Sie sind auf Seite 1von 11

1

Problem 1 Technical Paper BMED 1300 September 24, 2013 Langley/Tucker D

Improving the Lung Cancer Screening Process


K. Bai, R. Bonagura, A. Cavallaro, K. Fierro, P. Grob, M. Lewis, E. Lobben, A. Nicaretta, E. Peek

Abstract Purpose: Lung cancer is the most lethal type in the U.S., claiming 226,000 lives annually. Lung cancer has an
overall 5-year survival rate of <15%; however, if the cancer is caught at stage I, the 5-year survival rate for lung cancer
increases dramatically to around 50%. An evaluation of the effectiveness of current screening methods and creation of new
screening procedures stands to greatly decrease annual mortality due to this disease.
Experimental Design: Currently available screening procedures used for diagnosis of lung cancer were evaluated based
upon accuracy in detection and feasibility to administer to a large population. After weighing factors such as sensitivity,
specificity, cost, speed, invasiveness, and radiation, a best screening strategy was recommended. The process was then
repeated with newer methods currently in clinical trial, and a new procedure was also recommended that was designed to
increase sensitivity without sacrificing specificity while minimizing costs.
Results: A CT scan is currently the most effective screening method in detecting lung cancer with a 261% increase in the
number of lung cancer cases correctly diagnosed compared to the standard chest x-ray, potentially effecting up to 157,000
people. The recommended method using future screening strategies increases correct diagnoses by 172%, or 97,300 people,
while decreasing the amount of false positives and wasted tests by 397%.
Conclusion: Current screening strategies have been evaluated, and a best method with what is currently available and
potentially available in the future has been recommended. Further research into the viability of these recommendations
involving small cell lung cancer is needed, as well as validation in the actual population.
Index Terms blood protein, computed tomography, imaging, lung cancer, screening
I.

Introduction

Lung cancer is the second most prevalent form of cancer in the United States, as well as the most lethal, claiming 226,000
lives annually (Cancer.org, 2010.) This mortality rate is as much as prostate, pancreatic, breast, and colon cancer combined.
As with any cancer, the rate of survival increases the earlier that it is detected and diagnosed. Lung cancer has an overall 5year survival rate of <15%; however, if the cancer is caught at stage I, the 5-year survival rate for lung cancer increases
dramatically to around 50% (Cancer.org, 2013.) Unfortunately, with the current methods for screening and diagnosing lung
cancer, 75% of all lung cancers are diagnosed at an advanced stage not amenable to surgery. Most patients go undiagnosed
until symptoms arise, and by the time symptoms occur the cancer is usually in a very late stage. A variety of screening
methods currently exist, with variable efficacy and costs. A standardized screening protocol that is capable of
unambiguously identifying patients with lung cancer, regardless of stage, before symptoms become present, is needed. This
new screening strategy should be cost effective, effect only those at the greatest risk of lung cancer, and compared to current
strategies it should increase sensitivity without sacrificing specificity. This strategy would need to have the potential to
greatly reduce the annual mortality rate due to the disease. For this purpose, an evaluation of current methods available is
presented, followed by a recommended approach based on newly developing screening strategies.
II. Methods
Selection of evaluation criteria
The current approach to screening for lung cancer holds many problems, including late stage diagnosis, low
sensitivity, and undefined risk groups. Among current tests, there are many areas that can be improved upon. These
characteristics can be broken broadly into two categories: accuracy, or ability of the test to accurately discern presence or
absence of disease, and feasibility, including factors such as time, cost, availability, invasiveness, and procedural hazards
such as radiation. In evaluating testing methods that are currently available in clinics, two factors were deemed to be more
important than the others, based on the potential to prevent deaths in comparison to the current standard. These were the

