Patient Reported Experience with Treatment Modalities and Safety of Adjuvant Breast Radiotherapy - First Results of the Randomized HYPOSIB – Study

Abstract

HYPOSIB is a multicentric randomized study investigating hypofractionated adjuvant radiotherapy with a simultaneous integrated boost (comparable to RTOG 1005). In the control arm, adjuvant radiotherapy could be administered either in conventional fractionation plus boost or as hypofractionated radiotherapy with a sequential boost. In the experimental arm, patients received a total dose of 40Gy to the breast and 48Gy in the boost volume in 16 fractions with integrated boost. Primary endpoint is disease-free survival. Per protocol, a yearly safety report for the data safety monitoring board (DSMB) is prepared. Amendment 6 of the study included a questionnaire for measurement of patient reported outcome and experience with therapy modalities. We report first results with regard to safety and patients´ satisfaction with therapy. There were 2,324 patients were recruited by 88 active study centers in Germany and Austria from June 2015 through January 2019. For the safety report, all adverse events (AE), severe adverse events (SAE) and acute skin toxicity were analyzed. After June 2018, the remaining recruited patients were asked to fulfil a questionnaire by the end of radiotherapy with questions about symptoms and about satisfaction with therapy and quality of care. The median follow-up at the time of the safety report for the year 2019 was 28 months. 3398 AEs including 152 SAEs had been reported. 12.7% SAEs were probably or likely associated with radiation therapy. The incidence of AEs/SAEs was comparable in the control arm (1741 AEs, 80 SAEs) and experimental arm (1657 AEs, 72 SAEs). Skin reactions grade 2+ (grade 2 in nearly all cases, very few grade 3) were reported in weeks 3/ 4/ 5/ 6/ 7 after start of radiotherapy in 5.7%/ 14.6%/ 23.1%/ 23.9%/ 16.5% in patients in the control arm as compared to 12.3%/ 15.8%/ 13.8%/ 13.8%/ 4.8% in the experimental arm. By the end of radiotherapy, patient reported symptoms (on a scale from 1 = no symptoms to 10 = massive symptoms) mainly concerned hot flushes (4.3 + 3.2), breast problems (4.2 + 2.7), skin problems (3.8 + 2,8) and other complaints (6.3 + 2.8). Radiotherapy was experienced less exhausting (4.3 + 2.4) than other therapy modalities (6.2 + 2.1). Patients felt well informed about radiotherapy and other modalities. Care during therapy was rated very good for all treatment modalities with the top rating for radiotherapy (9.5 + 1.2). The preliminary safety data of the HYPOSIB-trial prove the safety of adjuvant breast radiotherapy in this nationwide study. Acute skin reactions were less pronounced and occurred two weeks earlier in the HYPOSIB-arm than in the control arm. Patients should be informed that hypofractionated irradiation is already finished before the peak skin reaction occurs. Satisfaction of patients with therapy was generally high, especially with radiotherapy. Patient-reported symptom burden by the end radiotherapy may help to better tailor individual treatment.