Abstract: Targeted therapy for patients with advanced non-small cell lung cancer (NSCLC) is often challenged by the arising of drug resistance. After progression to targeted therapy, treatment options include continued targeted therapy, definitive local therapy, and the combination of both. While there is evidence that local ablative radiotherapy may prolong the disease control by targeted therapy, little is known regarding the relevance of salvage thoracic surgery in this setting. Herein, we presented a case of stage IV lung adenocarcinoma with concurrent EML4-ALK  and TAC1-ALK  fusion who had long-term survival after salvage thoracic surgery. The patient underwent a multidisciplinary treatment scheme that consisted of radiotherapy, ALK inhibitor crizotinib, and surgery, with blood-based genomic profiling for monitoring disease progression. Notably, salvage thoracic surgery was performed after progression on the crizotinib therapy and acquired ALK  F1174C mutation was identified, which has been shown to be resistant to crizotinib and possibly sensitive to ceritinib. The patient benefited from salvage thoracic surgery with a remarkable progression-free survival of 31 months at last follow-up, and the patient maintained high-performance status throughout the course of management. To the best of our knowledge, this is the first case reporting on the long-term survival outcome from salvage thoracic surgery after crizotinib treatment in an NSCLC patient carrying double ALK  fusion.
Keywords: advanced non-small cell lung cancer, multidisciplinary treatment, salvage thoracic surgery, crizotinib, ALK  F1174C mutation