Neoadjuvant Radiotherapy After (m)FOLFIRINOX for Borderline Resectable Pancreatic Adenocarcinoma: A TAPS Consortium Study

Background: The value of neoadjuvant radiotherapy (RT) after 5-fluo-rouracil with leucovorin, oxaliplatin, and irinotecan, with or without dose modifications [(m)FOLFIRINOX], for patients with borderline resectable (BR) pancreatic ductal adenocarcinoma (PDAC) is uncertain. Methods: We conducted an international retrospective cohort study including consecutive patients with BR PDAC who received (m)FOLFIRINOX as initial treatment (2012-2019) from the TransAtlantic Pancreatic Surgery Consortium. Because the decision to administer RT is made after chemotherapy, patients with metastases or deterioration after (m)FOLFIRINOX or a performance score $2 were excluded. Patients who received RT after (m)FOLFIRINOX were matched 1:1 by nearest neighbor propensity scores with patients who did not receive RT. Propensity scores were calculated using sex, age (#70 vs.70 years), WHO performance score (0 vs 1), tumor size (0-20 vs 21-40 vs.40 mm), tumor location (head/uncinate vs body/tail), number of cycles (1-4 vs 5-8 vs.8), and baseline CA 19-9 level (#500 vs.500 U/mL). Primary outcome was overall survival (OS) from diagnosis. Results: Of 531 patients who received neoadjuvant (m)FOLFIRINOX for BR PDAC, 424 met inclusion criteria and 300 (70.8%) were propensity score-matched. After matching, median OS was 26.2 months (95% CI, 24.0-38.4) with RT versus 32.8 months (95% CI, 25.3-42.0) without RT (P5.71). RT was associated with a lower resection rate (55.3% vs 72.7%; P5.002). In patients who underwent a resection, RT was associated with a comparable margin-negative resection rate (.1 mm) (70.6% vs 64.8%; P5.51), more node-negative disease (57.3% vs 37.6%; P5.01), and more major pathologic response with,5% tumor viability (24.7% vs 8.3%; P5.006). The OS associated with conventional and stereotactic body RT approaches was similar (median OS, 25.7 vs 26.0 months; P5.92). Conclusions: In patients with BR PDAC, neoadjuvant RT following (m)FOLFIRINOX was associated with more node-negative disease and better pathologic response in patients who underwent resection, yet no difference in OS was found. Routine use of RT cannot be recommended based on these data.