title: Phase I study of individualized stereotactic body radiotherapy for hepatocellular carcinoma and intrahepatic cholangiocarcinoma.
abstract: OBJECTIVE
  To report outcomes of a phase I study of individualized stereotactic body radiotherapy treatment (SBRT) for unresectable hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (IHC).
  
  
  METHODS
  Patients with unresectable HCC or IHC, and who are not suitable for standard therapies, were eligible for six-fraction SBRT during 2 weeks. Radiation dose was dependent on the volume of liver irradiated and the estimated risk of liver toxicity based on a normal tissue complication model. Toxicity risk was escalated from 5% to 10% and 20%, within three liver volume-irradiated strata, provided at least three patients were without toxicity at 3 months after SBRT.
  
  
  RESULTS
  Forty-one patients with unresectable Child-Pugh A HCC (n = 31) or IHC (n = 10) completed six-fraction SBRT. Five patients (12%) had grade 3 liver enzymes at baseline. The median tumor size was 173 mL (9 to 1,913 mL). The median dose was 36.0 Gy (24.0 to 54.0 Gy). No radiation-induced liver disease or treatment-related grade 4/5 toxicity was seen within 3 months after SBRT. Grade 3 liver enzymes were seen in five patients (12%). Two patients (5%) with IHC developed transient biliary obstruction after the first few fractions. Seven patients (five HCC, two IHC) had decline in liver function from Child-Pugh class A to B within 3 months after SBRT. Median survival of HCC and IHC patients was 11.7 months (95% CI, 9.2 to 21.6 months) and 15.0 months (95% CI, 6.5 to 29.0 months), respectively.
  
  
  CONCLUSIONS
  Individualized six-fraction SBRT is a safe treatment for unresectable HCC and IHC.
authors.affiliation: Princess Margaret Hospital, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Regina V
authors.initials: RV
authors.lastname: Tse
authors.forename: Maria
authors.initials: M
authors.lastname: Hawkins
authors.forename: Gina
authors.initials: G
authors.lastname: Lockwood
authors.forename: John J
authors.initials: JJ
authors.lastname: Kim
authors.forename: Bernard
authors.initials: B
authors.lastname: Cummings
authors.forename: Jennifer
authors.initials: J
authors.lastname: Knox
authors.forename: Morris
authors.initials: M
authors.lastname: Sherman
authors.forename: Laura A
authors.initials: LA
authors.lastname: Dawson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000401:mortality / Q000532:radiotherapy*; D018281:Cholangiocarcinoma / Q000401:mortality / Q000532:radiotherapy*; D005260:Female; D006471:Gastrointestinal Hemorrhage / Q000209:etiology; D006801:Humans; D007415:Intestinal Obstruction / Q000209:etiology; D008113:Liver Neoplasms / Q000401:mortality / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D011832:Radiation Injuries / Q000209:etiology; D016634:Radiosurgery / Q000009:adverse effects; D011879:Radiotherapy Dosage; D015996:Survival Rate; D016896:Treatment Outcome