HPB O07 Neoadjuvant therapy response and survival in borderline resectable and locally-advanced pancreatic ductal adenocarcinoma; the largest UK case series

Abstract

Abstract Background Neoadjuvant chemo/radiotherapy (NAT) is the treatment of choice for borderline resectable/ locally-advanced (BR/LA) pancreatic ductal adenocarcinoma (PDAC). Current preoperative imaging modalities (CT/MRI) and biomarkers lack sensitivity to predict response following NAT. The aim of this study was to evaluate preoperative PETCT and CA19-9 in predicting NAT response and survival. Methods A retrospective analysis of consecutive patients who underwent NAT for BR/LA PDAC between January 2013 and January 2023 was performed. Clinicopathological characteristics, treatment, and outcome were analysed. Pre- and post-NAT CA 19-9 and PETCT findings were correlated with resectability and pathological response. Overall survival (OS) and disease-free survival (DFS) comparisons were performed using log-rank model and Kaplan–Meier analysis. Results Tumour response following completion of NAT was evaluated in 87 (BR, n=58 and LA, n=29) patients with a median age of 73.3 years (47-87 years). FOLFIRINOX alone (93%, n=81) was mostly used as chemotherapy versus gemcitabine/nab-paclitaxel (7%). Post NAT, 51% of patients had biochemical response (CA19-9>50% decrease) and 48% had metabolic response on PETCT. Overall, 31(35%) individuals (BR, n=27 and LA, n=4) underwent complete resection with 81% achieving R0 status. After univariate analysis, pre-operative PETCT metabolic response (HR, 2.1; 95% CI, 1-4.3) was the only pre-operative predictor of resectability and correlated significantly with pathological response (P<0.003). In multivariate analysis, pre-operative metabolic response was the best performing predictor for resectability (P<0.001), pathological response (P<0.003), DFS (HR, 1.34; 95% CI, 1.3-1.9) and OS (HR, 1.45; 95% CI, 1.2-1.8). NAT patients had a median OS of 19 months, improving to 36 months for patients receiving NAT followed by curative surgery (HR 0.3; 95% CI, 0.1-0.56. P < .0001). Conclusions PETCT metabolic response appears to be highly predictive of resectability, pathological response and survival following NAT for BR/LA PDAC. An adequate staging of PDAC and re-assessment of the tumour after neoadjuvant therapy using PETCT would allow the multidisciplinary team to choose the most appropriate treatment for the patient.