title: Dose-volume histogram analysis of the safety of proton beam therapy for unresectable hepatocellular carcinoma.
abstract: OBJECTIVE
  To evaluate the safety and efficacy of radiotherapy using proton beam (PRT) for unresectable hepatocellular carcinoma.
  
  
  METHODS
  Sixty consecutive patients who underwent PRT between May 1999 and July 2007 were analyzed. There were 42 males and 18 females, with a median age of 70 years (48-92 years). All but 1 patient had a single lesion with a median diameter of 45 mm (20-100 mm). Total PRT dose/fractionation was 76-cobalt Gray equivalent (CGE)/20 fractions in 46 patients, 65 CGE/26 fractions in 11 patients, and 60 CGE/10 fractions in 3 patients. The risk of developing proton-induced hepatic insufficiency (PHI) was estimated using dose-volume histograms and an indocyanine-green retention rate at 15 minutes (ICG R15).
  
  
  RESULTS
  None of the 20 patients with ICG R15 of less than 20% developed PHI, whereas 6 of 8 patients with ICG R15 values of 50% or higher developed PHI. Among 32 patients whose ICG R15 ranged from 20% to 49.9%, PHI was observed only in patients who had received 30 CGE (V30) to more than 25% of the noncancerous parts of the liver (n = 5) Local progression-free and overall survival rates at 3 years were 90% (95% confidence interval [CI], 80-99%) and 56% (95% CI, 43-69%), respectively. A gastrointestinal toxicity of Grade ≥2 was observed in 3 patients.
  
  
  CONCLUSIONS
  ICG R15 and V30 are recommended as useful predictors for the risk of developing PHI, which should be incorporated into multidisciplinary treatment plans for patients with this disease.
authors.affiliation: Division of Particle Therapy and Radiation Oncology, Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwa, Japan. mkawashi@east.ncc.go.jp
authors.forename: Mitsuhiko
authors.initials: M
authors.lastname: Kawashima
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Kohno
authors.forename: Kohei
authors.initials: K
authors.lastname: Nakachi
authors.forename: Teiji
authors.initials: T
authors.lastname: Nishio
authors.forename: Shuichi
authors.initials: S
authors.lastname: Mitsunaga
authors.forename: Masafumi
authors.initials: M
authors.lastname: Ikeda
authors.forename: Masaru
authors.initials: M
authors.lastname: Konishi
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Takahashi
authors.forename: Naoto
authors.initials: N
authors.lastname: Gotohda
authors.forename: Satoko
authors.initials: S
authors.lastname: Arahira
authors.forename: Sadamoto
authors.initials: S
authors.lastname: Zenda
authors.forename: Takashi
authors.initials: T
authors.lastname: Ogino
authors.forename: Taira
authors.initials: T
authors.lastname: Kinoshita
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D018572:Disease-Free Survival; D005260:Female; D048550:Hepatic Insufficiency / Q000209:etiology*; D006801:Humans; D008099:Liver / Q000528:radiation effects*; D008113:Liver Neoplasms / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D061766:Proton Therapy; D011522:Protons / Q000009:adverse effects; D011836:Radiation Tolerance; D011879:Radiotherapy Dosage; D015996:Survival Rate; D047368:Tumor Burden
chemical_list: D011522:Protons