title: Evaluation of Focal Liver Reaction after Proton Beam Therapy for Hepatocellular Carcinoma Examined Using Gd-EOB-DTPA Enhanced Hepatic Magnetic Resonance Imaging.
abstract: BACKGROUND
  Proton beam therapy (PBT) achieves good local control for hepatocellular carcinoma (HCC), and toxicity tends to be lower than for photon radiotherapy. Focal liver parenchymal damage in radiotherapy is described as the focal liver reaction (FLR); the threshold doses (TDs) for FLR in the background liver have been analyzed in stereotactic ablative body radiotherapy and brachytherapy. To develop a safer approach for PBT, both TD and liver volume changes are considered clinically important in predicting the extent of damage before treatment, and subsequently in reducing background liver damage. We investigated appearance time, TDs and volume changes regarding FLR after PBT for HCC.
  
  
  METHODS
  Patients who were treated using PBT and were followed up using gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (Gd-EOB-DTPA MRI) after PBT were enrolled. Sixty-eight lesions in 58 patients were eligible for analysis. MRI was acquired at the end of treatment, and at 1, 2, 3 and 6 months after PBT. We defined the FLR as a clearly depicted hypointense area on the hepatobiliary phase of Gd-EOB-DTPA MRI, and we monitored TDs and volume changes in the FLR area and the residual liver outside of the FLR area.
  
  
  RESULTS
  FLR was depicted in all lesions at 3 months after PBT. In FLR expressed as the 2-Gy equivalent dose (α/β = 3 Gy), TDs did not differ significantly (27.0±6.4 CGE [10 fractions [Fr] vs. 30.5±7.3 CGE [20 Fr]). There were also no correlations between the TDs and clinical factors, and no significant differences between Child-Pugh A and B scores. The volume of the FLR area decreased and the residual liver volume increased, particularly during the initial 3 months.
  
  
  CONCLUSIONS
  This study established the FLR dose for liver with HCC, which might be useful in the prediction of remnant liver volume for PBT.
authors.affiliation: Department of Radiotherapy, Kanazawa University Hospital, Ishikawa, Japan.|Proton Therapy Center, Fukui Prefectural Hospital, Fukui, Japan.
authors.forename: Shigeyuki
authors.identifier: http://orcid.org/0000-0002-0743-4413
authors.initials: S
authors.lastname: Takamatsu
authors.affiliation: Proton Therapy Center, Fukui Prefectural Hospital, Fukui, Japan.
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Yamamoto
authors.affiliation: Proton Therapy Center, Fukui Prefectural Hospital, Fukui, Japan.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Maeda
authors.affiliation: Department of Radiology, Nagoya University Graduate School of Medicine, Aichi, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Kawamura
authors.affiliation: Proton Therapy Center, Fukui Prefectural Hospital, Fukui, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Shibata
authors.affiliation: Proton Therapy Center, Fukui Prefectural Hospital, Fukui, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Department of Radiology, Hyogo Ion Beam Medical Center, Hyogo, Japan.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Terashima
authors.affiliation: Proton Therapy Center, Fukui Prefectural Hospital, Fukui, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Shimizu
authors.affiliation: Proton Therapy Center, Fukui Prefectural Hospital, Fukui, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Tameshige
authors.affiliation: Proton Therapy Center, Fukui Prefectural Hospital, Fukui, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Sasaki
authors.affiliation: Department of Radiology, University of Fukui, Fukui, Japan.
authors.forename: Satoko
authors.initials: S
authors.lastname: Asahi
authors.affiliation: Department of Diagnostic and Therapeutic Radiology, Kanazawa Medical University, Ishikawa, Japan.
authors.forename: Tamaki
authors.initials: T
authors.lastname: Kondou
authors.affiliation: Department of Radiology, Kanazawa University, Ishikawa, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kobayashi
authors.affiliation: Department of Radiology, Kanazawa University, Ishikawa, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Matsui
authors.affiliation: Department of Radiology, Kanazawa University, Ishikawa, Japan.
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Gabata
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000000981:diagnostic imaging* / Q000473:pathology* / Q000532:radiotherapy; D005500:Follow-Up Studies; D019786:Gadolinium DTPA; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008099:Liver / Q000000981:diagnostic imaging* / Q000473:pathology*; D008113:Liver Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology* / Q000532:radiotherapy; D008279:Magnetic Resonance Imaging / Q000379:methods; D061766:Proton Therapy / Q000379:methods; D012189:Retrospective Studies
chemical_list: C073590:gadolinium ethoxybenzyl DTPA; D019786:Gadolinium DTPA