Martín, M. (Miguel)

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    Biomarkers and polymorphisms in pancreatic neuroendocrine tumors treated with sunitinib
    (Impact Journals, 2018) Fuster, J. (Josep); Jiménez-Fonseca, P. (Paula); Grande, E. (Enrique); Raquel; Martín, M. (Miguel); Martínez-Lago, N. (Nieves); Muñarriz, J. (Javier); Cruz-Hernández, J.J. (Juan Jesús); Llanos, M. (Marta); Fernández-Mateos, J. (Javier); La-Casta-Muñoa, A. (Adelaida); Carmona-Bayonas, A. (Alberto); Barón, F. (Francisco); Redrado, M. (Miriam); Calvo-González, A. (Alfonso); Segura, Á. (Ángel); Castillo, A. (Alfredo); Capdevila, J. (Jaume)
    Several circulating biomarkers and single nucleotide polymorphisms (SNPs) have been correlated with efficacy and tolerability to antiangiogenic agents. These associations remain unexplored in well-differentiated, metastatic pancreatic neuroendocrine tumors treated with the multitargeted tyrosine kinase inhibitor sunitinib. We have assessed the effect on tumor response at 6 months, overall survival, progression-free survival and safety of 14 SNPs, and 6 soluble proteins. Forty-three patients were recruited. Two SNPs in the vascular endothelial growth factor receptor 3 (VEGFR-3) gene predicted lower overall survival: rs307826 with hazard ratio (HR) 3.67 (confidence interval [CI] 95%, 1.35-10.00) and rs307821 with HR 3.84 (CI 95%, 1.47-10.0). Interleukin-6 was associated with increased mortality: HR 1.06 (CI 95%, 1.01-1.12), and osteopontin was associated with shorter PFS: HR 1.087 (1.01-1.16), independently of Ki-67. Furthermore, levels of osteopontin remained higher at the end of the study in patients considered non-responders: 38.5 ng/mL vs. responders: 18.7 ng/mL, p-value=0.039. Dynamic upward variations were also observed with respect to IL-8 levels in sunitinib-refractory individuals: 28.5 pg/mL at baseline vs. 38.3 pg/mL at 3 months, p-value=0.024. In conclusion, two VEGFR-3 SNPs as well as various serum biomarkers were associated with diverse clinical outcomes in patients with well-differentiated pancreatic neuroendocrine tumors treated with sunitinib.