Impact of radiation dose to the immune system on disease progression and survival for early-stage non-small cell lung cancer treated with stereotactic body radiation therapy

Abstract

Objectives: Although the effects of estimated dose of radiation to immune cells (EDRIC) in stage III NSCLC, LA-NSCLC, LS-SCLC and esophageal cancer on clinical outcomes have been studied, its impact in early-stage non-small cell lung cancer (ES-NSCLC) is unknown. In this study, we evaluated the role of EDRIC and identified the factors influencing EDRIC in this population.

Methods and materials: We retrospectively analyzed 211 pathologically confirmed ES-NSCLC patients who were treated with SBRT between 2007 and 2020. EDRIC was calculated based on the model developed by Jin et al. and improved by Ladbury et al. Kaplan-Meier method and Cox proportional hazards regression were adopted to estimate CSS, PFS, LPFS, and DMFS. Pearson correlation was used to assess the correlation between variables. We further validated our findings in an independent cohort of 119 patients with ES-NSCLC.

Results: A total of 211 patients were included with median follow-up of 48 months in the training cohort. The median EDRIC was 2.178 Gy (range: 0.426-6.015). GTV showed a positive correlation with EDRIC (r = 0.707, P = 0.000). In multivariate analysis, higher EDRIC was significantly associated with worse CSS (HR = 1.468, P = 0.009) and DMFS (HR = 1.491, P = 0.016). Considering each EDRIC quartile, there was a significant difference in CSS between 1st and 4th and 1st and 3rd quartile (P = 0.000, P = 0.004, respectively); and DMFS between 1st and 4th,1st and 3rd, and 1st and 2nd quartile (P = 0.000, P = 0.000, P = 0.008, respectively). In the subgroup and validation cohort, EDRIC was also the important prognostic predictor of CSS and DMFS using multivariate analysis.

Conclusion: EDRIC was an independent predictor of CSS and DMFS in ES-NSCLC, and it was affected by GTV and tumor location. Though EDRIC is a critical determinant of treatment outcomes, it is quantifiable and potentially modifiable. Additional researches exploring the feasibility of achieving lower EDRIC while maintaining adequate tumor coverage during radiotherapy are warranted.

Keywords: Distant metastasis; Estimated dose of radiation to immune cells (EDRIC); Non-small cell lung cancer; Radiation-induced immunosuppression; Stereotactic body radiation therapy; Survival.