Transforming Growth Factor-Beta 1 as a Predictive Biomarker for Radiation-Induced Lung Toxicity and Treatment Response in Lung Cancer: A Systematic Review and Meta-analysis

Purpose: Radiation-induced lung toxicity (RILT) and variable treatment responses limit the effectiveness of radiation therapy in patients with lung cancer. Transforming growth factor-beta 1 (TGF-β1) has emerged as a potential predictive biomarker, but inconsistent findings across studies have limited its clinical implementation. Methods and Materials: We conducted a systematic review and meta-analysis following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, searching PubMed, Embase, Scopus, and the Cochrane Library through August 2025. Studies investigating TGF-β1 as a predictor of RILT or treatment response in patients with lung cancer receiving radiation therapy were included. Quality assessment used the Quality in Prognosis Studies tool. Random-effects models calculated pooled estimates for area under the curve, mean differences, and risk ratios. Results: < .0001), with particularly strong performance for RILT risk stratification (risk ratio [RR], 5.29, 95% CI, 2.53-11.07). Preliminary evidence from 1 study suggests potential utility for predicting treatment response (RR, 4.03, 95% CI, 2.18-7.45), requiring validation in larger cohorts. Conclusions: TGF-β1 ratio monitoring enables effective risk stratification for radiation toxicity in patients with lung cancer, supporting its clinical implementation for personalized radiation therapy planning. Further prospective studies are needed to confirm its predictive value for treatment response.