Effect of Diabetes and Smoking on the Pathological Response of Neoadjuvant Therapy in Pancreatic Adenocarcinoma

Presenter: Syed Omair Nadeem MD | Emory University Background: Increased utilization of neoadjuvant therapy (NT) for pancreatic adenocarcinoma (PDAC) has allowed for potential downsizing of the primary tumor, improved patient selection for curative resection and has demonstrated a safe and efficacious effect on survival of these patients. However, there exists limited data on patient factors that influence pathologic response in patients presenting with PDAC. We sought to explore the effect of diabetes and smoking on the pathologic response of tumors post NT. Methods: Patients with biopsy confirmed PDAC who received NT and underwent pancreaticoduodenectomy between January 2010 and December 2019 at a tertiary care center were reviewed. Surgical pathology reports were reviewed to determine treatment effect. Pathologic tumor response was assessed based on the College of American Pathologists (CAP) grading system. Grades 0-2 were defined as showing a treatment response while grade 3 was defined as no treatment response. Results: Overall 180 patients underwent pancreaticoduodenectomy at our institution. FOLFIRINOX was the most commonly employed neoadjuvant regimen (n=105, 58.3%) followed by Gemcitabine combination chemotherapy (n=68, 37.8%), while the rest got other treatment regimens. SBRT was utilized in 38 (21.1%) patients, while CRT was utilized in 17 (9.4%) patients. 20 patients (11.0%) had a complete or near complete pathologic response (CAP grade 0, 1 respectively), 53 (29.4%) patients had a partial response (CAP grade 2) and 107 (59.4%) patients had poor or no response to NT (CAP grade 3). Median overall survival was 13.6 months. On univariate analysis for factors predicting pathologic response, a diagnosis of Diabetes was associated with a significantly increased chance of poor or no pathologic response (p=0.033). On multivariate regression analysis, Diabetes again was culpable for predicting poor pathologic response (OR=0.262; 0.109-0.633, p=0.003). No other patient factors including age, gender, BMI, ethnicity, tobacco-use or other comorbidities and neoadjuvant treatment options (FOLFIRINOX vs Gemcitabine based therapy) were found to be significant for predicting pathologic tumor response. Despite Diabetes being associated with poor pathologic response, there were no differences in overall survival between diabetics and non-diabetics using Kaplan-Meier survival estimates (Figure1). Conclusion: Our results demonstrate that a diagnosis of Diabetes was associated with a significantly increased chance of predicting poor pathologic response to neoadjuvant therapy. This warrants the need for further discussion and randomized controlled trials to study patient factors which influence pathologic response to neoadjuvant therapy, which can help improve patient selection for neoadjuvant treatment.