Timing of brain metastases development in metastatic renal cell cancer patients treated with targeted therapies and survival outcomes: An Australian multicenter study

Francis J. Ha, Lavinia Spain, Anthony Dowling, Edmond M. Kwan, Carmel Pezaro, Daphne Day, Puey Ling Chia, Ben Tran, David Pook, Andrew J. Weickhardt

Research output: Contribution to journalArticleResearchpeer-review

Abstract

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.

Original languageEnglish
Number of pages6
JournalAsia-Pacific Journal of Clinical Oncology
DOIs
Publication statusAccepted/In press - 30 Jan 2019

Keywords

  • brain metastasis
  • prognosis
  • renal cell carcinoma
  • survival
  • targeted therapy

Cite this

@article{58e48821804f4b16b6aa9ec2ccc12eb7,
title = "Timing of brain metastases development in metastatic renal cell cancer patients treated with targeted therapies and survival outcomes: An Australian multicenter study",
abstract = "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.",
keywords = "brain metastasis, prognosis, renal cell carcinoma, survival, targeted therapy",
author = "Ha, {Francis J.} and Lavinia Spain and Anthony Dowling and Kwan, {Edmond M.} and Carmel Pezaro and Daphne Day and Chia, {Puey Ling} and Ben Tran and David Pook and Weickhardt, {Andrew J.}",
year = "2019",
month = "1",
day = "30",
doi = "10.1111/ajco.13109",
language = "English",
journal = "Asia-Pacific Journal of Clinical Oncology",
issn = "1743-7555",
publisher = "Wiley-Blackwell",

}

Timing of brain metastases development in metastatic renal cell cancer patients treated with targeted therapies and survival outcomes : An Australian multicenter study. / Ha, Francis J.; Spain, Lavinia; Dowling, Anthony; Kwan, Edmond M.; Pezaro, Carmel; Day, Daphne; Chia, Puey Ling; Tran, Ben; Pook, David; Weickhardt, Andrew J.

In: Asia-Pacific Journal of Clinical Oncology, 30.01.2019.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Timing of brain metastases development in metastatic renal cell cancer patients treated with targeted therapies and survival outcomes

T2 - An Australian multicenter study

AU - Ha, Francis J.

AU - Spain, Lavinia

AU - Dowling, Anthony

AU - Kwan, Edmond M.

AU - Pezaro, Carmel

AU - Day, Daphne

AU - Chia, Puey Ling

AU - Tran, Ben

AU - Pook, David

AU - Weickhardt, Andrew J.

PY - 2019/1/30

Y1 - 2019/1/30

N2 - 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.

AB - 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.

KW - brain metastasis

KW - prognosis

KW - renal cell carcinoma

KW - survival

KW - targeted therapy

UR - http://www.scopus.com/inward/record.url?scp=85060969927&partnerID=8YFLogxK

U2 - 10.1111/ajco.13109

DO - 10.1111/ajco.13109

M3 - Article

JO - Asia-Pacific Journal of Clinical Oncology

JF - Asia-Pacific Journal of Clinical Oncology

SN - 1743-7555

ER -