Abstract Compilation

JW Marriott Hotel Jakarta

Dharmais National Cancer Center Hospital
Cipto Mangunkusumo National General Hospital
Jakarta
18th – 21st July, 2019
 Table Of Content

Approach to Diagnosis and Treatment of Acute Leukaemia ................................................................................. 3

Diagnostic and Treatment Approach of Chronic Leukemia ................................................................................... 4
Nutrisi pada Pasien Kanker .................................................................................................................................. 6
Anti-Cancer Systemic (Chemotherapy) and Adverse Events ................................................................................. 8
Antibiotics in Cancer Patients with Febrile Neutopenia ........................................................................................ 9
Pathophysiology of Bone Disorder in Cancer ...................................................................................................... 10
The Role of Bisphosphonates in Bone Disorder Focused in Cancer Patients ........................................................ 11
Peran Radioterapi dalam Metastasis Tulang ...................................................................................................... 12
How to Calculate Nutrition Status in Cancer....................................................................................................... 14
Nutrition of Palliative Homecare ........................................................................................................................ 15
Nutrition in Critical Ill Patients ........................................................................................................................... 16
Should Cancer Patient with AF Take DOACs ....................................................................................................... 17
Update on Treatment of VTE in Cancer Patients ................................................................................................. 23
Role of Thyrosine Kinase Inhibitor in Renal Cancer............................................................................................. 24
Recent Update in Renal Cell Cancer Guidelines .................................................................................................. 26
Palliative Treatment in Renal Cell Carcinoma Patiens ......................................................................................... 29
Terapi Paliatif pada Pasien Renal Cell Carcinoma ............................................................................................... 31
Blood Transfusion in Cancer Patients ................................................................................................................. 33
Management of Major Incompatibility in Blood Transfusion .............................................................................. 34
Surgical Treatment in Early Breast Cancer .......................................................................................................... 35
Chemotherapy and Hormonal Therapy for Breast Cancer................................................................................... 36
Targeted Therapy in Breast Cancer .................................................................................................................... 37
Adjuvant and Neo-Adjuvant Chemotherapy for Head and Neck Cancer.............................................................. 38
Immunotherapy in Head and Neck Cancer ......................................................................................................... 40
Supportive Therapy in Head and Neck Cancer (Nutrition, Pain Management, and Infection) ............................. 41
Pathophysiology of Cancer Pain ......................................................................................................................... 43
Management of Pain in Cancer Patient .............................................................................................................. 44
How to Choose Pain Drugs in Cancer Pain .......................................................................................................... 46
Immunotherapy of Cancer: Past, Present and The Next Frontier ........................................................................ 48
Perioperative Anticoagulant Management......................................................................................................... 50
Perioperative VTE prophylaxis ........................................................................................................................... 51
Chemotherapy that can Induce Neutropenia ..................................................................................................... 52
Pedoman Penanganan Demam Neutropenia dalam Praktik Klinis ...................................................................... 53

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The Role of Internist in Cancer ........................................................................................................................... 54
Chemotherapy Preference in Metastatic Breast Cancer ..................................................................................... 55
Hodgkin Lymphoma and its Treatment .............................................................................................................. 56
Various Type of Cutaneous Lymphoma: Diagnosis and Treatment ..................................................................... 57
Early Detection and Surgical Management in Colorectal Cancer ......................................................................... 59
Chemotherapy in Colorectal Cancer ................................................................................................................... 60
Early Detection and Treatment of Breast Cancer ................................................................................................ 61
Terapi Sistemik pada Kanker Paru (Fokus pada Kanker Paru Bukan Sel Kecil Stadium Lanjut) ............................ 63
Early Detection and Surgery in Cervical Cancer .................................................................................................. 64
Immune Thrombocytopenia............................................................................................................................... 67
Epidemiology and Diagnostic in Gastric Cancer .................................................................................................. 68
Kemoterapi pada Kanker Lambung: Sebuah Pendekatan Paliatif........................................................................ 70
Terapi Target pada Kanker Lambung Stadium Lanjut.......................................................................................... 72
The Role of Flowcytometry in B Cell Malignancies.............................................................................................. 74
Update Guideline in Multiple Myeloma ............................................................................................................. 75
Novel Therapy in Chronic Lymphocytic Leukemia (CLL) ...................................................................................... 77
Terapi Terbaru pada Leukemia Limfositik Kronik (CLL) ....................................................................................... 78
Non-Hodgkin Lymphomas: Diagnosis, Staging & Management ........................................................................... 79
Management of Neutropenia as an Adverse Effect of Chemotherapy ................................................................ 82
Prevention, Screening and Early Detection in Gynecologic Cancer ...................................................................... 83
Onkogenesis Virus Pada Kanker Ginekologi........................................................................................................ 84
The Role of Chemotherapy in Cervical, Endometrium and Ovarian Cancer ......................................................... 86
Advanced Stage Adenocarsinoma Lung Cancer .................................................................................................. 87
Penatalaksaan Akut Mieloid Leukemia .............................................................................................................. 89
Acute Lymphoblastic Leukemia .......................................................................................................................... 92
Prevention Strategy for Chemotherapy-Induced Nausea and Vomiting (CINV) ................................................... 93
Anemia in Cancer Patients ................................................................................................................................. 94
Complication in Management of Chemotherapy in Geriatric Patient .................................................................. 95
What is the Meaning of Palliative Treatment? ................................................................................................... 96
Palliative Treatment in Cancer ........................................................................................................................... 97

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 Approach to Diagnosis and Treatment of Acute Leukaemia
Wulyo Rajabto

Acute leukaemia is one of category of blood cancers characterized by aggressive

proliferation of clonal blasts cells in the bone marrow. The classification of acute
leukaemia: acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML).
The annual number of new cases/100.000 was 1.7 for acute ALL and 4.0 for AML.
While ALL has its peak in childhood, AML is more common in adults and elderly. There
is a predilection for men in AML (4.8 versus 3.3 new cases) while in ALL there is no
gender difference (1.9 new cases in men and 1.5 in women).
Acute leukaemia pose a number of diagnostic and treatment challenges. Patient
symptoms maybe nonspecific (e.g., fatigue, weight loss) and the complete blood count
will often show one or more cytopenias. Frequently circulating blasts are present on the
peripheral blood, but not in all cases. Complications include severe anaemia, febrile
neutropenia, and major bleeding due to thrombocytopenia as a result of normal
hematopoietic cells in the bone marrow being replaced by leukemic blasts. Patients with
high number of circulating blasts can also develop severe pulmonary, ophthalmologic,
ear, and central nervous system complications due to leucostasis problem.
We perform bone marrow puncture (BMP) to collect bone marrow aspiration and
biopsy as initial workup when acute leukaemia is suspected. We send the sample of
bone marrow aspiration to the laboratories for:
(1) Morphologic analysis to confirm that blasts account at least >=20% of bone
marrow cells;
(2) Flowcytometry testing (immunophenotyping) to determine the leukemic blast
phenotype: myeloid or lymphoblastic or even biphenotype?
(3) Cytogenetic and molecular genetic testing to determine prognosis and guide
overall therapy.
Curative chemotherapy regimens for AML and ALL are very intensive and
aggressive. Treatment is usually delivered in hospital. Most patients will have severe
side effects that require hospital admission. Hospital stays can last several weeks, and
intensive care may be needed. Older patients are unlikely to tolerate curative regimens
and often have unfavorable cytogenetics. Palliative treatment is usually offered to these
patients. Young patients with unfavorable cytogenetics will be offered allogeneic bone
marrow transplantation if there is available resources.

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 Diagnostic and Treatment Approach of Chronic Leukemia
Ikhwan Rinaldi

Leukemia is one of hematological malignancy characterized by excessive

proliferation of leucocyte. Leukemia can be classified as acute and chronic leukemia.
This classification is determined by cell's ability to differentiate from immature cell into
more mature cell. Leucocytes in acute leukemia lack of this ability, while in chronic
leukemia this ability still persist. In acute leukemia, we always find depletion of cells
other than leucocyte in blood circulation due to excessive proliferation of leucocytes,
while in chronic leukemia there is no reduction of other blood cells. Besides, in chronic
granulocytic leukemia, we can find increment in other blood cell's count together with
leukocyte. Through the disease progression, chronic leukemia can be transformed into
acute phase, known as blastic crisis.
Both acute and chronic leukemia can be developed from myeloid or lymphoid
cell. Each cells has different developmental pathway in the bone marrow. According to
type of cells dominating in the circulation, acute leukemia can be classified as acute
myeloblastic leukemia and acute lymphoblastic leukemia, while chronic leukemia can be
classified as chronic myeloid leukemia and chronic lymphocytic leukemia.
Chronic myeloid leukemia is a chronic leukemia that was developed from myeloid
lineage cells that undergo proliferation due to reciprocal translocation on chromosome 9
and 22 resulting in BCR-ABL gene fusion. This gene is responsible in excessive
proliferation and differentiation of myeloid lineage resulting in granulocyte-type
hyperleukocytosis, sometimes accompanied by thrombocytosis. Chronic myeloid
leukemia (CML) consist of 3 developmental phases from mild to severe state, consist of
chronic phase, acceleration phase, and blastic crisis. Chronic phase is the first phase
of AML, usually characterized by splenomegaly with or without hepatomegaly due to
granulocyte infiltration to the organs and blast count less than 10%. Acceleration and
blastic crisis phases are the advanced phases of CML, marked by the increasing blast
cell count more than 10% in peripheral blood and bone marrow. Blast cell count in
blastic crisis phase is even higher, reaching 20% or more in peripheral blood and bone
marrow. This finding is similar with acute leukemia, especially acute myeloid leukemia.
Patient with CML usually develops from chronic phase to acceleration and then blastic
crisis in 4 years. Patient who is in blastic phase for 3-6 months usually will be deceased.

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 Diagnosing CML is not difficult. The most important test to be done is
cytomorphology examination of bone marrow. In order to verified the diagnosis of CML,
one should find the increasing myeloid series cells proliferation with blast count less
than 20% in bone marrow and the presence of “Philadelphia” chromosome with BCR-
ABL gene (translocation chromosome 9 and 22). Nowadays , peripheral blood is able to
be used as sample for BCR-ABL gene test. All these tests are supposed to be
conducted based on suggestive cinical findings of CML.
Treatment for CML has been found since 2000. This drug called tyrosine kinase
inhibitor, because it inhibits the binding of phosphate into BCR-ABL therefore it could
not progress to tyrosine kinase’s signal transduction which activate myeloid cell
proliferation. Recently in the world, this drug has been developed up to three
generation. This development is related to resistance in the first and second generation.
Examples of tyrosine kinase inhibitor are imatinib, nilotinib, dasatinib and ponatinib.
Development of this drug yields to change of bone marrow transplantation as not
becoming the first line therapy of CML anymore.
Chronic lymphocytic leukemia (CLL) happens because of over-proliferation of
immature lymphocyte immunologically. Often, CLL is diagnosed incidentally because of
the present of lymphocytosis in peripheral blood (>5000 monoclonal B lymphocyte/µL).
Diagnosis of CLL is done by examines CD protein in lymphocyte of peripheral blood
using immunophenotyping technique in flowcytometry. In CLL, there will be found
CD19, CD20, CD5 dan CD23. Immature lymphocyte could infiltrate to lymph node or
bone marrow as well as in peripheral blood, leads to increase the size of lymph node or
presses against the others blood cell’s line production in bone marrow.
Chronic lymphocytic leukemia could happen in mild condition, which only has
lymphocytosis without any decreases in the other blood serial or increases of lymph
node, or in more severe form with the presence of lymph node’s enlargement and
decrease of other blood cell’s line production. In milder form, CLL does not need
treatment. Follow up should be done every 6 months because of lymphocyte
proliferation in CLL patient is every 3-6 months. Treatment conducted with
chemotherapy using fludarabine-cyclophosphamide and rituximab if the disease
progresses to more severe form with lymph node’s enlargement and decrease of other
blood cell’s line production. In elderly patient whom could not be treated with
chemotherapy, other drugs such as idelalisib, obinutuzumab or ibrunitib is suggested.
The advancement of medicine has produced various drugs to treat CLL.

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 Nutrisi pada Pasien Kanker
Noorwati Sutandyo, Sugiyono Somoastro

Kanker merupakan penyebab kematian utama di negara berkembang dan

merupakan penyebab kematian kedua di negara maju yang terus meningkat di seluruh
dunia dengan jumlah kasus baru diperkirakan dapat mencapai 19,3 juta kasus per
tahun pada tahun 2025. Kanker seringkali dikaitkan dengan malnutrisi energi-protein
yang dapat berkembang menjadi kaheksia kanker. Diperkirakan sekitar setengah dari
semua pasien kanker mengalami sindrom kaheksia, di mana pasien kanker dengan
kaheksia berisiko mengalami peningkatan efek samping kemoterapi, berkurangnya
toleransi terhadap obat kemoterapi, perpanjangan masa pengobatan,dan penurunan
kualitas hidup.
Secara definisi, kaheksia merupakan sindrom multi-faktorial yang ditandai
dengan kehilangan massa otot sekeletal, baik dengan atau tanpa kehilangan massa
lemak, yang tidak sepenuhnya reversibel dengan dukungan nutrisi konvensional dan
mengarah kepada gangguan fungsional progresif. Insidensi penurunan berat badan
pada pasien kanker bervariasi bergantung pada lokasi kanker; dengan insidensi
tertinggi pada pasien kanker kepala dan leher (72-79%). Pasien kanker merupakan
kelompok yang berisiko tinggi mengalami malnutrisi, tidak hanya akibat penyakitnya
(disease-related malnutrition) namun juga efek terapi yang dapat memengaruhi status
gizi, misalnya mukositis pada kemoterapi ataupun radiasi.
Penyebab kaheksia bersifat multifaktorial dan dapat dibedakan menjadi 3
kategori besar, yaitu faktor tumor (obstruksi tumor, ataupun sitokin yang dikeluarkan
oleh tumor), faktor pasien (psikologi), dan faktor terapi (efek samping pembedahan,
kemoterapi, ataupun radiasi). Tumor menghasilkan berbagai sitokin proinflamasi (TNF-
a, IL-1, dan IL-6) yang dapat memengaruhi sistem saraf pusat (induksi anoreksia),
penurunan massa otot, dan berdampak pada semua jalur metabolisme. Perubahan
metabolisme protein ditandai dengan meningkatnya turn-over protein, kehilangan lemak
dan massa otot melalui jalur proteolitik-proteosom-ubiquitin,serta peningkatan produksi
protein fase akut.Metabolisme karbohidrat seringkali dikaitkan dengan resistensi insulin
dan gangguan toleransi glukosa, serta pergeseran utilisasi energi dari siklus Kreb
menjadi siklus Cori yang menghasilkan asam laktat.Kapasitas untuk oksidasi lipid pada
pasien kanker kaheksia umumnya dipertahankan atau bahkan meningkat, terutama
dengan adanya komponen lipolitik yang dihasilkan oleh tumor, Lipid Mobilizing factor
(LMF).
Kriteria diagnosis kaheksia didasarkan pada penurunan berat badan lebih dari
5% dalam waktu 3 bulan atau 10% dalam waktu tertentu, ditambah dengan 3 dari 5
kriteria minor yang mencakup penurunan kekuatan otot, anoreksia, fatigue, penurunan

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indeks massa otot skeletal, dan abnormalitas laboratorium
(IL6/CRP/anemia/hipoalbuminemia).
Perjalanan kaheksia kanker meliputi tiga tahapan yaitu pre-kaheksia, kaheksia,
dan kaheksia refrakter. Untuk mendeteksi gangguan gizi pada tahap awal, asupan gizi,
perubahan berat badan, dan indeks massa tubuh (IMT) harus dilakukan sejak kanker
didiagnosa dan diulang hingga klinis stabil. Skrining risiko malnutrisi dapat dilakukan
menggunakan berbagai kuisioner, dari yang paling sederhana (malnutrition screening
tool/MST) hingga yang paling umum digunakan, yaitu subjective global assessment
(SGA) patient-generated SGA (PG-SGA). Berat badan harus dikoreksi dari beban
cairan berlebihan (efusi pleura, asites dan/atau edema) dan penilaian cadangan otot
dan lemak sebaiknya dilakukan dengan dual energy X-ray absorptiometry (DXA),
bioelectrical impedance analysis (BIA), atau CT-scan pada lumbar level 3.
Terapi pada kaheksia kanker dilakukan melalui pendekatan multimodal, yang
terdiri dari terapi farmakologi dan non-farmakologi yang meliputi dukungan nutrisi,
latihan, dan intervensi sosial. Bentuk utama dari terapi nutrisi adalah konseling dengan
tujuan membantu mengelola gejala dan memberikan motivasi kepada pasien untuk
meningkatkan asupan makanan dan minuman. Pada umumnya,diet tinggi energi dan
tinggi protein (1-2gr/kg berdasarkan pertimbangan usia, aktivitas, ataupun inflamasi)
direkomendasikan dalam diet kaheksia kanker. Penggunaan tambahan oral nutrition
supplement (ONS) disarankan ketika asupan manual tidak efektif dalam mencapai
tujuan gizi. Nutrisi buatan (enteral ataupun parenteral, secara bertahap) diindikasikan
jika pasien tidak dapat makan secara memadai (misalnya tidak ada asupan selama
lebih dari satu minggu atau kurang dari 60% dari kebutuhan selama lebih dari 1-2
minggu). Nutrisi oral maupun buatan dapat dikombinasikan. Selain itu,terapi
farmakologi dapat diberikan pada pasien dengan asupan oral yang mengalami gejala
pencernaan yang mengakibatkan penurunan asupan, misalnya penurunan asupan
makan. Perlu diingat bahwa target utama terapi nutrisi adalah untuk mempertahankan
berat badan, membantu pasien mentoleransi pengobatan: prognosis lebih baik, dan
memaksimalkan kualitas hidup.

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 Anti-Cancer Systemic (Chemotherapy) and Adverse Events
Asrul Harsal

Management of cancer patients consists of three categories. Surgery and

Irradiations for local treatments and Systemic anti-cancer treatment for locally advanced
and metastasis cancer. In the new era of treatment cancer, there are many systemic
anti-cancer treatments for cancer patients, like hormonal therapy, chemotherapy, target
therapy, immunotherapy and maybe gene therapy.
Usually, advanced stage of cancer patient, will got systemic therapy and
chemotherapy is one of them. Chemotherapy will kill the cancer cells and also disturb
the normal cell especially for the high turn-over of cell, like membrane cell, hair,
leucocyte, thrombocyte, spermatogenesis, and others. Some agents of Chemotherapy
will influence organs like, liver, kidney and heart. So, the comorbidity of cancer patient
should be known before chemotherapy.
There are many types agents of chemotherapy:
1. Alkylating agents.
2. Anti-metabolites.
3. Antibiotics.
4. Plant Alkaloids.
5. Topoisomerase Inhibitors
6. Miscellaneous: Ribonuclease Inhibitors
Enzymes
Anti-microtubule.
Retinoid.
Steroid anti-DNA.
There are 5 phases of cell mitosis, and many agents works in specific site. The phases
of mitosis consist of:
1. G0 Phase (Resting phase)
2. S Phase (DNA synthesis)
3. G1 Phase (Cell growth).
4. M Phase (Mitosis).
5. G2 Phase (cell growth).
Chemotherapy is a systemic treatment, so beside it kills the cell cancer, it is also
killing the normal cell which is highly proliferative, like membrane mucous cell, hair, and
others. To get the good result of chemotherapy, chemotherapy consist of some agents
and usually works in different phase, in order to get maximal response with minimal
adverse events. There are many combinations of chemotherapy for one diagnosis of
cancer. To choose the right chemotherapy for the right diagnosis and the right patient,
we should know the risks and benefits of chemotherapy.

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 Antibiotics in Cancer Patients with Febrile Neutopenia
Indra Wijaya

Febrile neutropenia remains an important complication of treatment with cytotoxic

chemotherapy. It is often the first and sometimes the only sign or symptom of infection
in this vulnerable patient population. Urgent and appropriate evaluation and treatment
are imperative because delay in initiating appropriate antibiotic therapy may be life
threatening. Selection of antibiotics should be based on the patient's symptoms,
previous culture data, and institutional antibiograms. Ongoing therapy should be guided
by culture and clinical data. Antimicrobial resistance is of great concern, particularly in
this population, so careful attention to antibiotic selection and duration is needed.

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 Pathophysiology of Bone Disorder in Cancer
Ikhwan Rinaldi

Bone is one of the human organs that frequently involved in metastases of solid
tumors, such as prostate, breast, and lung. Bone abnormality is influenced by malignant
cells which lead to changes in bone resorption and bone formation activity by osteoclast
and osteoblast, respectively. Osteoclast has found to be more responsible than
osteoblast to cause bone abnormality in metastases of solid tumor cases. These
abnormal activities of osteoclast and osteoblast are influenced by several inflammatory
mediators. Based on this pathophysiology, bone disorders in malignancy is categorized
into three types: osteolytic, osteoblastic, and both of them. Various drugs have been
produced to prevent bone resorption by osteoclast, bisphosphonate and anti-RANKL
(Receptor Activator of Nuclear Factor-κB Ligand) antibody.

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 The Role of Bisphosphonates in Bone Disorder Focused in Cancer
Patients
Ami Ashariati

Bone metastases frequently occur in patients with advanced solid tumors,

particularly breast and prostate cancers, and nearly all patients with multiple myeloma
have some degree of skeletal involvement. The strides made in treating these primary
tumors have extended median survival times and thereby increased patient risk for
skeletal-related events (SREs), including pathologic fractures, spinal cord compression,
need for palliative radiation therapy or surgery to bone, and hypercalcemia.
Osteoclast inhibitors (also called bone-modifying agents) such as
bisphosphonates and denosumab significantly reduce the frequency of skeletal-related
events in patients with bone metastases from a wide variety of cancer types. The use of
bisphosphonates in patients with multiple myeloma, the use of osteoclast inhibitors for
patients with bone loss related to cancer treatment (eg., aromatase inhibitors for breast
cancer and androgen deprivation therapy for prostate cancer), the use of osteoclast
inhibitors in the adjuvant setting for breast cancer, and the risks of therapy with
osteoclast inhibitors in patients with advanced malignancy are clinically important for
management all malignant patients.
Also, bisphosphonates have demonstrated an ability to induce apoptosis in a
variety of cancer cell lines. These agents may also inhibit metastases by decreasing
tumor cell adhesion, migration, and invasion. Inhibition of angiogenesis is another
property associated with bisphosphonates. Furthermore, these pharmacologic agents
may modulate the immune system with subsequent antitumor activity.
Recent research also found that zoledronic acid may exert its antitumor activity
by inhibiting mesenchymal stem cell migration and blocking mesenchymal stem cell
secretion of factors involved in breast cancer progression. The results of a large,
randomized phase 3 study comparing zoledronic acid and pamidronate in breast cancer
or multiple myeloma patients with osteolytic lesions showed that the incidence of SREs,
time to first SRE, and risk of developing a SRE were similar between treatment groups.
However, in patients with solid tumors (excluding breast or prostate cancer) metastatic
to the bone, only zoledronic acid has demonstrated clinical efficacy.

