Review – molecular genetic oncotests used in Israel
It is a well-known fact – patients with the same diagnosis respond differently to standard treatment. That is why over the past two decades Israeli medicine is focused on innovative approaches. New molecular and genetic technologies as a part of the precision medicine help to diagnose malignant diseases and predict cancer progression for each patient.
Oncotests allow to create the unique genetic profile of tumor cells. It helps to obtain more accurate and effective treatment for each patient. Molecular tests allow:
- to evaluate disease progression;
- to confirm diagnosis;
- to determine the optimal treatment protocols;
- to monitor the patient’s response to therapy.
This gives an advantages such as saving patient’s time, decreasing treatment costs and reduce the body’s adverse reactions.
Israeli oncologists constantly use the results of the molecular oncotests when making decision about a treatment regimen. As well as in the rest of the world, personalized medicine (targeted therapy) is increasingly extending in Israel.
Oncotest for personalized and targeted cancer treatment
Below there is a brief overview of molecular genomic tests. These oncotests are used by Israeli oncologists for targeted (personalized) treatments.
Molecular genomic oncotests – 4 main groups
Oncotests are checking the presence or absence of special biomarkers in the body. Tests help to provide information about the patient at almost every stage of care. For their intended purpose they are divided into four groups:
- Predisposition tests
- Diagnostic tests
- Prognostic tests
- Predictive tests
Predisposition tests indicate an increased likelihood of a particular disease in the body. Typically, such tests are considered if patient has an indication of the risk for a specific disease in his family history because it can be inherited from relatives. For example, BRCA1 and BRCA2 are genes indicating an increased risk of breast cancer. This information can be used by the doctor to select the tactics for observation and treatment of such patients.
Diagnostic tests make possible to determine disease in the early stages by a surrogate gene, when health condition can’t be defined by a physical or instrumental examination. These tests also help diagnose a disease if it has similar symptoms to another one. For example, mutations in the CFTR gene indicate the presence of congenital cystic fibrosis. This information provide to confirm the clinical diagnosis and to decide about the desired treatment protocol in the early stages of the disease.
Prognostic oncotests allow to determine the progression of a diagnosed disorder. They provide information about the cancer recurrence risk and the therapy efficiency. Prognostic oncotests may be helpful for doctor to decide whether and when additional therapy is needed after the initial treatment or in order to change the ineffective therapy protocol.
Predictive oncotests are used with targeted therapy. They help to evaluate the effectiveness of a specific treatment before it starts, as well as prevents undesirable side effects of anticancer drugs on the patient’s body. It is known, the same disease in different patients can have a different biological mechanism and various treatment results. Due to predictive and diagnostic oncotests doctor gets information that helps him to make a decision about the most effective personalized treatment. It is also called targeted therapy.
Most of the mutations that cause cancer and rare genetic diseases has been already studied. This allows to create a genomic tumor profile of the patient, and to select the target therapy. It makes possible to affect the specific molecular mechanism of cancer.
Oncotests may often include several groups – diagnostic and prognostic, or prognostic and predictive, or other combinations.
There are several types of analyzes for targeted treatment. Following biological samples may be used for DNA test:
- blood (liquid biopsy);
- saliva (liquid biopsy);
- tumor or metastasis tissues.
Liquid Biopsy Based Oncotests in Israel
Guardant360 Liquid Biopsy
A mutation test for all types of cancer by blood analysis (identification and mapping of DNA segments) to determine the individual sensitivity of a tumor to certain drugs. Genomic transparency is achieved through the verification of 73 genes. Guardant360 oncotest is intended for patients with metastatic cancer in cases when:
- cancer continues to progress during treatment;
- patient cannot undergo a biopsy taking procedure;
- there is insufficient material for taking a tissue sample.
Liquid Biopsy also reveals rare mutations leading to tumor growth and its resistance to treatment. Guardant360 test is a new, effective and safe analysis for the cancer treatment at patients with solid visceral tumors or metastases that are resistant to chemotherapy or another drug therapy.
CTC liquid biopsy (liquid panel)
Oncotest uses blood sample to determine circulating cancer cells in the blood and sensitivity to drugs.
CTC liquid biopsy test is a diagnostic tool that providing doctors and patients with a dual diagnosis of a malignant disease. The test calculates number of tumor cells (CTCs) circulating in the bloodstream. Oncotest also provides a drug list for targeted treatment.
