Abstract GS2-12: Radiation doses and fractionation schedules in non-low-risk ductal carcinoma in situ in the breast (BIG 3-07/TROG 07.01): final 10-year analysis of a randomised, factorial, multicentre, open-label, phase 3 study

Abstract Background: Whole breast irradiation (WBI) after breast conserving surgery for ductal carcinoma in-situ (DCIS) reduces local recurrence. We aimed to evaluate whether a tumor bed boost after WBI improved long-term outcomes, and examine radiation dose fractionation sensitivity for non-low-risk DCIS. Methods: The study was an international, randomized, unmasked, phase 3 trial involving 136participating centers from six clinical trials organizations in 11 countries. Eligible patients were women aged ≥18 years who had breast conserving surgery with ≥1 mm of clear radial resection margins for unilateral, histologically proven, non-low-risk DCIS defined as age <50 years or age ≥50 years plus at least one of the risk factors for local recurrence (palpable tumor, multifocal disease, tumor size ≥1.5cm, intermediate or high nuclear grade, central necrosis, comedo histology and/or surgical margin<10 mm). Patients were stratified by age (<50 years vs ≥50 years), planned endocrine therapy (yes or no) and treating center. They were randomized to one of four groups (1:1:1:1) of no boost versus boost after conventional versus hypofractionated WBI, or to one of two groups (1:1) of no boost versus boost after each center-prespecified conventional or hypofractionated WBI. The conventional WBI was 50 Gy in 25 fractions, and hypofractionated WBI was 42·5 Gy in 16 fractions. A boost dose of 16 Gy in eight fractions, if allocated, was delivered after WBI. The primary endpoint was time to local recurrence. Secondary endpoints were time-to-disease recurrence, overall survival and treatment toxicity. Cosmetic outcome and health-related quality of life will be reported separately. This trial is registered with ClinicalTrials.gov (NCT00470236). Results: Between June 25, 2007, and June 30, 2014, 1608 patients were randomly assigned to no tumor bed boost (805 patients) or boost (803 patients). Conventional WBI was given to 831 patients, and hypofractionated WBI was given to 777 patients. Endocrine therapy was used in 13% of patients. Median follow-up was 10.2 years. The 10-year free-from-local-recurrence rates were 87% (95% CI 84-89%) in the no-boost group and 93% (91-95%) in the boost group (hazard ratio 0.49; 0.34-0.69;p<0.001). Fifty-four percent and 58% of local recurrences were invasive in the no-boost and boost groups, respectively. There were no significant differences in the 10-year free-from-local recurrence rates between the conventional WBI and hypofractionated WBI groups in the 4-arm randomization category (90% vs. 89%, P=0.82) or in all randomized patients (89% vs. 91%, P=0.80). The test for interaction between boost and dose-fractionation was not significant in the 4-arm randomization category (P=0.39) or in all randomized patients (P=0.77). The 10-year free-from-disease recurrence rates were lower in the no-boost group (79%) than in the boost group (87%; hazard ratio, 0.67;0.52−0.86; p=0.002). There was no statistically significant difference in 10-year overall survival rates between the no-boost (94%) and boost (96%) groups (0·73; 0·47-1·14; p=0·17). The boost group had higher rates of grade 2 or higher breast induration (7% [5-9%] vs 17% [14-19%], p<0.001) and breast pain (11% [9-13%] vs 17% [14-20%], p=0·002), with no suggestion of interaction with WBI dose fractionation. Conclusions: Our results provide the first long-term randomized trial data to demonstrate the efficacy of tumor bed boost radiation after postoperative WBI on local recurrence in patients with non-low-risk DCIS with an associated increase in grade 2 or greater breast induration and pain. Within the limits of the trial design, moderately hypofractionated WBI was not associated with an increase in local recurrence or toxicity. Citation Format: B. H. Chua, E. K. Link, I. A. Olivotto, I. Kunkler, T. Whelan, P. Deseyne, G. Gruber, BIG 3-07/TROG 07.01 trial investigators.. Radiation doses and fractionation schedules in non-low-risk ductal carcinoma in situ in the breast (BIG 3-07/TROG 07.01): final 10-year analysis of a randomised, factorial, multicentre, open-label, phase 3 study [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr GS2-12.