Molecular, clinicopathological characteristics and surgical results of resectable SMARCA4-deficient thoracic tumors

Abstract PurposeSMARCA4 deficient thoracic tumors are rapid aggressive malignancies, often diagnosed at an advanced and inoperable stage. The value of pulmonary resection for resectable SMARCA4 deficient thoracic tumors are largely unknown. MethodsIn this study, we included 45 patients who received surgery for stage I-III SMARCA4 deficient tumors. We compared the molecular, clinicopathological characteristics and survival between SMARCA4-dNSCLC and SMARCA4-deficient undifferentiated tumor (SMARCA4-dUT) patients. ResultsThirty-four SMARCA4-dNSCLC and 11 SMARCA4-dUT patients were included in this study. Molecular profiles were available in 33 out of 45 patients. The most common mutated gene was TP53 (21, 64%), and followed by STK11(9, 27%), KRAS (5, 15%), FGFR1 (4, 12%) and ROS1 (4,12%). There were 3 patients harbored ALK mutation including 1 EML4-ALK rearrangement. There were 2 patients harbored EGFR rare site missense mutation. SMARCA4-dUT patients had significance worse PFS (HR=4.35 95%CI 1.77-10.71, p=0.001) and OS (HR=4.27, 95%CI 1.12-16.35, p=0.022) compared to SMARCA4-dNSCLC patients. SMARCA4-dUT histologic type, stage II/III, R1/2 resection and lymphovascular invasion were independent poor prognostic predictors for both PFS and OS. There were 8 patients received immunotherapy, the objective response rate was 50%. The SMARCA4-dNSCLC patient with ALK rearrangement was treated with crizotinib as second line therapy, and achieved stable disease for 9.7 months.ConclusionPatients with SMARCA4 deficient tumors have a high probability of early recurrence after surgery, except for stage I patients. Immunotherapy seems to be a valuable strategy to treat recurrence.