The impact of effective dose to the immune cells on survival in breast cancer patients.

Purpose: In patients with thoracic cancers such as lung and esophageal cancer, higher radiation exposure to immune cells is associated with worse survival outcomes. This study aims to determine whether a similar association between Effective Dose to the Immune Cells (EDIC) and BC-specific survival (BCSS) also exists in BC patients. Methods: This retrospective cohort study included stage I to III invasive BC patients treated with adjuvant radiation therapy (RT) between January 2005 and June 2015. The EDIC was calculated as the equivalent uniform dose of the mean heart dose, mean lung dose and large and small blood vessels. The association between EDIC and BCSS was assessed using univariable and multivariable Cox proportional hazard regression models. Results: The study included 3423 BC patients (median age of 59 years, IQR 50-67) with a median follow-up of 7.7 years (IQR, 5.5-10.8). Overall, 710 patients (20.7%) died, including 323 (9.4%) from BC. The median EDIC was 2.1 Gy (IQR, 1.6-2.7). Higher EDIC, particularly >3.0 Gy, was associated with worse BCSS. In multivariable analysis, EDIC was independently associated with BC mortality (HR 1.66; 95%CI 1.44-1.91), consistent with worse BCSS. Conclusions: An association between higher EDIC and worse BCSS was observed in patients treated with adjuvant RT, with the association being most pronounced at EDIC levels >3.0 Gy. We hypothesize that this effect may be mediated by radiation-induced lymphopenia; however, whether strategies aimed at reducing EDIC translate into improved oncological outcomes requires prospective validation.