Visceral Obesity Is Associated with Shorter Progression-Free Survival in Well-Differentiated Gastro-Entero-Pancreatic Neuroendocrine Neoplasia

Ana P Santos; Jessica Rodrigues; Rui Henrique; M Helena Cardoso; Mariana P Monteiro

doi:10.3390/jcm11206026

Visceral Obesity Is Associated with Shorter Progression-Free Survival in Well-Differentiated Gastro-Entero-Pancreatic Neuroendocrine Neoplasia

J Clin Med. 2022 Oct 12;11(20):6026. doi: 10.3390/jcm11206026.

Authors

Ana P Santos^{1

2}, Jessica Rodrigues³, Rui Henrique^{4

5

6}, M Helena Cardoso^{7

8}, Mariana P Monteiro^{8

9}

Affiliations

¹ Department of Endocrinology, Portuguese Oncology Institute of Porto (IPO Porto), Porto Comprehensive Cancer Centre (P.CCC), 4200-072 Porto, Portugal.
² Precancerous Lesions and Early Cancer Management Group, Research Center of IPO Porto (CI-IPOP), RISE@CI-IPO (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto), Porto Comprehensive Cancer Centre (P.CCC), 4200-072 Porto, Portugal.
³ Cancer Epidemiology Group, Research Center of IPO Porto (CI-IPOP), RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto), Porto Comprehensive Cancer Centre (P.CCC), 4200-072 Porto, Portugal.
⁴ Department of Pathology, Portuguese Oncology Institute of Porto (IPO Porto), Porto Comprehensive Cancer Centre (P.CCC), 4200-072 Porto, Portugal.
⁵ Cancer Biology and Epigenetics Group, Research Centre of IPO Porto (CI-IPOP), RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto), Porto Comprehensive Cancer Centre (P.CCC), 4200-072 Porto, Portugal.
⁶ Department of Pathology and Molecular Immunology, ICBAS-School of Medicine and Biomedical Sciences, University of Porto, 4050-313 Porto, Portugal.
⁷ Department of Endocrinology, Centro Hospitalar Universitário do Porto (CHUPorto), 4099-001 Porto, Portugal.
⁸ UMIB-Unit for Multidisciplinary Research in Biomedicine, ICBAS-School of Medicine and Biomedical Sciences, University of Porto, 4050-313 Porto, Portugal.
⁹ ITR-Laboratory for Integrative and Translational Research in Population Health, 4200-450 Porto, Portugal.

Abstract

The association of well-differentiated gastro-entero-pancreatic neuroendocrine neoplasia (WD GEP-NEN) with metabolic syndrome (MetS), abdominal obesity, and fasting glucose abnormalities was recently described. However, whether obesity and metabolic syndrome risk factors are associated with GEP-NEN adverse outcomes and the poorer prognosis was unknown. The present study aimed to evaluate whether the presence of MetS or any of its individual components at WD GEP-NEN diagnosis influenced disease outcomes. A cohort of patients with non-localized WD GEP-NETs (n = 81), was classified according to the primary tumor site (gastrointestinal or pancreatic), pathological grading (G1 (Ki67 ≤ 2%) and G2 (3% ≤ Ki67 ≤ 20%) (WHO 2010)), disease extension (loco-regional or metastatic disease), presence of hormonal secretion syndrome (functioning or non-functioning), and evaluated for the presence of MetS criteria at diagnosis. MetS was present in 48 (59.3%) patients. During a median follow-up of 95.0 months (16.8-262.5), 18 patients died of the disease (10 with MetS vs. 8 without MetS). Overall survival (OS) at 5 years was 87.1% (95% CI: 73.6-94.0) for MetS and 90.9% (95% CI: 74.4-97.0) for non-Mets group, while OS at 10 years was 72.5% (95% CI: 55.3-84.0) for MetS, and 76.4% (95% CI: 53.6-89.0) for non-MetS group. Progression-Free Survival (PFS) at 5 years was 45.9% (95% CI: 30.8-59.8) for MetS and 40.0% (95% CI: 21.3-58.1) for non-MetS group, and PFS at 10 years was 18.1% (95% CI: 7.0-33.5) for MetS and 24.4% (95% CI: 9.0-43.7) for non-MetS group. Waist circumference (WC), a surrogate measure for visceral obesity, was associated with significantly shorter PFS (HR = 1.03; 95% CI: 1.01-1.06), although did not influence OS (HR = 1.01; 95% CI: 0.97-1.06). The findings of this study reinforce a potential link between visceral obesity and GEP-NEN and further suggest that obesity could influence disease prognosis.

Keywords: gastro-entero-pancreatic neuroendocrine neoplasia; metabolic syndrome; overall survival; progression-free survival; visceral obesity.

Grants and funding

Jéssica Rocha Rodrigues is funded by the Foundation for Science and Technology (FCT) through the following PhD grant: UI/BD/152282/2021.This work is funded by the Foundation for Science and Technology (FCT) through the following funds: UIDB/00215/2020, UIDP/00215/2020 and LA/P/0064/2020.