Integrating cytokines and angiogenic factors and tumour bulk with selected clinical criteria improves determination of prognosis in advanced renal cell carcinoma.

Abstract:

BACKGROUND:In two clinical trials of the vascular endothelial growth factor (VEGF) receptor inhibitor pazopanib in advanced renal cell carcinoma (mRCC), we found interleukin-6 as predictive of pazopanib benefit. We evaluated the prognostic significance of candidate cytokines and angiogenic factors (CAFs) identified in that work relative to accepted clinical parameters. METHODS:Seven preselected plasma CAFs (interleukin-6, interleukin-8, osteopontin, VEGF, hepatocyte growth factor, tissue inhibitor of metalloproteinases (TIMP-1), and E-selectin) were measured using multiplex ELISA in plasma collected pretreatment from 343 mRCC patients participating in the phase 3 registration trial of pazopanib vs placebo (NCT00334282). Tumour burden (per sum of longest diameters (SLD)) and 10 other clinical factors were also analysed for association with overall survival (OS; based on initial treatment assignment). RESULTS:Osteopontin, interleukin-6, and TIMP-1 were independently associated with OS in multivariable analysis. A model combining the three CAFs and five clinical variables (including SLD) had higher prognostic accuracy than the International Metastatic Renal Cell Carcinoma Database Consortium criteria (concordance-index 0.75 vs 0.67, respectively), and distinguished two groups of patients within the original intermediate risk category. CONCLUSIONS:A prognostic model incorporating osteopontin, interleukin-6, TIMP-1, tumour burden, and selected clinical criteria increased prognostic accuracy for OS determination in mRCC patients.

journal_name

Br J Cancer

authors

Zurita AJ,Gagnon RC,Liu Y,Tran HT,Figlin RA,Hutson TE,D'Amelio AM Jr,Sternberg CN,Pandite LN,Heymach JV

doi

10.1038/bjc.2017.206

subject

Has Abstract

pub_date

2017-08-08 00:00:00

pages

478-484

issue

4

eissn

0007-0920

issn

1532-1827

pii

bjc2017206

journal_volume

117

pub_type

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