Abstract
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a dismal prognosis. Approximately 30% of patients present with locally advanced disease, defined as pancreatic tumor with invasion to adjacent structures, including the vasculatures that preclude an upfront surgical resection. Emerging data suggest that neoadjuvant therapy, typically consisting of systemic chemotherapy followed by concurrent chemoradiation, increases the likelihood of potentially curative R0 resection by downstaging the tumor and improves survival in patients with locally advanced PDAC. PDAC with deficient DNA mismatch repair (dMMR)/microsatellite instability-high molecular signature is exceedingly rare. The role of immunotherapy is emerging in various dMMR gastrointestinal tumors, both in the metastatic and neoadjuvant settings. However, the efficacy of immunotherapy in the neoadjuvant setting in patients with dMMR locally advanced PDAC remains unknown. Herein, we describe a patient who presented with unresectable dMMR locally advanced PDAC and underwent neoadjuvant immunotherapy with pembrolizumab that resulted in a remarkable reduction of the tumor size, rendering the tumor resectable. Furthermore, the presence of dMMR signature in the tumor was detected by circulating tumor DNA analysis. This is the first report, to our knowledge, of the successful use of neoadjuvant immunotherapy in a patient with locally advanced PDAC.