What Questions To Ask Your Doctor About Lung Cancer & Next-Generation Sequencing

Dr. Jared Weiss, a medical oncologist specializing in lung and head and neck cancer at UNC Lineberger Comprehensive Cancer Center, explained to SurvivorNet several reasons why the drugs are a preferred treatment option.

“First, you get a treatment that is far more likely to work than chemotherapy [several fold more likely to shrink the cancer],” he said. “Number two: they last longer than chemo. Three: they are less toxic in getting you there. They have far, far fewer side effects than chemo.”

Finally, he said, “the cherry on top is that they are pills, instead of IVs. You’re not spending that time in the infusion room.”

In simple terms, NGS testing is a very advanced technology. Sometimes, it’s called molecular testing or profiling. What it does is it checks your tumor cells for mistakes in your genes, called mutations. These mistakes can make your cancer grow and spread. When your doctor does NGS testing, they’re basically looking at lots of genes together to find any mutations that might be causing your lung cancer to grow.

Why does NGS Matter?

One of the significant advancements in cancer care in the past decade comes from something called “targeted therapies,” and it all starts with NGS tests searching for specific mutations in your tumor. This testing dives deep into the genetic changes (somatic mutations) in your cancer cells to figure out the best treatment for your cancer. Scientists have identified several targets for therapy against these mutations, and this discovery could ultimately enhance the chance of survival and improve the quality of life for lung cancer patients.

NGS has completely transformed how we treat lung cancer. Unlike traditional chemotherapy, which can harm both cancer and healthy cells, targeted therapies are more precise. They only target the genes that have mutations, potentially causing fewer side effects while still improving the chances of beating cancer.

Lung Cancer Driver Mutations

NGS testing helps find important mutations that drive lung cancer. These are called “driver mutations,” and they’re mutations that can be specifically targeted with therapies.

The National Comprehensive Cancer Network (NCCN) suggests testing for 9 specific biomarkers (or mutations) before starting treatment for advanced lung cancer. These biomarkers are EGFR, ALK, ROS1, BRAF, KRAS, MET, HER2, RET, and NTRK. Your doctor will choose treatments that are most likely to work based on the mutations they find in your NGS test results.

Which Lung Cancer Patients Should have NGS Testing?

Molecular testing should always be part of discussions between you and your healthcare team. However, for patients with advanced lung cancer, NGS is essential.

“It’s absolutely clear that every stage four patient with non-squamous, non-small cell lung cancer should have comprehensive and sensitive molecular testing done early, and with that PD-L1,” Dr Weiss emphasizes.

You may be a candidate for NGS testing if you have been diagnosed with:

• Advanced stage adenocarcinoma of the lung
• Advanced stage squamous cell cancer of the lung
• Advanced stage adenosquamous cancer of the lung

In early stage lung cancer, you should discuss if NGS testing could be right for you, too.

Clinical Trials

Next-Generation Sequencing can help you pursue a clinical trial of a new lung cancer drug before they’re made available to the public.

Clinical trials might sound intimidating, but they’re actually the most reliable method researchers have for testing new treatments, techniques, or devices to make sure they’re safe and work well.

How is NGS Performed?

The NGS test is performed on the tissue that was collected during your lung cancer diagnosis biopsy or surgery. Hospitals typically save and store this tissue as part of their routine procedure. You won’t usually need to undergo any extra procedures to have the NGS test done.

In addition, your doctor may simultaneously ask for NGS testing on a liquid biopsy. A liquid biopsy is a blood test that analyzes circulating-tumor DNA (ctDNA), or DNA from dead cancer cells circulating in your blood stream.

Most results from the NGS testing on tissue biopsy are available within two to three weeks from the date the tumor sample is received by the laboratory. A liquid biopsy is much faster, Dr. Weiss explains, and typically arrives within a week.

“If I meet a patient for the first time and they haven’t yet had this testing [which I think is the case in most places in the country, where the medical oncologist meets the patient and nothing’s been ordered], I’d have the conversation in the plainest english that I can muster, about why it matters,” he says.

“And then I will talk to the pathologist and see if we have tissue left [from a previous biopsy or surgery], because nobody wants another needle stuck into them. If there’s adequate tissue remaining, it’s just an order, right?  I sign an order, the tissue goes off, and we test the tissue for these changes.”

