Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea.
Proton Therapy Center, Research Institute and Hospital, National Cancer Center, Goyang, Korea.
JAMA Oncol. 2022 Jan 1;8(1):96-105. doi: 10.1001/jamaoncol.2021.6036.
The benefit of internal mammary node irradiation (IMNI) for treatment outcomes in node-positive breast cancer is unknown.
To investigate whether the inclusion of IMNI in regional nodal irradiation improves disease-free survival (DFS) in women with node-positive breast cancer.
DESIGN, SETTING, AND PARTICIPANTS: This multicenter, phase 3 randomized clinical trial was conducted from June 1, 2008, to February 29, 2020, at 13 hospitals in South Korea. Women with pathologically confirmed, node-positive breast cancer after breast-conservation surgery or mastectomy with axillary lymph node dissection were eligible and enrolled between November 19, 2008, and January 14, 2013. Patients with distant metastasis and those who had received neoadjuvant treatment were excluded. Data analyses were performed according to the intention-to-treat principle.
All patients underwent regional nodal irradiation along with breast or chest wall irradiation. They were randomized 1:1 to receive radiotherapy either with IMNI or without IMNI.
The primary end point was the 7-year DFS. Secondary end points included the rates of overall survival, breast cancer-specific survival, and toxic effects.
A total of 735 women (mean [SD] age, 49.0 [9.1] years) were included in the analyses, of whom 373 received regional nodal irradiation without IMNI and 362 received regional nodal irradiation with IMNI. Nearly all patients underwent taxane-based adjuvant systemic treatment. The median (IQR) follow-up was 100.4 (89.7-112.1) months. The 7-year DFS rates did not significantly differ between the groups treated without IMNI and with IMNI (81.9% vs 85.3%; hazard ratio [HR], 0.80; 95% CI, 0.57-1.14; log-rank P = .22). However, an ad hoc subgroup analysis showed significantly higher DFS rates with IMNI among patients with mediocentrally located tumors. In this subgroup, the 7-year DFS rates were 81.6% without IMNI vs 91.8% with IMNI (HR, 0.42; 95% CI, 0.22-0.82; log-rank P = .008), and the 7-year breast cancer mortality rates were 10.2% without IMNI vs 4.9% with IMNI (HR, 0.41; 95% CI, 0.17-0.99; log-rank P = .04). No differences were found between the 2 groups in the incidence of adverse effects, including cardiac toxic effects and radiation pneumonitis.
This randomized clinical trial found that including IMNI in regional nodal irradiation did not significantly improve the DFS in patients with node-positive breast cancer. However, patients with medially or centrally located tumors may benefit from the use of IMNI.
ClinicalTrials.gov Identifier: NCT04803266.
重要性：对于淋巴结阳性乳腺癌患者，内乳淋巴结照射（IMNI）对治疗结果的获益尚不明确。
目的：研究局部区域淋巴结照射中纳入 IMNI 是否能改善淋巴结阳性乳腺癌患者的无病生存（DFS）。
设计、地点和参与者：这是一项多中心、3 期随机临床试验，于 2008 年 6 月 1 日至 2020 年 2 月 29 日在韩国的 13 家医院进行。入组标准为保乳手术后或腋窝淋巴结清扫术后病理证实为淋巴结阳性的乳腺癌患者，于 2008 年 11 月 19 日至 2013 年 1 月 14 日期间入组。排除远处转移患者和接受新辅助治疗的患者。数据分析采用意向治疗原则。
干预措施：所有患者均接受区域淋巴结照射和乳房或胸壁照射。他们以 1:1 的比例随机接受有或无 IMNI 的放疗。
主要结局和测量指标：主要终点为 7 年 DFS。次要结局包括总生存、乳腺癌特异性生存和毒性效应的发生率。
结果：共纳入 735 例患者（平均[标准差]年龄，49.0[9.1]岁），其中 373 例接受无 IMNI 的局部区域淋巴结照射，362 例接受有 IMNI 的局部区域淋巴结照射。几乎所有患者均接受了紫杉类药物为基础的辅助全身治疗。中位（IQR）随访时间为 100.4（89.7112.1）个月。无 IMNI 组和有 IMNI 组的 7 年 DFS 率无显著差异（81.9%比 85.3%；HR，0.80；95%CI，0.571.14；对数秩检验 P=0.22）。但是，一项亚组分析显示，对于肿瘤位于中央或中间部位的患者，IMNI 组的 DFS 更高。在此亚组中，无 IMNI 组和有 IMNI 组的 7 年 DFS 率分别为 81.6%和 91.8%（HR，0.42；95%CI，0.220.82；对数秩检验 P=0.008），7 年乳腺癌死亡率分别为 10.2%和 4.9%（HR，0.41；95%CI，0.170.99；对数秩检验 P=0.04）。两组间的不良反应发生率（包括心脏毒性和放射性肺炎）无差异。
结论和相关性：这项随机临床试验发现，在淋巴结阳性乳腺癌患者中，将 IMNI 纳入局部区域淋巴结照射并不会显著改善 DFS。然而，对于肿瘤位于中央或中间部位的患者，使用 IMNI 可能会获益。
试验注册：ClinicalTrials.gov 标识符：NCT04803266。
