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DIAGNOSIS PADA KANKER

DAN PENGUKURAN RESPON


TERAPI
DIAGNOSIS PADA KANKER

• Histopatology
• Sitologi
• Morfologi darah
• Radiologi
Cancer Staging

• Penentuan stadium berdasarkan lokasi tumor, ukuran tumor, jenis sel


kanker.
• Pemeriksaan fisik dan imaging dapat memberikan petunjuk dimana
letak tumor dan seberapa besar ukuran
• Imaging : x ray ; CT Scan ; PET ; MRI ; USG
Pathological Staging

• Biopsi dibutuhkan untuk konfirmasi apakah jaringan tersebut jaringan


kanker atau normal.
• Biopsi dilakukan bisa dengan jarum halus atau dengan prosedur
khusus misalnya endoscopy atau bronchoscopy
• Jaringan yang diperoleh dilihat di microscope untuk melihat histo
patologi sel kanker dengan pewarnaan Immuno Histokimia
• Kadang kala pemeriksaan histopatologi dilakukan pada jaringan yang
diambil melalui kegiatan operasi
• Hasil biopsi dapat menentukan derajat keganasan sel kanker serta
jenis sel kanker
• Hasil pathological staging penting untuk menentukan terapi,
memperkirakan respon terapi dan menilai prognosis suatu kanker
TNM Staging

• The American Joint Committee on Cancer (AJCC) & the International


Union for Cancer Control (UICC)  TNM classification system
• T  tumor. Berdasarkan ukuran primary tumor dan apakah
berkembang kejaringan sekitarnya
• N  node. Menggambarkan apakah sel kanker menyebar ke lymph
nodes disekitarnya.
• M  metastasis. Menggambarkan apakah kanker menyebar ke
bagian / organ lain dalam tubuh.
Penentuan Stadium

• TNM classification dapat dikombinasikan dengan overall stage yang


menggunakan angka romawi I – IV, semakin tinggi angkanya semakin
tinggi derajat keparahan.
• Kadang kala stage di subdivisi kan dengan A dan B  stage IA, IB, dst.
• Stage 0 adalah carcinoma in situ  stadium kanker yang sangat dini
• Sebagai contoh : T1, N0, M0 breast cancer  the primary breast
tumor < 2 cm (T1), tidak ada lymph node involvement (N0), dan
tidak ada spreading ke organ tubuh lainnya (M0)  stage I cancer.
Tumor Grading

• Tumor grading  melihat seberapa jauh abnormalitas sel kanker


dibawah mikroskop. Dikenal dengan differentiation
• Grading biasanya menggunakan huruf 1 – 3 (4)
• Grade yang rendah menunjukkan jumlah sel kanker yang menyerupai
sel normal banyak
• High grade cancer  bentuk sel kanker sangat berbeda dengan
bentuk sel normal
• Grading ini menentukan jenis pilihan terapi kanker
• Prognosis yang buruk terjadi pada high grade cancer
Tumor Marker

• Pada umumnya tumor markers tidak digunakan untuk diagnosis


kanker. Tetapi tumor marker dapat membantu mendiagnosis
kemungkinan adanya kanker terutama jika sel kanker sudah
menyebar sangat luas.
• Sebagai contoh jika seorang wanita mempunyai sel kanker didaerah
pelvis dan abdomen  CA 125 sangat kuat menunjukkan adanya
ovarian cancer
• Alpha fetoprotein (AFP) adalah contoh tumor marker yang digunakan
untuk diagnosis. Level AFP menunjukkan liver diseases, tetapi jika
sudah mencapai level yang sangat tinggi dapat dipastikan hal
tersebut adalah liver cancer (biopsy tetap dibutuhkan ).
Tumor Marker

• Tumor markers dapat diperiksa pada saat diagnosis; dan sebelum,


selama dan setelah terapi
• Pemeriksaan secara regular untuk beberapa tahun untuk mendeteksi
apakah kanker kambuh.
• Pemeriksaan selama terapi  perubahan pada tumor marker levels
dapat digunakan untuk mengukur apakah terapi efektif atau tidak .
Alpha-fetoprotein (AFP)
AFP can help diagnose and guide the treatment of liver cancer (hepatocellular
carcinoma). Normal levels of AFP are usually less than 10 ng/mL (nanograms per
milliliter). AFP levels are increased in most patients with liver cancer. AFP is also
elevated in acute and chronic hepatitis, but it seldom gets above 100 ng/mL in these
diseases.
In someone with a liver tumor, an AFP level over a certain value can mean that the
person has liver cancer. In people without liver problems, that value is 400 ng/mL.
But a person with chronic hepatitis often has high AFP levels. For them, AFP levels
over 4,000 ng/mL are a sign of liver cancer.
AFP is also useful in following the response to treatment for liver cancer. If the
cancer is completely removed with surgery, the AFP level should go down to normal.
If the level goes up again, it often means that the cancer has come back.
AFP is also higher in certain germ cell tumors, such as some testicular cancers (those
containing embryonal cell and endodermal sinus types), certain rare types of
ovarian cancer (yolk sac tumor or mixed germ cell cancer), and germ cell tumors
that start in the chest (mediastinal germ cell tumors). AFP is used to monitor the
response to treatment, since high levels should go down when treatment works. If
the cancer has gone away with treatment, the level should go back to normal. After
that, any increase can be a sign that the cancer has come back
Anaplastic lymphoma kinase (ALK)
Some lung cancers have changes in the ALK gene that cause the cancer cell to make
a protein that leads to out of control growth. Tumor tissues can be tested for this
gene change. If it’s found, the patient can be treated with a drug that targets the
abnormal protein, like crizotinib (Xalkori®).