Financial Burden: Will My Insurance Cover NGS Testing?

Cancer treatments are expensive, even with insurance. Some people lose income as they’re unable to work and/or they must pay for childcare while undergoing treatment. Even the cost of parking at the hospital can add an extra burden to any available funds. Often referred to as the financial toxicity of cancer, it can take a toll on anyone’s budget.

Medicare and many other insurance providers typically include NGS testing in their coverage. If you find out that your specific plan doesn’t cover the full NGS test, don’t hesitate to have a conversation with your cancer care team. They might be able to collaborate with your insurance company to secure approval for the test.

In some cases, the company conducting the test might directly communicate with your insurance provider to see if they can reduce or eliminate the cost for you. Additionally, there’s the Next Generation Sequencing (NGS) Affordability Program available to assist in lowering the expenses associated with the test.

PD-L1 Testing

PD-L1 testing is different from NGS Testing. It measures the level of certain proteins in cancer cells.

“It’s standard of care to get some kind of PD-L1 testing,” says Dr Weiss. “It’s really fast, it’s really cheap, it’s really easy. You can do it anywhere in the country.”

PD-L1, also know as programmed cell death 1, is a protein that is found on the outer surface of cells in your immune system. Dr Weiss also explains: “PD-L1 is not a mutation. It is an expression of a protein on the cancer surface, that it might be using to hide from the immune system”

If you were recently diagnosed with lung cancer, your oncologist should discuss PD-L1 testing with you. This laboratory test helps physicians determine whether a patient will likely benefit from immunotherapy, since a third of patients with late-stage NSCLC have high levels of PD-L1.

What is Immunotherapy for Cancer?

Our immune system employs white blood cells to go after unusual or foreign cells within our body. Yet, cancer cells are crafty and can hinder the immune system’s work. They create specific proteins that act as a shield, safeguarding the tumor from white blood cells. Consequently, the body fails to identify the tumor as something abnormal.

Immunotherapy drugs step in to break this defense mechanism. They make sure that the white blood cells correctly recognize the cancer cells and attack them as they should. The actual cancer cells aren’t necessarily tough to deal with, but they have a knack for multiplying rapidly. Therefore, immunotherapy drugs empower the patient’s immune system to take control of the cancer on its own before it can spread further.

For instance, if a biopsy and tumor analysis show that a cancer expresses a high level of a protein called PD-L1, there is a fairly good chance that a PD-1 inhibitor (a type of immunotherapy) will be effective. Research has found that the higher the level of PD-L1 in some lung cancer patients, the more effective the immunotherapy was, but there was even improvement with lower levels.

Potential Side Effects Of Immunotherapy

The negative effects of immunotherapy can be quite severe, so it’s important to inform your physician as soon as you experience any abnormal symptoms. Those who are taking more than one immunotherapy drug, referred to as combination therapy, are at an increased risk of experiencing side effects.

Common immunotherapy side effects include:

• Fatigue
• Nausea or upset stomach
• Joint pain
• Diarrhea or constipation
• Cough
• Rash
• Loss of appetite
• Changes in blood cell counts
• Fever

Lung Cancer: The Basics

Treating this disease can be particularly challenging since symptoms often remain undetectable until the cancer has already spread to other organs.

Doctors categorize lung cancer into two primary types based on their behavior and treatment approach:

• Non-small cell lung cancer (NSCLC) — This is the more frequent type, accounting for approximately 85% of cases. NSCLC grows at a slower pace compared to other types and is treated differently.
• Small cell lung cancer (SCLC) — Although less common, SCLC tends to exhibit rapid growth when compared to NSCLC. Consequently, it requires a distinct treatment approach.

Questions to Ask Your Doctor

• How aggressively should my lung cancer treatment be?
• Am I eligible for immunotherapy therapy for lung cancer? Am I more, or less, likely to respond to this treatment?
• Do I have any genetic mutation that would change the course of my treatment?
• How long does it take to get my NGS testing results?
• Do you need both the tissue sample and blood samples for NGS testing?
• Is there a clinical trial that would be relevant for me?

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