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

• Published in: British journal of cancer Vol. 117; no. 4; pp. 478 - 484
• Main Authors: Zurita, A J, Gagnon, R C, Liu, Y, Tran, H T, Figlin, R A, Hutson, T E, D'Amelio Jr, A M, Sternberg, C N, Pandite, L N, Heymach, J V
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 08.08.2017; Nature Publishing Group
• Subjects: 631/250/127; 692/53/2422; 692/699/67/589/1588/1351; Adult; Aged; Aged, 80 and over; Angiogenesis; Antineoplastic Agents - therapeutic use; Biomedical and Life Sciences; Biomedicine; Cancer Research; Carcinoma, Renal Cell - blood; Carcinoma, Renal Cell - drug therapy; Carcinoma, Renal Cell - mortality; Carcinoma, Renal Cell - pathology; Clinical Study; Clinical trials; Criteria; Cytokines; Cytokines - blood; Drug Resistance; E-selectin; E-Selectin - blood; Enzyme-linked immunosorbent assay; Epidemiology; Female; Hemoglobins - metabolism; Hepatocyte growth factor; Hepatocyte Growth Factor - blood; Humans; Interleukin 6; Interleukin 8; Interleukin-6 - blood; Interleukin-8 - blood; Kidney cancer; Kidney Neoplasms - blood; Kidney Neoplasms - drug therapy; Kidney Neoplasms - mortality; Kidney Neoplasms - pathology; L-Lactate Dehydrogenase - blood; Leukocyte Count; Male; Medical prognosis; Metastases; Middle Aged; Molecular Medicine; Neutrophils; Oncology; Osteopontin; Osteopontin - blood; Prognosis; Pyrimidines - therapeutic use; Renal cell carcinoma; Sulfonamides - therapeutic use; Survival Rate; Time-to-Treatment; Tissue inhibitor of metalloproteinase 1; Tissue Inhibitor of Metalloproteinase-1 - blood; Tumor Burden; Tumors; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - blood; angiogenic factors; cytokines; prognostic markers; advanced renal cell carcinoma
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/bjc.2017.206

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.