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The American Lung Association suggests thinking of DNA like words in a book. When something goes wrong, typos can alter the meaning of the words.1 This same concept can be applied to lung cancer progression – when changes occur at a cellular level that are not recognized by the body, it can lead to uncontrolled cell growth and the spread of cancer cells.1 There are now treatments available that can directly target these changes, focusing precisely on what is wrong with the cancer cells, with the possibility of less harm to normal cells and fewer off-target effects.1
Biomarker testing is part of diagnostic testing to help identify mutations, additions, deletions, or rearrangements in DNA, and also checks for key markers like protein levels or tumor DNA in the blood.1 This information can significantly influence treatment options.1 However, not all lung cancers have treatable biomarkers, so discussing biomarker testing and treatment options with your patients is essential.
Physician’s Weekly (PW) spoke with Debora Bruno, MD, associate professor of medicine at Case Western Reserve University and lead of the medical oncology thoracic group at University Hospitals Senet Cancer Center, to better understand the importance of biomarker testing in guiding treatment decisions, specifically for patients with NSCLC with ROS1+ mutations.
PW: To start, can you tell us why biomarker testing is so important?
Dr. Bruno: Yes, of course. According to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®), broader molecular profiling is strongly advised to identify rare driver mutations. This can help identify effective existing drugs or appropriately counsel patients about available clinical trials.2
PW: Could you speak to the significance of biomarker testing in guiding treatment decisions for patients with NSCLC ROS1+ mutations and how that contributes to precision medicine?
Dr. Bruno: Biomarker testing is crucial for guiding treatment decisions for patients with NSCLC ROS1+ mutations, contributing significantly to precision medicine. 3Multiplex testing, particularly next-generation sequencing (NGS), allows for comprehensive testing of multiple genomic alterations without exhausting the specimen.4
For ROS1+ NSCLC, it is essential to consider factors, such as brain metastasis, when tailoring a treatment plan, as ROS1+ NSCLC can often spread to the brain.5 NGS can analyze tissue biopsies and circulating tumor DNA from blood draws, providing a thorough understanding of the cancer’s genetic profile and enabling precise treatment strategies. 4
PW: How does your practice integrate biomarker testing into the management of NSCLC?
Dr. Bruno: In my practice, biomarker testing is integrated into the management of NSCLC by testing all patients upfront before deciding on the best therapy for them. My team performs reflex testing, where after a patient is diagnosed with NSCLC, the biopsy specimen is red-flagged and sent to our in-house molecular pathology lab for NGS.6 This NGS test focuses on 60 genomic alterations, including gene fusions with FDA-approved therapies and other genomic markers to understand the disease’s biological behavior and potential immunotherapy responses.
We also send liquid biopsies for patients when the initial tissue biopsy is insufficient or the patient is reluctant to undergo another procedure. This helps us understand what the tumor is shedding into the bloodstream. Additionally, we perform PD-L1 testing for all NSCLC patients using immunohistochemistry to guide immunotherapy decisions.1
Our molecular tumor board—which includes a navigator, molecular pathologist, and medical oncologist—meets twice a week to review test results and suggest clinical trials or standard-of-care options.7 This information is incorporated into the patient’s electronic medical record and our navigator communicates with providers across our hybrid academic-community network to ensure patients are informed about available clinical trials and treatment options. This approach helps us offer the most appropriate standard of care and access to clinical trials for our patients.
PW: What factors do you consider when tailoring a treatment plan for this patient population?
Dr. Bruno: When tailoring a treatment plan for NSCLC patients, I consider several key factors. Beyond the type and presence of specific genetic alterations or PD-L1 levels that guide immunotherapy and chemotherapy decisions, I also look at the patient’s overall disease burden.1 I take into account other health issues, overall physical condition and any side effects the patient could experience. It’s important to see the big picture, discussing the pros and cons of each therapy, potential side effects, and the logistics of treatment, including how often the patient needs to come in for infusions and tests.
The goal is to ensure comprehensive care while keeping the patient at the center of all decisions.
PW: How do you specialize biomarker testing teams to enhance the identification and management of patients with ROS1+ NSCLC?
Dr. Bruno: To enhance the identification and management of patients with ROS1+ NSCLC, our biomarker testing teams focus on several key areas.
First, we rely on our radiologists and pulmonologists to obtain sufficient biopsy samples for testing. Ensuring we have enough tissue is crucial for accurate diagnosis and subsequent testing, including NGS and PD-L1 analysis.
The pathology team must be aware to avoid unnecessary immunohistochemistry tests that can exhaust the tissue sample. We focus on essential tests to confirm NSCLC subtypes and reserve more detailed testing for when necessary.
Then, our molecular pathology lab is instrumental in processing samples quickly and accurately. It’s vital to ensure that test results are communicated effectively to the treating oncologist, who can then use this information to guide treatment decisions.
For ROS1+ NSCLC patients, accurate identification of ROS1 alterations enables us to provide the most effective targeted treatments.
Read on to learn more about a multidisciplinary care approach to ROS1+ NSCLC.