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 Peran Radioterapi dalam Metastasis Tulang
Arie Munandar

Metastasis tulang merupakan salah satu penyebab utama dan nyeri pada
kanker. Kejadian metastasis tulang ini bisa muncul dan diketahui setelah diagnosis
primer tumor ditegakkan, namun bisa juga terjadi bahwa nyeri yang diakibatkan
metastasis tulang menjadi keluhan awal yang membawa pasien berobat ke dokter. Hal
tersebut menurut Galasko terjadi pada 23% kasus, yang menunjukkan prevalensinya
berdasarkan hasil autopsi yang dilakukan. Tofe dalam penelitiannya menunjukkan
bahwa dari pemeriksaan 1143 pasien dengan tumor primer yang bukan berasal dari
tulang, terdapat temuan bone scan yang abnormal pada 61% pasien dan sebanyak
33% berasal dari tumor primer payudara, paru, atau prostat.
Tujuan utama dari tatalaksana terhadap metastasis tulang adalah
mempertahankan kualitas hidup pasien. Untuk mencapai tujuan ini, yang biasanya
menjadi target dalam tatalaksana adalah menurunkan derajat nyeri atau
menghilangkannya, dan menjaga atau memperbaiki kualitas dan fungsi dari tulang
tersebut. Yang perlu diperhatikan dalam memilih modalitas terapi untuk metastasis
tulang adalah kompleksitas dan prognosis dari kasus yang dihadapi, biaya dan lamanya
tatalaksana yang diberikan. Selain itu efek samping baik akut maupun lanjut juga harus
menjadi pertimbangan. Pemilihan terapi disesuaikan dengan masing – masing individu
sesuai dengan perjalanan penyakit yang dihadapi dan prognosisnya, karena pada
kasus tertentu masih memiliki potensi angka ketahanan hidup yang lebih dari 1 tahun.
Secara umum modalitas utama dalam metastasis tulang sebagaimana
metastasis jauh lainnya adalah terapi yang bersifat sistemik seperti kemoterapi,
hormonal, maupun yang memiliki target spesifik tulang seperti bisfosfonat. Modalitas
operasi atau radioterapi diberikan pada kondisi tertentu. Sasaran utama dalam
tatalaksana metastasis tulang umumnya adalah pengendalian nyeri. Yang harus dinilai
pertama kali adalah nyeri yang dirasakan pasien secara menyeluruh mulai dari derajat
nyeri hingga gangguan fungsional yang ditimbulkannya. Penanganan nyeri
menggunakan stepladder WHO tetap menjadi pilihan utama dalam tatalaksana awal ini.
Operasi umumnya dilakukan jika sudah terjadi fraktur patologis ataupun keadaan
yang dikhawatirkan akan terjadi fraktur. Terdapat beberapa panduan yang dapat
digunakan dalam menentukan indikasi operasi. Operasi untuk profilaksis pada kondisi
selain tersebut sebelumnya masih menjadi perdebatan saat ini.
Radiasi memiliki peran yang penting terutama untuk mengatasi nyeri, dan dalam
beberapa kondisi juga diberikan untuk menjaga kekuatan tulang terutama pada tulang
penyangga tubuh seperti tulang belakang. Banyak penelitian berupa systematic review
maupun meta analisis yang mengungkapkan efektifitas dari terapi radiasi, walaupun
dari segi dosis dan fraksinasi yang diberikan bervariasi. Masing – masing variasi dari

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dosis dan teknik tersebut memiliki kelebihan yang harus disesuaikan dengan kondisi
pasien. Pada dosis per fraksi tinggi dengan fraksinasi yang singkat, hilangnya nyeri
umumnya berlangsung lebih cepat namun angka kekambuhan nyeri dan reiradiasi lebih
tinggi. Pada dosis per fraksi yang lebih rendah sehingga fraksinasi lebih panjang,
proses hilangnya nyeri berjalan lebih lambat namun memiliki keuntungan untuk lebih
menguatkan stabilitas dari tulang dan angka reiradiasi yang lebih rendah. Saat ini
dengan berkembangnya teknologi banyak digunakan teknik Stereotactic Radiosurgery
(SRS) ataupun Stereotactic Body Radiotherapy (SBRT) untuk kasus metastasis tulang
yang masih terbatas pada vertebra 1 sampai 3 korpus saja.
Modalitas terapi nuklir lainnya adalah pemberian zat radioaktif secara sistemik
seperti strontium atau samarium. Modalitas ini dapat digunakan sebagai adjuvant pasca
pemberian radiasi untuk kasus dengan metastasis tulang yang luas.

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 How to Calculate Nutrition Status in Cancer
Nyoto Widyo Astoro
Cancers are among the leading causes of morbidity and mortality worldwide, and
the number of new cases is expected to rise significantly over the next decades. The
treatment of Cancer is impeded or precluded by the frequent development of
malnutrition and metabolic derangements in cancer patients, induced by the tumor or by
its treatment. Malnutrition and a loss of muscle mass are frequent in cancer patients
and have a negative effect on clinical outcome. They may be driven by inadequate food
intake, decreased physical activity and catabolic metabolic derangements
The World Health Organization (WHO) defined the “nutritional status” as the
condition of the body resulting from intake, absorption and utilization of nutrient and the
influence of particular physiological and pathological status. Nutritional screening should
provide the opportunity to identify malnutrition or individuals at high nutritional risk at an
early stage of medical care in a non-invasive, inexpensive and feasible way
Evaluate a simple screening tool for malnutrition (short screening sheet, SSM) of
patients in chemotherapy:
ü Nutrition assessment
ü Nutrition screening
ü Food Intake
ü Nitrogen balance
A full nutritional assessment by measure of:
ü BMI
ü Triceps skinfold Thickness (TST)
ü Mid-arm muscle circumference (MAMC)
ü Serum albumin (alb)
ü Serum prealbumin (palb),
ü Total lymphocyte count (TLC)
Unintentional weight loss of more than 5% within the preceding month or 10% or
more within the previous 6 months. The SSM sheet is made up of seven questions
covering BMI, weight loss, anorexia, surgery and other variables that may influence
nutritional status.

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 Nutrition of Palliative Homecare
Pandji Irani Fianza

Undernutrition in home care has been acknowledged as a situation with various

causes and significant consequences on both an individual and social level. Tackling
the problem of undernutrition in home care requires a multidisciplinary approach. Multi-
professional action is mandatory for the efficient management of palliative care patients,
and this should be achieved by means of better interaction among professionals,
considering the individualized choice of pharmacological and dietary therapy.
Early nutrition therapy may maintain body composition, improve life condition and
prolong survival of cancer patient under palliative care. Dietary prescription should offer
pleasure and comfort to patients, so patients’ autonomy should be respected.
Simultaneous medical and nutritional intervention has also resulted in improved
symptoms such as appetite loss, dysgeusia, oral candidiasis, mucositis, nausea and
constipation.
The first step of nutrition assessment in home care is to obtain the accurate
amount of food intake. The amount of food the patient has actually ingested is often
questionable. A simple method of nutritional assessment is regular monitoring of body
weight and blood tests to evaluate albumin or total protein, blood urea nitrogen,
creatinine, electrolyte levels, and anemic conditions. Malnutrition can be caused by a
reduced food intake due to dysphagia. The methods for assessing dysphagia are
screening and detailed examination; evaluation using questionnaire and clinical
observations. The daily nutritional goals should be a calorie intake of 20-25 kcal/kg, fluid
intake of >30 mL/kg, and protein intake of 60-70 g. Introducing fluid therapy,
supplementary meals/snacks, and/or nutritional supplements is considered when
patients are still in an early stage of dysphagia.
Providing nutrition in palliative home care requires collaboration of patient’s
family, a service provider under the national long-term care insurance, medical
institutions, and other professions. It is important that the team shares common
treatment policies and goals, knowledge about the underlying disease and provide
education to family members. The team should discuss and share information regarding
the type of oral care provided, contents of the meals, and method applied to assist with
eating.

15
 Nutrition in Critical Ill Patients
Mediarty Syahrir

Malnutrition is associated in critical ill patients with impaired immune function and
impaired ventilator drive, leading to prolonged ventilator dependence and increased
infectious morbidity and mortality. Medical nutrition therapy may lessen morbidity,
mortality, and length of ICU stay. Therefore, a timely assessment of nutritional status in
critically patients is important to prevent or minimize nutritional crises and to monitor
nutritional therapy. Critically ill patients have severely deranged physiology which
results in a significant alteration in their metabolism of essential nutrients. These may
result from the illness itself (diabetes, sepsis, pancreatitis, etc.) or physiological stress
due to severe illness in sepsis, burns, polytrauma, or due to derangement of organ
function as in hepatic or renal failure. Moreover, a significant number of critical ill
patients also have alteration in appetite and the function of the gastrointestinal tract.
Inadequate nutrition may alter immune response, integrity of the gut mucosal barrier,
protein synthesis and wound healing, thereby contributing to significant morbidity and
mortality. Therefore, nutrition is important a part of treatment of critically patient as are
drugs and organ support.
The concept of nutrition in critically patient was thought of as one of nutritional
support, where the main objective was to provide adequate calories and protein to
maintain normal body structure and weight during the catabolic phase of illness. This
concept has been replaced by one of nutritional therapy, where the aim is to modify the
contents of the diet in attempting to attenuate the metabolic response to stress, to
prevent oxidative cellular injury, and to favorably module immune response. These may
be expected to: 1. Preserve muscle mass and decrease autocannabolism (use of amino
acids for calories). 2. Decrease infection and improve wound healing. 3. Maintain gut
barrier functions and supporting immune, renal, hepatic, muscle function. 4. Reduce
ICU length of stay, reduce morbidity and mortality and decrease cost of healthcare.
Most critically ill patients have increased energy and protein requirements as a result of
the hypercatabolic or lytic state (glycolytic, proteolytic, lipolytic) state. The common
physiological derangements contributing to these include elevated levels of cortisol,
glucagon, catecholamines and insulin. Inflammatory cytokines TNFα and interleukin-6
(IL-6) and bacterial endotoxin alter glucose utilization and enhance protein catabolism.

16
 Should Cancer Patient with AF Take DOACs
Sally Aman Nasution

Atrial Fibrilasi dan Kanker

Kemajuan terapi kanker pada sebagian besar jenis keganasan telah
meningkatkan tingkat kelangsungan hidup dalam beberapa dekader terakhir. Akibatnya,
terdapat peningkatan cancer survivor yang diperkirakan mencapai 18 juta orang pada
2030 di USA dan Eropa. Menariknya, studi mengenai cancer survivor menunjukkan
bahwa meskipun sekitar setengah dari pasien ini akhirnya menniggal karena kanker,
sepertiga dari mereka meninggal karena penyakit kardiovaskular. Wanita dengan
diagnosis kanker payudara memiliki risiko tinggi untuk meninggal karena penyakit
jantung dibandingkan dengan kankernya. Selain itu, orang dewasa yang selamat dari
penyakit kanker sewaktu masa kecil memiliki delapan kali lipat risiko kardiovaskular
mortalitas dibandingkan dengan orang dewasa yang tidak mengalam kejadian kanker
ketika masa kecil. Komplikasi kardiovaskular pada pasien kanker merupakan hasil
interaksi dari tiga faktor utama yaitu: terapi kanker yang dapat memberikan toksisitas
terhadap jantung dan vascular, kanker itu sendiri yang mempengaruhi jantung baik
secara langsung dan tidak langsung dan status penyakit kardiovaskular yang sudah
ada dialami pasien. Komplikasi kardiovaskular pada pasien kanker cukup luas. Aritmia
menjadi komplikasi yang signifikan terutama atrial fibrilasi (AF).
Patofisiologi
Menurut studi epidemiologi, terdapat hubungan dua arah antara atrial fibrilasi
dan kanker. Hal ini sebagian dapat dijelaskan melalui mekanisme patogenetik dan
faktor risiko yang dimiliki oleh keduanya yaitu proses penuaan, inflamasi sistemik,
merokok dan obesitas. Penelitian yang dilakukan oleh Conen et al tahun 2016 dalam
JAMA Cardiology menyebutkan bahwa hubungan antara AF dan kanker pada wanita
adalah hubungan dua arah. Peneliti menyebutkan bahwa angka kejadian AF pada
wanita dengan kanker lebih tinggi dibandingkan wanita tanpa kanker. Selain itu, risiko
terjadinya kanker dalam tiga bulan terdiagnosis AF sebesar tiga kali lipat dan masih
meningkat melebihi satu tahun (hazard ratio, 1.42).
Di sisi lain, terapi pada kanker dapat menyebabkan aritmia seperti atrial fibrilasi
dengan menyebabkan toksisitas pada jantung, gangguan elektrolit dan gangguan
metabolik. Pengobatan anti kanker spektrum luas menunjukkan adanya hubungan
dengan kejadian AF. Pengobatan ini termasuk alkylating agents seperti cisplatin atau
cyclophosphamide; anthracyclines; antimetabolites, seperti 5-fluorouracil atau
gemcitabine; taxanes; topoisomerase II inhibitors, seperti etoposide dan vinca
alkaloids; targeted therapies, seperti rituximab atau small molecule tyrosine kinase
inhibitors (sorafenib, sunitinib); biological agents, seperti interferon or interleukin-2; dan

17
supporting therapies, seperti bisphosphonates. Selain itu, operasi reseksi paru pada
tumor paru juga sangat sering diikuti oleh kejadian AF.
Gambar 1. Patofisiologi AF pada keganasan.

Terapi DOAC pada AF dengan Kanker

Pemilihan jenis anti trombotik pada pasien AF dengan kanker masih menjadi
tantangan. Pedoman dari European Clinical Guideline mengenai terapi AF tidak
membuat perbedaan pada jenis kelainan patologi onkologi. Menerapkan kriteria yang
sama untuk tatalaksana anti trombotik sperti pada populasi umum. Pasien dengan AF
dan riwayat kanker memiliki risiko kardiovaskular yang berat. Terapi dengan anti
trombotik dan anti koagulan dalam beberapa studi memiliki risiko perdarahan yang lebih
tinggi dibandingkan dengan pasien yang mengalami AF tanpa kanker. Ning et al dalam
studinya yang diikuti oleh 1807 pasien dengan kanker selama 7 tahun mengungkapkan
bahwa hingga 33 persen penyebab kematiannya diakibatkan oleh penyakit
kardiovaskular. Hal ini menjelaskan bahwa pentingnya penyakit kardiovaskular pada
pasien dengan kanker. Pasien dengan kanker mengalami kontrol INR yang tidak baik.
Karena itu Vit K agonis (VKAS) mungkin tidak optimal untuk digunakan sebagai
antikoagulan untuk pasien dengan kanker, terutama ketika kemoterapi. Faktor nutrisi,
dan obat obatan lainnya juga dapat mempengaruhi aktivitas VKA pada pasien dengan
kanker. DOAC adalah jenis antikoagulan baru yang dapat menjadi alternatif pada
antikoagulan lama. DOAC merupakan antikoagulan yang bekerja dengan cara
menginhibisi secara spesifik dan langsung pada faktor koagulasi tunggal yaitu faktor II
(FIIa) dan faktor X (FXa).

18
 Gambar 2. Mekanisme DOAC.

Absorbsi pada DOAC dipengaruhi oleh intestinal P-glycoproteinI (P-gp). Namun

metabolisme Dabigatran tidak dipengaruhi oleh enzim sitokrom P-450. Sedangkan pada
semua inhibitor FXa dimetabolisme oleh sitokom CYP3A4.

Tabel 1. Farmakodinamik DOAC

Efek samping umum seperti mual, hipersensitivitas dan lain-lain dilaporkan pada
pada penggunaan DOAC dabigatran dikaitkan dengan efek samping dispepsia yang
signifikan (sekitar 10% pasien) dan sakit perut(1–10% pasien) terkait dengan
formulasinya dengan asam tartaric. Sedangkan antikoagulan Inhibitor FXa dikaitkan

19
dengan efek samping berupa ruam dan prurigo (1-10%) serta peningkatan enzim
transaminase (0,1-1%), meskipun efek samping ini lebih jarang dibandingkan dengan
pengobatan standar (enoxaparin dengan warfarin atau warfarin saja) dalam studi klinis.
Dalam terapi pemberian DOAC perlu dipertimbangkan mengenai profil darah, fungsi
renal, usia dan lain-lain.

Tabel 2. Dosis DOAC pada NVAF

Penggunaan direct-acting oral anticoagulants (DOAC) – dabigatran, apixaban,

rivaroxaban dan edoxaban – menjadi terapi anti trombotik revolusioner dalam
tatalaksana AF. Dalam studi pivotal, penggunaan dabigatran 150 mg dua kali sehari
mengurangi kejadian strok dan emboli sistemik dibandingkan dengan warfarin tanpa
perbedaan signifikan mengenai kejadian perdarahan. Sementara penggunaan
dabigatran dengan dosis 110 mg dua kali sehari tidak kalah dengan warfarin untuk
pencegahan stroke dan emboli dengan sedikit perdarahan. Namun pada penelitian ini
pasien dengan diagnosis kanker dieksklusikan.
Dosis apixaban 5 mg dua kali sehari juga menurunkan angka perdarahan dan
kematian dengan proteksi terhdap stroke dan emboli yang lebih baik dibandingkan
warfarin. Dalam penelitian ini pasien dengan harapan hidup kurang dari satu tahun
dieksklusikan.

20
 Penggunaan rivaroxaban sekali sehari terbukti tidak kalah dibandingkan warfarin
dalam pencegahan stroke dan emboli, dengan kejadian perdarahan intrakranial yang
lebih rendah. Dalam penelitian ini pasien dengan harapan hidup kurang dari 2 tahun
diekslusikan. Jadi masih sulit untuk mengambil kesimpulan yang valid pada pasien
dengan kanker. Penelitian yang spesifik mengenai keamanan dan potensi DOAC pada
pasien AF dan kanker masih jarang.
Hubungan antara stroke dan kanker sangat kompleks. Stroke sering pada pasien
dengan kanker, dan pasien kanker dengan stroke iskemik sering menunjukkan faktor
risiko dan etiologi yang berbeda dibandingkan dengan pasien stroke tanpa kanker.
Telah menjadi kontroversi mengenai patogenesis faktor risiko terhdapa stroke dengan
kanker. Kondisi hiperkoagulatif dan peningkatan kadar D-dimer sering terjadi. Dalam
studi subanalisis, rivaroxaban sekali sehari dibandingkan dengan vit k antagonis untuk
pencegahan stroke dan emboli dalam studi ROCKET-AF, menunjukkan bahwa kejadian
stroke iskemik dalam 1 tahun pada pasien dengan kanker dan AF adalah 1,4% (95% CI
[0,0 - 3,4]). Dalam studi subgrup ROCKET-AF dan studi RE-LY menunjukkan bahwa
risiko perdarahan pada pasien kanker adalah dua sampai enam kali lebih besar
dibandingkan pasien dengan tanpa kanker. Dalam studi Zhang et al juga menunjukkan
bahwa adanya kecenderungan perdarahan intracranial yang lebih besar pada pasien
kanker dengan AF. Analisis lebih lanjut mengenai pasien AF dengan kanker (n = 157)
atau riwayat keganasan (n = 1079) dalam studi ARISTOTLE menunjukkan secara
konsisten apixaban lebih superior dibandingkan dengan warfarin pada pasien dengan
dan tanpa kanker.
Penelitian terbaru oleh Surbhi et al tahun 2019 mengenai perbandingan
efektifitas DOAC dan warfarin pada pasien AF dan kanker menunjukkan angka
terjadinya perdaharan lebih rendah pada apixaban dibandingkan warfarin yang memiliki
angka perdarahan yang sama dengan dabigatran dan rivaroxaban. Selain itu risiko VTE
lebih rendah pada penggunaan DOAC dibandingkan dengan warfarin.

21
 Tabel 2. Atrial FIbrilasi dan Keganasan

Secara keseluruhan, terapi antitrombotik pada pasien dengan AF dan kanker

membutuhkan dedikasi tim interdisipliner. Terutama, ketika kemoterapi myelosupresif
atau terapi radiasi direncanakan, pengurangan dosis sementara atau penghentian
terapi NOAC perlu dievaluasi, dengan memperhitungkan profil darah lengkap termasuk
trombosit, fungsi ginjal / hati, dan tanda-tanda perdarahan. Pemberi an PPI atau H2
bloker perlu dipertimbangkan untuk diberikan pada semua pasien tersebut.

22
 Update on Treatment of VTE in Cancer Patients
Tutik Harjianti

Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and

pulmonary embolism (PE), is the third most common cardiovascular disease, with
annual incidence of more than 10 million people globally.

Patients with cancer are at higher risk of venous thromboembolism (VTE) than
the general population as the malignancy itself and treatment modalities, including
medication and surgery, contribute to the risk of developing VTE. Furthermore, patients
with cancer developing VTE have a worse prognosis than those without cancer. There
are many independent risk factors associated with venous thromboembolism (VTE),
such as surgery, trauma, hospitalization, malignant neoplasm with or without
chemotherapy and the use of central venous catheters. A combination of risk factors
usually precipitates the occurrence of VTE. The risk of VTE is four to seven times higher
among patients with cancer than that among the general population; cancer type, stage
or combination of various risk factors may contribute to increase VTE occurrence.
Symptoms of VTE are non-specific, and the diagnosis should actively be sought once
considered.

Anticoagulation is therefore challenging. For many years, long-term therapy with

Low-Molecular-Weight Heparin (LMWH) was the standard of care for the management
of cancer-associated VTE. Direct oral anticoagulants (DOAC), which offer the
convenience of an oral administration and have a rapid onset of action, have recently
been proposed as a new option in this setting. Head-to-head comparisons between
DOAC and LMWHs for the treatment of established VTE are now available, and data on
the efficacy and safety of these drugs for primary prophylaxis of VTE in ambulatory
cancer patients receiving systemic anticancer therapy are emerging

Efficient, cost effective diagnosis of VTE is facilitated by combining medical

history and physical examination with pre-test probability models, D dimer testing and
selective use of confirmatory imaging. Clinical prediction rules, biomarkers and imaging
can be used to tailor therapy to disease severity.

