Hypofractionated radiation therapy comparing a standard radiotherapy schedule (over 3 weeks) with a novel 1-week schedule in adjuvant breast cancer: an open-label randomized controlled study (HYPORT-Adjuvant)—study protocol for a multicentre, 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 1-week (5 fractions) regimen of radiotherapy will be non-inferior to a standard 3-week (15 fractions) schedule. Methods We describe a multicentre, 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). The 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 (December 31, 2018) as well as the ClinicalTrial.gov website at NCT03788213 (December 28, 2018).

Dosimetric Study Comparing 3D Conformal Radiotherapy (3D-CRT), Intensity Modulated Radiotherapy (IMRT) and Volumetric Modulated Arc Therapy (VMAT) in Hypofractionated One-Week Radiotherapy Regimen in Breast Cancer

“…A similar result was reported in previous studies for other hypofractionated regimens [5][6][7]. In the multicentric randomized trial protocol (HYPORT-Adjuvant) treatment planning achieving breast/chest wall coverage with 95% of the prescribed dose and limiting the maximum dose to less than 107% of the prescribed dose was allowed [9].…”

Effectiveness of hypofractionated and normofractionated radiotherapy in a triple‐negative breast cancer model

“…Equal effectiveness and toxicities of HypoRT compared to NormRT for breast cancer have been proven in several randomized clinical trials since the early 2000s (14,(26)(27)(28)(29)(30)(31)(32). However, little is known so far about the cellular processes that take place during the medical radiation, applied over time in different-sized fractions, though understanding the mechanisms of side-effect occurrence, or those which promote cancer cell survival, could improve treatment and patient outcome and identify new strategies for more precise intervention.…”

Effect of non-sentinel metastasis on adjuvant treatment decisions and survival in Z0011 eligible non-screened detected breast cancer population

“…The lateral edge of the tangential field was placed such that the apex of the axilla was spared. Matched supraclavicular field radiotherapy using Case bow’s technique [ 27 ] was used such that there was no overlap between supraclavicular fossa and tangential field.…”