers. Select the ONE lettered answer
that is BEST in each case unless instructed otherwise.
Question 24.2 BRCA1-associated breast cancers are characterized by: (Select two correct
responses)
A. Aggressive features.
B. ER positive.
C. Younger age at presentation.
D. All of the above.
Question 24.4 Which of the following statements about Luminal A subtype is TRUE?
A. It is more common in premenopausal black women
B. Luminal A breast cancers frequently carry TP53 mutations
C. It is characterized by high-expression levels of ER-related genes and low expression of
the HER2 cluster and proliferation-associated genes.
D. It has a worse prognosis than other molecular subtypes of breast cancer.
Question 24.5 NCCN, ASCO, and/or St. Gallen clinical practice guidelines support Oncotype
DX testing in which of the following scenarios?
A. ER positive HER2-negative patients with T1–3 and N0 or N1mi disease
B. As a marker of recurrence risk in untreated HER2 positive, node-negative patients
C. Predicts 10-year distant relapse risk in patients with early stage ER positive node-
negative breast cancer who will receive adjuvant hormonal therapy
D. A and C
Question 24.6 Which of the following factors is a risk factor for developing breast cancer?
A. Cowden syndrome
B. Early age at first full term pregnancy
C. Breast density <10%
D. Simple breast cysts
Question 24.7 American Cancer Society guidelines for magnetic resonance imaging (MRI)
screening is supported for which of the following patients?
A. A 47-year-old woman with a deleterious mutation in BRCA1
B. A 60-year-old woman with biopsy proven lobular carcinoma in situ (LCIS)
C. A 55-year-old woman with a personal history of ER positive breast cancer treated 8
years ago
D. A 65-year-old woman who underwent chest radiation at age 60 years
Question 24.8 Which of the following scenarios are considered a contraindication to the use
of tamoxifen?
A. Major surgical procedure within the previous 6 months
B. A history of deep vein thrombosis, stroke, pulmonary embolism, or transient ischemic
attack
C. A 60-year-old woman with bilateral asymptomatic cataracts
D. A 65-year-old woman currently on an SSRI for hot flashes
Question 24.9 A 44-year-old woman presents to your office with a new palpable breast
mass. A biopsy has been recommended based on the results of mammogram and ultrasound.
In general, the most appropriate way to diagnose suspected invasive carcinoma is:
A. Either a core or fine-needle biopsy.
B. An excisional biopsy.
C. Diagnosis by core needle biopsy.
D. A fine-needle aspiration biopsy.
Question 24.10 You are advising a 42-year-old premenopausal woman with a history of
atypical hyperplasia on prevention strategies. Which of the following is CORRECT?
A. Tamoxifen reduces her risk by #x223C;50%.
B. Oophorectomy reduces her risk by ∼50% to 65%.
C. Bilateral mastectomy completely eliminates her risk of breast cancer.
D. Raloxifene would provide similar benefit as tamoxifen.
Question 24.11 The Gail model includes which of the following risk factors?
A. Second-degree relatives with breast cancer
B. Previous breast biopsies
C. Age at first pregnancy conception
D. Age at menopause
Question 24.13 The use of radiation therapy (RT) after lumpectomy in patients with DCIS:
A. Improves overall survival (OS).
B. Reduces the risk of recurrent DCIS, but not invasive disease, in the treated breast.
C. Does not decrease local recurrence when tamoxifen therapy is administered.
D. None of the above.
Question 24.14 What stage describes a patient with a 2-cm primary breast tumor metastatic
to a movable ipsilateral lymph node?
A. T1N1M0 (IIA)
B. T2N0M0 (IIA)
C. T2N1M0 (IIB)
D. T3N1M0 (IIIA)
Question 24.15 Which of the following statements concerning local recurrences after breast-
conserving therapy is TRUE? (Select two correct responses)
A. The underlying molecular subtype is the most significant determinant of the likelihood
of local recurrence after breast-conserving therapy and mastectomy, particularly when
negative margins are achieved.
B. Most local recurrence events appear to be residual disease as opposed to second primary
cancers following BCS and RT.
C. Widely clear margins of at least 2 cm decrease the risk of a local recurrence in young
patients under 40 years.
D. Adjuvant chemotherapy affects the risk of both systemic and local recurrences.
Question 24.20 Identify the CORRECT statement regarding the use of taxanes in the
adjuvant setting:
A. Concurrent administration of docetaxel/doxorubicin/cyclophosphamide chemotherapy
is better tolerated than sequential dose-dense AC followed by paclitaxel due to lower
rates of neutropenia.
B. Weekly paclitaxel is associated with increased grade 3 and 4 neutropenia relative to
dose-dense paclitaxel.
C. Weekly paclitaxel is associated with increased grade 3 and 4 neuropathy relative to
dose-dense paclitaxel.
D. Incorporation of gemcitabine into adjuvant anthracyclines- and taxanes-based
chemotherapy improves efficacy.
Question 24.21 Risk factors for cardiac dysfunction with trastuzumab include:
A. Preexisting cardiac disease, age >65 years.
B. Non–anthracycline-based chemotherapy, age >60 years.
C. Age >65 years, current aspirin use for cardio protection, hyperthyroidism.
D. None of the above.
Question 24.22 A 57-year-old woman has been taking anastrozole as adjuvant therapy for a
moderately-differentiated T1N1 stage II breast cancer for 3 years. During a routine follow up
visit you recommend:
A. History and physical examination, complete blood count and liver function tests.
B. History and physical examination, complete blood count and liver function tests, cancer
antigen 15-3.
C. History and physical examination.
D. History and physical examination, complete blood count and liver function tests, cancer
antigen 15-3, and yearly computed tomography scans.
Question 24.24 With regard to the clinical and pathologic characteristics of male breast
cancer, which of the following is TRUE?
A. Male breast cancer is found, more often than female breast cancer, to be estrogen-
receptor negative, and the older a man is with breast cancer, the more likely the cancer
is estrogen-receptor negative.
B. Liver cirrhosis and mumps orchitis are associated with a decreased risk of male breast
cancer
C. The median age of onset is 10 years younger than the median age of onset for females.
D. Sentinel node biopsy is the preferred treatment for clinically node-negative patients.
Corresponding chapters in Cancer: Principles & Practice of Oncology, Tenth Edition: 78 (Molecular Biology of Breast Cancer),
79 (Malignant Tumors of the Breast), and 80 (Genetic Testing in Breast Cancer).
25 Cancers of the Central Nervous System
Tanner M. Johanns, Jian Li Campian and George Ansstas
QUESTIONS
Each of the numbered items below is followed by lettered answers. Select the ONE lettered answer
that is BEST in each case unless instructed otherwise.
Question 25.1 Linkage studies have identified genes associated with neurofibromatosis type
2 (NF2), Turcot syndrome, and Li–Fraumeni syndrome in which of the following
chromosomes?
A. 10q, 22q, and 17q
B. 22q, 5q, and 17p
C. 5q, 10q, and 17p
D. 5q, 10q, and 17q
Question 25.2 Of the following, the most common primary brain tumor in adults in the
United States is:
A. Glioblastoma.
B. Meningioma.
C. Astrocytoma.
D. Oligodendroglioma.
Question 25.3 The gene that is frequently altered and plays a key role in the development of
diffuse fibrillary astrocytoma is:
A. p53.
B. KRAS.
C. MDM2.
D. MDM4.
Question 25.4 Primary (de novo) glioblastoma multiforme (GBM) is commonly associated
with which of the following?
A. PTEN inactivation
B. Loss of heterozygosity of chromosomes 1p and 19q
C. IDH1 mutation
D. Median age <40 years
Question 25.5 Which gene mutation identified in GBM is frequently seen in younger
patients, and is associated with better prognosis:
A. EGFR.
B. p53.
C. IDH1.
D. Gain in chromosome 4.
Question 25.7 The central nervous system (CNS) tumor that is commonly associated with
NF2 mutations is:
A. GBM.
B. Spinal ependymoma.
C. Cerebral ependymoma.
D. Oligodendroglioma.
Question 25.8 Patients with GBM have a higher likelihood of responding to therapy with
epidermal growth factor receptor tyrosine kinase (EGFR-TK) inhibitors if which of the
following biomarkers is present?
A. Methyl guanine methyl transferase (MGMT) gene methylation
B. Activated EGFRvIII
C. Retained PTEN function
D. B and C
Question 25.9 The primary CNS neoplasm that is associated with Epstein–Barr virus (EBV)
is:
A. Primary CNS lymphoma.
B. Ependymoma.
C. Oligodendroglioma.
D. GBM.
Question 25.10 Which of the following tumors exhibit contrast enhancement on magnetic
resonance imaging (MRI) scan?
A. Pilocytic astrocytoma
B. Grade 2 oligodendroglioma
C. Grade 2 astrocytoma
D. Craniopharyngioma
Question 25.11 Which of the following is associated with good prognosis in patients with
low-grade gliomas?
A. Age ≥40 years
B. Tumor diameter ≥6 cm
C. Tumor crossing midline
D. Oligodendroglioma
Question 25.12 A 45-year-old man presents with generalized seizures, and MRI of the brain
reveals a nonenhancing mass measuring 7 cm. Biopsy is done, and the tumor histology is
reported as grade II astrocytoma. The patient undergoes surgery, and a partial (85% to 90%)
tumor resection is achieved. Further treatment should include:
A. Watchful waiting.
B. Chemotherapy.
C. Radiotherapy with 50.4 Gy in 1.8 Gy fractions.
D. Radiotherapy with chemotherapy (procarbazine, CCNU, and vincristine).
Question 25.13 In patients with GBM, who have disease recurrence following initial
treatment with temozolomide and radiation, the second-line treatment of choice is:
A. Erlotinib.
B. Imatinib.
C. Topotecan.
D. Bevacizumab.
Question 25.14 A 55-year-old man presents with headache and mental status changes. MRI
scan of the brain reveals a 5-cm contrast-enhancing mass with surrounding edema. A
stereotactic biopsy reveals GBM. The patient undergoes gross total resection of the tumor.
Further treatment should include:
A. Focal external beam irradiation with 45 Gy in 30 fractions plus concurrent
temozolomide.
B. Focal external beam irradiation with 60 Gy plus a 10 Gy boost plus concurrent
temozolomide.
C. Focal external beam irradiation with 60 Gy in 30 fractions plus concurrent
temozolomide.
D. Hyperfractionated dose of 72 Gy in 1.2 Gy fractions plus concurrent temozolomide.
Question 25.15 A 62-year-old man presents with nausea, vomiting, and severe headache.
MRI scan of the brain reveals a 5-cm mass in the posterior fossa. The patient undergoes
surgical resection of the mass, and pathology is reported as ependymoma. Further treatment
should include:
A. Radiation therapy.
B. Concurrent chemoradiation with temozolomide.
C. Chemotherapy alone with temozolomide if MGMT gene methylated.
D. Chemotherapy alone with cisplatin plus etoposide.
Question 25.16 A 53-year-old woman presents with mental status changes; brain MRI
identifies a left frontal tumor with dural marginal thickening. She undergoes a gross total
resection of the tumor and the involved dural attachments. The histopathology is WHO grade
I meningioma. Further treatment should include:
A. Watchful waiting.
B. Adjuvant radiation therapy.
C. Chemotherapy.
D. Radiosurgery.
Question 25.17 In immunocompetent patients with primary CNS lymphoma, with good
performance status and adequate renal function, appropriate first-line therapy comprises of:
A. High-dose methotrexate.
B. R-CHOP.
C. Whole brain radiation.
D. None of the above.
Question 25.18 Long-term follow-up data showed improved survival for patients with GBM,
receiving concurrent brain radiation with temozolomide compared to radiation alone, with
the exception of patients with:
A. Age >50 years.
B. Unmethylated MGMT.
C. EGFR mutation positive.
D. None of the above.
Question 25.20 In adult patients diagnosed with ependymoma, adjuvant radiation therapy
after resection is associated with improved overall survival in patients with:
A. Supratentorial location.
B. High-grade tumors.
C. Incomplete resection.
D. Poor performance status.
Question 25.23 Which three core pathways are commonly mutated in primary GBMs?
A. SHH, NF2, TRAF7
B. WNT, SHH, MAPK
C. PI3K, p53, Rb
D. NF-kB, p53, STAT
Question 25.24 Which somatic mutation is most often associated with Grade II
astrocytomas?
A. CIC
B. ATRX
C. FUBP1
D. TERT promoter
ANSWERS
Corresponding chapters in Cancer: Principles & Practice of Oncology, Tenth Edition: 96 (Molecular Biology of Central Nervous
System Tumors) and 97 (Neoplasms of the Central Nervous System).
26 Sarcomas
Brian A. Van Tine and Angela C. Hirbe
QUESTIONS
Each of the numbered items below is followed by lettered answers. Select the ONE lettered answer
that is BEST in each case unless instructed otherwise.
Question 26.1 Which of the following inherited syndromes represent a predisposing factor
for the development of soft tissue sarcoma?
A. Retinoblastoma
B. Li–Fraumeni syndrome
C. Neurofibromatosis type I
D. All of the above
Question 26.2 Which of the following are TRUE about radiation-induced sarcomas?
A. Cancer history usually includes breast cancer, lymphoma, and cervical cancer.
B. They usually occur 10 to 30 years after radiation exposure.
C. Osteogenic sarcoma, undifferentiated pleomorphic sarcoma (UPS), angiosarcoma, and
lymphangiosarcoma are the usual histologic subtypes.
D. All of the Above.
Question 26.3 Which clonal cytogenetic abnormality is associated with the CORRECT
sarcoma subtype?
A. Ewing sarcoma and t(11;22) (q24;q12)
B. Synovial sarcoma and t(12;16) (q13;p11)
C. Myxoid liposarcoma and t(X;18) (p11;q11)
D. Alveolar rhabdomyosarcoma and t(17;22) (q22;q13)
Question 26.4. A 20-year-old man presents with right knee pain. X-ray reveals a “sun-burst”
appearance in the distal femur. Biopsy reveals high-grade osteosarcoma. No distant
metastases are identified. Which of the following is the most appropriate treatment?
A. Limb-sparing resection
B. Limb-sparing resection and adjuvant chemotherapy
C. Definitive radiation
D. Neoadjuvant chemotherapy, limb-sparing resection, and adjuvant chemotherapy
Question 26.5 In addition to site, which of the following variables is used to estimate the
risk of sarcoma-specific death for a given patient?
A. Tumor grade and histology
B. Tumor size and depth
C. Age
D. All of the above
Question 26.6 Which of the following is TRUE regarding the staging of soft tissue sarcomas?
A. Staging involves a four grade system.
B. Stage IV includes N1 disease.
C. High-grade tumors can be classified as stage I depending on the size of the tumor.
D. Histologic grade, size, depth, and presence or absence of nodal and distant metastases
are variables used to determine tumor stage.
Question 26.7 A 52-year-old man underwent resection of a 3-cm mass from the lateral left
thigh. Pathology revealed a high-grade leiomyosarcoma, and the lateral surgical margin was
positive. The most appropriate next step in the treatment of this patient’s cancer would be:
A. Radiation.
B. Adjuvant chemotherapy.
C. Reresection.
D. Observation.
Question 26.8 A 68-year-old woman presented with a purplish nodular lesion in the occipital
scalp. Resection revealed an angiosarcoma measuring 3 cm. Surgical margins were negative.
What is the most appropriate next step in the treatment of this patient’s cancer?
A. Radiologic imaging to look for nodal metastases and referral for adjuvant radiation
B. Monitoring
C. Adjuvant chemotherapy with an anthracycline
D. Adjuvant chemotherapy with paclitaxel
Question 26.9 A 65-year-old woman presented with abdominal pain and iron-deficiency
anemia. Workup revealed a gastric mass and multiple large intra-abdominal masses and liver
hypodensities. Biopsy of the gastric mass revealed a spindle cell neoplasm thought to be a
leiomyosarcoma. After three cycles of doxorubicin and ifosfamide, imaging showed disease
progression. The appropriate next step in the management of this patient’s cancer would be:
A. Docetaxel and gemcitabine.
B. Dacarbazine.
C. Request the pathologist to perform a CD117 (c-Kit) stain.
D. Palliative radiation.
Question 26.10 A 55-year-old man presented with a 10-cm mass in the medial left thigh.
Biopsy revealed a high-grade liposarcoma. Imaging revealed no evidence of distant
metastases. The most appropriate treatment of this patient’s cancer would be:
A. Definitive radiation.
B. Definitive radiation and concurrent doxorubicin.
C. Limb-sparing resection followed by adjuvant radiation.
D. Preoperative chemotherapy followed by resection.
Question 26.12 Which of the following factors are independent predictors of poorer disease-
specific survival in patients with nonmetastatic soft tissue sarcoma?
A. Large tumor size (>10 cm)
B. High-grade histology
C. Older age (>60 years)
D. All of the above
Question 26.14 Which of the following is TRUE about patients with metastatic or locally
recurrent soft tissue sarcoma?
A. Median survival is 12 months, although 20% to 25% of patients are alive 2 years after
diagnosis.
B. Complete resection of oligometastases to the lung never results in long-term survival.
C. Radiation is the preferred treatment of a locally recurrent sarcoma.
D. Combination chemotherapy improves overall survival compared with single-agent
chemotherapy.
Question 26.16 A 30-year-old man presents with a permeative bone tumor in the distal
femur. Open biopsy reveals a MFH. Radiologic imaging does not find distant metastases.
What is the most appropriate treatment?
A. Limb-sparing resection with wide margins
B. Definitive radiation
C. Chemotherapy
D. Preoperative chemotherapy, limb-sparing resection, and adjuvant chemotherapy
Question 26.18 A 45-year-old man presents with a left-sided pelvic pain. CT reveals a 5 cm
mass with appearance of chondroid matrix, arising from the left side of the pelvic girdle.
Bone biopsy reveals chondrosarcoma. Which of the following is TRUE regarding
chondrosarcomas?