2
Problem 1 Technical Paper BMED 1300 September 24, 2013 Langley/Tucker D
sensitivity, especially for stage I or II lung cancers, or value in preventing false negative readings that would lead to a lack
of treatment or further screening which would drastically lower survival rate, and feasibility, which was defined as being
able to perform the test on a large target population with minimized costs, time, and risks.
Identifying population to minimize costs
In considering the feasibility of all the above-mentioned tests, as well as future screening procedures, it was
recognized that costs would be astronomical if the entire population would be screened regularly; even all smokers, who
make up about a fifth of the total population (U.S. Census, 2010) could not be processed within a reasonable span of time by
all the CT machines available in the U.S. Therefore, the first step to creating an improved screening procedure would be to
separate the population into a risk group that could feasibly be tested by any method recommended later. The current
population of the U.S. encompasses 320,000,000 people (U.S. Census, 2010,) which would be far too costly to recommend
for even annual screening. Even with a chest x-ray, the projected cost would be $56,000,000,000 annually (Healthcare
Quality and Cost Council, 2010) Therefore, a process was sought out that could separate individuals into risk populations
based on their environment, lifestyle, or genetics.
According to the recent publication in the New England Journal of Medicine, Probability of Cancer in Pulmonary
tumors Detected on First Screening CT, the main Lung cancer screening update
LDCT screening for patients who are 50 years or older with 20 pack years or more smoking history and who have an
additional lung cancer risk factor, like environmental exposure or family history.
Looking at previous lung cancer screening trials, two main factors, age and smoking history, were most strongly correlated
with increased risk of lung cancer. These include the American Cancer Society, American Lung Association, and National
Comprehensive Cancer Network. These associations all independently determined that the highest risk group consists of
smokers over the age of 55 who have a 30+ pack year history of smoking (NLST, 2011.) However, it was recognized that
many environmental or genetic risk factors also exist, and that these, too, play an important role in determining risk for lung
cancer.
It was recommended to break up qualifiers for a screening procedure into two groups. The first risk group which is
the high risk group a subject only needs to meet two standards, they need to be over the age of 55 and have a history of 30
or more pack years. The second group needs to meet three requirements: over the age of 55, 20 plus pack year of smoking
history and one or more of the four risk factors defined below. Significant exposure to secondhand smoke this means there
is a person in their direct household who is a heavy smoking, not a Light or Intermittent Smoker (LITS), who smokes more
than 5 cigarettes per week for more than 4 days a week. Qualifying for this risk factor would increase the persons risk of
getting lung cancer by a 1.25 fold (Coggins 2009). The second supplementary risk factor was environmental exposure. This
means the subject has a history of heavy exposure to asbestos which is around 100 fibers/ml-years. A normal individual gets
about 15 fibers/ml-year. If the subject has worked at the following lists of jobs for more than 5 years they also qualify for
environmental exposure: asbestos worker, insulator lagger, plasterboard worker, drywaller, ship fitter, shipyard
electrician/coppersmith, plumber/pipefitter, steamfitter, or sheet metal worker. The next supplemental risk factor is a family
history of lung cancer, meaning that the subject has a sibling who has been diagnosed with lung cancer and has no smoking
history. Having this risk factor would increase the chance of getting lung cancer by 1.51 fold (McCarthy, 2012.) The final
supplemental risk factor is a history of cancer (any type) or if the subject has Chronic Obstructive Pulmonary Disease, such
as emphysema or chronic bronchitis. This last risk factor would increase the chance of lung cancer by 1.41 fold
(McWilliams, 2013.)
By narrowing down the population according to these risk factors the approximate number of people entering our
first round of screening would be 9.8 million people. This number was determined using the population information from
the US Census. The total population of adults in the US is 234,564,000 adults 19% of adults smoke, this narrows down our
risk group to 44,567,160 people. Of these people 22% of adult smokers are older than the age of 50. This means 9.804,775
people would enter our screening. These numbers are not exact because the US Census does not report the amount of
smokers over the age of 55, only 50. Due to this, the number above is a worst-case estimate; the actual number of people
entering the recommended screening trial would almost certainly be lower.