During the laboratory examination the sensitivity of circulating tumor cells in the blood to more than 110 drugs and oncological procedures is verified. Tested drugs include both FDA-approved innovative and promising therapies, which are still in clinical trials but may already be included in a patient therapy program.
FoundationOne Liquid Biopsy
It is comprehensive genetic test for tumors, which is performed using a simple non-invasive blood test and helps to determine the target treatment. Oncotest examines 70 oncogenes and identifies all possible mutations and relevance in these genes. DNA of cancer cells is isolated from the blood in FoundationOne Liquid Biopsy test. This technology has the high MSI index approved by the FDA and examines the immunotherapy drugs for many cancers. In patients with advanced cancer, the oncotest helps to monitor the cancer progression over time.
CellMax-PanCa Monitoring Test
This test allows to perform an early diagnosis of cancer disease and it is based on a blood sample. Circulating tumor cells (or CTC) are cells that break away from the primary tumor and enter into the bloodstream at a very early stage of cancer progression.
Since at this stage the concentration of cancer cells is low, less than five cells per billion compared with normal body cells, until now it has been impossible to detect them with high accuracy. Oncotest is isolating rare free-circulating tumor cells from a single blood sample.
CellMax-PanCa Monitoring Test is a molecular genetic analysis aimed at the early detection and cancer treatment using innovative methods.
Tissue Sample Based Oncotests in Israel
This is a unique molecular genomic oncotest that provides patients and physicians with a reliable prognosis of the response to cancer treatment.
This functional test allows to give in advance the most accurate results of therapy for each patient and to choose a personal effective treatment protocol, including targeted and immunological therapy.
CANscript oncotest helps to select a personal treatment protocol for each patient, based on the individual characteristics of his body, the tumor and its reactions to certain drugs.
The test is performed on a “live” tumor tissue which is immediately delivered to the laboratory after surgery or biopsy. Due to a complicated, clinically prepared method, the laboratory biologists create the natural environment for a tumor from a patient’s blood sample. This oncotest provides a prognosis for a treatment response that has been tested with a various anticancer drugs.
Oncotest Teva – Primary Tumor Definition
Oncotest for Primary Tumor Definition is the newest method of examination at the molecular level, which helps to determine a tumor metastases source. Since metastasis preserves the molecular pattern from beginning, it is possible to locate the source of the primary tumor.
Triple Genomic Molecular Test Paradigm
This is a complex onco-test, which includes genomic and molecular cancer diagnostics using three separate tests:
- 1. Deep genetic sequencing to detect DNA mutations.
- 2. Detection of genomic RNA expression.
- 3. Characterization of tumor proteins.
These three oncotests are performed in order to predict the reaction for a certain patient and his tumor to targeted chemotherapy, immunotherapy and biological therapy. Genomic-molecular Paradigm oncotest ideally maps a tumor, creates genetic tumor profile and predicts the whole list of the treatment options most suitable for this person.
This is a molecular genetic oncotest, which uses the new generation method of sequencing. Cancerplex KEW can analyze more than 400 known cancer genes in solid tumors. Unlike hot spot analysis, which can miss up to 20% of clinically significant mutations, Cancerplex oncotest detects all possible changes in a genes group. This test helps determine drugs are appropriate for a particular patient and his specific tumor.
CancerSELECT 125 Oncotest
This predictive oncotest is used for all cancer types and allows to find out biological and immunotherapeutic methods will be suitable for a patient’s cancer. Due to information about the genome, which is obtained by sequencing 125 genes from tumor tissue, and comparing with normal tissue genes (saliva sample), the doctor receives a report with a list of suitable biological and immunological treatments. It needs a tissue of malignant tumor fixed in paraffin and a patient’s saliva sample for examination using CancerSELECT 125.
Oncotest is performed for all types of cancer. The target group is patients and their doctors who want to know which biological, immunotherapeutic, chemotherapeutic and target therapies will be suitable to treat their disease.
GPS Cancer test provide the genome complete sequencing (23,000 genes). This leading technology extracts DNA and RNA from tumor tissue and compares it with genome sequencing from a patient’s normal tissue (blood sample). It may help to adapt chemotherapy, immunotherapy and targeted treatment. Oncotest uses tissues and samples for examination:
- a cancerous tumor extracted during surgery;
- a biopsy fixed in paraffin;
- blood sample.
