Huntsman Cancer Hospital, University of Utah, Salt Lake City, Utah.
Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey.
Int J Radiat Oncol Biol Phys. 2020 Jul 15;107(4):694-700. doi: 10.1016/j.ijrobp.2020.03.020. Epub 2020 Apr 11.
Hypofractionation in the setting of postmastectomy radiation (PMRT) is not currently the standard of care in most countries. Here we present a 5-year update of our multi-institutional, phase 2 prospective trial evaluating a novel 15-day hypofractionated PMRT regimen.
Patients were enrolled to receive 3.33 Gy daily to the chest wall (or reconstructed breast) and regional lymphatics in 11 fractions with an optional 4-fraction mastectomy scar boost. The primary endpoint was freedom from grade 3 or higher late non-reconstruction-related radiation toxicities. Toxicities were scored using Common Terminology Criteria for Adverse Events v4.0. Secondary endpoints included local and locoregional recurrence rates, cosmesis, and reconstruction complications.
After enrolling 69 patients with stage II-IIIa breast cancer, 67 women were eligible for analysis. At a median follow up of 54 months, there were no acute or late grade 3 and 4 nonreconstruction reported toxicities. The grade 2 or greater late toxicity rate was only 12% and comprised grade 2 pain, fatigue, and lymphedema that persisted beyond 6 months after completion of radiation therapy. Only 3 women (4.6%) experienced a chest wall or nodal recurrence as a first site of relapse. Freedom from local failure, including local failure after distant relapse, was 92% at 5 years, and the 5-year overall survival was 90%.
This is the first prospective trial conducted in the United States to demonstrate the safe and effective use of hypofractionated PMRT. We have demonstrated a low complication rate while achieving excellent local control. Toxicity was better than anticipated based on previously published series of PMRT toxicities. Although our fractionation was novel, the radiobiological equivalent dose is similar to other hypofractionation schedules. This trial was the basis for the creation of Alliance A221505 (RT CHARM), which is currently accruing patients in a phase 3 randomized design.
在乳房切除术后放疗（PMRT）中，目前在大多数国家都不采用分割剂量放疗。在此，我们报告了一项多机构、2 期前瞻性试验的 5 年更新结果，该试验评估了一种新的 15 天分割剂量 PMRT 方案。
患者被纳入研究，接受每日 3.33 Gy 的胸部（或重建乳房）和区域淋巴结放疗，共 11 个分次，可选择 4 个分次进行乳房切除术瘢痕加量。主要终点是无 3 级或更高级别的非重建相关迟发性放射性毒性。毒性采用通用术语标准 4.0 进行评分。次要终点包括局部和局部区域复发率、美容效果和重建并发症。
在入组了 69 例 II-IIIa 期乳腺癌患者后，有 67 例女性符合分析条件。中位随访 54 个月时，无急性或迟发性 3 级和 4 级非重建相关毒性报告。2 级或更高级别的迟发性毒性发生率仅为 12%，包括 2 级疼痛、乏力和淋巴水肿，这些毒性在放疗结束后 6 个月以上仍持续存在。只有 3 例女性（4.6%）首先出现胸壁或淋巴结复发。5 年局部无失败率（包括远处复发后的局部失败）为 92%，5 年总生存率为 90%。
这是在美国进行的首个前瞻性试验，证明了分割剂量 PMRT 的安全有效使用。我们在实现优异局部控制的同时，降低了并发症发生率。毒性低于基于之前发表的 PMRT 毒性系列研究的预期。尽管我们的分割剂量方案是新颖的，但放射生物学等效剂量与其他分割剂量方案相似。这项试验是 Alliance A221505（RT CHARM）试验的基础，该试验目前正在以 3 期随机设计入组患者。
