Genetic profiling-based prognostic prediction of patients with advanced small-cell lung cancer in large scale analysis. (December 2018)

• Record Type: Journal Article
• Authors: Udagawa, Hibiki; Umemura, Shigeki; Murakami, Isao; Mimaki, Sachiyo; Makinoshima, Hideki; Ishii, Genichiro; Miyoshi, Tomohiro; Kirita, Keisuke; Matsumoto, Shingo; Yoh, Kiyotaka; Niho, Seiji; Tsuchihara, Katsuya; Goto, Koichi
• Is Part Of: Lung cancer. Volume 126(2018)
• Page Start: 182
• Page End: 188
• Publication Date: 2018-12
• Subjects: CI confidence interval -- ECOG PS Eastern Cooperative Oncology Group performance status -- ED extensive disease -- HR hazard ratio -- LD limited disease -- NSCLC non-small cell lung cancer -- OS overall survival -- PFS progression-free survival -- SCLC small-cell lung cancer -- SNVs single-nucleotide variants; Small-cell lung cancer -- Genome -- Genetic alterations -- Survival -- Chemotherapy; Lungs -- Cancer -- Periodicals; Lung Neoplasms -- Abstracts; Lung Neoplasms -- Periodicals; Poumons -- Cancer -- Périodiques; Lungs -- Cancer; Periodicals; Electronic journals; Electronic journals; 616.99424
• DOI: 10.1016/j.lungcan.2018.11.014
• Languages: English
• ISSNs: 0169-5002

Abstract

Highlights: Impact of genetic alterations on outcome of SCLC has not been well investigated. Genetic alterations in PI3K pathway were associated with poor prognosis of ED-SCLC. TP53 and RB1 mutations were associated with prognosis in LD-SCLC. Sequencing-based genetic profiling is useful to predict prognosis in advanced SCLC. Abstract: Objectives: Comprehensive genomic analysis of small-cell lung cancer (SCLC) revealed various genetic alterations. However, obtaining suitable samples for genetic analysis is difficult in advanced SCLC. Thus, the prognostic effect of genetic alterations on the outcome of SCLC patients has not been well investigated. Therefore, this study evaluated the effect of genetic alterations on the survival of SCLC patients. Materials and methods: We collected samples obtained from 220 patients with advanced SCLC before cancer treatment. Genomic DNA extracted from the samples was subjected to a 1.499 Mb-sized custom panel that captured all exons of 244 cancer-related genes, and the captured DNA was analyzed through next-generation sequencing. The associations between genetic alterations and overall survival were evaluated. Results: Genetic analysis was successful in 204 samples (93%). Genetic alterations in the PI3K/AKT/mTOR pathway and inactivating mutations in TP53 and RB1 were detected in 14 (7%), 150 (74%), and 85 (42%) of the tumors. In extensive disease (ED, N = 126) patients, multivariate analysis revealed that the presence of genetic alterations in the PI3K/AKT/mTOR pathway was significantly associated with unfavorable survival [hazard ratio (HR), 2.14; 95% CI 1.02–4.06; P = 0.04]. In limited disease (LD, N = 78) patients, the presence of TP53 mutation and the absence of RB1 mutation were significantly associated with unfavorable survival (HR, 2.41; 95% CI 1.21–5.34; P = 0.01, and HR, 0.45; 95% CI 0.25–0.79; P < 0.01, respectively). Conclusions: Sequencing-based genetic profiling is feasible and useful to predict the prognosis in advanced SCLC. Genetic alterations in the PI3K/AKT/mTOR pathway, TP53 mutations and RB1 mutations were associated with prognosis in SCLC patients. The genetic alterations associated with the prognosis were different between ED-SCLC and LD-SCLC.