The impact of low serum sodium on treatment outcome of targeted therapy in metastatic renal cell carcinoma: Results from the international metastatic renal cell cancer database consortium

Fabio A.B. Schutz, Wanling Xie, Frede Donskov, Monica Sircar, David F. McDermott, Brian I. Rini, Neeraj Agarwal, Sumanta Kumar Pal, Sandy Srinivas, Christian Kollmannsberger, Scott A. North, Lori A. Wood, Ulka Vaishampayan, Min Han Tan, Mary J. MacKenzie, Jae Lyun Lee, Sun Young Rha, Takeshi Yuasa, Daniel Y.C. Heng, Toni K. Choueiri

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Background Hyponatremia has been associated with poor survival in many solid tumors and more recently found to be of prognostic and predictive value in metastatic renal cell cancer (mRCC) patients treated with immunotherapy. Objective To investigate the influence of baseline hyponatremia in mRCC patients treated with targeted therapy in the International Metastatic Renal Cell Carcinoma Database Consortium. Design, setting, and participants Data on 1661 patients treated with first-line vascular endothelial growth factor (VEGF) or mammalian target of rapamycin (mTOR) targeted therapy for mRCC were available from 18 cancer centers to study the impact of hyponatremia (serum sodium level <135 mmol/l) on clinical outcomes. Outcome measurements and statistical analysis The primary objective was overall survival (OS) and secondary end points included time to treatment failure (TTF) and the disease control rate (DCR). The chi-square test was used to compare the DCR in patients with and without hyponatremia. OS and TTF were estimated with the Kaplan-Meier method and differences between groups were examined by the log-rank test. Multivariable logistic regression (for DCR) and Cox regression (for OS and TTF) were undertaken adjusted for prognostic risk factors. Results and limitations Median OS after treatment initiation was 18.5 mo (95% confidence interval [CI], 17.5-19.8 mo), with 552 (33.2%) of patients remaining alive on a median follow-up of 22.1 mo. Median baseline serum sodium was 138 mmol/l (range: 122-159 mmol/l), and hyponatremia was found in 14.6% of patients. On univariate analysis, hyponatremia was associated with shorter OS (7.0 vs 20.9 mo), shorter TTF (2.9 vs 7.4 mo), and lower DCR rate (54.9% vs 78.8%) (p < 0.0001 for all comparisons). In multivariate analysis, these effects remain significant (hazard ratios: 1.51 [95% CI, 1.26-1.80] for OS, and 1.57 [95% CI, 1.34-1.83] for TTF; odds ratio: 0.50 [95% CI, 34-0.72] for DCR; adjusted p < 0.001). Results were similar if sodium was analyzed as a continuous variable (adjusted p < 0.0001 for OS, TTF, and DCR). Conclusions This is the largest multi-institutional report to show that hyponatremia is independently associated with a worse outcome in mRCC patients treated with VEGF- and mTOR-targeted agents.

Original languageEnglish
Pages (from-to)723-730
Number of pages8
JournalEuropean Urology
Volume65
Issue number4
DOIs
Publication statusPublished - 2014 Apr 1

Fingerprint

Hyponatremia
Renal Cell Carcinoma
Treatment Failure
Sodium
Databases
Survival
Serum
Confidence Intervals
Sirolimus
Therapeutics
Vascular Endothelial Growth Factor A
Chi-Square Distribution
Immunotherapy
Neoplasms
Multivariate Analysis
Logistic Models
Odds Ratio

