Division of Surgery and Interventional Science, University College London, London, United Kingdom.
Department of Biostatistics, University of Notre Dame, Fremantle, West Australia, Australia.
JAMA Oncol. 2020 Jul 1;6(7):e200249. doi: 10.1001/jamaoncol.2020.0249. Epub 2020 Jul 9.
Conventional adjuvant radiotherapy for breast cancer given daily for several weeks is onerous and expensive. Some patients may be obliged to choose a mastectomy instead, and some may forgo radiotherapy altogether. We proposed a clinical trial to test whether radiotherapy could be safely limited to the tumor bed.
To determine whether delayed second-procedure targeted intraoperative radiotherapy (TARGIT-IORT) is noninferior to whole-breast external beam radiotherapy (EBRT) in terms of local control.
DESIGN, SETTING, AND PARTICIPANTS: In this prospective, randomized (1:1 ratio) noninferiority trial, 1153 patients aged 45 years or older with invasive ductal breast carcinoma smaller than 3.5 cm treated with breast conservation were enrolled from 28 centers in 9 countries. Data were locked in on July 3, 2019.
The TARGIT-A trial was started in March 2000; patients were randomized after needle biopsy to receive TARGIT-IORT immediately after lumpectomy under the same anesthetic vs EBRT and results have been shown to be noninferior. A parallel study, described in this article, was initiated in 2004; patients who had their cancer excised were randomly allocated using separate randomization tables to receive EBRT or delayed TARGIT-IORT given as a second procedure by reopening the lumpectomy wound.
A noninferiority margin for local recurrence rate of 2.5% at 5 years, and long-term survival outcomes.
Overall, 581 women (mean [SD] age, 63 [7] years) were randomized to delayed TARGIT-IORT and 572 patients (mean [SD] age, 63 [8] years) were randomized to EBRT. Sixty patients (5%) had tumors larger than 2 cm, or had positive nodes and only 32 (2.7%) were younger than 50 years. Delayed TARGIT-IORT was not noninferior to EBRT. The local recurrence rates at 5-year complete follow-up were: delayed TARGIT-IORT vs EBRT (23/581 [3.96%] vs 6/572 [1.05%], respectively; difference, 2.91%; upper 90% CI, 4.4%). With long-term follow-up (median [IQR], 9.0 [7.5-10.5] years), there was no statistically significant difference in local recurrence-free survival (HR, 0.75; 95% CI, 0.57-1.003; P = .052), mastectomy-free survival (HR, 0.88; 95% CI, 0.65-1.18; P = .38), distant disease-free survival (HR, 1.00; 95% CI, 0.72-1.39; P = .98), or overall survival (HR, 0.96; 95% CI, 0.68-1.35; P = .80).
These long-term data show that despite an increase in the number of local recurrences with delayed TARGIT-IORT, there was no statistically significant decrease in mastectomy-free survival, distant disease-free survival, or overall survival.
ISRCTN34086741, ClinicalTrials.gov Identifier: NCT00983684.
重要性： 乳腺癌常规辅助放疗需要连续数周进行，每天一次，既繁琐又昂贵。有些患者可能被迫选择乳房切除术，而有些患者可能完全放弃放疗。我们提出了一项临床试验，旨在检验肿瘤床内放疗（TARGIT-IORT）能否安全地替代全乳外照射放疗（EBRT）。
目的： 确定延迟的第二阶段靶向术中放疗（TARGIT-IORT）在局部控制方面是否不劣于全乳外照射放疗（EBRT）。
设计、地点和参与者： 这是一项前瞻性、随机（1:1 比例）非劣效性试验，纳入了 28 个国家 9 个中心的 1153 名年龄在 45 岁及以上、接受保乳治疗的浸润性导管乳腺癌患者，肿瘤直径小于 3.5cm。数据于 2019 年 7 月 3 日锁定。
干预措施： TARGIT-A 试验于 2000 年 3 月启动；患者在经皮活检后随机分为即刻在同一麻醉下接受 TARGIT-IORT 与 EBRT，结果显示非劣效性。本文描述的一项平行研究于 2004 年启动；接受癌症切除术的患者通过单独的随机分组表被随机分配接受 EBRT 或延迟 TARGIT-IORT，后者作为第二阶段通过重新打开乳房切除术伤口进行。
主要结局和测量指标： 局部复发率 5 年非劣效性边界为 2.5%，以及长期生存结果。
结果： 总体而言，581 名女性（平均[SD]年龄，63[7]岁）被随机分配至延迟 TARGIT-IORT 组，572 名女性（平均[SD]年龄，63[8]岁）被随机分配至 EBRT 组。60 名患者（5%）肿瘤大于 2cm，或有阳性淋巴结，仅有 32 名（2.7%）患者年龄小于 50 岁。延迟 TARGIT-IORT 不比 EBRT 差。5 年完整随访时的局部复发率为：延迟 TARGIT-IORT 组 vs EBRT 组（分别为 23/581[3.96%]与 6/572[1.05%]，差异为 2.91%，90%置信区间上限为 4.4%）。长期随访（中位数[IQR]，9.0[7.5-10.5]年）时，局部无复发生存率（HR，0.75；95%CI，0.57-1.003；P=0.052）、乳房切除术无复发生存率（HR，0.88；95%CI，0.65-1.18；P=0.38）、远处无病生存率（HR，1.00；95%CI，0.72-1.39；P=0.98）和总生存率（HR，0.96；95%CI，0.68-1.35；P=0.80）均无统计学差异。
结论和相关性： 这些长期数据表明，尽管延迟 TARGIT-IORT 后局部复发的数量增加，但在乳房切除术无复发生存率、远处无病生存率或总生存率方面没有统计学意义的下降。
试验注册： ISRCTN34086741，ClinicalTrials.gov 标识符：NCT00983684。
