M.P. Martos1, M.S. Lee2,3, D. Franceschi1,2, A. Livingstone1,2, N.B. Merchant1,2, E. Kobetz2,3, S.K. Maithel4, V. Stathias2,5, S.C. Schürer2,5, C.A. Hester1,2, J. Datta1,2 5University Of Miami, Department Of Molecular And Cellular Pharmacology, Miami, FL, USA 1University Of Miami, Department Of Surgery, Miami, FL, USA 2University Of Miami, Sylvester Comprehensive Cancer Center, Miami, FL, USA 3University Of Miami, Department Of Public Health Sciences, Miami, FL, USA 4Emory University School Of Medicine, Department Of Surgery, Atlanta, GA, USA
Introduction: Neighborhood disadvantage is associated with worse outcomes in patients with pancreatic ductal adenocarcinoma (PDAC). While neighborhood disadvantage correlates with reduced access to equitable treatment, its effect on biologic outcomes in PDAC has not been explored. Using data from two diverse cohorts, we investigate the association of neighborhood disadvantage with pathologic response to neoadjuvant chemotherapy (NAC) in patients with localized PDAC undergoing curative-intent treatment.
Methods: We reviewed 317 patients with localized PDAC who underwent NAC and pancreatectomy at UMiami and Emory (01/2020-10/2022). Neighborhood disadvantage was reported using Area Deprivation Index (ADI), a calculation of 17 U.S. Census variables. The 2020 state ADI tertile rankings were assigned using patients’ census block groups. Pathologic response was dichotomized into major (MPR; College of American Pathologists [CAP] grade 0/1) or limited pathologic response (LPR; CAP 2/3). The association between CAP response and ADI tertiles was performed using Cochran-Armitage testing. Statistical significance was considered p≤0.05. Geospatial maps were created by overlaying ADI tertiles and pathologic response with patient catchment areas within each census block group.
Results: Of 317 patients, median age was 67 years and 54% were female. At UMiami, 48% of patients were Hispanic and 5% were Non-Hispanic Black; at Emory, 2% Hispanic and 17% Non-Hispanic Black. Patients received a median of 3.5 (range: 0.2-19) months NAC, with the majority (69%) receiving mFOLFIRINOX; 19% received neoadjuvant radiotherapy. MPR was observed in 47 (15%) patients, and LPR in 85%. Patients were stratified by ADI tertiles: 176 (55.5%) in tertile-1, 110 (34.7%) in tertile-2, and 31 (9.8%) in tertile-3. Higher ADI tertile reflects increased neighborhood disadvantage. Patients across ADI tertiles received similar NAC regimen (p=0.53), duration of NAC (p=0.97), and rates of neoadjuvant radiation (p=0.22). Those in the highest ADI tertile had significantly reduced rates of MPR (0% in tertile-3 vs. 17.6% in tertile-1 and 14.6% in tertile-2, p<0.00; Fig. 1A). The geospatial distribution of this association is depicted in Fig. 1B. In a binary regression model, increasing ADI rank was independently associated with decreased odds of MPR (OR 0.86, 95% CI 0.73–0.99), while receipt of radiotherapy (p=0.22) and number of NAC cycles (p=0.50) were not significant predictors.
Conclusion: Neighborhood disadvantage is associated with worse pathologic response following NAC in patients with resected PDAC. Our data suggest that environmental and psychosocial stressors in patients’ built environments influence biologic responses in the pancreatic tumor environment.