Trivella Marialena, Pezzella Francesco, Pastorino Ugo, Harris Adrian L, Altman Douglas G
Cancer Research UK/NHS Centre for Statistics in Medicine, Oxford, UK.
Lancet Oncol. 2007 Jun;8(6):488-99. doi: 10.1016/S1470-2045(07)70145-6.
Angiogenesis is a potential prognostic factor that has been investigated in patients with non-small-cell lung carcinoma. However, published studies of the role of angiogenesis as a prognostic factor are inconclusive. We aimed to collect individual patient data to assess microvessel-density counts (ie, a measure of angiogenesis) as a prognostic factor in non-small-cell lung carcinoma.
We obtained published and unpublished datasets and extracted appropriate data, taking particular care to ensure data quality. Detailed information was obtained for the laboratory methods used by every research centre that generated the data. The outcome of interest was overall survival. We did a meta-analysis to estimate the prognostic role of microvessel density by combining separately estimated hazard ratios (HR) from every study, which were adjusted for tumour stage and age. Analyses were done separately for studies that used the Chalkley method or for those that counted all microvessels.
17 centres provided data for 3200 patients, 2719 of which were included in the analysis. All but three centres (datasets 9, 10, and 13-367 cases) had already published their findings, and six had updated follow-up information (datasets 1, 2, 3, 6, 7, and 8-1273 cases). For all but three centres (datasets 4, 11, and 13) some data corrections were necessary. For microvessel density counts obtained by the Chalkley method, the HR for death per extra microvessel was 1.05 (95% CI 1.01-1.09, p=0.03) when analysed as a continuous variable. For microvessel density counts obtained by the all vessels method, the HR for death per ten extra microvessels was 1.03 (0.97-1.09, p=0.3) when analysed as a continuous variable.
Microvessel density does not seem to be a prognostic factor in patients with non-metastatic surgically treated non-small-cell lung carcinoma. This conclusion contradicts the results of a meta-analysis of published data only. Therefore, the methodology used to assess prognostic factors should be assessed carefully.
血管生成是一种潜在的预后因素，已在非小细胞肺癌患者中进行了研究。然而，关于血管生成作为预后因素作用的已发表研究尚无定论。我们旨在收集个体患者数据，以评估微血管密度计数（即血管生成的一种测量方法）作为非小细胞肺癌的预后因素。
我们获取了已发表和未发表的数据集，并提取了适当的数据，特别注意确保数据质量。获取了生成数据的每个研究中心所使用实验室方法的详细信息。感兴趣的结局是总生存期。我们进行了一项荟萃分析，通过合并每项研究分别估计的风险比（HR）来评估微血管密度的预后作用，这些风险比针对肿瘤分期和年龄进行了调整。对使用Chalkley方法的研究和对所有微血管进行计数的研究分别进行分析。
17个中心提供了3200例患者的数据，其中2719例纳入分析。除三个中心（数据集9、10和13 - 367例）外，所有中心均已发表其研究结果，六个中心有更新的随访信息（数据集1、2、3、6、7和8 - 1273例）。除三个中心（数据集4、11和13）外，对一些数据进行校正很有必要。对于通过Chalkley方法获得的微血管密度计数，作为连续变量分析时，每增加一个微血管的死亡风险比为1.05（95%CI 1.01 - 1.09，p = 0.03）。对于通过所有血管方法获得的微血管密度计数，作为连续变量分析时，每增加十个微血管的死亡风险比为1.03（0.97 - 1.09，p = 0.3）。
微血管密度似乎不是接受手术治疗的非转移性非小细胞肺癌患者的预后因素。这一结论与仅对已发表数据进行的荟萃分析结果相矛盾。因此，应仔细评估用于评估预后因素的方法。
