New Research Touts Advantages in Next-Generation Sequencing for Cancer
- A new study by researchers at Brigham and Women’s Hospital suggests that roughly 6,000 additional colorectal and endometrial cancer patients can benefit from immunotherapy if they can undergo next-generation sequencing, which better detects the conditions within these patients than the existing standard of care.
- Next-generation sequencing (NGS) helps doctors analyze hundreds to thousands of potential DNA mutations in a single test. It uses a tumor or blood biopsy to analyze large portions of your DNA to identify specific mutations in cancer cells, detect hereditary cancer mutations inherited from parents, and identify appropriate targeted therapies and other potential treatments. This test can be given upon diagnosis, so it’s important you ask your doctor about it early on.
- Immunotherapy is a cancer treatment that triggers your immune system to search for and attack cancer cells, microscopic or more extensive tumors.
- Several mistakes in the DNA may help fuel tumor growth. Some of the most common mutations that drive colon cancer are MMR/MSI, KRAS/NRAS, BRAF, APC, and HER2. NGS helps with this detection. It’s essential to know what mutations you have since they can affect your treatment.
A new study published in “Cancer Cell” suggests that more colorectal cancer patients could benefit from immunotherapy. This cancer treatment triggers your immune system to search for and attack cancer cells. However, as it stands now, roughly 6,000 patients are shut out from this treatment due to existing cancer care guidelines.
Researchers from Brigham and Women’s Hospital in Boston found nearly “six percent of endometrial cancer patients and one percent of colorectal cancer patients with mismatch repair deficiency were missed by immunohistochemistry, the current standard of care for this condition,” according to a BWH news release.
Read More“In colorectal cancer and endometrial cancer, which are the two types of cancer where mismatch repair deficiency is most commonly seen, immunotherapy is not the standard treatment unless a patient has this condition,” said first author Dr. Elias Bou Farhat, a postdoctoral research fellow in the division of Pulmonary and Clinical Care Medicine at Brigham and Women’s Hospital in the news release.
“In patients with this condition, even in late-stage cancer, those who receive immunotherapy can live for years and, in some cases, be potentially cured. Including next-generation sequencing as a complimentary testing practice could benefit patients in all phases of cancer, from pre-treatment to advanced stages,” Dr. Farhat continued.
While no changes in the standard of care for patients with colorectal and endometrial cancer are expected anytime soon following this one study, it does add credence to the value of next-generation sequencing.
Helping You Understand the Impacts of Next-Generation Sequencing
- Next-Generation Sequencing (NGS) for Colon Cancer: Who Should Get Tested?
- How Can Next-Generation Sequencing Help You Find a More Effective Cancer Treatment?
- The Cost Of Next-Generation Sequencing
- Digital Guide: Dr. Jessica Tao Explains Next-Generation Sequencing for Breast Cancer
- Digital Guide: Dr. Jared Weiss on Next-Generation Sequencing & Lung Cancer Treatment
The Power of Next-Generation Sequencing
Next-generation sequencing has several names, including molecular testing, comprehensive genomic profiling, broad molecular profiling, and high-throughput sequencing. Despite its various names, NGS helps doctors analyze hundreds to thousands of potential DNA mutations in a single test. It uses a tumor or blood biopsy to analyze large portions of your DNA to identify specific mutations in cancer cells, detect hereditary cancer mutations inherited from parents, and identify appropriate targeted therapies and other potential treatments.
“Molecular profiling is actually utilizing various tests — one of the tests is next-generation sequencing — to generate a genomic profile for cancer, as well as identify important biomarkers that can define diagnosis, prognosis, and predict response to treatment,” Dr. Ankit Madan, a medical oncologist at MedStar Health in Washington, D.C., tells SurvivorNet.
Colorectal cancer affects your large intestine (colon) or the end of your intestine (rectum). The study done by BWH includes this kind of cancer patient.
Colon Cancer Mutations
These are specific mistakes in the DNA that fuel tumor growth. The most common mutations that drive colon cancer.
- MMR/MSI
- KRAS
- BRAF
- NRAS
- APC
- TP53
- HER2
MSI testing and KRAS testing are some of the most common tests used.
“A very significant part of colon cancer treatment involves testing for a mismatch repair and MSI microsatellite instability testing, which is done through immunohistochemistry, says Dr. Madan.
Mismatch repair (MMR) genes are responsible for helping to correct a specific type of error in which the DNA might be accidentally “mismatched” when cells replicate. When the MMR system is defective, it causes specific proteins (MLH1, MSH6, PMS2, MSH2) cannot perform this job. Thus, a mismatch repair deficiency (dMMR) allows errors to accumulate due to the lack of repairs.
The accumulation of errors affects areas of the cell’s genes responsible for keeping the cell from dividing out of control (a hallmark of cancer). It is known as High Microsatellite Instability (MSI-H).
There are two laboratory tests for this biomarker; both involve a tissue sample (biopsy) of the tumor. Depending on the method used, an abnormal result is called either microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR)
Patients with MSI-H or dMMR make up about 15% of patients with colorectal cancer, and it is recommended that all patients with newly diagnosed colon cancer, regardless of stage or spread, undergo MMR/MSI testing.
When Should You Undergo NGS Testing for Colon Cancer?
When considering molecular testing in colon cancer, two broad categories of testing are available, each with different indications and potential benefits. We typically refer to germline and tumor-based somatic testing when discussing molecular testing. Germline testing looks at inheritable DNA passed on from generation to generation. Somatic tumor testing attempts to understand what mutations are in the DNA and what molecular alterations in the tumor drive the cancer.