23
 Role of Thyrosine Kinase Inhibitor in Renal Cancer
Wulyo Rajabto

The renal cell carcinoma (RCC) is the most common form of kidney cancer (85-
90% of cases). It is nearly twice as common in men as in women, with a median age at
diagnosis of 64 years. Clear cell tumors are the most common pathological subtype of
RCC (80% of cases). It primarily metastasized to the lung, bone, liver, lymph nodes,
adrenal gland, and brain. Although the 5-year overall survival (OS) of early-stage RCC
is as high as 66%, but metastatic or advanced stage disease is only 8%–10%.
In the past decade, treatment options for mRCC have expanded dramatically
with better understanding of the tumor biology and underlying molecular mechanisms
responsible for tumor angiogenesis and metastases. Surgical operation and systemic
therapy are the most effective causal therapies. Systemic therapy is given to RCC
patients stage IV with distant metastases. The overall therapy concept must be defined
before the first therapeutic measure is applied.
Therapy of metastatic RCC (mRCC) is almost always applied for palliative
reasons and responds very poorly to conventional chemotherapy. Cytokines (e.g.,
interferon-alfa and interleukin-2) have been largely replaced by targeted agents, having
favorable toxicity profiles and associated with higher response rates, longer PFS, or
both. These agents, including anti-angiogenic drugs (e.g., TKIs), mTOR inhibitors, and
immune checkpoint inhibitors, have improved the clinical outcomes of this difficult-to-
treat metastatic cancer, which is otherwise universally resistant to conventional
chemotherapeutic agents. Currently, pazopanib, sorafenib, and sunitinib are oral multi-
targeted TKIs which have been approved by the Food and Drug Administration for the
treatment of mRCC.
Pazopanib is another oral tyrosine kinase inhibitor, which displays a somewhat
different kinase profile than that of sorafenib and sunitinib. Pazopanib significantly
improve progression-free survival period with RR 30%. Attention should be paid to
hepatic toxicity.
Sorafenib is an oral inhibitor of several tyrosine kinases, for example, of the
VEGF receptors, PDGFRB, Flt-3 and c-KIT. In the pivotal trial, sorafenib was
investigated as a second- line therapy option for low and intermediate-risk patients.
Progression-free survival was found to be significantly prolonged. In first-line therapy,
no significant difference in the remission rate and progression-free survival could be
revealed in comparison with interferon alpha. Sunitinib is an oral inhibitor which blocks
several VEGF, PDGF receptors as well as c-KIT and Flt-3 on the level of tyrosine
kinase. In the marketing authorization study sunitinib was applied to patients in first-line
therapy and compared with IFN alpha. Progression-free survival was significantly
longer, the rate of remission was at 47% according to the final evaluation.

24
 Attention should be paid to a serious adverse effect (grade 3/4), which appeared
in more than 5% of the patients, consisted in a hand-foot syndrome (grade 3/4),
hypotension, fatigue, diarrhea, and asthenia. Endocrine (hypothyroidism), hematological
or cardiac side effects can occur in patients if they are treated with multikinase inhibitors
over a longer period of time.

25
 Recent Update in Renal Cell Cancer Guidelines
Ketut Suega

Renal cell carcinoma (RCC) accounts for 2% to 3% of all malignant disease in

adults, representing the seventh most common cancer in men and tenth most common
cancer in women in the United States. The increase in the incidental finding of small
renal tumors has increased the application of nephron-sparing procedures, while ten
novel agents targeting the vascular endothelial growth factor (VEGF) or the mammalian
target of rapamycin pathways, or inhibiting the interaction of the programmed death 1
receptor with its ligand, have been approved since 2006 and have dramatically
improved the prognosis of metastatic RCC (mRCC). The landscape of local and
systemic therapy of renal cell carcinoma (RCC) is rapidly changing. These rapid
developments have resulted in continuous changes in the respective Clinical Practice
Guidelines/Expert Recommendations. Several national and international urological and
medical oncology societies and associations have published guidelines on RCC.
Nevertheless, their utility in everyday practice may be associated with a variety of
limitations. This variation underlines the considerable heterogeneity in the development
and reporting of guidelines. And also generating several agreement as well as
uncertainty among them. The major areas of uncertainty were as follows: (a) selection
criteria for nonsurgical approaches in renal masses;(b) the role of modern laparoscopic
techniques, especially in the context of PN; (c) selection criteria for CN and
metastasectomy in mRCC; (d) systemic therapy of metastatic NCC renal cancers; e
optimal sequence of available agents in mRCC relapsed after anti-VEGF/VEGFR
therapy.
EAU, ESMO, Japanese Urological Association (JUA), African Middle East
(AfME), Sociedad Espanola de Oncologıa Medica (SEOM), and SOS published
guidelines for the whole spectrum of RCC management. The NCCN guidelines were
focused on systemic therapy, while the AUA, the 2011 EAU International Consultation
on Urologic Diseases (ICUD), and the Japanese Society of Endourology and
Extracorporeal Shockwave Lithotripsy (JSEE) published guidelines on localized or
locoregional disease.
In patients with a clinical T1a renal mass for which intervention is indicated,
the American Urological Association (AUA) guideline recommends prioritizing partial
nephrectomy, as National Comprehensive Cancer Network (NCCN) lists their treatment
options. The 2019 European Society for Medical Oncology (ESMO) guidelines also
recommend partial nephrectomy as the preferred option in tumors measuring up to 7
cm. Partial nephrectomy is also recommended in patients with compromised renal
function, solitary kidney, or bilateral tumors, with no tumor size limitation.

26
 For stage II and III renal tumors, the National Comprehensive Cancer Network
(NCCN) guideline recommends radical nephrectomy in most cases. The European
Society for Medical Oncology (ESMO) guideline recommends laparoscopic radical
nephrectomy for T2 tumors (> 7 cm). For locally advanced RCC (T3 and T4), open
radical nephrectomy is the standard of care, though a laparoscopic approach can be
considered. However, systemic adrenalectomy or extensive lymph node dissection is
not recommended when there is no evidence of adrenal or lymph node invasion.
Adjuvant and neoadjuvant treatment should not be considered outside of clinical trials.
Primary Treatment of Stage IV Kidney Cancer according to National
Comprehensive Cancer Network (NCCN) are : Radical nephrectomy plus surgical
metastatectomy if feasible with consideration of first-line systemic therapy if relapse
occurs, cytoreductive nephrectomy in selected patients prior to systemic therapy,
followed by first-line systemic therapy and first line systemic therapy for unresected
case. For patients with predominantly clear cell cancer, considerations for first-line
therapy are best supportive care and one of the following: Clinical trial, Pazopanib
(category 1, preferred), Sunitinib (category 1, preferred), Bevacizumab + interferon alfa-
2b (category 1), Temsirolimus (category 1 for poor-prognosis patients, category 2B for
selected patients of other risk groups), Axitinib, Cabozantinib (for poor- and
intermediate-risk groups), High-dose IL-2 for selected patients (with excellent
performance status and normal organ function), Active surveillance for select,
asymptomatic patients). For patients with previously treated predominantly clear cell
renal cell cancer, NCCN considerations for subsequent therapy include the following:
Clinical trial, Cabozantinib (category 1, preferred), Nivolumab (category 1, preferred),
Axitinib (category 1), Lenvatinib + everolimus (category 1), Everolimus, Pazopanib,
Sorafenib, Sunitinib, Bevacizumab (category 2B), High-dose IL-2 for selected patients
(category 2B), Temsirolimus (category 2B)
For patients with non–clear cell histology, NCCN recommendations for systemic
therapy include the following: Clinical trial (preferred), Sunitinib (preferred), Axitinib,
Bevacizumab, Bevacizumab + erlotinib for selected patients with advanced papillary
RCC, including hereditary leiomyomatosis–associated RCC (HLRCC), Bevacizumab +
everolimus for selected patients with advanced papillary RCC including HLRCC,
Cabozantinib, Erlotinib, Everolimus, Lenvatinib + everolimus, Nivolumab, Pazopanib,
Sorafenib, Temsirolimus (category 1 for poor-prognosis patients;hcategory 2A for other
risk groups)
Follow-up, long-term implications and survivorship. So far, there is no evidence
that early treatment of metastasis results in better outcome of metastatic disease when
compared with delayed treatment. Overall, there is no evidence that any particular
follow-up protocol influences the outcome in early RCC as well as in advanced RCC. It
is recommended to perform CT scans every 3–6 months in high-risk patients for the first

27
2 years, while a yearly CT scan is probably sufficient in low risk patients (expert
opinion). Long-term follow-up is proposed in some institutions, due to the possibility of
late relapse, but its benefit has never been demonstrated [NCCN].
The Memorial Sloan Kettering Cancer Center (MSKCC) system was the gold
standard for the risk assessment during cytokine treatment in metastatic RCC (mRCC),
and it is still commonly used. Further refinement was introduced with the International
Metastatic RCC Database Consortium (IMDC) score, which extended the previous
factors to a total number of six in order to increase concordance.

28
 Palliative Treatment in Renal Cell Carcinoma Patiens
Andi Fachruddin Benyamin

Kidney cancer accounts for 5% of all adult malignancies in men and 3% in

women, representing the 7th most common cancer in men and the 10th most common
cancer in women. Approximately one in three cases will present at an advanced stage
as a newly diagnosed Renal Cell Cancer (RCC). Metastatic RCC (mRCC) are poorly
responsive to treatment with poor prognosis. The median survival of patients with
mRCC is approximately eight months.
Cancer and kidney disease patients both have two things in common: they have
a shortened life expectancy and a high symptom burden. Both benefit from early
palliative care interventions. The goal of palliative care is to relieve suffering and to
support the best possible quality of life for patients and their families, regardless of their
stage of disease or the need for other therapies, in accordance with their values and
preferences. Palliative care can be active treatment to shrink or stop the cancer
growing. Cancer treatments such as surgery, chemotherapy, immunotherapy, targeted
therapy and radiation therapy may be used as part of palliative treatment.
The role of surgery in palliative treatment in the cytokine era is cytoreductive
nephrectomy (CN), recommended in patients with good patient status. CARMENA
randomised trials no longer be considered CN as the standard of care in intermediate
and poor-risk mRCC patients with asymptomatic primary tumors when medical
treatment is required.
Radiation therapy (RT) is still a valid local, non-invasive treatment alternative to
surgery and can be used for the palliation of painful bone metastases, spinal cord
compression and brain metastases. Significant technological advances in RT, such as
intensity-modulation RT, image-guidance RT, stereotactic body RT and stereotactic
radiosurgery (SRS), have enabled the delivery of high doses, with accuracy within
millimeters.
About one-third of patients with mRCC have bone metastasis that are often
osteolytic and cause substantial morbidity, such as pain, pathologic fracture, spinal cord
compression and hypercalcemia. Bone-targeted treatment using bisphosphonate and
denozumab can reduce skeletal complications in RCC, but does not cure the disease or
improve survival. Zoledronic acid, a third-generation amino-bisphosphonate, is a potent
inhibitor of osteoclast activity and widely used in the management of bone metastases
from various malignancies, including RCC. Denosumab, a fully human monoclonal
antibody that binds to and neutralizes RANKL, inhibits osteoclast function, prevents
generalized bone resorption and local bone destruction, and has become a therapeutic

29
option for preventing or delaying on-study skeletal-related events in various
malignancies.
First line immunotherapy combination represents standard of care for
intermediate to poor risk treatment naive mRCC. Moreover, immunotherapy and anti
VEGF antibody combination represents a treatment option across all risk levels in
patient with PDL1 expression at least 1%. In addition, immunotherapy monotherapy
(nivolumab) represents one of two ideal treatment options for second-line mRCC
patients.
Cryoablation is currently used to treat either RCC primary tumours or
metastases, including lesions of the bone, and is an alternative to radiofrequency
ablation.
Multimodal, multi-disciplinary therapy is vital in the management mRCC, which
remains a challenging especially in patients with terminal disease.

30
 Terapi Paliatif pada Pasien Renal Cell Carcinoma
Andi Fachruddin Benyamin

Kanker ginjal merupakan 5% semua keganasan dewasa pada pria dan 3% pada
wanita, selain itu menjadi penyebab ke-7 paling sering pada pria dan kanker ke-10
paling sering pada wanita. Sekitar satu pertiga kasus baru didiagnosis pada stadium
lanjut dengan Renal Cell Carcinoma (RCC). Metastatic RCC (mRCC) memiliki karakter
kurang responsif terhadap pengobatan dan memiliki prognosis yang buruk.
Kelangsungan hidup rata-rata pasien dengan mRCC sekitar delapan bulan sejak
terdiagnosis.
Dua hal yang umum yang paling sering terjadi pada keganasan organ ginjal:
yaitu harapan hidup yang pendek dan gejala klinis yang berat. Perawatan paliatif dini
memberikan perbaikan akan dua hal tersebut, tujuan perawatan paliatif adalah untuk
meringankan penderitaan dan memperbaiki kualitas hidup terbaik untuk pasien dan
keluarga terlepas dari tahap penyakit atau kebutuhan untuk terapi lain. Perawatan
paliatif merupakan pengobatan aktif untuk mengecilkan atau menghentikan
pertumbuhan kanker. Modalitas perawatan kanker meliputi; operasi, kemoterapi,
imunoterapi, terapi bertarget, serta terapi radiasi merupakan bagian dari pengobatan
paliatif bagi pasien mRCC.
Peran operasi dalam perawatan paliatif di era Sitokin berupa Cytoreductive
Nephrectomy (CN), direkomendasikan pada pasien dengan status patein yang baik.
Study oleh CARMENA, CN tidak lagi direkomendasikan pada pasien mRCC
asimptomatik dengan risiko menengah hingga berat.
Radiation therapy (RT) masih merupakan alternatif pengobatan tumor lokal non-invasif
dan dapat digunakan sebagai terapi paliatif metastasis tulang dengan gejala cancer pain
dominan, kompresi sumsum tulang belakang, dan metastasis otak. Kemajuan teknologi yang
signifikan dalam RT, seperti intensity-modulation RT, image-guidance RT, stereotactic body RT
and stereotactic radiosurgery (SRS), telah memungkinkan penggunaan dosis tinggi, dengan
akurasi dalam satuan milimeter.

Sekitar sepertiga dari pasien dengan mRCC memiliki metastasis tulang yang
memperburuk morbiditas dan bermanifestasi sebagai nyeri, fraktur patologis, kompresi
medula spinalis dan hiperkalsemia. Bisphosphonate dan denozumab dapat mengurangi
komplikasi skeletal pada RCC, tetapi tidak menyembuhkan penyakit atau
memerpanjang kelangsungan hidup. Asam Zoledronic, amino-bifosfonat generasi
ketiga, merupakan penghambat aktivitas osteoklas yang kuat dan banyak digunakan
dalam pengelolaan metastasis tulang dari berbagai keganasan, termasuk RCC.
Denozumab, antibodi monoklonal mengikat dan menetralkan RANKL, menghambat

31
fungsi osteoklas, mencegah resorpsi tulang umum dan destruksi lokal tulang menjadi
pilihan terapeutik untuk mencegah atau menunda efek dari keganasan pada skeletal.
Terapi imunologi kombinasi lini pertama merupakan standar perawatan untuk
mRCC naif berisiko rendah dan menengah. Selain itu, kombinasi antibodi anti-VEGF,
antibodi immune-oncology anti VEGF merupakan pilihan pengobatan di semua tingkat
risiko pada pasien dengan ekspresi PDL1 setidaknya 1%. Selain itu, monoterapi
imunooncologi (nivolumab) merupakan salah satu dari dua pilihan pengobatan yang
ideal untuk pasien mRCC lini kedua.
Cryoablation saat ini digunakan untuk mengobati baik tumor primer RCC atau
metastasis, termasuk lesi tulang, dan merupakan alternatif untuk radio ablasi frekuensi.
Terapi multimodal dan multidisiplin sangat penting dalam manajemen mRCC,
penanganan pasien dengan stadium terminal membutuhkan pemilihan dan kolaburasi
beberapa modalitas yang dapat memperbaiki kualitas hidup pasien.

32
 Blood Transfusion in Cancer Patients
Ronald A. Hukom

Cancer patients often need blood transfusions during the course of the disease.
Giving blood transfusions can be related to therapeutic measures such as surgery,
chemotherapy, and radiation. If there are comorbidities, such as lung and heart
problems, or in the elderly, administration of blood components (e.g. red blood cells to
increase Hb) needs to be done earlier.
Severe anemia will increase the problem of cancer management, contribute to
fatigue and reduced quality of life. Anemia may even delay or limit further treatment.
Blood transfusion is currently the most common form of treatment. The symptoms for
which transfusion was given were lethargy, tiredness, breathlessness, and pallor. One
study shows that the proportion of people complaining of breathlessness was
significantly higher in lung cancer patients, while a significantly higher proportion of
testicular cancer patients reported tiredness. The possibility of receiving a transfusion is
not related to age, but does vary with the tumour type and stage. Other studies have
shown that patients receiving certain chemotherapy regimens (e.g. platinum-based)
frequently require transfusions.
Recommendation for platelet transfusion is based on data from some
randomized controlled trials. Adult patients who undergo autologous stem-cell
transplantation at experienced centers may receive a platelet transfusion at the first sign
of bleeding, rather than prophylactically. Prophylactic platelet transfusion is still
recommended for patients undergoing allogeneic stem-cell transplantation. Platelet
transfusion is also needed in certain patients with hematologic malignancies, or solid
tumors, or in those who need invasive procedures.

33
 Management of Major Incompatibility in Blood Transfusion
Djoko H. Hermanto

Blood transfusion can be lifesaving for patients with severe

anemia and/or bleeding. However, transfused blood is a foreign substance that has the
potential to elicit an immune response that may cause transfusion reaction. The timely
recognition and treatment of transfusion reactions and related conditions is importance
for clinicians. Transfusion reactions can be divided in several ways. One way to classify
is using the 24h limit into acute or delayed transfusion reaction. The other way to
classify is using the degree of severity reaction which divide into minor or major
transfusion reaction. Major incompatibility which result in blood hemolysis is one of
major tranfusion reaction that may cause critical condition in a patient having a
tranfusion. Acute Hemolytics Transfusion Reactions (AHTRs) are usually due to ABO
incompatibility, most often the result of clerical or procedural error. Pathologically, HTRs
are associated with accelerated destruction of RBCs. In the most common situation,
transfusion of RBCs leads to hemolysis of the transfused cells by a host immune
response against a foreign antigen on these RBCs. Recognize the tranfusion reaction
and stop the tranfusion is the first step managing patient who suffers from transfusion
reaction including major incompatibility.

34
 Surgical Treatment in Early Breast Cancer
Bayu Brahma

Surgical treatment in breast cancer has evolved from Halstedt’s concept of

radical surgery into less extensive breast conserving surgery which adopted Fisher’s
theory. As today we have accepted multimodality treatment approach, the
advancement of systemic and radiation therapy which play along with surgery, can
achieve a better survival and quality of life (QOL). Oncoplastic breast surgery (OPS)
has become a trend and will be the future in surgical technique that could increase
patient’s QOL. Various breast reconstruction methods and the application of
microsurgical reconstructions have opened a new insight and challenge among surgical
oncologists and reconstructive surgeons. In addition to local treatment, regional surgery
namely, axillary lymph nodes dissection (ALND), has also been replaced by sentinel
nodes biopsy (SNB) for node-negative breast cancer. The risk of upper extremity
lymphedema (UEL) due to ALND and adjuvant radiation has been the main concern to
selectively performing ALND and promoting SNB as a standard of care in early breast
cancer to minimize the occurrence of UEL. Lastly, the knowledge of surgical treatment
for UEL has emerged as a new field to treat breast cancer treatment-related
lymphedema (BCRL). Supermicrosurgery reconstructions hold as a promising method
and will be the future of BCRL treatment and lymphatic surgery development.

35
 Chemotherapy and Hormonal Therapy for Breast Cancer
Ami Ashariati

Breast cancer is the most common malignant neoplasm in women, with an

estimated 25% 0f new cancer diagnoses and 13% of cancer death in woman in 2017.
Although often curable when localized to the breast and local lymph nodes, but if the
disease becomes metastatic it is usually not curable.
Breast cancer is a heterogeneous disease comprising several molecular
subtypes, which are commonly extrapolated into clinical subtypes based on receptor
status. The specific receptors that are assessed in standard clinical practice are the
estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth
factor 2-neu (HER2) receptor. These receptors are both prognostic but also predictive of
response to targeted therapy; thus, when metastasis is suspected it is crucial to perform
a biopsy not only to confirm recurrent disease, but also to confirm receptor status.
In addition, tissue availability may increase clinical trial access because many
studies now assess targetable molecular aberrancies. Considerable advances have
been made in treatment of certain subtypes of breast cancer, for example, HER2-
positive disease. In this subtype, targeted therapies against HER2 have changed the
clinical outcome for patients with metastatic disease by providing them with several
effective therapies that can extend survival by many years. The ER- and PR-positive
subtypes also have several targeted therapies available using endocrine therapies;
however, when the disease becomes metastatic, all patients eventually develop
endocrine resistance and eventually require cytotoxic chemotherapy.
Patients with ER-, PR-, and HER2-negative tumors, the so-called triple-negative
breast cancers (TNBCs), biologically tend to display an aggressive phenotype, currently
do not have targeted therapy options as a standard of care, and have only a limited
amount of cytotoxic agents available to treat their disease.
This review narrates and expands on some of the recent efforts in drug
(chemotherapy and or hormonal therapy) development for breast cancer.

36
 Targeted Therapy in Breast Cancer
Cosphiadi Irawan

Breast cancer is the most common cancer in woman globally, as well as leading
cause of death in woman. Indonesia contributed almost 350.000 all cancer new cases,
and there is 58.256 (19.18%) breast cancer new cases, with 22.692 (12.75%) death.
There is a wide ranged types of treatment modality, starting with anti-hormonal,
chemotherapy, targeted therapy and immuno-checkpoint inhibitor. Further on, targeted
cancer therapies are define as: drugs or other substances that block the growth and
spread of cancer by interfering with specific molecules ("molecular targets") that are
involved in the growth, progression, and spread of cancer. This will reveals with a long
list of targeted therapy including everolimus, tamoxifen, toremifene , trastuzumab
fulvestrant ,anastrozole, pertuzumab, ado-trastuzumab emtansine, palbociclib,
ribociclib, neratinib maleate, abemaciclib , olaparib , and atezolizumab
There is four subtype group of breast cancer by molecular classification (-luminal
A/B, HER-2, and TNBC), with many trial showed when combination targeted therapy
given with chemotherapy or as a single agent as a maintenance, may prolonged DFS
(-disease free survival-), PFS (-progression free survival-), and OS in early or advanced
breast cancer respectively. Patient “tailor made” treatment especially with hormonal
receptor positive should be based and considered cross talk that exist with HER2
status. Post-menopausal and HER2 negative patients, whose relapse either primary or
secondary with hormonal treatment, should consider combination everolimus (-mTOR
inhibitor-) and exemestane, and those with HER2 positive, may gain modest PFS
benefit with adds trastuzumab to anastrozole or letrozole with lapatinib
Patients showed different sensitivities to anti-HER2 agents, depending on
whether they present with de novo metastases and thus have not received trastuzumab
or they developed metastatic disease after adjuvant trastuzumab. In the latter group,
patients whose relapse 1 year or longer seem to be more sensitive to anti-HER2
therapies than those whom disease progressed within 1 year. There is lapatinib
combine with capecitabine, or ado-trastuzumab emtansine or combination pertuzumab-
trastuzumab and docetaxel for HER-2 positive relapse patients, or now as 1st line in
metastatic setting in the later as; but still there is no predictive biomarker to guide which
patients are more likely to benefit from ado-trastuzumab emtansine or pertuzumab.

