对于转移性恶性肿瘤的临床试验越来越多地扩展到具有脑转移的患者。虽然无进展生存期（PFS）是主要的肿瘤学终点，但对于接受立体定向放射外科（SRS）治疗的具有脑转移病人的颅内进展（ICP）和颅外进展（ECP）事件与总生存期（OS）的相关性仍不清楚。为确定完成首次SRS课程的脑转移患者颅内进展和颅外进展与OS的相关性，我们进行了这项多机构回顾性队列研究，研究时间为2015年1月1日至2020年12月31日期间，分析数据的时间为2022年11月15日。我们纳入了在研究期间完成脑转移SRS首次治疗的患者，包括单次和/或多次分次SRS治疗，先前接受全脑放疗和脑转移切除的患者。非OS终点包括颅内PFS、颅外PFS、PFS、颅内进展时间、颅外进展时间和任何进展时间，进展事件由多学科临床共识定义。主要结果是代理终点与OS的相关性。通过Kaplan-Meier方法估计临床终点，使用迭代多重插补方法测量终点与OS的相关性。该研究包括1383名患者，平均年龄为63.1岁（范围为20.9-92.8岁），中位随访时间为8.72个月（IQR，3.25-19.68个月）。大多数参与者为白人（1032名[75%]），超过一半（758名[55%]）为女性。常见的原发肿瘤部位包括肺（757名[55%]）、乳腺（203名[15%]）和皮肤（黑色素瘤；100名[7%]）。颅内进展观察到698例患者（50%），在观察到的1000个死亡事件中先行492例（49%）。颅外进展观察到800名患者（58%），在观察到的1000个死亡事件中先行627例（63%）。在死亡无关的情况下，482名患者（35%）同时经历了ICP和ECP，534名（39%）患者经历了ICP（216名[16%]）或ECP（318名[23%]），而367名（27%）患者则没有经历任何一种情况。中位总生存期为9.93个月（95% CI，9.08-11.05个月）。颅内PFS与OS的相关性最高（ρ=0.84 [95% CI，0.82-0.85]；中位数为4.39个月[95% CI，4.02-4.92个月]）。颅内进展时间与OS的相关性最低（ρ=0.42 [95% CI，0.34-0.50]），发生事件的中位数最长（中位数为8.76个月[95% CI，7.70-9.48个月]）。在特定的原发肿瘤类型中，尽管相应的中位数终点持续时间存在差异，但颅内PFS和颅外PFS与OS的相关性始终很高。脑转移患者完成SRS的队列研究结果表明，颅内PFS、颅外PFS和PFS与OS的相关性最高，颅内进展时间与OS的相关性最低。这些数据可能有助于未来的患者纳入和终点选择的临床试验。

Clinical trials for metastatic malignant neoplasms are increasingly being extended to patients with brain metastases. Despite the preeminence of progression-free survival (PFS) as a primary oncologic end point, the correlation of intracranial progression (ICP) and extracranial progression (ECP) events with overall survival (OS) is poorly understood for patients with brain metastases following stereotactic radiosurgery (SRS).To determine the correlation of ICP and ECP with OS among patients with brain metastases completing an initial SRS course.This multi-institutional retrospective cohort study was conducted from January 1, 2015, to December 31, 2020. We included patients who completed an initial course of SRS for brain metastases during the study period, including receipt of single and/or multifraction SRS, prior whole-brain radiotherapy, and brain metastasis resection. Data analysis was performed on November 15, 2022.Non-OS end points included intracranial PFS, extracranial PFS, PFS, time to ICP, time to ECP, and any time to progression. Progression events were radiologically defined, incorporating multidisciplinary clinical consensus.The primary outcome was correlation of surrogate end points to OS. Clinical end points were estimated from time of SRS completion via the Kaplan-Meier method, while end-point correlation to OS was measured using normal scores rank correlation with the iterative multiple imputation approach.This study included 1383 patients, with a mean age of 63.1 years (range, 20.9-92.8 years) and a median follow-up of 8.72 months (IQR, 3.25-19.68 months). The majority of participants were White (1032 [75%]), and more than half (758 [55%]) were women. Common primary tumor sites included the lung (757 [55%]), breast (203 [15%]), and skin (melanoma; 100 [7%]). Intracranial progression was observed in 698 patients (50%), preceding 492 of 1000 observed deaths (49%). Extracranial progression was observed in 800 patients (58%), preceding 627 of 1000 observed deaths (63%). Irrespective of deaths, 482 patients (35%) experienced both ICP and ECP, 534 (39%) experienced ICP (216 [16%]) or ECP (318 [23%]), and 367 (27%) experienced neither. The median OS was 9.93 months (95% CI, 9.08-11.05 months). Intracranial PFS had the highest correlation with OS (ρ = 0.84 [95% CI, 0.82-0.85]; median, 4.39 months [95% CI, 4.02-4.92 months]). Time to ICP had the lowest correlation with OS (ρ = 0.42 [95% CI, 0.34-0.50]) and the longest median time to event (median, 8.76 months [95% CI, 7.70-9.48 months]). Across specific primary tumor types, correlations of intracranial PFS and extracranial PFS with OS were consistently high despite corresponding differences in median outcome durations.The results of this cohort study of patients with brain metastases completing SRS suggest that intracranial PFS, extracranial PFS, and PFS had the highest correlations with OS and time to ICP had the lowest correlation with OS. These data may inform future patient inclusion and end-point selection for clinical trials.