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. 2021 Feb 25:11:571855.
doi: 10.3389/fonc.2021.571855. eCollection 2021.

Glycemic Control as an Early Prognostic Marker in Advanced Pancreatic Cancer

Affiliations

Glycemic Control as an Early Prognostic Marker in Advanced Pancreatic Cancer

Ipek Alpertunga et al. Front Oncol. .

Abstract

Purpose: Impaired glucose metabolism is present in most patients with pancreatic ductal adenocarcinoma (PDAC). Whereas previous studies have focused on pre-treatment glycemic indices and prognosis in those with concomitant diabetes, the effects of glycemic control during chemotherapy treatment on prognosis, in patients with and without diabetes, have not been well characterized. We examined the relationship between early glycemic control and overall survival (OS) in a cohort of patients with advanced PDAC treated in a community setting.

Patients and methods: Seventy-three patients with advanced PDAC (38% with diabetes) receiving chemotherapy while participating in a biobanking clinical trial were included. Clinical characteristics and laboratory results during 1 year were obtained from the electronic medical record. Kaplan-Meier estimate, log-rank test and hazard ratios were computed to assess the effect of glycemic control on OS. The Cox proportional hazards regression model was applied to ascertain the significance of glycemic control with other survival variables.

Results: One thousand four hundred eighteen random blood glucose (RBG) values were analyzed. In accord with previous findings, a 50% decline in the serum tumor marker CA 19-9 at any time was predictive of survival (P=0.0002). In univariate analysis, an elevated pre-treatment average RBG, 3-month average RBG (RBG-3) and the FOLFIRINOX regimen were associated with longer survival. Based on ROC analysis (AUC=0.82), an RBG-3 of 120 mg/dl was determined to be the optimal cutoff to predict 12-month survival. In multivariate analysis that included age, stage, BMI, performance status, presence of diabetes, and chemotherapy regimen, only RBG-3 maintained significance: an RBG-3 ≤120 mg/dl predicted for improved OS compared to >120 mg/dl (19 vs. 9 months; HR=0.37, P=0.002). In contrast, an early decline in CA 19-9 could not predict OS.

Conclusion: Lower glucose levels during the first 3 months of treatment for advanced PDAC predict for improved OS in patients both with and without diabetes. These results suggest that RBG-3 may be a novel prognostic biomarker worthy of confirmation in a larger patient cohort and that studies exploring a possible cause and effect of this novel survival-linked relationship are warranted.

Keywords: diabetes mellitus; glycemic control; hyperglycemia; pancreatic cancer; prognostic marker.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
(A) Kaplan–Meier (K-M) survival analysis showing overall survival of the PDAC cohort in this study (n=73). (B) K-M survival analysis showing that patients who had 50% drop at any point after diagnosis have significantly longer survival than patients who did not. Only patients who had a baseline CA 19-9 (>100 U/ml) and survived at least 2 months were considered (n=42). (C) K-M survival analysis showing median survival and HR of the patients with and without DM. No survival difference was found. (D) Survival according to pre-RBG (≤ 140 mg/dl >). K-M survival analysis showing patients who had a pre-treatment RBG of ≤140 mg/dl survived longer than those with pre-RBG >140 mg/dl. In (B–D), median survival and hazard ratio (HR) with log-rank test significance are indicated.
Figure 2
Figure 2
DM status of the patient cohort. (A) Table displaying number of patients in each group with No DM, new-onset DM (NOD) and long standing DM (LS), select medications and percentages of patients who had HbA1C levels take at baseline and at 3 months. (B) K-M survival analysis showing median survival and HR of the patients according to DM status. No survival differences were observed between groups.
Figure 3
Figure 3
RBG-3 levels predict survival. (A) ROC curve showing RBG-3 of 119 with highest sensitivity (73) and specificity (77) to predict survival at 12 months (AUC 0.82). (B) Table shows median survival, HR and significance of RBG-3 values at 10 mg/dl intervals. 120 mg/dl shows the highest median survival differences and HR with at least 20 patients in each group.
Figure 4
Figure 4
Effect of RBG-3 above or below 120 mg/dl on OS and 12 months survival (RBG-3=average glucose values of the first 3 months of treatment. N.B. Only patients who survived at least 3 months were considered for analysis (n=54). (A) K-M survival analysis showing that patients with RBG-3 values ≤120 mg/dl survived significantly longer (19 months) than patients with RBG-3 >120 mg/dl (9 months) (p=0.002, HR = 0.37). (B) One-way analysis of patients separated by RBG-3 of 120 mg/dl predicts for survival at 12 months with sensitivity of 73% (TP = 11) and specificity 77% (TN=30). Dots are color coded by DM status.

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