Germline testing looks at inherited DNA that is passed from parents to children. Specific changes or mutations in the DNA are known to increase an individual’s risk of cancer. Each mutation typically predisposes a person to developing cancer in specific organs or tissue types. By testing for inherited DNA mutations, you can uncover valuable information.
If the testing is negative for inherited DNA mutations, it gives the family peace of mind that there is no clear inherited increased risk of cancer.
If results are positive, certain inherited mutations can help future treatment with targeted therapies, and other related families can then be tested to evaluate their risk for subsequently developing cancer.
If you are concerned about your personal or family history of cancer and would like to know more about germline testing, please discuss it further with your healthcare team so you may get appropriate help.
Somatic tumor testing analyzes the cancer itself “to figure out what mutations or molecular alterations within the tumor itself may be driving the cancer or may produce treatment vulnerabilities that we can exploit to try to address the tumor,” says Dr. Eric Christenson, a Medical Oncologist at Johns Hopkins with a focus in gastrointestinal malignancies.
This additional testing gives us a few pieces of information that are important in guiding future therapy.
Patients can present at any stage in their disease with colon cancer thanks to effective screening and early detection with colonoscopies. With earlier-stage disease that is more localized and has not spread distantly, fewer molecular testing options are recommended.
If colon cancer is metastatic (Stage IV), meaning it has spread distantly, additional molecular testing is indicated to identify other potential targeted therapies that can be used.
The main types of somatic tumor testing used include:
- Mismatch Repair (MMR)/Microsatellite Instability (MSI)
- KRAS
- NRAS
- BRAF
- Human Epidermal Growth Factor Receptor 2 (HER2)
NGS Testing Can be Costly
NGS is still relatively expensive and “can be in the order of several thousand dollars,” according to Dr. Valsamo Anagnostou, a thoracic oncologist and the leader of the Johns Hopkins Molecular Tumor Board at The Sidney Kimmel Comprehensive Cancer Center. Despite the price tag, NGS is a relatively new technology, and the price has continued to decrease for several reasons over the past decade, including continued technological advancements, market competition, and economic scalability. “There is a lot of effort to decrease the cost of next-generation sequencing down to below a thousand dollars,” says Dr. Anagnostou.
Your financial responsibility and medical insurance coverage vary significantly based on your insurance provider, cancer type, and disease status.
How Immunotherapy Works, and Its Pros and Cons
Immunotherapy is a medicine that triggers your immune system to search for and then attack cancer cells, whether microscopic or in the form of more extensive tumors.
“Immunotherapy originally started as being an indication for patients who had stage four disease,” Dr. Anna Pavlick, a medical oncologist at Weill Cornell Medicine, tells SurvivorNet.
“In the beginning, we began making vaccines to trick the immune system into attacking a protein that we thought was important in the cancer. These vaccines for cancer rarely worked. The problem was the cancer was using a different track of the immune system to block it from attacking,” Dr. Ronald Natale, director of the Lung Cancer Clinical Research Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center in Los Angeles, previously told SurvivorNet during an interview on the subject.
“Well, scientists developed treatments, antibodies that would block PD-L1 from blocking the immune system. This unleashed the immune system to resume its attack on the cancer very successfully, at least in some patients,” Dr. Natale added.
“We have now done studies looking at using immunotherapy for patients who have stage three disease. Because we know that these patients have a 50/50 chance of whether this is going to come back or not, we want to make those odds of it coming back even less. But it is not chemotherapy. It does not bring down your immune system. It does not predispose patients to infection. It does not make them lose their hair,” Dr. Pavlick continued.
While immunotherapy is adequate for most patients, it has some side effects, most related to inflammation. You might experience diarrhea when your colon is inflamed or itching when your skin is inflamed. You can also have pain in your liver or pancreas if you have pancreatitis or hepatitis.
RELATED: Immunotherapy in Recurrence
WATCH: Understanding immunotherapy side effects.
Common Immunotherapy side effects include:
- Fatigue
- Nausea or stomach discomfort
- Joint pain
- Diarrhea or constipation
- Cough
- Rash
- Loss of appetite
- Changes in blood cell counts
- Fever
More severe adverse reactions include:
- Pancreatitis: Inflammation of the pancreas
- Colitis: Inflammation of the large intestine
- Pneumonitis: Inflammation of the lungs
- Hepatitis: Inflammation of the liver
- Thyroiditis: Inflammation of the thyroid gland
If you experience severe side effects, your doctor may need to temporarily or permanently stop your immunotherapy treatment.
“The side effects of immunotherapy are not, quote, forever. Depending upon the severity depends upon how we manage it. There are some patients who will get diarrhea, and we can give them treatments to calm down their diarrhea, which lasts a couple of days. It might be sporadic over a couple of weeks,” Dr. Pavlick said.
WATCH: Why immunotherapy Isn’t for Everyone
Immunotherapy doesn’t work for everyone with cancer. Dr. Vamsidhar Velcheti, the director of thoracic oncology at NYU Perlmutter Cancer Center, says that, unfortunately, it’s still difficult to predict which patients will respond well to immunotherapy treatments.
“The ways cancer generally escapes the body’s immune system is by protecting itself by producing certain proteins,” said Dr. Velcheti. “PD-L1 is one of those proteins that actually helps protect the cancer from the body’s immune system. For patients that have high levels of PD-L1, you could potentially use single-agent immunotherapy with good outcomes. The problem is that these proteins are constantly in flux.”
Learn more about SurvivorNet's rigorous medical review process.