Early Safety of Ultra-Hypofractionated Whole Breast Irradiation and Sequential Tumor Bed Boost for Early Breast Cancer (SHIFT): A Multicenter, Phase 2 Trial

PURPOSE: The multicenter, single-arm, phase 2 SHIFT trial evaluated an ultra-hypofractionated radiation therapy regimen that completes both whole breast irradiation and a sequential tumor bed boost within 1.5 weeks, with the primary endpoint of acute toxicity. METHODS AND MATERIALS: Patients at 4 tertiary hospitals in China aged 18 years or above with invasive breast carcinoma (pT1-3, N0-1mic, M0) or ductal carcinoma in situ after BCS were eligible. All enrolled patients underwent whole breast irradiation of 26 Gy in 5 fractions over 5 days. A sequential tumor bed boost of 10.4 Gy in 2 fractions over 2 days was at the discretion of the radiation oncologist. The primary endpoint was the incidence of grade ≥2 acute radiation-induced toxicity within 6 months after RT, including fatigue, dermatitis, and breast pain. This trial is registered at ClinicalTrials.gov (NCT04926766). RESULTS: Between January 2021 and July 2023, recruitment of 217 patients has been completed, of whom 209 received tumor bed boost. Within 6 months after RT, 157 (72.4%) patients experienced G1 acute toxicity only, 16 (7.4%) patients experienced G2 acute toxicity, with no G3 events observed. No toxicity event was reported in 44 (20.3%) patients. At a median follow-up of 28.3 months, no severe toxicities were found in any patient at any time during follow-up. No locoregional recurrence, distant metastasis, or death occurred. Dosimetric analysis demonstrated high protocol compliance across all centers. CONCLUSIONS: The integrated ultra-hypofractionated radiation therapy regimen is well-tolerated, with acute toxicity profiles confirming its favorable safety profile. Long-term follow-up is ongoing to assess late effects and efficacy.