Radiotherapy for Locally Advanced Pancreatic Cancer in the Modern Era: A Systematic Review and Meta-Analysis

Background: The optimal treatment strategy for locally advanced unresectable pancreatic cancer (LAPC) is still investigated. Therefore, we evaluated the role of radiotherapy (RT) in the management of LAPC in the modern era. Methods: A systematic review was conducted following the Preferred Reporting Items for Systemic Review and Meta-Analyses guidelines. Eligible studies were about for LAPC treated with curative-intent modern RT techniques including intensity-modulated radiotherapy (IMRT), stereotactic body radiotherapy (SBRT), and particle beam therapy (PBT) until September 2024. Results: In total, 53 observational studies, encompassing 2548 patients (993 treated with IMRT, 998 with SBRT, and 557 with PBT), met the inclusion criteria. Concurrent chemoradiotherapy (CCRT) was implemented in 28 studies, including only 3 studies in the SBRT group. Elective nodal irradiation (ENI) was adopted in 22%. The pooled 2-year overall survival (OS) rate was 29% (95% confidence interval [CI], 25-34%) for all patients, with no significant differences among RT techniques: 28% (95% CI, 22-34%) for IMRT, 26% (95% CI, 19-34%) for SBRT, and 43% (95% CI, 28-57%) for PBT (p = 0.1121). The pooled rate of acute hematologic toxicity (HT) ≥ grade 3 was 17% (95% CI, 9-26%), with significant differences among RT techniques: 23% (95% CI, 9-40%) for IMRT, 4% (95% CI, 0-11%) for SBRT, and 20% (95% CI, 6-37%) for PBT (p = 0.0181). In addition, CCRT (p = 0.0084) and ENI (p = 0.0145) significantly increased the risk of acute HT. Gastrointestinal toxicities rarely occurred. Conclusions: This systematic review and meta-analysis showed similar efficacy among modern RT techniques for LAPC management. Since almost all studies have single-arm design, and chemotherapy regimens have changed over time, conclusions must be drawn with caution. The use of modern RT techniques is individually selected according to clinical practice and resource availability.