Retrospective Cohort Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 28, 2017; 23(28): 5187-5195
Published online Jul 28, 2017. doi: 10.3748/wjg.v23.i28.5187
Clinical significance of glycemic parameters on venous thromboembolism risk prediction in gastrointestinal cancer
Fiorella Guadagni, Silvia Riondino, Vincenzo Formica, Girolamo Del Monte, Anna Maria Morelli, Jessica Lucchetti, Antonella Spila, Roberta D’Alessandro, David Della-Morte, Patrizia Ferroni, Mario Roselli
Fiorella Guadagni, David Della-Morte, Patrizia Ferroni, San Raffaele Roma Open University, 00166 Rome, Italy
Fiorella Guadagni, Silvia Riondino, Antonella Spila, Roberta D’Alessandro, Patrizia Ferroni, Interinstitutional Multidisciplinary Biobank, IRCCS San Raffaele Pisana, 00166 Rome, Italy
Silvia Riondino, Vincenzo Formica, Anna Maria Morelli, Jessica Lucchetti, Mario Roselli, Department of Systems Medicine, Medical Oncology Unit, Tor Vergata Clinical Center, University of Rome Tor Vergata, 00133 Rome, Italy
Girolamo Del Monte, Department of Palliative Care, San Raffaele Cassino, Clinical Center, 03043 Cassino, Italy
David Della-Morte, Department of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, Italy
Author contributions: Guadagni F, Ferroni P and Roselli M designed the study, analyzed the data and wrote the paper; Riondino S and Della-Morte D analyzed the data and wrote the paper; Formica V, Del Monte G, Morelli AM and Lucchetti J enrolled the patients and collected clinical data; Spila A and D’Alessandro R performed the assays and collected laboratory data; all authors have read and approved the final version to be published; Ferroni P and Roselli M are co-senior authors for equal contribution.
Institutional review board statement: The study was reviewed and approved by the Scientific Institute for Research, Hospitalization and Health Care San Raffaele Pisana and by the Tor Vergata University Institutional Review Boards.
Informed consent statement: All study participants or their legal guardian provided informed written consent about personal and medical data collection prior to study enrolment.
Conflict-of-interest statement: All the Authors have no conflict of interest related to the manuscript.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Patrizia Ferroni, MD, PhD, San Raffaele Roma Open University, Via di Val Cannuta 247, 00166 Rome, Italy. patrizia.ferroni@sanraffaele.it
Telephone: +39-6-52253733 Fax: +39-6-52255668
Received: January 28, 2017
Peer-review started: February 9, 2017
First decision: April 21, 2017
Revised: May 4, 2017
Accepted: July 13, 2017
Article in press: July 13, 2017
Published online: July 28, 2017
Processing time: 181 Days and 3.1 Hours
Abstract
AIM

To investigate the possible predictive role of routinely used glycemic parameters for a first venous thromboembolism (VTE) episode in gastrointestinal (GI) cancer ambulatory patients - with or without clinically diagnosed type 2 diabetes (T2D) or obesity - treated with chemotherapy.

METHODS

Pre-treatment fasting blood glucose, insulin, glycated hemoglobin (HbA1c) and homeostasis model of risk assessment (HOMA) were retrospectively evaluated in a cohort study of 342 GI cancer patients. Surgery was performed in 142 (42%) patients with primary cancer, 30 (21%) and 112 (79%) of whom received neoadjuvant and adjuvant therapies, respectively. First-line chemotherapy was administered in 200 (58%) patients with metastatic disease. The study outcome was defined as the occurrence of a first symptomatic or asymptomatic VTE episode during active treatment.

RESULTS

Impaired glucose tolerance (IGT) or T2D were diagnosed in 30% of GI cancer patients, while overweight/obesity had an incidence of 41%. VTE occurred in 9.4% of patients (7% of non-diabetic non-obese), especially in those with a high ECOG score (P = 0.025). No significant association was found between VTE incidence and T2D, obesity, different tumor types, metastatic disease, Khorana class of risk, or different anti-cancer drugs, although VTE rates were substantially higher in patients receiving bevacizumab (17% vs 8%, P = 0.044). Conversely, all glucose metabolic indexes were associated with increased VTE risk at ROC analysis. Multivariate Cox proportional analyses confirmed that HOMA index (HR = 4.13, 95%CI: 1.63-10.5) or fasting blood glucose (HR = 3.56, 95%CI: 1.51-8.39) were independent predictors of VTE occurrence during chemotherapy.

CONCLUSION

The results here reported demonstrate that evaluating glucose metabolic asset may allow for VTE risk stratification in GI cancer, helping to identify chemotherapy-treated patients who might benefit from thromboprophylaxis. Further multicenter prospective studies involving a larger number of patients are presently needed.

Keywords: Gastrointestinal cancer; Type 2 diabetes; Venous thromboembolism; Chemotherapy; Insulin resistance

Core tip: The predictive value of pre-treatment fasting blood glucose, insulin, HbA1c and homeostasis model of risk assessment (HOMA) was investigated in a cohort of gastrointestinal (GI) cancer patients. Despite all investigated metabolic markers were associated with an increased VTE risk during chemotherapy at ROC analysis, only elevated HOMA index (HR = 4.13) or fasting blood glucose (HR = 3.56) had an independent predictive value in survival analyses after adjustment for major confounders. These results suggest that glycemic metabolic markers, mainly HOMA index, should be carefully monitored in chemotherapy-treated GI cancer patients, as they could help to identify patients who might benefit from thromboprophylaxis.