Purpose To perform joint estimation of the risk of recurrence caused by inadequate radiation dose coverage of lymph node targets and the risk of cardiac toxicity caused by radiation exposure to the heart. Delivered photons plans are compared to realistic proton plans thereby providing evidence-based estimates of the heterogeneity of treatment effects in consecutive cases for the two radiation modalities. Methods and Materials Forty-one patients referred for post-lumpectomy comprehensive nodal photon irradiation for left-sided breast cancer were included. Comparative proton plans were optimized using spot scanning technique with single field optimization from two enface beams. Cardiotoxicity risk was estimated using the model by Darby et al and risk of recurrence following a compromise of lymph node coverage was estimated by a linear dose-response model fitted to the recurrence data from the recently published EORTC 22922/10925 and NCIC-CTG MA.20 randomized controlled trials. Results Excess absolute risk (EAR) of cardiac morbidity was small with photon therapy at an attained age of 80 years with a median (range) of 1.0% (0.2%-2.9%) /0.5% (0.03%-1.0%) with/without cardiac risk factors (CRFs), but even lower with proton therapy (0.13% (0.02%-0.5%)/0.06% (0.004%-0.3%)), respectively. The median estimated EAR of breast cancer recurrence after 10 years was 0.10% (range: 0.0%-0.9%) with photons and 0.02% (range 0.0%-0.07%) with protons. The association between age of the patient and benefit from proton therapy was weak, almost non-existing (Spearman’s rank correlation: -0.15/−0.30 with/without CRFs). Conclusions Modern photon therapy yields limited risk of cardiac toxicity in most patients, but proton therapy can reduce the predicted risk of cardiac toxicity by up to 2.9% and the risk of breast cancer recurrence by 0.9% in individual patients. Predicted benefit correlates weakly with age. Combined assessment of the risk from cardiac exposure and inadequate target coverage is desirable for rational consideration of competing photon and proton therapy plans.</p