3
Problem 1 Technical Paper BMED 1300 September 24, 2013 Langley/Tucker D
Ranking current methods based on criteria
Table I summarizes the results of all currently available screening procedures for lung cancer, defined as postclinical trial procedures that are capable of being recommended by physicians.
The current standard for screening for lung cancer is the chest x-ray. The chest X-ray is relatively inexpensive at
about $200, only takes about ten to fifteen minutes to run, and is not an invasive screening method. However, due to the
nature of the chest X-ray, it can be difficult to detect tumors in the lung that are stage 1 and stage 2. Consequently, many of
the tumors detected with a chest X-ray are in stage 3. This late detection severely decreases the five year survival rate to
14% (Cancer.org, 2013.) Similarly, the chest X-ray has a low sensitivity of only 26%, resulting in almost a quarter of
patients who may have lung cancer being falsely diagnosed as having the disease. The patient is exposed to minimal
amounts of radiation of about 8 mrem (McCarthy, 2012; Carcinog, 2013). Despite high specificity and cheap cost, the chest
X-ray is not the recommended technique for lung cancer screening due to its trends of late detection and low sensitivity. In
fact, it has been shown that annual chest x-rays for at risk lung cancer patients do not decrease their risk of dying of the
disease (Aberle, 2011.) Therefore, alternative techniques for screening for lung cancer must be considered.
Due to the fact that Low-Dose Computed Tomography, Magnetic Resonance Imaging, and Positron Emission
Tomography are imaging techniques, follow up scans are necessary when a mass is found because a lung tumor does not
necessarily imply cancer; detected growth in a lung tumor is what implies cancer. A LDCT scan has a sensitivity of 93% and
a specificity of 73% when tested on a high risk population of 55 or more years of age and at least 30 pack years. A LDCT
scan also takes about 30 minutes to run and costs around $1700. A positive quality of the LDCT scan is it able to detect
cancer that is in stage 1 or 2 by detecting lung tumors that are less than 4 mm. As a result of this added precision, many nonmalignant tumors also frequently appear on the image; only about 3.6% of the lung tumors detected are cancerous (Tamura,
2013.) The patient is exposed to minimal amounts of radiation of 20 mrem (McWilliams, 2013.)
A standard MRI produces an image by using a strong magnetic field to align the intrinsic spin of proton nuclei
inside the body to form an image; this takes about 15-20 minutes to run and has a sensitivity and specificity of 89% and
95% respectively. The patient is not exposed to any radiation, and the method is especially efficient in providing contrast for
soft tissues such as tumors. The machinery required to give an MRI is available in most large hospitals or specialized clinics
(Molnar, 1999).
A PET scan uses a glucose analogue 2-18F-fluoro-2-deoxy-D-glucose (FDG) injected into the body. FDG is
commonly used for detecting lung cancer because of the enhanced glucose metabolism of lung cancer cells (Schrevens,
2004). The FDG targets areas of the body with high energy consumption such as tumors, therefore the tumors show up
clearly in the image. It has a sensitivity and specificity of 97% and 82% respectively (Duhaylongsod, 1995). The patient is
also exposed to a significant amount of radiation of about 500 mrem (McCarthy, 2012; Carcinog, 2013). The equipment
required to do a PET scan is the most limited of the three imaging methods evaluated above.
In addition to imaging techniques, sputum cytology or a bronchoscopy can also be used to screen for lung cancer.
For both of these methods, a local anesthetic is necessary in order to perform the test. Sputum cytology takes about two
weeks to process and requires taking a sample of the sputum that is in the patients throat that is then grown for a
confirmation of disease. The test costs about $175 and has a sensitivity of 53% and a specificity of 78% (Jiang, 2011). The
final and most invasive technique for screening for lung cancer is using a bronchoscopy. This requires putting a patient all
the way to sleep and running a bronchoscope down a patients throat in order to get a visual of and tumors in the lung. This
costs about $650 and takes 30 minutes to perform. It has a sensitivity of 78% and a specificity of 98% (Dobbler, 2009.)
Recommendation of best current screening method
Because these tests would essentially be performed as stand alone confirmations of the presence of a malignant
neoplasm, invasiveness was a major determining factor in the feasibility of the tests. It would be impractical to subject all
individuals at risk for lung cancer, or even a narrowed population, to a highly invasive surgery just for prospective diagnosis
of a tumor (Aberle, 2013.) For this reason, both the sputum cytology and bronchoscopy tests were eliminated as
recommendations over the chest x-ray, despite the formers lower price and the latters very high sensitivity.
Of the three latter imaging methods available, the PET scan initially appeared the most promising with its
extremely high sensitivity. However, the PET scan renders it highly sensitive to inflammation in addition to cancerous
growth, which is greatly exacerbated in patients with a heavy smoking history that are at the highest risk for lung cancer

