Oncologists use genomic sequencing to try to refine the treatment of rare cancers - about this and more in the following interview with Dr. Sharon Pels - an oncology expert
Harala Halevi
"The tests show that you have a cancerous tumor" - a sentence that instantly changed the world of every person who ever heard it. After the initial shock, everyone is faced with a collection of questions and challenges - both difficult and frightening. What does this mean for my future? Can I get out of this? What will my life look like with the treatments? And how will the children receive it? And the challenges are even greater when it comes to a rare cancer.
A rare cancer is one whose incidence in the population is not high. "There are tumors that are considered rare all over the world and there are tumors that are rare only in certain regions, but common in other regions. For example, in Israel, tumors in the esophagus are considered rare tumors. On the other hand, in China and Japan, esophageal tumors are actually common. Just as here we treat breast and colon cancer as a common cancer, similar to Western Europe and the USA, in the East it is actually relatively rare," says Dr. Sharon Pels, oncology specialist, director of the service for gastrointestinal tumors, and deputy director of the oncology department, Ichilov, Tel Medical Center -Aviv by Souraski, in a conversation we are having about the treatment of rare cancers.
״The problem with rare cancers is that there are fewer drugs that have been studied and fewer drugs in the health care basket, so the medical world has less knowledge and experience in these types," explains Dr. Pels.
So if a cancer that is rare here is common in other countries, can you learn from them how to treat it?
We can certainly learn from what has been studied in the Eastern countries and from their clinical experience with tumors that are considered rare here, but we know that there is also a genetic difference that can have an effect, so we are careful to draw conclusions about specific treatments that are given in countries whose population is genetically different from ours.
Does the fact that esophageal cancer and biliary tract cancer are rare tumors in Israel mean that they are discovered at a relatively late stage?
"Since there are no screening tests that are accepted for rare tumors, and since in many cases bile duct and esophageal cancer in the early stages do not cause significant symptoms, it is difficult to detect them at an early stage. In later-stage esophageal tumors, they may cause difficulties in swallowing, chest pain, heartburn, hoarseness, and more. When a patient complains of these symptoms, the initial diagnosis is usually made by a gastroenterologist who will perform an endoscopy in the esophagus and stomach (gastroscopy). If a suspicious finding is discovered, the doctor will take a biopsy and send it to pathology - examination of the sample under a microscope - which can determine if it is a tumor. At this stage it is also important to determine whether it is squamous cell carcinoma or adenocarcinoma. This classification is significant because the treatment of these two types is different.
Biliary tract cancer is also very rare. In the past, 8% to 10% of cancers diagnosed were of unknown origin - the various tests indicated a malignant disease but they did not know what its source was. Thanks to the innovative imaging, we know today that the origin of many of these tumors is in the gallbladder and bile ducts (intrahepatic and extrahepatic). The main symptoms are jaundice of the skin, the cornea (the white of the eyes), the tongue and other mucous membranes, the stool is greasy and the urine is dark, and there can be pain in the upper right abdomen, there is usually a loss of weight and sometimes pain that radiates to other areas. Unfortunately, tumors in the bile ducts and esophagus are usually discovered at a relatively advanced stage.'
How do you decide how to treat rare cases that do not have a clear and fixed treatment protocol?
"The oncology team gathers and examines each case individually - we go over all the known data regarding the patient - laboratory test results, symptoms, the health background and pathological findings, find out the stage of the disease ("staging") and examine the appropriate options for the particular patient. The progress of recent years is that with the help of genomic sequencing, which is done through comprehensive genomic tests, we can today diagnose the unique genomic profile of the tumor and thus gather more information about the tumor.'
For more information on comprehensive genomic testing, click here>>
So it sounds like comprehensive genomic testing is basically like a magnifying glass for a detective.
"Comprehensive genomic tests allow us to investigate in depth the tumor tissue taken in the biopsy. If we do not have a biopsy from the tissue, we can use a liquid biopsy (liquid) - a special blood test that can locate DNA segments of cancer cells that have come from the tumor into the bloodstream. These tests give us information about the tumor's unique genomic profile, information that until recently we would not have been able to discover. The genomic profile is the composition of the changes of the tumor, and each tumor has a biological composition that is unique to it. These tests can expose us to appropriate treatment options that we may be able to use. In this way we can sometimes build a more accurate treatment plan and know what we will have to offer within the therapeutic arsenal.'
These tests are especially important in rare cancers for which there are usually fewer treatment options. Today we know that different types of gallbladder and bile duct cancer develop from certain genomic changes or mutations, and each area, whether it is a gallbladder or intrahepatic or extrahepatic bile ducts, has mutations that are characteristic of it. For example, a mutation in the IDH gene can appear in up to 40% of cases of intrahepatic bile duct cancer or a mutation in the FGFR gene appears in almost 50% of cases. Those mutations have dedicated biological treatments - precise treatments that target certain mutations. Therefore, if we know what the unique genomic profile of the particular tumor is, we can tailor the treatment better.'
So the main advantage of genomic sequencing is in adjusting the treatment?
"True, but the flooring is also important in other aspects. For example, through the genomic tests we can find out if the patient has genetic mutations that pass from generation to generation. If a patient has inherited the mutation from one of his two parents, this knowledge can affect the rest of the family. With this knowledge, siblings, parents and children can find out if they are in a risk group and if they should be tested more often."
Sounds a little scary. After all, when someone is sick, we want to focus on his recovery and not worry about the rest of the family.
"There is no need to be afraid. Many times when you know about the genetic mutations in the context of the family members, you can prevent the development of cancer. After all, the most effective way to fight cancer is to prevent it.'
Are the comprehensive genomic tests available to every patient who requests them?
"Meanwhile, in most types of cancer the genomic sequencing is not yet in the basket, but in certain tumors, such as colon cancer, lung cancer, bladder cancer and more, comprehensive genomic sequencing can be done as part of the basket. There is also an option to use private insurance.'
How do you know which test to choose?
"It is advisable to choose the test that the attending physician recommends - it is important that he knows the report and knows how to read it, and that he trusts the company that performs the test."
For more information about comprehensive genomic tests, you can read here>>
| The importance of genomic testing in rare cancers Tumors in the salivary gland, esophagus, biliary tract and sarcoma (connective tissue tumor) are examples of types of cancer that are considered rare in Israel. One of the biggest hurdles in rare cancers is diagnosis. The problem is that when you don't look for certain mutations, you don't find them and you don't recognize them. This means that in rare cancer it is sometimes possible to miss diagnoses or to diagnose only at a later stage what the specific type of tumor is, which may affect the type of treatment given and its results. Clear cell sarcoma is an example of a rare soft tissue cancer that occurs in young adults. Under a microscope, this tumor has characteristics that resemble a certain type of melanoma (skin cancer), which is a more common cancer, so the diagnosis of sarcoma may be missed. But in clear cell sarcoma there are two genes (ATF1 and EWSR1) that undergo a genomic change, something that does not happen in melanoma. A comprehensive genomic test can diagnose the complete genomic profile of the tumor and thus locate this genomic change. For example, the Foundation One test can simultaneously sequence the DNA of 324 to 406 genes (depending on the type of test) and thus enable a more accurate initial diagnosis. This is in contrast to a genomic test for a mutation in a single gene (which does not detect other mutations that may be present in the tumor) or a hot spot test that tests predetermined mutations and only in certain areas of the tumor, and may miss other relevant mutations. The more rare cases are diagnosed more accurately, the more it will be possible to promote research in these types of cancer and develop new treatments for these types. |
The article was written in collaboration with Roche, the representative of Foundation Medicine in Israel
