Hypofractionated versus conventional fractionated postmastectomy radiotherapy for patients with high-risk breast cancer (CHN HYPOPMRT): 10-year outcomes from a randomised, non-inferiority, open-label, phase 3 trial.

We aimed to assess the long-term efficacy and adverse eventprofile of hypofractionated versus conventional fractionated postmastectomy radiotherapy in high-risk breast cancer.

我们的目标是评估高风险乳腺癌患者在乳腺癌切除术后接受低分割与常规分割放射治疗的长期疗效和不良事件特征。

Methods

This randomised, non-inferiority, open-label, phase 3 trial was done at a national cancer centre in China.

这是一项在中国国家癌症中心进行的随机、非劣效、开放标签的III期试验。

Eligible patients were women aged 18-75 years with high-risk breast cancer who had undergone modified radical mastectomy and axillary dissection with a Karnofsky performance score 60% or higher.

符合条件的患者是年龄在18-75岁之间，接受过改良根治性乳腺癌切除术和腋窝清扫术，且卡氏功能状态评分在60%或以上的高风险乳腺癌女性。

Participants were randomly assigned (1:1) to conventional fractionated radiotherapy (50 Gy in 25 fractions over 5 weeks) or hypofractionated radiotherapy (43·5 Gy in 15 fractions over 3 weeks) to the chest wall and supraclavicular region, using a computer-generated sequence with concealed allocation and no masking.

参与者被随机分配（1:1）接受常规分割放射治疗（50 Gy，25次分割，5周内完成）或低分割放射治疗（43.5 Gy，15次分割，3周内完成），使用计算机生成的序列进行分配，分配过程是隐藏的，没有使用盲法。

The primary endpoint was 5-year cumulative incidenceof locoregional recurrence, analysed in the modified intention-to-treatpopulation (including all eligible patients who underwent randomisation, but excluding those who were considered ineligible or withdrew consent after randomisation) and a 5% margin was used to establish non-inferiority.

主要终点是5年局部区域复发的累积发生率，分析在修改意向治疗人群中（包括所有符合条件并进行了随机化的患者，但排除了那些在随机化后被认为不符合条件或撤回同意的患者），并使用5%的边界来确定非劣效性。

In this prespecified long-term analysis, outcomes at 10 years were analysed without additional confirmatory non-inferiority testing.

在这项预先设定的长期分析中，对10年的结果进行了分析，没有进行额外的确认性非劣效性测试。

Safety was analysed in the modified intention-to-treatpopulation.

安全性分析在修改意向治疗人群中进行。

This trial is registered with ClinicalTrials.gov, NCT00793962, and is closed to enrolment.

该试验已在ClinicalTrials.gov注册，编号为NCT00793962，并已停止招募。

Results

Between June 12, 2008, and June 16, 2016, 2157 patients were assessed for eligibility. 1337 were excluded and 820 patients were enrolled and randomly assigned (414 to conventional fractionated radiotherapy and 406 to hypofractionated radiotherapy).

在2008年6月12日至2016年6月16日期间，共有2157名患者被评估是否符合入组条件。其中1337名被排除，820名患者被纳入并随机分配（414名接受常规分割放疗，406名接受低分割放疗）。

Five patients were excluded in each group and 810 were included in the analyses (409 to conventional fractionated radiotherapy and 401 to hypofractionated radiotherapy).

每组各有5名患者被排除，共有810名患者被纳入分析（409名接受常规分割放疗，401名接受低分割放疗）。

Median follow-up was 11·5 years (IQR 9·6-13·8).

中位随访时间为11.5年（四分位数间距9.6-13.8）。

Median patient age was 49 years (range 24-74), and 761 (94%) patients had stage III disease.

患者中位年龄为49岁（范围24-74岁），761名（94%）患者患有III期疾病。

All patients were female, and data on race and ethnicity were not collected.

所有患者均为女性，未收集种族和民族数据。

At 10 years, cumulative locoregional recurrence was 10·3% (95% CI 7·3-13·3) with conventional fractionated radiotherapy and 12·0% (8·8-15·2) with hypofractionated radiotherapy (hazard ratio1·19, 95% CI 0·79-1·82).

在10年时，常规分割放疗的累积局部区域复发率为10.3%（95% CI 7.3-13.3），低分割放疗为12.0%（8.8-15.2）（风险比1.19，95% CI 0.79-1.82）。

The most common grade 3 adverse events at 10 years were ischaemic heart disease (five [1%] of 409 patients in the conventional fractionated radiotherapy group vs five [1%] of 401 patients in the hypofractionated radiotherapy group), lymphoedema (four [1%] vs three [<1%]), shoulder dysfunction (two [<1%] vs one [<1%]), and skin adverse events (none vs one [<1%]).

在10年时，最常见的3级不良事件是缺血性心脏病（常规分割放疗组409名患者中有5名[1%]，低分割放疗组401名患者中有5名[1%]），淋巴水肿（分别为四名[1%]和三名[<1%]），肩部功能障碍（分别为两名[<1%]和一名[<1%]），以及皮肤不良事件（无与一名[<1%]）。

No grade 4-5 events, brachial plexopathy, serious adverse events, or treatment-related deaths occurred.

未发生4-5级事件、臂丛神经病变、严重不良事件或与治疗相关的死亡事件。

interpretation

Hypofractionated postmastectomy radiotherapy provided durable locoregional control with no increase in severe late adverse events compared with conventional fractionation, supporting its use as a more time-efficient option than conventional fractionated radiotherapy.

低分割剂量的术后放疗提供了持久的局部区域控制，与常规分割相比，并未增加严重的晚期不良事件，支持其作为比常规分割放疗更节省时间的选择。

funding

Noncommunicable Chronic Diseases-National Science and Technology Major Project, National Natural Science Foundation of China, National High Level Hospital Clinical Research Funding, Cooperation Fund of CHCAMS, and CAMS Innovation Fund for Medical Sciences.

非传染性慢性疾病-国家科技重大专项、中国国家自然科学基金、国家高水平医院临床研究资金、中国医学科学院合作基金和中国医学科学院医学创新基金。