See list of members in acknowledgements section, UK.
Cochrane Database Syst Rev. 2010 Jan 20;2010(1):CD008285. doi: 10.1002/14651858.CD008285.
After a 1999 National Cancer Institute (NCI) clinical alert was issued, chemoradiotherapy has become widely used in treating women with cervical cancer. Two subsequent systematic reviews found that interpretation of the benefits was complicated and some important clinical questions were unanswered.
We initiated a meta-analysis seeking updated individual patient data (IPD) from all randomised controlled trials (RCTs) to assess the effect of chemoradiotherapy on all outcomes. We pre-specified analyses to investigate whether the effect of chemoradiotherapy differed by trial or patient characteristics.
We supplemented MEDLINE, LILACS and CANCERLIT searches with information from trial registers, by handsearching relevant meeting proceedings and by discussion with relevant trialists and organisations. Searches were updated until October 2009.
Both published and unpublished trials were eligible for inclusion provided the patients had been randomised between radiotherapy (with or without surgery) versus concomitant chemoradiotherapy (with or without surgery); that the method of randomisation precluded prior knowledge of the treatment to be assigned; and that the trial had completed patient recruitment before the date of the final analyses.
We carried out a quantitative meta-analysis using updated information from individual patients from all available RCTs. We sought data from all patients randomised in all eligible trials. We obtained updated information on survival, recurrence and date of last follow up. To avoid potential bias, we requested information for all randomised patients, including those who had been excluded from the investigators' original analyses.
Eighteen trials were identified and 15 of these were eligible for inclusion in the main analysis. On the basis of 13 trials that compared chemoradiotherapy versus the same radiotherapy, there was a 6% improvement in 5-year survival with chemoradiotherapy (hazard ratio (HR) = 0.81, P < 0.001). A larger survival benefit was seen for the two further trials in which chemotherapy was administered after chemoradiotherapy. There was a significant survival benefit for both the group of trials that used platinum-based (HR = 0.83, P = 0.017) and non-platinum based (HR = 0.77, P = 0.009) chemoradiotherapy, but no evidence of a difference in the size of the benefit by radiotherapy or chemotherapy dose or scheduling was seen. Chemoradiotherapy also reduced local and distant recurrence and progression and improved disease-free survival (DFS). There was a suggestion of a difference in the size of the survival benefit with tumour stage, but not across other patient subgroups. Acute haematological and gastro-intestinal toxicity were increased with chemoradiotherapy, but data were too sparse for an analysis of late toxicity.
AUTHORS' CONCLUSIONS: These results endorse the recommendations of the NCI alert, but also demonstrate their applicability to all women and a benefit of non-platinum based chemoradiotherapy. Furthermore, although these results suggest an additional benefit from adjuvant chemotherapy this requires testing in RCTs.
1999年美国国立癌症研究所（NCI）发布临床警报后，放化疗已广泛应用于宫颈癌女性患者的治疗。随后的两项系统评价发现，对其益处的解读很复杂，一些重要的临床问题仍未得到解答。
我们开展了一项荟萃分析，从所有随机对照试验（RCT）中获取最新的个体患者数据（IPD），以评估放化疗对所有结局的影响。我们预先设定了分析内容，以研究放化疗的效果是否因试验或患者特征而异。
我们通过试验注册库信息补充MEDLINE、LILACS和CANCERLIT检索结果，手工检索相关会议论文集，并与相关试验人员和组织进行讨论。检索更新至2009年10月。
已发表和未发表的试验均符合纳入条件，前提是患者在单纯放疗（有或无手术）与同步放化疗（有或无手术）之间进行了随机分组；随机化方法排除了对所分配治疗的先验了解；且试验在最终分析日期之前完成了患者招募。
我们使用所有可用RCT中个体患者的最新信息进行了定量荟萃分析。我们从所有符合条件的试验中随机分组的所有患者中获取数据。我们获得了生存、复发和末次随访日期的最新信息。为避免潜在偏倚，我们要求提供所有随机分组患者的信息，包括那些被研究者原始分析排除的患者。
共识别出18项试验，其中15项符合纳入主要分析的条件。基于13项比较放化疗与单纯放疗的试验，放化疗使5年生存率提高了6%（风险比（HR）=0.81，P<0.001）。在另外两项放化疗后给予化疗的试验中，观察到更大的生存获益。使用铂类（HR = 0.83，P = 0.017）和非铂类（HR = 0.77，P = 0.009）放化疗的试验组均有显著的生存获益，但未发现放疗或化疗剂量或方案在获益程度上存在差异的证据。放化疗还降低了局部和远处复发及进展，并改善了无病生存期（DFS）。生存获益程度在肿瘤分期方面存在差异的迹象，但在其他患者亚组中未观察到差异。放化疗会增加急性血液学和胃肠道毒性，但数据过于稀疏，无法分析晚期毒性。
这些结果支持了NCI警报的建议，但也证明了其对所有女性的适用性以及非铂类放化疗的益处。此外，尽管这些结果表明辅助化疗有额外益处，但这需要在RCT中进行验证。
