Concurrent Versus Sequential Radiation Dose Escalation to the Surgical Cavity for Conservative Treatment of High-Risk Early Breast Cancer: NRG/RTOG 1005 Phase III Trial.

This phase III trial investigated whether boost delivery during WBI versus after WBI provides noninferior IBR and preserves cosmetic appearance.

这项III期临床试验研究了在WBI期间与WBI后进行增强放疗是否能提供非劣效的IBR并保持美容效果。

Methods

NRG/RTOG 1005 randomly assigned patients at higher risk for IBR after lumpectomy and axillary surgery 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 radiation therapy (RT) or intensity-modulated RT.

NRG/RTOG 1005随机将接受乳房切除术和腋窝手术后有较高保乳失败（IBR）风险的患者分配至序贯推量治疗组（12 Gy，6次分割）或（14 Gy，7次分割）在全乳放疗（WBI）50 Gy，25次分割或42.7 Gy，16次分割后进行，或同时推量治疗组（8 Gy，15次分割）与WBI 40 Gy，15次分割同时进行，每天0.53 Gy，使用三维适形放疗（RT）或强度调制放疗（IMRT）。

Based on 1.59% 5-year IBR for the sequential arm, defining the noninferiority margin as a hazard ratioupper limit on the 90% CI of 2.12, 2,312 patients provide 80% power for noninferiority of IBR as first recurrence for the concurrent arm.

基于序贯组5年IBR为1.59%，将非劣效性边界定义为90%置信区间上限的风险比为2.12，2312名患者为同时组首次复发的IBR提供了80%的非劣效性检验功效。

Secondary end points included disease-free survival and overall survival, adverse events (AEs), and cosmetic outcomes.

次要终点包括无病生存期和总生存期、不良事件（AEs）以及美容结果。

Results

Between May 24, 2011, and June 20, 2014, 2,354 patients were randomly assigned, with 2,255 eligible for analysis (sequential arm, n = 1,118; concurrent arm, n = 1,137).

在2011年5月24日至2014年6月20日期间，共有2,354名患者被随机分配，其中2,255名患者符合分析条件（序贯组，n=1,118；同步组，n=1,137）。

With median follow-up of 7.3 years, there were 56 IBR events; 5- and 7-year IBR were 2.1% and 2.2% on the sequential arm and 1.9% and 2.6% on the concurrent arm, respectively.

中位随访时间为7.3年，共发生56例IBR事件；顺序治疗组5年和7年的IBR分别为2.1%和2.2%，同时治疗组则为1.9%和2.6%。

The noninferiority criterion was met: HR (90% CI): 1.31 (0.84 to 2.04), P = .037.

非劣效性标准得到满足：风险比（90%置信区间）为1.31（0.84至2.04），P值为0.037。

No differences were observed in AEs, cosmetic outcomes, or survival between arms.

在不良事件、美容结果或生存率方面，两组之间未观察到差异。

Conclusions

Concurrent boost during WBI results in noninferior IBR compared with sequential boost without worsening toxicity or cosmetic outcomes and reduces overall treatment time.

在全乳放疗期间进行同时性推量与顺序性推量相比，不会增加毒性或影响美容结果，并且可以减少总体治疗时间，同时保持与顺序性推量相当的即时乳房重建（IBR）效果。