All Science Journal Classification (ASJC) codes

  • Urology

Cite this

Schutz, Fabio A.B. ; Xie, Wanling ; Donskov, Frede ; Sircar, Monica ; McDermott, David F. ; Rini, Brian I. ; Agarwal, Neeraj ; Pal, Sumanta Kumar ; Srinivas, Sandy ; Kollmannsberger, Christian ; North, Scott A. ; Wood, Lori A. ; Vaishampayan, Ulka ; Tan, Min Han ; MacKenzie, Mary J. ; Lee, Jae Lyun ; Rha, Sun Young ; Yuasa, Takeshi ; Heng, Daniel Y.C. ; Choueiri, Toni K. / The impact of low serum sodium on treatment outcome of targeted therapy in metastatic renal cell carcinoma : Results from the international metastatic renal cell cancer database consortium. In: European Urology. 2014 ; Vol. 65, No. 4. pp. 723-730.
@article{b35499f449924205befa3dd4c7b2641b,
title = "The impact of low serum sodium on treatment outcome of targeted therapy in metastatic renal cell carcinoma: Results from the international metastatic renal cell cancer database consortium",
abstract = "Background Hyponatremia has been associated with poor survival in many solid tumors and more recently found to be of prognostic and predictive value in metastatic renal cell cancer (mRCC) patients treated with immunotherapy. Objective To investigate the influence of baseline hyponatremia in mRCC patients treated with targeted therapy in the International Metastatic Renal Cell Carcinoma Database Consortium. Design, setting, and participants Data on 1661 patients treated with first-line vascular endothelial growth factor (VEGF) or mammalian target of rapamycin (mTOR) targeted therapy for mRCC were available from 18 cancer centers to study the impact of hyponatremia (serum sodium level <135 mmol/l) on clinical outcomes. Outcome measurements and statistical analysis The primary objective was overall survival (OS) and secondary end points included time to treatment failure (TTF) and the disease control rate (DCR). The chi-square test was used to compare the DCR in patients with and without hyponatremia. OS and TTF were estimated with the Kaplan-Meier method and differences between groups were examined by the log-rank test. Multivariable logistic regression (for DCR) and Cox regression (for OS and TTF) were undertaken adjusted for prognostic risk factors. Results and limitations Median OS after treatment initiation was 18.5 mo (95{\%} confidence interval [CI], 17.5-19.8 mo), with 552 (33.2{\%}) of patients remaining alive on a median follow-up of 22.1 mo. Median baseline serum sodium was 138 mmol/l (range: 122-159 mmol/l), and hyponatremia was found in 14.6{\%} of patients. On univariate analysis, hyponatremia was associated with shorter OS (7.0 vs 20.9 mo), shorter TTF (2.9 vs 7.4 mo), and lower DCR rate (54.9{\%} vs 78.8{\%}) (p < 0.0001 for all comparisons). In multivariate analysis, these effects remain significant (hazard ratios: 1.51 [95{\%} CI, 1.26-1.80] for OS, and 1.57 [95{\%} CI, 1.34-1.83] for TTF; odds ratio: 0.50 [95{\%} CI, 34-0.72] for DCR; adjusted p < 0.001). Results were similar if sodium was analyzed as a continuous variable (adjusted p < 0.0001 for OS, TTF, and DCR). Conclusions This is the largest multi-institutional report to show that hyponatremia is independently associated with a worse outcome in mRCC patients treated with VEGF- and mTOR-targeted agents.",
author = "Schutz, {Fabio A.B.} and Wanling Xie and Frede Donskov and Monica Sircar and McDermott, {David F.} and Rini, {Brian I.} and Neeraj Agarwal and Pal, {Sumanta Kumar} and Sandy Srinivas and Christian Kollmannsberger and North, {Scott A.} and Wood, {Lori A.} and Ulka Vaishampayan and Tan, {Min Han} and MacKenzie, {Mary J.} and Lee, {Jae Lyun} and Rha, {Sun Young} and Takeshi Yuasa and Heng, {Daniel Y.C.} and Choueiri, {Toni K.}",
year = "2014",
month = "4",
day = "1",
doi = "10.1016/j.eururo.2013.10.013",
language = "English",
volume = "65",
pages = "723--730",
journal = "European Urology",
issn = "0302-2838",
publisher = "Elsevier",
number = "4",

}

Schutz, FAB, Xie, W, Donskov, F, Sircar, M, McDermott, DF, Rini, BI, Agarwal, N, Pal, SK, Srinivas, S, Kollmannsberger, C, North, SA, Wood, LA, Vaishampayan, U, Tan, MH, MacKenzie, MJ, Lee, JL, Rha, SY, Yuasa, T, Heng, DYC & Choueiri, TK 2014, 'The impact of low serum sodium on treatment outcome of targeted therapy in metastatic renal cell carcinoma: Results from the international metastatic renal cell cancer database consortium', European Urology, vol. 65, no. 4, pp. 723-730. https://doi.org/10.1016/j.eururo.2013.10.013

The impact of low serum sodium on treatment outcome of targeted therapy in metastatic renal cell carcinoma : Results from the international metastatic renal cell cancer database consortium. / Schutz, Fabio A.B.; Xie, Wanling; Donskov, Frede; Sircar, Monica; McDermott, David F.; Rini, Brian I.; Agarwal, Neeraj; Pal, Sumanta Kumar; Srinivas, Sandy; Kollmannsberger, Christian; North, Scott A.; Wood, Lori A.; Vaishampayan, Ulka; Tan, Min Han; MacKenzie, Mary J.; Lee, Jae Lyun; Rha, Sun Young; Yuasa, Takeshi; Heng, Daniel Y.C.; Choueiri, Toni K.

In: European Urology, Vol. 65, No. 4, 01.04.2014, p. 723-730.

Research output: Contribution to journalArticle

TY - JOUR

T1 - The impact of low serum sodium on treatment outcome of targeted therapy in metastatic renal cell carcinoma

T2 - Results from the international metastatic renal cell cancer database consortium

AU - Schutz, Fabio A.B.

AU - Xie, Wanling

AU - Donskov, Frede

AU - Sircar, Monica

AU - McDermott, David F.

AU - Rini, Brian I.

AU - Agarwal, Neeraj

AU - Pal, Sumanta Kumar

AU - Srinivas, Sandy

AU - Kollmannsberger, Christian

AU - North, Scott A.

AU - Wood, Lori A.

AU - Vaishampayan, Ulka

AU - Tan, Min Han

AU - MacKenzie, Mary J.

AU - Lee, Jae Lyun

AU - Rha, Sun Young

AU - Yuasa, Takeshi

AU - Heng, Daniel Y.C.

