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

Abstract

Purpose/Objective(s)

The Phase 3 FAST-Forward trial showed that 26 Gy in 5 fractions over 1 week for whole breast irradiation (WBI) was safe and efficacy for early breast cancer patients, in which a sequential tumor bed boost was allowed (10 Gy or 16 Gy in 2-Gy fractions). Current trial delivers 26 Gy in 5 fractions over 1 week for WBI and 10.4 Gy in 2 fractions once daily for sequential tumor bed boost, to keep the total duration of radiotherapy (RT) to no more than 1.5 weeks if tumor bed boost is required. Here we report the early safety of this ultra-hypofractionation regimen.

Materials/Methods

This is a multicenter, single-arm, phase 2 trial carried out at 4 tertiary hospitals in China. Patients aged at least 18 years with invasive breast carcinoma (pT1-3, N0-1mic, M0) or ductal carcinoma in situ (DCIS) after lumpectomy were eligible. All enrolled patients underwent WBI 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 radiation oncologist. The primary endpoint was acute radiation-induced toxicity within 6 months after RT, aiming for a 10% non-inferiority margin based on a projected 50% baseline incidence of ≥Grade 2 (G2) acute toxicity. Acute toxicity was assessed using CTCAE v5.0 at 1 week and 2 weeks during RT, and at 1 month and 6 months after RT completion. This trial is registered at ClinicalTrials.gov (NCT04926766).

Results

Between January 2021, and July 2023, recruitment of 217 patients has been completed, of whom 210 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. Detailed assessments at each time point are presented in Table 1. Of the 122 patients who had chest CT for evaluation at 6 months after RT, 26 (21%) experienced G1 radiation pneumonitis. No significant changes in echocardiography or cardiac biomarkers after RT were found. At a median follow-up of 16.3 months (interquartile range [IQR] = 7.3 to 37.6), no severe toxicities were found, and no locoregional recurrence, distant metastasis or death occurred. A second primary cancer of urothelial carcinoma was reported in a patient with germline BRCA1/2 mutation.

Conclusion

Ultra-hypofractionated RT of WBI and sequential tumor bed boost administrated within 1.5 weeks using 5.2 Gy per fraction is well-tolerated in early breast cancer patients. Further follow-up is needed in order to assess late toxicity and long-term efficacy.