Abstract PD8-10: No increased cardiovascular mortality after twenty years in a randomized trial of radiotherapy after breast conserving surgery, SweBCG 91RT, from the Swedish breast cancer group

Abstract

Introduction Breast conserving surgery (BCS) with postoperative radiotherapy (RT) is recommended for the majority of patients with early breast cancer. Meta-analyses of randomized trials have shown reduction of breast cancer and overall mortality after RT but increased cardiovascular mortality Aim To evaluate side effects of RT after BCS Patients and Methods Trial SweBCG 91RT randomized 1187 women with stage 1-IIA breast cancer after BCS to RT or to no further treatment. RT was administered as tangential opposing beams to the breast to a target dose of 48-54 Gy. Three-dimensional dose planning on multiple CT slices 10 mm apartwas used for 69% of the patients and for the remainder two-dimensional planning. All hospital records and radiotherapy charts were monitored. Update of mortality, cause of death and morbidity was made using the Swedish personal identification numbers and the following Swedish national registers: the Cancer Register, the Population Register, the Cause of Death Register, the Inpatient and the SWEDEHEART registers. For analyses the diagnoses were grouped as follows: breast cancer, cardiovascular disease, cerebrovascular disease, lung cancer and benign pulmonary disease Statistics Overall mortality was calculated using the Kaplan-Meier method, whereas cumulative incidence functions with other causes of death as competing events were used for cause-specific mortality and morbidities. For all outcomes, log-rank tests were used to compare between treatment groups up to 20 years. We studied two populations: 1) patients according to intention to treat for overall and breast cancer mortality and 2) patients treated per protocol for side effects. Cause-specific death was allocated to a certain group when either the underlying or a contributing cause belonged to the disease group Results After 20 years, overall mortality was 42.9% after BCS and 42.5% after BCS+RT (p=0.8), and breast cancer mortality was 18.0% vs 15.8% (p=0.3). The cumulative incidence of mortality from heart disease was 12.4% after BCS and 13.0% after BCS+RT (p=0.8) with no difference for left or right side. Ischemic heart disease and congestive heart failure were the most common cardiac diagnoses. The cumulative incidence of cerebrovascular mortality was 3.4% among controls and 6.7% after RT (p=0.016). Of the patients with cerebrovascular death, 50% also had a cardiac cause of death. Other cause-specific mortalities investigated were similar regardless of RT: lung cancer 1.7% vs 1.9% (p=1.0), benign pulmonary disease 7.1% vs 6.4% (p=0.5) Morbidity Morbidity outcomes were also similar in control and irradiated patients: the cumulative incidence of hospital admissions with cardiac diagnoses 29.7% vs 31.0% (p=0.7), and for cerebrovascular morbidity 11.6% vs 13.7% (p= 0.33) respectively Radiation exposure The original dose plans were retrieved from 125 patients. Doses to organs at risk were recalculated. Median of mean heart dose was 3.0 Gy (1.1-8.2) for left and 1.0 Gy (0.5-2.5) for right-sided RT Conclusions After 20 years tangential RT in a randomized trial was not associated with increased cardiac mortality. A minor increase in cerebrovascular mortality was seen, but the causality is unclear. Citation Format: Malmström P, Karlsson P, Holmberg E, Lundstedt D, Holmberg L, Werner-Hartman L, Koul S, Kjellén E, Killander F. No increased cardiovascular mortality after twenty years in a randomized trial of radiotherapy after breast conserving surgery, SweBCG 91RT, from the Swedish breast cancer group [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr PD8-10.