Grant: Project Grant

This proposal evaluates a new radiotherapy approach for patients with early-stage, high-risk breast cancer treated with breast-conserving surgery. The current standard of care consists of whole-breast irradiation (WBI) followed by a sequential boost to the surgical bed. WBI is now commonly delivered as 26 Gy in 5 daily fractions over one week, followed by a boost of 10 Gy in 5 daily fractions over an additional week, for a total treatment duration of two weeks. Advances in radiation delivery now enable the boost dose to be administered as a simultaneous integrated boost (SIB) during WBI. This approach shortens overall treatment time by one week and may reduce both acute and late toxicites, as the total radiation dose is lower. The SIB technique also has the potential to improve patient quality of life, increase convenience, and reduce costs to both patients and the healthcare system. We propose a randomized trial comparing standard treatment (WBI 26 Gy in 5 fractions over one week plus a sequential boost of 10 Gy in 5 fractions over one week; total 36 Gy in 10 fractions over two weeks) with an SIB approach (an additional 4 Gy delivered in 5 fractions concurrently with WBI, for a total dose of 30 Gy in 5 fractions over one week). The primary endpoint is local recurrence. Key secondary outcomes include acute and late toxicity, cosmetic outcomes, quality of life, and cost-utility. The planned sample size is 1,646 patients, to be enrolled across 31 cancer centers in Canada, with participation from 12 centers in Australia. Accrual is expected to occur over four years, with a minimum follow-up of three years. Previous radiotherapy trials have demonstrated that evidence-based treatment de-escalation can reduce morbidity while improving patient convenience. By reducing treatment duration from two weeks to one, the SIB approach has the potential to further decrease toxicity, enhance quality of life, and optimize healthcare resource utilization.