How Can Next-Generation Sequencing Help You Find a More Effective Cancer Treatment?

Our body is composed of microscopic building blocks called cells. Every cell in your body carries genetic codes that instruct your body to run properly. If there is any change or error that occurs at your gene level, your healthy cells stop working properly. These errors can lead to gene mutations, which can fuel the development of cancer.

“One of these healthy cells is sitting put, it’s doing its job and it makes mistakes in its instructions. These instructions are called ‘DNA’, and mistakes are called ‘mutations,'” says Dr. Jared Weiss, section Chief of Thoracic and Head/Neck Oncology at the University of North Carolina Lineberger Comprehensive Cancer Center.

According to Weiss, “These mistakes make the cell forget how to do its job; instead it learns how to make copies of itself spread and grow, which is what cancer is.”

What is Next-Generation Sequencing (NGS)?

Researchers have found a way to examine the genetic material of a patient’s tumors. In the last few decades, they have learned a great deal about how changes in our genes can affect our health and increase the risk of cancer.

“NGS testing can look at both DNA and RNA within a patient’s tumor. And this allows us to identify specific mutations which we may have a targeted therapy for, meaning a treatment that is specifically targeted against a specific change,” says Dr. Katherine A. Scilla, a thoracic oncologist at the University of Maryland Greenebaum Comprehensive Cancer Center.

NGS testing offers the most comprehensive molecular testing for cancer management and can essentially answer the question: What are the mutations or alterations in my cancer cells and how can we target them for treatment?

“Molecular profiling is a broad term that we use to describe a variety of tests that look really at the molecular level of cancer,” says Dr. Hannah McManus, genitourinary medical oncologist at Duke Cancer Center, Durham, NC. “So NGS testing is really one of the more common things that we use in molecular testing and cancer. And this genetic testing lets us sequence the DNA or building blocks of the DNA in a really fast and efficient way to be able to profile someone’s cancer.”

Who Qualifies For NGS

NGS is currently the standard of care for many advanced-stage cancers. However, in some instances, this testing may be useful even if the cancer is in an early stage.

Your care team may use other information they have about your cancer to determine their recommendations for this testing.

Types of NGS Testing On The Market

There are a number of tests you may encounter, depending on where you are getting treatment and what you are getting treatment for. Here are some of the common ones currently on the market:

• FoundationOne®CDx looks at 324 genes in solid tumors and says it can takes up to 12 days for results. Test results include microsatellite instability (MSI) and tumor mutational burden (TMB) to help inform immunotherapy decisions.
• OmniSeq Insight provides comprehensive genomic and immune profiling for all solid tumors. It looks for 523 different genes. Test results include microsatellite instability (MSI) and tumor mutational burden (TMB), as well as PD-L1 by immunohistochemistry (IHC).
• Cobas EGFR Mutation Test v2 identifies 42 mutations in exons 18, 19, 20 and 21 of the epidermal growth factor receptor (EGFR) gene. It is designed to test both tissue and plasma specimens with a single kit, and allows labs to run tissue and plasma on the same plate simultaneously.

You should ask your healthcare team if the brand of molecular testing they are doing is optimal for your cancer type.

How is NGS Testing Conducted?

The first step is to ask your doctor about NGS testing. Your doctor should walk you through whether it is right for you at your stage of cancer.

The test uses a sample of the tumor (removed during a biopsy or surgery) to look for a variety of mutated genes and alterations. Your doctor may also consider sending a blood sample for something called a “liquid biopsy.”

The blood sample will then be sent to a laboratory where the test is carried out. NGS results can take a few weeks. Liquid biopsy results can come back in less than a week.

Your doctor should go through your results with you and discuss how they may impact your treatment plan.

How to Prepare for NGS Testing

You don’t need to do anything specific to prepare for an NGS test. It’s performed in a laboratory using a small tissue sample that is obtained during a biopsy or surgery. Occasionally, your doctor may need a second biopsy if there is not enough remaining tissue.

Nowadays, many doctors obtain a liquid biopsy in addition to a tissue biopsy. This helps to compare results between the tissue biopsy and liquid biopsy. It is also a faster and easier way to monitor for changes in your tumor over time.

“Most patients when they come to see their oncologist have already had a biopsy or a sample taken of the tumor, and that sample can be used [for] testing. Other times we’ll talk about whether a blood test or what we call a liquid biopsy is the best option for you. That’s looking for the cancer DNA in the bloodstream,” explains Dr. McManus.

Ask your cancer care team if they will need to draw the liquid biopsy sample on your initial visit.

Should You Do Testing More Than Once?

Cancer cells can change their behavior over the course of a lifetime. Your doctor may recommend obtaining NGS testing more than once during your cancer treatment to detect additional information that may change the treatment.

It can be very situation-dependent, says Dr. McManus. “Cancer changes over time; if your cancer has changed in how it’s growing or has moved to another place in your body, we may talk about resending this testing to see if there has been a change in the mutations that might help guide those treatment decisions.”

What the Results Mean for Me

The result from an NGS test comes back as a broad panel of mutations with the recommendation of targeted agents.

Generally, the test results also have other mutations that may not have any targetable drugs available in the market; it may, however, be a beneficial part of enrollment in a clinical trial.

The results of the NGS test help:

• Determine the treatment plan after cancer diagnosis based on your cancer cells’ genetic makeup
• Determine if adding a targeted agent may provide more benefit than chemotherapy
• Guide your eligibility for a clinical trial

NGS Testing For Common Cancers

Depending on the type and stage of your cancer, the NGS test may be helpful in planning treatment for advanced, recurrent, or difficult-to-treat cancers.

The NGS test is frequently done for the following cancers:

• Breast
• Lung
• Colon
• Prostate

The most common genetic mutations linked with these cancers are:

• EGFR
• KRAS
• BRAF
• TP53
• HER2
• MMR/MSI

Questions To Ask Your Doctor:

• Am I a good candidate for next-generation sequencing?
• What are my chances of having a mutation that has a targetable drug?
• How long will it take to get my NGS testing results?
• Do you need a second biopsy to get more samples?
• Is there a clinical trial that is available for me?
• Is there any indication for NGS testing in early-stage cancer?

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