Multidisciplinary Coordination and the Importance of Complete Biomarker Testing Before Treatment Initiation in ROS1-Positive Non-Small Cell Lung Cancer

The panel discusses how patients with ROS1-positive advanced NSCLC arrive in clinic through in-system diagnosis, second opinions, or new patient referrals and the detective work required to ensure complete molecular testing is available before treatment decisions. NCCN guidelines recommend comprehensive genomic profiling for all patients with advanced NSCLC before treatment initiation, regardless of histology, as morphology alone is insufficient to predict driver alterations.

A case is shared of a young woman with brain metastases whose multiple liquid biopsies were negative and initial tissue was insufficient (quantity not sufficient, or QNS). A repeat biopsy one and a half months later identified a ROS1 fusion, validating the decision to delay treatment until complete testing was available. The panel's communication strategy is to tell patients: "I want to give you the best treatment for your cancer, not just a generic treatment", reflecting that the wait is a personalized investment rather than a delay.

Dr. Riedlinger advises that coordinating closely with interventional radiology colleagues to obtain adequate tissue on the first biopsy is critical, as repeat procedures require significant time and logistical coordination. Pathologists can enrich specimens for tumor content to improve the probability of interpretable NGS results from lower-cellularity samples, which is a practical tip that may not be widely known in community settings. The panel cautions against starting immunotherapy before obtaining full molecular profiling, given the potential for significant toxicity if a driver-positive patient subsequently requires targeted therapy.