The Impact of a High Radiation Dose to the Immune Cells on Tumor Control and Survival in Patients with Non-Small Cell Lung Cancer Undergoing Postoperative Radiotherapy

Abstract

Previous studies showed that the estimated dose of radiation to immune cells (EDRIC) was correlated with the overall survival (OS) of patients who received definitive thoracic radiotherapy. However, planning target volume (PTV) may be a confounding factor. The PTV is relatively uniform for patients undergoing postoperative radiotherapy (PORT). We further assessed the prognostic value of EDRIC on survival in patients with non-small cell lung cancer (NSCLC) undergoing PORT. Patients with NSCLC who received PORT between 2004 and 2019 were analyzed. EDRIC was calculated as a function of the number of radiation fractions and mean doses to the lung, heart, and remaining body based on a model developed by Jin et al. The correlation between EDRIC and OS, PFS, local progression-free survival (LPFS), and distant metastasis-free survival (DMFS) were analyzed using univariable and multivariable Cox models. Kaplan-Meier method was used to show the survival difference between patients with high and low EDRIC. A total of 345 patients were eligible. The mean EDRIC was 7.6 Gy. Multivariate analysis showed that EDRIC was associated with OS (HR 1.14, P = 0.002), PFS (HR 1.08, P = 0.016), LRFS (HR 1.111, P = 0.008), and DMFS (HR 1.10, P = 0.018). Patients were divided into low and high EDRIC groups according to median EDRIC. The 3-year OS was 82.7% and 72.2% (p = 0.03). The 3-year PFS was 40.3% and 17.8% (p < 0.01). The 3-year LRFS was 71.39% and 59.18% (p = 0.05). The 3-year DMFS was 74.4% and 63.4% (p = 0.06). EDRIC was an independent prognostic factor for survival. Higher doses of radiation to the immune system were associated with tumor progression and death after the PORT of NSCLC. The organ at risk for the immune system should be considered during radiotherapy planning.