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Poor Glycemic Control is Associated With Failure to Complete Neoadjuvant Therapy and Surgery in Patients With Localized Pancreatic Cancer
Eunice Paul Rajamanickam*, Mohammed Aldakkak, Kathleen Christians, Ben George, Paul S. Ritch, Beth A. Erickson, Fabian Johnston, Douglas B. Evans, Susan Tsai
Medical College of Wisconsin, Milwaukee, WI
Background: Diabetes mellitus has a complex association with pancreatic cancer (PC). The impact of glycemic control during neoadjuvant therapy has not been well described among patients with localized PC.
Methods: Glycated hemoglobin (HbA1c) values were measured in patients with resectable and borderline resectable (BLR) PC at two time points: prior to any therapy (pretreatment) and after neoadjuvant therapy prior to surgery (preop). HbA1c levels were classified as normal or elevated based on a cutoff of 6.5%. Patients were categorized based on the change in HbA1c levels from pretreatment to preop: GrpA, always normal; GrpB, normal to elevated; GrpC, elevated to normal; and GrpD, always elevated.
Results: Pretreatment HbA1c levels were evaluable in 114 patients; normal in 68 (60%) and elevated in 46 (40%). No differences were observed in baseline clinical/demographic characteristics or clinical stage. Preop HbA1c levels were normal in 82 (72%) and elevated in 32 (28%) patients. When comparing pretreatment and preop HbA1c levels, there were 62 (54%) patients in GrpA, 6 (5%) in GrpB, 20 (18%) in GrpC, and 26 (23%) in GrpD. Of the 114 patients, 87 (76%) completed all neoadjuvant therapy to include surgery; 54 (87%) of 62 patients in GrpA, 3 (50%) of 6 patients in GrpB, 15 (75%) of 20 patients in GrpC, and 15 (58%) of 26 patients in GrpD (p=0.008). In an adjusted logistic regression, patients in GrpB had a7.62-fold increased odds of developing metastatic disease prior to surgery (95%CI:0.88-66.01;p=0.07). Completion of all intended therapy to include surgery was negatively associated with elevated preoperative CA19-9 value (OR: 0.20; 95%CI: 0.06-0.66; p=0.009), BLR disease (OR: 0.26; 95%CI: 0.07-0.91; p=0.04), and elevated HbA1c levels at both pretreatment and preop (GrpD) (OR: 0.23; 95%CI: 0.06-0.87; p=0.03). Median progression free survival (PFS) of all 114 patients was 18.2 months; median PFS for patients in Grps A, B, C, and D was not reached, 6, 13 and 16 months, respectively (p=0.06).
Conclusions: Worsening glycemic control during neoadjuvant therapy is associated with failure to complete neoadjuvant therapy and surgery, and a trend for an increased risk of metastatic progression and decreased progression free survival. These data suggest that glycemic control during the neoadjuvant period may be an important modifiable prognostic factor in the successful treatment of PC.
Table 1: Multi-variable Logistic Regression Analysis for Completion of Neoadjuvant Therapy to include Surgery (n= 114)
| Co-variate | OR | 95% CI | p value | | Adjusted Charlson Comorbidity Index | 0.86 | 0.62-1.20 | 0.39 | | Borderline Resectable Disease (ref: resectable) | 0.26 | 0.07-0.91 | 0.04 | | Elevated Preop CA19-9 (ref: < 35) | 0.20 | 0.06-0.66 | 0.009 | | HbA1c Categories (ref: Grp A; always normal) | -- | -- | -- | | Grp B; normal -> elevated | 0.16 | 0.02-1.19 | 0.07 | | Grp C; elevated -> normal | 0.44 | 0.10-1.92 | 0.27 | | Grp D; always elevated | 0.23 | 0.06-0.87 | 0.03 |
 Progression Free Survival by Change in HbA1c During Neoadjuvant Therapy
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