Treatment prognostic signature of patients with non-small cell lung cancer: a retrospective single-institutional study

Abstract Introduction: Currently, several types of treatment can be used to treat non-small cell lung cancer (NSCLC) depending on a potential druggable mutation or stage of cancer. However, a limited number of biomarkers are available to guide clinicians in selecting the most effective therapy for all patients. Methods: The clinical characteristics of 642 NSCLC patients and tumor sequencing data were collected retrospectively at Atrium Health Wake Forest Baptist. Cox-proportional hazard regression models were fit to identify mutations that were “beneficial” (hazard ratio < 1) or “detrimental” (hazard ratio > 1) for patients on different treatment regimens, followed by the generation of mutation composite scores (MCS) for each treatment. The overall survival (OS) of patients receiving each treatment was plotted based on the patients’ MCS, and receiver operating characteristics (ROC) curves tested the predictive power of each MCS for each treatment group. We also identified novel co-occurring and mutually exclusive mutations in each treatment group by mutation interaction analysis. Results: We identified treatment-specific mutations associated with either a better or worse OS. The MCS generated for each treatment group significantly enhanced the prediction power compared to a single mutation with limited application in patients with rare mutations. Mutation signatures to chemotherapy (NTRK1, FBXW7, BRAF, MPL, KRAS, and GATA3) and immunotherapy (MAP2K1, EGFR, CDK4, NTRK1, and NOTCH1) have a comparable prediction power with actual clinical response. Conclusions: NSCLC patients’ responses to specific treatments are diverse because of tumor heterogeneity. Our work demonstrates how analyzing patients’ sequencing data facilitates the clinical selection of optimized treatment strategies. Citation Format: Margaret R. Smith, Yuezhu Wang, Ralph D' Agostino, Yin Liu, Jimmy Ruiz, Thomas Lycan, George Oliver, Umit Topaloglu, Jireh Pinkney, Mohammed N. Abdulhaleem, Michael D. Chan, Michael Farris, Jing Su, Fei Xing. Treatment prognostic signature of patients with non-small cell lung cancer: a retrospective single-institutional study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 975.