Abstract
Relevance: ROS1 gene rearrangements are observed in 1–2% of non-small cell lung cancer (NSCLC) cases. Access to suitable targeted therapy may be limited if rare fusion variants, such as TPM3-ROS1, are not detected by traditional diagnostic methods.The study aimed to demonstrate the clinical efficacy of next-generation sequencing (NGS) and to inform the selection of tailored targeted therapy for a patient with significant brain metastases from ROS1-positive non-small cell lung cancer.Materials and Methods: The paper presents a clinical case of metastatic non-small cell lung cancer and multiple brain metastases in a non-smoking 68-year-old woman after brain surgery. Initial immunohistochemistry revealed no common driver mutations. Next-generation sequencing (NGS) revealed a unique rearrangement in the TPM3-ROS1 gene. Ceritinib was initiated after induction chemotherapy because of its limited availability in Kazakhstan at the time of treatment.Results: The best overall response to treatment was stable disease (SD) according to RECIST 1.1 criteria. Radiological surveillance of intracranial lesions continued for several months. Grade 4 gastrointestinal toxicity prevented further treatment and required dose reduction and discontinuation of therapy. Overall survival was more than 10 months.Conclusion: This case highlights the importance of next-generation sequencing (NGS) for identifying rare, treatable mutations. Molecularly targeted therapy may help control the disease in selected patients; however, the study results are limited by the single-case design.