37
Adjuvant and Neo-Adjuvant Chemotherapy for Head and Neck Cancer
Santosa

The annual incidence of head and neck cancers worldwide is more than 550,000
cases with around 300,000 deaths each year. Male to female ratio ranges from 2:1 to
4:1. About 90% of all head and neck cancers are squamous cell carcinomas (HNSCC).
HNSCC is the sixth leading cancer by incidence worldwide. Presentation with distant
metastases occurs in about 10% of newly diagnosed patients with HNSCC. In a similar
way, more than 50% of newly diagnosed patients with HNSCC will relapse locally or at
a distant site and patients with recurrent and/or metastatic SCCHN have a poor
prognosis with a median survival time of less than a year. Most HNSCCs arise in the
epithelial lining of the oral cavity, oropharynx, larynx and hypopharynx. Among all head
and neck (H&N) cancers, nasopharyngeal carcinoma (NPC) represents a distinct entity
regarding epidemiology, clinical presentation, biological markers, carcinogenic risk
factors, and prognostic factors. NPC is endemic in certain regions of the world,
especially in Southeast Asia, and has a poor prognosis. In Indonesia, the recorded
mean prevalence is 6.2/100 000, with 13 000 yearly new NPC cases, but otherwise little
is documented on NPC in Indonesia. The prognosis of these patients is substantially
better than those associated with tobacco. The five-year overall survival rate of patients
with HNSCC is about 40-50%. About one third of patients present with early stage
disease (T1-2, N0).
Currently, three multimodality treatment approaches are used. The first approach
is surgery followed by adjuvant concurrent chemo radiotherapy, which enables precise
pathologic staging and identification of high-risk features that influence the choice of
adjuvant treatment. This approach can have limitations, such as poor organ
preservation, depending on the anatomic location (e.g. larynx) and the majority of loco
regionally advanced tumors are unresectable, especially if organ preservation is the
goal. Treatment for early HNSCC usually involves single-modality therapy with either
surgery or radiation. Survival is comparable for the two approaches. Early stage
cancers have a very favourable prognosis with high cure rates with surgery or radiation
alone and chemotherapy or concurrent chemo radiotherapy is not indicated.
The second approach is definitive concurrent chemo radiotherapy with surgery
as an optional salvage or completion treatment. Although no pathologic information is
obtained with this approach, it has the advantage of improved organ preservation. This
benefit is most clearly established for laryngeal cancer but is increasingly recognized for
other anatomic locations; however, this approach remains controversial for oral cavity
tumors. For patients with pathologically staged III, IVa/b head and neck cancer,
postoperative concomitant chemo-radiation with cisplatin has shown improvement in

38
local-regional control and survival rates for those with positive microscopic surgical
margins and/or extra-capsular nodal extension.
The third approach is neo-adjuvant chemotherapy, the induction chemotherapy
followed by definitive local therapy. Advantages include the potential to decrease the
risk of distant failure and a rapid reduction in tumor bulk in responders. A response to
induction appears to predict responsiveness to chemo radiotherapy. Nonetheless, this
can result in prolonged treatment and additional chemotherapy-related toxic effects from
systemic doses.

39
 Immunotherapy in Head and Neck Cancer
Mardiah Suci Hardianti

The conventional anticancer treatment such as surgery, chemotherapy, and

radiotherapy have offered substantial benefit for eradication of primary tumors.
However, disease refractory and relapse that occurred due to the residual of malignant
cells are still very hard to treat. The advances in understanding the relationship between
cancer and immunity opened promising approaches in cancer care so called
immunotherapy. Basically, this approach is developed to harness the function of the
immune system to present, recognize and eventually destroy the tumor cells. The
orchestra is started from antigen presenting cells (APCs) such as dendritic cells (DC)
and macrophages (M) to present tumor associated antigen (TAA) to the CD4 and CD8
T cells, which involves the arms of major histocompatibility complex (MHC), T cell
receptors (TCR), co-stimulatory and co-inhibitory molecules or immune checkpoint as
well as cytokines. Enhancing the ability of APC to present the tumor associated antigen
may be achieved by increasing either the amount of antigens or APCs. Adoptive T cell
transfers may also expand the number of cytotoxic T cells (CTLs). The development of
immune checkpoint inhibitor to block the signals from inhibitory molecules which
attenuate the clonal expansion of T cells followed by decreased production of antitumor
cytokines are also essential for effective destruction of the tumor cells. Immunotherapy
in head and neck cancer has also been developing. Beginning from the recognition of
several viruses as the etiological factors followed by the development of either
protective and therapeutic vaccine to HPV and EBV. The applications of immune
checkpoint inhibitors have also been promising in this particular type of cancer.

40
 Supportive Therapy in Head and Neck Cancer
(Nutrition, Pain Management, and Infection)
Diana Paramita

Head and neck cancers (HNC) patients often face multiple symptoms related to
cancer or the side effects of its treatment. Pain, infection related treatment, and
malnutrition are associated with poorer treatment outcomes, increased morbidity and
mortality, and poorer quality of life. HNC patients are often malnourished at time of
diagnosis with 25–50% of patients having involuntary weight loss prior to starting
treatment. Common treatment-related side effects, such as dysphagia, odynophagia,
dysgeusia, xerostomia, thick saliva, mucositis, nausea, and vomiting, all further impair
the patient’s ability to maintain adequate oral intake. Urgent nutritional management is
necessary for patients that lose >10% body weight within 6 months of treatment or >5%
within one month of treatment. HNC patients should then be reassessed on a weekly
basis during treatment. Nutrition assessments consist of medical history, social history,
physical examination, anthropometric assessment, relevant laboratory data, and
nutrition intake history. Nutrition risk screening can be done by measurement of body
mass index, weight loss, index of food intake may be obtained directly, or via validated
nutrition screening tools, e.g. Nutrition Risk Screening 2002 (NRS-2002), Malnutrition
Universal Screening Tool (MUST), Malnutrition Screening Tool (MST), and Mini
Nutritional Assessment Short Form Revised. The goal of nutrition intervention is to
continue a safe oral diet, manage symptoms, and supplement as necessary during
treatment. Nutritional support is indicated when there is malnutrition or risk of
malnutrition; when the patient is not expected to be able to eat food for 1 week or more,
or if their intake is less than 60% of their needs for more than 1–2 weeks.

HNC-specific pain is often a combination of somatic and neuropathic pain that

may be acute or chronic and may be a direct consequence of the tumour or secondary
to treatment. The incidence and intensity of pain are dependent upon the complexity of
the cancer treatment itself. Pain assessment may be evaluated using Brief Pain
Inventory, Numerical Rating Scale (NRS), Categorical Scale (CRS), or Visual Analog
Scale (VAS). The effective management of HNC pain requires a multidisciplinary, non-
pharmacological, pharmacological, and procedural approach. Algorithm for the
treatment of cancer pain was developed by the WHO. It suggests that patients with pain
be started on acetaminophen or a nonsteroidal anti-inflammatory drug (NSAID). If this is
not sufficient, the patient should be escalated to a weak opioids and subsequently to a
“strong opioid,” such as morphine.

41
 Radiotherapy for head and neck cancers (HNC) causes alteration of oral
mucosal barrier predisposing it to oral mucositis, colonization of opportunistic
mucosal infection, abrupt deterioration in oral health, neurosensory disorders, and
tissue fibrosis. Anatomical factors may also predispose patients to infection, for
example head and neck tumors may cause erosion through the neck and floor of the
mouth and oesophageal cancer may increase the risk of aspiration pneumonia.
Infection of vital organs can turn lethal if the immune system is compromised e.g. use
of chemotherapeutic agents. Neutropenia may develop independently after
chemotherapy and it may also be a risk factor for infection. Preventing, assessing, and
managing oral complications throughout the active continuum of care are required
to promote the best possible patient quality of life. The pre-treatment dental
management should be directed at necessary assessment including complete oral,
dental, and periodontal examination and baseline range of jaw movement and saliva
production is the best approach to achieving the best possible clinical outcomes.

42
 Pathophysiology of Cancer Pain
Asrul Harsal

Pathophysiology of cancer pain involved the inflammatory, neuropathic and a

unique change in sensory processing. In addition, cancer-induced bone pain results in
progressive bone destruction, elevated osteoclast activity and distinctive nocifensive
behaviors (indicating the triad of ongoing, spontaneous and movement-induced
hyperalgesia). In addition, cancer cells induce an inflammatory infiltrate and release
growth factors, cytokines, interleukins, chemokines, prostanoids and endothelins,
resulting in a reduction of pH to below 5 and direct deformation of primary afferents
within bone. These peripheral changes, in turn, drive hypersensitivity of spinal cord
sensory neurons, many of which project to the parts of the brain involved in the
emotional response to pain. Within the spinal cord, a unique neuronal function
reorganization within segments of the dorsal horn of the spinal cord receiving
nociceptive input from the bone are discussed. Changes in certain neurotransmitters
implicated in brain modulation of spinal function are also altered with implications for the
affective components of cancer pain. Treatments are described in terms of mechanistic
insights and in the case of opioids, which modulate pain transmission at spinal and
supraspinal sites, their use can be compromised by opioid-induced hyperalgesia.

43
 Management of Pain in Cancer Patient
Resti Mulya Sari

INTRODUCTION
Chronic pain that is severe enough is experienced by 30 to 50 percent of patients
undergoing active neoplastic therapy and by 75 to 90 percent of those with advanced
diseases.
Adequate of pain relief can be achieved in 70 to 90 percent of patients when
well-accepted treatment guidelines for cancer pain are followed. Pain affects the
psychological, cognitive, social, and spiritual domains of patients' lives; the experience
of pain can be influenced by emotional, cognitive, social, and spiritual factors.
The causes of pain under treatment are multifactorial and reflect the combined
effects of clinician, patient and systems related barriers, including inadequate of
clinician knowledge skills and attitudes; patients may under report pain; systems wide
impairment to optimal analgesic therapy.

ASSESTMENT AND ETIOLOGY OF CANCER PAIN

Cancer pain assessment is a complex undertaking. Because of the potential
impact of pain on quality of life, it is also essential to determine the adverse effects of
pain on physical and psychosocial wellbeing, as well as the spiritual impact of the pain.
The causes of chronic pain and both prevalence and severity vary with the type
of neoplasm, stage, extent of disease, prior treatment, comorbidities and other factors.
Tissue injury produced by neoplasms is the primary of etiology of chronic cancer pain.
When the etiology of the pain is related to the disease, it usually involves direct invasion
of pain-sensitive structures by the neoplasm. Bone is the most common pain-sensitive
structure affected by the tumor. Other etiologies include injury to or invasion of a
component of the nervous system, obstruction of a hollow viscus, distention of organ
capsules, distortion or occlusion of blood vessels, or infiltration of adjacent soft tissues

GENERAL PRINCIPLES OF CANCER PAIN MANAGEMENT

Pain and its associated outcomes may be ameliorated by a diverse array of
interventions. Opioid-based pharmacotherapy is a mainstay of treatment for moderate
to severe pain in patients with active cancer. Non pharmacologic strategies may provide
satisfactory pain relief with fewer drug side effects, and/or better outcomes to physical
and psychosocial functioning. Non pharmacologic therapies for cancer pain include
primary treatment for the etiology of the pain, invasive symptomatic therapies and
noninvasive symptomatic therapies, including psychological, rehabilitative and
integrative (complimentary) approaches.

44
 An effective strategy of cancer pain management is based on several broad
principles, including:
1. A detailed assessment of pain should be performed initially. The approach may
be conceptualized as collecting data sufficient to characterized key element of
the pain:
a. A specific cancer pain syndrome.
b. The inferred pathophysiology of the pain.
c. The etiology of cancer pain.
d. The goal of care relative to cancer pain management
e. Other palliative care concern
2. The second principle recognizes that pain may be addressed by disease
modifying antineoplastic therapy and other interventions directed against the
etiology of the pain.
3. A large proportion of patients with pain due to active cancer require symptomatic
treatment.
4. Patients with cancer pain that is generally mild should first be treated with
acetaminophen or a nonsteroidal anti-inflammatory agent (NSAID).
5. Patients with moderate to severe pain and those with chronic pain that is less
intense but does not responds adequately to trial of NSAID alone, should be
treated with an opioid.

CONCLUSION
1. Chronic cancer pain is experienced by 30 to 50 percent of cancer patients.
2. Adequate of pain relief can be achieved in 70 to 90 percent of patients when
well-accepted treatment guidelines for cancer pain are followed.
3. Cancer pain assessment is a complex undertaking. Chronic pain in a cancer
patient usually has a cause related to the disease itself or its treatment.
4. Pain may be ameliorated by a diverse array of interventions. Opioid-based
pharmacotherapy is a mainstay of treatment for moderate to severe pain in
patients with active cancer.
5. Non pharmacologic strategies may provide satisfactory pain relief including
psychological, rehabilitative and integrative (complimentary) approaches.

45
 How to Choose Pain Drugs in Cancer Pain
Amaylia Oehadian

Pain is highly prevalent in the cancer population. Virtually all patients with
malignant disease experience recurrent episodes of acute pain, which may accompany
surgery, invasive procedures, or complications, such as a pathological fracture. In
addition, chronic pain that is severe enough to warrant opioid therapy is experienced by
30 to 50 percent of patients undergoing active antineoplastic therapy and by 75 to 90
percent of those with advanced disease. Opioid therapy is the first-line approach for
moderate or severe chronic cancer pain.
An effective strategy for cancer pain management is predicated on several broad
principles: A detailed assessment of the pain, recognizing that pain may be addressed
by disease-modifying antineoplastic therapy and other interventions directed against the
etiology of the pain, whether or not primary disease-modifying therapy is possible. The
appropriate pain management need consideration of several factors such as pain
intensity , type of pain, pain crises, treatment goal, opioid naïve or tolerant , life
expectancy and drugs side effects
A stepwise and systematic approach to pain control should consider selection of
appropriate drugs and prescribing techniques that can optimize their pharmacological
outcomes .The basic principles of the analgesic ladder apply to cancer patients with
active disease. Patients with cancer pain that is generally mild should first be treated
with acetaminophen or a nonsteroidal anti-inflammatory agent (NSAID) with /without
adjuvant drug. Patients with moderate to severe pain, and those with chronic pain that is
less intense but does not respond adequately to a trial of an NSAID alone, should be
treated with an opioid. The analgesic effect of the drugs typically used to manage
cancer pain is a consequence of agonist action at the mu receptor. Based upon their
effects on the mu receptor, opioids are conventionally divided into pure agonists,
agonist-antagonists, and pure antagonists
Conventionally, patients who are opioid naïve and have pain severe enough to
warrant opioid therapy have been offered one of the opioid-nonopioid combination
products or one of the pure mu agonists at a low initial dose (acetaminophen-
oxycodone, acetaminophen-hydrocodone ). If a patient is given a short-acting drug and
needs several doses per day (or if a bedtime dose does not permit uninterrupted sleep
through the night), a switch to a long-acting formulation is commonly undertaken in an
effort to improve convenience and adherence (morphine, hydromorphone, oxycodone,
oxymorphone, and fentanyl ). Typically, a short-acting supplemental opioid is offered on
an as needed basis for breakthrough pain in conjunction with a fixed scheduled long-
acting drug. Depending on the dose required and other factors, the rescue drug may be
a single entity oral formulation, such as immediate release morphine, oxycodone,

46
hydromorphone, or oxymorphone, or one of the combination products. A typical dose
chosen for rescue is 5 to 15 percent of the basal daily requirement of opioid.
Breakthrough pain also may be targeted with one of the newer rapid onset,
transmucosal fentanyl formulations, which are specifically indicated for cancer-related
breakthrough pain.
The oral and transdermal routes are preferred for chronic treatment of cancer
pain. Short-acting pure mu receptor agonists such as morphine, oxycodone,
hydromorphone, or oxymorphone are the preferred agents for moderate to severe
cancer pain in the patient who is opioid-naïve.
Several guidelines for management of cancer pain in adult patients are European
Society of Medical Oncology (ESMO) Clinical Practice Guidelines 2018 and National
Comprehensive Cancer Network (NCCN) 2019.

47
 Immunotherapy of Cancer: Past, Present and The Next Frontier
Catharina Suharti

Cancer immunotherapy is rapidly advancing and can be considered to be the

“fifth pillar” of cancer therapy included surgery, cytotoxic chemotherapy, radiation
therapy, targeted therapy, and immunotherapy. The definition of immunotherapy is a
treatment of a disease by inducing, enhancing, or suppressing an immune response.
There are five classes of immunotherapy: monoclonal antibodies, vaccine, cytokines,
adoptive T-cell therapy, and checkpoint inhibitors.
In 1891, William Coley followed up on his own independent observation of a
long-term regression of a sarcoma after an erysipelas infection, by injection of heat-
inactivated bacteria (“Coley-toxins) into patients with inoperable cancers. However, the
development of radiation therapy and chemotherapy contributed to the loss of interest in
using this type of therapy to treat cancer. Until 1976, Morales et al established the
effectiveness the bacterium Bacillus Calmette-Guerin (BCG) in the treatment of
superficial bladder cancer.
Immunostimulatory cytokines such interferon-alpha and interleukin-2 were
previously mainstay treatments of metastatic renal-cell carcinoma and melanoma.
Interleukin-2 is still used in some countries in a limited highly restricted patient
population.
Oncolytic viruses are an emerging class of cancer therapeutics. These viruses
are attenuated or genetically modified, that can be injected directly into tumor masses or
administered intravenously. Infection of tumor cells is associated with activation of an
immune response, that in some patients can spread to other, uninjected tumor sites.
The oncolytic virus is a herpes simplex-1 virus named “T-VEC” which approved by FDA
in 2015 to treat advanced melanoma.
Vaccine for cancer which have received approval by the FDA in 2010 is
sipuleucel-T for metastatic castrate-resistant prostate carcinoma. Dendritic cells from
the patient are exposed to prostatic acid phosphatase and granulocyte-macrophage
colony-stimulating factor and reinfused to the patient.
Adoptive cell therapy (ACT) involves the isolation and in-vitro expansion of
tumor-specific-T cells, followed by infusion back into the cancer patient. There are many
forms of ACT, one of these by using T-cells that have been engineered in-vitro to
potently recognize and attack tumors, which technique is known as chimeric antigen
receptor T-cell (CART-cell) therapy. Relapsed and refractory B-cell acute lymphoblastic
leukaemia in paediatric and young adult patients is the first disease to receive approval
from the FDA for CART-cell therapy.
Humanised monoclonal antibodies cause cancer cell death by a variety of
mechanisms, including direct action of antibody (receptor blockade or agonist activity,

48
delivery of a drug or cytotoxic agent: e.g. trastuzumab in HER2 positive breast cancer),
complement dependent cytotoxicity, antibody-dependent cellular cytotoxicity (e.g.
rituximab).
Recognising the importance of immune checkpoints for cancer immune-evasion,
is a rapidly increasing number of immune checkpoint inhibitors. Manipulation of immune
checkpoint signalling has focused on the negative regulatory molecules to date.
Antibodies block interaction of the checkpoint and its binding partner. When checkpoints
are appropriately activated, then the immune system is in balance. When the tumor cell
increase checkpoint signalling (e.g. more CTLA4 or PDL1) then the immune system is
inhibited. Blocking antibodies that block CTLA4 signalling, or PD1/PDL1 signalling can
redress this balance, allowing the immune system to re-establish control of the cancer.
Current examples of immune checkpoint inhibitors are: Pembrolizumab and
Nivolumab (block the binding of PD1 to PDL1 and PDL2), Ipilimumab (block CTLA4, a
negative regulatory checkpoint), Tremelimumab, is another anti CTLA4 antibody that
inhibits the CTLA4 checkpoint protein, and Azetolizumab, Avelumab, Duvalumab are
anti PDL1 antibodies. Combination of checkpoint inhibitors and combination with other
anticancer treatments are being vigorously studied.

49
 Perioperative Anticoagulant Management
Ronald A. Hukom

Patients with anticoagulant who will undergo surgical procedures are in difficult
situation, because interrupting anticoagulation for a procedure transiently will increase
the risk of thromboembolism. On the other hand, surgery and other invasive procedures
have associated bleeding risks, that are increased by the anticoagulant(s) used for
prevention.

The timing of anticoagulant interruption depends on the specific agent the patient
is using. Patients taking a vitamin K antagonist (eg, warfarin), will need several days
until the anticoagulant effect is reduced and then resumed perioperatively. The newer
direct oral anticoagulants (eg, dabigatran, rivaroxaban, apixaban, edoxaban) have
shorter half-lives, making them easier to discontinue and resume rapidly. One problem
is that the direct factor Xa inhibitors lack an approved drug-specific antidote, which
raises concerns about treatment of bleeding.
Some patients on warfarin with an especially high thromboembolic risk (eg,
mechanical heart valve, recent stroke) may benefit from ‘bridging’ with heparin or low
molecular weight (LMW) heparin. Additional considerations may be required for people
with reduced renal and/or hepatic function.

50
 Perioperative VTE prophylaxis
Susanna Hilda Hutajulu

Venous thromboembolism (VTE) is a leading cause of disability and death in

hospitalized patients. It can be categorized as deep venous thrombosis (DVT) and
pulmonary embolism (PE). Despite of it’s killing potential, VTE is known as the most
preventable problem for patients with medical illness. Understanding high risk
population of VTE supports physicians to identify those who may benefit from
prophylaxis. The management of antithrombotic therapy in the peri-operative setting is a
common problem. Balance of haemorrhagic risk with continued treatment and
thrombotic risk when discontinued is a challenging situation in patients undergoing
surgical procedure. Optimal time to start prophylaxis is between 2 hours before and 10
hours after surgery. The risk of PE may persist for weeks afterward, thus treatment
duration needs to be extended. Thromboprophylaxis anticoagulants include vitamin K
antagonist, unfractionated heparin, low molecular weight heparin, factor Xa indirect
inhibitor, and factor IIa inhibitor.

