No increased cardiac mortality or morbidity of radiotherapy in breast cancer patients after breast conserving surgery: 20 years follow-up of the randomised x trial.

Abstract Purpose Radiotherapy (RT) after breast conserving surgery reduces loco-regional recurrences and improves survival, but may cause late side effects. The main purpose of this paper was to investigate long-term side effects after whole breast RT in a randomised clinical trial initiated in 1991 and to report dose-volume data based on individual 3D treatment plans for organs at risk (OR). Materials and methods The trial included 1187 T1-2 N0 breast cancer patients randomised to postoperative tangential whole breast radiotherapy or no further treatment. The prescription dose to the clinical target volume was 48-54 Gy. We present 20 year follow-up on survival, cause of death, morbidity and later malignancies. For a cohort of patients (n=157) with accessible CT-based 3D treatment plans in Dicom-RT format, dose-volume descriptors for OR were derived. In addition, these were compared with dose-volume data for a cohort of patients treated with contemporary RT techniques. Results The cumulative incidence of cardiac mortality was 12.4 % in the control group and 13.0 % in the RT group (P= 0.8). There was an increase in stroke mortality, 3.4 % in the control group versus 6.7 % in the RT group (P=0.018). Incidences of contra lateral breast cancer and lung cancer were similar between groups. The median Dmean (range) heart dose for left-sided treatments was 3.0 Gy (1.1-8.1) and the corresponding value for patients treated in 2017 was 1.5 Gy (0.4-6.0). Conclusion In this trial serious late side effects of whole breast radiotherapy were limited and less than previously reported in large meta-analyses. We observed no increased cardiac mortality in irradiated patients with doses to the heart were median Dmean 3.0 Gy for left-sided RT. The observed increase in stroke mortality may partly be secondary to cardiac side effects, complications to anticoagulant treatment, or to chance, rather than a direct side effect of tangential whole breast irradiation.