4
Problem 1 Technical Paper BMED 1300 September 24, 2013 Langley/Tucker D
(Bunyaviroch, 2006.) This reason, combined with its massive cost of $4500, limited availability, and extremely high dosage
of radiation of 500 mrem, five times higher than the recognized safe limit of annual exposure for civilians (EPA, 2012)
eliminated it as a recommendation as a primary screening method.
An MRI scan costs about $3500. Although the MRI is not invasive and has an acceptable sensitivity and specificity
value, it is significantly more expensive than the other screening techniques, takes a relatively long time to run, and is
limited in availability. Since sensitivity was deemed as one of the most important values, the CT scans better ability to
predict presence of cancer combined with its cost that was half that of the MRI, greater availability, and only requiring a
fraction of the time to perform caused it to be ranked higher than the MRI.
The CT scan costs much more than a chest x-ray, but it was decided that a quadrupling of sensitivity as well as a
time reduction was more than enough to offset the increase in price. Calculations were performed in the potential number of
deaths due to a false negative were determined, and it was decided that the CT scan possessed the best balance of positive
characteristics in current methods to be recommended as a replacement for, or supplement to, the chest x-ray.
Approximately 72 million (Brenner, 2009) CT scans were performed in 2007, more than enough for the recommended
target audience of 10 million individuals.
Ranking of new methods based on criteria
With a risk population identified, the next step was to identify a highly accurate, easy to administer test to further
eliminate at risk patients who did not have lung cancer in order to conserve resources for further screening and testing.
Because one of the stated goals was to increase sensitivity without sacrificing specificity in recommending a screening
procedure, it made the most sense to run tests sequentially. Table II shows a number of currently available publications
aimed towards identifying lung cancer tumors in their early stages, with accuracy and sample sizes included where possible.
Because all of these tests were primarily clinical trials, costs, projected time, and availability have not been included in the
table, being mentioned where applicable in the discussion.
Because the tests would be run in sequence to increase sensitivity, the first qualification for a test to be considered
would be a very high specificity which would be sacrificed to run in sequence; thus, all tests with specificities lower than
90% were eliminated, because using them would preclude the ability to match the chest x-rays specificity. Of the remaining
tests (dog, digital breath, various blood proteins,) each was evaluated based on specificity, and an attempt was made to
contact the publisher of each paper in order to discern the cost, invasiveness, and amount of time required for each test to be
enacted. Of all the researchers that responded, one of the co-authors of the blood protein test published by Dr. Farlow
seemed to hold the most promising results; he revealed that the test had cost $17,000 to develop, but the statistics were good
enough that a large pharmaceutical had purchased the process from him and had patented the process (U.S. patent number
20130225442,) although he could not provide the name based on a financial agreement. The blood-protein test cost only $40
to administer, was completely independent on the stage of cancer, so long as a tumor was present, and could be performed
thousands of times very quickly on a bioassay machine.
Other tests produced less satisfactory results. The investigator of the dog breath test revealed that they did not
know what the dog was smelling, only that the test worked, which made it difficult to recommend. The other blood protein
test had only been done in rats; no human trials had yet been performed. Because of these factors, in addition to the
excellent sample size in comparison to the other tests and extremely high sensitivity, the blood-protein published by Dr.
Farlow was chosen to be the first step recommended in the new screening procedure.
Development of new screening procedure
A blood protein test for high risk patients could only confirm the existence of a malignant tumor; it does not
determine the location, stage, or size of tumors inside the lung. For this reason, a screening procedure was required to
physically identify where the tumor was. Evaluating the current methods from above, it was decided that a CT scan was the
most favorable way to proceed; with a limited population further filtered by a test with a very strong sensitivity, it was
decided that it would be feasible to give a CT to all members of the population who tested positive on the blood protein test.
These two tests done in sequence give a net sensitivity of 88% and a specificity of 98%, are both minimally invasive,
minimize costs out of the available options presented, and can be performed in under an hour. If a patient receives a positive
on both of these tests, it is concluded that there is reasonable suspicion for the presence of a tumor, and therefore more

