Murphy JE, et al. - In this single-arm phase 2 trial of 49 patients, researchers sought to determine the relation of total neoadjuvant therapy with FOLFIRINOX (fluorouracil, leucovorin, oxaliplatin, and irinotecan), losartan, and chemoradiation therapy with margin-negative (R0) resection rates in patients with previously untreated locally advanced pancreatic adenocarcinoma. For 8 cycles, patients were given FOLFIRINOX and losartan. Short-course chemoradiotherapy (5 GyE × 5 with protons) with capecitabine was used in cases with radiographically resectable tumor post-chemotherapy. Long-course chemoradiotherapy (50.4 Gy with a vascular boost to 58.8 Gy) with fluorouracil or capecitabine was used to treat patients with persistent vascular involvement. Findings revealed an R0 resection rate of 61% in relation to total neoadjuvant therapy with FOLFIRINOX, losartan, and chemoradiotherapy. This treatment regimen provides downstaging of locally advanced pancreatic ductal adenocarcinoma.