Clinical Case 1: Newly Diagnosed Patient with ROS1-Positive Advanced Non-Small Cell Lung Cancer and High PD-L1

The first clinical case presents a 58-year-old female never-smoker with persistent cough, mild dyspnea, and new right-sided pleural effusion. Workup reveals a 7 cm solid right middle lobe mass, 20 mm ipsilateral lymph nodes, FDG-avid osseous disease (L3-L5 and bilateral iliac crests), adenocarcinoma on biopsy, elevated ROS1 protein on IHC (H-score greater than 150), PD-L1 TPS 95%, and CD74-ROS1 fusion by molecular profiling with no other actionable alterations. ECOG performance status is 1. The patient does not have brain metastases.

The panel highlights that CD74 is the most common ROS1 fusion partner, with IHC concordance with NGS-detected fusions being imperfect at approximately one-third of ALK-rearranged cases, and potentially a similar proportion of ROS1-rearranged cases, may be missed by IHC or FISH compared to NGS. The key takeaway is that this patient has a targetable driver alteration and urgent symptomatic disease requiring rapid treatment that should effectively address both systemic and potential CNS disease. The panel notes the high PD-L1 result should not redirect treatment toward immunotherapy, consistent with prior discussion.