The test is performed for all types of cancer and determines which biological and immunotherapeutic methods will be suitable for treatment of a particular patient and his tumor. During the test, 595 genes are sequenced at the DNA level and RNA is isolated from the tumor tissue. These genes are compared to the patient’s normal tissue (blood sample). Tempus xT oncotest is applied on:
- a tumor tissue extracted during surgery;
- a biopsy tissue fixed in paraffin (paraffin block or slides);
- a patient’s blood sample.
This is a comprehensive genomic diagnostic test of tumor tissue. FoundationOne CDx test helps doctor to choose the personalized treatment for a specific tumor with the most effective and less toxic anticancer drugs for the patient’s body. Oncotest is based on new generation of genome sequencing (NGS) technology. It allows to simultaneously identify hundreds of genes and all genetic mutations that can cause cancer.
CDX Foundation One scans 324 different oncogenes and identifies all changes in tumor DNA when it may be cause for cancer progression. Diagnostic oncotest detects the TMB and MSI biomarkers in a malignant tumor, which help to predict the patient’s respond to immunotherapy.
FoundationOne Heme for hematological cancer
Tissue oncotest for complex genomic diagnosis of hematological malignant neoplasms – leukemia, lymphoma, multiple myeloma and sarcoma. This test provides clinical information for the oncologist. It collects data on risk factors and prognosis, as well as helps to select the targeted treatment according to the genome profile of a specific tumor. Therefore personalized treatment adapted to the genomic profile is more effective and less toxic.
FoundationOne Heme оncotest simultaneously scans 406 different oncogenes at the DNA level (hereditary material) and detects all types of mutations that cause hematological tumors and sarcomas. The test also identifies 265 genes at the RNA level (responsible for the protein production in the body) in order to find the corresponding changes common in hematological diseases.
Prostate cancer tests
The following oncotests are used in Israel:
- Decipher prostate
- ProMark Prostate
- Prolaris Prostate
- Oncotype DX Prostate
Due to detection of prognostic biomarkers, these oncotests help the onco-urologist to understand how prostate cancer will develop over a long time, and when to move from active observation to the choice of the desired treatment.
Tests for colon cancer
The following oncotests are used in Israel:
- CTS – Immunoscore Colon
- OncotypeDX Colon Cancer oncotest
These tests are intended for patients with locally advanced colon cancer with stage II or stage III. Oncotests are used by oncologists to assess the recurrence risk after surgery and the need for additional therapy.
Oncotests for breast cancer
The following oncotests are used in Israel:
- EndoPredict test
- OncotypeDX test
These oncotests are used to determine the risk of distant metastases in patients with locally advanced breast cancer with stage I-III, positive expression of estrogen receptors and / or progesterone, and negative expression to the HER2 gene. Molecular tests for breast cancer provides the oncologist with information that allows him to cancel chemotherapy without harm to the body in addition to hormone therapy.
Oncotests for thyroid cancer
Afirma oncotest. Test allows to provide a detailed genomic analysis for the patient’s thyroid node biopsy and to select the optimal treatment. The obtained information helps doctor to identify if a suspicious node is benign or malignant, and to reduce the amount of a surgical procedure on the thyroid gland.
Molecular testing for breast cancer in Israel
Even when breast cancer has been diagnosed, it is often hard to define the most effective treatment option.
For ER + positive and HER2-negative tumors that produce the ER – protein associated with an estrogen receptor, additional tests may help your doctor to define the best course of treatment.
This allows to calculate a long-term prognosis of the disease recurrence for patients in 10 years after treatment. Aggressiveness of tumor cells provides information for the oncologist and patient to select a reasonable type of treatment.
Oncotests for breast cancer use hereditary information, as well as the genetic profile of other tumors (if they are present). This makes it possible to obtain accurate data when making long-term decisions identifying patients who can safely avoid chemotherapy.
In the presence of ER positive breast cancer, hormone therapy is the standard treatment protocol, which allows to halve the risk of cancer recurrence. In some cases, chemotherapy is additionally used. When prescribing this type of treatment, the doctor analyzes several factors and decides on the potential benefits and risks for the patient.
Genetic tests for breast cancer allow to determine accurately the low or high risk of cancer recurrence, and get the most out of the main treatment without the side effects of chemotherapy, where applicable.
How to understand and interpret the results of oncotests for breast cancer?
The results of the conducted oncotests will affect your further treatment. After a detailed analysis of the genes associated with breast cancer, the doctor receives a report that contains information about the low or high risk of recurrence (return) of the disease over the next ten years. Together with other factors, doctor defines the best treatment for the patient.
