Department of Clinical Oncology, Leiden University Medical Center, Leiden, Netherlands.
Lancet. 2010 Mar 6;375(9717):816-23. doi: 10.1016/S0140-6736(09)62163-2.
After surgery for intermediate-risk endometrial carcinoma, the vagina is the most frequent site of recurrence. This study established whether vaginal brachytherapy (VBT) is as effective as pelvic external beam radiotherapy (EBRT) in prevention of vaginal recurrence, with fewer adverse effects and improved quality of life.
In this open-label, non-inferiority, randomised trial undertaken in 19 Dutch radiation oncology centres, 427 patients with stage I or IIA endometrial carcinoma with features of high-intermediate risk were randomly assigned by a computer-generated, biased coin minimisation procedure to pelvic EBRT (46 Gy in 23 fractions; n=214) or VBT (21 Gy high-dose rate in three fractions, or 30 Gy low-dose rate; n=213). All investigators were masked to the assignment of treatment group. The primary endpoint was vaginal recurrence. The predefined non-inferiority margin was an absolute difference of 6% in vaginal recurrence. Analysis was by intention to treat, with competing risk methods. The study is registered, number ISRCTN16228756.
At median follow-up of 45 months (range 18-78), three vaginal recurrences had been diagnosed after VBT and four after EBRT. Estimated 5-year rates of vaginal recurrence were 1.8% (95% CI 0.6-5.9) for VBT and 1.6% (0.5-4.9) for EBRT (hazard ratio [HR] 0.78, 95% CI 0.17-3.49; p=0.74). 5-year rates of locoregional relapse (vaginal or pelvic recurrence, or both) were 5.1% (2.8-9.6) for VBT and 2.1% (0.8-5.8) for EBRT (HR 2.08, 0.71-6.09; p=0.17). 1.5% (0.5-4.5) versus 0.5% (0.1-3.4) of patients presented with isolated pelvic recurrence (HR 3.10, 0.32-29.9; p=0.30), and rates of distant metastases were similar (8.3% [5.1-13.4] vs 5.7% [3.3-9.9]; HR 1.32, 0.63-2.74; p=0.46). We recorded no differences in overall (84.8% [95% CI 79.3-90.3] vs 79.6% [71.2-88.0]; HR 1.17, 0.69-1.98; p=0.57) or disease-free survival (82.7% [76.9-88.6] vs 78.1% [69.7-86.5]; HR 1.09, 0.66-1.78; p=0.74). Rates of acute grade 1-2 gastrointestinal toxicity were significantly lower in the VBT group than in the EBRT group at completion of radiotherapy (12.6% [27/215] vs 53.8% [112/208]).
VBT is effective in ensuring vaginal control, with fewer gastrointestinal toxic effects than with EBRT. VBT should be the adjuvant treatment of choice for patients with endometrial carcinoma of high-intermediate risk.
Dutch Cancer Society.
在中危子宫内膜癌手术后，阴道是最常见的复发部位。本研究旨在确定阴道近距离放疗（VBT）是否与盆腔外照射放疗（EBRT）同样有效预防阴道复发，同时具有更少的不良反应和更高的生活质量。
在这项由 19 个荷兰放射肿瘤学中心进行的开放性、非劣效性、随机试验中，427 名具有高-中高危特征的 I 期或 IIA 期子宫内膜癌患者通过计算机生成的、有偏硬币最小化程序随机分配至盆腔 EBRT（46 Gy，23 个分次；n=214）或 VBT（21 Gy 高剂量率，3 个分次，或 30 Gy 低剂量率；n=213）。所有研究者均对治疗分组情况设盲。主要终点是阴道复发。预先设定的非劣效性边界为阴道复发的绝对差异 6%。分析采用意向治疗，使用竞争风险方法。该研究已在 ISRCTN 注册，编号为 ISRCTN87352658。
中位随访 45 个月（范围 18-78）时，VBT 组有 3 例阴道复发，EBRT 组有 4 例。VBT 组和 EBRT 组 5 年阴道复发率分别为 1.8%（95%CI 0.6-5.9）和 1.6%（0.5-4.9）（危险比[HR] 0.78，95%CI 0.17-3.49；p=0.74）。VBT 组和 EBRT 组 5 年局部区域复发率（阴道或盆腔复发，或两者均有）分别为 5.1%（2.8-9.6）和 2.1%（0.8-5.8）（HR 2.08，95%CI 0.71-6.09；p=0.17）。VBT 组和 EBRT 组分别有 1.5%（0.5-4.5）和 0.5%（0.1-3.4）的患者出现孤立性盆腔复发（HR 3.10，0.32-29.9；p=0.30），远处转移率相似（8.3%[5.1-13.4] vs 5.7%[3.3-9.9]；HR 1.32，0.63-2.74；p=0.46）。我们未发现总体生存（84.8%[95%CI 79.3-90.3] vs 79.6%[71.2-88.0]；HR 1.17，0.69-1.98；p=0.57）或无病生存（82.7%[76.9-88.6] vs 78.1%[69.7-86.5]；HR 1.09，0.66-1.78；p=0.74）方面的差异。VBT 组在放疗完成时的急性 1-2 级胃肠道毒性发生率显著低于 EBRT 组（12.6%[27/215] vs 53.8%[112/208]）。
VBT 可有效确保阴道控制，且胃肠道毒性反应少于 EBRT。VBT 应为中高危子宫内膜癌患者的辅助治疗选择。
荷兰癌症协会。