5
Problem 1 Technical Paper BMED 1300 September 24, 2013 Langley/Tucker D
invasive methods are used to confirm its presencevisually, through a bronchoscopy, and then finally through a biopsy. The
procedure is outlined in Image I.
CT scan picks up different types of tumor, based on their compositions. These tumors can be mostly solid,
calcified, or liquid; different tumors have different amounts of aggression and growth rates if they are actually malignant.
The Mayo clinic recommends different follow-ups based on type of tumor spotted in the CT; these, too, are included in the
recommendation, and are summarized in image 2. Because initial cost of the blood test is fairly low and painless, and the
only way for a high-risk patient to remove themselves from the group is to stop smoking for an extended period of time, it is
recommended that all high-risk patients return annually for screening, even if they tested negative the first time, because
risk of lung cancer increases with age.
III. Results
Final accuracy of recommended procedures
The final sensitivity and specificity of the procedures done sequentially is 67% and 99%, respectively, an increase
of 41% in sensitivity and 6% in specificity. A patient that receives a negative from this procedure can almost be 100%
certain that their test result is indeed negative, and that there is nothing to worry about currently. There is also a tripling in
sensitivity, greatly decreasing the rate of false negatives and the drastic increase in mortality rate that follow false diagnosis;
the results are calculated below. Both of the accuracy goals have been met and exceeded; the other factor, maximizing
feasibility by keeping costs low and the process expedient, has also been met by running tests in sequence and selecting the
most cost-efficient tests for each step of the procedure. Finally, the new recommended procedure works equally well for all
stages of lung cancer, not sacrificing early accuracy for late or vice-versa, and aggressively targets the part of the population
at the highest risk of contracting the disease when they are still asymptomatic, as well as most curable.
Projected decrease in mortality rate
Table 3 summarizes the projected net benefits of implementing either of the screening procedures outlined above.
In order to project benefits for a theoretical population, consider the current U.S. population of 320,000,000 people. Of
those people there are 226,000 people with a new diagnosis of lung cancer and 373,000 people currently living with lung
cancer. That makes 226,000 people with lung cancer, 312,774,000 people without lung cancer. Those 226,000 people with
lung cancer have lung cancer based on the risks they had for getting it. Population prevalence is 226,000 out of 313,000,000
which is a ratio of 0.072%. By simplifying numbers, 72 people have lung cancer out of a population of 10,000 people.
In considering the current method, the chest X-ray is 26% sensitive and 93% specific compared to a future
screening method in sequence is 67% sensitive and 99% specific. Using the numbers found earlier and considering these
percentages, of the 72 people that have lung cancer the chest X-ray will diagnose 18 of them, 54 people will be given a false
negative result.
Of the 9928 people that don't have lung cancer, 9,223 people will get a true negative result, therefore 695 people
will be given a false positive resulting in unnecessary worry, money, and time. Multiplying these results to get the total
population of 320 million gives a potential 99,200 people that would otherwise have been missed using only a chest x-ray.
IV. Discussion
The chest x-ray offers many areas of potential improvement; the recommendation outlined above seeks to remedy
as many areas as possible. However, limitations to the proposed screening method do exist. Because of the specificity
benchmark of 93% identified above and a preference for sequential testing to minimize costs, many future tests with
significantly higher sensitivities were unable to be recommended; specifically, the viability of a blood miRNA test with
100% sensitivity looks to be an equally viable approach if done in parallel with a screening method such as a PET scan that
would provide 97% sensitivity and specificity, but would be much more expensive and pose a much higher radiation hazard.
Since saving lives was deemed important, but not the sole deciding factor, sensitivity was compromised to preserve
specificity to maintain feasibility. Similarly, many other tests currently in trial with less evidence of actually becoming
usable in the near future were discarded as being too far away to rely on for a recommendation. The final sensitivity of the
proposed solution, 66%, still leaves a third of the target population at risk for false negatives, but is still a threefold
improvement from the current standard.

6
Problem 1 Technical Paper BMED 1300 September 24, 2013 Langley/Tucker D
Simply looking at the sensitivities and specificities alone, it appears that almost any test performed on its own
would have a better ability to detect true positives; indeed, using only a CT scan as displayed in Table III with calculations
of number of deaths prevented saves more lives from misdiagnoses than using both at the same time, could be done more
quickly, and would cost less to administer by itself. The rational for using multiple tests was the tremendous reduction in
false positives that arise from doing tests in series. Although using only a CT scan produces a much higher proportion of
lives saved (89%,) it also generates 397% more wasted tests in the form of false positives, almost quadrupling the cost in
comparison to the recommended screening method from wasted follow-ups. In this case, the excess false negatives result in
more bronchoscopies and biopsies, both of which are highly invasive, time consuming, and expensive, which is why the
evaluation of future methods placed a very high rating on the blood biomarker test and its ease of repetition. By using two
tests in series with high specificity, the false positive rate drops to nearly 0%, saving money in the long run; each wasted CT
scan costs $1700, while each wasted blood test before that which prevents a wasted CT costs only $40.
Other areas of improvement include the recommended process' ambiguitiy concerning small cell lung cancer,
which makes up 10% of all cases; the blood test was not developed for SCLC (Farlow, 2013,) but does share one biomarker,
ubiquitin, with a test that is 55% sensitive and 99% specific (Chapman, 2011.)
V. Conclusion
After rigorously evaluating current and future screening methods based on a number of criteria, the new proposed
method of lung cancer screening is a blood-protein test, followed by a low dose CT scan if the blood-protein test is positive,
followed by a bronchoscopy for confirmation if the prior two tests are positive. This combination of tests is logistically
feasible when weighing cost, availability, reliability, and designating a population of high-risk individuals that would
undergo this series of tests. Another achievement through this series of tests is that lung cancer can be caught at an earlier
stage (stages 1 and 2) than was previously possible due to the technology of the blood-protein test. In the future, tests may
look at detecting cancer even earlier and including more reliable scanning methods but at this time, this series of tests is
readily implementable and has the best chance of saving more lives while not causing people to undergo unnecessary
testing.

