局部晚期非小细胞肺癌预防性颅脑照射的个体化患者数据荟萃分析。
Individual patient data meta-analysis of prophylactic cranial irradiation in locally advanced non-small cell lung cancer.
机构信息
Department of Clinical Epidemiology and Medical Technology Assessment, Maastricht University Medical Centre (MUMC), The Netherlands.
Department of Clinical Epidemiology and Medical Technology Assessment, Maastricht University Medical Centre (MUMC), The Netherlands.
出版信息
Radiother Oncol. 2021 May;158:40-47. doi: 10.1016/j.radonc.2021.02.002. Epub 2021 Feb 13.
BACKGROUND
Prophylactic cranial irradiation (PCI) was compared to observation in several randomized trials (RCTs), and a reduction greater than 50% was shown regarding the incidence of brain metastases (BM). However, none of these studies showed an improvement of overall survival (OS), possibly related to relatively small sample sizes and short follow-up. The aim of this meta-analysis was therefore to assess the impact of PCI on long term OS for stage III non-small cell lung cancer (NSCLC) compared to observation based on the pooled updated individual patient RCT data.
METHODS
Seven RCTs were eligible, and data from the four most recent trials (924 patients) could be retrieved. The log-rank observed minus expected number of events and its variance were used to calculate individual and overall pooled hazard ratios (HRs) and 95% confidence intervals (95% CIs) with a fixed effects model. Inter-trial heterogeneity was studied using the I test. In addition, the 5-year absolute survival difference between arms was calculated for all endpoints. The pre-specified toxicities were reported descriptively.
RESULTS
The median follow-up was 97 months (74-108). Compared to observation, no statistically significant impact of PCI on OS was observed (HR 0.90 [0.76-1.07] p = 0.23, 5-year absolute difference 1.8% [-5.2-8.8]). PCI significantly prolonged progression-free survival (HR 0.77 [0.66-0.91] p = 0.002) and BM-free survival (HR 0.82 [0.69-0.97] p = 0.02). The number of patients with high-grade (≥3) toxicity was 6.4% (21/330) for PCI.
CONCLUSION
No OS benefit by PCI was observed, but PCI prolonged the progression-free survival and BM-free survival at an increased risk of late memory impairment and fatigue.
背景
预防性颅照射（PCI）已在几项随机对照试验（RCT）中与观察进行了比较，结果显示脑转移（BM）的发生率降低了 50%以上。然而，这些研究均未显示出总生存（OS）的改善，这可能与样本量相对较小且随访时间较短有关。因此，本荟萃分析的目的是评估与观察相比，PCI 对 III 期非小细胞肺癌（NSCLC）患者长期 OS 的影响，其依据是汇总更新的个体患者 RCT 数据。
方法
共有 7 项 RCT 符合条件，可检索到其中 4 项最新试验（924 例患者）的数据。使用对数秩观察到的减去预期事件数及其方差来计算个体和总体汇总的风险比（HR）和 95%置信区间（95%CI），采用固定效应模型。使用 I 检验研究试验间异质性。此外，还计算了所有终点的手臂间 5 年绝对生存差异。报告了预先指定的毒性的描述性结果。
结果
中位随访时间为 97 个月（74-108）。与观察相比，PCI 对 OS 无显著影响（HR 0.90 [0.76-1.07]，p=0.23，5 年绝对差异 1.8% [-5.2-8.8]）。PCI 显著延长了无进展生存期（HR 0.77 [0.66-0.91]，p=0.002）和无 BM 生存期（HR 0.82 [0.69-0.97]，p=0.02）。PCI 组中发生 3 级（≥3）以上毒性的患者为 6.4%（21/330）。
结论
未观察到 PCI 的 OS 获益，但 PCI 延长了无进展生存期和无 BM 生存期，但增加了迟发性记忆障碍和疲劳的风险。
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