51
 Chemotherapy that can Induce Neutropenia
Ibnu Purwanto

Neutropenia is an abnormally low neutrophil count, defined as absolute

neutrophil count (ANC) less than 1500/ml. Neutropenia is usually acquired due to
medication or post-infections state. Drug-induced neutropenia is a potentially serious
and life-threatening adverse event that may occurs secondary to therapy with a variety
of agents. Cytotoxic chemotherapy can cause a predictable and dose-related decrease
in neutrophil count. Neutropenia secondary to other medications tends to be an
idiosyncratic reaction either as an immune-mediated reaction or because of direct
myeloid cell line damage.
Most cytotoxic chemotherapy exerts its pharmacological activity by causing DNA
damage in either a cell-specific or cell-nonspecific manner. By damaging the DNA of
malignant cells, chemotherapy is able to produce killer malignant cells. Many
chemotherapy agents are causing bone marrow suppression that resulting in
neutropenia, which leads to increased risk of infection. Patients with mild neutropenia
rarely develop complications, but the risk of infection increases as the ANC drops below
500/µL. Infectious complications have been blamed for 75% of chemotherapy-related
mortality . The risk of infection increases with the depth and duration of neutropenia,
with the greatest risk occurring in patients who experience profound, prolonged
neutropenia after chemotherapy, Neutropenia, the most serious hematologic toxicity, is
associated with the risk of life-threatening febrile neutropenia infections, prolonged
hospitalization thus increasing the costs for hospital stay, as well as chemotherapy dose
reductions and delays that may compromise treatment outcomes.
Several meta-analyses indicate that primary prophylaxis with GCSF (i.e. G-CSF
administered immediately after cycle 1 of chemotherapy ) reduces the risk of Febrile
Neutropenia (FN) by at least 50% in patients with solid tumors without significantly
affecting tumor response or overall survival, so it makes sense to recommend primary
prophylaxis for the patients at risk rather than to systematically resort to secondary
prophylaxis. Secondary prophylaxis. granulocyte colony-stimulating Factor (G-CSF)
given for a course of chemotherapy following a course with Febrile Neutropenia is
indicated if dose reduction below threshold or delay of chemotherapy is not desirable
such as treatment with a curative intent.
The incidences of Chemotherapy-induced Neutropenia (CIN) and its
complications, such as fever, infections, and chemotherapy doses alterations, vary by
the type of malignancy. One large prospective registry reported CIN rates of 15% to
65% in patients with major types cancer: breast cancer, colon cancer, lymphoma, lung
cancer, and ovary cancer.

52
 Pedoman Penanganan Demam Neutropenia dalam Praktik Klinis
Ugreseno

Demam neutropenia/Febrile Neutropenia adalah komplikasi serius dari kemoterapi

kanker yang dapat menyebabkan tertundanya terapi dan perlunya pengurangan dosis
kemoterapi, sehingga berdampak pada efikasi terapi. Sekitar 1% pasien kanker yang mendapat
kemoterapi mengalami FN, yang berkontribusi terhadap morbiditas dan mortalitas, Neutropenia
ditandai dengan adanya reduksi neutrofil dibawah angka normal, umumnya terjadi dalam 7
hingga 12 hari paska kemoterapi kanker. Pada kondisi sebagai mengkonfirmasi jumlah neutrofil
absolut (absolute neutrophil count-ANC) yang kurang dari 500 sel per mikroliter paska
kemoterapi sitotoksik, atau penurunan ANC hingga kurang dari 500 sel per mikroliter dalam 48
jam. Sedangkan Febrile Neutropenia didefinisikan sebagai temperatur oral lebih dari 101°F
yang ditemukan pada satu kali pemeriksaan atau temperatur oral setidaknya 100,4°F yang
bertahan lebih dari 1 jam atau pada lebih dari 2 kali pengukuran dalam rentang waktu periode 2
jam.1,4. Pasien Febrile Neutropenia harus menjalani penilaian risiko awal terjadinya komplikasi
serius terhadap infeksi, untuk menentukan terapi yang sesuai. Penilaian stratifikasi risiko
berdasarkan Indeks dari The Multinational Association of Supportive Care in Cancer (MASCC)
menjadi risiko tinggi (Indeks Risiko MASCC >21a) dan rendah (Indeks Risiko MASCC ≤21a).
Intensitas kemoterapi merupakan salah satu faktor yang menentukan risiko seorang pasien
timbul Febrile Neutropenia. Sedangkan tatalaksana pasien Febrile Neutropenia sesuai dengan
konsensus dari IDSA, NCCN, dan ESMO.

53
 The Role of Internist in Cancer
Ugroseno

Dengan kemampuannya dalam melakukan suatu diagnosis bidang hematologi

endokrinologi, dan fisiologi jantung, pernapasan, gastroenterologis, dan neurologis,
maka kontribusi dokter penyakit dalam terhadap perawatan total pasien kanker semakin
penting. Sebenarnya, tanggung jawab ahli penyakit dalam bisa pada semua fase
kanker, yaitu dari diagnosis utama sampai kestadium terminal. Peran utama seorang
dokter penyakit dalam pada awal perawatan kanker adalah menggunakan semua teknik
yang tersedia untuk deteksi dini kanker. seorang ahli penyakit Dalam tidak hanya
mengetahui teknik-teknik baru untuk deteksi ini tetapi juga mempraktikkannya. Namun
saat ini seorang internist telah meninggalkan pemeriksaan serviks dan vagina,
pemeriksaan laring dengan laringoskopi , proktoskop, pemeriksaan darah samar/ Tes
guaiac. Pemeriksaan payudara wanita bukan hanya organ yang disingkirkan untuk
memeriksa jantung atau paru-paru agar lebih jelas. Peran kedua dari internis adalah
membuat keputusan terhadap kanker yang ditemukannya. Seorang internist harus
mengetahui keterampilan ahli bedah dan radioterapi di komunitasnya sehingga ia dapat
memberikan pelayan yang terbaik kepada pasiennya.
Partisipasi aktif internis dalam perawatan segera pasca operasi pasien sering
mengurangi morbiditas dan kadang-kadang mencegah kematian. Tindak lanjut pasca
operasi pasien adalah tanggung jawab dokter penyakit dalam agar tindak lanjut dapat
dilakukan, ahli penyakit dalam harus mengetahui riwayat penyakit yang pernah dialami
biasa terjadi sehingga dapat dapat dicegah komplikasi yang lebih berat.

54
 Chemotherapy Preference in Metastatic Breast Cancer
Heri Fadjari

Advanced Breast Cancer (ABC) comprises both locally advanced breast cancer
(LABC) and metastatic breast cancer (MBC). Although treatable, MBC remains virtually
an incurable disease with a median overall survival (OS) of 3- years and a 5-year
survival about 25%.
The choice of therapy for patients with MBC typically depends on the risks and
benefits of each treatment option, the disease burden and subtype, prior therapeutic
exposure, availability, and the patient and physician preference. Both combination and
sequential single agent chemotherapy are reasonable options. Most available
guidelines recommend sequential monotherapy as the preferred choice for ABC. In
patients pre-treated (in the adjuvant and/or metastatic setting) with an anthracycline and
a taxane, single-agent eribulin, capecitabine, or vinorelbine are the preferred choices.
In the EMBRACE trial, with OS as primary endpoint, eribulin therapy was
demonstrated to increase median OS with respect to treatment physician choice (13.1
vs 10.6 months, p=0.041), the result was confirmed in an updated analysis (13.2 vs 10.5
months, respectively). Recently, pooled data from two trials (STUDY 301 and 305)
showed to be associated with improved OS in the overall patient population when
compared with the control arm (15.0 vs 12.6 months, HR 0.85; 95% CI 0.76 to 0.94;
p<0.01). Overall incidence of adverse events (AEs) and serious AEs were similar in
both treatment groups, the most common toxicities being asthenia/fatigue, alopecia and
neutropenia.
Data from the real-world practice in heavily pre-treated population, observed
similar outcomes to those reported in the pivotal trials. Of note, the benefit was superior
in patients who received fewer than four previous chemotherapy regimens.
Although still on debate, the specific biochemical effects of eribulin may underlie
its unique effects on antiproliferative effects, induces re-oxygenation, angiogenesis,
vascular remodelling, and epidermal to mesenchymal transformation.
Based on EMBRACE trial, STUDY 301, STUDY 305, and real-world data (RWD),
eribulin mesylate offers clinical activity in advanced breast cancer through improved
overall survival, its favourable side-effect profile and convenience of preparation and
administration.

55
 Hodgkin Lymphoma and its Treatment
Muhammad Darwin Prenggono

HL is a cancer of the lymphatic system that commonly occurs in the lymph nodes
of the neck. Almost all classical Hodgkin Lymphoma (cHL) immunohistochemistry
expressing CD30 positivity (98,4%). There are estimated 1.047 cases/year in Indonesia
according to Globocan 2018. HL is histopathologically defined by the presence of
CD30-positive Reed-Sternberg cells and CD30 become an important biomarker in HL.
There are high unmet needs in patients with Relapsed/Refractory HL: up to 20%
of patients will relapse after frontline therapy; current multi-agent chemotherapy
regimens are associated with severe toxicities and side effects; limited treatment
options for those that are ineligible ASCT due to frailty and level of comorbidities. These
require regimens that highly effective with manageable safety profile for
relapsed/refractory HL and for ineligible ASCT patients.
Brentuximab vedotin is the Novel Targeted Therapy-Antibody Drug Conjugate
(ADC) for CD30+ Lymphomas. Phase II pivotal study with follow up to 5-years shown
that Brentuximab vedotin demonstrated the efficacy in 75% ORR and tumour reduction
in 94% patients, with median PFS and OS not yet reached in patients who achieved
CR. Real-World Evidence data also showed the efficacy of Brentuximab vedotin in
Relapsed/Refractory HL patients who are ineligible ASCT with 74.3% ORR, median
PFS and OS for all type of response patients: 15.1 and 17.8 months respectively.

56
 Various Type of Cutaneous Lymphoma: Diagnosis and Treatment
Catharina Suharti

Primary cutaneous lymphomas (PCLs) are defined as non-Hodgkin lymphomas

(NHL) that present in the skin with no evidence of extracutaneous disease at the time of
diagnosis. PCLs are the second most common group of extra nodal NHL, which an
estimated annual incidence of 1/100.000 in western countries. There are two distinct
types of PCLs, these are cutaneous T cell lymphoma (CTCL) which constitutes 75%-
80%, with mycosis fungoides (MF) as the most common type, and cutaneous B cell
lymphoma (CBCL) which constitutes 20-25% of all PCLs.
The pathogenesis of CTCL is complex. Slow progression of MF suggests that
neoplastic T cells may not initially have autonomous proliferative capacity. The loss of
immunological surveillance, which allows for the clonal proliferation of mature
lymphocytes in the skin, may be attributed to the changes of micro-environment.
The diagnosis and classification of PCLs are based on combination of clinical,
histological, immunophenotypical and genetic data. Adequate staging should be carried
out to exclude the presence of extracutaneous disease. Recommendations for staging
evaluation in patients with MF/Sezary syndrome (SS) include complete physical
examination, skin biopsy, blood tests, radiological tests, and lymph node biopsy.
The choice of treatment depends on the type of PCL and the stage of disease.
Recommendations of treatment are largely based on retrospective cohort studies and
expert opinions, because controlled clinical trial in PCLs are almost non-existence due
to their heterogenicity and rarity of the disease.
Patients with MF stage IA-IIA should be treated with skin directed therapies
(SDT) including topical steroids, PUVA, nb-UVB, or mechlorethamine. Patients with MF
stage IIB, additional low dose local radiotherapy may be sufficed. For patients with more
extensive infiltrated plaques and tumors, or patients refractory to SDT, a combination of
PUVA and IFNα or PUVA and retinoids (including bexarotene), a combination of IFNα
and retinoids or TSEBT (total skin electron beam therapy) can be considered.
In patients with advanced or refractory disease, gemcitabine or liposomal
doxorubicin may be considered, but responses are generally short-lived. Multi-agent
chemotherapy is only indicated in MF patients with effaced lymph nodes or visceral
involvement (stage IV), or in patients with widespread tumor stage MF, which cannot be
controlled with skin-targeted and immunomodulating therapies, or who fail single agent
chemotherapy. In relatively young patients with refractory, progressive MF, alloSCT
should be considered.
Patients with SS, systemic treatment is required in combination with SDT.
Extracorporeal photopheresis, either alone or in combination with IFNα, retinoids,
TSEBT and PUVA, has been suggested as treatment of choice in SS and erythrodermic

57
MF. In relatively young patients with refractory, progressive MF, alloSCT should be
considered. Low-dose alemtuzumab, single agent chemotherapy, multi-agent
chemotherapy, and alloSCT, are recommended as second-line treatment of SS.
Patients with Primary cutaneous CD30+ lymphoproliferative disorders (cutaneous
anaplastic large cell lymphoma/C-ALCL and lymphomatoid papulosis/LyP), low-dose
oral MTX and PUVA are the most effective therapies for reducing the number of skin
lesions. Local radiotherapy is the first-choice treatment in patients with C-ALCL
presenting with solitary or localised skin lesions. C-ALCL patients presenting with
multifocal skin lesions can best be treated with low-dose MTX, as in LyP, or RT in the
case of only a few lesions. Brentuximab vedotin should be considered in C-ALCL with
multifocal skin lesions refractory to conventional therapies and patients developing
extracutaneous disease. Multi-agent chemotherapy is only indicated in patients
presenting with or developing extracutaneous disease and in rare patients with rapidly
progressive skin disease.
Primary cutaneous extranodal NK/T cell lymphoma, nasal type is an aggressive
lymphoma. Treatment with L-asparaginase containing chemotherapy combined with RT
for patients with localised disease is the preferred mode of treatment.
Patients with cutaneous B cell lymphoma, e.g. primary cutaneous marginal zone
lymphoma (PCMZL) and primary cutaneous follicle centre lymphoma (PCFCL),
treatment with RT is recommended (24-30Gy). For the more aggressive primary
cutaneous diffuse large B-cell lymphoma leg type (PCLBCL-LT), systemic therapy with
R-CHOP combined with RT (36-40Gy) is recommended for localized disease. If the
patient cannot tolerate with multi-agent chemotherapy, RT 40Gy as monotherapy is
recommended.
Brentuximab vedotin is an anti-CD30 antibody-drug conjugate that has received
approval for the treatment of relapsed or refractory Hodgkin lymphoma and systemic
anaplastic large-cell lymphoma. The ALCANZA study is an international, open label,
randomised, phase 3, multicentre study of brentuximab vedotin versus conventional
therapy for previously treated patients with CD-30 positive cutaneous T-cell lymphoma.
The results of the study indicated, a significant improvement in objective response
lasting at least 4 months was seen with brentuximab vedotin versus physician choice of
methotrexate or bexarotene.

58
 Early Detection and Surgical Management in Colorectal Cancer
Wifanto Saditya

Colorectal cancer (CRC) is the second most cancer in male and the third cancer
in females. Trend incidence arise in age of 40-50 years. Overall survival was 65%, if
progression to metastatic disease drop until 10%. Median survival of advance cases
only 24-30 months. Diagnosis and early detection were important to increase survival.
Many diagnostic tools in CRC including initial evaluation (colonoscopy, biopsy,
CEA) and evaluation of metastatic spreading (CT scan, MRI or PET scan). Early
detection is the key in prevention and management to have a better outcome.
Surgical management in CRC depend on the staged of disease. Primary colon
cancers without systemic spreading is complete mesocolic excision (CME). Colonic
segmental resection is performed according to the site of the tumour; and it is always
indicated in absence of metastases. In the emergency case (presenting symptoms of
obstruction, perforation and bleeding) the resection of segmental colectomy with or
without fecal diversion. Approach of surgery can be open surgery or laparoscopy.
Option of minimally invasive surgery is a safe and valid alternative surgery in the
treatment of colorectal cancer.
Liver is the most site of metastasis. Hepatectomy in metastasis CRC has
increase survival in many cases. Resectability of the liver, medical fitness and adequate
functional of the liver should be evaluated before surgery. The strategies to increase
resectability are conversion therapy with chemotherapy, portal vein embolization, two
stages hepatectomy and some special techniques. Multidiscipline teams in CRC are
fundamental in management and improving outcomes of the patients.

59
 Chemotherapy in Colorectal Cancer
Yenny Dian Andayani

Colorectal carcinoma (CRC) is the 2nd most common malignancy after lung
carcinoma. Approximately 1.2 billion new cases found annually in global population with
mortality 600,000 deaths every year. In 2014, in the USA, there were 136,830 new
cases with 50,310 deaths. CRC incidence decreased within the last 25 years due to
improvement in screening and detection and also improvement in management.
Prognosis of metastatic CRC is also improving, contributed by the new and efficient
systemic therapy, especially RAS and BRAF-based therapy. Current research
discovered the increasing of overall survival (OS) for CRC with metastasis to 30
months, compared to the last 20 years.
CRC treatment modalities are surgery, chemotherapy, radiotherapy and
biological therapy. Guidelines recommends chemotherapy based on the AJCC stage.
NCCN recommends multiple agents used to optimized adjuvant effect of chemotherapy.
Stage I CRC doesn’t require systemic therapy; however, in patients with high risk of
poor differentiated and lymphovascular invasion treatment option is adjuvant
chemotherapy and radiotherapy. High risk and moderate risk of stage II CRC are
recommended with FOLFOX regiment. Stage III systemic therapy based on the risk
status; low risk’s regiment of choice is 3 months of CAPEOX and for the high risk 3-6
months of CAPEOX or 6 months of FOLFOX.
Optimal strategy for metastatic CRC is a multidiscipline approach in order to
improve the quality of life. In metastatic CRC to lung and liver, we give 6 months
systemic therapy after resection or 3 months preoperative systemic therapy and 3
months post resection chemotherapy. Treatment regiments are double cytotoxic
(FOLFOX/FOLFIRI) or triple cytotoxic (FORFOXIRI) plus anti-EGFR or anti-VEGFR,
depends on the RAS-status. In inoperable metastatic CRC with symptoms related to the
cancer, palliative chemotherapy or double cytotoxic chemotherapy plus monoclonal
antibody can be given. While in cases with symptoms not related with cancer, double or
single cytotoxic with/without monoclonal antibody can be given to increase life
expectancy and prevent the progression.
Rectal carcinoma management is different with CRC because of the anatomical
aspect and relapse frequency. Neoadjuvant radiotherapy decreases relapse incidence,
improve prognosis and increase life expectancy. Preoperative radiotherapy combined
with systemic chemotherapy (such as 5FU or capecitabine) give the same result.
Combination with oxaliplatin and irinotecan is still in phase II and III of clinical trials.
Post-operative adjuvant chemotherapy regiment recommended is capecitabine, 5-
FU/LV, FOLFOX.

60
 Early Detection and Treatment of Breast Cancer
Eko A. Pangarsa

Breast cancer is the most commonly diagnosed cancer in women and is the
second most common cause of cancer death in women; this is true for advanced and
metastasis breast cancer. Increased public awareness and screening programs have
shifted the stage at which women received the diagnosed in the earlier stage. By virtue
of early detection via mammogram, the majority of breast cancers in developed parts of
world are diagnosed in the early stage of the disease. About 75% of newly diagnosed
cases are classified as early breast cancer. Demographic features in Indonesia may
show a different pattern with regard to the number of patients with early breast cancer.
In general, early stage breast cancers can be completely resected by surgery giving its
considerably better prognosis than advanced diseases.
Early-stage breast cancer is categorized as clinical stage I or II or IIIA. Ductal
carcinoma in situ (DCIS), which is stage 0, is also often included in term of early breast
cancer. Patients with DCIS may be considered for treatment with surgical excision only
or offered for a mastectomy if high risk factors of recurrence are exist.
Patients with early breast cancer may undergo primary breast surgery
(lumpectomy or mastectomy) and regional lymph node excision with or without radiation
therapy with an ultimate goal of cure.4 Adjuvant systemic therapy may be offered,
following definitive local treatment, and is based on the characteristics of the clinical
features and molecular biology, such as age, menopausal status, tumor size, grade,
number of involved lymph nodes and molecular biology phenotype such as the status of
estrogen(ER) and progesterone receptors (PR), expression of the HER2 receptors and
Ki-67.
Patients with estrogen receptor (ER) and progesterone receptor (PR) –positive
breast cancer may benefit from the use of hormone therapy. Adjuvant chemotherapy
may or may not be added to hormone therapy or targeted therapy, in patients who have
breast cancer with ‘high risk’ factors for recurrence. Patients with triple-negative breast
cancer (TNBC) which is ER, PR and HER2 negative, may be offered chemotherapy and
radiotherapy. Patients with HER2-positive breast cancer can benefit from treatment with
a HER2 targeted drug such as trastuzumab, with or without pertuzumab. If the patient’s
tumor is > 1 cm in diameter. However, the treatment of small breast cancers that
measure ≤ 1 cm in diameter is controversial, with any benefit remaining unproven.
Breast cancer patients who have completed treatment should undergo regular
clinical follow-up to exclude symptoms and signs that may indicate recurrence or
metastasis. Moreover, a better understanding of the underlying biology of the
heterogenic nature of breast cancer has already enabled the development of targeted
therapy and profiling tools to reduce the disease recurrence and mortality rate caused

61
by breast cancers. However, there are still many questions to be answered, and
patients to be saved. The most critical point for best prognosis is to identify early-stage
cancer cells. Here we review the most up to date conventional and developing
treatments for different subtypes of early stage breast cancer.

