Prognostic factors and combined histologies in 205 resected small cell lung cancer (SCLC) patients.

Abstract

e20009 Background: SCLC accounts for 15%-20% of all lung cancer, 2%-5% of them are combined SCLC. The objectives of this study were to evaluate the prognostic factors in a large series of resected SCLC patients, and to perform genetic analysis of combined forms. Methods: 205 SCLC cases were resected at Tianjin Cancer Hospital between 1/2005 and 12/2015. We analyzed: gender, age, type of resection, cigarette index (CI), tumor markers (CEA, SCC, NSE, Cyfra21-1), R resection type, number of resected lymph nodes (LNs), ratio of metastatic LNs, and pathological stage. All combined SCLC cases were identified by H&E staining and confirmed by immunohistochemistry. The different components were microdissected using an automated dissection system (MillisectTM, Roche Diagnostics) and DNA was extracted and subjected to targeted exome sequencing. Results: The median follow-up time was 24 (2-121) months. Median survival time of all the patients was 24 months; 5-year survival rates were 51.4% overall, and 69.5%, 66.5%, 34.4%, and 0% for pathological stage I, II, III, and IV, respectively. Multivariate analysis indicated age, CI, complete resection, number of resected LNs and the ratio of metastatic LNs as independent prognostic factors. Twelve cases of combined SCLC were identified out of 170 with adequate histological material: 6/12 were combined with squamous cell carcinoma. 1-, 3-, 5-year survival rates were 73.3%, 0% and 0%. There were no significant differences between combined SCLC and pure SCLC with respect to gender, age, pathological stage, LN status and tumor markers. Three cases were successfully sequenced. Around 50% gene mutations were present in both components (10/24; 14/27; 4/5 respectively). TP53 mutations were present in all three cases. One case displayed amplification of 2 genes in both components. Interestingly, there were also gene mutations and amplifications that are unique to one of the components. Conclusions: In this large resected SCLC series we identified CI, complete resection, resected number of LNs and ratio of metastatic LNs to be prognostic. Combined SCLC had worse survival than pure SCLC. The histologically different components had a significant number of common as well as unique genetic alterations.