Internal mammary chain and medial supraclavicular lymph node irradiation in stage I-III breast cancer (EORTC trial 22922/10925): an unplanned subset analysis of 20-year outcomes in patients with node-negative breast cancer.

Here, we present the scheduled 20-year analysis of the EORTC trial 22922/10925, evaluating the role of internal mammary and medial-supraclavicular (IM-MS) nodal irradiation in patients with stage I-III breast cancer.

在这里，我们展示了EORTC试验22922/10925的预定20年分析结果，评估了I-III期乳腺癌患者中内乳和内上锁骨下淋巴结（IM-MS）照射的作用。

Patients without confirmed axillary nodal involvement (pathological N stage 0 [pN0]) were eligible for the trial when the primary tumours were centrally or medially located.

当原发肿瘤位于中心或内侧时，没有确认腋窝淋巴结受累（病理N分期0 [pN0]）的患者符合试验资格。

Methods

EORTC 22922/10925 was a randomised, open-label, phase 3 trial done across 46 radiation oncology departments from 13 countries.

EORTC 22922/10925是一项随机、开放标签、3期试验，在来自13个国家的46个放射肿瘤科进行。

Eligible participants were women up to 75 years of age with unilateral, histologically confirmed, stage I-III breast adenocarcinoma with involved axillary nodes or a central or medially located primary tumour.

符合条件的参与者是年龄不超过75岁的女性，患有单侧、组织学证实的I-III期乳腺腺癌，伴有腋窝淋巴结受累或中央或内侧位置的原发肿瘤。

Patients were randomly assigned (1:1) centrally using minimisation to receive IM-MS irradiation at 50 Gy in 25 fractions (IM-MS irradiation group) or no IM-MS irradiation (control group).

患者按1:1的比例通过中心最小化随机分配接受IM-MS照射（IM-MS照射组）或不接受IM-MS照射（对照组），IM-MS照射剂量为50 Gy，分25次进行。

Stratification was done for institution, menopausal status, site of the primary tumour within the breast, type of breast and axillary surgery, and pathological T and N stage.

对机构、绝经状态、肿瘤在乳房中的位置、乳房和腋窝手术类型以及病理T和N分期进行了分层。

Patients and investigators were not masked to treatment allocation.

患者和研究人员未对治疗分配进行盲法处理。

Only patients without clinically and histopathologically confirmed nodal involvement (pN0) were included in this unplanned subgroup analysis.

只有在临床上和组织病理学上未证实有淋巴结受累（pN0）的患者被纳入这项非计划的亚组分析中。

The primary outcome was overall survivalanalysed according to the intention-to-treatprinciple.

主要结果是根据意向治疗原则分析的总生存期。

Safety analyses were conducted in the subset of eligible patients treated per protocol.

安全性分析是在符合方案治疗的合格患者子集中进行的。

This trial is registered with ClinicalTrials.gov (on Nov 1, 1999; NCT00002851) and closed after its final analysis.

该试验已在ClinicalTrials.gov注册（1999年11月1日；NCT00002851），并在最终分析后关闭。

Results

Between Aug 5, 1996, and Jan 13, 2004, 4004 patients were randomly assigned. 890 (44·5%) of 2002 patients in the IM-MS irradiation group and 888 (44·4%) of 2002 patients in the control group had pN0 disease.

1996年8月5日至2004年1月13日期间，共有4004名患者被随机分配。在IM-MS照射组的2002名患者中，有890名（44.5%）和对照组的2002名患者中，有888名（44.4%）患有pN0疾病。

The median age of participants was 55 years (IQR 48-63).

参与者的中位年龄为55岁（四分位数间距48-63岁）。

At a median follow-up of 22·2 years (IQR 20·1-24·5), 276 (31·1%) of 888 patients in the IM-MS irradiation group and 277 (31·1%) of 890 patients in the control group died because of any cause; 87 (31·5%) of 276 and 122 (44·0%) of 277 patients died due to breast cancer, respectively.

在中位随访时间为22.2年（四分位数间距20.1-24.5）时，接受IM-MS放疗的888名患者中有276名（31.1%）和对照组890名患者中有277名（31.1%）因任何原因死亡；分别有87名（31.5%）和122名（44.0%）患者因乳腺癌死亡。

At 20 years, the overall survivalrate was 69·0% (95% CI 65·4-72·3) in the IM-MS irradiation group and 68·4% (64·8-71·6%) in the control group (hazard ratio[HR] 0·98 [95% CI 0·83-1·15], p=0·77).

在20年时，IM-MS放疗组的总生存率为69.0%（95%置信区间65.4-72.3），对照组为68.4%（64.8-71.6%）（风险比[HR] 0.98 [95%置信区间0.83-1.15]，p=0.77）。

The breast cancer mortality rate was 10·0% (8·0-12·3) in the IM-MS irradiation group and 14·2% (11·9-16·8) in the control group (HR 0·70 [95% CI 0·53-0·92], p=0·010), but cumulative mortality of unknown cause or not breast cancer cause was 20·9% (95% CI 17·9-24·1) in the IM-MS irradiation group and 17·4% (14·7-20·3) in the control group (HR 1·24 [95% CI 1·00-1·53]; p=0·048).

在IM-MS照射组中，乳腺癌死亡率为10.0%（8.0-12.3），对照组为14.2%（11.9-16.8）（HR 0.70 [95% CI 0.53-0.92], p=0.010），但未知原因或非乳腺癌原因的累积死亡率为IM-MS照射组的20.9%（95% CI 17.9-24.1）和对照组的17.4%（14.7-20.3）（HR 1.24 [95% CI 1.00-1.53]; p=0.048）。

In patients with left-sided breast cancer, late cardiac fibrosis occurred in 15 (3·4%) of 445 patients in the IM-MS irradiation group and 12 (2·8%) of 436 patients in the control group.

在左侧乳腺癌患者中，晚期心脏纤维化在IM-MS照射组的445名患者中有15例（3.4%），对照组的436名患者中有12例（2.8%）。

Lung fibrosis at any grade occurred in 55 (6·4%) of 855 patients in the IM-MS irradiation group and 18 (2·1%) of 877 patients in the control group.

在855名接受IM-MS照射的患者中，有55名（6.4%）出现任何级别的肺纤维化，而在877名对照组患者中，有18名（2.1%）出现肺纤维化。

interpretation

Breast cancer mortality at 20 years was significantly lower in the IM-MS irradiation group, whereas non-breast cancer mortality was numerically higher in the IM-MS irradiation group after 15 years, resulting in no long-term benefit of IM-MS irradiation on overall survival. Our results emphasise the importance of very long-term follow-up and advanced irradiation techniques to reduce the dose to organs of interest.

在20年的随访中，IM-MS照射组的乳腺癌死亡率显著降低，而在15年后的非乳腺癌死亡率在IM-MS照射组中数值上更高，导致IM-MS照射对总生存没有长期益处。我们的结果强调了非常长期随访和先进照射技术的重要性，以减少对感兴趣器官的剂量。

funding

Ligue Nationale contre le Cancer, KWF Kankerbestrijding, and EORTC Cancer Research Fund.

法国国家抗癌联盟、荷兰癌症基金会（KWF Kankerbestrijding）和欧洲癌症研究与治疗组织（EORTC）癌症研究基金