3053 - Comparison of External Beam Radiation Modalities (Photon vs. Proton vs. Carbon Ion) in the Treatment of Hepatocellular Carcinoma: A Network Metanalysis

D. Nganga¹, O. Yariv^2,3, F. E. Escorcia⁴, X. Tan⁵, H. Makishima⁶, S. Apisarnthanarax⁷, M. Reig^8,9, A. M. Moon¹⁰, and T. K. Yanagihara¹¹; ¹Department of Radiation Oncology, University of North Carolina Hospitals, Chapel Hill, NC, ²Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, ³Davidoff Cancer Center, Rabin Medical Center – Beilinson Hospital, Petah Tikva, Israel, ⁴Molecular Imaging Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, ⁵Lineberger Comprehensive Cancer Center, University of North Carolina Hospitals, Chapel Hill, NC, ⁶Proton Medical Research Center, Department of Radiation Oncology, University of Tsukuba, Tsukuba, Japan, ⁷Department of Radiation Oncology, University of Washington/ Fred Hutchinson Cancer Center, Seattle, WA, ⁸BCLC group, Liver Unit, ICMDM, IDIBAPS, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain, ⁹Liver Oncology Unit Liver Unit, Hospital Clinic de Barcelona, Barcelona, Spain, ¹⁰Division of Gastroenterology and Hepatology, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, ¹¹Department of Radiation Oncology, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, Chapel Hill, NC

Purpose/Objective(s): We sought to compare disease outcomes and treatment toxicities with photon, proton, and carbon ion radiotherapy in prospective studies using ablative external beam radiotherapy (EBRT) in the treatment of hepatocellular carcinoma (HCC). Materials/

Methods: A systematic literature review of PubMed, Embase (Elsevier), Scopus (Elsevier), the Cochrane Library and ClinicalTrials.gov was performed by a health science librarian for available literature focused on studies that evaluate the role of EBRT in patients with HCC. The last search date was December 15, 2022. Only studies that were written in English and treated patients with an ablative EBRT technique (defined by previously published expert consensus) were included. We excluded studies of < 10 patients, combined therapies, or when EBRT was used as salvage. Studies were screened by two independent reviewers with discrepancies resolved by consensus or a third reviewer when needed. A secondary screen was performed by two additional reviewers to include only studies that prospectively collected toxicity data, which were extracted using Covidence systematic review software (Veritas Health Innovation, Melbourne, Australia), with discrepancies resolved by consensus or a third reviewer. Conference abstracts were permitted if all inclusion criteria were met. In these cases, the corresponding author of each abstract was contacted, and the data were included only if the full published manuscript was provided.
Results: A total of 1389 studies were screened for eligibility. 46 studies met criteria for inclusion in this study and 13 of these were conference abstracts. Of these 13, six authors responded to requests for the published manuscript and two were provided. 33 studies with 1924 patients had complete manuscripts. Most patients were treated with photons compared to protons and carbon ion (1382 vs 358 vs 184, respectively). The dose fractionation schedules varied across studies ranging from 1 to 15 fractions (mean 7.2; median 5) with a reported minimum median dose of 36Gy and maximum median dose of 54.5Gy. Of the 10 studies that reported rates of radiation induced liver disease (RILD), both classic and non-classic, rates were 1.2% (photon), 0.27% (proton), and 0% (carbon ion).
Conclusion: External beam radiation has an established role in the treatment of HCC and is well tolerated. Photons are currently the most utilized modality, but there is a growing role for proton and carbon ion radiotherapy. Future analyses will focus on other measures of hepatotoxicity and disease control rates.