A. Most are low-grade tumors.
B. Most are treated with resection and radiation therapy.
C. Children have a better prognosis than adults.
D. Adjuvant chemotherapy has no role in the management of nonmetastatic disease.
Question 26.19 A 22-year-old woman presents with a giant cell tumor (GCT) of the distal
femur. Appropriate treatment would be:
A. Curettage and debridement.
B. Amputation.
C. Radiation.
D. Preoperative chemotherapy, resection, and adjuvant chemotherapy.
Question 26.20 A 16-year-old female patient presents with a painful rapidly growing
scapular mass. Core needle biopsy reveals a Ewing sarcoma. Staging evaluation shows no
evidence of metastatic disease. The most appropriate therapy is:
A. Resection.
B. Preoperative chemotherapy (with vincristine, doxorubicin, and cyclophosphamide
alternating with ifosfamide and etoposide, IE), resection, and adjuvant chemotherapy.
C. Resection and radiation.
D. Preoperative chemotherapy (with vincristine, doxorubicin, and cyclophosphamide),
resection, and adjuvant chemotherapy.
Question 26.21 A 25-year-old woman presents with a painless right thigh mass, which has
been slowly growing over a span of 8 years. Core needle biopsy reveals alveolar soft part
sarcoma. What cytogenetic abnormality would you expect to see in this tumor?
A. t(11;22) (q24;q12)
B. t(12;16) (q13;p11)
C. der (17) t(X;17) (p11;q25)
D. t(X;18) (p11;q11)
Question 26.22 Which of the following targeted agents is used to treat alveolar soft part
tissue sarcoma?
A. Imatinib
B. Sunitinib
C. Dasatinib
D. Nilotinib
Question 26.23 Which of the following sites of soft tissue sarcomas carries the best
prognosis?
A. Head and neck
B. Extremity
C. Visceral
D. Retroperitoneal
Question 26.24 A 60-year-old woman with advanced soft tissue sarcoma is on third-line
therapy with pazopanib and develops jaundice. Which of the following should be done next?
A. Abdominal imaging
B. Laboratory testing
C. Dose reduction
D. Immediately discontinue pazopanib
Question 26.25 Which of the following criteria are predictive of the behavior of GIST
tumors and are useful for stratification of risk of recurrence and metastasis? (Select two
correct responses)
A. Mitotic rate
B. Nuclear atypia
C. Tumor site
D. Mucosal invasion
Corresponding chapters in Cancer: Principles & Practice of Oncology, Tenth Edition: 89 (Molecular Biology of Sarcomas), 90
(Soft Tissue Sarcoma), and 91 (Sarcomas of Bone).
27 Cancer of the Skin and Melanoma
Gerald P. Linette
QUESTIONS
Each of the numbered items below is followed by lettered answers. Select the ONE lettered answer
that is BEST in each case unless instructed otherwise.
Question 27.1 What is the most prevalent significantly mutated gene in cutaneous
melanoma?
A. BRAF V600K
B. BRAF V600R
C. BRAF V600E
D. NRAS Q61R
E. NRAS Q61K
Question 27.2 Which of the following is included in referral criteria for hereditary
melanoma genetic counseling?
A. Parent with multiple skin cancers.
B. Pancreatic cancer and melanoma on the same side of the family.
C. Three or more siblings with actinic keratosis.
D. Two relatives on the same side of the family with melanoma and prostate cancer.
Question 27.3 Which of the following genes act as founding mutations implicated in the
early transformation of cutaneous melanoma (Select two correct responses)?
A. NRAS
B. BRAF
C. TP53
D. MEK1
Question 27.4 Which of the following statements best explains the increased incidence of
melanoma over the past 25 years?
A. Decreasing use of sunscreen among middle age persons.
B. High penetrance rate of CDKN2A mutations.
C. Increasing exposure to ultraviolet light.
D. Increasing use of birth control pills.
Question 27.5 What is the most common site for primary skin melanoma in females?
A. Back
B. Face
C. Lower extremities
D. Scalp
Question 27.6 Which one of the following features of primary melanoma is the most
important prognostic factor?
A. Clark level
B. Breslow thickness
C. Mitotic rate
D. Anatomical location
Question 27.7 Basal cell nevus syndrome has been associated with mutations in which one
of the following genes?
A. Patched gene 1
B. Sonic hedgehog
C. MEK1
D. NF1
Question 27.8 A 48-year-old woman was recently diagnosed with a nonulcerated 1.6-mm
depth primary superficial-spreading melanoma excised from her back. The melanoma is
nonmitogenic and the margins are negative. She is referred to you for further evaluation and
no adenopathy is noted on examination. Which of the following is the most appropriate next
step in clinical management?
A. PET-CT to complete the staging evaluation.
B. Referral back to the Dermatologist for annual skin checks.
C. Wide excision and sentinel lymph node mapping.
D. Wide excision followed by interferon for 1 year.
Question 27.10 A 29-year-old man is recently diagnosed with primary cutaneous melanoma.
The pathology report confirms a T3b N2b M0 primary nodular melanoma excised from the
left shoulder. The primary lesion was ulcerated and mitogenic (4/mm2). The patient is in
excellent health and has no significant past medical history. The patient is referred to you for
adjuvant treatment. What is the final stage of this patient’s melanoma?
A. Stage IIIA
B. Stage IIIB
C. Stage IIIC
D. Stage IV, M1A
Question 27.11 A 40-year-old woman with a history of ulcerative colitis, mitral valve
prolapse, eczema, and stage 1 cutaneous melanoma presents with right inguinal adenopathy.
Physical examination confirms a 4-cm node and core biopsy confirms malignant melanoma.
BRAF mutational analysis is requested and BRAF V600E mutation is detected. Brain MRI is
unremarkable; however, CT examination reveals numerous (>10) bilateral pulmonary
metastases with the largest lesion measuring 1.2 cm in the left upper lobe. No other sites of
distant metastases are evident and you conclude that this patient has stage IV, M1b disease.
The patient does not want to participate in a clinical trial and wants to begin treatment as
soon as possible. What is the best initial treatment for this individual?
A. Ipilimumab
B. BRAF inhibitor
C. MEK inhibitor
D. BRAF and MEK inhibitor combination
Question 27.12 A 73-year-old man with a past history of stage IIC nodular melanoma
excised from his back 3 years ago presents to your office with lower back pain and fatigue
for the past 2 weeks. Your physical examination is unrevealing. However, several
laboratories are elevated, including serum alkaline phosphatase, and serum LDH (two times
upper limit of normal). PET-CT examination the following day documents metastatic disease
involving lungs, liver, peritoneum, and multiple osseous areas, including the lumbar spine.
What is the most appropriate next step in management?
A. Request a brain MRI and a biopsy of a lung lesion.
B. Request a palliative care consultation.
C. Request a second opinion review of the primary cutaneous lesion excised 3 years ago.
D. Begin systemic therapy as soon as possible.
Question 27.13 A 36-year-old woman with a past history of cutaneous melanoma (stage IIB)
has been followed by her dermatologist. She has active rheumatoid arthritis and is receiving
methotrexate under the care of a local rheumatologist. She recently presented to the
emergency department with complaints of headaches and was found to have a 3.5-cm solitary
right parietal metastasis. The metastasis was surgically resected and confirmed as metastatic
melanoma, BRAF V600E mutated. A postoperative body PET-CT examination was negative
for additional disease and the hospital physicians told her that she has no additional evidence
of disease. She is referred to you for treatment recommendations. What is the next best step
in the management of her care?
A. Request radiation oncology consultation for stereotactic radiosurgery.
B. Request radiation oncology consultation for whole brain radiation.
C. Administer adjuvant chemotherapy.
D. Administer adjuvant interferon.
Question 27.14 A 27-year-old woman has metastatic melanoma, BRAF wild type (no
mutation), stage IV, M1B. You recommended initial systemic treatment with ipilimumab and
she completed four doses with no side effect or toxicity. Two weeks after the four dose a
restaging CT examination is performed which reveals the appearance of a new 6-mm left
upper lobe lesion as well as an increase of a baseline right lower lung lesion from 17 mm to
23 mm. The other lung metastases remain unchanged. You see the patient in your office the
following day. She feels fine and has no complaints. Her laboratories are all within normal
limits. However, the patient is anxious after you discuss the CT imaging results with her. She
and her husband have many questions regarding other treatment options. What is your
recommendation to this patient?
A. Despite the fact that her tumor is BRAF wild type, there is some evidence that
treatment with a MEK inhibitor would be beneficial.
B. You recommend a repeat CT scan in 4 weeks based upon reports that 10% to 15% of
patients treated with ipilimumab can have evidence of progression prior to documented
response.
C. You recommend retreatment with four additional doses of ipilimumab.
D. You recommend immediate surgical consultation.
Question 27.15 A 66-year-old man with metastatic melanoma is receiving treatment with
combination ipilimumab and nivolumab on a clinical trial. Fourteen days after the second
dose, he calls your office to tell you that he has been having watery loose stools up to ten
times a day for the past week. However, you are out of town and your nurse practitioner
called in sick for the day. What is your recommendation to this patient?
A. Call your primary physician immediately.
B. Keep your scheduled appointment next week for the third dose but call sooner if the
diarrhea gets worse.
C. Take loperamide as directed and keep hydrated.
D. Go to the local emergency department immediately for evaluation.
Question 27.16 A 70-year-old man from out of town presents to the emergency department
with complaints of profound fatigue and headaches for the past 3 days. His vital signs are
normal except for a blood pressure of 90/50. He denies fevers and diarrhea. His medical
history is significant for gout, type 2 diabetes, and metastatic melanoma. He is receiving
treatment with ipilimumab along with an experimental immunotherapy drug but he can’t
remember the name of the investigational drug. He has received four cycles of treatment and
is due for a restaging evaluation when he returns home in a week. Unfortunately, it’s a
holiday weekend and no medical records are available. You request a CBC, CMP, and EKG
along with a head CT and CT examination of the chest, abdomen, and pelvis. The chest CT
confirms the presence of innumerable (>20) pulmonary metastases but none greater than 2
cm. The head CT is unremarkable. You are perplexed and unsure of the cause of his
symptoms. You decide to order additional blood work. What is the most appropriate test to
order?
A. Blood cultures
B. Serum LDH
C. Thyroid function tests
D. C-reactive protein
E. Discharge to home with instructions to call his oncologist
Question 27.17 A 75-year-old woman with a past history of recurrent basal cell carcinoma
of the skin was recently found to have bilateral lung lesions. CT examination confirms 10
pulmonary lesions as well as several liver lesions. The 2.5-cm right upper lobe lesion is
biopsied and confirmed as basal cell carcinoma. Her primary care physician tells her that she
will need chemotherapy. She arrives in your office along with several additional family
members, including her daughter who is a physician. They are distraught over the recent
diagnosis and have solicited the opinions of various physicians. They understand her
condition is incurable but desire the best treatment. What is your treatment
recommendation?
A. Platinum-based chemotherapy for six cycles
B. Vismodegib
C. Trametinib
D. Immediate radiation oncology consultation
E. Immediate surgical consultation
ANSWERS
Corresponding chapters in Cancer: Principles & Practice of Oncology, Tenth Edition: 92 (Cancer of the Skin), 93 (Molecular
Biology of Cutaneous Melanomas), 94 (Cutaneous Melanomas), and 95 (Genetic Testing in Skin Cancer).
28 Lymphomas
Nina Wagner-Johnston and Dilan Patel
QUESTIONS
Each of the numbered items below is followed by lettered answers. Select the ONE lettered answer
that is BEST in each case unless instructed otherwise.
Question 28.1 An 8-year-old child is brought to clinic by his mother due to a jaw lump that
has been increasing in size over the past month. The mother states that the lump is
preventing her child from eating. Physical examination reveals a child in moderate distress
with a left jaw mass that displaces teeth and is impinging on the trachea. Biopsy reveals
sheets of atypical lymphocytes with areas of necrosis and hemorrhage. Ki-67 is 99%. Flow
cytometry shows B-cell markers as well as CD10 and BCL-6. CD5, BCL-2, and TdT are absent.
Which of the following is the most common translocation in this malignancy?
A. t(1;14)
B. t(2;8)
C. t(8;14)
D. t(8;22)
Question 28.2 Which of the following characterize/s a difference between endemic and
sporadic Burkitt lymphoma in children?
A. Endemic disease occurs more commonly in Africa and is associated with EBV infection.
B. Common sites of endemic disease are the mediastinal and hilar lymph nodes, which
often leads to rapid respiratory compromise.
C. Dysregulation of both c-myc and BCL-2 are required for tumor cell growth.
D. Sporadic Burkitt lymphoma occurs in nonmalaria endemic areas, with common areas of
development including the abdomen.
Question 28.3 Which one of the following syndromes is associated with a higher risk of
adult lymphoma as opposed to childhood lymphoma?
A. Ataxia-telangiectasia
B. HIV/AIDS
C. Wiskott–Aldrich syndrome
D. X-linked lymphoproliferative syndrome
Question 28.4 A 35-year-old Caucasian male presents to his primary doctor due to 2 months
of gradually worsening fevers, chills, and night sweats that soak through multiple pillows. He
recalls having lost some weight over the past months, involuntarily, but is most bothered by
an itchy rash on his abdomen that has recently started to ulcerate. Physical examination
reveals painless lymphadenopathy. Biopsy shows pleomorphic large cells with prominent
nucleoli. Immunophenotyping shows cells positive for CD30 and ALK, and negative for B-cell
markers. Which of the following is TRUE regarding this condition?
A. ALK-positive cases are more common in adults.
B. ALK protein is detected in a minority of cases.
C. Cells are often derived from mature, activated T cells.
D. Prognosis in ALK-positive cases is worse than ALK-negative cases.
Question 28.5 A 55-year-old African-American man presents to his PCP with abdominal pain
that has been gradually increasing over 3 months. He notes that he has been urinating less
than normal. Furthermore, he complains of persistent fevers and drenching night sweats. His
wife notes that he looks thinner than before. The patient is less active than his baseline but is
able to perform light housework without difficulty. Physical examination reveals nontender
adenopathy in the bilateral cervical and left axillary regions. PET/CT shows FDG-avid
bilateral cervical, left axillary, and mediastinal lymphadenopathy as well as a 7-cm
retroperitoneal mass resulting in bilateral hydronephrosis. CBC is within normal limits. LDH
is 210 IU/L (upper limit of normal 250 IU/L). Bone marrow biopsy demonstrates no evidence
of disease. Which of the following best describes the patient’s International Prognostic Index
(IPI) score?
A. 0
B. 1
C. 2
D. 3
Question 28.8 Which of the following B-cell lymphomas may have CD10 positivity and the
t(14;18) translocation? (Select two correct responses)
A. Diffuse large B-cell lymphoma
B. Follicular lymphoma
C. Lymphoplasmacytic lymphoma
D. Mantle cell lymphoma
Question 28.9 A 66-year-old Caucasian male with HIV and CD4 count of 53 is being worked
up by his oncologist for a new diagnosis of diffuse large B-cell lymphoma, which involves
diffuse lymphadenopathy, the paranasal sinuses, testes, and bone marrow based on initial
studies. What is the next best step in management?
A. Initiation of testicular radiation
B. Lumbar puncture
C. Orchiectomy
D. Upper and lower endoscopy
Question 28.10 A 71-year-old man presents to clinic with abdominal pain. Review of
systems is also positive for fatigue and easy bleeding from the nose and gums. Physical
examination reveals splenomegaly. Pertinent labs include hemoglobin of 12 g/dL, platelets of
16,000, LDH of 400 IU/L (upper limit of normal 250 IU/L), and albumin of 3.6 g/dL.
Peripheral smear reveals “villous lymphocytes.” Flow cytometry is positive for CD19, CD20,
and CD22 and negative for CD5, CD25, and CD103. Which of the following are possible steps
in initial management? (Select three correct responses)
A. Autologous stem cell transplantation
B. Chemotherapy with alkylating agents
C. Splenectomy
D. Single agent rituximab
Question 28.11 Which of the following findings portend a shorter survival/worse prognosis
for patients with splenic marginal zone lymphoma? (Select three correct responses)
A. Albumin <3.5 g/dL
B. Hemoglobin <12 g/dL
C. LDH >normal
D. Presence of villous lymphocytes
Question 28.12 A 69-year-old Caucasian man presents to his primary care doctor for
persistent nausea associated with nonbloody, nonbilious emesis, loss of appetite, and 30-lb
weight loss over approximately 1 year. He also recalls having occasional dark stools. Physical
examination reveals splenomegaly. PET/CT reveals FDG avidity of intra-abdominal lymph
nodes as well as uptake in the stomach and small and large bowel. Upper and lower
endoscopy reveals a nonbleeding gastric ulcer and diffuse polyps in the colon. Biopsies are
performed. Cells express surface IgM and IgD along with CD5, CD19, and CD20.
Cytogenetics reveals t(11;14). Which of the following statement(s) is/are accurate regarding
the next step in management?
A. Consolidation with autologous stem cell transplantation in first remission is an approach
often considered for fit patients.
B. Treatment with ibrutinib in the upfront setting is limited because of its association with
peripheral neuropathy.
C. Front-line therapy for elderly patients with good performance status includes
bendamustine and rituximab.
D. Hyper-CVAD with rituximab may be administered to patients with more aggressive
disease.
Question 28.13 A 46-year-old Caucasian man presents to clinic due to drenching night
sweats associated with persistent, high-grade fevers and 40-lb weight loss over the past 6
months. Physical examination reveals lymphadenopathy of the cervical and axillary nodes as
well as hepatospenomegaly. PET/CT reveals avid uptake throughout the mediastinum,
stomach, and small bowel, with multiple nodes measuring up to 2 cm. FISH reveals BCL-
1/IgH fusion gene product. Additional studies show decreased expression of p21, p27, and
p53. Which of the following statement(s) regarding the illness is/are CORRECT?
A. Cells arise from antigen-naive B-cells of the inner mantle zone.
B. Most patients present in early-stage disease.
C. The condition is more common in females.
D. Tumor cells strongly express surface IgG and IgD as well as CD19 and CD20.
Question 28.14 A 26-year-old Caucasian man with no past medical history presents to the
emergency department with right knee pain that occurred suddenly while playing volleyball.
He is found to have a pathologic fracture of the right distal femur. Further imaging with
PET/CT reveals localized uptake of the right femur and tibia. Flow cytometry shows that
cells are CD19, CD20, and CD22 positive. Immunohistochemistry also reveals that cells are
CD10 positive and negative for BCL-6 and MUM-1. Which of the following statement(s)
regarding disease subtype is/are accurate?
