Abstract
Abstract Background: Empiric prognostic scoring systems for metastatic renal cell carcinoma (mRCC) are routinely employed as baseline risk stratification tools for clinical trials. However, these systems have limited clinical utility after therapeutic intervention has begun. The goal of the current study was to develop clinically useful, hypothesis-driven, kinetic risk assessment tools based exclusively on biomarkers of systemic inflammation. Methods: A retrospective chart review was conducted with authorization from the Emory University Institutional Review Board. Inclusion criteria included treatment at the Winship Cancer Institute with a targeted agent for mRCC as well as concomitant serum C-reactive protein (CRP) and albumin levels on at least three occasions that were at least 10 days apart. The modified Glasgow Prognostic Score (mGPS) was used to quantify the intensity of systemic inflammation and to formulate the Inflammation Intensity Index for kinetic risk assessment. Findings: Intensity of systemic inflammation was assessed 2465 times in 135 patients with cohorts used for training (n = 55; cutoff date 06/30/2012) and validation (n = 80; cutoff date 06/30/2014). Kinetic risk was assigned on the basis of time to onset of refractory systemic inflammation. The median overall survival (OS) was 44.7, 19.8, 13.0, and 6.7 months for kinetic risk categories A, B, C and D, respectively, with a median follow up of 29.3 months for the combined cohorts and none lost to follow up (censored log rank p <.0001). OS was 40.6 months for whites (n = 99) vs. 9.8 months for blacks (n = 30; p <.0001). Conclusions: The correlation of dramatic differences in OS with the onset of refractory systemic inflammation provides strong evidence in support of the clinical utility of the Inflammation Intensity Index and, as a consequence, the underlying theoretical constructs, including a plausible biological hypothesis for differences in clinical outcome by race. Citation Format: Wayne B. Harris, Omer Kucuk, Bradley Carthon, Yuan Liu, John Pattaras, Kenneth Ogan, Viraj Master. Kinetic risk assessment with biomarkers of systemic inflammation in patients with metastatic renal cell carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 593. doi:10.1158/1538-7445.AM2015-593
Published Version
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