AU - Choueiri, Toni K.

PY - 2014/4/1

Y1 - 2014/4/1

N2 - Background Hyponatremia has been associated with poor survival in many solid tumors and more recently found to be of prognostic and predictive value in metastatic renal cell cancer (mRCC) patients treated with immunotherapy. Objective To investigate the influence of baseline hyponatremia in mRCC patients treated with targeted therapy in the International Metastatic Renal Cell Carcinoma Database Consortium. Design, setting, and participants Data on 1661 patients treated with first-line vascular endothelial growth factor (VEGF) or mammalian target of rapamycin (mTOR) targeted therapy for mRCC were available from 18 cancer centers to study the impact of hyponatremia (serum sodium level <135 mmol/l) on clinical outcomes. Outcome measurements and statistical analysis The primary objective was overall survival (OS) and secondary end points included time to treatment failure (TTF) and the disease control rate (DCR). The chi-square test was used to compare the DCR in patients with and without hyponatremia. OS and TTF were estimated with the Kaplan-Meier method and differences between groups were examined by the log-rank test. Multivariable logistic regression (for DCR) and Cox regression (for OS and TTF) were undertaken adjusted for prognostic risk factors. Results and limitations Median OS after treatment initiation was 18.5 mo (95% confidence interval [CI], 17.5-19.8 mo), with 552 (33.2%) of patients remaining alive on a median follow-up of 22.1 mo. Median baseline serum sodium was 138 mmol/l (range: 122-159 mmol/l), and hyponatremia was found in 14.6% of patients. On univariate analysis, hyponatremia was associated with shorter OS (7.0 vs 20.9 mo), shorter TTF (2.9 vs 7.4 mo), and lower DCR rate (54.9% vs 78.8%) (p < 0.0001 for all comparisons). In multivariate analysis, these effects remain significant (hazard ratios: 1.51 [95% CI, 1.26-1.80] for OS, and 1.57 [95% CI, 1.34-1.83] for TTF; odds ratio: 0.50 [95% CI, 34-0.72] for DCR; adjusted p < 0.001). Results were similar if sodium was analyzed as a continuous variable (adjusted p < 0.0001 for OS, TTF, and DCR). Conclusions This is the largest multi-institutional report to show that hyponatremia is independently associated with a worse outcome in mRCC patients treated with VEGF- and mTOR-targeted agents.

AB - Background Hyponatremia has been associated with poor survival in many solid tumors and more recently found to be of prognostic and predictive value in metastatic renal cell cancer (mRCC) patients treated with immunotherapy. Objective To investigate the influence of baseline hyponatremia in mRCC patients treated with targeted therapy in the International Metastatic Renal Cell Carcinoma Database Consortium. Design, setting, and participants Data on 1661 patients treated with first-line vascular endothelial growth factor (VEGF) or mammalian target of rapamycin (mTOR) targeted therapy for mRCC were available from 18 cancer centers to study the impact of hyponatremia (serum sodium level <135 mmol/l) on clinical outcomes. Outcome measurements and statistical analysis The primary objective was overall survival (OS) and secondary end points included time to treatment failure (TTF) and the disease control rate (DCR). The chi-square test was used to compare the DCR in patients with and without hyponatremia. OS and TTF were estimated with the Kaplan-Meier method and differences between groups were examined by the log-rank test. Multivariable logistic regression (for DCR) and Cox regression (for OS and TTF) were undertaken adjusted for prognostic risk factors. Results and limitations Median OS after treatment initiation was 18.5 mo (95% confidence interval [CI], 17.5-19.8 mo), with 552 (33.2%) of patients remaining alive on a median follow-up of 22.1 mo. Median baseline serum sodium was 138 mmol/l (range: 122-159 mmol/l), and hyponatremia was found in 14.6% of patients. On univariate analysis, hyponatremia was associated with shorter OS (7.0 vs 20.9 mo), shorter TTF (2.9 vs 7.4 mo), and lower DCR rate (54.9% vs 78.8%) (p < 0.0001 for all comparisons). In multivariate analysis, these effects remain significant (hazard ratios: 1.51 [95% CI, 1.26-1.80] for OS, and 1.57 [95% CI, 1.34-1.83] for TTF; odds ratio: 0.50 [95% CI, 34-0.72] for DCR; adjusted p < 0.001). Results were similar if sodium was analyzed as a continuous variable (adjusted p < 0.0001 for OS, TTF, and DCR). Conclusions This is the largest multi-institutional report to show that hyponatremia is independently associated with a worse outcome in mRCC patients treated with VEGF- and mTOR-targeted agents.

UR - http://www.scopus.com/inward/record.url?scp=84894412753&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84894412753&partnerID=8YFLogxK

U2 - 10.1016/j.eururo.2013.10.013

DO - 10.1016/j.eururo.2013.10.013

M3 - Article

C2 - 24184025

AN - SCOPUS:84894412753

VL - 65

SP - 723

EP - 730

JO - European Urology

JF - European Urology

SN - 0302-2838

IS - 4

ER -