Elevation of tumor mutation burden in ROS1-fusion lung adenocarcinoma resistant to crizotinib: A case report.

Rationale: Although most of non-small cell lung cancer (NSCLC) patients with ROS1-fusions respond to crizotinb, acquired resistance eventually develop. The next-generations of ROS1 inhibitors have made some achievements, but the effects of immunotherapy have not been explored. Patient concerns: A 44-year-old Chinese women presented with cough and dyspnea with a history of advanced lung adenocarcinoma. Diagnosis: A PET/CT scan revealed primary tumors in bilateral lung lobes and multiple metastases in lymph nodes and bones. And ultrasound-guided left cervical lymph node biopsy revealed the pathological diagnosis was poor differentiated lung adenocarcinoma. Interventions: The patients was started to be treated with 4 cycles of pemetrexed, carboplatin and bevacizumab, followed by one cycle of docetaxel, cisplatin and bevacizumab. As the ROS1-fusion was found by next generation sequencing, the patient received crizotinib treatment about 3 months. Outcomes: After 5 cycles of chemotherapy, CT scans revealed increased size of bilateral lobe nodules indicative of progressive disease (PD). Then the patient received treatment of crizotinib and his progression-free survival reached 3 months. Due to uncontrollable disease progression, the patient expired. Lessons: The genetic profile of NSCLC patients might be altered in various therapeutic processes. Thus, repeated genetic testing might be important at each progression. Moreover, immunotherapy might be a powerful weapon to overcome the resistance to Tyrosine kinase inhibitors (TKIs) in future.