HYPOfractionated Radiation Therapy comparing a standard radiotherapy schedule (over three weeks) with a novel one week schedule in Adjuvant breast cancer: An open-label randomised controlled study (HYPORT- Adjuvant): study protocol for a multicenter, randomized phase III trial.

Abstract

Background Hypofractionated radiotherapy is the current standard for adjuvant radiotherapy across many centres. Further hypofractionation may be possible but remains to be investigated in non-caucasian populations with more advanced disease, with a higher proportion of patients requiring mastectomy as well as tumour bed boost. We are reporting the design of randomized controlled trial testing the hypothesis that a one week (5 fractions) regimen of radiotherapy will be non-inferior to a standard three week (15 fractions) schedule. Methods We describe a multicenter, randomized controlled trial recruiting patients at large academic centres across India. Patients without distant metastases who merit adjuvant radiotherapy will be eligible for inclusion in the study. Patients in the control arm will receive adjuvant radiotherapy to the breast or chest wall (with/without regional nodes) to a dose of 40 Gy / 15 fractions / 3 weeks, while those in the experimental arm will receive a dose of 26 Gy / 5 fractions / 1 week (to the same volume). Use of a simultaneous integrated boost (dose of 8 Gy and 6 Gy respectively) is allowed in patients who have undergone breast conservation. A sample size of 2100 patients provides an 80% power to detect a non-inferiority of 3% in the 5-year locoregional recurrence rate with a one-sided type I error of 2.5%, assuming that the locoregional recurrence rate in the control arm is 5% at 5 years (corresponding to a hazard ratio of 1.63). Patients will be recruited over a period of 5 years, and followed up for a further 5 years thereafter. Discussion If a five-fraction regimen of breast cancer is proven to be non-inferior, this will result in a significant improvement in the access to radiotherapy, as well as reduced costs of treatment. The trial gives an opportunity to standardize and quality assure radiotherapy practices across the nation at the same time. Along with the results of the FAST Forward trial, the safety of this intervention in advanced node-positive disease requiring regional nodal radiation will be established. Trial Registration The trial has been registered at the Clinical Trial Registry of India (CTRI) vide registration number: CTRI/2018/12/016816 (31/12/2018) as well as the clinical trial.gov website at NCT03788213 (28/12/2018).