A. Ig gene shows intraclonal homogeneity.
B. Nuclear factor kappa beta signaling is the primary driver of proliferation and
metastases.
C. Survival is worse compared to other subtypes.
D. The subtype is often associated with t(14;18).
Question 28.15 A 63-year-old African-American woman with a past medical history of HIV
presents to the emergency room with shortness of breath. She notes that it has been
worsening over the past 3 to 4 months, but became unbearable over the past week. Review
of systems is positive for involuntary weight loss of 30 lb over 4 months and pedal edema.
Physical examination reveals pitting edema to the knees bilaterally. PET/CT scan shows
diffuse adenopathy of the mediastinum and the pelvis, with the largest nodes measuring 2.5
cm. No extranodal disease is appreciated. Excisional biopsy reveals proliferating large and
small lymphocytes. Ki-67 is 85%. Flow cytometry reveals cells that are CD19, CD20, and
CD22 positive and negative for CD10 and BCL-6. Which of the following statements
regarding management is accurate?
A. R-CHOP chemotherapy is appropriate.
B. ABVD chemotherapy is preferred as first-line management.
C. Allogeneic stem cell transplant is the treatment of choice if the patient were to relapse
with chemosensitive disease.
D. Rituximab with CHOP confers greater benefits in patients who lack BCL-6 expression,
based on the GELA R-CHOP trial.
Question 28.16 A 55-year-old Chinese man presents to his primary care physician due to
chronic sinus pain that has been present for 5 months. He also complains of epistaxis, fevers,
drenching night sweats, and 30-lb weight loss. Physical examination is pertinent for temporal
wasting and tenderness to palpation around the paranasal sinuses as well as cervical
adenopathy. Labs reveal LDH of 425 IU/L (upper limit of normal 250 IU/L). CT of the
sinuses reveals an infiltrating mass in the midline nasal sinus. Immunophenotype reveals
atypical cells that are positive for CD2, CD56, and cytoplasmic CD3, and negative for CD4,
CD8, and surface CD3. EBV is detected. The cytoplasmic granule proteins, granzyme B and
TIA-1, are present. Cytogenetics reveals del(6)(q21;q25). Which of the following
statement(s) regarding treatment is/are CORRECT?
A. Allogeneic stem cell transplantation is a standard first-line therapy in fit patients.
B. EBV-related hemophagocytic syndrome is often fatal and treated with front-line
radiation.
C. Localized disease is initially managed with concurrent chemotherapy and radiation
D. Patients with disseminated disease that is chemotherapy sensitive are effectively treated
with a combination of R-CHOP and radiotherapy
Question 28.17 A 43-year-old woman presents to a dermatologist with a diffuse skin rash,
described as red and itchy with associated thickening of the palms and soles that has been
slowly progressing for the past 4 years. Physical examination reveals erythematous plaques
on 20% of the body surface area. FDG PET reveals absence of extracutaneous disease. Skin
biopsy reveals Pautrier microabscesses. Immunophenotyping reveals expression of CD2, CD3,
CD5, and CD7. What is the next best step in management?
A. EPOCH chemotherapy combined with pentostatin and fludarabine with interferon alpha
B. Extracorporeal photochemotherapy
C. Locally applied denileukin diftitox with or without vorinostat
D. Topical carmustine or mechlorethamine, bexarotene, or ultraviolet B with or without
interferon alpha
Question 28.18 Which of the following accurately describes an aspect of primary CNS
lymphoma (PCNSL)?
A. AIDS patients tend to have large, invasive unifocal masses that rapidly progress without
HAART therapy.
B. Incidence has decreased fivefold from 1985 to 1997 due to advances in treatment of
immunosuppressed patients.
C. Many masses are periventricular, allowing tumor cells access to cerebrospinal fluid.
D. Presents most commonly in the occipital lobe, manifesting as vision changes and gait
abnormalities.
Question 28.19 Which of the following statement(s) regarding the presentation of primary
CNS lymphoma is/are CORRECT?
A. Approximately 20% of patients have ocular involvement at the time of presentation,
particularly of the optic nerve, vitreous, retina, and choroid.
B. Most patients present in stage I, explaining the good prognosis of the condition.
C. Primary leptomeningeal lymphoma in the absence of a brain mass accounts for 40% of
cases, with symptoms including leg weakness and incontinence/retention.
D. Studies have shown that 10% of patients can have spread of disease outside of the CNS,
mostly to the bone marrow and lymph nodes.
Question 28.20 A 71-year-old Caucasian man is brought to his primary care physician by his
wife, who says that he has been exhibiting increasingly aggressive behavior over the past 5
months, manifesting as irritability and outbursts of anger, both of which are outside of his
norm. She also says that he has had two motor vehicle accidents in the same time period, due
to not noticing traffic lights. Neurologic examination reveals decreased ability to follow
commands, 20/200 vision in both eyes, and left-sided weakness. Brain MRI shows a 4 × 5
cm solitary, nonhemorrhagic mass in the right frontal lobe. Lumbar puncture reveals
predominance of clonal lymphocytes. Biopsy indicates cells positive for BCL-2, BCL-6, and
MUM1 as well as CD19, CD20, and CD22. What is the next best step in management?
A. High-dose methotrexate and rituximab, with or without Ara-C and temozolomide.
B. R-CHOP chemotherapy with intrathecal methotrexate.
C. Six weeks of concurrent chemotherapy with methotrexate and dexamethasone combined
with focal radiation therapy.
D. Systemic adriamycin and etoposide with high-dose dexamethasone.
Question 28.21 Which of the following statements best characterizes nodular lymphocyte-
predominant Hodgkin lymphoma (NLPHL) in contrast to classic Hodgkin lymphoma (cHL)?
A. Approximately 80% of patients with NLPHL have stage I to II disease at the time of
diagnosis.
B. Bone marrow involvement is frequent with stage III to IV disease.
C. Disease presentation manifests predominantly in thoracic nodes before spreading to the
mediastinum.
D. NLPHL cells express CD30 and CD45 as well as B-cell antigens.
Question 28.22 A 24-year-old G1P0 woman presents to her physician with fever, neck pain,
fatigue, and 10-lb weight loss during the first trimester of pregnancy. She is concerned about
the health of her fetus. Physical examination reveals nontender cervical adenopathy, leading
to a biopsy, which reveals cells that are positive for CD15 and CD30 and negative for CD3,
CD7, CD20, and CD45. Morphology is pertinent for Reed–Sternberg cells in a background of
inflammatory cells. Which of the following accurately describe(s) an aspect of care for such
patients?
A. BEACOPP chemotherapy is preferred to ABVD for treatment during the first trimester
due to the lack of antimetabolites in the regimen.
B. MRI scanning is preferred for staging because it is nonteratogenic.
C. Long-term survival of treated pregnant women is inferior to that of nonpregnant
women with the disease.
D. Radiation therapy with abdominal shielding can be safely used for bulky disease above
the diaphragm.
ANSWERS
Corresponding chapters in Cancer: Principles & Practice of Oncology, Tenth Edition: 101 (Molecular Biology of Lymphomas),
102 (Hodgkin Lymphoma), 103 (Non-Hodgkin Lymphoma), 104 (Cutaneous Lymphomas), and 105 (Primary Central Nervous
System Lymphomas)
29 Acute Leukemias
Amanda F. Cashen
QUESTIONS
Each of the numbered items below is followed by lettered answers. Select the ONE lettered answer
that is BEST in each case unless instructed otherwise.
Question 29.1 The (8;21) cytogenetic rearrange, which is associated with favorable risk in
acute myeloid leukemia (AML), juxtaposes which genes?
A. AML1-ETO
B. RUNX1-RUNX1T1
C. A core-binding factor and a zinc finger protein
D. All of the above
Question 29.2 You are caring for a 25-year-old woman with AML-M2 and normal
cytogenetics. She receives 7 + 3 induction therapy, and her day-14 bone marrow biopsy is
ablated. She returns to clinic and her day-45 bone marrow shows normal hematopoiesis.
However, she relapses after 18 months. Which of the following likely contributed to her
relapse?
A. DNMT3A mutation
B. CEBPA mutation
C. NPM mutation without FLT3-ITD
D. Her age
Question 29.3 Your well-read 30-year-old patient with AML asks you how you will follow
her disease once she is in remission. She asks which is the most sensitive test for minimal
residual disease. In which order are these assays most sensitive (least to most sensitive)?
A. Cytopathology < fluorescence in situ hybridization (FISH) < polymerase chain
reaction (PCR)
B. FISH < cytogenetics < PCR
C. PCR < cytopathology < FISH
D. Cytogenetics < PCR < flow cytometry
Question 29.4 Mutation of which of the following genes is associated with a worse
prognosis in core-binding factor AML?
A. ABL
B. CKIT
C. NPM1
D. GATA-1
Question 29.5 A 52-year-old man presents with AML. On day 2 of induction therapy, he
develops diffuse alveolar hemorrhage. An expected physical finding on examination would
be:
A. Diffuse ecchymosis.
B. Diffuse intravascular coagulopathy.
C. Swollen gums.
D. Cardiac rub.
Questions 29.6–7 You have been following a 75-year-old woman in clinic with mild renal
insufficiency and progressive anemia. She has good performance status and presents to clinic
with a 3-day history of progressive fatigue and new headaches. Her white blood cell (WBC)
count is 53,000 with 50% blasts.
Question 29.6 Given her history, what is the expected finding in the cytogenetics?
A. t(15;17)
B. –7
C. inv(16)
D. t(8;21)
Question 29.7 Which of the following is associated with improved prognosis in this patient?
A. Probable leukostasis
B. Her age
C. Prior myelodysplastic syndrome (MDS)
D. Good performance status
Question 29.8 Which of the following cytogenetic profiles from an AML patient is an
example of monosomal karyotype?
A. −7
B. +8, inv(3), del(5q)
C. inv(16)
D. −7, −5, t(3;21)
Question 29.9 Which of the following is a poor prognostic factor in adult ALL?
A. Age <55 years
B. WBC <10,000
C. Diploid chromosomes on karyotyping
D. t(4;11)
Question 29.10 A 70-year-old man presents with newly diagnosed AML-M4 with
eosinophilia. Which of the following factors will have the greatest impact on the choice of
therapy?
A. His age
B. His performance status
C. His cytogenetics
D. Excellent response to 7 + 3 induction therapy in the elderly
Question 29.11 You have been following a 54-year-old woman with acute promyelocytic
leukemia (APL) in clinic. After 2 years she returns to clinic with fatigue, an elevated WBC,
and increased promyelocytes. Peripheral blood PCR confirms recurrence of her t(15;17)
translocation. Before starting arsenic salvage therapy, which test you obtain?
A. Liver function test
B. Erythrocyte sedimentation rate
C. D-dimer
D. Electrocardiogram
Question 29.12 You have been caring for a 65-year-old woman with a distant history of
breast cancer treated with adjuvant cyclophosphamide and adriamycin. During the last year,
she developed progressive anemia and thrombocytopenia. She also recently developed
leukopenia. Her bone marrow biopsy shows decreased cellularity with dysplastic features and
25% blasts. Which of the following cytogenetic changes might you expect to find?
A. t(15;17)
B. t(9;21)
C. Complex cytogenetics
D. Trisomy 21
Question 29.13 Which of the following statements is TRUE regarding elderly patients (age
>65 years) with AML? (Select two correct responses)
A. In general, older patients with AML have poor outcomes when compared to younger
patients.
B. Treatment with hypomethylating agents leads to the same response rate as more
intensive chemotherapy.
C. Older patients are more likely to have favorable risk cytogenetics than younger
patients.
D. Treatment with decitabine leads to better response rates but similar survival compared
to low-dose cytarabine.
Questions 29.14–18 You are consulted to see a 20-year-old Hispanic woman who presented
with progressive fatigue during the last week and then significant epistaxis. Her WBC is
12,000/μL with 40% promyelocytes and a platelet count of 15,000/μL. Her international
normalized ratio (INR) is 2.7 with a prothrombin time of 45 and partial thromboplastin time
of 65. Her fibrinogen is 82. On review of her peripheral smear, you observe many
promyelocytes with large granules and multiple Auer rods.
Question 29.14 After review of her peripheral smear, you suspect that she has APL. While
awaiting confirmation of the diagnosis, your initial therapy should include which of the
following?
A. Steroids
B. Cytarabine
C. Fresh-frozen plasma
D. Arsenic trioxide
Question 29.15 Three days after starting idarubicin and ATRA, her coagulopathy has
improved. She has shortness of breath in the morning and rapidly becomes hypoxic over the
course of the day. Which of the following would prove most helpful in treating her hypoxia?
A. High-flow facemask oxygen
B. Lasix
C. Methylprednisolone
D. Albuterol
Question 29.16 Fifteen days into treatment she develops a severe headache. Her neurologic
and fundoscopic evaluations are normal. Review of her morning laboratory tests reveal a
WBC of 0.6/μL, hematocrit of 9.8, platelet count of 25,000/μL, INR of 1.4, and fibrinogen of
190. You obtain a noncontrast head computed tomography scan but are more worried that
this is a result of:
A. Relapse.
B. ATRA.
C. Idarubicin.
D. Transfusion reaction.
Question 29.17 Six months later you are reviewing her chart. Her CBC has normalized, and
she has tolerated consolidation therapy. Her most recent PCR showed no sign of residual
disease. You are most concerned about relapse because of:
A. Her microgranular variant presentation.
B. Her presenting coagulopathy.
C. Her presenting WBC.
D. Her ethnicity.
Question 29.18 Three years later she presents to clinic with an elevated leukocyte count.
PCR of peripheral blood confirms the presence of her initial t(15;17) translocation. Treatment
options at this point include which of the following?
A. Arsenic trioxide
B. Gemtuzumab ozogamicin
C. Autologous transplant after achieving CR
D. All of the above
Question 29.20 Which of the following regimens require graft-versus-tumor effects to treat
residual AML blasts?
A. Busulfan-cyclophosphamide
B. Cyclophosphamide-TBI
C. Busulfan-fludarabine
D. Busulfan-VP16
Question 29.21 Central nervous system (CNS) prophylaxis should be considered in which of
the following patients?
A. A 25-year-old Hispanic woman with APL who presents with a WBC of 2500/μL, an INR
of 2.5, and fibrinogen of 100
B. A 78-year-old man with AML evolved from MDS
C. A 30-year-old woman with AML who develops headaches while receiving ondansetron
for nausea on day 9 of induction therapy
D. A 20-year-old man with Down syndrome and ALL who presents with leukocytosis (WBC
120,000/μL)
Question 29.22 Dexamethasone has replaced prednisone in ALL induction therapy because
of improved penetration in which tissue?
A. Testes
B. Spleen
C. Bone marrow
D. Brain
Question 29.23 How long should maintenance therapy for ALL with daily 6-mercaptopurine,
weekly methotrexate, and monthly vincristine and prednisone be continued?
A. 6 months
B. 12 months
C. 24 to 36 months
D. Until relapse
Question 29.24 Which of the following targeted agents have been shown to be beneficial in
adult ALL?
A. Imatinib
B. Alemtuzumab
C. Gemtuzumab ozogamicin
D. Sunitinib
Question 29.25 For which of the following patients would you consider myeloablative stem
cell transplantation in CR1?
A. A 30-year-old woman with inv(16) AML-M4 with eosinophilia
B. A 50-year-old man with complex cytogenetics AML-M1
C. A 65-year-old man with complex cytogenetics AML-M1
D. A 50-year-old woman with t(15;17) AML-M3
Question 29.26 Which of the following statements is TRUE regarding the nucleophosmin 1
(NPM1) mutation in AML? (Select two correct responses)
A. In normal karyotype AML, NPM1 mutation without FLT3-ITD confers a prognosis
similar to good-risk cytogenetics.
B. NPM1 mutations are found mostly in patients with AML with normal karyotype.
C. NPM1 mutation combined with FLT3-ITD is associated with good prognosis.
D. All the above
ANSWERS
Corresponding chapters in Cancer: Principles & Practice of Oncology, Tenth Edition: 106 (Molecular Biology of Acute
Leukemias) and 107 (Management of Acute Leukemias).
30 Chronic Leukemias
Pavan Bhamidipati and Keith Stockerl-Goldstein
QUESTIONS
Each of the numbered items below is followed by lettered answers. Select the ONE lettered answer
that is BEST in each case unless instructed otherwise.
Question 30.1 The Sokal score was developed to predict the probability of disease
progression in CML. Which of the following variables are used to calculate this score?
A. Percentage of blasts in peripheral blood
B. Platelet count
C. Spleen size (centimeters below the costal margin)
D. Age of the patient
E. All of the above
Question 30.3 Real-time quantitative polymerase chain reaction (RQ-PCR) has emerged as
the most effective and sensitive way to assess response to therapy in CML and has the added
flexibility of utilizing peripheral blood instead of bone marrow for the measurement of
cytogenetic response. How does molecular response correspond to complete cytogenetic
response (CCyR)?
A. 2-log reduction in transcript levels or 1% International scale (IS) or MR2
B. 3-log reduction in transcript levels or 0.1% IS or MR3
C. 4-log reduction in transcript levels or 0.01% IS or MR4
D. 3-log reduction in transcript levels or 1% IS or MR2
Question 30.4 A 59-year-old male with a history of coronary artery disease and diabetes
mellitus was diagnosed with chronic-phase chronic myeloid leukemia (CML). What is the
most appropriate therapeutic intervention?
A. Imatinib 400 mg QD
B. Dasatinib 100 mg QD
C. Nilotinib 300 mg BID
D. Ponatinib 30 mg QD
Question 30.5 A 60-year-old female has been under your care for chronic-phase CML for the
past 2 years. She achieved complete response on nilotinib. She subsequently developed
thrombocytopenia with elevated RQ-PCR and a bone marrow biopsy showed 42% Ph-positive
metaphases. Mutational analysis showed T315I mutation in the ABL domain. What is the
appropriate treatment for this patient?
