Abstract GS2-04: A randomized phase III study of radiation doses and fractionation schedules in non-low risk ductal carcinoma in situ (DCIS) of the breast (BIG 3-07/TROG 07.01)
Authors: Chua Boon Hui , Link Emma , Kunkler Ian , Olivotto Ivo , Westenberg Antonia Helen , Whelan Timothy , Gruber Guenther ,   Breast International Group (BIG)-aisbl, Trans Tasman Radiation Oncology Group, Scottish Cancer Trials Breast Group, Canadian Cancer Trials Group, European Organization for Research and Treatment of Cancer, International Breast Cancer Study Group, Cancer Trials Ireland
Published: February 2021

Abstract
Background: Wholebreast irradiation (WBI) after breast conserving surgery for DCIS reduces therisk of local recurrence including invasive recurrence. The objective of BIG3-07/TROG 07.01 is to test radiation dose escalation to the tumor bed (tumorbed boost) and fractionation sensitivity of whole breast irradiation (WBI) inpatients with non-low risk DCIS treated with breast conserving therapy.
Methods: BIG3-07/TROG 07.01 is an international, multicenter, randomized, controlled, phase 3 trial. Eligible women were ≥18 years ofage with completely resected non-low risk DCIS defined as age &lt;50 years orage ≥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 histologyand/or surgical margin &lt;10 mm). Patients were randomized to have tumor bedboost (16 Gy in 8 daily fractions) or no boost following conventional WBI (50Gy in 25 daily fractions) or hypofractionated WBI (42.5 Gy in 16 dailyfractions) in one of three randomization categories selected by centers priorto study activation. Randomization A was a 4-arm randomization of no boost vs. boostfollowing conventional WBI vs. hypofractionated WBI. Patients in RandomizationB and Randomization C were assigned no boost or boost following conventional WBIand hypofractionated WBI, respectively. The primary endpoint was time to localrecurrence, analyzed by intention to treat. The trial was designed to detect a3% difference in 5-year free-from- local recurrence rates between the no boostand boost groups (93% vs 96%; hazard ratio, 0.56) with 90% power and 2-sidedalpha level of 5%. The primary effect of boost was assessed on all randomizedpatients. The secondary effect of WBI dose-fractionation and the interactionbetween boost and WBI dose-fractionation were assessed on patients in RandomizationA and additionally on all patients.
Results: BetweenJune 2007 and June 2014, 1608 patients were randomized to have no boost (805patients) or boost (803 patients) after WBI. Conventional WBI was given in 831 patients(no boost in 416 patients; boost in 415 patients). Hypofractionated WBI wasgiven in 777 patients (no boost in 389 patients; boost in 388 patients). Adjuvantendocrine therapy was planned in 106 patients (13%) in the no boost group and105 patients (13%) in the boost group. Median follow-up was 6.6 years. The 5-yearfree-from- local recurrence rates were 93% in the no boost group and 97% in theboost group (hazard ratio, 0.47; 95% confidence interval [CI], 0.31 to 0.72;P&lt;0.001). Forty-four percent and 45% of LRs were invasive in the no boostgroup and boost group, respectively. The effect of boost did not vary significantlyby age, tumor size, nuclear grade, surgical margin or endocrine therapy. Therewere no significant differences in the 5-year free-from- local recurrence ratesbetween the conventional WBI group and hypofractionated WBI group inRandomization A (94% vs. 94%, P=0.84) and in all randomized patients (95% vs.95%, P=0.89). The test for interaction between boost and dose-fractionation wasnot significant in Randomization A or in all randomized patients (both P=0.89).The rates of grade ≥2 breastpain (12% vs. 16%, P=0.84) and skin and subcutaneous tissue fibrosis (6% vs.15%, P=0.14) did not differ significantly between the groups.
Conclusions: Inwomen with non-low risk DCIS treatedwith breast conserving surgery, the addition of tumor bed boost followingconventional or hypofractionated WBI reduced local recurrence rates. There wasno difference in local recurrence rates between conventional WBI andhypofractionated WBI. (Registered with ClinicalTrials.gov, NCT00470236.)
Citation Format: Boon Hui Chua, Emma Link, Ian Kunkler, Ivo Olivotto, Antonia Helen Westenberg, Timothy Whelan, Guenther Gruber, Breast International Group (BIG)-aisbl, Trans Tasman Radiation Oncology Group, Scottish Cancer Trials Breast Group, Canadian Cancer Trials Group, European Organization for Research and Treatment of Cancer, International Breast Cancer Study Group, Cancer Trials Ireland. A randomized phase III study of radiation doses and fractionation schedules in non-low risk ductal carcinoma in situ (DCIS) of the breast (BIG 3-07/TROG 07.01) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr GS2-04.