These factors are:
- Health condition and other diseases
- Possible effects of chemotherapy
Proper and safe treatment of a patient with breast cancer allows to choose the most appropriate treatment, to avoid harm from unnecessary chemotherapy, and to reduce the total cost of treatment.
Breast EndoPredict testing
This diagnostic test is designed to determine the risk of distant metastases in patients with primary breast cancer that has positive expression of estrogen receptors (ER +) and negative expression of HER2 protein during hormone therapy. The oncotest determines the expression levels of 8 genes associated with estrogen receptors and rapid cell proliferation. EndoPredict is a diagnostic tool that helps the doctor to make an informed decision, avoid chemotherapy, if possible, and choose an individual treatment method for each patient.
OncotypeDX testing for breast cancer
Oncotest is performed on a sample of tumor tissue obtained during surgery or biopsy. It is intended for women with a diagnosis of stage I-III breast cancer and positive expression of estrogen and / or progesterone receptors, and negative expression with respect to HER2. It helps the oncologist to decide whether chemotherapy should be considered as a preventive measure for relapse in addition to hormone replacement therapy.
Molecular testing for prostate cancer in Israel
Biomarkers are the measured molecules, which indicate the health state of a patient.
High level of PSA biomarker can point to the occurrence of prostate cancer. Israeli oncologists use molecular testing for prostate cancer to determine the growth rate of the tumor and to assess the treatment results. In particular, it is used for evaluating the progression of local prostate cancer.
In men who have low or medium risk of prostate cancer progression, molecular genomic testing can tell doctor how the cancer will behave in the future. Today, Israeli oncologists use the following molecular tests:
- Oncotype DX Prostate
- Prolaris Prostate
- Promark prostate
Molecular testing is performed on prostate tissue, which is taken using a biopsy for diagnosis. Molecular prostate tests complement standard lab tests and diagnostics, including:
- PSA level
- Gleason score
- Cancer stage
- Ultrasound and CT diagnostic images.
Numerous studies carried out continuously with molecular genomic testing and their results are evaluated over time. This helps to increase their accuracy, as well as to explore new tumor biomarkers and to assess their prognostic properties for the cancer progression.
This oncotest is intended for patients with a low or very low risk factor of prostate cancer in accordance with NCCN guide. It is about those who have not yet received treatment for prostate cancer, and the doctor has to choose either an active monitoring or starting a treatment. Prostate Decipher testing is also used when a patient has signs on the classification of TNM as follows:
- pT2 with positive fields;
- malignant tumor with pT3;
- PSA level above normal.
ProMark Prostate testing
It is used as a prostate cancer testing in patients with a low risk factor in accordance with NCCN. ProMark Prostate testing allows the doctor to understand how cancer can develop after a diagnosis. Thanks to prognostic biomarkers, the oncologist make an informed decision regarding the appointment either of active screening or various types of treatment.
Prolaris Prostate testing
This is recommended by NCCN for patients with very low, low risk and favorable intermediate risk of prostate cancer. These are patients who have not received treatment for prostate cancer and they are candidates for active monitoring or therapy.
Oncotype DX Prostate
A biopsy of prostate tissue is taken in paraffin during genomic analysis. Thanks to the detection of prognostic biomarkers, the Oncotype DX Prostate testing helps the doctor to understand how prostate cancer will develop for a long time, and in time to move from active screening to the selection of the right treatment – prostatectomy or radiation therapy. This group of patients already have a diagnosis of prostate cancer at an early stage and have undergone a biopsy with a Gleason score:
- 6 points – low risk;
- 7 points – moderate risk.
♦ Diagnosis of prostate cancer in Israel.
♦ Molecular oncotests help to obtain more accurate and effective treatment for each patient. ⇒ See review of all the molecular oncotests done in Israel.
Oncotest for thyroid cancer
During cytological assessment of thyroid cancer about 20-25% of cases are reported indeterminate or ITC (indeterminate thyroid cytology) in accordance to Bethesda III and Bethesda IV value score, because cytological examination has its own limitations. In the meantime, thyroid cancer takes the place of the most frequent endocrine malignancy.
Physicians have an important task to determine further patient’s care and make better decisions when:
- nodule of thyroid gland has malignancy – to perform a surgery;
- nodule has benign nature – to give recommendation for follow-up and screening.
