Normo- or Hypo-Fractionated Photon or Proton Radiotherapy in the Management of Locally Advanced Unresectable Pancreatic Cancer: A Systematic Review

Simple Summary Locally advanced pancreatic carcinoma (LAPC) is one of the most challenging tumors that requires multimodality management including chemotherapy and/or radiotherapy. Local radiotherapy toxicity is a fundamental problem for dose escalation, so advances in radiation therapy using different techniques or fractionations are being developed. We focus this systematic review on the outcome of the photon and proton radio (chemo) therapy with normo- or hypo-fractionation schedules in management of patients with locally advanced pancreatic carcinoma. LAPC is associated with a poor prognosis and requires a multimodal treatment approach. However, the role of radiation therapy in LAPC treatment remains controversial. This systematic review aimed to explore the role of proton and photon therapy, with varying radiation techniques and fractionation, in treatment outcomes and their respective toxicity profiles. Methods: Clinical studies published from 2012 to 2022 were systematically reviewed using PubMed, MEDLINE (via PubMed) and Cochrane databases. Different radiotherapy-related data were extracted and analyzed. Results: A total of 31 studies matched the inclusion criteria. Acute toxicity was less remarkable in stereotactic body radiotherapy (SBRT) compared to conventionally fractionated radiotherapy (CFRT), while in proton beam therapy (PBT) grade 3 or higher acute toxicity was observed more commonly with doses of 67.5 Gy (RBE) or higher. Late toxicity was not reported in most studies; therefore, comparison between groups was not possible. The range of median overall survival (OS) for the CFRT and SBRT groups was 9.3-22.9 months and 8.5-20 months, respectively. For the PBT group, the range of median OS was 18.4-22.3 months. Conclusion: CFRT and SBRT showed comparable survival outcomes with a more favorable acute toxicity profile for SBRT. PBT is a promising new treatment modality; however, additional clinical studies are needed to support its efficacy and safety.