Adjuvant external beam radiotherapy in the treatment of endometrial cancer (MRC ASTEC and NCIC CTG EN.5 randomised trials): pooled trial results, systematic review, and meta-analysis.
Adjuvant external beam radiotherapy in the treatment of endometrial cancer (MRC ASTEC and NCIC CTG EN.5 randomised trials): pooled trial results, systematic review, and meta-analysis.
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DOI：
10.1016/s0140-6736(08)61767-5
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发表时间：
2009-01-10
期刊：
影响因子：
168.9
通讯作者：
Qian, W.
中科院分区：
文献类型：
--
作者：
Blake, P.;Swart, Ann Marie;Orton, J.;Kitchener, H.;Whelan, T.;Lukka, H.;Eisenhauer, E.;Bacon, M.;Tu, D.;Parmar, M. K. B.;Amos, C.;Murray, C.;Qian, W.
具有低风险病理特征的早期子宫内膜癌可以通过单独手术成功治疗。在几项小型试验中研究了在手术中加入外束放疗，这些试验主要包括复发风险中等的妇女。在这些试验中，术后放疗已被证明可以降低局部孤立复发的风险，但没有证据表明它可以提高无复发或总生存期。我们报告了ASTEC和EN.5试验的结果，这两项试验调查了子宫内膜癌早期疾病和提示中度或高风险复发和死亡的病理特征的妇女的辅助外束放疗。1996年7月至2005年3月期间，来自7个国家（英国、加拿大、波兰、挪威、新西兰、澳大利亚、美国）112个中心的905名（789名ASTEC患者，116名EN.5患者）中危或高危早期疾病妇女在手术后被随机分配到观察组（453名）或外束放疗组（452名）。靶剂量为40-46戈瑞，分20-25次每日一次，每周治疗5次。主要结局指标为总生存期，所有分析均为意向治疗。这些试验注册为ISRCTN 16571884 （ASTEC）和NCT 00002807 （EN.5）。中位随访58个月后，135名妇女（68名观察，67名外束流放疗）死亡。无证据表明外束放疗总生存率优于观察，风险比为1.05 （95% CI 0.75 - 1.48; p= 0.77）。两组患者的5年总生存率均为84%。综合来自ASTEC和EN.5的数据进行荟萃分析的试验证实，在总生存期方面没有获益（风险比1.04;95% CI 0.84 - 1.29），并且可以可靠地排除5年外部放射治疗的绝对获益超过3%。53%的ASTEC/EN患者使用近距离治疗。5、观察组5年局部复发率为6.1%。对于中危或高危早期子宫内膜癌患者，不能推荐辅助外束放疗作为常规治疗的一部分，以提高生存率。外束放疗在预防局部孤立性复发方面的绝对益处很小，而且并非没有毒性。医学研究委员会，国家癌症研究网络，加拿大国家癌症研究所，由加拿大癌症协会提供资金。
Early endometrial cancer with low-risk pathological features can be successfully treated by surgery alone. External beam radiotherapy added to surgery has been investigated in several small trials, which have mainly included women at intermediate risk of recurrence. In these trials, postoperative radiotherapy has been shown to reduce the risk of isolated local recurrence but there is no evidence that it improves recurrence-free or overall survival. We report the findings from the ASTEC and EN.5 trials, which investigated adjuvant external beam radiotherapy in women with early-stage disease and pathological features suggestive of intermediate or high risk of recurrence and death from endometrial cancer. Between July, 1996, and March, 2005, 905 (789 ASTEC, 116 EN.5) women with intermediate-risk or high-risk early-stage disease from 112 centres in seven countries (UK, Canada, Poland, Norway, New Zealand, Australia, USA) were randomly assigned after surgery to observation (453) or to external beam radiotherapy (452). A target dose of 40–46 Gy in 20–25 daily fractions to the pelvis, treating five times a week, was specified. Primary outcome measure was overall survival, and all analyses were by intention to treat. These trials were registered ISRCTN 16571884 (ASTEC) and NCT 00002807 (EN.5). After a median follow-up of 58 months, 135 women (68 observation, 67 external beam radiotherapy) had died. There was no evidence that overall survival with external beam radiotherapy was better than observation, hazard ratio 1·05 (95% CI 0·75–1·48; p=0·77). 5-year overall survival was 84% in both groups. Combining data from ASTEC and EN.5 in a meta-analysis of trials confirmed that there was no benefit in terms of overall survival (hazard ratio 1·04; 95% CI 0·84–1·29) and can reliably exclude an absolute benefit of external beam radiotherapy at 5 years of more than 3%. With brachytherapy used in 53% of women in ASTEC/EN.5, the local recurrence rate in the observation group at 5 years was 6·1%. Adjuvant external beam radiotherapy cannot be recommended as part of routine treatment for women with intermediate-risk or high-risk early-stage endometrial cancer with the aim of improving survival. The absolute benefit of external beam radiotherapy in preventing isolated local recurrence is small and is not without toxicity. Medical Research Council, National Cancer Research Network, National Cancer Institute of Canada, with funds from the Canadian Cancer Society.