title: Analysis of repeated proton beam therapy for patients with hepatocellular carcinoma.
abstract: To evaluate the feasibility and efficacy of repeated proton beam therapy (PBT) and to analyze the dose-volume relationship.
  
  
  
  A retrospective analysis was performed in 83 patients who received definitive repeated PBT. Proton beams were delivered with expiratory gating. The numbers of treatment courses were 2, 3, and 4 in 68, 12, and 3 patients, respectively. MIM software was used for dose analysis.
  
  
  
  The planned median total dose was 70.5 GyE for all tumors and the median doses for the 1st, 2nd, 3rd and 4th treatments were 71.0, 70.0, 70.0, and 69.3 GyE, respectively. There was no severe acute toxicity, and no radiation-induced liver dysfunction (RILD) was observed. The median overall survival (OS) period from the first PBT was 61months (95% CI: 50-71months), and the 2- and 5-year OS rates were 87.5% (95%CI: 80.2-94.8%) and 49.4% (95%CI: 37.6-61.2%), respectively. The maximal delivered dose to the liver ranged from 66.7 to 248.1 GyE (mean: 124.93 GyE) and the mean liver dose ranged from 5.4 to 66.5 GyE (mean: 24.23 GyE).
  
  
  
  Repeated PBT was well tolerated and safe, even though the liver doses in many patients deviated substantially from well-known critical levels for RILD.
authors.affiliation: Department of Radiation Oncology, University of Tsukuba, Japan; Tsukuba Medical Center Hospital, Japan. Electronic address: ooyoshiko@hotmail.com.
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Oshiro
authors.affiliation: Department of Radiation Oncology, University of Tsukuba, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Mizumoto
authors.affiliation: Department of Radiation Oncology, University of Tsukuba, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Okumura
authors.affiliation: Department of Gastroenterology, University of Tsukuba, Japan.
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Fukuda
authors.affiliation: Department of Radiation Oncology, University of Tsukuba, Japan.
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Fukumitsu
authors.affiliation: Department of Gastroenterology, University of Tsukuba, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Abei
authors.affiliation: Department of Radiation Oncology, University of Tsukuba, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ishikawa
authors.affiliation: Department of Radiation Oncology, University of Tsukuba, Japan.
authors.forename: Daichi
authors.initials: D
authors.lastname: Takizawa
authors.affiliation: Department of Radiation Oncology, University of Tsukuba, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Sakurai
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000532:radiotherapy*; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D061766:Proton Therapy / Q000009:adverse effects; D011879:Radiotherapy Dosage; D012189:Retrospective Studies
keywords: Dose–volume histogram (DVH); Hepatocellular carcinoma (HCC); Proton therapy; Radiotherapy; Repeated proton therapy; Repeated radiotherapy