title: Sequential phase I and II trials of stereotactic body radiotherapy for locally advanced hepatocellular carcinoma.
abstract: OBJECTIVE
  To describe outcomes of prospective trials of stereotactic body radiotherapy (SBRT) for hepatocellular carcinoma (HCC).
  
  
  METHODS
  Two trials of SBRT for patients with active HCC unsuitable for standard locoregional therapies were conducted from 2004 to 2010. All patients had Child-Turcotte-Pugh class A disease, with at least 700 mL of non-HCC liver. The SBRT dose range was 24 to 54 Gy in six fractions. Primary end points were toxicity and local control at 1 year (LC1y), defined as no progressive disease (PD) of irradiated HCC by RECIST (Response Evaluation Criteria in Solid Tumors).
  
  
  RESULTS
  A total of 102 patients were evaluable (Trial 1, 2004 to 2007: n = 50; Trial 2, 2007 to 2010: n = 52). Underlying liver disease was hepatitis B in 38% of patients, hepatitis C in 38%, alcohol related in 25%, other in 14%, and none in 7%. Fifty-two percent received prior therapies (no prior sorafenib). TNM stage was III in 66%, and 61% had multiple lesions. Median gross tumor volume was 117.0 mL (range, 1.3 to 1,913.4 mL). Tumor vascular thrombosis (TVT) was present in 55%, and extrahepatic disease was present in 12%. LC1y was 87% (95% CI, 78% to 93%). SBRT dose (hazard ratio [HR] = 0.96; P = .02) and being in Trial 2 (HR = 0.38; P = .03) were associated with LC1y on univariate analysis. Toxicity ≥ grade 3 was seen in 30% of patients. In seven patients (two with TVT PD), death was possibly related to treatment (1.1 to 7.7 months after SBRT). Median overall survival was 17.0 months (95% CI, 10.4 to 21.3 months), for which only TVT (HR = 2.47; P = .01) and being in Trial 2 (HR = 0.49; P = .01) were significant on multivariate analysis.
  
  
  CONCLUSIONS
  These results provide strong rationale for studying SBRT for HCC in a randomized trial.
authors.affiliation: Princess Margaret Hospital, University Health Network, University of Toronto, Canada. abujold.hmr@ssss.gouv.qc.ca
authors.forename: Alexis
authors.initials: A
authors.lastname: Bujold
authors.forename: Christine A
authors.initials: CA
authors.lastname: Massey
authors.forename: John J
authors.initials: JJ
authors.lastname: Kim
authors.forename: James
authors.initials: J
authors.lastname: Brierley
authors.forename: Charles
authors.initials: C
authors.lastname: Cho
authors.forename: Rebecca K S
authors.initials: RK
authors.lastname: Wong
authors.forename: Rob E
authors.initials: RE
authors.lastname: Dinniwell
authors.forename: Zahra
authors.initials: Z
authors.lastname: Kassam
authors.forename: Jolie
authors.initials: J
authors.lastname: Ringash
authors.forename: Bernard
authors.initials: B
authors.lastname: Cummings
authors.forename: Jenna
authors.initials: J
authors.lastname: Sykes
authors.forename: Morris
authors.initials: M
authors.lastname: Sherman
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Knox
authors.forename: Laura A
authors.initials: LA
authors.lastname: Dawson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis / Q000601:surgery*; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000175:diagnosis / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016634:Radiosurgery / Q000379:methods