Multicenter phase 3 trial of concurrent versus sequential dose escalation to the lumpectomy cavity in high-risk early breast cancer

For patients with breast cancer undergoing breast conservation, escalating the dose (boost) of radiation to the lumpectomy cavity after whole-breast irradiation (WBI) reduces ipsilateral breast recurrence (IBR) but extends treatment duration. The multicenter phase 3 NRG/RTOG 1005 trial investigated whether boost delivery during WBI versus after WBI provides noninferior IBR and preserves cosmetic appearance. Patients at higher risk for IBR after lumpectomy and axillary surgery were randomized to either a sequential boost of 12 Gy in six fractions (F) or 14 Gy in 7F after WBI of 50 Gy in 25F or 42.7 Gy in 16F (sequential arm) or a concurrent boost of 8 Gy in 15F of 0.53 Gy per day with WBI of 40 Gy in 15F (concurrent arm) using 3-dimensional conformal radiotherapy (RT) or intensity-modulated RT. A total of 2354 patients were randomly assigned, with 2255 eligible for analysis (1118 in the sequential arm and 1137 in the concurrent arm). The median follow-up was 7.3 years. Five-and 7-year IBR rates were 2.1% and 2.2% in the sequential arm and 1.9% and 2.6% in the concurrent arm, respectively, meeting the noninferiority criterion (p=0.037). No differences between arms were observed in adverse events, cosmetic outcomes, or survival. The authors conclude that concurrent boost during WBI results in noninferior IBR compared with sequential boost, without worsening toxicity of cosmetic outcomes, and reduces overall treatment time.