Five-fraction stereotactic magnetic resonance-guided adaptive radiotherapy targeting the primary tumor in metastatic pancreatic cancer

Abstract

BACKGROUND

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with most patients present with or develop metastatic disease. Despite modern multiagent chemotherapy, survival remains poor. Locoregional progression of the primary tumor often causes pain, biliary obstruction, and gastrointestinal complications. Magnetic resonance-guided radiotherapy (MRgRT) enables daily adaptive planning and real-time motion control, allowing safe dose escalation in anatomically constrained regions. We hypothesized that stereotactic magnetic resonance–guided radiotherapy provides effective and safe local tumor control in patients with metastatic PDAC (mPDAC).

AIM

To investigate the feasibility, efficacy, and safety of MRgRT in mPDAC.

METHODS

This prospective single-center observational study enrolled consecutive patients with synchronous or metachronous mPDAC treated between January 2020 and January 2025. Radiotherapy was delivered on a 0.35-T MR-Linac with 33-40 Gy in five fractions. Primary endpoint was local control; secondary endpoints included overall survival (OS), time to distant progression, toxicity, and pain relief. Prognostic clinical and treatment parameters were explored using subgroup analyses.

RESULTS

Twenty-four patients were included. Local control at 12 months and 24 months was 76% and 67%, respectively. Median time to distant progression was 3 months. Median OS in the entire cohort was 13 months after radiotherapy and 20 months from diagnosis, with a 1-year OS rate of 49%. Palliative treatment intent was associated with shorter survival (5 months, P = 0.001). OS was longer in patients with single-organ disease (P = 0.003), stable metastatic disease after systemic therapy (P = 0.0027), carbohydrate antigen 19-9 < 500 U/mL (P = 0.03), and Eastern Cooperative Oncology Group 0 (P = 0.023). Two acute grade 3 gastrointestinal events (duodenal hemorrhage, biliary duct obstruction) occurred; no late grade ≥ 3 toxicities were observed. Pain relief was reported by 89% of symptomatic patients.

CONCLUSION

MRgRT is a feasible and well-tolerated treatment providing high local control and effective pain palliation in selected patients with mPDAC.

Keywords: Pancreatic cancer; Pancreatic ductal adenocarcinoma; Radiotherapy; Stereotactic body radiotherapy; Metastatic pancreatic ductal adenocarcinoma; Magnetic resonance-guided radiotherapy

Core Tip: Local progression of the primary tumor remains a major cause of morbidity in metastatic pancreatic ductal adenocarcinoma, even in the era of modern chemotherapy. This prospective observational study demonstrates that five-fraction stereotactic magnetic resonance-guided radiotherapy to the primary tumor is feasible and safe in patients with metastatic pancreatic ductal adenocarcinoma, achieving good local control, meaningful pain palliation, and low rates of high-grade toxicity. These findings support magnetic resonance-guided radiotherapy as a promising local treatment option within multimodal strategies for carefully selected patients with controlled metastatic disease.