62
 Terapi Sistemik pada Kanker Paru
(Fokus pada Kanker Paru Bukan Sel Kecil Stadium Lanjut)
Johan Kurnianda

Kanker paru merupakan kanker yang paling sering ditemukan di dunia. Jumlah
kasus baru kanker paru yang ditemukan didunia pada tahun 2018 adalah lebih dari 2
juta kasus dan merupakan 11,6% dari seluruh kasus baru. Selain itu di tahun yang
sama, kanker paru juga merupakan kanker penyebab kematian tersering dengan
jumlah kematian sekitar 1,76 juta (18,4% dari seluruh kematian akibat kanker). Sekitar
80% kanker paru adalah jenis kanker paru bukan sel kecil (KPBSK) dan sekitar 65%
KPBSK terdiagnosis pada stadium lanjut atau metastasis. Hingga tahun 2000an
prognosis kanker paru stadium lanjut sangat buruk, dengan median kesintasan 8-10
bulan dan harapan hidup 5 tahun kurang dari 5%.
Sesudah tahun 2000an manajemen KPBSK stadium lanjut berkembang pesat
dan menghasilkan perpanjangan harapan hidup yang signifikan. Perkembangan positif
ini dicapai, terutama, karena terjadi perbaikan dalam penegakan diagnosis melalui
teknik pencitraan, patologi dan molekular yang lebih akurat serta kemajuan di bidang
terapi, terutama, dengan ditemukannya terapi target dan imun sehingga memungkinkan
untuk melakukan personalisasi terapi dengan lebih tepat. Saat ini dengan berbagai
kemajuan tersebut, harapan hidup 5 tahun KPBSK stadium lanjut subtipe epidermal
growth factor receptor (EGFR) mutasi positif mencapai lebih dari 20% dan penderita
dengan subtipe ekspresi tinggi programmed death ligand-1 (PDL-1) mencapai 25%.
Terdapat beberapa syarat yang diperlukan untuk mencapai luaran optimal dari
KPBSK stadium lanjut yaitu: pertama, manajemen medik multi disiplin; kedua, diagnosis
yang akurat secara pencitraan, histopatologi, molekular dan genomik; ketiga, terapi
sistemik yang bersifat personal baik dengan kemoterapi, terapi target dan imunoterapi;
serta keempat intervensi terapi paliatif dan suportif yang paripurna sedini mungkin.
Pada presentasi akan dibicarakan lebih detil manajemen terapi sistemik KPBSK
stadium lanjut berdasarkan studi-studi dan panduan klinik mutakhir.

63
 Early Detection and Surgery in Cervical Cancer
M Yusuf

Cervical cancer is the fourth most frequently diagnosed cancer and the fourth
leading cause of cancer death in women, 570,000 cases and 311,000 deaths in 2018
worldwide within an estimated. Cervical cancer ranks second in incidence and mortality
behind breast cancer in lower HDI settings. Around 32,469 new cervical cancer cases
are diagnosed annually in Indonesia (estimates for 2018). Cervical cancer ranks as the
2nd leading cause of female cancer in Indonesia, and the 2nd most common female
cancer in women aged 15 to 44 years in Indonesia.
Human papillomavirus (HPV) infection is now a well-established cause of cervical
cancer, The International Agency for Research on Cancer has designated as
carcinogenic 12 HPV types: HPV-16, -18, -31, -33, -35, -39, -45, -51, -52, -56, -58, and -
59. HPV-16 is the most oncogenic, accounting for more than 50% of cervical cancers.
HPV-18 is found in 10% of cervical cancers and plays a particularly important role in
adenocarcinogenesis. Types 31, 33, and 45 each account for around 5% of cancers.
The other types are less oncogenic but have been reported in large typing studies of
cervical cancers. HPV-18 and related HPV-45 are linked to cancers found at a younger
age.
Screening has relied on Papanicolaou cytology testing followed by colposcopic
assessment of women with Pap abnormalities, directed biopsy of the worst colposcopic lesion,
and treatment of biopsy proven high-grade lesions. Papanicolaou testing is relatively insensitive:
A single Pap test may be negative in almost half of women with high-grade CIN.
Cytology-based screening has several weaknesses. Most fundamentally, the process of
screening, triage, and treatment is cumbersome, and noncompliance at any point renders it
ineffective. Cytology results are reported in ways that can be confusing, and efficient, effective
management may require integration of current results with prior abnormalities.
The most cited guidelines were released in 2012, guidelines by the US
Preventive Services Task Force (USPSTF) and a consensus conference sponsored the
American Cancer Society (ACS), the American Society for Colposcopy and Cervical
Pathology (ASCCP), and the American Society for Clinical Pathology (ASCP).
The two guidelines were developed from a common evidence assessment and
reached similar conclusions. In both sets, screening is recommended to begin at 21
years of age, continuing at 3-year intervals until 65 years of age, when screening should
stop if the patient is adequately screened and has no history or prior high grade CIN.
Screening also should stop at the time of total hysterectomy for indications other than
high-grade CIN or cervical cancer. The ACS/ASCCP/ASCP guidelines contain a
preference for screen- ing using combination cytology and HPV testing beginning at 30

64
years of age; the USPSTF considered co-testing between 30 and 65 years of age to be
acceptable but did not find evidence sufficiently compelling to prefer it.
In 2014, the Food and Drug Administration approved HPV testing as a primary
screening test for cervical cancer. Approval was granted only for the cobas HPV test
(Roche). At a consensus meeting sponsored by the Society of Gynecologic Oncologists
and ASCCP, this consensus meeting delegates developed guidelines to inform
clinicians and women at risk on strategies to incorporate primary screening into
practice.

Radical hysterectomy is the procedure involves removal of the uterus, the upper
25% of the vagina, the entire uterosacral and uterovesical ligaments and all of the
parametrium on each side, along with pelvic node dissection encompassing the four
major pelvic lymph node chains: ureteral, obturator, hypogastric, and iliac. The
procedure is complex because the tissues removed are in close proximity to many vital
structures such as the bowel, bladder, ureters and great vessels of the pelvis. The
object of the dissection is to preserve the bladder, rectum, and ureters without injury but
to remove as much of the remaining tissue of the pelvis as is feasible.

65
Rutledge and colleagues devised a system of rating radicality of hysterectomy
1. Class I hysterectomy
2. Class II extended hysterectomy is described as a modified radical hysterectomy.
3. Class III procedure is a wide radical excision of the parametrial and paravaginal
tissues in addition to the removal of the pelvic lymphatic tissue.
4. Class IV radical hysterectomy is complete removal of all periureteral tissue; a
more extensive excision of the paravaginal tissues; and, when indicated, excision
of the internal iliac vessels along an involved portion of the medial pelvic wall
tissue. This differs from the class III operation in three respects
5. class V hysterectomy is to remove a central recurrent cancer involving portions of
the distal ureter or bladder.

Complications of the procedure:

1. Vesicovaginal fistula
2. Ureterovaginal fistula
3. Severe bladder atony
4. Bowel obstruction
5. Lymphocyst
6. Thrombophlebitis
7. Pulmonary embolus

66
 Immune Thrombocytopenia
Heri Fadjari

Primary immune thrombocytopenia (ITP) is an autoimmune disorder defined

currently as isolated thrombocytopenia (peripheral blood platelet count < 100.000/mm3)
in the absence of conditions known to cause thrombocytopenia.
Traditionally ITP is regarded as an antibody-mediated disease in which the
patient’s immune system reacts with a platelet autoantigen(s) resulting in
thrombocytopenia due to autoantibody-mediated platelet destruction and/or suppression
of platelet production.
Childhood ITP differs from adult ITP in pathogenesis, diagnosis, management,
and prognosis. However, the pathogenesis of ITP has proven complex with diverse pre-
existing challenges to the immune system in the form of infection, genetic
predisposition, underlying autoimmune repertoire, inhibition of platelet production,
perturbations of cell mediated affector and effector pathways, sequestered harbours
within lymphoid organs, and responsiveness to intervention.
Recent insights into the pathogenic mechanisms underlying ITP and the advent
of rituximab and thrombopoietin receptor agonists (TRAs) have changed the paradigm
of ITP treatment. Still, a challenging minority of patients remains refractory to multiple
lines of treatment and develops chronic thrombocytopenia, haemorrhage, poor health-
related quality of life, and high mortality.
This article addresses current understanding of immune dysregulation in adult
ITP only.

67
 Epidemiology and Diagnostic in Gastric Cancer
Murdani Abdullah

Gastric cancer has been one of the world’s major cancers and remains one of
the major causes of malignant disease morbidity and mortality. Gastric cancer is the
fourth most common cancer diagnosis worldwide in men following lung, prostate, and
colorectal. Approximately 8% of total cases and 10% of annual cancer deaths worldwide
are attributed to gastric cancer. More than 70% of gastric cancer occurs in developing
countries. Currently, three East Asia countries (China, Japan, and Korea) account for
60% of total cases. Even though the highest incidence of gastric cancer has been
reported in the Asia-Pacific region, some studies have shown a decrease in gastric
cancer incidence in several countries. The most frequent gastric cancer type is
adenocarcinoma, which accounts for 90-95% of adenocarcinoma cases, and the
remaining 5-10% are carcinoma of nonepithelial origin.
How about epidemiology of gastric cancer in Indonesia? An epidemiology study
conducted in Indonesia from 2007-2011 showed that 78,4% of gastric cancer patients
are men and 82,4% gastric cancer patients were in the age between 30-60 years. In
Indonesia, the mean age at diagnosis of gastric cancer was decreased from 52,02 in
2002-2006 to 50,43 in 2007-2011. Similar with worldwide data, the histopathology of
gastric cancer in Indonesia showed that 84,3% of gastric cancers are adenocarcinoma.
Gastric cancer is a multifactorial disease, and both environmental and genetic
factors have a role in its etiology. Some of the risk factors, such as age and sex are not
modifiable, whereas others such as smoking, and H. pylori infection potentially are. A
study conducted in 6 cities in Indonesia from 2014 – 2015 showed that 22.1% of gastric
cancer cases were H. pylori positive. Identification of risk factors in each carcinogenic
step and appropriate management of these risk factors could reduce the incidence of
gastric cancer.
Diagnosis of gastric cancer should be made from a gastroscopic or surgical
biopsy reviewed by an experienced pathologist. Initial staging and risk assessment
should include physical examination, blood count and differential, liver and renal
function tests, endoscopy and contrast-enhanced computed tomography (CT) scan of
the thorax, abdomen and pelvis. Early diagnosis of gastric cancer remains challenging
because the existing circulating biomarkers for gastric cancer diagnosis and prognosis
display low sensitivity and specificity. There is a huge need for less invasive or non-
invasive tests with highly specific biomarkers in gastric cancer.
In recent years, many studies have detected abnormal expression forms of
microRNAs (miRNAs). Some specific miRNAs can regulate many important tumor-
related genes involved in tumor progression to inhibit or promote invasion and
metastasis of gastric cancer cells. It may become valuable diagnostic markers and

68
therapeutic targets for gastric cancer. Until now, there was a significant difference in
expression levels among 38 kinds of miRNAs in gastric cancer tissue. A study showed
that combination of miR-627, miR-629, and miR-652 obtained the highest area under
curve with a cut-off at 0,373, with a sensitivity of 86,7% and a specificity of 85,5%.
Nowadays, it is also recommended that all patients with gastric cancer be tested
for HER2 to inform treatment decision-making, preferably using immunohistochemistry
(IHC) as the initial testing modality. The frequency of HER2 overexpression in gastric
and gastroesophageal cancer ranges from 4,4% to 53,4% with a mean of 17,9%. This
recommendation is based on the ToGA (Trastuzumab for Gastric Cancer) findings that
the subgroup of patients with higher HER2 protein expression gained the greatest
survival benefit. Gastric cancer patients with HER2 positive tumors experienced clinical
benefit from chemotherapy plus trastuzumab (a HER2-targeting antibody) relative to
chemotherapy alone.
Gastric cancer remains a major diagnostic and therapeutic challenge. Despite
the declining incidence, gastric cancer remains a disease with high mortality rate with
nearly three quarter of a million people dying annually. Therefore, early diagnosis of
gastric cancer is needed.

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 Kemoterapi pada Kanker Lambung: Sebuah Pendekatan Paliatif
Aru W. Sudoyo

Kanker lambung merupakan keganasan dengan angka kematian yang tinggi

terutama di Asia Timur (Cina, Korea dan Jepang). Di Indonesia, jenis kanker ini berada
di luar “10 besar” (GLOBOCAN 2018) bahkan termasuk jarang, namun angka kematian
amat tinggi karena kebanyakan penderita datang dalam keadaan lanjut dengan tumor
yang tidak dapat direseksi.
Pembedahan merupakan modalitas utama dan bisa bersifat kuratif bila penyakit
ditemukan dalam stadium cukup dini dan dilakukan di sentra peayanan medik yang
berpengalaman serta mempunyai jam terbang tinggi dalam mengobatu kanker ini.
Modalitas berikut adalah terapi sistemik yang dikenal sebagai kemoterapi dan / atau
kemoradioterapi.
Kemoterapi sitostatika / antikanker sudah digunakan sebagai terapi ajuvan pada
ca gaster sejak era tahun-tahun 60an. Kemoterapi “single agent” digunakan di tahun
70an dengan laju respons sebesar 20 persen menggunakan obat-obatan seperti 5-
fluorourasil (5-FU), mitomisin, BCNU dan doxorubisin. Kemudian muncul kombinasi
seperti 5-FU, antrasiklin dan cisplatin. Di Amerika dikembangkan kombinasi ECP
(etosposide, Cyclophosphamid dan Cisplatin) dan pemakaian Taxane; tingginya kanker
lambung di Asia Timur (Cina, Korea dan Jepang) membawa pada pengembangan
pengentahuan dan terapi yang berbeda di mana digunakan regimen mirip dengan
kanker usus besar yaitu FOLFOX (5-FU, Leucovorin, oxaliplatin) berdasarkan
perbedaan pada karakter tumor serta respons yang mungkin didasarkan pada etnisitas.
Pada pertemuan Kanker Gastrointestinal Sedunia (WCGC ESMO) 2019 di Barcelona
baru-baru ini dibahas tentang regimen FLOT yaitu FOLFOX yang mendapat tambahan
Taxane.
Pasien kanker lambung pada umunya sudah berusia di atas setengah umur,
datang dalam stadium yang sudh lanjut dan sudah ada kormobiditas. Hal ini lebih
terasa di Indonesia, di mana akibat jarangnya kanker ini maka gejala sering tidak dirasa
serta pemeriksaan lambung secara endoskopi bukan menjadi bagian dari pemeriksaan
fisik (medical check up) rutin. Situasi itu membuat pendekatan klinik secara multidisplin
(multidisciplinary treatment planning) suatu keharusan. Keanggotaan “inti” sebuah tim
MDT (multidisciplinary team) harus terdiri dari ahli bedah, onkologi medik, radioterapi ,
patologi. Sebaiknya juga ada internist umum untuk menanggulangi keadaan-keadaan
penyerta baik sebelum diagnosis maupun sesudah pengobatan.
Pengalaman penulis adalah bahwa sebagian besar kanker lambung datang
sudah dalam keadaan lanjut sehingga kemoterapi sudah bersifat paliatif. Keadaan ini
penting untuk diketahui spesialis penyakit dalam subspesialis lain maupun umum –
dengan pengetahuan mengenai efek sitostastik terhadap tubuh pasien – karena

70
sasaran bukan lagi kuratif dan pasien sudah “dilemahkan” oleh berbagai penyakit
penyerta. Protocol kemoterapi dapat dilihat di berbagai panduan (NCCN, ESMO)
namun tidak dapat menggantikan kerja tim yang baik serta pengetahuan penanganan
komplikasi-komplikasi yang terjadi.

71
 Terapi Target pada Kanker Lambung Stadium Lanjut
Johan Kurnianda

Data epidemiologi menunjukkan kanker lambung masih merupakan problem

besar kesehatan di dunia. Data Globocan (badan WHO yang khusus menangani
epidemiologi kanker) 2018, menunjukkan kanker lambung merupakan kanker tersering
kelima sesudah kanker paru, payudara, kolorektal dan prostat; dengan insidensi 5,7%
serta merupakan kanker penyebab kematian ketiga terbanyak sesudah kanker paru dan
kolorektal dengan angka kejadian 8,2%.
Ada beberapa penyebab mengapa kanker lambung masih menjadi salah satu
kanker yang paling mematikan. Pertama, sebagian besar kanker lambung terdiagnosis
pada stadium lanjut. Studi epidemiologi menunjukkan, meskipun di negara-negara
maju, hanya 26% kasus kanker lambung yang terdiagonosis pada stadium awal (T1N0)
dan kanker lambung dengan stadium > T1N0 mempunyai prognosis yang buruk.
Sebagai akibatnya harapan hidup 5 tahun penyakit ini di negara-negara maju, seperti di
Eropa, hanya bervariasi dari 10%-30%. Kedua, kanker lambung merupakan salah satu
kanker dengan index komorbiditas yang tinggi. Suatu studi yang dilakukan di Amerika
Serikat pada lebih dari 12.000 penderita kanker lambung ditemukan ada setidaknya 17
jenis komorbiditas penyakit dengan insidensi yang tinggi (≥ 8%), diantaranya adalah
penyakit jantung koroner, gagal jantung, aritmia, penyakit serebro vaskular, hipertensi,
tromboemboli vena dan diabetes melitus. Penyakit-penyakit komorbid ini selain
menurunkan kualitas hidup, juga berpengaruh pada kemampuan penderita dalam
menjalani pengobatan kanker, baik operasi, terapi sistemik maupun radioterapi. Ketiga,
kanker lambung mempunyai profil molekuler yang sangat heterogen dan kompleks
yang menyebabkan penyakit ini cenderung bersifat silent hingga sering ditemukan pada
stadium lanjut saat diagnosis, progresif dan resisten terhadap terapi sistemik
konvensional seperti kemoterapi. Keempat, meskipun kemoterapi dapat memperbaiki
kesintasan hidup penderita kanker lambung stadium lanjut, tetapi median kesintasan
hidup masih kurang dari satu tahun. Semua data tersebut menunjukkan manajemen
kanker lambung stadium lanjut masih sangat perlu ditingkatkan.
The Cancer Genome Atlas Group, berdasarkan profil molekularnya, berhasil
mengindentifikasi 4 subtipe kanker lambung yaitu : subtipe 1, ditandai dengan
amplifikasi gen dan chromosomal instability (CIN), yang merupakan subtipe mayoritas
dengan jumlah populasi 50% ; subtipe 2, tumor dengan microsatellites instability yang
ditandai dengan mutasi dan metilasi DNA yang tinggi (22% populasi); subtipe 3, tumor
dengan genomik yang stabil (20% populasi) dan subtipe 4, tumor dengan virus Epstein
Barr yang positif dan ditandai dengan hipermetilasi DNA, frekuensi tinggi mutase
PIK3CA dan peningkatan ekspresi PDL1/PDL2 (8% populasi). Klasifikasi molekular
kanker lambung ini tidak mempunyai nilai prognostik, karena pada keempat subtipe

72
molekular ini waktu kesintasan hidupnya sama. Meskipun demikian, klasifikasi
molekular ini memberi inspirasi untuk manajemen baru kanker lambung, khususnya
dalam mengembangkan konsep terapi individual berbasis terapi target dan imun.
Saat ini banyak terapi target yang dikembangkan pada manajemen kanker
lambung berdasarkan proses proliferasi, invasi, angiogenesis dan anti-apoptosis sel-sel
tumor, seperti : anti Epidermal Growth Factor Receptor (EGFR), Human Epidermal
Receptor 2 (HER2), Mammalian Target of Rafamicin (mTOR), Vascular Endothelial
Growth Factor (VEGF) dan Vascular Endothelial Growth Factor Receptor (VEGFR).
Selanjutnya pada presentasi akan dibahas lebih detil tentang peran terapi target anti
VEGF pada manajeman kanker lambung stadium lanjut.

73
 The Role of Flowcytometry in B Cell Malignancies
Lyana Setiawan

B-cell neoplasms are clonal tumors of mature and immature B cells at various
stages of differentiation. Although B lymphocytes constitute a minority of normal
peripheral blood lymphoid cells, B-cell lymphoproliferative disorders (BCLPD) are
significantly more common than T-CLPD.
Flow cytometry (FCM) analysis for BCLPDs can be used in diagnosis and
monitoring of disease, ncluding minimal residual disease (MRD). Clinical indications to
perform FCM studies when considering a possible diagnosis of LPD includes significant
lymphocytosis (>6 × 109/L), lymphadenopathy and lymphocytosis, abnormal lymphoid
morphology, splenomegaly +/− cytopenias, unexplained cytopenias, persistent
unexplained erythroderma, or splenomegaly and lymphadenopathy where a node
biopsy is not possible.
Lymphoid gated CD2+ versus CD19+ plot will help differentiate BCLPD from
TCLPD. An excess of CD19+ cells will generate further analysis using antibodies
comprising a chronic B-cell panel. Normal B-cells account for 10–20% of peripheral
blood lymphocytes, with an absolute level of 0.07 to 0.52 × 109/L. Mature B-cells
express surface CD19, CD79a and usually CD20. Immature B-cells characteristically
express cytoplasmic +/− surface CD19 and CD79a, but are usually CD20 negative.
Cytoplasmic CD79a is the gold standard for identifying cells of B-cell lineage. CD19 is
usually also a reliable B-cell marker but can be aberrantly expressed in some non-B-cell
neoplastic diseases. Peripheral blood B-cells normally express CD22 and FMC7 with
surface light chain expression, either kappa or lambda at a ratio of between 2:1 and 3:2.
Normal B-cells express HLA-DR whereas normal non-activated T-cells do not.
Features useful in making a diagnosis of clonal B-cell disorders include: (1)
Skewing of kappa:lambda ratio greater than 10:1 or less than 1:10, (2) Weak or absent
surface light chain expression, (3) Aberrant CD5 expression, (4) CD10 expression, (5)
CD11c, CD103, CD123 and CD25 expression, (6) CD23 expression, (7) Weak, dim or
absent CD79a, CD19, CD22 or CD20 expression, (8) Aberrant CD2, CD4, CD7 or CD8
expression. The BCLPDs can be classified by their antigen expression into CD5 positive
(including CLL, PLL, mantle cell), CD10 positive (including follicular lymphoma, DLBCL,
B-ALL), or CD5-/CD10-, which requires additional panel (hairy cell leukemia and splenic
marginal zone lymphoma). The absolute relevance of FCM findings must always be
interpreted with respect to the patient’s clinical presentation, physical signs and
peripheral blood cell morphology.

