Queen's Centre for Oncology and Haematology, Castle Hill Hospital, Cottingham, UK.
Clin Oncol (R Coll Radiol). 2011 Dec;23(10):696-705. doi: 10.1016/j.clon.2011.05.005. Epub 2011 Jun 17.
The optimal neoadjuvant therapy option for locally advanced oesophageal cancer remains elusive. Neoadjuvant chemoradiotherapy (CRT) is the preferred modality of choice in the USA. In contrast, neoadjuvant chemotherapy is commonly used in the UK. We provide a comprehensive overview of the available evidence for defining the ideal neoadjuvant treatment algorithm.
The PubMed database combined with American Society of Clinical Oncology and American Society for Therapeutic Radiology and Oncology websites were searched online to identify randomised studies and published meta-analyses that have compared these modalities compared with surgery alone. In particular, we searched for randomised trials that may have directly compared outcomes after neoadjuvant CRT or chemotherapy.
We identified 17 published randomised studies of neoadjuvant CRT (n = 9) and chemotherapy (n = 8) compared with surgery alone and one prospective series that compared the above modalities against each other. Studies evaluating CRT have reported pathological complete response rates of 15-40% and no increase in postoperative mortality was observed, except in one study that used a hypofractionated radiation schedule. Two randomised studies showed significant survival benefit and the remaining (n = 7) were negative, but showed a trend towards improved survival. Furthermore, at least four meta-analyses have shown improved survival in favour of CRT extending up to an absolute benefit of 13% at 2 years. In comparison, five studies of neoadjuvant chemotherapy showed no survival difference and two of the remaining studies that showed significant benefit included gastric adenocarcinomas and used peri-operative chemotherapy. All the above studies have shown uniformly poor pathological complete response rates of less than 10 percent. Moreover, three meta-analyses were negative, but two showed up to 7% absolute survival benefit at 2 years in favour of chemotherapy. The trial comparing the above modalities showed a trend towards improved survival in favour of CRT, but closed early due to poor recruitment.
Data from the above studies are potentially conflicting and inconclusive for defining the optimal neoadjuvant treatment schedule. In our opinion, the above question can only be answered within the context of a randomised control trial. We have included a proposal for a trial design for direct comparison of these modalities.
局部晚期食管癌的最佳新辅助治疗选择仍未确定。新辅助放化疗（CRT）是美国的首选治疗方式。相比之下，新辅助化疗在英国更为常见。我们提供了一个全面的概述，以确定理想的新辅助治疗方案的现有证据。
通过在线搜索 PubMed 数据库以及美国临床肿瘤学会和美国治疗放射肿瘤学会的网站，我们确定了比较这些方式与单独手术的随机研究和已发表的荟萃分析。特别是，我们搜索了可能直接比较新辅助 CRT 或化疗后结果的随机试验。
我们确定了 17 项新辅助 CRT（n=9）和化疗（n=8）与单独手术比较的已发表随机研究，以及一项比较上述治疗方式的前瞻性系列研究。评估 CRT 的研究报告了 15-40%的病理完全缓解率，并且没有观察到术后死亡率增加，除了一项使用低分割放射方案的研究。两项随机研究显示出显著的生存获益，其余（n=7）则为阴性，但显示出生存改善的趋势。此外，至少有四项荟萃分析显示 CRT 有利于生存，2 年时的绝对获益高达 13%。相比之下，五项新辅助化疗研究没有显示出生存差异，其中两项显示出显著获益的研究包括胃腺癌并使用围手术期化疗。所有上述研究均显示病理完全缓解率均低于 10%。此外，三项荟萃分析为阴性，但两项荟萃分析显示化疗的 2 年绝对生存获益高达 7%。比较上述治疗方式的试验显示，CRT 有利于生存的趋势，但由于招募不佳而提前关闭。
上述研究的数据在确定最佳新辅助治疗方案方面存在潜在的冲突和不确定性。在我们看来，只有在随机对照试验的背景下才能回答这个问题。我们提出了一个直接比较这些方式的试验设计方案。