BCR-ABL
Chronic myeloid leukemia (CML) cancer cells contain a new, abnormal gene called
BCR-ABL. A test called PCR can find this gene in very small amounts in blood or
bone marrow. In someone with blood and bone marrow changes that look like
those seen with CML, finding the gene confirms the diagnosis. Also, the level of the
gene can be measured and used to guide treatment.
BRAF
Defects (mutations) in the BRAF gene can be found in melanoma, thyroid
cancer, and colorectal cancer. About half of melanomas have a BRAF mutation,
most often the one called BRAF V600. This mutation causes the gene to make
an altered BRAF protein that signals melanoma cells to grow and divide. This
mutation can be tested for in tumor tissue. If it’s found, the patient can be
treated with a drug that targets the altered BRAF protein, such as vemurafenib
(Zelboraf®).

CA 15-3
CA 15-3 is mainly used to watch patients with breast cancer. Elevated blood
levels are found in less than 10% of patients with early disease and in about
70% of patients with advanced disease. Levels usually drop if treatment is
working, but they may go up in the first few weeks after treatment is started.
(This rise is caused when dying cancer cells spill their contents into the
bloodstream.)
The normal level is usually less than 30 U/mL (units/milliliter), depending on
the lab. But levels as high as 100 U/mL can be seen in women who do not have
cancer. Levels of this marker can also be higher in other cancers, like lung,
colon, pancreas, and ovarian, and in some non-cancerous conditions, like
benign breast conditions, ovarian disease, endometriosis, and hepatitis.
CA 125
CA 125 is the standard tumor marker used to follow women during or after
treatment for epithelial ovarian cancer (the most common type of ovarian
cancer).
Normal blood levels are usually less than 35 U/mL (units/milliliter). More than
90% of women with advanced ovarian cancer have high levels of CA 125. If the
CA-125 level is increased at the time of diagnosis, changes in the CA-125 level
can be used during treatment to get an idea of how well it’s working.
Levels are also elevated in about half of women whose cancer has not spread
outside of the ovary. Because of this, CA 125 has been studied as a screening
test. But the trouble with using it as a screening test is that it would still miss
many early cancers, and problems other than ovarian cancer can cause an
elevated CA-125 level. For example, it’s often higher in women with uterine
fibroids or endometriosis. It may also be higher in men and women with lung,
pancreatic, breast, liver, and colon cancer, and in people who have had cancer
in the past. Because ovarian cancer is a rather rare disease, an increased CA-
125 level is more likely to be caused by something other than ovarian cance
Calcitonin
Calcitonin is a hormone produced by cells called parafollicular C cells in the thyroid
gland. It normally helps regulate blood calcium levels. Normal calcitonin levels are
below 5 to 12 pg/ml (picograms per milliliter). In medullary thyroid carcinoma (MTC), a
rare cancer that starts in the parafollicular C cells, blood levels of this hormone are
often greater than 100 pg/ml.
This is one of the rare tumor markers that can be used to help detect early cancer.
Because MTC is often inherited, blood calcitonin can be measured to detect the cancer
in its very earliest stages in family members known to be at risk.
Other cancers, like lung cancers and leukemias, can also elevate calcitonin levels, but
calcitonin blood tests are not usually used for detecting these cancers.
Carcinoembryonic antigen (CEA)
CEA is not used to diagnose or screen for colorectal cancer, but it’s the preferred
tumor marker to help predict outlook in patients with colorectal cancer.
The normal range of blood levels varies from lab to lab, and smokers often have
higher levels. But even in smokers, levels higher than 5.5 ng/mL (nanograms per
milliliter) are not normal. The higher the CEA level at the time colorectal cancer is
detected, the more likely it is that the cancer is advanced.
CEA is also the standard marker used to follow patients with colorectal cancer
during and after treatment. In this way CEA levels are used to see if the cancer is
responding to treatment or if it has come back (recurred) after treatment.
CEA may be used for lung and breast cancer. This marker can be high in some
other cancers, too like melanoma, lymphoma, thyroid, pancreas, liver, stomach,
kidney, prostate, ovary, cervix, and bladder cancer. If the CEA level is high at
diagnosis, it can be used to follow the response to treatment. CEA can also be
elevated in some non-cancerous diseases, like hepatitis, chronic obstructive
pulmonary disease (COPD), colitis, rheumatoid arthritis, and pancreatitis, and in
otherwise healthy smokers.
Epidermal growth factor receptor (EGFR)
This protein, also known as HER1, is a receptor found on cells that helps
them grow. Tests done on a piece of the cancer tissue can look for increased
amounts of these receptors, which is a sign that the cancer may grow fast,
spread quickly, and be harder to treat. Patients with elevated EGFR may
have poorer outcomes and need more aggressive treatment, particularly