74
 Update Guideline in Multiple Myeloma
Cosphiadi Irawan

Multiple myeloma (MM) is a plasma cell neoplasm that accumulate in bone

marrow, leading to bone destruction and marrow failure. MM accounts for 1% (-1.8%
USA-) of all cancers and ~10% (-slightly over 17% USA-) of all hematological
malignancies globally, meanwhile, in Indonesia, MM ranked 20th for new cases rate and
ranked 18th in mortality rate among all cancers. Myeloma is most frequently diagnosed
among people aged 65 to 74 years, with the median age being 69 years. The course of
MM is highly variable, and the clinical behavior is remarkably heterogeneous. Major
advances have been made in the diagnosis, risk stratification and treatment of MM in
the recent past. The reclassification of a subset of patients with smoldering MM, based
on high-risk biomarkers, and the development of the revised international staging
system are among the key new developments in diagnosis and staging. Many studies
have identified prognostic factors capable of predicting this heterogeneity in survival
including serum b2-microglobulin, albumin, C-reactive protein and lactate
dehydrogenase (LDH).
Newly diagnosed MM is typically sensitive to a variety of cytotoxic drugs1.
Although responses are typically durable, relapse is an expected part of the disease
course and MM is not considered curable with current approaches. The goal of therapy
is to maximize treatment responses while minimizing treatment-related toxicities. High-
dose therapy followed by autologous stem cell transplantation (ASCT) has been shown
to prolong survival in both the pre-novel agent and novel agent eras. Patients below 65
years of age with an acceptable comorbidity profile and performance status are
considered transplant eligible. Selected patients aged above 65 years with good
performance status and minimal comorbidities may be considered for reduced-intensity
transplant. Patients who are above 65 years of age or have significant comorbidities are
generally ineligible for high-dose therapy. Categorization of their fitness to receive
intensive treatment should be based on comorbidities and performance status.
In the last 5 years, several new drugs have been introduced into clinical practice
treatment of MM, evolving with the introduction of new classes and newer generation of
drugs like: immunomodulatory drugs (IMiDs): pomalidomide, proteasome inhibitors
(PIs): carfilzomib, or ixazomib; monoclonal antibodies: elotuzumab, daratumumab, and
histone deacetylase (HDAC) inhibitors: panobinostat. Other emerging immunotherapy
approaches such as chimeric antigen receptor (CAR) T-cell therapy and bi-specific T-
cell engagers (BiTEs) appear quite promising and will further change the treatment
landscape and greatly expanding treatment options. The use of novel agent-based
treatment has resulted in significant improvements in the survival and quality of life of
many patients with MM. Determining the optimal use of proteasome inhibitors,

75
immunomodulators and, more recently, monoclonal antibodies and other
immunotherapy are an area of ongoing investigation.
Patients who are candidates for ASCT are treated with induction therapy for
approximately 3 to 4 cycles with a triplet regimen consisting of bortezomib and
dexamethasone combined with either lenalidomide (VRD), thalidomide (VTD), or
cyclophosphamide (VCD), followed by stem cell harvest and ASCT, continue with
maintenance therapy for at least 1 to 2 years. Generally, lenalidomide is the drug of
choice for maintenance, but patients with intermediate- and high-risk disease some
experts prefer bortezomib-based. Those who are not candidates for ASCT are treated
with either a triplet regimen for 12 to 18 months or alternatively with Rd until
progression. The choice of the triplet regimen varies, but in general melphalan-based
regimens are being replaced by newer regimens such as such as VRD or VCD. Almost
all patients with myeloma relapse after initial therapy, at a median duration of 4 years
after ASCT plus maintenance, or 2.5 years without ASCT. The disease is then
characterized by multiple relapses and remissions, with the number of remissions
dependent on the available treatment options.

76
 Novel Therapy in Chronic Lymphocytic Leukemia (CLL)
Andi Fachruddin Benyamin

Chronic Lymphocytic Leukemia (CLL) is a common type of leukemia in adult, the

disease is twice as common in males as females. Chronic Lymphocytic Leukemia is a
neoplasm of lymphoid origin; more specifically, it is a malignancy of mature B
lymphocytes. Chronic Lymphocytic Leukemia is extremely heterogeneous in its clinical
course. Some patients live for decades with indolent disease and do not require
treatment, whereas others suffer an aggressive course with intrinsic resistance to
chemotherapy, eventually leading to death.
Many people with CLL have no early symptoms but in other case, typical B
symptoms of lymphoma may be present. Performance status should be recorded at
diagnosis.
The Rai (stage 0–IV) and the Binet (stage A–C) systems are two widely accepted
staging methods for use in both patient care and clinical trials. These staging systems
are simple, inexpensive, and can be applied by physicians worldwide.
Criteria for initiating treatment may vary depending on whether or not the patient
is part of a clinical trial. In general practice, newly diagnosed patients with asymptomatic
early stage disease (i.e., Rai 0, Binet A) should be monitored without therapy unless
they have evidence of disease progression. Therapy for symptomatic CLL has
comprised predominantly chemotherapeutic agents, including chlorambucil,
cyclophosphamide, fludarabine, bendamustine, and combinations of these agents.
These therapies are effective for palliation but have not been shown to improve survival.
Combining rituximab, a monoclonal antibody directed against the CD20 antigen on B
lymphocytes, to chemotherapy (fludarabine in combination with cyclophosphamide)
results in higher response rates, prolonged remissions, and improved overall survival.
As an effort to optimize treatment outcomes, novel molecularly targeted therapies
have been developed. In February 2014, the Food and Drug Administration (FDA)
granted an accelerated approval to ibrutinib, an innovative, promising targeted
treatment option for patients with CLL. Ibrutinib is an orally administered, highly potent,
selective, and irreversible small-molecule inhibitor of Bruton’s tyrosine kinase. This
inhibition prevents downstream activation of the B cell receptor pathway and
subsequently blocks cell growth, proliferation, and survival of malignant B cells.
Published clinical trials suggest ibrutinib is highly active in the treatment of CLL in the
relapsed/refractory setting and induces durable remissions in predominantly elderly,
heavily pre-treated patients with high-risk disease characteristics.

77
 Terapi Terbaru pada Leukemia Limfositik Kronik (CLL)
Andi Fachruddin Benyamin

Chronic Lymphocytic Leukemia (CLL) adalah leukemia yang paling umum pada
dewasa, lebih umum pada pria dibandingkan wanita. CLL adalah neoplasma yang
berasal dari jaringan limfoid; dan merupakan keganasan limfosit B matang. CLL sangat
heterogen dalam perjalanan klinisnya, beberapa pasien hidup selama beberapa dekade
dan tidak memerlukan pengobatan, sedangkan penderita lainnya menunjukan
perjalanan yang agresif dan resisten terhadap kemoterapi hingga menyebabkan
kematian.
Beberapa pasien CLL tidak memiliki gejala awal, tetapi dalam kasus lain
menunjukan gejala B yang khas Status tmpilan harus dinilai pada saat diagnosis.
Terdapat dua metode staging yang paling banyak digunakan dalam perawatan
pasien dan uji klinis: sistem Rai (stadium 0-IV) dan Binet (tahap A – C). Sistem staging
ini cukup sederhana, tidak mahal, dan dapat diterapkan oleh dokter di seluruh dunia.
Kriteria untuk memulai pengobatan bervariasi tergantung pada apakah pasien
merupakan bagian dari uji klinis. Dalam praktik umum, pasien yang baru didiagnosis
dengan CLL asimptomatik tahap dini (mis., Rai 0, Binet A) harus dipantau tanpa terapi
kecuali mereka memiliki bukti perkembangan penyakit. Terapi CLL simtomatik terdiri
dari agen-agen kemoterapi termasuk Chlorambucil, Cyclophosphamide, Fludarabine,
Bendamustine, dan kombinasi-kombinasi dari agen-agen ini. Terapi-terapi ini efektif
untuk palitif tetapi belum terbukti memperpanjang angka kesintasan. Mengkombinasi
Rituximab (antibodi monoklonal terhadao antigen CD20 pada limfosit B) dengan
kemoterapi (fludarabine dalam kombinasi dengan cyclophosphamide) menghasilkan
tingkat respon yang lebih tinggi, remisi yang lebih panjang, dan peningkatan angka
kesintasan umum.
Dalam upaya untuk mengoptimalkan hasil pengobatan, terapi target molekuler
telah dikembangkan. Pada bulan Februari 2014, Food and Drug Administration (FDA)
memberikan persetujuan terhadap Ibrutinib, sebuah pilihan pengobatan yang
ditargetkan dan menjanjikan bagi pasien-pasien CLL. Ibrutinib diberikan secara oral,
sangat potent, selektif, dan ireversibel menghambat tirosin kinase Bruton.
Penghambatan ini mencegah aktivasi jalur reseptor sel B dan selanjutnya menghambat
pertumbuhan sel, proliferasi, dan kelangsungan hidup sel B maligna. Clinical trials yang
dipublikasikan menunjukkan Ibrutinib aktif pada pengobatan CLL relaps / refrakter dan
menginduksi remisi yang cukup lama pada pasien yang lebih tua, pasien yang sudah
menjalani perawatan awal dengan karakteristik penyakit berisiko tinggi.

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 Non-Hodgkin Lymphomas: Diagnosis, Staging & Management
Tubagus Djumhana Atmakusuma

In the management of non-Hodgkin lymphomas (NHLs) the histological types

and subtypes as well as the staffing are highly required to determine the treatment of
choice

Histological diagnoses of lymphoid cell malignancies

The new histological diagnoses using the cellular markers of the
immunophenotyping tests (by CD markers using IHC technique) and if necessary, FISH
and molecular analysis will more precisely determine the appropriate subtypes
diagnosis and specific cellular and molecular patterns of non-Hodgkin lymphomas
(NHLs). That information is required to determine the regimens of cytotoxic
chemotherapies, targeted therapies and immunotherapies of all types and subtypes of
the NHLs as well as to assess the prognosis of the diseases. Prognosis of the diseases
is highly correlated with the proper types and subtypes as well as the certain cellular or
molecular markers. For example, the information of Ki67 (marker of cell proliferation)
will discriminate the grade of the malignancies. In low grade lymphomas (e.g. follicular
lymphomas) the Ki67 is low (low proliferation). This means the patient will receive the
less heavy cytotoxic regimens (e.g. CVP). If the CD 20 marker is positive (for B cells)
the patient will be treated by rituximab (R) plus CVP (R-CVP regimen). If Ki67 is high
this means a high grade of malignancy e.g diffuse large B cell lymphomas (DLBCL) and
if CD 20 is positive the patient will receive R-CHOP. Meanwhile, there have been newer
histological types or subtypes developed. For example, germinal center B cell (GCB)
and non-GCB, which are identified by CD markers, also are correlated with the proper
diagnosis and the prognosis of the patients.

Non-Hodgkin Lymphoma’s staging and response criteria

Previously Ann-Arbor staging has been adopted from the Hodgkin Disease
(Hodgkin lymphoma) staging to become a standard criteria for NHLs staging. However,
the 2017 NCCN showed that there has been a new staging system used which is called
as Lugano Modification of Ann-Arbor Staging System (LMAASS) for primary nodal
lymphomas. The differences of the LMAASS from the Ann-Arbor Staging System are
the LMAASS has divided the stage of NHL into limited stages: stage I, stage II, and
stage II Bulky (a new category) and advanced stages: Stage III and stage IV.

79
 PET CT scan with contrast has become the essential procedure to determine a
stage of lymphoid malignancies, either for NHL or for Hodgkin lymphomas. The Lugano
Response Criteria for NHL also recommended PET CT scan with contrast to assess the
response of NHL to the treatment; complete responses, partial responses, no-response
or stable disease and progressive disease, using WHO or RECIST criteria.

Systemic therapies (cytotoxic chemotherapies, targeted therapies,

immunotherapies) in NHLS
1. Indolent lymphomas
For an indolent/slower growing lymphomas (FL, MZL, SLL/CLL and WM) a “watch
and wait” rule (wait to treat until a patient is symptomatic) is recommended for patiens
who fulfill the criteria for delaying treatment, i.e. maximum 7 cm in diameter size, < 3
nodal sites, absence of B symptoms, no circulating follicular cells and no bone marrow
compromise.
Stage I of indolent NHLs patients who need curative treatment, radiation is the
treatment choice. Stage III and IV symptomatic NHLs patients are treated by the upfront
regimens rituximab/R (a targeted therapy of monoclonal antibodies) based
chemotherapy, i.e. a combination between R- and cytotoxic chemotherapy, i.e. R-
CHOP or R-CVP with or without R- maintenance or in low risk disease, elderly/poor
performance status, R-monotherapy.
In relapsed NHLs without evidence of transformation if durable initial response (eg.
TTP > 6 months), the previous regimens (as mentioned above) can be used again.
While if the TTP < 6 months, the Fludarabine (F) based therapy; e.g. FC (F-
cyclophosphamide) with / without R, followed by with / without R maintenance, is
recommended. Other choices are a high dose chemotherapy which is supported by
Autologous/ Allogeneic Stem Cell Transplantations (ASCT/AlloSCT),
radioimmunotherapy, or ifosfamide, carboplatin, etoposide (IEC) with / or without R and
clinical trials.

2. Chronic lymphocytic leukemia (CLL) / small lymphocyte lymphomas (SLL)

The treatment of CLL /SLL depends on the cytogenetic patterns. There have been
three (3) categories of CLL/SLL based on the cytogenetic patterns; (a) with no deletion
(11q) nor deletion(p17) in a first line treatment and in relapsed/refractory cases, (b) with
deletion (11q) in a first line treatment and in relapsed / refractory cases, and (c) with
deletion (17p) in a first line treatment and in relapsed / refractory cases. When choosing
the regimens age of patients should be considered, if the patients < 70 years or ≥ 70
years of age.
Fludarabine is suggested in CLL/SLL patients with no deletion (11q) nor (17p), either
in patients < 70 years of age (FCR, FR regimens) or in patients ≥ 70 years of age (FR)

80
as a .first line treatment. Meanwhile, in relapsed / refractory cases if patients ≥ 70 years
of age, reduced dose FCR is recommended and if patients < 70 years of age FCR is
recommended. In CLL / SLL patients with deletion (11 q), FCR is recommended if
patients < 70 years of age and reduced dose FCR if patients ≥ 70 years of age, all
regimens are for a first line treatment. Meanwhile, in relapsed / refractory cases reduced
dose FCR is recommended if patients ≥ 70 years of age, and FCR, F-alemtuzumab are
recommended if patients < 70 years of age. In CLL/SLL patients with deletion (17 p),
FCR and FR regimens are not recommended as a first line as well as in relapsed /
refractory cases.

3. Mantle cell lymphomas (MCL)

In MCL the treatment is divided into (a) induction therapy with aggressive therapy;
i.e. CALGB regimen, HyperCVAD regimen, NORDIC regimen, alternating
RCHOP/RDHAP and a sequential RCHOP/RICE, and (b) with less aggressive
regimens; i.e. bendamustine-R, VR-CAP, cladribine-R, lenalidomide – R, modified R-
HyperCVAD, After the induction therapy the patients have 2 choices (a) a consolidation
for patients who are candidate for high dose chemotherapy (HDC) with autologous
stem cell rescue (ASCR) with / without R maintenance, and (b) for patients who are not
candidate for HDC/ASCR: R – maintenance. In second line treatment there are
Fludarabine (FC) with / without R, bendamustine with/without R, BBR (bendamustine,
bortezomib and R) regimens, and others.

4. Diffuse large B cell lymphomas (DLBCL)

In DLBCL fludarabine is not recommended as a first line treatment nor in relapsed/
refractory cases. Rituximab (R) based regimens are recommended. RCHOP, dose-
dense RCHOP14 and adjusted RCHOP are recommended as a first line treatment. In
patients > 80 years of age with comorbidities R-miniCHOP is recommended.
Meanwhile, as a second line or subsequent treatment, DHAP, ESHAP, ICE, MIN, GDP,
GeMOX regimens are recommended with / without R (as an intention to proceed to high
dose chemotherapy. In addition, if patients are not candidate for high-dose therapy,
bendamustin with/without R, brentuximab vedotin for CD 30+ disease, CEPP,CEOP,
DA-EPOCH,GDP with / without R, GemOX with/without R, Gemcitabin, vinorelbin with /
without R, lenalidomide with/without R are recommended.

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 Management of Neutropenia as an Adverse Effect of Chemotherapy
Yenny Dian Andayani

Neutropenia is a blood disorder characterized by low neutrophil count. It defines

as absolute neutrophil count less than 500/mm3. Neutropenia can be both hereditary
and iatrogenic blood disorder, where almost 90% iatrogenic neutropenia as a
consequence of chemotherapy drugs. Febrile neutropenia (FN) is defined as a single
oral temperature measurement above 38,3 ⸰C or oral temperature above 38,0 ⸰C on
twice measurement in an hour accompanied by neutrophil count less than 500/mm3 or
neutrophil count less than 1.000/mm3 in the prediction of decreasing to 500/mm3 within
48 hours. The incidence of chemotherapy induced FN for solid tumors are 10-50 %, less
for hematologic malignancies that reaches 80 %. FN is accounted for 20-30 % morbidity
and 10% mortality rate as a complication of chemotherapy. FN can interfere with
treatment effectiveness. The complication of drugs side effects is due to the impairment
of the normal mucosal barrier and the drugs toxic effects. The risk factors for therapy
induced FN are previous chemotherapy, the regimen, history of previous neutropenia,
and including age, immune-tolerant, nutritional status, COPD, cardiovascular disease,
liver disease, diabetes, and impaired renal function. High risk chemotherapy regimen
attributed to FN risk for over 20% are TAC, CHOP, and R–ICE. Intermediate risk
regimen accounted for 10-20% FN are CMF and FEC. For the last 25 years, it is well
known that there has been an alteration in the pathogen responsible for fever in
neutropenia. The worst prognoses for FN are patients with bacteremia state, accounted
for 18% and 56% morbidity for negative and positive gram bacteria, respectively. The
prognosis is based on Multinational Association of Supportive Care in Cancer (MASCC)
score as a prognostic index. Each patient diagnosed with FN must be first assessed
and examined to evaluate high or low risk FN. Antibiotics can be given empirically, for
low risk and outpatient setting FN, oral ciprofloxacin + amoxicillin/clavulanate,
moxifloxacin or levofloxacin can be considered. For high risk FN, broad spectrum
antibiotics such as ceftazidime, cefepime, imipenem, meropenem and piperacillin–
tazobactam can be chosen single or in combination with aminoglycosides. The
administration of G-CSF as primary prophylaxis has been considered for a group of FN
incident > 20% while secondary prophylaxis is meant for a group of patients with a
history previous FN. Chemoprophylaxis that aimed to lessen the incidence of FN is still
controversial, mainly due to the increased risk of drugs resistance. The drugs that have
been usually given are cotrimoxazole, ciprofloxacin or levofloxacin. ASCO and EORTC
recommends administration of antibacterial as a prophylaxis for high risk FN cases.

82
 Prevention, Screening and Early Detection in Gynecologic Cancer
Marlina Tasril

All women are at risk for gynecologic cancers and risk increase with age.
Gynecologic cancers are cancers of women’s reproductive organ. The five main types
are cervical, ovarian, uterine, vaginal and vulvar cancer. Symptom are not the same for
everyone and each type of gynecologic cancer has its own symptoms.
Some gynecologic cancers are caused by the human papiloma virus (HPV), a
very common sexually transmitted infection. A vaccine protects againts the HPV that
most often cause cervical, vaginal and vulvar cancers.
Cervical cancer is the most gynecological malignancy. This is a disease that has
a known cause and has been known to travel the disease. Cervical cancer is also a
method of early detection and prevention of vaccination, the incidence and death rates
from cervical cancer can be reduced. Cervical cancer is only gynecologic cancer that
has recommended screening test. Screening tests can help prevent cervical cancer or
find it early.
The number of cervical cancer cases in Indonesia is due to lack of knowledge
about cervical cancer so that public awareness for early detection is still low.

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 Onkogenesis Virus Pada Kanker Ginekologi
Bambang Karsono

Hubungan antara infeksi virus dan kanker sebenarnya telah diketahui sejak
hampir seabad yang lampau, yaitu ketika pada tahun 1911 Peyton Rous dapat
menularkan sarkoma unggas kepada unggas sehat dengan menyuntikkan filtrat bebas
sel dari tumor ini. Lebih kurang seperempat abad kemudian Bittner melaporkan tentang
tumor payudara tikus yang dapat ditularkan dari induk ke anaknya melalui ASI, virus ini
dinamainya mouse mammary tumour virus (MMTV).
Pada 1963 Vogt dan Dulbecco menemukan bahwa kultur sel normal yang
diinfeksi secara in vitro dengan polyomavirus mengalami perubahan menjadi sel-sel
yang berperangai ganas, seperti bersifat klonal, dapat dikultur untuk waktu yang tak
terbatas, poliploidi, kehilangan inhibisi kontak dan sebagainya. Perubahan ini kemudian
dikenal dengan istilah transformasi.
Onkogen pada virus DNA memang berasal dari virus itu sendiri, onkogen pada
virus ini memang dibutuhkan secara hakiki oleh virus ini untuk replikasi dan
mentransformasi sel pejamu. Oleh karena virus ini memiliki perkakas yang terbatas
untuk berreplikasi maka virus ini, dengan menggunakan onkogen virus, membuat
protein-protein non struktural (tidak dibuat oleh sel pejamu) yang dapat memaksa sel
pejamu memasuki fase S dari siklus sel. Dengan masuknya sel pejamu ke dalam fase S
maka virus memperoleh enzim-enzim dan lingkungan yang kondusif untuk replikasi
DNA virus.
Meskipun banyak retrovirus yang dapat menginsersi proto-onkogen sel
pejamu atau menginsersi provirus sebagai promoter atau enhancer pada proto-
onkogen dan virus DNA yang dapat menghambat tumor supressor protein,
namun demikian sampai saat ini hanya sedikit virus yang terbukti dapat
menyebabkan kanker manusia. Virus-virus tersebut ialah:
1. Virus Hepatitis B (HBV), virus DNA
2. Virus Epstein-Barr (EBV), virus DNA
3. Human T-cell Leukemia Virus type I (HTLV-I), retrovirus
4. Human Papilloma Virus jenis risiko tinggi (High risk HPV), virus DNA
5. Virus Hepatitis C (HCV), virus RNA
6. Simian virus 40 (SV40), virus DNA

Human Papillomavirus (HPV) memiliki beberapa serotipe di antaranya tipe 6

dan 11 yang disebut sebagai tipe risiko rendah dan serotipe 16, 18, 31, 33 dan
35 yang disebut sebagai tipe risiko tinggi. Infeksi oleh HPV tipe risiko rendah
hanya akan berakibat timbulnya kondiloma dan displasia ringan pada epithel

84
serviks uteri (CIN I) yang biasanya tidak akan berkembang menjadi penyakit
invasif.

Sedangkan infeksi oleh HPV tipe risiko tinggi akan berakibat timbulnya
displasia sedang dan displasia berat atau karsinoma in situ serviks uteri (CIN II
dan CIN III). HPV tipe risiko tinggi juga dijumpai pada sebagian besar penderita
karsinoma serviks uteri. Genom HPV terdapat dalam bentuk episomal pada CIN ,
sedangkan pada karsina serviks uteri invasif dalam bentuk terintegrasi dalam
DNA khromosom sel pejamu.HPV menghasilkan berbagai protein dan 2 di
antaranya yaitu E6 dan E7 dapat menginaktifkan protein tumor supressor yaitu
p53 dan pRb. Protein E6 menginaktifasi p53 dengan cara meningkatkan
degradasinya. Berkurangnya aktivitas p53 dan pRb akan memudahkan sel untuk
masuk fase S dari siklus sel.

