BRAF p.V600E Mutation as Acquired Resistance Mechanism of Lorlatinib in a ROS1 Rearrangement Lung Adenocarcinoma Patient with Primary Ceritinib Resistance

Both crizotinib and ceritinib are recommended as first-line theray for NSCLC with ROS1 rearrangements, with the latter having stronger infiltration ability across blood-brain barrier. Here we report for the first time that a brain metastatic adenocarcinoma patient with CD74-ROS1 rearrangement was sensitive to crizotinib but resistant to ceritinib. Intracranial progression happened after 7 months of crizotinib, and sencond-line lorlatinib resulted in partial response and a PFS of 8 months. Upon lorlatinib resistance, repeated NGS detection of ctDNA from peripheral blood showed BRAF p.V600E, CD74-ROS1 and ROS1 pG2032R. Then, Trametinib, dabrafenib, and cabozantinib was administered to the patient. However, disease progressed very quickly and the patient passed away only one month later, with a overall survival of months. The last ctDNA test, one week before death of the patient, found that BRAF p.V600E disappeared, leaving only CD74-ROS1and ROS1 pG2032R,with a very high frequency. To our knowledge, this is the first case report of a ROS-1 rearrangement lung cancer patient that is sensitive to crizotinib but resistant to ceritinib, and BRAF p.V600E as resistant mechanism for lorlatinib.

Peripheral Lung Squamous Carcinoma With ROS1 Rearrangement Sensitive to Crizotinib: A Case Report

ROS1 rearrangements have been identified as driver mutations, accounting for 1–2% of lung adenocarcinoma, but are extremely rare in case of lung squamous cell carcinoma. In this work, we report a lung squamous cell carcinoma in a patient with peripheral lung cancer radiological manifestation, harboring ROS1 rearrangement, with high sensitivity to crizotinib. Our findings suggest that clinicians should pay more attention toward the occurrence of ROS1 rearrangements and the application of crizotinib for lung squamous cell carcinoma treatment.

ROS1 positive non-small cell lung cancer with pulmonary embolism in a 22-year woman

ROS1-rearrangement occurs in 1-2% of non-small cell lung cancer (NSCLC). This mutation is predominantly seen in relatively young, non-smoker, female with adenocarcinoma. Association of pulmonary embolism with ROS1-rearranged NSCLC has been suggested. We report a case of a 22-year-old woman with ROS1-positive NSCLC and pulmonary embolism. This case possibly represents the youngest patient in the literature.