Prognostic significance of estimated radiation dose to immune cells in cancer patients undergoing thoracic irradiation: A meta-analysis.

Abstract

Emerging evidence suggests that excessive radiation dose to immune cells may impair host immunity and negatively affect cancer prognosis. However, the prognostic impact of the estimated radiation dose to immune cells across different cancer types and treatment modalities remains inconclusive. This meta-analysis aimed to systematically evaluate the association between estimated radiation dose to immune cells and survival outcomes in patients with lung and esophageal cancers undergoing radiotherapy. We systematically searched PubMed, EMBASE, and Cochrane Library up to April 2025 following PRISMA guidelines. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using a random-effects model for overall survival (OS), progression-free survival (PFS), disease-free survival (DFS), locoregional progression-free survival (LPFS), and distant metastasis-free survival (DMFS). Sixteen studies comprising 4511 patients were included, with 1073 patients diagnosed with esophageal cancer and 3438 with lung cancer. The pooled analysis demonstrated that higher estimated radiation dose to immune cells was significantly associated with inferior OS (HR = 1.228; 95 % CI, 1.135-1.329; p < 0.001) and PFS (HR = 1.265; 95 % CI, 1.134-1.412; p < 0.001). Similar associations were observed for DFS (HR = 1.227; 95 % CI, 1.009-1.492), LPFS (HR = 1.091; 95 % CI, 1.042-1.141), and DMFS (HR = 1.172; 95 % CI, 1.066-1.290). Subgroup analyses revealed consistent findings across tumor types, geographic regions, age groups, sample sizes, and the estimated radiation dose to immune cells cutoff values. Funnel plot asymmetry and statistical tests suggested potential publication bias; however, trim-and-fill analyses confirmed the robustness of the results. Sensitivity analyses further supported the stability of pooled estimates. Higher estimated radiation dose to immune cells is linked to adverse survival outcomes. Immune-sparing radiotherapy strategies may improve prognosis and warrant further investigation.