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.
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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DOI：
10.1016/j.eururo.2013.10.013
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发表时间：
2014-04
期刊：
影响因子：
23.4
通讯作者：
Choueiri, Toni K.
中科院分区：
文献类型：
--
作者：
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.
低钠血症与许多实体瘤的生存率差相关，最近发现其在接受免疫治疗的转移性肾细胞癌（mRCC）患者中具有预后和预测价值。在国际转移性肾细胞癌数据库联盟中研究基线低钠血症对接受靶向治疗的mRCC患者的影响。来自18个癌症中心的1661例接受一线血管内皮生长因子（VEGF）或哺乳动物雷帕霉素靶点（mTOR）靶向治疗的mRCC患者的数据可用于研究低钠血症（血清钠水平<135 mmol/l）对临床结局的影响。主要目标是总生存率（OS），次要终点包括治疗失败时间（TTF）和疾病控制率（DCR）。采用卡方检验比较有无低钠血症患者的DCR。采用Kaplan-Meier方法估计OS和TTF，并采用对数秩检验检查组间差异。多变量逻辑回归（DCR）和考克斯回归（OS和TTF）进行调整的预后危险因素。治疗开始后的中位OS为18.5个月（95%置信区间[CI]，17.5 - 19.8个月），552例（33.2%）患者在中位随访22.1个月时仍然存活。中位基线血清钠为138 mmol/l（范围：122 - 159 mmol/l），14.6%的患者出现低钠血症。在单变量分析中，低钠血症与OS较短（7.0 vs 20.9个月）、TTF较短（2.9 vs 7.4个月）和DCR率较低（54.9% vs 78.8%）相关（所有比较p <0.0001）。在多变量分析中，这些影响仍然显着（OS的风险比：1.51 [95%CI，1.26 - 1.80]，TTF的风险比：1.57 [95%CI，1.34 - 1.83]; DCR的优势比：0.50 [95%CI，34 - 0.72];调整后p <0.001）。如果将钠作为连续变量进行分析，结果相似（OS、TTF和DCR的校正p <0.0001）。这是最大的多机构报告，表明低钠血症与接受VEGF和mTOR靶向药物治疗的mRCC患者的预后不良独立相关。
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. To investigate the influence of baseline hyponatremia in mRCC patients treated with targeted therapy in the International Metastatic Renal Cell Carcinoma Database Consortium. 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. 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. 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). 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.
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影响因子：
45.3
作者：
Motzer, RJ;Mazumdar, M;Ferrara, J
通讯作者：
Ferrara, J
影响因子：
3.1
作者：
Berghmans, T;Paesmans, M;Body, JJ
通讯作者：
Body, JJ
影响因子：
6.2
作者：
Macfarlane, Robyn;Heng, Daniel Y. C.;Choueiri, Toni K.
通讯作者：
Choueiri, Toni K.
影响因子：
3.5
作者：
Kim, Hyo Song;Yi, Seong Yoon;Kang, Won Ki
通讯作者：
Kang, Won Ki
影响因子：
11.5
作者：
Vasudev, Naveen S.;Brown, Janet E.;Banks, Rosamonde E.
通讯作者：
Banks, Rosamonde E.