Determinants of radiation dose to immune cells during breast radiotherapy.

Background: The immune system has been identified as an organ at risk in esophageal and lung cancers. However, the dosimetric impact of radiotherapy on immune system exposure in patients treated for breast cancer has never been studied.

Methods: A monocentric retrospective dosimetric study included 163 patients treated at the Institut Curie (Paris, France) between 2010 and 2016 with locoregional helical tomotherapy after conservative surgery or total mastectomy. The effective dose to the immune system (EDIC) was calculated based on diverse dosimetric parameters. The clinical and volumetric determinants of EDIC in adjuvant radiotherapy of breast cancer were analyzed.

Results: The median EDIC for the population was 4.23 Gy, ranging from 1.82 to 6.19 Gy. Right-sided radiotherapy and regional lymph node irradiation were associated with significantly higher EDIC in univariate (4.38 Gy vs. 3.94 Gy, p < 0.01, and 4.27 Gy vs. 3.44 Gy, p < 0.01, respectively) and multivariate analyses (p < 0.01 and p < 0.01). Liver overexposure was the main contributor to EDIC increase in right-sided breast cancer patients (+0.38 Gy [95%CI: +0.30; +0.46]), while the integral total dose increase was the main contributor to EDIC increase in cases of regional node irradiation (+0.63 Gy [95%CI: +0.42; +0.85]).

Conclusion: The EDIC score during adjuvant radiotherapy after breast cancer was statistically significantly higher in the case of right-sided radiotherapy and regional lymph node irradiation. Liver irradiation is the main contributor to immune system exposure in adjuvant irradiation of right-sided breast cancer. Populations in which an association between EDIC and survival would exist have yet to be identified but could potentially include patients treated for triple-negative breast cancer with a poor response to neoadjuvant chemoimmunotherapy.