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Timing of brain metastases development in metastatic renal cell cancer patients treated with targeted therapies and survival outcomes: An Australian multicenter study
Author(s) -
Ha Francis J.,
Spain Lavinia,
Dowling Anthony,
Kwan Edmond M.,
Pezaro Carmel,
Day Daphne,
Chia Puey Ling,
Tran Ben,
Pook David,
Weickhardt Andrew J.
Publication year - 2019
Publication title -
asia‐pacific journal of clinical oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.73
H-Index - 29
eISSN - 1743-7563
pISSN - 1743-7555
DOI - 10.1111/ajco.13109
Subject(s) - medicine , renal cell carcinoma , proportional hazards model , stage (stratigraphy) , confidence interval , incidence (geometry) , gastroenterology , cancer , oncology , paleontology , physics , optics , biology
Aim 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. Methods 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. Results 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). Conclusion 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.