A phase II trial proposal of total neoadjuvant treatment with primary chemotherapy, stereotactic body radiation therapy, and intraoperative radiation therapy in borderline resectable pancreatic adenocarcinoma
Salvatore Paiella,
Giuseppe Malleo,
Nicola Simoni,
Renato Micera,
Stefania Guariglia,
Carlo Cavedon,
Giovanni Marchegiani,
Alessandro Esposito,
Luca Landoni,
Luca Casetti,
Massimiliano Tuveri,
Michele Milella,
Erica Secchettin,
Gessica Manzini,
Chiara Bovo,
Matteo De Pastena,
Martina Fontana,
Roberto Salvia,
Renzo Mazzarotto,
Claudio Bassi
Affiliations
Salvatore Paiella
Unit of General and Pancreatic Surgery, University of Verona Hospital Trust
Giuseppe Malleo
Unit of General and Pancreatic Surgery, University of Verona Hospital Trust
Nicola Simoni
Unit of Radiation Oncology, University of Verona Hospital Trust
Renato Micera
Unit of Radiation Oncology, University of Verona Hospital Trust
Stefania Guariglia
Unit of Medical Physics, University of Verona Hospital Trust
Carlo Cavedon
Unit of Medical Physics, University of Verona Hospital Trust
Giovanni Marchegiani
Unit of General and Pancreatic Surgery, University of Verona Hospital Trust
Alessandro Esposito
Unit of General and Pancreatic Surgery, University of Verona Hospital Trust
Luca Landoni
Unit of General and Pancreatic Surgery, University of Verona Hospital Trust
Luca Casetti
Unit of General and Pancreatic Surgery, University of Verona Hospital Trust
Massimiliano Tuveri
Unit of General and Pancreatic Surgery, University of Verona Hospital Trust
Michele Milella
Unit of Medical Oncology, University of Verona Hospital Trust
Erica Secchettin
Unit of General and Pancreatic Surgery, University of Verona Hospital Trust
Gessica Manzini
Unit of General and Pancreatic Surgery, University of Verona Hospital Trust
Chiara Bovo
University of Verona Hospital Trust Management Unit
Matteo De Pastena
Unit of General and Pancreatic Surgery, University of Verona Hospital Trust
Martina Fontana
Unit of General and Pancreatic Surgery, University of Verona Hospital Trust
Roberto Salvia
Unit of General and Pancreatic Surgery, University of Verona Hospital Trust
Renzo Mazzarotto
Unit of Radiation Oncology, University of Verona Hospital Trust
Claudio Bassi
Unit of General and Pancreatic Surgery, University of Verona Hospital Trust
Abstract Background The current management guidelines recommend that patients with borderline resectable pancreatic adenocarcinoma (BRPC) should initially receive neoadjuvant chemotherapy. The addition of advanced radiation therapy modalities, including stereotactic body radiation therapy (SBRT) and intraoperative radiation therapy (IORT), could result in a more effective neoadjuvant strategy, with higher rates of margin-free resections and improved survival outcomes. Methods/design In this single-center, single-arm, intention-to-treat, phase II trial newly diagnosed BRPC will receive a “total neoadjuvant” therapy with FOLFIRINOX (5-fluorouracil, irinotecan and oxaliplatin) and hypofractionated SBRT (5 fractions, total dose of 30 Gy with simultaneous integrated boost of 50 Gy on tumor-vessel interface). Following surgical exploration or resection, IORT will be also delivered (10 Gy). The primary endpoint is 3-year survival. Secondary endpoints include completion of neoadjuvant treatment, resection rate, acute and late toxicities, and progression-free survival. In the subset of patients undergoing resection, per-protocol analysis of disease-free and disease-specific survival will be performed. The estimated sample size is 100 patients over a 36-month period. The trial is currently recruiting. Trial registration NCT04090463 at clinicaltrials.gov.
