乳腺癌术后要不要内乳淋巴结放疗
对于早期乳腺癌术后患者，胸壁、乳房、区域淋巴结放疗已被随机对照研究证实可以显著减少复发率和死亡率。不过，乳房内侧（内乳）淋巴结放疗能否获益仍然存在巨大争议，既往研究结果互相矛盾，而且当时紫杉类和曲妥珠单抗尚未成为术后全身辅助治疗标准。
2021年10月25日，《美国医学会杂志》肿瘤学分册在线发表韩国延世大学医院、延世癌症中心、江南世福兰斯医院、成均馆大学三星首尔医院、蔚山大学首尔峨山医院、梨花女子大学医院、首尔大学医院、国家癌症中心、全南大学和顺医院、东亚大学医院、釜山大学医院、启明大学东山医院、嘉泉大学吉医院、抱川医科大学盆唐医院的多中心随机对照研究报告，对区域淋巴结放疗±内乳淋巴结放疗能否提高淋巴结阳性乳腺癌女性无病生存率进行了比较。
NCT04803266: Elective Internal Mammary Node Irradiation in Women With Node-positive Breast Cancer: A Randomized, Phase 3 Trial
该多中心随机对照三期临床研究于2008年6月1日～2020年2月29日在韩国13家医院开展。入组标准为2008年11月19日～2013年1月14日接受保乳手术或乳房切除术并进行腋窝淋巴结清扫术后经病理证实为淋巴结阳性乳腺癌的女性。排除标准为远处转移患者和接受术前新辅助治疗的患者。根据意向治疗原则进行数据分析。全部患者都进行区域淋巴结放疗以及乳房或胸壁放疗。按1∶1的比例随机接受或不接受内乳淋巴结放疗。主要终点为7年无病生存率，次要终点包括乳腺癌相关生存率、无远处转移生存率、总生存率、毒性反应。
结果，共计735例女性（平均年龄49.0±9.1岁）被纳入分析。几乎全部患者都接受了术后紫杉类全身辅助治疗，77.2%的HER2阳性乳腺癌患者接受了术后曲妥珠单抗全身辅助治疗。
中位随访时间为100.4个月（四分位：89.7～112.1）。
未接受（373例）与接受（362例）内乳淋巴结放疗相比：
7年无病生存率稍低：81.9%比85.3%（风险比：0.80，95%置信区间：0.57～1.14，对数秩P=0.22）
7年乳腺癌死亡率稍高：10.8%比8.4%（风险比：0.74，95%置信区间：0.47～1.16，对数秩P=0.19）
7年无远处转移生存率稍低：83.2%比85.8%（风险比：0.81，95%置信区间：0.56～1.16，对数秩P=0.25）
7年总生存率稍低：88.2%比89.4%（风险比：0.87，95%置信区间：0.57～1.31，对数秩P=0.50）
心脏毒性反应和放射性肺炎等不良反应发生率相似
不过，亚组分析表明，对于306例（41.6%）肿瘤位于乳房内侧或中央的患者，未接受（153例）与接受（153例）内乳淋巴结放疗相比：
7年无病生存率显著较低：81.6%比91.8%（风险比：0.42，95%置信区间：0.22～0.82，对数秩P=0.008）
7年乳腺癌死亡率显著较高：10.2%比4.9%（风险比：0.41，95%置信区间：0.17～0.99，对数秩P=0.04）
7年无远处转移生存率显著较低：82.3%比91.8%（风险比：0.44，95%置信区间：0.23～0.85，对数秩P=0.01）
7年总生存率稍低：88.5%比93.2%（风险比：0.51，95%置信区间：0.24～1.11，对数秩P=0.08）
因此，该随机对照临床研究结果表明，内乳淋巴结放疗并未显著提高淋巴结阳性早期乳腺癌术后区域淋巴结放疗患者的无病生存率、乳腺癌相关生存率、无远处转移生存率、总生存率。不过，对于肿瘤位于乳房内侧或中央的患者，内乳淋巴结放疗可能显著获益，故有必要进一步开展更大样本、更长随访的随机对照研究进行验证。
相关链接
JAMA Oncol. 2021 Oct 25. Online ahead of print.
Effect of Elective Internal Mammary Node Irradiation on Disease-Free Survival in Women With Node-Positive Breast Cancer: A Randomized Phase 3 Clinical Trial.
Kim YB, Byun HK, Kim DY, Ahn SJ, Lee HS, Park W, Kim SS, Kim JH, Lee KC, Lee IJ, Kim WT, Shin HS, Kim K, Shin KH, Nam CM, Suh CO.
Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea; Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea; Yonsei University College of Medicine, Seoul, Korea; Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; Asan Medical Center, University of Ulsan, College of Medicine, Seoul, Korea; Ewha Womans University School of Medicine, Seoul, Korea; Seoul National University College of Medicine, Seoul, Korea; National Cancer Center, Goyang, Korea; Chonnam National University Hwasun Hospital, Hwasun, Korea; Dong-A University Hospital, Dong-A University College of Medicine, Busan, Korea; Pusan National University School of Medicine, Busan, Korea; Dongsan Medical Center, Keimyung University School of Medicine, Daegu, Korea; Gachon University Gil Medical Center, Incheon, Korea; Bundang CHA Medical Center, CHA University, Gyeonggi-do, Korea.
This randomized clinical trial evaluates the effect of internal mammary node irradiation in regional nodal irradiation on disease-free survival among women with node-positive breast cancer in South Korea.
QUESTION: Does internal mammary node irradiation (IMNI) improve disease-free survival in patients with node-positive breast cancer?
FINDINGS: In this randomized clinical trial of 735 women with node-positive breast cancer, 7-year disease-free survival did not significantly differ between those who were randomized to receive regional nodal irradiation with IMNI and those who were randomized to receive regional nodal irradiation without IMNI. However, in a subgroup analysis of patients with mediocentrally located tumors, the 7-year disease-free survival rate was improved by 10% in the IMNI group.
MEANING: While this randomized clinical trial found no difference in 7-year disease-free survival between the the IMNI and no IMNI groups, the findings of an unprespecified subgroup analysis suggest that including IMNI in regional nodal irradiation might be considered for patients with medially or centrally located tumors.
IMPORTANCE: The benefit of internal mammary node irradiation (IMNI) for treatment outcomes in node-positive breast cancer is unknown.
OBJECTIVE: 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.
INTERVENTIONS: 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.
MAIN OUTCOMES AND MEASURES: 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.
RESULTS: 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=0.22). 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=0.008), 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=0.04). No differences were found between the 2 groups in the incidence of adverse effects, including cardiac toxic effects and radiation pneumonitis.
CONCLUSIONS AND RELEVANCE: 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.
TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04803266
PMID: 34695841
DOI: 10.1001/jamaoncol.2021.6036