Background The absence of a survival benefit for whole brain radiotherapy (WBRT) among randomized trials has been attributed to a competing risk of death from extracranial disease. We re-analyzed EORTC 22952 to assess the impact of WBRT on survival for patients with controlled extracranial disease or favorable prognoses. Patients and methods We utilized Cox regression, landmark analysis, and the Kaplan-Meier method to evaluate the impact of WBRT on survival accounting for (i) extracranial progression as a time-dependent covariate in all patients and (ii) diagnosis-specific graded prognostic assessment (GPA) score in patients with primary non-small-cell lung cancer (NSCLC). Results A total of 329 patients treated per-protocol were included for analysis with a median follow up of 26 months. One hundred and fifteen (35%) patients had no extracranial progression; 70 (21%) patients had progression <90 days, 65 (20%) between 90 and 180 days, and 79 (24%) patients >180 days from randomization. There was no difference in the model-based risk of death in the WBRT group before [hazard ratio (HR) (95% CI)=0.70 (0.45-1.11), P = 0.133), or after [HR (95% CI)=1.20 (0.89-1.61), P = 0.214] extracranial progression. Among 177 patients with NSCLC, 175 had data available for GPA calculation. There was no significant survival benefit to WBRT among NSCLC patients with favorable GPA scores [HR (95% CI)=1.10 (0.68-1.79)] or unfavorable GPA scores [HR (95% CI)=1.11 (0.71-1.76)]. Conclusions Among patients with limited extracranial disease and one to three brain metastases at enrollment, we found no significant survival benefit to WBRT among NSCLC patients with favorable GPA scores or patients with any histology and controlled extracranial disease status. This exploratory analysis of phase III data supports the practice of omitting WBRT for patients with limited brain metastases undergoing SRS and close surveillance. Clinical Trials Number NCT00002899.

中文翻译：

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有 1 到 3 处脑转移且预后良好的患者在立体定向放射外科或手术切除后进行全脑放疗：对 EORTC 22952-26001 的二次分析。

背景 在随机试验中，全脑放疗 (WBRT) 缺乏生存获益被归因于颅外疾病死亡的竞争风险。我们重新分析了 EORTC 22952，以评估 WBRT 对颅外疾病受控或预后良好的患者生存的影响。患者和方法 我们利用 Cox 回归、界标分析和 Kaplan-Meier 方法来评估 WBRT 对生存的影响，将 (i) 颅外进展作为所有患者的时间依赖性协变量和 (ii) 诊断特异性分级预后原发性非小细胞肺癌（NSCLC）患者的评估（GPA）评分。结果共有 329 名按方案接受治疗的患者被纳入分析，中位随访时间为 26 个月。115 (35%) 名患者没有颅外进展；70 名 (21%) 患者进展 <90 天，65 名 (20%) 患者在 90 至 180 天之间，79 名 (24%) 患者在随机分组后 >180 天。在 [风险比 (HR) (95% CI)=0.70 (0.45-1.11), P = 0.133) 之前或 [HR (95% CI) 之后，WBRT 组基于模型的死亡风险没有差异=1.20 (0.89-1.61), P = 0.214] 颅外进展。在 177 名 NSCLC 患者中，175 名有数据可用于 GPA 计算。在 GPA 评分良好 [HR (95% CI)=1.10 (0.68-1.79)] 或 GPA 评分不佳 [HR (95% CI)=1.11 (0.71-1.76)] 的 NSCLC 患者中，WBRT 没有显着的生存获益。结论 在入组时颅外疾病局限和 1 至 3 处脑转移的患者中，我们发现，在 GPA 评分良好的 NSCLC 患者或具有任何组织学和颅外疾病状态受控的患者中，WBRT 没有显着的生存获益。这项对 III 期数据的探索性分析支持对接受 SRS 和密切监测的有限脑转移患者省略 WBRT 的做法。临床试验编号 NCT00002899。