Until 2009, patients with indeterminate diagnosis of nodule have been undergo a diagnostic surgery based on the malignancy probability from 15 to 40%, even if histopathology has proven to be benign. Surgical procedures thyroidectomy and thyroid lobectomy leads to hypothyroidism with long-life hormone treatment and health conditions such as fatigue, sleepiness and weight gain.
Today, Israel offers a valuable solution for this problem such as molecular genetic testing, which helps doctors to select the best treatment options for patients who require it.
Genetic molecular testing for thyroid cancer such as Afirma or ThyroSeq gives the opportunity to avoid unnecessary risks and costs related to thyroid surgery.
Afirma oncotest for thyroid cancer testing
Performing a detailed genomic analysis of a patient’s biopsy at DNA lab, Afirma testing helps to make a decision about optimal treatment. The testing report allows oncologists:
- to determine the benignity or malignancy of indeterminate nodules
- to get confirmed type of thyroid cancer
- to reduce the surgery amount.
Genomic and clinically proven testing is improving the cytological diagnosis of thyroid nodules. Afirma helps doctors to diagnose and make better decisions about the treatment for each patient avoiding unnecessary thyroid surgery where it is indicated. The Afirma test was developed by experts in the field of oncogenetics science. During analyzing, it examines the expression of more than 100 genes that help to find gene’s biomarkers referring to benign or suspected of being malignant tumors.
Genetic testing for hereditary cancer in Israel
It’s has been proven that 5% to 10% of cancer are associated with gene mutations. Every cell of the body has it inherited or transferred to the next generation. A hereditary genetic mutation does not mean that a man will have cancer disease, but he is at higher risk for developing certain types of cancer.
Genetic testing for cancer is performed when a specific type of cancer has been identified in the family or with the next of kin and a gene mutation is suspected. Predisposition testing can be used to find many hereditary gene mutations – oncogenes and tumor suppressor genes.
Genetic predisposition testing can be used for the following hereditary cancers:
- breast cancer – BRCA1 and BRCA2 genes
- bowel cancer
- pancreatic cancer
- uterus cancer
- ovarian cancer
- colon cancer
- bladder cancer
- thyroid cancer
When are genetic testing performed to detect cancer risks?
A diagnostic genetic test is recommended if the family has:
- Relatives from the same side of your family have the same type of cancer.
- First-degree relatives (mother, father, sisters, brothers, children) are diagnosed with cancer.
- A family cancer group is associated with a single gene mutation (for example, breast, ovarian, colorectal and pancreatic cancers).
- Early cancer incidence.
- Information about Hereditary Cancer Syndromes.
- Rare types of cancer (for example, eye cancer – rentinoblastoma or breast cancer in men).
- A family member has more than one type of cancer.
- Race or ethnicity (e.g. Hebrew Ashkenazi).
- Physiological precancerous conditions.
- Predisposition testing has been performed previously and a mutation has been detected.
Where to start?
If there are cancer cases in your family and if you believe that molecular genetic testing can be beneficial to you, consult your doctor or Israeli specially trained genetic counselor.
A genetic counselor can help to determine the desired test for you and your family. After undergoing the genetic predisposition tests, you will receive a report with the research results.
It is important to consult with a highly professional genetics, because the test results themselves provide only incomplete and limited results to understand a risk of getting cancer disease. The geneticist correctly interprets the results and provides the basis for further individual diagnosis and therapeutic strategy.
Genetic molecular tests based on a blood sample or saliva, allow to understand the type of a specific mutation and get new options available to people at cancer risk. For example, if hereditary breast cancer is suspected, the presence of the brca1 and brca2 genes indicates it. In this way patients will be ready for a personal treatment protocol based on known hereditary oncogene. This protocol is used in personalized medicine and targeted treatment, and is being actively introduced in Israel.
Ethical side of genetic predisposition testing
Cancer mutations inherited by kinship affect not only you, but also family members who share your hereditary information. A report on the results of genetic research can lead to a variety of emotions – from anger to guilt. Nevertheless, it is necessary to do this for the early detection of hereditary oncogenes and to select an individual screening for cancer together with the doctor.
Genetic predisposition oncotests may require additional testing and procedures
In some cases, additional medical tests, regular cancer screening or procedures based on the results of genetic testing may be required. These activities can detect cancer at an earlier stage when it can be cured.
Cost of predisposition genetic oncotests
The cost of genetic testing for hereditary cancer can vary and depends on the genes number and the test purpose.