A. Imatinib
B. Ponatinib
C. Dasatinib
D. Nilotinib
Question 30.6 A 56-year-old female was diagnosed with chronic-phase CML 6 months ago
and was started on imatinib at 400 mg QD. Treatment however, was discontinued due to skin
rash and diarrhea and replaced by dasatinib at 100 mg QD. She came to the ER 2 weeks later
with new onset of dyspnea and found to have moderate bilateral pleural effusions. What is
the appropriate management?
A. Diagnostic thoracentesis
B. Temporary dasatinib discontinuation
C. Prednisone 0.5 mg/kg for 1 or 2 weeks
D. Start diuresis with furosemide
E. B, C, and D
Question 30.7 What is the appropriate frequency of testing for responses in CML patients
who are currently on imatinib therapy?
A. Bone marrow biopsy every 6 months, RQ-PCR every 3 months for first 2 years, then
q4–6 months
B. Bone marrow biopsy every 3 months, RQ-PCR every 6 months for first 2 years, then
q4–6 months
C. Bone marrow biopsy every 12 months, RQ-PCR every 3 months for first 2 years, then
q4–6 months
D. None of the above
Question 30.8 What constitutes a relapse in a patient with CML who achieved complete
hematologic response while on tyrosine kinase inhibitor therapy? (Select two correct
responses)
A. Rise of RQ-PCR from 0.01% to 0.05%
B. Drop in platelets from 180,000 to 80,000 ten months into therapy
C. Rise in the Ph-positive metaphase levels from 0% to 20% on bone marrow biopsy ten
months into therapy
D. None of the above
Question 30.9 What are the expected landmarks that are known to be associated with better
outcomes while on imatinib therapy?
A. Complete hematologic response (CHR) at 3 months
B. Major cytogenetic response (MCyR) at 6 months
C. Complete cytogenetic response (CCyR) at 12 months
D. 3-log reduction in BCR-ABL transcripts (MR3) measured by RQ-PCR at 12 months
E. All of the above
Question 30.10 With the advent of tyrosine kinase inhibitors (TKIs), allogeneic stem cell
transplantation (allo-HCT), once a primary therapy for CML, is now reserved for specific
CML patients. What are the indications for allo-HCT in CML? (Select two correct responses)
A. Progression to CML accelerated/blast phase
B. Resistance to multiple lines of TKIs but continues to be in chronic phase
C. Availability of a matched sibling donor
D. Young patients (<50 years of age)
Question 30.11 What are the current accepted criteria to define accelerated phase in CML?
A. Progressive splenomegaly and/or myelofibrosis
B. Bone marrow or peripheral blood blasts ≥15% but <30%
C. Platelet count <100 × 109/L unrelated to therapy
D. Clonal evolution in a Ph-chromosome–positive clone
E. All of the above
Question 30.12 BCR-ABL translocation leads to the synthesis of the fusion oncoprotein that
has constitutive tyrosine kinase activity seen in CML and Ph-chromosome–positive ALL. What
are the resultant BCR-ABL fusion proteins that are commonly found in these patients?
1. p210BCR-ABL
2. p230BCR-ABL
3. p190BCR-ABL
4. p250BCR-ABL
A. 1, 3 only
B. 1, 2, 3 only
C. 1, 2, 4 only
D. 2, 3 only
Question 30.13 What are the mutations that are commonly observed in CML blast-phase
transformation? (Select three correct responses)
A. Homozygous deletion of p16 tumor suppressor gene
B. Lengthened telomeres
C. Shortened telomeres
D. Loss of BCR-ABL
E. Acquired additional cytogenetic abnormalities.
Question 30.14 Important factors associated with poor prognosis in CLL include the
following:
A. CD38 positivity
B. IGHV-unmutated status
C. ZAP-70 expression
D. Short lymphocyte doubling time (<6 months)
E. All of the above
Question 30.15 A 49-year-old business man was diagnosed with CML 6 months ago and was
started on imatinib therapy. He initially achieved CHR and MCyR at 3 and 6 months,
respectively. He does travel frequently and missed a follow-up appointment and saw you at
12 months. A repeat bone marrow biopsy showed 45% Ph-positive metaphases. What is the
best next approach?
A. Change imatinib to dasatinib/nilotinib
B. Send blood for ABL kinase domain sequencing for possible mutations
C. Address the importance of therapy adherence
D. Refer to a transplant physician for allo-HCT
Question 30.17 A 67-year-old male presented with a 3-month history of progressive weight
loss, weakness, and night sweats. Initial examination showed massive splenomegaly. Initial
CBC revealed WBC of 2.1 cells/uL (differential 67% lymphocytes, 15% Neutrophils, 12%
monocytes), platelets are 45,000/uL. Peripheral smear showed few large lymphocytes with
open chromatin and cytoplasmic projections. Bone marrow biopsy showed that these cells are
positive for CD19, CD20, CD22, CD25, CD103, FMC7, and surface immunoglobulins but
negative for CD5 and CD23. What is the recommended treatment? (Select two correct
responses)
A. Cladribine at 0.1 mg/kg/d—continuous infusion for 7 days
B. Cladribine at 0.14 mg/kg/d—2-hour infusion for 5 days
C. Interferon-α
D. Alemtuzumab
Question 30.18 A 56-year-old man was recently diagnosed with Rai stage 0 CLL. He read
about newer therapies and wanted to know when he can start treatment. Which of the
following findings would be an indication for initiation of systemic therapy?
A. Availability of newer treatment modalities such as ibrutinib, idelalisib, and CAR-T cells
B. An increase in his absolute lymphocyte count from 25 × 109/L to 40 × 109/L over the
last 2 years
C. Recent diagnosis of hypogammaglobulinemia
D. Fever of 38°C for the last 2 weeks without evidence of infection
Question 30.19 Which of the following statements are TRUE about rituximab in the
treatment of CLL?
A. By targeting CD 20 on normal B-cells, it can lead to hypogammaglobulinemia requiring
immunoglobulin replacements.
B. Maintenance rituximab has shown to improve overall survival in CLL.
C. Rituximab monotherapy with 375mg/m2 IV weekly in frontline setting can achieve 60%
CR rates.
D. Along with fludarabine and cyclophosphamide, chemoimmunotherapy with rituximab
can achieve excellent remission rates.
Question 30.20 A 61-year-old female with a history of CLL and 17p deletion was treated
with six cycles of FCR and subsequently achieved complete remission. One year later, she
started noticing increased diffuse lymph node swelling and progressive unintentional weight
loss. Initial workup demonstrated WBC count of 1.2 × 105 cu mL and a platelet count of
65,000 cu mL. A repeat lymph node biopsy showed CLL. What is the next best treatment?
A. Ibrutinib 420 mg PO Q daily
B. Ibrutinib 840 mg PO Q daily
C. Ofatumumab
D. Fludarabine + cyclophosphamide + rituximab
E. Allo-HCT
F. None of the above
Question 30.21 Which actionable mutation is present in almost all patients with hairy cell
leukemia?
A. EGFR
B. FLT-3
C. BRAF
D. No actionable mutation
One of the most prognostically significant landmarks is achieving CCyR at 12 months and
many other parameters are based on the likelihood of obtaining this response. For
example, for patients who do not achieve a MCyR by 6 months, the probability of
obtaining a CCyR at 12 months is 50% or lower.
Corresponding chapters in Cancer: Principles & Practice of Oncology, Tenth Edition: 108 (Molecular Biology of Chronic
Leukemias), 109 (Chronic Myelogenous Leukemia), and 110 (Chronic Lymphocytic Leukemias).
31 Plasma Cell Neoplasms
Ravi Vij and Jesse Keller
QUESTIONS
Each of the numbered items below is followed by lettered answers. Select the ONE lettered answer
that is BEST in each case unless instructed otherwise.
Question 31.1 A healthy and active 62-year-old man presents to his primary care physician
for a routine annual physical. A complete metabolic panel is significant for an elevated total
protein of 10 mg/dL, an albumin of 4 mg/dL, a creatinine of 0.6 mg/dL, and a calcium of 8.8
mg/dL. A complete blood count shows a white blood cell count of 5.2, a hemoglobin of 12
g/dL, and a platelet count of 242. Subsequent serum protein electrophoresis and
immunofixation shows an IgG kappa monoclonal peak of 0.9 g/dL. Serum-free light chains
show a total kappa-free light chain concentration of 242 mg/dL and a lambda-free light chain
concentration of 1.2 mg/dL. A skeletal survey shows no evidence of lytic lesions and a bone
marrow biopsy reveals a monoclonal plasma cell population comprising 70% of the core
biopsy sample. Which of the following management options should be pursued next?
A. Initiation of antimyeloma therapy
B. Repeat SPEP in 12 months
C. Obtain a HeavyLite Assay
D. Fusion PET/MRI scanning to assess need for therapy
Question 31.2 A 65-year-old man presents to a local emergency room with fatigue,
myalgias, and lightheadedness. Laboratory evaluation reveals a white blood cell count of 7.5,
a hemoglobin of 6.3 g/dL and a platelet count of 135. Chemistry panel shows a creatinine of
1.56 mg/dL and a calcium of 14.0 mg/dL. Workup of his anemia includes a serum protein
electrophoresis that shows a monoclonal protein at a concentration of 4.0 g/dL. Serum
immunofixation reveals an IgA kappa monoclonal protein. Bone marrow biopsy shows a
kappa-restricted plasma cell population comprising 30% of the core biopsy. Cytogenetics
reveal hypodiploidy and FISH studies show t(4;14). Which of the following best characterizes
the risk category of this patient’s multiple myeloma?
A. High Risk due to FISH findings of t(4;14)
B. High Risk due to cytogenetic findings of hypodiploidy
C. Intermediate Risk by FISH and cytogenetics
D. Standard Risk by FISH and cytogenetics
Question 31.4 A 69-year-old woman is diagnosed with an IgG lambda multiple myeloma.
Her initial labs reveal a monoclonal peak of 4.5 g/dL, with lambda-free light chains of 120
mg/dL and kappa-free light chains of 1.1 mg/dL. A bone marrow biopsy showed 50%
involvement by a lambda-restricted plasma cell population. She began induction with
lenalidomide and dexamethasone and attained a very good partial response after four cycles
of therapy. She undergoes autologous stem cell transplant and on workup 100 days post-
transplant, a bone marrow biopsy shows no evidence of persistent plasma cells. Serum
protein electrophoresis and immunofixation are negative for any evidence of monoclonal
protein. Serum-free light chains are repeated and are normal. She has minimal residual
disease testing performed as part of a clinical trial, which shows her to have persistent
disease by multiparameter flow cytometry (MFC). What would be the appropriate
information to pass onto the patient regarding this finding?
A. She needs to have the testing repeated using next-generation–based sequencing
technology.
B. The patient should undergo repeat ASCT with a goal to obtain minimal residual disease
(MRD) negativity.
C. MRD positive patients have inferior PFS when compared to patients achieving stringent
CR who are MRD negative.
D. There are no differences in outcomes among patients achieving a CR regardless of MRD
status.
Question 31.5 A 59-year-old man has a new diagnosis of multiple myeloma made after he
presented with a monoclonal peak of 6.0 g/dL, IgG-Lambda by serum immunofixation. CBC
showed a hemoglobin of 9.5 g/dL and a metabolic panel revealed no abnormalities. Bone
marrow biopsy reveals evidence of 65% involvement by a lambda-restricted monoclonal
plasma cell population. He is deemed to be an appropriate candidate for autologous
transplantation. He starts therapy with bortezomib, lenalidomide, and dexamethasone which
he tolerates well. After 3 cycles of therapy, his M-spike has improved to 4.8 g/dL, and after 6
cycles of therapy his M-spike is 4.0 g/dL. Which of the following is the next best step in
management?
A. Continue bortezomib, lenalidomide, and dexamethasone until nadir value achieved and
then proceed to autologous transplantation
B. Proceed to autologous stem cell transplantation
C. Carfilzomib-based salvage therapy for 4 to 6 cycles and then proceed to autologous
transplantation
D. Switch to carfilzomib-based regimen and abandon plans for autologous transplantation
Question 31.6 A patient with a history of multiple myeloma presents to your clinic with a
newspaper clipping describing some recent successes with monoclonal antibodies in this
disease. The patient is curious about the role of these potential new drugs in therapy and
inquires about their mechanism of action. Which of the following is accurate regarding the
new medications in this class?
A. In a phase III trial, the PFS difference noted at 1 year was maintained at 2 years on
therapy with elotuzumab, lenalidomide, and dexamethasone versus lenalidomide and
dexamethasone.
B. Daratumumab had a high rate of discontinuation due to adverse events.
C. Daratumumab has no activity in patients with extra-medullary disease.
D. In a phase III trial, elotuzumab in combination with lenalidomide and dexamethasone
produced responses even in lenalidomide refractory patients.
Question 31.7 A 63-year-old man with a history of multiple myeloma presents to clinic for
ongoing evaluation. He was diagnosed 3 years ago, and received induction treatment with
bortezomib, lenalidomide, and dexamethasone followed by autologous stem cell
transplantation. On workup today, he has evidence of progressive disease with a rising
monoclonal protein from 1.0 g/dL to 3.2 g/dL. His performance status is ECOG 0, and the
treating physician makes the decision to initiate panibinostat, bortezomib, and
dexamethasone. Which of the following regarding panibinostat should the physician inform
the patient prior to initiation?
A. Potential for serious and possibly fatal arrhythmia
B. Risk of Stevens–Johnson syndrome
C. Diarrhea is self-limiting and transient
D. Risk for hemolytic uremic syndrome
Question 31.8 A 65-year-old man with a history of multiple myeloma presents for initial
evaluation. He was diagnosed 1 year ago and underwent initial induction therapy with
bortezomib, cytoxan, and dexamethasone, followed by autologous stem cell transplantation
approximately 6 months ago. He was not treated with maintenance therapy following
transplant due to his personal preference. He presents now with worsening anemia
(hemoglobin 9 g/dL) and a rising M-protein level (0.8 g/dL to 4.5 g/dL). What is the most
appropriate statement regarding the role of carfilzomib therapy in this setting?
A. In a phase III trial, patients treated with lenalidomide and dexamethasone had improved
progression-free survival compared to those treated with carfilzomib, lenalidomide, and
dexamethasone.
B. In a phase III trial, patients treated with the combination of carfilzomib, lenalidomide,
and dexamethasone had inferior health-related quality of life compared to those treated
with lenalidomide and dexamethasone alone.
C. In a phase III trial, the benefit of carfilzomib (20/56 mg/m2) and dexamethasone was
limited to patients who had no prior exposure to bortezomib.
D. In a phase III trial, carfilzomib (20/56 mg/m2) and dexamethasone was associated with
a doubling of PFS when compared to bortezomib (1.3 mg/m2) and dexamethasone.
Question 31.9 A 57-year-old previously healthy woman presents to her primary care
physician with fatigue and weight loss over the preceding 3 months. Physical examination
reveals palpable lymphadenopathy in the axilla bilaterally. Workup is significant for a WBC
count of 7.3, a hematocrit of 21%, and a platelet count of 42. A metabolic panel is within
normal limits. SPEP and immunofixation reveal an IgM monoclonal protein and a bone
marrow biopsy shows a lymphoplasmacytic infiltrate comprising 20% of the marrow. Serum
viscosity is within normal limits. She is initially treated with bortezomib, rituximab, and
dexamethasone with a partial response. One year later she now has a recurrence of
symptoms. A tumor sample is sent for exome sequencing studies. Which of the following is
most likely to predict for best response to BTK inhibitor therapy?
A. MYD88 L365P mutation positive and CXCR4 mutation negative
B. MYD88 L365P mutation negative and CXCR4 mutation negative
C. MYD88 L365P mutation positive and CXCR4 mutation positive
D. Presence of CXCR4 WHIM mutation irregardless of MYD88 status
Question 31.10 A 52-year-old man presents to your clinic for an initial consultation. He was
referred after he was noted to have lower extremity edema and further workup revealed the
presence of a nephrotic syndrome. He underwent a renal biopsy which showed evidence of
amyloid deposition, positive by Congo red staining. His labs revealed a kappa-free serum
light chain concentration of 140 mg/L and a lambda-free light chain concentration of 2 mg/L.
His NT-proBNP is 10,000 ng/L and his troponin is 0.09 ng/mL. His performance status is
rated as an ECOG 1. What should be the next step in management?
A. Start cyclophosphamide, bortezomib, and dexamethasone
B. Autologous stem cell transplantation with melphalan 140 g/m2
C. Autologous stem cell transplantation with melphalan 200 g/m2
D. Start therapy with ixazomib-based therapy
ANSWERS
Corresponding chapter in Cancer: Principles & Practice of Oncology, Tenth Edition: 112 (Plasma Cell Neoplasms).
32 Immunosuppression-Related Malignancies
Lee Ratner
QUESTIONS
Each of the numbered items below is followed by lettered answers. Select the ONE lettered answer
that is BEST in each case unless instructed otherwise.
Question 32.2 Cytotoxic chemotherapy is NOT well tolerated with which of the following
antiretroviral medications?
A. Zidovudine, nucleoside reverse transcriptase inhibitor therapy
B. Protease inhibitors
C. Raltegravir, integrase inhibitor
D. Fuzeon, HIV entry inhibitor
Question 32.3 What is the response rate to HAART therapy, in a treatment-naive patient
with favorable-risk Kaposi sarcoma (KS)?
A. 20%
B. 40%
C. 60%
D. 80%
Question 32.4 Which of the following is TRUE about the combination of rituximab with
chemotherapy for AIDS-associated lymphomas?
A. Adding rituximab to cyclophosphamide, doxorubicin, vincristine, and prednisone
(CHOP) chemotherapy in patients with CD4 <50/mm3 may result in higher rate of
neutropenic infections.
B. Rituximab is of no added benefit to CHOP or infusional etoposide, vincristine, and
doxorubicin, bolus cyclophosphamide, and daily prednisone (EPOCH) chemotherapy for
AIDS-associated diffuse large B-cell lymphoma (DLBCL).
C. Rituximab with chemotherapy is usually beneficial in plasmablastic lymphoma.
D. Rituximab with chemotherapy is usually beneficial in primary effusion lymphoma.
Question 32.5 Which is TRUE concerning primary central nervous system (CNS) lymphoma
in AIDS?
A. Positive cerebrospinal fluid (CSF) Epstein–Barr virus (EBV) polymerase chain reaction
(PCR) test and a consistent radiologic picture are sufficient to diagnose primary CNS
AIDS lymphoma.
