Ha Francis J, Spain Lavinia, Dowling Anthony, Kwan Edmond M, Pezaro Carmel, Day Daphne, Chia Puey Ling, Tran Ben, Pook David, Weickhardt Andrew J
Olivia Newton-John Cancer Wellness & Research Centre, Austin Hospital, Melbourne, Victoria, Australia.
Department of Medical Oncology, St Vincent's Hospital, Melbourne, Victoria, Australia.
Asia Pac J Clin Oncol. 2019 Oct;15(5):e97-e102. doi: 10.1111/ajco.13109. Epub 2019 Jan 30.
Targeted therapy (TT) has improved survival for metastatic renal cell carcinoma (mRCC). However, survival is usually limited if brain metastases (BMs) develop. We aimed to evaluate survival outcomes in mRCC patients based on timing of BM diagnosis.
We conducted a multicenter, retrospective study of mRCC patients with BM who received TT at any point between 2005 and 2014. We determined overall survival (OS) from stage IV diagnosis, TT initiation and BM diagnosis, and prognostic factors. Patients were grouped into three categories: synchronous-BM, metachronous-BM diagnosed while conservatively managed (metachronous-BM before TT) and metachronous-BM diagnosed during TT. Survival was calculated by Kaplan-Meier method and predictors were calculated using Cox hazards regression.
Incidence of BM was 17% in mRCC patients treated with TT (two centers). Fifty-four mRCC-BM patients were identified from five tertiary centers. Twenty-eight percentage (15/54) had synchronous-BM, 28% (15/54) had metachranous-BM before TT and 44% (24/54) had metachronous-BM during TT. Most had central nervous system (CNS) symptoms at BM diagnosis (78%; 42/54). Median OS from stage IV diagnosis, TT commencement and BM diagnosis was 28 months (95% confidence interval [CI] 16-43), 19 months (95% CI 9-26) and 9 months (95% CI 5-16), respectively. Synchronous-BM group trended toward poorer survival from TT commencement (P = 0.06). Metachronous-BM during TT group had lower survival from BM diagnosis than synchronous-BM and metachronous-BM before TT group (P < 0.001). Eight of 50 deaths (16%) were from neurological complications. The presence of CNS symptoms did not predict worse survival from stage IV diagnosis (P = 0.73).
In patients with mRCC, the development of BM while on TT portends shorter prognosis compared with synchronous diagnosis of BM at stage IV disease or metachronous BM developed prior to commencing TT. The presence of CNS symptoms does not predict worse survival.
靶向治疗（TT）已改善转移性肾细胞癌（mRCC）患者的生存率。然而，如果发生脑转移（BM），生存率通常会受限。我们旨在根据BM诊断时间评估mRCC患者的生存结局。
我们对2005年至2014年期间在任何时间接受TT治疗的mRCC合并BM患者进行了一项多中心回顾性研究。我们确定了从IV期诊断、TT开始和BM诊断的总生存期（OS）以及预后因素。患者分为三类：同步性BM、在保守治疗期间诊断的异时性BM（TT前异时性BM）和在TT期间诊断的异时性BM。采用Kaplan-Meier方法计算生存率，并使用Cox风险回归计算预测因子。
在接受TT治疗的mRCC患者中（两个中心），BM的发生率为17%。从五个三级中心共识别出54例mRCC-BM患者。28%（15/54）为同步性BM，28%（15/54）为TT前异时性BM，44%（24/54）为TT期间异时性BM。大多数患者在BM诊断时出现中枢神经系统（CNS）症状（78%；42/54）。从IV期诊断、TT开始和BM诊断的中位OS分别为28个月（95%置信区间[CI]16 - 43）、19个月（95%CI 9 - 26）和9个月（95%CI 5 - 16）。同步性BM组从TT开始的生存率有较差趋势（P = 0.06）。TT期间异时性BM组从BM诊断的生存率低于同步性BM组和TT前异时性BM组（P < 0.001）。50例死亡中有8例（16%）死于神经系统并发症。CNS症状的存在并不能预测从IV期诊断的较差生存率（P = 0.73）。
在mRCC患者中，与IV期疾病时同步诊断BM或在开始TT之前发生的异时性BM相比，在TT期间发生BM预示着更短的预后。CNS症状的存在并不能预测较差的生存率。
