Recognizing and Testing for ROS1 in NSCLC

Recognition and testing for ROS1 rearrangements in non-small cell lung cancer (NSCLC) have significantly advanced in recent years. Initially, ROS1 was identified using single-gene techniques such as fluorescence in situ hybridization (FISH), but the field has shifted toward broader genomic profiling using next-generation sequencing (NGS). These modern methods allow for simultaneous detection of multiple actionable alterations, which is critical as the list of targetable mutations in NSCLC continues to expand. Testing both tissue and plasma is now considered best practice, with a preference for RNA-based sequencing in tissue due to its improved sensitivity in detecting gene fusions like ROS1.

Comprehensive molecular testing at the time of diagnosis is essential to ensure patients are matched with the most effective targeted therapies from the outset. ROS1 rearrangements, while relatively rare (about 2% of NSCLC), can significantly impact treatment decisions. Broad molecular profiling not only identifies ROS1 but also detects numerous other alterations, including EGFR, ALK, MET, RET, BRAF, and KRAS mutations, among others. Many of these alterations have first- or second-line therapies approved or in development. Starting patients on a matched targeted agent rather than standard chemotherapy can lead to improved outcomes and quality of life.

Despite its importance, comprehensive testing is sometimes underutilized due to barriers like long turnaround times, limited tissue availability, and insurance issues. These challenges can delay treatment decisions, creating anxiety for patients. In urgent cases, some clinicians may start patients on a single cycle of chemotherapy without immunotherapy while awaiting results to avoid overlapping toxicities. Communication and reassurance are key during this period. Increasing the use of both tissue and plasma testing together can improve detection rates, and efforts must continue to streamline access and coverage for molecular testing to ensure optimal care for all patients.