B. In patients with CD4 count <50/mm3 and poor performance status, high dose
methotrexate should be instituted.
C. In patients with CD4 count >50/mm3 and good performance status, cranial
radiotherapy provides potentially curative therapy.
D. HAART has no role in the treatment of primary CNS lymphoma.
Question 32.6 A 38-year-old man with HIV infection presents with 3-month history of
weight loss and night sweats. He is not on antiretroviral therapy and his last CD4 count 3
months ago was 300/mm3. On examination, he has multiple enlarged cervical lymph nodes.
His hemoglobin is 10 g/dL, white blood cell count is 3.6 × 103 /mm3, and platelet count is
190 × 103/mm3. Serum LDH is 300. Infectious workup is negative. CT of the neck and chest
demonstrates diffuse cervical and mediastinal lymphadenopathy. You suspect lymphoma and
arrange for an excisional biopsy of a neck lymph node. Which of the following lymphomas is
a non-AIDS defining cancer?
A. Hodgkin lymphoma
B. Diffuse large B-cell lymphoma
C. Burkitt lymphoma
D. Primary CNS lymphoma
Question 32.8 How does the presentation of HIV-associated Hodgkin lymphoma (HL) differ
from that of HL in immunocompetent patients?
A. Patients with HIV-associated HL present at an older age.
B. B symptoms are rare in patients with HIV-associated HL.
C. Extranodal sites are less frequently involved in patients with HIV-associated HL.
D. Mediastinal involvement is less frequent in patients with HIV-associated HL.
Question 32.9 Which of the following is CORRECT regarding anogenital cancers in patients
infected with HIV?
A. In HIV-infected women with preinvasive cervical neoplasia, standard therapy results in
a comparable rate of recurrence, compared to their immunocompetent counterparts.
B. In patients with a CD4 count of less than 200/mm3, who are treated with chemotherapy
and radiation for invasive anal cancer, the side effect profile is similar to that of HIV-
negative patients
C. In patients with HIV, anal cancer and cervical cancer are associated with high-risk
subtypes of human papilloma virus (HPV) infection in the large majority of individuals.
Question 32.10 Which of the following viruses are implicated in the development of cancers
in patients with HIV infection?
A. EBV
B. Hepatitis C virus
C. Human herpes virus-8 (HHV-8)
D. All of the above
Question 32.11 A 43-year-old HIV-positive man presents with multiple pigmented skin
nodules, hemoptysis and dyspnea without fever or chills, a bloody pleural effusion, and
diffuse adenopathy. Biopsy of a 4-cm supraclavicular lymph node is most likely to show:
A. Kaposi Sarcoma.
B. Non-Hodgkin Lymphoma.
C. Tuberculosis.
D. Hodgkin Lymphoma.
Question 32.12 A 45-year-old HIV-positive man on HAART with CD4 240, presents with an
anal mass and 3-cm R inguinal node, and biopsy of the anal mass and inguinal node reveal
moderately differentiated squamous cell carcinoma. PET examination showed no other
evidence of disease. The most appropriate initial treatment is:
A. Cisplatin–Fluorouracil therapy
B. Mitomycin–Fluorouracil therapy concurrent with radiation
C. Abdominoperineal resection
D. Radiation therapy alone
Question 32.13 Sorafenib therapy for hepatocellular carcinoma is well tolerated with which
of the following antiretroviral combinations?
A. Truvada and ritonavir boosted prezista
B. Truvada and Raltegravir
C. Atripla
D. Stribild
ANSWERS
Corresponding chapters in Cancer: Principles & Practice of Oncology, Tenth Edition: 117 (HIV-Associated Malignancies) and
118 (Transplantation-Related Malignancies).
33 Stem Cell Transplantation
Brian Hess and Rizwan Romee
QUESTIONS
Each of the numbered items below is followed by lettered answers. Select the ONE lettered answer
that is BEST in each case unless instructed otherwise.
Question 33.1 The curative potential of allogeneic stem cell transplantation (allogeneic SCT)
may be derived from which of the following?
A. High-dose chemotherapy
B. Graft-versus-leukemia (GVL) effect
C. Graft-versus-host effect
D. A and B
Question 33.2 The allogeneic SCT conditioning regimen serves to achieve which of the
following?
A. Provide immunosuppression to prevent rejection
B. Provide immunosuppression to prevent graft-versus-host disease (GVHD)
C. Eradicate malignant cells
D. A and C
Question 33.3 A 54-year-old male is diagnosed with AML with complex cytogenetics. After
achieving complete remission with standard 7+3 chemotherapy he is evaluated for
allogeneic SCT from his HLA-matched brother. Which of the following regimens is considered
myeloablative for his upcoming transplant?
A. Cyclophosphamide 60 mg/kg/d intravenously (IV) × 2 days plus 1,200 cGy total body
irradiation (TBI)
B. Cyclophosphamide 60 mg/kg/d IV × 2 days plus busulfan 3.2 mg/kg/d IV × 4 days
C. Fludarabine 30 mg/m2 × 3 days plus 200 cGy TBI
D. A and B
Question 33.5 Which of the following drugs used in the conditioning regimens for stem cell
transplant (SCT) is the most common cause of acute cardiac toxicity?
A. Cytarabine
B. Fludarabine
C. Cyclophosphamide
D. Busulfan
Question 33.6 A 64-year-old female is diagnosed with multiple myeloma. She has
experienced a very good partial response after four cycles of induction therapy but her
creatinine remains elevated at 3.9 g/dL and her creatinine clearance remains less than 15
mL/min. What is the most appropriate management in regards to her conditioning regimen
for upcoming autologous stem cell transplant?
A. Melphalan 200 mg/m2
B. Dose reduce melphalan to 140 mg/m2
C. Dose reduce melphalan to 100 mg/m2
D. Her elevated creatinine is a contraindication to autologous transplant
Question 33.7 The GVL effect after transplant is most pronounced in which of the following
malignancies?
A. Acute myelogenous leukemia (AML)
B. Acute lymphoblastic leukemia (ALL)
C. Chronic-phase CML
D. Accelerated-phase CML
Question 33.8 Which of the following increases the risk of relapse after allogenic stem cell
transplantation?
A. Human leukocyte antigen (HLA)-mismatched transplant
B. CD34 cell dose >2 × 106 but <5 × 106/kg recipient body weight
C. Acute and chronic GVHD
D. Use of T-cell–depleted graft
Question 33.9 Which of the following therapies in a patient with multiple myeloma would
potentially hinder stem cell mobilization and collection for future autologous stem cell
transplant?
A. Melphalan
B. Long-term use of lenalidomide
C. Velcade
D. A and B
Question 33.10 Sinusoidal obstruction syndrome (SOS) of the liver is associated with which
of the following factors?
A. TBI 12 Gy conditioning
B. Oral busulfan conditioning
C. Advanced age
D. All of the above
Question 33.11 Which of the following factors is associated with increased risk of
engraftment failure in allogeneic stem cell transplantation?
A. T-cell depletion of the product
B. Less than 1 × 106 CD34+ cells/kg recipient body weight
C. HLA-mismatched stem cell donor
D. All of the above
Question 33.12 In which setting is the risk of CMV reactivation the highest after allogeneic
SCT?
A. CMV-positive donor to a CMV-negative recipient
B. CMV-negative donor to a CMV-positive recipient
C. CMV-negative donor to a CMV-negative recipient
D. CMV-positive donor to a CMV-positive recipient
Question 33.13 Peripheral blood mobilized stem cell allografts, compared with bone
marrow, are associated with which of the following?
A. Shorter period of neutropenia
B. Shorter period to platelet recovery
C. Equivalent T-cell numbers
D. Equivalent incidence of acute GVHD
E. A, B, and D
Question 33.14 For which of the following patients with an HLA-matched donor is
allogeneic SCT most appropriate?
A. A 35-year-old man with AML with inversion 16 in CR1 after 7+3
B. A 40-year-old woman with AML and complex cytogenetics in first clinical remission
(CR)
C. A 48-year-old woman with diffuse large B-cell lymphoma with chemosensitive relapse
after initial remission of 18 months
D. A 55-year-old man with RAI stage III chronic lymphocytic leukemia (CLL) in first
remission
Question 33.15 Which of the following are potential complications of donor lymphocyte
infusion (DLI)?
A. Bone marrow aplasia
B. GVHD flare
C. SOS
D. A and B
Question 33.16 Factors that influence the choice of conditioning regimen in allogeneic stem
cell transplantation include:
A. Underlying malignancy and prior treatment.
B. Patient age and comorbidity.
C. Donor:recipient HLA compatibility.
D. All of the above.
Question 33.18 What is the most common cause of late hemorrhagic cystitis in patients
undergoing allogeneic SCT?
A. Cyclophosphamide
B. BK virus
C. EBV
D. CMV
Question 33.19 Autologous stem cell transplantation is indicated in certain situations for
which of the following solid tumors?
A. Testicular cancer
B. Neuroblastoma
C. Breast cancer
D. A and B
Question 33.20 Graft manipulation ex vivo to purge contaminating tumor cells is a strategy
that has been successful in reducing the rate of relapse after autologous stem cell
transplantation.
A. True
B. False
Question 33.21 Which of the following should be considered for autologous stem cell
transplant?
A. DLBCL that has relapsed after first-line R-CHOP chemotherapy
B. Follicular lymphoma that has relapsed after first-line Bendamustine and Rituxan
C. ALK-positive T-cell lymphoma in first remission
D. Nodal Marginal zone lymphoma that has progressed after a 6-month period of
observation
Question 33.22 A mismatch of which of the following HLA genes would NOT adversely
influence the outcome in an HLA mismatched unrelated donor allogeneic SCT?
A. HLA-A
B. HLA-B
C. HLA-C
D. HLA-DQB1
E. HLA-DRB1
Question 33.23 Which of the following cells present in the stem cell graft are thought to
play a major role in mediating GVL effect seen in allogeneic stem cell transplants?
A. Donor T lymphocytes
B. Donor B cells
C. Donor NK cells
D. A and C
Question 33.24 A 42- year-old male is undergoing transplant for relapsed AML. He has no
matched related or unrelated donors available and thus he is undergoing referral for a
haploidentical transplant from his brother. Which of the following would be appropriate in
order to decrease the likelihood of acute GVHD in this setting?
A. Post transplant Cytoxan 50 mg/m2 on day +3 and day +4
B. Reduce dose of calcineurin inhibitor started on day 0
C. Reduced intensity conditioning
D. Posttransplant Rituximab 375 mg/m2 on day +4
ANSWERS
Corresponding chapters in Cancer: Principles & Practice of Oncology, Tenth Edition: 130 (Autologous Stem Cell
Transplantation) and 131 (Allogeneic Stem Cell Transplantation).
34 Oncologic Emergencies
Preet Paul Singh
QUESTIONS
Each of the numbered items below is followed by lettered answers. Select the ONE lettered answer
that is BEST in each case unless instructed otherwise.
Questions 34.1–3 A 48-year-old White man presents with a history of progressive facial
swelling, fullness in the head and shortness of breath for 1 month. He has a 40 pack-year
smoking history. On examination, the patient has venous distention of the neck and chest
wall. Laboratory test results revealed normal blood counts, basic metabolic profile, and liver
functions. Computed tomography (CT) scan revealed an 8 × 6-cm lung mass with multiple
liver lesions.
Question 34.2 Biopsy was performed and showed small cell lung cancer. Which is the best
initial modality of treatment for this patient?
A. Surgery
B. Radiation therapy
C. Chemotherapy
D. SVC stent
Question 34.3 What is the most likely location for the primary tumor?
A. Peripheral left lung
B. Peripheral right lung
C. Central left lung
D. Central right lung
Question 34.4 Which among the following is the earliest fundoscopic sign for increased
intracranial pressure?
A. Papilledema with blurring of the disc margins
B. Foster–Kennedy syndrome
C. Disc hemorrhage
D. Absence of venous pulsations within the center of the optic disc
Questions 34.5–6 A 57-year-old man presents with severe back pain and bilateral leg
weakness for 3 days. Magnetic resonance imaging (MRI) of the spine reveals metastatic
lesion at T10 vertebral body with significant cord compression.
Question 34.5 Which of the following are most likely primary cancers in this patient?
A. Lung cancer and breast cancer
B. Lung cancer and lymphoma
C. Colon cancer and lymphoma
D. Colon cancer and prostate cancer
Question 34.6 What is the most appropriate initial therapy for this patient with malignant
spinal cord compression?
A. Chemotherapy
B. Radiation therapy
C. Strontium-89
D. Dexamethasone
Question 34.7 In patients with increased intracranial pressure, which of the following signs
indicates midbrain dysfunction?
A. Midsize pupils unresponsive to light
B. Coma
C. Absence of oculocephalic reflex
D. Ataxic breathing
Question 34.8 Which of the following laboratory abnormalities are associated with tumor
lysis syndrome? (Select two correct responses)
A. Hypokalemia
B. Hypophosphatemia
C. Hypocalcemia
D. Hyperuricemia
Question 34.9 A 28-year-old man presents with newly diagnosed acute myeloid leukemia.
He has a white cell count of 140,000/mm3, glucose of 96 mg/dL, sodium of 138 mEq/L,
potassium of 4 mEq/L, creatinine of 1.1 mg/dL, blood urea nitrogen (BUN) of 15 mg/dL, uric
acid of 4.8 mg/dL, albumin of 5.2 g/dL, and calcium of 10.2 mg/dL. He is started on
induction chemotherapy, aggressive intravenous fluids and allopurinol. Twelve hours later,
the patient developed cardiac arrest not responsive to cardiopulmonary resuscitation and
died. What is the most likely cause of his death?
A. Leukostasis
B. Severe hyperkalemia
C. Pulmonary embolism
D. Chemotherapy-induced cardiac arrhythmia
Questions 34.10–11 A 40-year-old woman presents with fever and headache 3 days after
receiving chemotherapy. Her blood pressure is 130/85 and heart rate 101. Laboratory tests
revealed hemoglobin of 8.5 g/dL, WBC of 11,500/mm3, platelets of 69,000/mm3, sodium of
142 mEq/L, potassium of 4.3 mEq/L, bicarbonate of 24 mEq/L, BUN of 44 mg/dL, creatinine
of 1.8 mg/dL, albumin of 3.8 g/dL, total bilirubin 2.4 mg/dL, and direct bilirubin 0.3 mg/dL.
Her prothrombin time and partial thromboplastin time were normal. Peripheral blood smear
showed several fragmented red blood cells and helmet cells. Direct Coombs test is negative.
Question 34.11 Which of the following chemotherapy drugs are implicated in the etiology
of this syndrome? (Select two correct responses)
A. Paclitaxel
B. Mitomycin
C. Gemcitabine
D. Pemetrexed
Question 34.12 A 63-year-old man with metastatic squamous cell carcinoma of the lung
presents with constipation and nausea for 3 days. Laboratory tests revealed hemoglobin of
13.5 g/dL, WBC of 12,500/mm3, platelets of 155,000/mm3, sodium of 146 mEq/L, potassium
of 4.8 mEq/L, bicarbonate of 28 mEq/L, BUN of 44 mg/dL, creatinine of 1.7 mg/dL, albumin
of 2.8 g/dL, and calcium of 13.1 mg/dL. What is the most appropriate therapy, in addition to
intravenous fluids?
A. Gallium nitrate
B. Furosemide
C. Bisphosphonates
D. Calcitonin
Question 34.14 Which of the following findings are required for diagnosis of syndrome of
inappropriate antidiuretic hormone secretion (SIADH)? (Select two correct responses)
A. Decreased effective serum osmolality (<275 mOsm/kg of water)
B. Inappropriate urinary concentration: Urine osmolality >100 mOsm/kg of water with
normal renal function
C. Clinical evidence of hypovolemia (orthostasis, tachycardia, decreased skin turgor, dry
mucous membranes)
D. Urine sodium <10 mmol/L in the face of normal salt and water intake
Corresponding chapter in Cancer: Principles & Practice of Oncology, Tenth Edition: 119 (Superior Vena Cava Syndrome), 120
(Increased Intracranial Pressure), 121 (Spinal Cord Compression), and 122 (Metabolic Emergencies).
