Biomarkers and polymorphisms in pancreatic neuroendocrine tumors treated with sunitinib.

Journal: Oncotarget
Published Date: Dec 11, 2018

Abstract

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.

Authors

  • Paula Jiménez-Fonseca
    Medical Oncology Department, Hospital Universitario Central de Asturias, Oviedo, Spain.
  • Miguel Navarro Martín
    Medical Oncology Department, Hospital Universitario de Salamanca, IBSAL, Salamanca, Spain.
  • Alberto Carmona-Bayonas
    Hematology and Medical Oncology Department, Hospital Universitario Morales Meseguer, UMU, IMIB, Murcia, Spain.
  • Alfonso Calvo
    IDISNA and Program in Solid Tumors and Biomarkers, Center for Applied Medical Research (CIMA), Department of Histology and Pathology, University of Navarra, CIBERONC, ISC-II, Pamplona, Spain.
  • Javier Fernández-Mateos
    Molecular Medicine Unit, IBSAL, Department of Medicine, University of Salamanca, Salamanca, Spain.
  • Miriam Redrado
    IDISNA and Program in Solid Tumors and Biomarkers, Center for Applied Medical Research (CIMA), Department of Histology and Pathology, University of Navarra, Pamplona, Navarra, Spain.
  • Jaume Capdevila
    Medical Oncology Department, Hospital Universitario Vall d'Hebron, Autonomous University of Barcelona, Barcelona, Spain.
  • Nieves Martínez Lago
    Medical Oncology Department, Hospital Universitario de A Coruña, La Coruña, Spain.
  • Adelaida Lacasta
    Medical Oncology Department, Hospital Universitario Donostia, Guipúzcoa, Spain.
  • Javier Muñarriz
    Medical Oncology Department, Hospital General Universitario de Castellón, Castellón, Spain.
  • Ángel Segura
    Medical Oncology Department, Hospital Universitario La Fe, Valencia, Spain.
  • Josep Fuster
    Medical Oncology Department, Hospital Universitario Son Espases, Palma de Mallorca, Spain.
  • Francisco Barón
    Medical Oncology Department, Hospital Universitario de Santiago de Compostela, Santiago de Compostela, Spain.
  • Marta Llanos
    Medical Oncology Department, Hospital Universitario de Canarias, Santa Cruz de Tenerife, Spain.
  • Raquel Serrano
    Medical Oncology Department, Hospital Universitario Reina Sofia, Cordoba, Spain.
  • Alfredo Castillo
    Medical Oncology Department, Hospital Universitario Central de Asturias, Oviedo, Spain.
  • Juan Jesús Cruz Hernández
    Medical Oncology Department, Hospital Universitario de Salamanca, IBSAL, Salamanca, Spain.
  • Enrique Grande
    Medical Oncology Department, MD Anderson Cancer Center, Madrid, Spain.

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