Non-thermal focused ultrasound with FOLFIRINOX for borderline resectable or locally advanced pancreatic cancer: An explorative phase II trial.

INTRODUCTION

FOLFIRINOX is standard chemotherapy for borderline resectable (BRPC) or locally advanced pancreatic cancer (LAPC), but response rates remain suboptimal. Mechanical effect-dominant non-thermal focused ultrasound (FUS) may enhance drug delivery. This study prospectively evaluated the safety and efficacy of FUS plus FOLFIRINOX in patients with BRPC or LAPC.

METHODOLOGY: In this exploratory phase II trial (NCT05262452), participants with BRPC or LAPC received FUS plus FOLFIRINOX chemotherapy during the first four cycles, followed by FOLFIRINOX continuation. The primary endpoint was objective response rate (ORR); secondary endpoints included overall survival (OS), progression-free survival (PFS), and treatment-related toxicity. A propensity score matched historical cohort of patients treated with FOLFIRINOX alone served as a control group.

RESULTS

Of 60 enrolled patients, 56 completed four cycles of combined therapy and were matched to 56 FOLFIRINOX-only controls. ORR was higher with FUS plus FOLFIRINOX than with FOLFIRINOX alone (64.3% vs. 35.7%; P = 0.003). Median OS was 24.0 versus 17.0 months (hazard ratio [HR], 0.63; 95% CI, 0.41-0.97; P = 0.029), and median PFS was 16.0 versus 11.0 months (HR, 0.65; 95% CI, 0.43-0.99; P = 0.039) for FUS plus FOLFIRINOX and FOLFIRINOX-only groups, respectively. Grade ≥ 3 toxicities occurred in 55.4% and 57.1% of patients (P = 0.849), with no FUS-related or collateral organ injuries.

DISCUSSION: Mechanical effect-dominant non-thermal FUS combined with FOLFIRINOX improved response rate and survival outcome without increasing toxicity compared with FOLFIRINOX alone in BRPC or LAPC. These exploratory findings support further evaluation in randomized phase III trials.

TRIAL REGISTRATION: This study is registered at clinicaltrials.gov (study identifier: NCT05262452).