INDEX
A
AAW. See Antiandrogen withdrawal (AAW)
Abiraterone, 82, 86, 128
Abscopal effect of radiation, 70, 75
Absolute risk reduction, 44, 48
ABT-737, 17, 24
Accelerated fractionation, 75–76
ACOG. See American College of Obstetricians and Gynecologists (ACOG)
ACP. See American College of Physicians (ACP)
Acquired immunodeficiency syndrome (AIDS)
AIDS-defining cancer, 327, 330
CNS lymphoma in, 328, 330
non–AIDS-defining cancer, 328, 330
Acute lymphoblastic leukemia (ALL)
CNS prophylaxis in, 297, 302
imatinib in, 297, 302
maintenance therapy for, 297, 302
Acute megakaryocytic leukemia, mediastinal NSGSTs and, 142, 148
Acute myeloid leukemia (AML), 293, 299
BEP and, 217, 221
consolidation therapy in, 296, 302
core-binding factor, 293, 299
cytopathology, 293, 299
DNMT3A mutations in, 293, 299
in elderly, treatment of, 294, 295, 300, 301
induction therapy in, 294, 299
monosomal karyotype, 294, 300
nucleophosmin 1 (NPM1) mutation in, 298, 303
poor prognostic factor in, 294, 300
prognostic factors for, 294, 300
residual AML blasts, treatment of, 297, 302
Acute promyelocytic leukemia (APL)
arsenic salvage therapy in, 295, 300
ATRA and headache, 296, 301
and differentiation syndrome, 296, 301
fresh-frozen plasma in, 295, 301
relapsed, treatment in, 296, 301–302
risk of relapse in, 296, 301
ADCC. See Antibody-dependent cell-mediated toxicity (ADCC)
Adenocarcinomas
endometrioid, 225, 232
esophageal, 151, 156
of gastroesophageal (GE) junction, 152, 157
of pancreas, 165, 174
small bowel, 183, 186
Adjuvant chemotherapy
purpose of, 98, 102
relapses in early-stage colon cancer treated with, 98, 103
Adoptive cell therapy, 92, 95
purpose of, 91, 95
Afatinib, 131, 136
AIDS. See Acquired immunodeficiency syndrome (AIDS)
AIDS-associated lymphomas, combination of rituximab with chemotherapy for, 327, 330
Akt, 12
Alcohol consumption, and risk of cancer, 35, 40
Alemtuzumab, 302–303
ALK. See Anaplastic lymphoma kinase (ALK)
ALL. See Acute lymphoblastic leukemia (ALL)
Allele-specific oligonucleotide-based quantitative polymerase chain reaction (ASO-PCR), 321
Allogeneic stem cell transplantation, 333, 338
candidate for, 335, 339–340
choice of conditioning regimen, 335, 340
cyclophosphamide and cardiac toxicity, 334, 338
graft-versus-host disease, 337, 341
HLA mismatched unrelated donor allogeneic SCT, 336, 341
late complications after, 336, 340
late hemorrhagic cystitis in, causes of, 336, 340
myeloablative conditioning regimens in, 333, 338
objectives of, 333, 338
risk of CMV reactivation after, 335, 339
All-trans retinoic acid (ATRA), topical, 55
5-alpha-steroid reductase inhibitors, in prostate cancer, 53, 56
Alpha-Tocopherol, Beta-Carotene Trial (ATBC), 55
Alveolar rhabdomyosarcoma, 270
Alveolar soft part sarcoma
cytogenetic abnormality with, 268, 273
sunitinib for, 268, 273
American College of Obstetricians and Gynecologists (ACOG), 45, 48
American College of Physicians (ACP), 45, 48
AML. See Acute myeloid leukemia (AML)
Amyloidosis, 318, 324–325
Anal cancer, early localized, therapy for, 192, 196
Anaplastic large-cell ymphoma, 284, 289
Anaplastic lymphoma kinase (ALK), 84
Anaplastic oligodendroglioma, IDH1 mutations in, 258, 263
Androgen receptor, 206, 213
Angiogenesis, 2, 7, 38
Angiogenesis inhibitors, and apoptosis induction, 17, 24
Angiosarcoma, and risk of nodal metastases, 266, 271
Anthracycline cardiotoxicity, 80, 85
Antiandrogen withdrawal (AAW), 205, 212
Antiangiogenesis agents, 82, 87
Antiangiogenic therapy, side effects of, 19, 26
Antibody-dependent cell-mediated toxicity (ADCC), 87
Anti-CD19 CAR T cells, immunotherapy with, 92, 95
Antimitogenic signaling, activation of, 16, 22–23
APC gene mutation, 195
APL. See Acute promyelocytic leukemia (APL)
Apoptosis, 7, 16, 23
and lysosome activation, 18, 24
Aromatase inhibitors, use of, in breast cancers, 250, 254
Arsenic trioxide, 301
Asparaginase and methotrexate, 82, 86
ASPIRE trial, 323
Aspirin, in colorectal cancer, 52, 56
Astrocytomas, 260
alterations of p53 gene in, 255, 260
grade II, 257, 261
grade II, somatic mutation in, 259, 264
Ataxia-telangiectasia mutated (ATM) kinase, 39
Atelomeric chromosomes, 12
ATR/CHK1 signaling, 4, 10
Aurora kinase B, role of, 4, 10
Autoantibodies in CLL, 308, 313
Autoimmune adverse events, 89, 93
Autologous stem cell transplantation, 320–322, 324–325
DLBCL in first relapse and, 336, 341
in multiple myeloma, 316, 320–322
neuroblastoma and, 336, 340
testicular cancer and, 336, 340
Autophagy, 7, 17, 24
5-Azacytidine, 3, 9
5-Aza-2′-deoxycytidine, 9
B
Bacillus Calmette–Guérin (BCG) vaccine, intravesical, 201, 208
Bad, 24
BAP1 tumor suppressor gene, mutations in, 133, 137
Barrett esophagus, 151, 156
high-grade dysplasia in, 152, 157
Basal cell nevus syndrome, mutations in PTCH1 gene and, 276, 280
Base excision repair (BER), 4, 10
Bayesian methods, in planning phase I and II trials, 110, 116
B-cell lymphomas, 284, 289
Bcl-2 inhibitors, 17, 24
BCS. See Breast-conserving surgery (BCS)
Benign teratoma, 141, 147
BEP. See Bleomycin, etoposide, and cisplatin (BEP)
BER. See Base excision repair (BER)
Berry formulations, 53, 57
Beta-human chorionic gonadotropin (hCG), 231, 237
Bevacizumab, 18, 25, 87, 102
for recurrent GBM, 257, 261
Bicalutamide, 128
discontinuation of, 205, 212
Bilateral salpingo-oophorectomy (BSO), in BRCA carriers, 61, 66
Biliary cancers, adjuvant therapy for, 168, 176–177
Bim, 17, 24
Birt–Hogg–Dubé syndrome, 208
Bisphosphonates
for malignancy-associated hypercalcemia, 345, 349
nitrogen-containing, 349
for pain associated with bone metastases, 251, 254
and risk of recurrent breast cancer, 53, 57
Bladder cancer
cisplatin-based multiagent chemotherapy for, 201, 208–209
combined radiation and chemotherapy in, 202, 209
intravesical therapy, 201, 208
muscle-invasive, 208–209
neoadjuvant chemotherapy for, 202, 209
Schistosoma haematobium and, 204, 211
tumor suppressor genes in pathogenesis of, 201, 208
urinary diversion after cystectomy, options for, 202, 209
Bleomycin, etoposide, and cisplatin (BEP)
for granulosa cell tumors, 244
for nonseminomatous germcell tumor, 216, 217, 220, 221
Bone marrow and GI precursor cells, 99, 104
Bortezomib, 24, 87, 290
anticancer activity of, 98, 103
for multiple myeloma, 82, 86
Brachytherapy, 72, 77
BRAF inhibitors, 81, 86
BRAF V600E mutations
and resistance to cetuximab in colorectal cancer, 99, 103
treatment in, 81, 86
BRCA1 and BRCA2 gene mutations, 62, 66–67
BRCA2 gene variant, and genetic testing, 61, 66
BRCA1 mutation, and risk of ovarian cancer, 243
Breakage–fusion–bridge cycles, 5, 12
Breast cancer
ACS guidelines for MRI screening, 248, 252
adjuvant tamoxifen and, 250, 253
annual mammography and MRI at age 30, 44, 48
aromatase inhibitors and, 250, 254
BRCA1-associated, 247, 252
core needle biopsy for diagnosis of, 248, 252
Cowden syndrome and, 248, 252
DCIS, 249, 253
Gail model, 249, 253
by germline mutations, 247, 252
Her2/neu amplification in, 3, 10
incidence of, 32
inflammatory, 251, 254
Li–Fraumeni syndrome and, 247, 252
local recurrence after breast-conserving therapy, 249, 253
Luminal A subtype, 247, 252
male, 251, 254
obesity and physical activity as risk factors for, 36, 41
oncotype DX testing in, 248, 252
oophorectomy before menopause and risk of, 248, 253
preoperative chemotherapy for HER2+ breast cancer, 250, 253
P1 trial, 253
routine surveillance for early stage cancer patients, 251, 254
screening for, 44, 45, 48
stage IIA, 249, 253
STAR trial, 253
tamoxifen and raloxifen, contraindications to use of, 248, 252
taxanes, use of, 250, 254
Breast-conserving surgery (BCS)
contraindication to, 249, 253
local recurrences after, 249, 253
Breast self-examination (BSE), 44, 48
Bruton tyrosine kinase (BTK) inhibitor, 314
BSE. See Breast self-examination (BSE)
Burkitt lymphoma, 184, 187
endemic and sporadic, 283, 289
translocation t(8;14) in, 283, 289
C
CA 19-9, 171
CA-125, and ovarian cancer, 240, 243
Cabazitaxel, 81, 85
Cadherins, 20, 27
Calcitonin, 349
Calcium, and recurrent colorectal adenoma, 52, 56
Calretinin, 133, 137
Cancer. See also specific type
cell culture experiments in preclinical studies of, 1, 7
cytogenetic abnormalities in, 4, 10–11
gene amplification in, 3, 9–10
genetic mutations in, 1, 7
as hereditary disease, 60, 65
progression of, 2, 7
risk of
alcohol consumption and, 35, 40
dietary influence on, 35, 40
fruit and vegetable consumption and, 36, 40
specific nutrients and, 36, 40–41
strategy to promote apoptosis in, 5, 12
Cancer immunotherapy, approaches to, 90, 93
Cancer vaccines, treatment with, 90, 91, 94–95
Carbamazepine, 84
Carboplatin and paclitaxel, for NSCLC with squamous histology, 130, 134–135
Carcinogenic effects of chemicals, 34, 38–39
Carcinoids of small bowel, 183, 186
Carfilzomib, 86
in multiple myeloma, 317, 323–324
Carney triad, and GIST, 183, 186
Carotene and Retinol Efficacy Trial (CARET), 55
CARs, 95
Case-control studies, 29, 31
Caspases, role in apoptosis, 98, 102
Castrate-resistant prostate cancer (CRPC), 211, 212
Catenins, 27
CD 10, 222
CD 20, 222
CD 30, 222
CDH1 carriers, optimal surgical therapy for, 54, 57–58
CDH1 gene, mutations in, 154, 159
CDK2, 213
CDKs. See Cyclin-dependent kinases (CDKs)
CD117 (c-Kit) stain, 266, 271
CEBPA gene, 299
Celecoxib, 56, 87
Cell culture experiments, in studies of cancer cells, 1, 7
Cell cycle, 1, 7
DNA damage checkpoints, 2, 8
regulation of, 7
Cell-cycle exit, 15, 22
Cell lysis, 24
Cellular assays, 7
Central nervous system (CNS) prophylaxis, 297, 302
Central nervous system (CNS) tumor
contrast-enhanced MRI images, 256, 261
primary CNS lymphoma, 256, 261
spinal ependymoma, 256, 260
Cerebrospinal fluid (CSF) Epstein–Barr virus (EBV) polymerase chain reaction (PCR) test,
328, 330
Cervical cancer
cervical conization, 227, 233
epidemiology of, 226, 232–233
extracervical involvement, 227, 233
in HIV-infected patients, 327, 330
locoregionally advanced, treatment of, 228, 234
recurrence after combined chemoradiotherapy, 228, 234
screening for, 45, 48–49
small stage IB1 tumors, therapy for, 227, 233
spread of, 227, 233
staging of, 227, 233
Cetuximab, 136
in colorectal cancer, 100, 104
in HNSCC, 121, 125, 126
Charged particle beams, 73, 77
Chemical carcinogens, 34, 35, 38–39
Chemotherapy. See also specific type of cancer
in incurable, advanced, metastatic disease, goals of, 97, 102
indicator of effectiveness of, 98, 102–103
and radiation therapy, combining of, 71, 76
Child–Pugh C cirrhosis and unresectable HCC, 170, 179
Cholangiocarcinoma, risk factor for, 167, 176
Chondrosarcomas, 268, 272
Chromosomal rearrangements, 12
Chronic lymphocytic leukemia (CLL)
autoimmune complications in, 308, 313
ibrutinib in, 309, 314
IWCLL revised criteria, 308, 313–314
rituximab in, 309, 314
Chronic myeloid leukemia (CML)
adherence to therapy in, 308, 313
BCR-ABL fusion proteins in, 307, 312
blast-phase transformation, mutations in, 307, 312
conditioning regimens in, 333, 338
criteria for diagnosis of accelerated phase, 307, 312
cytogenetic response in, 305, 310
GVL effect in, 334, 338
hematopoietic cell transplantation (HCT) in, 307, 312
imatinib in, 306, 310–312
minimal residual disease in, 310
ponatinib in, 306, 311
poor prognosis in, factors associated with, 308, 313
relapse on therapy in, 306, 311
Sokal risk score, 305, 310
T315I mutation in, 306, 311
Cigarette smoking, and lung cancer, 33, 37
Circulating tumor cells (CTCs), 20, 27
extravasation of, 20, 27
Cisplatin radiosensitization, 76
Clinical trials, 107, 113
Bayesian methods in planning of, 110, 116
planning with interim analyses, 111, 116
power and hypothesis testing in, 110, 115
survival data. analysis of, 111, 116
CLL. See Chronic lymphocytic leukemia (CLL)
Clonidine, for tobacco dependence, 51, 55
Clonorchis sinensis, 211
ClonoSEQ MRD assessment, 321
CML. See Chronic myeloid leukemia (CML)
C-myc amplification, in small cell lung cancer, 3, 9–10
60Cobalt teletherapy unit, 75
Cobicistat, 332
Cohort studies, 29, 31
Colitis from T-cell activation, 89, 93
Colon cancer, obesity and physical activity as risk factors for, 36, 41
Colorectal cancer (CRC), 9. See also Hereditary nonpolyposis colon cancer (HNPCC)
BRAF V600E in, 193, 197
colonoscopy for screening for, 46, 49
endoscopy with polypectomy for, 46, 49
HNPCC and, 194
incidence of, 32
maintenance therapy with capecitabine and bevacizumab, 193, 196–197
microsatellite instability (MSI) and, 189, 194
resistance to cetuximab in, 99, 103
resistant to treatment with cetuximab, 192, 196
stage II, high-risk features for, 193, 197
stage III, adjuvant therapy for, 190, 195
Compton scattering, 76
Computed tomography contrast perfusion, 100, 104–105
Conditioning regimen, choice of, 335, 340
Confidence intervals, 29, 31
Confounding factors and interaction, 29, 31
Conventional 3 + 3 phase I designs, 107, 113
Core-binding factor (CBF) AML, 293, 299
Cowden syndrome, 186
and risk of breast cancer, 248, 252
Craniopharyngioma, sexual dysfunction in, 258, 263
CRC. See Colorectal cancer (CRC)
Crizotinib, 136
Crizotinib resistant tumors, treatment for, 131, 136
CROSS trial, 157–158
CRPC. See Castrate-resistant prostate cancer (CRPC)
CT colonography, 46, 49
CTCs. See Circulating tumor cells (CTCs)
CTLA-4, 91, 94
and inhibition of T cells, 90, 94
CXCL12, 20, 27
CXCR4, 20, 27
Cyclin-dependent kinase 4, 7
Cyclin-dependent kinases (CDKs), 7, 15, 22
Cyclins, 22
B-type, 15, 22
Cyclophosphamide, cardiac toxicity by, 334, 338
Cytokeratin, 222
Cytostatic agents, 114
early-phase trials of, 109, 114
Cytotoxic chemotherapy, zidovudine and, 327, 330
D
Daratumumab, 322
Dasatinib, 310
side effects of, 306, 311
Death receptor pathway, 17, 24
Denosumab, mechanism of action of, 345, 349
Depsipeptide, 9
DES. See Diethylstilbestrol (DES)
Desmoid tumors, 189, 194
Dexamethasone
in ALL induction therapy, 297, 302
in malignant spinal cord compression, 344, 348
DIC. See Disseminated intravascular coagulopathy (DIC)
Dicentric chromosome, 12
Diet-derived natural products, 53, 57
Diethylstilbestrol (DES), 234
exposure in utero and clear cell vaginal cancer, 228, 234
Differentiation syndrome, 296, 301
Diffuse alveolar hemorrhage, induction therapy in AML and, 294, 299
Diffuse large B-cell lymphoma (DLBCL), 284, 289, 347
advanced-stage, 286, 290
extranodal NK/T-cell, 287, 291
germinal center B-cell (GCB), 286, 290
R-CHOP chemotherapy for, 286, 290
Dihydropyrimidine dehydrogenase (DPD), 195
deficiency and risk for 5FU toxicities, 190, 195
deficiency of, 80, 84
Disseminated intravascular coagulopathy (DIC), 348
DLBCL. See Diffuse large B-cell lymphoma (DLBCL)
DLI. See Donor lymphocyte infusion (DLI)
DLL4, 26
DNA double-strand breaks
dose-related cellular response to, 70, 74
mechanisms of repair for, 69, 74
radiation-induced, 69, 74
DNA hypomethylating agents, 3, 9
DNA mismatch repair (MMR) gene, germline mutations in, 189, 194
genetic counseling and testing of at-risk family members, 190, 194–195
DNMT3A gene, 299
Donor lymphocyte infusion (DLI), 335, 340
Dose-dense chemotherapy, 99, 103
Double-strand breaks (DSBs), 10. See also DNA double-strand breaks
DPD. See Dihydropyrimidine dehydrogenase (DPD)
Drop-ins and drop-outs, effect of, 43, 47
DSBs. See Double-strand breaks (DSBs)
Dutasteride, and prostate cancer, 53, 56
Dynamic-contrast magnetic resonance imaging, 100, 104–105
E
EBV. See Epstein-Barr virus (EBV)
E-cadherin, 20, 27
E-cadherin mutation testing, 154, 159
