Biomarkers and polymorphisms in pancreatic neuroendocrine tumors treated with sunitinib

[EN]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...

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Detalhes bibliográficos
Autores: Jiménez Fonseca, Paula, Martín, Miguel Navarro, Carmona Bayonas, Alberto, Calvo, Alfonso, Fernández Mateos, Javier, Redrado, Miriam, Capdevila, Jaume, Lago, Nieves Martínez, Lacasta, Adelaida, Muñarriz, Javier, Segura, Ángel, Fuster, Josep, Barón, Francisco, Llanos, Marta, Serrano, Raquel, Castillo,Alfredo, Cruz Hernández, Juan Jesús, Grande, Enrique
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2018
País:España
Recursos:Universidad de Salamanca (USAL)
Repositorio:GREDOS. Repositorio Institucional de la Universidad de Salamanca
OAI Identifier:oai:gredos.usal.es:10366/146569
Acesso em linha:http://hdl.handle.net/10366/146569
Access Level:acceso abierto
Palavra-chave:IL-6
Osteopontin
Pancreatic neuroendocrine tumors
Sunitinib
VEGFR-3
Neuroendocrine Tumors
Pancreatic Neoplasms
3201.01 Oncología
tumores neuroendocrinos
neoplasias pancreáticas
osteopontina
Descrição
Resumo:[EN]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.

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