Survival benefit of particle chemoradiotherapy in locally advanced unresectable pancreatic cancer: a systematic review and meta-analysis
Cheng-Shien Shieh, Po-Long Cheng, I-Chun Lai, Wei-Yu Kao, Meng-Huang Wu, Jeng-Fong Chiou, Ping-Hsiu Wu, Hsin-Lun LeeBackground:
The pros and cons of incorporating radiotherapy (RT) into chemotherapy (CT) for locally advanced unresectable pancreatic cancer (LAPC) have been debated for decades. Recently, particle (proton and carbon-ion) therapy has emerged as a new radiotherapy modality. Given the unclear benefits of this approach, we summarized clinical outcomes of LAPC treated with concurrent chemoradiotherapy (CRT) using particle therapy to compare outcomes with current treatments.
Objectives:
To evaluate the efficacy and safety of particle therapy-based CRT in patients with LAPC and compare survival outcomes with photon CRT, combination CT, and single-agent CT.
Design:
Systematic review and single-arm meta-analysis.
Data sources and methods:
Studies evaluating LAPC treated with first-line particle CRT, photon CRT, combination CT, and single-agent CT were included. A single-arm meta-analysis was performed to calculate a pooled effect size using the DerSimonian and Laird random-effects model. The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), response rate, and adverse events.
Results:
Across 42 studies and 3161 patients with LAPC, particle CRT achieved a pooled 1-year OS of 75.8% (95% confidence interval (CI) 71.3–79.7), 2-year OS of 41.3% (95% CI 35.6–47.3), and 1-year PFS of 51.7% (95% CI 43.2–60.0). Photon CRT achieved a 1-year OS of 59.4% and 2-year OS of 21.0%; combination chemotherapy 64.4% and 30.8%; and single-agent chemotherapy 37.2% and 13.1%. Pooled response rate after particle CRT was 48.8%. Grade ⩾3 upper gastrointestinal events (ulcer/bleeding) were more frequent after particle CRT (4.3%) than after photon CRT (2.1%).
Conclusion:
Particle therapy CRT might have comparable survival outcomes in treating LAPC with combination CT, photon CRT, and single-agent CT. These findings support considering particle CRT as a valuable first-line treatment option for LAPC, which should be validated in randomized clinical trials.
Trial registration:
The final search was conducted on December 31, 2024. The review protocol was registered in PROSPERO with the registration number CRD42023493665.