Stereotactic body radiation therapy for inoperable non-metastasized pancreatic adenocarcinoma: a randomised phase II study (TORPEDO).

BACKGROUND: Patients with pancreatic ductal adenocarcinoma face a poor prognosis, with radical resection being the only potential cure. Because symptoms typically appear late, many patients are diagnosed with advanced disease. Locally advanced pancreatic tumours are characterised by extensive vascular involvement, which precludes R0 resection. Systemic therapy is therefore indicated, not only for palliation but also for reducing the risk of metastatic disease. Locoregional control remains paramount, irrespective of distant metastases as progressive tumours can cause considerable morbidity, negatively affecting patients' quality of life. Previous studies investigating conventionally fractionated (chemo)radiotherapy have yielded mixed results, indicating opportunities for further research to optimise treatment outcomes. The TORPEDO study aims to prospectively assess whether adding stereotactic body radiation therapy (SBRT) to standard chemotherapy can improve outcomes in patients with initially inoperable, non-metastasized pancreatic ductal adenocarcinoma. METHODS: This study is a multicentre randomised phase II trial. While it primarily targets locally advanced lesions, patients with borderline resectable tumours who are either medically inoperable or decline surgery are also eligible. After twelve weeks of induction chemotherapy (modified FOLFIRINOX or gemcitabine/nab-paclitaxel), patients without development of distant metastases are randomised 1:1 to receive either continued chemotherapy alone (arm A) or one month of chemotherapy followed by SBRT (5 × 8 Gy) (arm B). Resectability is evaluated through a multidisciplinary tumour board. The primary endpoint is the 2-year progression-free survival. Secondary endpoints include overall survival, local progression-free survival, metastasis-free survival, objective response rate, resectability, R0 resection rates, surgical morbidity, toxicity, quality of life, and the impact of radiation doses on outcomes. DISCUSSION: We evaluate the efficacy and safety of SBRT following induction chemotherapy in patients with inoperable, non-metastasized pancreatic ductal adenocarcinoma. We hypothesize that adding SBRT enhances outcome by improving local control and increasing overall survival. Effective control of the pancreatic primary tumor may help reduce pain and thereby improve quality of life. TRIAL REGISTRATION: The ethics committee of the GZA Hospitals approved this study on April 8, 2024. It was registered on ClinicalTrials.gov (NCT06691425) on November 15, 2024.