Hyperglycemia and survival in solid tumors: A systematic review and meta-analysis.
e18158 Background: Diabetes is associated with adverse cancer outcomes. However, the effect of hyperglycemia independent of diabetes is unclear. Here we report on a meta-analysis exploring the effect of hyperglycemia on outcomes of solid tumors, and the influence of clinical factors on this association. Methods: A systematic search of electronic databases identified publications exploring the effect of hyperglycemia on overall (OS), disease-free (DFS) or progression-free survival (PFS). Definitions of hyperglycemia (fasting blood glucose, random blood glucose or HbA1c) and cut-offs varied between studies. Data from studies reporting a hazard ratio (HR) and 95% confidence interval (CI) or a p -value were pooled in a meta-analysis using generic inverse-variance and random effects modeling. Subgroup analyses were conducted based on method of hyperglycemia measurement (HbA1c, other) and tumor stage (early, advanced, mixed). Meta-regression was performed to evaluate the influence of clinical characteristics including baseline diabetes status on the HR for OS. All statistical tests were two-sided. Results: Eight studies comprising a total of 4342 patients were included. All studies reported HRs for OS. Two studies reported DFS outcomes, and two reported PFS. Hyperglycemia was associated with worse OS (HR 2.07, 95% CI = 1.70 - 2.52; P < 0.001) and DFS (HR 1.61, 95% CI = 1.04 - 2.49; P < 0.001), but did not decrease PFS (HR 1.08, 95% CI = 0.72 - 1.62; P = 0.71). The association with worse OS maintained in subgroups based on method of hyperglycemia measurement (subgroup difference P = 0.65) and tumor stage ( P= 0.47). Meta-regression analyses did not identify any factors significantly altering the magnitude of association between hyperglycemia and OS (see Table). Conclusions: Hyperglycemia is associated with adverse OS and DFS in patients with cancer, and the therapeutic role of optimal glycemic control warrants further investigation. [Table: see text]