Meta-Analysis of Definitive Photon and Particle Irradiation for Locally Advanced Pancreatic Cancer

Abstract

The optimal treatment for unresectable pancreatic cancer remains unclear, as patients with locally advanced pancreatic cancer (LAPC) have poor outcomes despite aggressive therapies. Due to these poor outcomes, there has been interest in advanced techniques for definitive radiation, and robust literature has emerged for the definitive irradiation of LAPC, including photon-based techniques such as SBRT and IMRT/VMAT, proton, and carbon-ion irradiation. Despite promising early results, there are few advanced-stage clinical trials comparing these modalities.A systematic review was performed in December 2020 on PubMed/Medline using the following search terms: "pancreas" and "carbon ion radiotherapy," "proton," "stereotactic body radiation therapy," "SBRT," "IMRT," or "VMAT," which yielded 860 results. Retrospective or prospective studies using either SBRT, IMRT, VMAT, proton, or carbon ion radiotherapy for definitive radiation with or without concurrent chemotherapy were included. Resectable/borderline resectable, adjuvant radiation, and trials using older radiation techniques (3D conformal, 2D planning) were excluded from analysis. The primary outcomes were grade 3-5 acute and late toxicity, with secondary outcomes including 1-year overall survival (OS) and 1-year local control (LC). Random effects meta-analyses were conducted for each primary and secondary outcome using the restricted maximum likelihood method. The Wald-type test was used to compare treatment modalities, where the null hypothesis was rejected for P < 0.05.A total of 6 particle studies (proton and carbon ion) and 11 photon studies (IMRT/VMAT and SBRT) were included in the final analysis. The summary effect size for acute grade 3-5 toxicity was 4.9% for photon irradiation compared to 2.7% with particles (P = 0.46). The summary effect size for late grade 3-5 toxicities were 3.7% and 1.0% for photons and particles, respectively (P = 0.13). At 1 year, LC was 71.6% with photons and 86.7% with particles (P = 0.07), with OS of 59.3% and 74.4%, respectively (P = 0.09).Particle therapy with protons or carbon appears to be at least equally efficacious and safe compared to advanced photon-based treatment techniques in the treatment of unresectable pancreatic cancer. These findings are hypothesis generating and should be validated in well-designed prospective trials.