7
Problem 1 Technical Paper BMED 1300 September 24, 2013 Langley/Tucker D
Appendix
Table I. Factors used in Evaluation of Current Screening Methods
Ranking

Cost

Time

Sensitivity

Specificity

Invasive

Radiation

Availability (ppm)

Chest X-Ray
(Aberle, 2013)

$200

10-15 minutes

26

93

No

8 mrem

40.9

CT (McWilliams,
2013)

$1700

5 minutes

93

73

No

20 mrem

34.3

MRI (Molnar,
1999)

$3500

15-20 minutes

89

95

No

No

25.9

PET (Schrevens,
2004)

$4500

180 minutes

97

82

No

500 mrem

32

Sputum (Jiang,
2011)

$175

2 weeks

53

78

Moderate

No

N/A

Bronchoscopy

$650

30 minutes

78

98

High

No

2950

8
Problem 1 Technical Paper BMED 1300 September 24, 2013 Langley/Tucker D
Table II. Newer Screening Procedures for Lung Cancer
Sensitivity

Specificity

Sample Size

Invasiveness/Notes

Airway Epithelium
(Roy, 2010)

84

80

135

Moderate (airway probe)

Airway Epithelium
(Spira, 2007)

95

78

77

Moderate (wave spectroscopy)

Breath (Phillips,
2003

85

81

108

None (breath into tube)

Breath (Poli, 2005)

72

94

146

None

Dog (Ehmann,
2012)

71

93

220

None

Dog(Amundsen,
2013)

99

63

93

None; researcher does not know


WHAT dogs are detecting

Blood miRNA
(Foss, 2011)

100

84

140

MiRNA 15b + 27b

Blood Protein
(Takano, 2009)

54

98

295

Nectin-4

Blood Protein
(Leidinger, 2008)

93

93

80

Autoantibody

Blood Protein
(Farlow, 2010)

95

91

193

6-protein combination

Table III. Deaths Prevented (Arbitrary Population of 100,000 People, 0.72% prevalence)
True Positives

False Positives

True Negatives

False Negatives

Lives Saved

Tests Wasted

Chest X-ray

18

6994

92933

54

CT Scan

67

26981

72947

+49 (+261%)

+49 (+261%)

Future

48

490

99438

23

+31 (+172%)

-6504 (-93%)

