Understanding How Molecular Testing Works — Next-Generation Sequencing For Lung Cancer

“It’s always a good idea for the patient to ask about molecular testing,” Dr. Mohamed Mohamed, a thoracic medical oncologist at Cone Health Cancer Center, tells SurvivorNet.

How reliable is NGS testing?

While medical tests are generally beneficial, no test is 100% reliable. So, how do you know if you can trust the results from NGS testing?

“I look for the company and the agency that provides the best in the field and the ones that are really supported by publications,” Dr Mohamed explains. “You cannot just get tests from anyone who said: oh, I have molecular testing.”

NGS often provides more complete and accurate information than traditional single-gene tests, especially for patients with advanced lung cancer who may have multiple genetic alterations. Factors that can affect the reliability of NGS results include:

• Tissue sample’s size and quality
• Sensitivity and specificity of the NGS platform
• Interpretation and reporting of NGS results
• Validation and verification of the NGS method used

To improve the accuracy of your NGS results, your doctors will try to get enough tissue samples and then use a validated NGS platform that specifically looks at  lung cancer genes and biomarkers. They will usually compare NGS results to other tests, such as single-gene analysis.

At Cone Health Cancer Center, a team of experts will help you make sense of your test results and what they mean for next steps.

Types of NGS testing

The type and number of tests you will have depends on your diagnosis and treatment. Your doctor may recommend some of the following:

• FoundationOne®CDx: This test looks at 324 genes in solid tumors. Test results include microsatellite instability (MSI) and tumor mutational burden (TMB). These are key factors in deciding on immunotherapy. MSI indicates how well a tumor might respond to immunotherapy, while TMB measures the number of mutations within a tumor’s genes.
• OmniSeq Insight: This test provides comprehensive genomic and immune profiling for all solid tumors by looking at 523 different genes. Test results include MSI and TMB. It also measures PD-L1  protein levels using immunohistochemistry (IHC). PD-L1 levels to help predict a tumor’s response to certain immunotherapies.
• Cobas EGFR Mutation Test v2: This test identifies 42 mutations in exons 18, 19, 20 and 21 of the epidermal growth factor receptor (EGFR) gene, which is crucial in many cancers. It works with both tissue and plasma samples and allows simultaneous testing on the same plate, which makes it more efficient.
• Labcorp Plasma Focus: This tests for non-small cell lung cancer (NSCLC), colorectal, breast, esophageal, gastric, gastroesophageal junction carcinomas and melanoma. This non-invasive test analyzes circulating tumor DNA (ctDNA) in blood to assess cancer characteristics and monitor treatment response.

You should ask your healthcare team if the brand of molecular testing is right for your cancer type. It can take from a few days to a few weeks to get your test results back.

How is NGS performed?

You won’t usually need to undergo any extra procedures to have the NGS test done.

NGS testing uses the tissue that was collected during your lung cancer diagnosis biopsy or surgery. It’s routine for hospitals to save and store this tissue after a procedure.

In addition, your doctor may order NGS testing with a liquid biopsy. This is a blood test that analyzes circulating-tumor ctDNA circulating in your blood stream.

Most results from the NGS testing on tissue biopsy are available within two to three weeks. A liquid biopsy is usually much faster — you can get results in as little as a week.

Dr. Valsamo Anagnostou explains how liquid biopsies are performed.

Questions to ask your doctor

If you are considering molecular testing such as NGS, you should have a discussion to make sure you are comfortable with the process and the type of information your doctor expects to find. Some questions to consider asking:

• Should I have comprehensive and sensitive molecular testing?
• How will the molecular profiling be performed?
• Should I consider a liquid biopsy?
• How reliable are these tests?
• Will you compare the results to other types of testing?
• What mutations does my tumor have?
• Once the testing is completed, what are the recommended next steps?

Genetic tests to assess cancer risk

Cone Health Cancer Center has partnered with Helix, a leading gene testing company to introduce a population genomics testing initiative. This program may be of particular interest to individuals who want to understand their individual genetic risks of being diagnosed with lung cancer.

This collaboration aims to enroll 100,000 healthy participants over a span of five years. Leveraging Helix’s population genomics platform, genetic testing will offer medical insights for Cone Health patients.

The  goal of the initiative is to improve care for people developing health issues and provide important information to patients and doctors. The information doctors find could help delay, lessen, or even prevent some illnesses.

The program will also help Cone Health spot higher health risks in certain communities. This insight can lead to prevention and screening programs for the people who might benefit from it the most.

Enrolling in this program is optional and does not cost anything. Participants will be screened for genetic predisposition for certain diseases and conditions, such as lung, breast and ovarian cancer, colorectal cancer, and high cholesterol. Nationwide, nearly five million people are at an increased risk of one of these conditions because of a genetic mutation.

Learn more about SurvivorNet's rigorous medical review process.

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