Ecologic studies, 30, 32
Efavirenz, 332
Effect modification. See Confounding factors and interaction
EGFR mutations, 129, 134
EGFR–tyrosine kinase inhibitors (TKIs), 131, 134, 135
ELOQUENT-2 trial, 322
Elotuzumab, 322
EML4-ALK translocation, 134
ENDEAVOR trial, 324
Endometrial cancer
hysterectomy for grade 2 endometrioid cancer, 230, 236
IIIC1 stage, 231, 236
radiation and chemotherapy for, 231, 237
risk factors for, 226, 232
risk factors for development of, 230, 236
type I, 225, 232
type II, 225, 232
Endometrioid adenocarcinomas
genetic changes in, 225, 232
risk factors for, 225, 232
Enzalutamide, 128
EORTC 40983 study, 196
Ependymoma, 260
adjuvant radiation therapy after resection in, 258, 263
radiation therapy for, 257, 262
surgical resection for, 262
Epidermal growth factor receptor (EGFR), role of, in head and neck SCC (HNSCC), 119, 124
Epigenetic therapy, 81, 86
Epithelial mesotheliomas, 133, 137
Epstein–Barr virus (EBV), 34, 38, 256, 261
Epstein–Barr virus latent gene EBNA, 89, 93
Erlotinib, 85, 97, 102, 136, 145
resistance to, 129, 134
Esophageal adenocarcinoma, risk factors for, 151, 156
Esophageal cancer, 151, 152, 156–157
molecular biology of, 152, 157
perioperative chemotherapy in, 153, 158
European Organization for Research and Treatment of Cancer (EORTC) trial, 261
Ewing sarcoma, 268, 273
and cytogenetic abnormalities, 265, 270
Excisional biopsy, 252
Excision repair mechanisms, 4, 10
Exclusive inhibitors, 87
EXTREME trial, 125, 128
Ezrin, 27
F
Familial adenomatous polyposis (FAP), 54, 58
Familial cancer syndromes, germ line mutations in, 1, 7
Familial malignant melanoma syndrome, 23
Fanconi anemia
defects in, 10
Fanc genes, abnormalities in, 4, 10
FAP. See Familial adenomatous polyposis (FAP)
Fibrolamellar HCC, 168, 177
Finasteride, and prostate cancer, 53, 56
Fluorescence in situ hybridization (FISH), 299
5-Fluorouracil (5-FU), 21, 28, 80, 84
and leucovorin, 155, 160
and mitomycin for anal cancer, 192, 196
FOLFIRINOX, in adenocarcinoma of pancreas, 165, 174
FOLFOX, in pancreatic cancer, 174
Folic acid, in children with lymphoblastic leukemia, 97, 102
Follicular lymphoma, 284, 289, 341
Follicular thyroid cancer, 67
Foster–Kennedy syndrome, 347
FOXA1, 213
5-FU. See 5-Fluorouracil (5-FU)
Fumarate hydratase gene, 208
Furosemide, 349
Fusion PET-MRI, in multiple myeloma, 319
G
Gail model, breast cancer, 249, 253
Gallbladder cancer
and cholecystectomy, 168, 176
T2 NX (stage II), 167, 176
Gallium nitrate, 349
Gardasil vaccine for HPV, 33, 37–38
Gastric cancer, 151, 154, 156, 158–159
diagnostic modalities in, 154, 159
early-onset diffuse, 154, 159
metastatic, combination chemotherapy for, 155, 160
Gastroesophageal reflux disease (GERD), 151, 156
Gastrointestinal stromal tumors (GISTs), 181, 185, 271
criteria predictive of behavior of, 269, 273
familial and genetic syndromes with, 183, 186
imatinib for, 267, 271
imatinib-resistant, 182, 185
KIT mutations in, 185
regorafenib for, 182, 186
from small intestine, 183, 187
sunitinib therapy for, 182, 185
GBM. See Glioblastoma multiforme (GBM)
Gefitinib (Iressa), 12
Gemcitabine, 76, 97, 102
and cisplatin, 169, 178
and hemolytic uremic syndrome, 345, 348
Gemtuzumab ozogamicin, 301–302, 303
Gene amplification, 3, 9–10
Gene array technology, 3, 8–9
Genetic testing, noninformative, 62, 66, 67
Genome-wide association studies (GWAS), 30, 32
GERD. See Gastroesophageal reflux disease (GERD)
German Rectal Cancer Study, 195–196
Germ-cell cancers, 97, 102
Germ cell tumors of ovary, 242, 245
Germinal center B-cell (GCB) diffuse large B-cell lymphoma, 286, 290
Gestational trophoblastic disease (GTD) with complete mole, 226, 232
Gestational trophoblastic neoplasia (GTN), 231, 237
methotrexate for low-risk disease, 231, 237
Giant cell tumor (GCT), of bone, 268, 272
GISTs. See Gastrointestinal stromal tumors (GISTs)
Glasgow prognostic score (GPS), 34, 38
Glioblastoma, 260
Glioblastoma multiforme (GBM), 255, 256, 260
concurrent brain radiation with temozolomide in, 258, 263
dysregulated core pathways in, 259, 263
gene expression profiling, 263
mesenchymal group and loss of NF1 expression, 258, 263
radiation therapy for, 257, 261–262
recurrent, 257, 261
Gompertzian kinetics, 99, 103
Graft manipulation ex vivo to purge tumor cells, 336, 341
Graft-versus-leukemia (GVL) effect, 338
in chronic-phase CML, 334, 338–339
donor T lymphocyte and, 336, 341
NK cells and, 336, 341
Granulosa cell tumors, 223
of ovary, 241, 244
G1/S phase, cell cycle, 2, 8
G1/S-phase transition, cyclins E and A accumulation for, 15, 22
GTN. See Gestational trophoblastic neoplasia (GTN)
Guanase, 349
GVL effect. See Graft-versus-leukemia (GVL) effect
Gynecologic Oncology Group (GOG), 231, 237
H
Hairy cell leukemia (HCL), 308, 313
BRAF V600E mutation in, 309, 314
Hayflick phenomenon, 4, 11
HCC. See Hepatocellular carcinoma (HCC)
hCG. See Beta-human chorionic gonadotropin (hCG)
HCL. See Hairy cell leukemia (HCL)
HDGC. See Hereditary diffuse gastric cancer syndrome (HDGC)
Head and neck squamous cell carcinoma (HNSCC)
adjuvant chemotherapy in, 121, 126
cetuximab in, 121, 126
combinations of chemotherapy agents, 120, 125
concurrent chemotherapy and radiation therapy in, 121, 125
epidermal growth factor receptor in, role of, 119, 124
HPV-related, 120, 124
induction chemotherapy in, 122, 127–128
locally advanced, 122, 127
neck dissections, complications from, 120, 125
risk factors for, 119, 124
second primary cancers with, 122, 127
stage IVA, 120, 124
Helicobacter pylori infection, 151, 156
and risk of intestinal-type gastric adenocarcinoma, 53, 57
Hemolytic uremic syndrome (HUS), 345, 348
gemcitabine and, 345, 348
mitomycin and, 345, 348
Hemorrhagic cystitis, 80, 84
Hepatitis B virus, 177
Hepatitis C infection, 169, 177
Hepatitis C virus, 34, 38
Hepatitis D virus (HDV), 38
Hepatoblastoma, 168, 177
Hepatocellular carcinoma (HCC), 34, 38, 166, 175
clinical suspicion for, 168, 177
fibrolamellar, 168, 177
hypoglycemia and, 166, 175
liver transplantation in, criteria for, 166, 175
paraneoplastic syndromes with, 166, 175
risk factors for, 167, 175
screening and prevention for, 167, 175–176
staging systems for, 166, 175
surveillance for, 170, 178
Hereditary cancer syndromes, expression in, 60, 64
Hereditary diffuse gastric cancer syndrome (HDGC), 61, 65–66, 159
informative genetic test, 61, 66
noninformative genetic test, 66
Hereditary leiomyomatosis and renal cancer syndrome, 208
Hereditary nonpolyposis colon cancer (HNPCC), 9, 10, 159
and colorectal cancer, 194
diagnosis of, 190, 194
microsatellite instability (MSI) by mutations in DNA MMR genes, 194
MSH2 gene and, 190, 195
Hereditary nonpolyposis colorectal cancer syndrome, 230, 236
Hereditary papillary renal cancer, 207, 208
MET mutations in, 199, 207
Her2/neu amplification, in breast cancer, 3, 10
HER2 testing, 153, 158
HevyLite assay, 319
Hierarchy model of tumor heterogeneity, 21, 27
HIF. See Hypoxia-inducible factor (HIF)
High-grade dysplasia, in Barrett esophagus, 152, 157
Hilar cholangiocarcinoma, 167, 176
HIV. See Human immunodeficiency virus (HIV)
HIV-associated Hodgkin lymphoma (HL), 328, 331
HIV-infected patients
anogenital cancers in, 328, 331
cervical cancer in, 327, 330
stage IIIB anal carcinoma, treatment for, 329, 331–332
viruses in development of cancers in, 329, 331
HNPCC. See Hereditary nonpolyposis colon cancer (HNPCC)
HNSCC. See Head and neck squamous cell carcinoma (HNSCC)
Hodgkin lymphoma, 327, 330, 347
in pregnancy, 288, 292
Homologous recombination (HR), 69, 74
Hoosier Oncology Group (HOG), 136
Hormonal therapy in ovarian cancer, 240, 244, 245
Hormone replacement therapy (HRT), decline in use of, 30, 32
HOVON-65/GMMG-HD4 trial, 320
HPV. See Human papilloma virus (HPV)
HPV-associated vulvar cancer, 228, 235
HPV vaccines, 233
Human cancers, cytogenetic abnormalities in, 4, 10–11
Human cells, expressed genes in, 1, 7
Human Genome Project, 1, 7
Human herpesvirus-8, and primary effusion lymphoma, 284, 289
Human immunodeficiency virus (HIV), 227, 233
Human papillomavirus (HPV), 226, 232
prevention and treatment of infection, 226, 233
Human papilloma virus (HPV)
related HNSCC, 120, 124
vaccine, 90, 93
HUS. See Hemolytic uremic syndrome (HUS)
Hyperfractionation, 71, 75
Hyperkalemia, tumor lysis syndrome and, 344, 348
Hypoxanthine phosphoribosyltransferase, 349
Hypoxia-inducible factor (HIF), 208
pathway, 85
and tumor angiogenesis, 200, 208
I
IBC. See Inflammatory breast cancer (IBC)
Ibrutinib, 290
in chronic lymphocytic leukemia, 309, 314
IGRT. See Image-guided radiation therapy (IGRT)
IL-2 for melona, 90, 93–94
Image-guided radiation therapy (IGRT), 78
Imatinib, 12, 24, 81, 85, 100, 104, 145, 181, 185
in chronic myeloid leukemia, 306, 310–312
Immune lymphocytes, 89, 93
Immunotherapy to destroy cancer cells, mechanism for, 89, 93
IMRT. See Intensity-modulated radiation therapy (IMRT)
Inflammation, role of, in carcinogenesis, 34, 38
Inflammatory breast cancer (IBC), 251, 254
INK family proteins, 23
Intensity-modulated radiation therapy (IMRT), 71, 76, 78
and risk of xerostomia, 122, 127
Intention-to-treat analysis, 111, 116
Intention to treat (ITT) analysis, 99, 103
Interferon (IFN)-α, 16, 22
Intergroup Trial, 155, 160
International Gastric Cancer Linkage Consortium (IGCLC), 159
International Germ Cell Consensus Classification, 219, 222
International Myeloma Working Group, 319
Intracranial pressure, increased
and midbrain dysfunction, 344, 348
signs of, 343, 347
Intraepithelial neoplasias, 52, 55
Intravesical therapy, for bladder cancer, 201, 208
Ionizing radiation (IR)
and DNA damage/repair process, 69, 74
repair of damage from, 35, 39
risk of cancer from, 35, 39
Ipilimumab, and nivolumab, 91, 94
Ipilimumab-related endocrinopathy, 278, 281
IR. See Ionizing radiation (IR)
Irinotecan, and neutropenia, 191, 195
Isochromosome 12p (i[12p]), 147
Isocitrate dehydrogenase 1 (IDH1) gene, 260
Ixazomib, 325
K
Kaposi sarcoma (KS), 329, 331
and HAART therapy, 327, 330
staging system for, 328, 331
Ketoconazole, 84
Kidney cancer, anti-VEGF drugs in, 81, 85
Klinefelter syndrome
and germcell tumor, 216, 220–221
mediastinal NSGSTs and, 142, 148
KRAS mutation, 84
KS. See Kaposi sarcoma (KS)
L
Lapatinib, 81, 85
Large B-cell lymphoma, 219, 223
Laryngeal squamous cell carcinoma (SCC)
adjuvant chemotherapy in, 121, 126
concurrent chemotherapy and radiation therapy in, 119, 121, 124, 126
Lead-time bias, 43, 47, 49
Leiomyosarcoma
intra-abdominal, 266, 271
lung metastases, 267, 271
recurrence of, 266, 270
Lenalidomide, 334, 339
Length bias, 47
Leukoplakia, 52, 55
Leuprolide, 128
Leydig cell tumor, 223
Li–Fraumeni syndrome, 23, 186, 247, 252, 255, 260
and soft tissue sarcomas, 265, 270
Linear accelerator (LINAC), modern, 70, 75
Liposarcoma, high-grade extremity, 266, 271
Liver, sinusoidal obstruction syndrome of, 334, 339
Liver transplantation, 169, 178
Lovastatin, 56
LS. See Lynch syndrome (LS)
Lumbar puncture, 285, 289–290
Luminal A breast cancer, 247, 252
Lung Adjuvant Cisplatin Evaluation (LACE) meta-analysis, 137
Lung cancers
CT-guided biopsy, 129, 134
genomic profile of, 134
tumors from never smokers, 134
tumors from smokers, 129, 134
incidence of, in women, 32
and malignant spinal cord compression, 344, 347
platinum-based doublet chemotherapy, 130, 134
Lymphoma
adult, 283, 289
anaplastic large-cell, 284, 289
B-cell, 284, 289
Burkitt, 283, 289
childhood, 283, 289
International Prognostic Index (IPI) score for, 284, 289
and malignant spinal cord compression, 344, 347
mantle cell, 285, 290
primary effusion, 284, 289
T-cell neoplasms, 284, 289
Lynch II syndrome, 230, 236
Lynch syndrome (LS), 54, 57, 59, 64
autosomal-dominant inheritance in, 64
cancer risk from, 64
and cancer screening, 60, 64
and cervical cancer, 63, 67
and endometrial cancer risk, 54, 57
gastric cancers and, 154, 159
and genetic testing, 60, 65
MSH2 gene mutation, inheritance of, 64
M
Malabsorption after Whipple surgery, 164, 172–173
Male breast cancer, 251, 254
Male urethral cancers, risk factors for, 201, 209
Malignant mesotheliomas
epithelial, 133, 137
immunohistochemistry markers in, 133, 137
poor prognostic factors in, 133, 137
Malignant spinal cord compression (MSCC), 347
causes of, 344, 347
corticosteroids in, 344, 348
Malignant teratoma, 147
Mammography, 48
Mantle cell lymphoma, 285, 286, 290
Maximum tolerated dose, 113
Mayo Stratification for Myeloma and Risk-adapted Therapy (mSMART) criteria, 319–320
MBL. See Monoclonal B lymphocytosis (MBL)
MDS. See Myelodysplastic syndrome (MDS)
Mediastinal germ cell tumors, 141, 146–147
Mediastinal seminoma, 142, 148
cisplatin plus etoposide for, 143, 148
Medullary thyroid carcinoma (MTC), and preoperative basal calcitonin levels, 54, 57
MEK mutations, 79, 84
Melanoma
adjuvant stereotactic radiosurgery for, 277, 281
anatomical sites for, 276, 280
BRAF V600E mutation in, 275, 280
brain MRI for suspected solitary intracranial metastasis, 276, 280
Breslow thickness, 276, 280
cutaneous, 275, 280
genetic counseling, 275, 280
grade III autoimmune colitis, 278, 281
incidence of, 30, 32
ipilimumab in metastatic melanoma, 278, 281
risk factor for, 275, 280
stage IIIC, 277, 281
tumor biopsy and brain MRI examination, 277, 281
wide excision and sentinel lymph node mapping, 276, 280
Melphalan, 334, 339
Memorial Sloan Kettering Cancer Center (MSKCC) nomogram, for sarcoma-specific mortality,
266, 270
Meningioma, 255, 260
grade II resection for, 257, 262
6-Mercaptopurine (6MP), 80, 84
Mesna
hemorrhagic cystitis and, 80, 84
mechanism of action of, 269, 273
Meta-analysis, 112, 117
Metastasis progression genes, 20, 26
Metastasis, risk of, 19, 26
Metformin, 57
Methotrexate
for gestational trophoblastic neoplasia, 231, 237
high-dose, for immunocompetent patients with primary CNS lymphoma, 258, 262–263
Methylation, 12
Methyl guanine methyl transferase (MGMT) gene methylation, 261
Metronomic low-dose chemotherapy, 19, 26
Microarray technology, 2, 8
MicroRNA (miRNA), 2, 8, 16, 23
Microsatellite instability (MSI), 10, 189, 194
in colon cancer, 3, 10
and 5-fluorouracil chemotherapy, 3, 9
in type I endometrial cancers, 232
Minimum Information About A Microarray Experiment (MIAME), 2, 8
miRNA array signatures, 8
Mismatch repair machinery of cell, 4, 10
Missense variants, 66
Mitomycin, and hemolytic uremic syndrome, 345, 348
Mitosis, 15, 22
Mitoxantrone, 102
MMR mutation testing, 190, 194
Modified radical neck dissection (MRND), 125
Monoclonal B lymphocytosis (MBL), 309, 314
Monosomal karyotype, 294, 300
MOSAIC study, 195
MSCC. See Malignant spinal cord compression (MSCC)
MSI. See Microsatellite instability (MSI)
Mucosal-associated lymphoid tissue (MALT) lymphoma, 183, 186
Muir–Torre syndrome, 194
Multiple myeloma
antimyeloma therapy for, 315, 319
autologous stem cell transplantation in, 316, 320–322
carfilzomib therapy in, 317, 323–324
conditioning regimen for autologous stem cell transplant, 334, 338
depth of response and prolonged survival in, link between, 316, 320–321
diagnosis of, 319
FISH and cytogenetic studies, 315, 319–320
genomic sequencing in, 316, 320
monoclonal antibodies under investigation in, 322
MRD assessment, 321
panibinostat in, 317, 323
prognosis in, 319
risk classification system, 315, 319–320
Myasthenia gravis, 139, 144
Mycosis fungoides, 287, 291
MYD88, 324
Myeloablative transplantation in CR1, 297, 303
Myelodysplastic syndrome (MDS), 295, 301