9
Problem 1 Technical Paper BMED 1300 September 24, 2013 Langley/Tucker D
Image I Annual Screening Process

Image II Follow-up CT Scan Chart

10
Problem 1 Technical Paper BMED 1300 September 24, 2013 Langley/Tucker D
carried out routinely? Intern Med J, 39(12), 806References
811. doi: 10.1111/j.1445-5994.2008.01882.x
Aberle, Denise R., DeMello, Sarah, Berg, Christine D.,
Black, William C., Brewer, Brenda, Church,
Timothy R., . . . Sicks, JoRean. (2013). Results of Duhaylongsod, F. G., Lowe, V. J., Patz, E. F., Jr., Vaughn, A.
L., Coleman, R. E., & Wolfe, W. G. (1995). Lung
the Two Incidence Screenings in the National Lung
tumor growth correlates with glucose metabolism
Screening Trial. New England Journal of
measured by fluoride-18 fluorodeoxyglucose
Medicine, 369(10), 920-931. doi:
positron emission tomography. Ann Thorac Surg,
doi:10.1056/NEJMoa1208962
60(5), 1348-1352. doi: 10.1016/0003-4
Amundsen, T., Sundstrom, S., Buvik, T., Gederaas, O. A., &
975(95)00754-9
Haaverstad, R. (2013). Can dogs smell lung cancer?
First study using exhaled breath and urine screening in
Ehmann, R., Boedeker, E., Friedrich, U., Sagert, J., Dippon,
unselected patients with suspected lung cancer. Acta Oncol.
J., Friedel, G., & Walles, T. (2012). Canine scent
doi:
10.3109/0284186x.2013.819996
detection in the diagnosis of lung cancer: revisiting
a puzzling phenomenon. Eur Respir J, 39(3), 669Bach, P. B., Kattan, M. W., Thornquist, M. D., Kris, M. G.,
676. doi: 10.1183/09031936.00051711
Tate, R. C., Barnett, M. J., . . . Begg, C. B. (2003).
Variations in lung cancer risk among smokers. J
Farlow, E. C., Patel, K., Basu, S., Lee, B.-S., Kim, A. W.,
Natl Cancer Inst, 95(6), 470-478.
Coon, J. S., . . . Borgia, J. A. (2010). Development
of a Multiplexed Tumor-Associated AutoantibodyBoffetta, Paolo. (2010). Causation in the Presence of Weak
Based Blood Test for the Detection of NonSmall
Associations. Critical Reviews in Food Science
Cell Lung Cancer. Clinical Cancer Research,
and Nutrition.50 pp.13-16.
16(13), 3452-3462. doi: 10.1158/1078-0432.ccr-09Brenner, David. "Minimizing Medically Unwarranted CT
3192
Scans."International Commission on Radiological
Foss, K. M., Sima, C., Ugolini, D., Neri, M., Allen, K. E., &
Protection. N.p., 2009. Web. 24 Sept. 2013.
Weiss, G. J. (2011). miR-1254 and miR-574-5p:
Bunyaviroch T, Coleman RE. PET evaluation of lung
serum-based microRNA biomarkers for early-stage
cancer. J Nucl Med. 2006 Mar;47(3):451-69.
non-small cell lung cancer. J Thorac Oncol, 6(3),
Review. PubMed PMID: 16513615.
482-488. doi: 10.1097/JTO.0b013e318208c785
Chapman, C. J., Thorpe, A. J., Murray, A., Parsy-Kowalska, Health Forum, LLC. American Hospital Association
C. B., Allen, J., Stafford, K. M., . . . Robertson, J.
Hospital Statistics, 2011 (2009 survey data).
F. (2011). Immunobiomarkers in small cell lung
Chicago, IL: American Hospital Association; 2011.
cancer: potential early cancer signals. Clin Cancer
Jiang, Y., Jin, P., Chang, R. S., Yao, S. X., Zhou, Q. H., Fan,
Res, 17(6), 1474-1480. doi: 10.1158/1078Y. G., & Qiao, Y. L. (2011). [Analysis of sensitivity
0432.ccr-10-1363
and specificity of sputum cytology screening for
lung cancer with different positive criteria].
"Census Bureau Homepage." Census Bureau Homepage.
Zhonghua Yu Fang Yi Xue Za Zhi, 45(7), 605-608.
N.p., 5 Aug. 2010. Web. 24 Sept. 2013.
Coggins, C. R. E., Murrelle, E. L., Carchman, R. A., &
Heidbreder, C. (2009). Light and intermittent
cigarette smokers: a review (1989-2009).
Psychopharmacology, 207(3), 343-363. doi:
10.1007/s00213-009-1675-4

Leidinger, P., Keller, A., Ludwig, N., Rheinheimer, S.,


Hamacher, J., Huwer, H., . . . Meese, E. (2008).
Toward an early diagnosis of lung cancer: An
autoantibody signature for squamous cell lung
carcinoma. International Journal of Cancer, 123(7),
1631-1636. doi: 10.1002/ijc.23680
Cot, Michele L., Liu, Mei, Bonassi, Stefano, Neri, Monica,
Schwartz, Ann G., Christiani, David C., . . . Hung, McCarthy, W. J., Meza, R., Jeon, J., & Moolgavkar, S. H.
Rayjean J. (2012). Increased risk of lung cancer in
(2012). Chapter 6: Lung cancer in never smokers:
individuals with a family history of the disease: A
epidemiology and risk prediction models. Risk
pooled analysis from the International Lung Cancer
Analysis: An Official Publication Of The Society
Consortium. European Journal of Cancer, 48(13), 1957For Risk Analysis, 32 Suppl 1, S69-S84. doi:
1968. doi:
http://dx.doi.org/10.1016/j.ejca.2012.01.038
10.1371/journal.pgen.1001051. Current Imprints:
Publication: 2002- : Malden, MA : Blackwell
Dobler, C. C., & Crawford, A. B. (2009). Bronchoscopic
Publishers; Original Imprints: Publication: New
diagnosis of endoscopically visible lung
York : Plenum Press
malignancies: should cytological examinations be

