Gastrointestinal Cancer

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SU_17_2176 - The impact of serum glucose and antidiabetic agents in the treatment of locoregionally advanced pancreatic cancer

Sunday, October 21
1:15 PM - 2:45 PM
Location: Innovation Hub, Exhibit Hall 3

The impact of serum glucose and antidiabetic agents in the treatment of locoregionally advanced pancreatic cancer
N. A. Iarrobino1, B. S. Gill2, M. E. Bernard3, and C. E. Champ4; 1University of Pittsburgh School of Medicine, Pittsburgh, PA, 2UPMC Hillman Cancer Center, Pittsburgh, PA, 3Department of Radiation Medicine, University of Kentucky, Lexington, KY, 4Department of Radiation Oncology, Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, PA

Purpose/Objective(s): Epidemiological data have consistently identified an increased risk of pancreatic cancer in diabetics, yet the role hyperglycemia may play in predicting prognosis is less clear. Preclinical data consistently reveal that hyperglycemia may interfere with the “five R’s” of radiobiology to decrease the efficacy of radiation therapy. This work aims to robustly evaluate the impact of glycemic state and antidiabetics on outcomes after systemic and local treatment for locoregionally advanced pancreatic cancer.

Materials/Methods: After institutional review board approval, we conducted a retrospective-cohort study consisting of 303 patients with newly diagnosed advanced-stage pancreatic cancer treated between 2004 and 2014. All patients received stereotactic body radiation therapy as single or three-fractions regimens as either monotherapy or in combination with surgery and systemic therapy. The Kaplan-Meier survival analysis method was used to estimate time-to-event for overall survival, distant metastasis, and locoregional control. Blood glucose values (n=8599) were assessed both as continuous and categorical variables in univariate and multivariable Cox proportional hazard regression models to estimate hazard ratios and identify independent prognostic factors. Further, we conducted a 6-month conditional landmark analysis in which patients with less than 6 months follow-up or survival were excluded.

Results: Median follow-up and survival was 18.1 and 18.4 months, respectively. On univariate analysis, maximum pre-treatment glucose value was associated with reduced overall survival (unadjusted HR 1.005, p=0.023) and locoregional control (unadjusted HR 1.001, p=0.001). A pre-treatment glucose value ≥200 mg/dl was associated with increased mortality, which remained significant in multivariable analysis (adjusted HR 1.01, p=0.015). When applying the conditional 6-month landmark, a glucose value ≥200 mg/dl prior to local treatment was associated with reduced overall survival (adjusted HR 1.562; 95% CI, 1.16-2.11; p=0.003). Antidiabetic usage was not associated with any improved outcomes.

Conclusion: Elevated blood glucose around the time of treatment with radiation therapy is associated with poorer outcomes, including overall survival, in locoregionally advanced pancreatic cancer, while antidiabetics were not associated with outcomes. These results should be confirmed by subsequent high quality prospective studies, and the metabolic effects by which hyperglycemia may interact with, and reduce treatment efficacy, should be explored.

Author Disclosure: N.A. Iarrobino: None. B.S. Gill: None. M.E. Bernard: None. C.E. Champ: None.

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