MYH-associated polyposis, 192, 195, 196
Myxoid liposarcoma, 270
N
Nasopharyngeal carcinomas, 126–127 121
subtypes of, 126
treatment for, 127
National Comprehensive Cancer Network, 194
National Lung Screening Trial (NLST) eligibility criteria, 46, 49
Nbk/Bik, 24
NBS1 gene, 16, 23
Necitumumab, 136
Necrosis, 24–25
Negative predictive value (NPV), 47
Neoadjuvant chemotherapy, 98, 102
Neuroblastoma, N-myc amplification in, 3, 9
Neurofibromatosis, and GIST, 183, 186
Neurofibromatosis type 2 (NF2), 255, 260
Neurofibromatosis type I, 270
Next-generation sequencing (NGS), 321
NGS. See Next-generation sequencing (NGS)
Nicotine replacement therapy (NRT), 51, 55
Nijmegen breakage syndrome 1, 23
Nijmegen disease, 16, 23
Nilotinib, 310
Nitrogen-containing bisphosphonates, 349
Nivolumab, 91, 94
ipilimumab and, 91, 94
in lung cancer, 91, 94
N-myc amplification, in neuroblastoma, 3, 9
Nodal Marginal zone lymphoma, 341
Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL), 288, 291
Non-Hodgkins lymphoma, 23
Nonhomologous end-joining (NHEJ) pathway, 69, 74
Non–HPV-associated invasive squamous vulvar cancer, 228, 235
Noninformative censoring, 111, 117
Nonseminomatous germ cell tumor (NSGCT), 141, 146, 220
bleomycin, etoposide, and cisplatin (BEP) for, 216, 217, 220, 221
chemotherapy in, 215, 218, 220, 222
and CNS metastases, 215, 220
in first relapse, 219, 223
and hyperthyroidism, 219, 222–223
late relapse, 217, 221
mediastinal, 146–149, 216, 220–221
risk factor for recurrence of, 218, 222
and surgical resection, 216, 220
Non–small cell lung cancer (NSCLC)
adjuvant chemotherapy after resection for, 130, 135
concurrent chemoradiation for locally advanced NSCLC, 131, 135
concurrent definitive cisplatin and etoposide therapy for, 132, 136
with nonsquamous histology, 134
pemetrexed maintenance therapy in, 130, 135
ROS1 translocations in, 132, 136
with squamous histology, 130, 134–135
Nonsteroidal anti-inflammatory drugs (NSAIDs), in colorectal cancer, 52, 56
Nortriptyline, for tobacco dependence, 51, 55
NRIP1, 213
NRT. See Nicotine replacement therapy (NRT)
NS5A protein product of HCV genome, 169, 177
NSCLC. See Non-small cell lung cancer (NSCLC)
NSGCT. See Nonseminomatous germ cell tumor (NSGCT)
Nucleotide excision repair (NER) pathway, 4, 10
Nurse’s Health Study, 56
O
OCT3/4, 222
Octreotide, 140, 145
Ofatumumab, and rituximab, 83, 87
Oligodendroglioma
allelic loss of chromosome 1p and 19q in, 256, 260
IDH1 mutations in, 258, 263
prognosis of, 256, 261
Oncogenes, 1, 7
Opisthorchis viverrini, 211
Oral cavity SCC
stage II (T2N0M0), close monitoring in, 123, 128
stage IVA (T4aN1M0), surgery for, 120, 125
Osteosarcomas, 268, 272
treatment of, 265, 270
Ovarian cancer, 239, 243
advanced-stage, and risk of relapse, 241, 244
Ashkenazi-Jewish ancestry and, 239, 240, 243, 244
BRCA1 or BRCA2 mutations and, 240, 243, 244
CA-125 and, 240, 243
clinical surveillance in, 242, 245
elevated CA-12, and hormonal therapy, 240, 244
germ cell tumors, 242, 245
granulosa cell tumors, 241, 244
intraperitoneal chemotherapy, use of, 242, 245
nodal metastases, 241, 244
nulliparity and risk of, 240, 243
oral contraceptives and, 241, 243, 244
recurrent, and platinum-based chemotherapy, 242, 245
screening for, 45, 48
stage IA grade 1 mucinous tumor, 239–240, 243
tumor of low malignant potential, therapy for, 240, 243
Overdiagnosis, 45, 49
Oxygen enhancement ratio (OER), 71, 75
P
p53, 99, 104
alterations of, in astrocytoma, 255, 260
mutations of, 3, 9
and senescence, 5, 12
urothelial carcinoma of bladder, alterations in, 202, 210
Paclitaxel radiosensitizing, 76
Pair production, 76
Palbociclib, 100, 104
Pancoast tumor of lung, therapy for, 132, 136
Pancreatic cancer, 163, 171
adjuvant therapy for, 164, 173
familial, BRCA2 gene mutation in, 165, 174
KRAS mutation and development of, 163, 171–172
locally advanced, 164, 173
multiphase CT scan for, 164, 172
nab-paclitaxel and gemcitabine in, combination of, 165, 173
OFF chemotherapy regimen in, 165, 174
p16-mediated CDK inhibition and, 166, 174
risk factors for, 165, 174
stage III, T4N1M0, 163, 172
telomere shortening and, 166, 174
TGF-β receptors in, underexpression of, 166, 174
tobacco smoke and, 171
Pancreatic enzyme supplementation, 164, 172–173
Pancreatic intraepithelial neoplasms (PanINs), 171
Panibinostat, adverse events from, 317, 323
Parosteal osteosarcoma, 268, 272
Parotid gland cancers, treatment for, 122, 127
Partial response, definition of, 98, 103
Patched gene 1, 276, 280
Pazobanib, hepatotoxicity from, 269, 273
Pazopanib, 79, 84
PCNSL. See Primary CNS lymphoma (PCNSL)
PD-1, 91, 94
Pemetrexed, 21, 28
Penetrance, 64
reduced, 59, 64
Penile carcinoma, 206, 213
Peptidome, 3, 9
Pericytes, 18, 25
Peripheral blood mobilized stem cell allografts, 335, 339
Peritoneal mesothelioma, 133, 137–138
Peutz–Jeghers syndrome, 63, 68
Phase III trials, 109, 114–115
Phase II trials, 108, 113
early elimination of ineffective drugs, 108, 113–114
two-stage design, 108, 114
and welfare of patients, 108, 114
Phase I trials, 107, 113
limitations of, 107, 113
Phase 0 trials, 112, 117
Phenytoin, 79, 84
Photoelectric effect, 72, 76
PI3-kinase pathway, 28
Pilocytic astrocytoma, 256, 261
p16INK4a, 1, 7
and senescence, 5, 12
Placental alkaline phosphatase (PLAP), 222
Platinum-based doublet chemotherapy, for metastatic disease, 130, 134
Platinum-resistant tumor cells, 80, 85
Pleural mesothelioma
cisplatin and pemetrexed for, 133, 138
unresectable, 133, 137
Polymerase chain reaction (PCR), 299
Poly (ADP-ribose) polymerase (PARP) inhibition, 82, 86
Positive predictive value (PPV), 47
decrease in, 43, 47
Posttransplant disease relapse risk, 334, 339
Prednisone, 82, 86
Primary CNS lymphoma (PCNSL), 287, 291
methotrexate and rituximab for, 288, 291
Primary (de novo) glioblastoma multiforme (GBM), 255, 260
Primary intestinal lymphomas and secondary intestinal lymphomas, distinction between, 183,
186–187
Primary leptomeningeal lymphoma, 291
Prognostic biomarker, 79, 84
Programmed-cell death pathway, 100, 104
Prolymphocytic leukemia (PLL), 313
Prophylactic total gastrectomy, 57–58
Prostate cancer
adjuvant radiotherapy in, 204, 211
androgen ablation and risk of osteoporosis, 204, 211–212
androgen ablation in high-risk patients, 203, 211
androgen receptor and, 206, 213
antiandrogen withdrawal response, 204, 211
chromosomal translocations involving TMPRSS2 in, 201, 209
high-risk features and therapy, 203, 210
metastasis to liver, 20, 27
nonmetastatic CRPC, 205, 212
and osteoblastic bone metastases, 20, 27
predictors of cancer on biopsy, 203, 210
PTEN and, 206, 212–213
radical retropubic prostatectomy and complications, 204, 211
risk factors, 205, 212
risk factors for, 203, 210
surveillance in, 205, 212
Proteome, 2, 8
Proteomic signatures, 9
Proteomic technologies, 3, 8–9
Protonation, 8
Protooncogene, 23
definition of, 2, 7
Pulmonary carcinoid tumors, 131, 135
Puma, 24
Q
Quiescence, 5, 11
R
Radiation
adverse effects of, 77
depth dose characteristics of, 72, 77
subacute toxicity from, 72, 77
tissue effects from, 71, 76
Radiation effects, role of oxygen in, 71, 75
Radiation-induced cell death, 70, 75
Radiation-induced pneumonitis, 77
Radiation-induced sarcomas, 265, 270
Radiation Therapy Oncology Group (RTOG 9704), 173
Radical neck dissection (RND), 125
Radiotherapy, for localized mediastinal seminoma, 142, 148
Raloxifene, 52, 56
and risk of stroke, 53, 56
Raltitrexed, 174
Ramucirumab (IMC-1121B), 155, 161
Randomized assignment to treatment, 109, 115
Randomized discontinuation design, 100, 104
RANK-ligand inhibitors, for pain associated with bone metastases, 251, 254
Rasburicase, 346, 349
R-CHOP, 263
Real-time quantitative polymerase chain reaction (RQ-PCR), 305, 310
REAL-2 trial, 155, 160
Receptor phosphotyrosine phosphatases (RPTPs), 6, 13
Receptor tyrosine kinases, 6, 12, 13
RECIST criteria, 100, 104
Rectal cancer
T3+/N0-2, 191, 195–196
transanal excision, 191, 196
Reduced penetrance, 59, 64
REGARD study, 160–161
Regorafenib, for GIST, 182, 186
Relative risk reduction, 48
Renal cell cancer, 199, 207
Memorial Sloan Kettering Cancer Center (MSKCC) risk factors, 200, 207
prognostic factors, 200, 207
recurrent metastatic disease, 200, 207
subtypes, 207
temsirolimus in, 200, 208
Renal pelvis urothelial cancers
radical nephroureterectomy and bladder cuff resection for, 202, 210
Replicative senescence, 16, 23
Repopulation, during fractionated radiotherapy, 70, 74–75
Retinoblastoma, 270
Retinoids and beta-carotene, and skin cancer incidence in xeroderma pigmentosum, 52, 55
RET protooncogene, germ line mutations in, 54, 58
Rituximab, in chronic lymphocytic leukemia, 309, 314
Rofecoxib, 56
RTOG 91-11, 124, 126
RUNX1, 299
S
Salivary gland cancers, 128
expression of androgen receptor in, 123, 128
histologic types, 128
Salpingo-oophorectomy, 54, 57
Sarcomas
Ewing sarcoma, and cytogenetic abnormalities, 265, 270
MSKCC nomogram for sarcoma-specific mortality, 266, 270
radiation-induced, 265, 270
soft tissue, 265, 270
Schistosoma haematobium, bladder cancer by, 204, 211
SCLC. See Small cell lung cancer (SCLC)
Selection bias, 30, 31, 47, 49
Selective neck dissection (SND), 125
SELECT trial, 55
Selenium supplementation, and nonmelanoma skin cancer, 52, 55
Seminoma, chemotherapy for, 217, 221
Senescence, 2, 7
and quiescence, 11
as tumor suppressor mechanism, 5, 12
Sensitivity of test, 47
Sequenced human genome, analysis of, 1, 7
Sex cord–stromal tumors, 244
Sexual dimorphism, pharmacokinetic, 79, 84
Sexual dysfunction, in craniopharyngioma, 258, 263
SIADH. See Syndrome of inappropriate antidiuretic hormone secretion (SIADH)
Simon phase 2.5 designs, 109, 114
Sinusoidal obstruction syndrome (SOS), 334, 339
Sipuleucel-T, 91, 95
SIRIUS trial, 322
Small bowel adenocarcinomas, 183, 186
Small cell lung cancer (SCLC)
C-myc amplification in, 3, 9–10
combination chemotherapy for, 343, 347
genomic characterization of, 132, 137
limited-stage, management of, 130, 135
location for primary tumor, 343, 347
and SVC syndrome, 343, 347
Smoking
and lung cancer, 33, 37
and radiotherapy-associated toxicities, 51, 55
SN-38, 195
and glucuronidation, 195
and neutropenia, 191, 195
Soft tissue sarcomas, 265, 270
extremity, 269, 273
of head and neck, 271
locally recurrent, 267, 272
metastatic, 267, 272
chemotherapy treatment of, 267, 272
nonmetastatic, independent predictors of prognosis of, 267, 271
staging of, 266, 270
Sokal risk score, 305, 310
Sorafenib, 17, 24
for hepatocellular carcinoma, 329, 332
Southwest Oncology Group (SWOG), 136
Specificity of test, 47
Spermatic cord liposarcomas, 223
Spinal ependymoma, 256, 260
Splenic marginal zone lymphoma (SMZL), 285, 290
Src, 8
Stage shift, 48, 49
Standard fractionation for radiation therapy, 76
Statins, and cancer risk, 53, 56
Stem cell engraftment, 335, 339
Stem cell transplantation, 333–341. See also Allogeneic stem cell transplantation; Autologous
stem cell transplantation
Stochastic model of tumor heterogeneity, 21, 27
Strontium-89, 348
Suberoylanilide hydroxamic acid (SAHA), 9
Sulindac, 56
Sunitinib-associated hypothyroidism, 182, 185–186
Sunitinib, for alveolar soft part sarcoma, 268, 273
Superior vena cava syndrome, in thymic carcinoma, 140, 145–146
Superior vena cava (SVC) thrombosis, 347
Surveillance, Epidemiology, and End Results (SEER) Program, 30, 32
Survival data. analysis of, 111, 116, 117
Survival time after diagnosis, 48
Syndrome of inappropriate antidiuretic hormone secretion (SIADH), 346, 349
Synovial sarcoma, 270
T
Tamoxifen, 52, 56
for breast cancer, 252–253
TAMs. See Tumor-associated macrophages (TAMs)
Tartrate-resistant acid phosphatase (TRAP) testing, 313
Taxanes, 17, 24
T-cell depletion, and risk of engraftment failure, 335, 339
T-cell–mediated immunity, 89, 93
Telomerase, 5, 11, 23
Telomerase-null mice, 5, 12
Telomeres, 11
Temozolomide, 102
Temsirolimus, 21, 28, 207
Testicular cancer. See also Nonseminomatous germcell tumor (NSGCT)
hCG in, 219, 222–223
immunohistochemical proteins and, 218, 222
large B-cell lymphoma, 219, 223
long-term sequelae of cisplatin-based chemotherapy for, 219, 223
risk factors for, 218, 222
The Cancer Genome Atlas (TCGA), 263
Therapeutic equivalence trials, 110, 115
confidence interval, 110, 116
Thiopurine methyltransferase (TPMT) deficiency, 80, 84
Thymic carcinoid, and multiple endocrine neoplasia type 1, 141, 146
Thymoma, 139, 144
classification schemes and staging systems for, 144–145
incidence of, 144
molecularly targeted agents in, 140, 145
paraneoplastic syndromes with, 140, 145
predictor of long-term prognosis for people with, 139, 144
stage IV thymoma, systemic treatment for, 140, 145
Thyroid function tests, 278, 281
Time to tumor progression, as end point in clinical trials, 101, 105
T315I mutation, 84
TLS. See Tumor lysis syndrome (TLS)
T790M mutation, 84, 99, 103
Tobacco dependence, second-line pharmacotherapy for, 51, 55
Tobacco-induced cancers, 33, 37
Transarterial chemoembolization (TACE), 178
Transformation, 38
Transforming growth factor (TGF)-β, 16, 22
Trastuzumab, 153, 158
risk factors for cardiac dysfunction with, 250, 254
Treatment planning process, 72, 77
TSP-1, 26
Tumor angiogenesis, 18, 25
IL-6/8 and, 19, 26
Tumor-associated macrophages (TAMs), 20, 26–27
Tumor cells, and metastases, 19, 26
Tumor colonies, growth of, 18, 25
Tumor heterogeneity
hierarchy model of, 21, 27
stochastic model of, 21, 27
Tumor lysis syndrome (TLS), 344, 348
and hyperkalemia, 344, 348
Tumor suppressor genes, 1, 7, 16, 23
Tumor vasculature, 18, 25
Turcot syndrome, 222, 255, 260
Type II programmed cell death, 17, 24
Tyrosine kinases, 6, 12
U
UK-ABC-02 trial, 178
Ulcerative colitis, 277, 281
Ultraviolet (UV) light, 35, 40
Undifferentiated pleomorphic sarcoma (UPS) of soft tissue, 272
United States Preventive Services Task Force (USPSTF), 45, 48
Urate oxidase, 349
Uridine diphosphate glucuronosyltransferase (UGT) 1A1, 84
U.S. Preventive Services Task Force (USPSTF), 44, 47
Uterine corpus cancers, 230, 236
V
Vaginal cancers, 228, 234
stage II, 228, 234
Vandetanib, 85
Varenicline (Chantix), side effects of, 51, 55
Vascular endothelial growth factor (VEGF), 19, 25–26
in CTC extravasation, 20, 27
H1F1α and, 19, 26
Vasohibin, 26
VEGF. See Vascular endothelial growth factor (VEGF)
Vemurafenib (PLX4032), 21, 28
Veterans Administration Laryngeal Study Group Trial, 126
VHL gene, 200, 208
Villous lymphocytes, 285, 290
Vincristine, doxorubicin, and cyclophosphamide (VAC), 268, 273
Viral oncogenes (v-oncogenes), 8
Vismodegib, 279, 281
Vitamin B12 and folic acid supplementation, for hematologic toxicities with pemetrexed, 80,
85
Von Hippel–Lindau disease, 200, 208
Von Hippel–Lindau (VHL) tumor suppressor gene, loss of function in, 85
Vorinostat, 87
Vulvar cancer
HPV-associated, 228, 235
invasive, 228, 229, 235
local recurrence of, 229, 235
lymph node involvement and patient’s ultimate survival, 229, 235
non-HPV-associated, 228, 235
repeat resection for recurrent cancers, 229, 235
staging for, 229, 235
W
Waldenstrom’s macroglobulinemia (WM), 324
Warburg effect, 18, 25
Well-differentiated squamous cell carcinoma, thymic carcinoma, 141, 146
WHIM syndrome (warts, hypogammaglobulinemia, infection, and myelokathexis), 324
WHI trial, 56
WM. See Waldenstrom’s macroglobulinemia (WM)
Women’s Health Initiative, 56, 57
X
Xerostomia, 122, 127
X-rays, effects of, 69, 74
Z
Zidovudine, and cytotoxic chemotherapy, 327, 330