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 |
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| Institution: | 1. Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA;2. Aarhus University Hospital, Aarhus, Denmark;3. Brigham & Women''s Hospital, Harvard Medical School, Boston, MA, USA;4. Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA;5. Cleveland Clinic, Taussig Cancer Institute, Cleveland, OH, USA;6. Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA;7. City of Hope Comprehensive Cancer Center, Duarte, CA, USA;8. Stanford Medical Center, Stanford, CA, USA;9. British Columbia Cancer Agency, Vancouver, BC, Canada;10. Cross Cancer Institute, Edmonton, AB, Canada;11. Dalhousie University, Halifax, NS, Canada;12. Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA;13. National Cancer Centre Singapore, Singapore;14. London Regional Cancer Program, London, ON, Canada;15. Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea;p. Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea;q. Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan;r. Tom Baker Cancer Center, Calgary, AB, Canada;1. Department of Urology, University Hospital “Carl Gustav Carus”, Dresden University of Technology, Fetscherstrasse 74, D-01307 Dresden, Germany;2. Department Biometry and Medical Statistics, University Hospital “Carl Gustav Carus”, Dresden University of Technology, Fetscherstrasse 74, D-01307 Dresden, Germany;1. Higher Technical School of Architecture, Universidad de Sevilla, C/Torres, 7-9.3P, CP 41002 Seville, Spain;2. Higher Technical School of Building Engineering, Universidad de Sevilla, C/ Guadalbullón, 19, 4ºC. CP 41013, Seville, Spain;1. Department of Surgery and Perioperative Sciences, Urology and Andrology, Umeå University, Umeå, Sweden;2. Department of Surgery, Urology Service, Memorial Sloan-Kettering Cancer Centre, New York, NY, USA;3. Department of Urology, New York University and Manhattan Veterans Affairs Medical Centre, New York, NY, USA;1. Airways Disease Section, National Heart and Lung Institute, Imperial College London, London SW3 6LR, UK;2. Service de chirurgieorthopédique, Hôpital Cochin, Assistance PubliqueHôpitaux de Paris, Université Paris Descartes, Paris, France |
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| Abstract: | BackgroundHyponatremia 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.ObjectiveTo 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 participantsData 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 analysisThe 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 limitationsMedian 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).ConclusionsThis 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. |
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| Keywords: | Hyponatremia Renal cell cancer Anti-VEGF Prognostic factors |
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