with drugs that block (or inhibit) the EGFR receptors.
EGFR may be used to guide treatment and predict outcomes of non-small
cell lung, head and neck, colon, pancreas, or breast cancers. The results are
reported as a percentage based on the number of cells tested.
Some lung cancers have certain defects (mutations) in the EGFR gene that
make it more likely that certain drugs will work against the cancer. These
gene changes are more common in lung cancer patients who are women,
non-smokers, or Asian.
HER2 (or HER2/neu, erbB-2, or EGFR2)
HER2 is a protein that tells some cancer cells to grow. It’s present in larger
than normal amounts on the surface of breast cancer cells in about 1 out
of 5 people with breast cancer. Higher than normal levels can be found in
some other cancers, too, such as some stomach and esophageal cancers.
HER2 is usually found by testing a sample of the cancer tissue itself, not
the blood. Cancers that are HER2-positive tend to grow and spread faster
than other cancers.
All newly diagnosed breast cancers and advanced stomach cancers should
be tested for HER2. HER2-positive cancers are more likely to respond to
drugs that work against the HER2 receptor on cancer cells.
Hormone receptors
Breast tumor samples – not blood samples – from all people with breast
cancer are tested for estrogen and progesterone receptors. These 2
hormones often fuel the growth of breast cancer cells. Breast cancers that
contain estrogen receptors are often called ER-positive; those with
progesterone receptors are PR-positive. About 2 out of 3 breast cancers test
positive for at least one of these markers. Hormone receptor-positive breast
cancers tend to grow more slowly and may have a better outlook than
cancers without these receptors. Cancers that have these receptors can be
treated with hormone therapy such as tamoxifen or aromatase inhibitors.
Some gynecologic tumors, such as endometrial cancers and endometrial
stromal sarcomas, are also checked for hormone receptors to see if they can
be treated with hormone therapy drugs.
KRAS
Cetuximab (Erbitux®) and panitumumab (Vectibix®) are two drugs that
target the EGFR protein and can be useful in the treatment of
advanced colorectal cancer. But these drugs don’t work in colorectal
cancers that have mutations (defects) in the KRAS gene. Doctors now
commonly test the tumor for this gene change and only use these
drugs in people whose cancers do not have the mutation.
KRAS mutations can also help guide treatment for some types of lung
cancer. For instance, tumors with the mutations do not respond to
treatment with drugs erlotinib (Tarceva®) or gefitinib (Iressa®). Doctors
are looking at how KRAS may be used in many other types of cancer,
too.
Lactate dehydrogenase (LDH)
LDH is used as a tumor marker for testicular cancer and other germ cell
tumors. It’s not as useful as AFP and HCG for diagnosis because it goes up
with many other things besides cancer, including blood and liver problems.
Still, high levels of LDH predict a poorer outlook for survival. LDH levels are
also used to monitor the effect of treatment and to watch for recurrent
disease. LDH may be used in other cancers, too, including lymphoma,
melanoma, and neuroblastoma
Prostate-specific antigen (PSA)
PSA is a tumor marker for prostate cancer. PSA is a protein made by cells of the
prostate gland, which is found only in men. It’s the only marker used to screen for a
common type of cancer, but most medical groups do not recommend using it
routinely to screen all men. (The American Cancer Society recommends that men
talk to a doctor and make informed decisions about testing.)
The level of PSA in the blood can be elevated in prostate cancer, but PSA levels can
be affected by other things, too. Men with benign prostatic hyperplasia (BPH), a
non-cancerous growth of the prostate, often have higher levels. The PSA level also
tends to be higher in older men and those with infected or inflamed prostates. It
can also be elevated for a day or 2 after ejaculation.
PSA is measured in nanograms per milliliter (ng/mL). Most doctors feel that a blood
PSA level below 4 ng/mL means cancer is unlikely. Levels higher than 10 ng/mL
mean cancer is likely. The area between 4 and 10 is a gray zone. Men with PSA levels
in this borderline range have about a 1 in 4 chance of having prostate cancer. A
doctor may recommend a prostate biopsy (getting samples of prostate tissue to look
for cancer) for a man with a PSA level above 4 ng/mL.
Not all doctors agree with these cutoff points. This is because some men with
prostate cancer do not have an elevated PSA level, while some others with a
borderline or elevated level will not have cancer.
Response Criteria

• Complete Response : Hilangnya semua target lesi


• Partial response : Sedikitnya terdapat penurunan sebanyak 30% dari
ukuran tumor diukur dari diameter lesi terpanjang
• Stable disease : pengecilan ukuran tumor bisa sampai pada partial
response atau lebih kecil dan tidak ada penambahan lesi baru.
• Progressive Disease : Terjadi peningkatan ukuran massa tumor
sedikitnya 20% dari ukuran massa tumor yang terpanjang.
PENGGOLONGAN KANKER PAYUDARA

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