Thoracic radiotherapy may enhance the survival of patients with low‐risk advanced lung adenocarcinoma based on protein biomarkers

Abstract Objectives Several clinical trials have demonstrated promising outcomes with thoracic radiotherapy (TRT) in patients with advanced lung adenocarcinoma (LUAD). However, a subset of patients derives no significant survival benefit from TRT. This study aimed to develop a risk model integrating biomarkers and clinical factors to identify patients most likely to benefit from TRT. Methods Prognostic proteins associated with LUAD survival were identified using data from The Cancer Proteome Atlas. Immunohistochemical analysis was performed to evaluate protein expression in patients with advanced LUAD treated at our institution between 2015 and 2019. Univariate and multivariate Cox regression analyses were conducted to determine clinical factors influencing prognosis. A risk model combining biomarkers and clinical variables was constructed to generate individualized risk scores. Results Four proteins, PAI‐1, KU80, FOXO3A_pS318S321, and CKIT, were selected for further analysis. A total of 272 patients were divided into training ( n = 181) and validation ( n = 91) cohorts. Six prognostic factors including N‐stage, presence of sensitive mutations, brain metastasis, adrenal metastasis, leukocyte count, and expression levels of PAI‐1 and KU80 were incorporated into the risk model. Patients were stratified into low‐ and high‐risk groups based on calculated risk scores. TRT significantly improved median survival time (69.0 vs . 39.3 months, p = 0.003) and overall survival (67.4 vs . 33.0 months, p = 0.035) in low‐risk patients, but not in high‐risk patients (median survival time: 19.8 vs . 18.2 months, p = 0.186; overall survival: 19.4 vs . 19.9 months, p = 0.607) for two cohorts. Conclusion Multiple biomarkers and clinical variables are associated with prognosis in LUAD. The risk model developed herein indicates that TRT confers a survival benefit exclusively in patients classified as low risk.