Clinical significance of glycemic parameters on venous thromboembolism risk prediction in gastrointestinal cancer

World J Gastroenterol. 2017 Jul 28;23(28):5187-5195. doi: 10.3748/wjg.v23.i28.5187.

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

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anticoagulants / therapeutic use
  • Antineoplastic Agents / adverse effects
  • Bevacizumab / adverse effects
  • Biomarkers / blood
  • Blood Glucose / analysis
  • Chemotherapy, Adjuvant / adverse effects
  • Diabetes Mellitus, Type 2 / epidemiology*
  • Female
  • Gastrointestinal Neoplasms / blood
  • Gastrointestinal Neoplasms / complications*
  • Gastrointestinal Neoplasms / drug therapy
  • Gastrointestinal Neoplasms / pathology
  • Glucose / metabolism*
  • Glucose Intolerance / blood
  • Glucose Intolerance / epidemiology*
  • Glycated Hemoglobin / analysis
  • Humans
  • Incidence
  • Insulin / blood
  • Male
  • Middle Aged
  • Neoadjuvant Therapy / adverse effects
  • Obesity / blood
  • Obesity / epidemiology*
  • Retrospective Studies
  • Risk Assessment / methods
  • Risk Factors
  • Venous Thromboembolism / blood
  • Venous Thromboembolism / epidemiology*
  • Venous Thromboembolism / metabolism
  • Venous Thromboembolism / prevention & control

Substances

  • Anticoagulants
  • Antineoplastic Agents
  • Biomarkers
  • Blood Glucose
  • Glycated Hemoglobin A
  • Insulin
  • Bevacizumab
  • Glucose