Impact of guideline changes on adoption of hypofractionation and breast cancer patient characteristics in the randomized controlled HYPOSIB trial.

PURPOSE: Hypofractionated radiotherapy is the standard of care for adjuvant whole breast radiotherapy (RT). However, adoption has been slow. The indication for regional nodal irradiation has been expanded to include patients with 0-3 involved lymph nodes. We investigated the impact of the publication of the updated German S3 guidelines in 2017 on adoption of hypofractionation and enrollment of patients with lymph node involvement within a randomized controlled phase III trial. METHODS: In the experimental arm of the HYPOSIB trial (NCT02474641), hypofractionated RT with simultaneous integrated boost (SIB) was used. In the standard arm, RT could be given as hypofractionated RT with sequential boost (HFseq), normofractionated RT with sequential boost (NFseq), or normofractionated RT with SIB (NFSIB). The cutoff date for the updated German S3 guidelines was December 17, 2017. Temporal trends were analyzed by generalized linear regression models. Multiple logistic regression models were used to investigate the influence of time (prior to/after guideline) and setting (university hospital/other institutions) on the fractionation patterns. RESULTS: Enrollment of patients with involved lymph nodes was low throughout the trial. Adoption of HFseq increased over time and when using the guideline publication date as cutoff. Results of the multiple logistic regressions showed an interaction between time and setting. Furthermore, the use of HFseq was significantly more common in university hospitals. CONCLUSION: The use of HFseq in the standard arm increased over the course of the HYPOSIB trial and after publication of the S3 guideline update. This was primarily driven by patients treated in university hospitals. Enrolment of patients with lymph node involvement was low throughout the trial.

Hypofractionation with simultaneous integrated boost for early breast cancer: results of the German multicenter phase II trial (ARO-2010-01).

PURPOSE: To evaluate the feasibility of hypofractionation with SIB in all settings in Germany to prepare a multicenter treatment comparison. METHODS: Eligible patients had histopathologically confirmed breast cancer operated by BCS. Patients received WBI 40.0 Gy in 16 fractions of 2.5 Gy. A SIB with 0.5 Gy per fraction was administered to the tumor bed, thereby giving 48.0 Gy in 16 fractions to the boost-PTV sparing heart, LAD, lung, contralateral breast. The primary study objective was feasibility, administration of specified dose in 16 fractions within 22-29 days with adherence to certain dose constraints (heart; LAD; contralateral breast); secondary endpoints were toxicity, QoL. RESULTS: 151 patients were recruited from 7 institutions between 07/11-10/12. 10 patients met exclusion criteria prior to irradiation. All but two patients (99%) received the prescribed dose in the PTVs. Adherence to dose constraints and time limits was achieved in 89% (95% CI 82% to 93%). 11 AE were reported in 10 patients; five related to concurrent endocrine therapy. Two of the AEs were related to radiotherapy: grade 3 hot flushes in two cases. QoL remained unchanged. CONCLUSION: Hypofractionation with a SIB is feasible and was well tolerated in this study.