85
 The Role of Chemotherapy in Cervical, Endometrium and Ovarian
Cancer
Toman L. Toruan

Kanker serviks uteri, kanker endometerium dan kanker ovarium masih

merupakan penyebab morbiditas dan mortalitas yang utama pada perempuan. Data
GLOBOCAN 2018 menunjukkan bahwa insiden untuk ketiga penyakit tersebut di atas
adalah (secara berurutan) 569.847 jiwa, 382.069 jiwa, dan 295.414 jiwa. Sedangkan
untuk angka mortalitasnya adalah 311.365 jiwa, 89.929 jiwa, dan 184.799 jiwa. Hal ini
terjadi antara lain karena pasien yang mendatangi fasilitas kesehatan sudah berada
dalam tahap lanjut.
Pengobatan stadium lanjut dan stadium menengah pada ketiga kanker tersebut
di atas memiliki hasil yang lebih baik jika di dalamnya terdapat komponen terapi
sistemik, baik itu kemoterapi maupun terapi target. Tetapi perlu dipahami juga bahwa
terapi sistemik memiliki efek samping sehingga dibutuhkan pengetahuan yang baik
guna penanganan yang lebih baik yang dapat memberi hasil lebih baik

86
 Advanced Stage Adenocarsinoma Lung Cancer
Eko Adi Pangarsa, Noorwati Sutandyo

In oncology, few treatment landscapes have changedas dramatically over the

last several decades as that for non-small cell lung cancer (NSCLC). The changes were
certainly welcomed, considering the difficult reality of treating NSCLC. Of all lung cancer
cases, approximately 80% are NSCLC, and the disease often presents at an advanced
stage. Recent studies for the metastatic non-small cell lung cancer led to the
ascertainment that the NSCLC does not constitute exclusively a disease entity, but
different neoplasms guided from different molecular paths, different biological behavior
and at extension requires different confrontation. The identification of specific molecular
targets against which therapies for NSCLC can be directed has prompted a shift
towards personalized treatment and improved survival rates. In the tumors of patients
with NSCLC of adenocarcinoma histology, three out of four of the known driver gene
mutations are targetable with regulatory approved, specifically targeted treatments;
these are: activating mutations in the epidermal growth factor receptor (EGFR);
activating translocations of anaplastic lymphoma kinase (ALK); rearrangements of ROS
proto-oncogene 1, receptor tyrosine kinase (ROS1); and the kinase activating mutation
V600E in the BRAF oncogene.
Generally, EGFR mutations noticed more often in adenocarcinomas, in patients
without prior history of smoking, and in females and more commonly in those of Asian
origin. Gefitinib, erlotinib, and afatinib are used in patients with adenocarcinomas with
known EGFR mutations. First and second-generation EGFR TKIs, which were designed
against the wild-type EGF receptor, yield robust and relatively durable responses in the
majority of lung cancer patients whose tumors harbor EGFR sensitizing mutations. The
first-generation drugs, including erlotinib and gefitinib, are reversible inhibitors. The
second-generation inhibitors afatinib are irreversible inhibitors which covalently bind to
EGFR. Afatinib has affinity for three of the four ErbB family members: EGFR, HER2,
and HER4. Approximately 60% of patients with acquired resistance to the EGFR TKIs
(erlotinib, gefitinib, and afatinib) develop a new mutation within the drug target. This
mutation—T790M—has been shown to alter drug binding and enzymatic activity of the
mutant EGF receptor.
Few data are available that have assessed the cumulative benefit of sequential
EGFR TKIs in patients with EGFR mutation-positive NSCLC. Study by Hochmair et al
demonstrated that the second-generation ErbB family blocker, afatinib, and the third-
generation EGFR TKI, osimertinib, are superior to first-generation TKIs in a first-
linesetting in patients with EGFR mutation-positive NSCLC. First-line afatinib followed
by osimertinib in patients with EGFR mutation-positive NSCLC who acquire T790M is a

87
feasible therapeutic strategy, resulting in a median time on chemotherapy-free
treatment of 27.6 months.
These findings demonstrate that afatinib can provide an effective and tolerable
treatment for patients with EGFRm+ NSCLC.

88
 Penatalaksaan Akut Mieloid Leukemia
Nugroho Prayogo

Pendahuluan:
AML merupakan keganasan hematologi, ditandai adanya proliferasi tidak terkendali dari sel
blast sistem non-limfoid /mieloid.
Etiologi dan Pathogenesis
Penyebab adalah adanya faktor ekternal: lingkungan, kimiawi, radiasi, virus, mungkin internal:
faktor genetik defek, instabilitas, atau kombinasi keduanya.
Dimulai dari mutasi satu sel, membelah tidak terkendali, sel tidak mengalami maturasi (arrest),
mutasi-mutasi selanjutnya, menyebabkan apoptosis terhambat, dan manifestasi selanjutnya di
dalam sumsum tulang dipenuhi sel blast, menghambat pertumbuhan sel lainnya (lymphoid,
eritrosit dan trombopoeitik) sehingga daya imunitas menurun, hemostasis terganggu dan
anemia.
Gambaran Klinis
Gejala dan Tanda
Letih lesu ,pucat, gampang infeksi, bisa terdapat pembesaran kelenjar, mudah terjadi
perdarahan di bawah kulit atau perdarahan nyata,
Laboratorium
Darah perifer: anemia, leukositosis /leukopenia, trombositopenia.
Aspirasi sumsum tulang: morfologi menunjukkan sel blast abnormal dan berlebih.
Immunophenotyping: menunjukkan garis mieloid.
Sitogenetik: terdapat tanda mutasi, delesi, translokasi kromosom
Semua pemeriksaan ini (MIC) dapat memberi informasi prognosis .
Rencana Diagnosis
RPD, pemeriksaan fisis, tes darah, HLA typing, BMP biopsi sumsum tulang untuk diagnosis dan
persiapan transplantasi bila diperlukan, sitogenetik, genetik molekuler.
Klasisifikasi
Bermacam klasifikasi: FAB 1976, revisi FAB 1981, revisi FAB 1985, MIC 1986, WHO 1997 dan
WHO 2016.

Keberhasilan Pengobatan.
Tergantung faktor utama: faktor pasien, faktor penyakit, faktor manajemen.
Faktor pasien: usia, performance status, penyakit penyerta.
Faktor penyakit; MIC, sitogenetik.
Faktor manajemen: keahlian dan pengalaman, fasilitas ruang, alat dan tenaga.
Interaksi ketiga faktor berperan besar menentukan outcome.
Pengobatan AML.
Persiapan/work up; induksi 1kali/2kali; Evaluasi; Reinduksi/transplantasi; Konsolidasi 1kali/2kali;
Evaluasi; Maintenance 6 kali/tidak; Terapi relaps.

89
Work up;
Sesudah rencana diagnosis dilakukan à Diagnostik MIC à Inventarisasi kumanàEliminasi
fokus infeksi (THT, Gigi dan Mulut , wasir, luka-luka, hepatitis B/C, dll.)àPemasangan
CVCàPersiapan donor in vivo (donor siap pakai)àPersiapan logistik, antibiotik, nutrisi
parenteral, albumin, dll.
Penetalaksanaan
— Induksi =kemo agresif, aplasià infeksi dan perdarahan.
— Ruang rendah kuman, makanan bebas/rendah kuman.
— Bila trombosit rendah: bed rest dan hindari mengejan dan cegah batuk.
— Suportif gizi cukup enteral dan bila perlu parenteral.

① Persiapan/work up
② Induksi 1kali/2kali
③ Evaluasi
④ Reinduksi/transplantasi
⑤ Konsolidasi 1kali/2kali
⑥ Evaluasi
⑦ Maintenance 6 kali/tidak

Kemoterapi
— Induksi; D3-7 (daunorubicin 45 mg/m2, 3hari + ara-C 100 mg/m2, 7hari C.I.)
— Alternatif daunorubicin =idarubicin.
— Post remisi /konsolidasi (daunorubicin 80 mg/m2 d1 + araC 200mg/m2, 5hari C.I.)
— Alternatif lain: LAM 10 (lebih agresif), LAM 12 (untuk geriatri).
Ruang perawatan
— Satu kamar satu pasien, cegah cross infeksi
— Bertekanan positif dari udara bersih. (High Efficiency Particulate Air Filter)
— Petugas masuk, berpakaian steril.
Induksi
Protokol standar RSKD:
a. LAM 8 / D 3-7
b. Alternatif : LAM 10, LAM 12 (geriatri)
c. FLAG/mini-FLAG, HOVON (alternatif)
Lokasi perawatan ;
Tidak harus di RIIM, tapi RIIM lebih baik; Tekanan positif, mencegah penularan;
Single room; Alternatif: satu satu kamar satu pasien, semi steril.
Koreksi setiap kelainan :
Hb <9 g/dl; Trombosit < 30.000/mcl; ANC < 500-1000/mcl; Pemeriksaan DPL 2 setiap hari, lab
berkala diperiksa setiap minggu termasuk kultur.

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Konsolidasi
— Terapi standar LAM 8 = dauno 45 mg/m2 d1 + ara-C 200mg/m2 d1-5, C.I.
— Prinsip sama dengan penatalaksanaan induksi.
— Pasien dan tim medis lebih pengalaman.

Outcome
— Outcome bervariasi;
— D 3-7= CR sekitar 45-65%, namun angka relaps masih 85%.
— 2 tahun CR masih < 10%
— Bila 3 tahun masih CR, secara potensial cure.
— D14 BMPàCR teruskan konsolidasi, bila blast > 5 %, reinduksi.
— CR= blast <5%, leukosit > 1.000/mcl; trombosit > 100.000/mcl.
TRD (treatment Related Death)
— Pasien meninggal < 21 hari dihubungkan dengan gagal dalam supportive care.
— Meninggal 21-35 hari, lebih dihubungkan dengan gagal untuk mencapai CR.
— Meninggal > 35 hari jarang ( <10%).
— TRD =kematian berhubungan dengan pengobatan.
— Erat dengan komorbid dan supportive care.
Prediksi TRD
Usia, fungsi organ dan performance status mempunyai peranan besar.
Fungsi ginjal dan liver merupakan prediktor penting.
Lama perawatan
— Umumnya 21-28 hari sudah pulih.
— Penyulit selama perawatan: infeksi dan perdarahan.
— Evaluasi post-induksià klinis, lab, dan BMP.
— Interval induksi-konsolidasi.
— Pemberian GF selama induksi

Ringkasan
— Telah dipresentasikan pendekatan diagnosis dan penatalaksanaan AML secara ringkas.
— Diagnosis yang akurat membuat terapi lebih akurat.
— Ketelitian dan perhatian dan koreksi terhadap kelainan mengurangi mortalitas.

91
 Acute Lymphoblastic Leukemia
Resti Mulya Sari, Ruth Vonky Rebecca

Acute Lymphoblastic Leukemia (ALL) is a type of blood cancer that comes on quickly
and is fast growing, characterized with many lymphoblasts (immature white blood cells) in the
blood and bone marrow. The estimated annual incidence of ALL worldwide is 1 to
5 cases/100,000 population, and more than two-thirds of cases of ALL are B cell phenotype. In
Indonesia, incidence rate of leukemia is 4,46% & ranked 9th position meanwhile mortality rate is
6,36% & ranked 5th position from all of cancer cases (GLOBOCAN 2018). ALL classified by the
precursor of cell lymphoblast, B-cell (B-ALL) and T-cell (T-ALL). B-ALL is primarily a disease of
children, with three-quarters of cases occurring in children <6 years old and a second peak of
incidence in adults >60 years old. Meanwhile T-ALL Occurs most frequently in late childhood,
adolescence, & young adulthood.
ALL clinical manifestations are not specific and can resemble other disease. Diagnostic
of ALL requires detection of lymphoblasts with the characteristic immunophenotype in peripheral
blood, bone marrow, or other involved tissue; although there is no consensus regarding a
minimal proportion of lymphoblasts in bone marrow, the diagnosis of B-ALL/LBL should be
avoided when there are <20 percent lymphoblasts. Cytogenetic by conventional chromosomal
banding with or without FISH (Fluorescence In Situ Hybridization) or molecular analysis should
be performed for the classification of ALL.
There are several modalities for ALL therapy such as chemotherapy, radiation therapy,
targeted therapy, allogeneic HSCT (Hematopoietic Stem Cell Transplant), and immunotherapy.
They can be used either alone or combination.

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Prevention Strategy for Chemotherapy-Induced Nausea and Vomiting
(CINV)
Ibnu Purwanto

Most anti-cancer therapies caused nausea and vomiting as side effects of the
treatment. These adverse events can significantly affect the patient’s quality of life,
leading to poor compliance with further chemotherapy treatment, and may lead to dose
reductions or discontinuation of chemotherapy. Chemotherapy-induced nausea and
vomiting (CINV) is classified into five categories, based on the time when the symptom
first starts to appear in relation to the course of chemotherapy.
Chemotherapy-induced nausea and vomiting (CINV) is one of the most feared
side effects experienced by patients with cancer. Before the 1980s, prolonged hospital
stays for nausea after chemotherapy became the biggest problem at that time. In 1979,
a randomized trial in cancer patients showed that overall incidence of CINV was
approximately 83%. The development of new antiemetic agents has dramatically
changed the landscape of CINV. Advances during the past three decades have helped
to elucidate some of the CINV mechanisms. Several neurotransmitters, including
dopamine, serotonin, and substance P, have been identified as important mediators of
CINV event.
In 1991, the first 5-HT3–receptor antagonist, ondansetron, was approved by the
FDA for the treatment of CINV and was immediately incorporated into routine oncology
practice. After 2003, the treatment landscape was radically altered by the FDA approval
of two new compounds: palonosetron and aprepitant. Furthermore in 2013 and 2015,
phase 2 and phase 3 trials of two new NK1-receptor antagonists, netupitant
(administered as an oral fixed-dose combination of netupitant [300 mg] and
palonosetron [0.50 mg] [NEPA]) and rolapitant, were completed and led to a substantial
improvement in prophylaxis for CINV.
Two decades later, with newly available anti-emetics, an observational study
reported incidences of acute nausea and vomiting of 35% and 13%, respectively,
among patients receiving highly and moderately emetogenic chemotherapy. Although
the majority of CINV cases can be prevented with appropriate administration of
available anti-emetics, fear of CINV incidence may affect patient’s decision from sticking
to their treatment regimen.

93
 Anemia in Cancer Patients
Irza Wahid

Anemia is a common clinical finding in cancer patients. Approximately 40% of

cancer patients is associated with anemia, the incidence will be increase to 90% in
cancer patients with chemotherapy. Knight K et al (2004) reported that Cancer and
Chemotherapy-induced anemia (CIA) occurred in 30%-90% cancer patients.
Causes of anemia in patients with cancer are often multifactorial, adding to the
complexity of evaluation. Anemia may be attributed to underlying comorbidities such as
bleeding, hemolysis, nutritional deficiencies, hereditary disease, renal insufficiency,
hormone dysfunction, or a combination of these factors.
The malignancy itself can lead to or exacerbate anemia in a number of ways.
Cancer cells may directly suppress hematopoiesis through bone marrow infiltration.
They may also produce cytokines that lead to iron sequestration, which decreases RBC
production and may even shorten RBC survival. Chronic blood loss at tumor sites from
blood vessels or organ damage can further exacerbate anemia in patients with cancer.
Additional indirect effects may include nutritional deficiencies caused by loss of appetite,
hemolysis by immune-mediated antibodies, or changes in coagulation capability. In
addition, the myelosuppressive effect of many chemotherapy agents is a significant
contributing factor to anemia for patients undergoing cytotoxic treatment. Radiation
therapy to the skeleton is also associated with hematologic toxicity. Newer modalities,
such as immunotherapies, may also have an associated risk of anemia, though data are
limited.
Anemia decreases quality of life of cancer patients, contributed to cancer-
induced fatigue and increases morbidity and mortality of cancer patients. Anemia could
also be used as prognostic factor in cancer patients.
Treatment of anemia in cancer patients could be achieved by treating underlying
disease or supportive therapy with blood cell transfusion, erythropoiesis-stimulating
agents (ESA), with or without iron supplemental. In cancer patients, iron status
assessment is necessary before starting ESA therapy to evaluate absolute iron
deficiency. Absolute iron deficiency could be treated with oral or parenteral iron therapy
without using ESA. Iron status assessment included serum iron, TIBC, ferritin, and
transferrin saturation.

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 Complication in Management of Chemotherapy in Geriatric Patient
Hilman Tadjoedin

Global burden of cancer in geriatric population is increasing. In 2012, new cancer

cases diagnosed in adults 65 years and older comprised 47.5% of all cancer cases.
Increase of cancer incidence in geriatric population is estimated to reach 60% by 2035.
There are several challenges of cancer treatment in geriatric population. Older
patients are at risk of chemotherapy toxicity, mainly due to decrease of functional organ
capacities related to aging. There are also multiple comorbidities in older population
with cancer affecting treatment options. Moreover, given only few clinical trials
conducted in older patients demographic to investigate chemotherapy efficacy and
tolerability, it is harder to predict chemotherapy intolerance in this specific population.
A major issue in treating geriatric cancer patients is how to decide patients’
eligibility for chemotherapy while facing potential toxicity. Comprehensive Geriatric
Assessment (CGA) is an approach to evaluate elderly patients’ global health status.
CGA provides information regarding geriatric-specific domains and other health
problems beyond standard assessment. CGA consists of multiple tools mainly to
identify functional status, physical performance, fall and fall risks, comorbid medical
conditions, depression, social activity and support, nutritional status, and cognition.
CGA classifies elderly patients into 3 categories: fit, vulnerable, and frail. Fit
elderly patients do not have any serious comorbidity and no dependence and thus are
good candidates for cancer treatment. Frail patients have significant dependency and
comorbidities and are at risk of toxicity. Generally, frail patients are given supportive
care or single-agent palliative chemotherapy. Patients considered as vulnerable are
patients with some functional dependency with or without severe comorbidity of which
individualized approaches are needed to decide chemotherapy eligibility.
Problems identified by CGA can impact decision-making for cancer treatment.
Cancer treatment might be modified and tailored to specific problems (eg, dose
reduction, dose delay, etc.). Integrated and individualized intervention plan are also
needed for specific vulnerabilities (eg, mobility deficits, nutritional intervention, etc.).
There are also several tools to specifically estimate risk of chemotherapy toxicity
based on cohort studies. Either the Cancer and Aging Research Group (CARG) tool or
Chemotherapy Risk Assessment Scale for High-Age Patients (CRASH) tool could be
used to identify estimates on risk of chemotherapy toxicity.

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 What is the Meaning of Palliative Treatment?
Urip Murtedjo

Palliative care is an approach that improves the quality of life of patients and their
families facing the problem associated with life-threatening illness, through the
prevention and relief of suffering by means of early identification and impeccable
assessment and treatment of pain and other problems, physical, psychosocial and
spiritual (WHO, 2012, 2016).
The field of palliative care and hospice beginning in England in 1960’s an
became established in the united states in the early 1980’s. 1979 US federal
government to study the phenomenon of hospice care in the united states
Development of palliative medicine in Asia, palliative care service including
Hongkong, Japan, Singapore, South Korea and Taiwan. The Asia Pacific Hospice and
Palliative Care Network (APHN) was established in 2001 to promote a network of
individuals and organization actively involved in palliative care in Asia Pacific Region.
APHN consist of members from Australia, Bangladesh, China, Hongkong, India,
Indonesia, Japan, Macau, Malaysia, Mongolia, Myanmar, Philippines, Singapore, South
Korea, Srilanka, Taiwan, Thailand and Vietnam
In Indonesia, Palliative care service have been established in Surabaya and
Jakarta since 1992. The problem, however, coverage is low and accessibility to opioids
outside the hospital continues to be a problem. The Indonesian Palliative Society
established in 2000 continues to hold annual meeting.
Palliative care began with Palliative Care and Pain Free Outpatient Clinic in
Soetomo Hospital in 19th February 1992. It was a pioneer and pilot project for Palliative
Care in Indonesia. The journey was long and winding, full of challenges and obstacles.

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 Palliative Treatment in Cancer
Pandji Irani Fianza

Palliative treatment is designed to improve the quality of life of patients and their
families who are facing problems associated with life-threatening illness. It prevents and
relieves suffering through the early identification, correct assessment and treatment of
pain and other problems, whether physical, psychosocial or spiritual. Cancer is one of
chronic diseases that requires palliative treatment. All cancer patients should be
screened for palliative treatment, beginning with their initial diagnosis and thereafter as
clinically indicated. Early palliative treatment led to significant improvements in both
quality of life and mood. Patients who received early palliative care had longer survival
than patients who received standard oncologic care alone.
Palliative treatment can be used to reduce or control the side effects of cancer
treatments. It might help patients in advanced cancer to live longer and to live
comfortably, even if they cannot be cured. The treatment is not limited to painkillers and
anti-sickness drugs, but it can also reduce or get rid of symptoms. Treatments such as
chemotherapy, radiotherapy, hormone therapy, targeted cancer drugs can help to
reduce pain by shrinking a tumor and reducing pressure on nerves or surrounding
tissues.
While treatment advances have changed the course of cancer, they have also
created a need for increased clinician skill in discussing other bad news. These
situations include disease recurrence, spread of disease or failure of treatment to affect
disease progression, the presence of irreversible side effects, and raising the issue of
hospice care and resuscitation when no further treatment options exist. Breaking bad
news is a complex communication task that requires verbal component, and other skills
in responding to patients' emotional reactions, involving the patient in decision-making,
dealing with the stress created by patients' expectations for cure, the involvement of
multiple family members, and the dilemma of how to give hope when the situation is
bleak. There are six steps of SPIKES (Setting up the interview, assessing the patient’s
Perception, obtaining the patient’s Invitation, giving Knowledge and information to the
patient, addressing the patient’s Emotions with empathic responses, Strategy and
Summary) protocol to meet the goals of bad news interview.
When patients in advanced cancer can no longer be cured or controlled, hospice
care is used. Hospice care should be used when a person is expected to live about 6
months or less if the illness runs its usual course. The main goal of including palliative
care into hospice services is to help patients be comfortable while allowing them to
enjoy the last stage of life. Since people differ in their spiritual needs and religious
beliefs, spiritual care is set up to meet the specific needs that might include helping the

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patients look at what death means to them and helping with a certain religious
ceremony or ritual.

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