Acute skin toxicity comparison of adjuvant two-weekly accelerated hypofractionated versus three-weekly moderately hypofractionated radiotherapy in breast cancer: A phase 2, open label, randomized control trial.

Abstract

TPS68 Background: Moderately hypo-fractionated radiotherapy (40 Gy/15 fractions/3 weeks) is the established adjuvant standard after breast-conserving surgery or mastectomy. Subsequent trials validated further treatment acceleration, consistent with the low α/β ratio (~3 Gy). Indian phase II data using 34 Gy/10 fractions/2 weeks showed acceptable ≥Grade 2 dermatitis; however, no Indian randomized study directly compares this 2-week regimen with contemporary 3-week schedules incorporating regional nodal irradiation and simultaneous integrated boost despite 33% shorter treatment duration. Methods: The study is prospective, non-stratified, randomized phase II, open labelled, enrolls women with histologically confirmed invasive carcinoma (pT0–3, pN0–2a), According to AJCC 8 th edition, following breast-conserving surgery or mastectomy with negative margins. Eligible patients are ≥18 years without advanced loco-regional disease, prior malignancy, distant metastasis, prior thoracic irradiation, indication for internal mammary nodal irradiation or pregnancy. Participants are assigned 1:1 through computer-generated block (size 4 and 6) randomization with allocation concealment. Control arm: moderately hypo-fractionated radiotherapy (40 Gy/15 fractions/3 weeks) with regional nodal irradiation (RNI) as indicated and simultaneous integrated boost (SIB) of 8 Gy in 15 fractions. Interventional arm: accelerated hypo-fractionated radiotherapy (34 Gy/10 fractions/2 weeks) with RNI as indicated and SIB of 8 Gy in 10 fractions. CT simulation with immobilization, ESTRO-guided target delineation, image-guided verification, and protocol-specified organ-at-risk constraints are mandated. The primary endpoint is cumulative ≥Grade 2 acute radiation dermatitis (RTOG; CTCAE v5.0) during treatment and within 3 months. Secondary endpoints include loco-regional control, Quality of life assessment (EORTC c30 and BR45) late toxicity at 6 months (RTOG; CTCAE v5.0), and dosimetric outcomes. Assuming dermatitis rates of 68% versus 32%, 64 patients provide 80% power (two-sided α=0.05); 72 will be enrolled allowing 10% attrition. Statistical analyses for primary outcome will include Chi-square/Fisher’s exact tests, Kaplan–Meier estimates with log-rank comparison, and Cox proportional hazards modelling. Secondary outcome will use Independent T test and chi square or fisher exact test. Accelerated 34 Gy/10 fractions is expected to achieve non-inferior acute toxicity, comparable early loco-regional control, and improved treatment efficiency, supporting its potential adoption in high-volume, resource-constrained oncology settings. Clinical trial information: CTRI/2024/10/074718 .