11
Problem 1 Technical Paper BMED 1300 September 24, 2013 Langley/Tucker D
McWilliams, Annette, Tammemagi, Martin C., Mayo, John Roy, H. K., Subramanian, H., Damania, D., Hensing, T. A.,
R., Roberts, Heidi, Liu, Geoffrey, Soghrati, Kam, . .
Rom, W. N., Pass, H. I., . . . Backman, V. (2010).
. Lam, Stephen. (2013). Probability of
Cancer in
Optical Detection of Buccal Epithelial
Pulmonary tumors Detected on First
Screening CT.
Nanoarchitectural Alterations in Patients Harboring
New England Journal of Medicine, 369(10), 910-919. doi:
Lung Cancer: Implications for Screening. Cancer
doi:10.1056/NEJMoa1214726
Research, 70(20), 7748-7754. doi: 10.1158/00085472.can-10-1686
Molnr TF, Juhsz E, Benk I, Horvth OP. Predictive value
Schrevens, L., Lorent, N., Dooms, C., & Vansteenkiste, J.
of MRI in lung cancer. Acta Chir Hung.
(2004). The role of pet in diagnosis, staging, and
1999;38(1):95-9. PubMed PMID: 10439106.
management of non-small cell lung cancer . The
Oncologist, 9(6), 633-644. doi:
"My Health Care Options." My Health Care Options.
10.1634/theoncologist.9-6-633
Healthcare Quality and Cost Council, 2010. Web.
24 Sept. 2013.
Spira, A., Beane, J. E., Shah, V., Steiling, K., Liu, G.,
Schembri, F., . . . Brody, J. S. (2007). Airway
"Non-small Cell Lung Cancer Survival Rates by
epithelial gene expression in the diagnostic
Stage."Non-small Cell Lung Cancer Survival
evaluation of smokers with suspect lung cancer.
Rates by Stage. American Cancer Society, 12 July
Nat Med, 13(3), 361-366. doi: 10.1038/nm1556
2013. Web. 24 Sept. 2013.
OECD (2011), Medical technologies, in Health at a
Glance 2011: OECD Indicators, OECD
Publishing.
http://dx.doi.org/10.1787/health_glance-2011-30en
OECD (2013), "Computed tomography scanners, total",
Health: Key Tables from OECD, No. 37. doi:
10.1787/comptomoscan-table-2013-1-en
Phillips, M., Cataneo, R. N., Cummin, A. R., Gagliardi, A.
J., Gleeson, K., Greenberg, J., . . . Rom, W. N.
(2003). Detection of lung cancer with volatile
markers in the breath. Chest, 123(6), 2115-2123.

Taguchi, A., Politi, K., Pitteri, Sharon J., Lockwood, William


W., Faa, Vitor M., Kelly-Spratt, K., . . .
Hanash, Samir
M. (2011). Lung Cancer Signatures
in Plasma Based
on Proteome Profiling of Mouse Tumor Models. Cancer
Cell, 20(3), 289-299. doi:
http://dx.doi.org/10.1016/j.ccr.2011.08.007
Takano, A., Ishikawa, N., Nishino, R., Masuda, K., Yasui,
W., Inai, K., . . . Daigo, Y. (2009). Identification of
nectin-4 oncoprotein as a diagnostic and
therapeutic target for lung cancer. Cancer Res,
69(16), 6694-6703. doi: 10.1158/0008-5472.can09-0016

Poli, D., Carbognani, P., Corradi, M., Goldoni, M., Acampa, Tamura, K., Kurihara, H., Yonemori, K., Tsuda, H., Suzuki,
J., Kono, Y., . . . Fujiwara, Y. (2013). 64Cu-DOTAO., Balbi, B., . . . Mutti, A. (2005). Exhaled volatile
Trastuzumab PET Imaging in Patients with HER2organic compounds in patients with nonsmall cell lung
Positive Cancer. J Nucl Med. doi:
cancer: cross sectional and nested short-term follow-up
10.2967/jnumed.112.118612
study. Respiratory Research,
6(1), 71.
"Radiation Health Effects."EPA. Environmental Protection
Agency, 17 Oct. 2012. Web. 24 Sept. 2013.

Wender, R., Fontham, E. T., Barrera, E., Jr., Colditz, G. A.,


Church, T. R., Ettinger, D. S., . . . Smith, R. A.
(2013). American Cancer Society lung cancer
Rinck P. Magnetic Resonance in Medicine. The Basic
screening guidelines. CA Cancer J Clin, 63(2),
Textbook of the European Magnetic Resonance
107-117. doi: 10.3322/caac.21172
Forum. 7th edition. 2013. Electronic version 7.1; 1
October 2013. www.magnetic-resonance.org

Das könnte Ihnen auch gefallen