一线放化疗治疗成人局部晚期非小细胞肺癌的临床疗效：系统评价。

Clinical effectiveness of first-line chemoradiation for adult patients with locally advanced non-small cell lung cancer: a systematic review.

机构信息

Liverpool Reviews and Implementation Group, University of Liverpool, Liverpool, UK.

出版信息

Health Technol Assess. 2013 Feb;17(6):1-99. doi: 10.3310/hta17060.

DOI:10.3310/hta17060

PMID:23411071

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4780920/

Abstract

BACKGROUND

The National Institute for Health and Clinical Excellence has issued guidelines on the treatment of non-small cell lung cancer (NSCLC) and recommends that patients with stage IIIA-IIIB disease who are not amenable to surgery be treated with potentially curative chemoradiation (CTX-RT). This review was conducted as part of a larger systematic review of all first-line chemotherapy (CTX) and CTX-RT treatments for patients with locally advanced or metastatic NSCLC. However, it was considered that patients with potentially curable disease (e.g. stage IIIA) are different from those with advanced disease, who are suitable for palliative treatment only, and therefore the results should be reported separately.

OBJECTIVE

To evaluate the clinical effectiveness of first-line CTX in addition to radiotherapy (RT) (CTX-RT vs CTX-RT) for adult patients with locally advanced NSCLC who are suitable for potentially curative treatment.

DATA SOURCES

Three electronic databases (MEDLINE, EMBASE and The Cochrane Library) were searched from January 1990 to September 2010.

REVIEW METHODS

Inclusion criteria comprised adult patients with locally advanced NSCLC, trials that compared any first-line CTX-RT therapy (induction, sequential, concurrent and consolidation) and outcomes of overall survival (OS) and/or progression-free survival (PFS). The results of clinical data extraction and quality assessment were summarised in tables and with narrative description. Direct meta-analyses using OS data were undertaken where possible: sequential CTX-RT compared with concurrent CTX-RT; sequential CTX-RT compared with concurrent/consolidation CTX-RT; and sequential CTX-RT compared with concurrent CTX-RT with or without consolidation. There were not sufficient data to perform meta-analysis on PFS.

RESULTS

Of the 240 potentially relevant studies that were published post 2000, 19 met the inclusion criteria and compared CTX-RT with CTX-RT. The results from the OS meta-analysis comparing sequential CTX-RT with concurrent CTX-RT appear to show an OS advantage for concurrent CTX-RT arms over sequential arms; this result is not statistically significant [hazard ratio (HR) 0.79; 95% confidence interval (CI) 0.50 to 1.25)]. The results from the OS meta-analysis comparing sequential CTX-RT with concurrent/consolidation CTX-RT appear to show a statistically significant OS advantage for concurrent/consolidation CTX-RT treatment over sequential treatment (HR 0.68; 95% CI 0.55 to 0.83). The results from the OS meta-analysis comparing sequential CTX-RT with concurrent CTX-RT with or without consolidation appear to show a statistically significant OS advantage for concurrent CTX-RT with or without consolidation over sequential treatment (HR 0.72; 95% CI 0.61 to 0.84).

LIMITATIONS

This report provides a summary and critical appraisal of a comprehensive evidence base of CTX-RT trials; however, it is possible that additional trials have been reported since our last literature search. It is disappointing that the quality of the research in this area does not meet the accepted quality standards regarding trial design and reporting.

CONCLUSIONS

This review identified that the research conducted in the area of CTX-RT was generally of poor quality and suffered from a lack of reporting of all important clinical findings, including OS. The 19 trials included in the systematic review were too disparate to form any conclusions as to the effectiveness of individual CTX agents or types of RT. The focus of primary research should be good methodological quality; appropriate allocation of concealment and randomisation, and comprehensive reporting of key outcomes, will enable meaningful synthesis and conclusions to be drawn.

FUNDING

The National Institute for Health Research Health Technology Assessment programme.

摘要

背景

英国国家卫生与临床优化研究所（NICE）发布了非小细胞肺癌（NSCLC）治疗指南，建议不能手术的 IIIA 期-IIIB 期疾病患者采用潜在可治愈的放化疗（CTX-RT）治疗。本综述是对所有局部晚期或转移性 NSCLC 患者一线化疗（CTX）和 CTX-RT 治疗进行的更大系统综述的一部分。然而，人们认为潜在可治愈疾病（如 IIIA 期）的患者与晚期疾病患者不同，后者仅适合姑息治疗，因此应单独报告结果。

目的

评估对于适合潜在治愈治疗的局部晚期 NSCLC 成年患者，一线 CTX 联合放疗（RT）（CTX-RT 与 CTX-RT）的临床疗效。

数据来源

从 1990 年 1 月至 2010 年 9 月，三个电子数据库（MEDLINE、EMBASE 和 The Cochrane Library）进行了检索。

研究选择

纳入标准包括局部晚期 NSCLC 成年患者，比较任何一线 CTX-RT 治疗（诱导、序贯、同步和巩固）的试验，以及总生存（OS）和/或无进展生存（PFS）的结果。临床数据提取和质量评估的结果以表格和叙述性描述进行总结。在可能的情况下，使用 OS 数据进行直接荟萃分析：序贯 CTX-RT 与同步 CTX-RT 比较；序贯 CTX-RT 与同步/巩固 CTX-RT 比较；序贯 CTX-RT 与同步 CTX-RT 加或不加巩固比较。没有足够的数据进行 PFS 的荟萃分析。

结果

在 2000 年后发表的 240 篇可能相关的研究中，有 19 项符合纳入标准并比较了 CTX-RT 与 CTX-RT。OS 荟萃分析比较序贯 CTX-RT 与同步 CTX-RT 的结果似乎表明同步 CTX-RT 臂的 OS 优势优于序贯臂；但这一结果没有统计学意义[风险比（HR）0.79；95%置信区间（CI）0.50 至 1.25]。OS 荟萃分析比较序贯 CTX-RT 与同步/巩固 CTX-RT 的结果似乎表明同步/巩固 CTX-RT 治疗的 OS 优势具有统计学意义，优于序贯治疗（HR 0.68；95%CI 0.55 至 0.83）。OS 荟萃分析比较序贯 CTX-RT 与同步 CTX-RT 加或不加巩固的结果似乎表明同步 CTX-RT 加或不加巩固的 OS 优势具有统计学意义，优于序贯治疗（HR 0.72；95%CI 0.61 至 0.84）。

局限性

本报告提供了对 CTX-RT 试验全面证据基础的总结和关键评估；然而，自我们上次文献检索以来，可能有其他试验已被报道。令人失望的是，该领域的研究质量不符合关于试验设计和报告的公认质量标准。

结论

本综述确定，CTX-RT 领域的研究总体质量较差，并且缺乏对所有重要临床发现的报告，包括 OS。系统综述中纳入的 19 项试验差异太大，无法就个别 CTX 药物或 RT 类型的有效性得出任何结论。主要研究的重点应该是良好的方法学质量；适当分配隐匿性和随机化，以及全面报告关键结局，将能够得出有意义的综合结论。