title: Phase I study of individualized stereotactic body radiotherapy of liver metastases.
abstract: OBJECTIVE
  To report on the outcomes of a phase I study of stereotactic body radiotherapy (SBRT) for treatment of liver metastases.
  
  
  METHODS
  Patients with liver metastases that were inoperable or medically unsuitable for resection, and who were not candidates for standard therapies, were eligible for this phase I study of individualized SBRT. Individualized radiation doses were chosen to maintain the same nominal risk of radiation-induced liver disease (RILD) for three estimated risk levels (5%, 10%, and 20%). Additional patients were treated at the maximal study dose (MSD) in an expanded cohort. Median SBRT dose was 41.8 Gy (range, 27.7 to 60 Gy) in six fractions over 2 weeks.
  
  
  RESULTS
  Sixty-eight patients with inoperable colorectal (n = 40), breast (n = 12), or other (n = 16) liver metastases were treated. Median tumor volume was 75.2 mL (range, 1.19 to 3,090 mL). The highest RILD risk level investigated was safe, with no dose-limiting toxicity. Two grade 3 liver enzyme changes occurred, but no RILD or other grade 3 to 5 liver toxicity was seen, for a low estimated risk of serious liver toxicity (95% CI, 0 to 5.3%). Six (9%) acute grade 3 toxicities (two gastritis, two nausea, lethargy, and thrombocytopenia) and one (1%) grade 4 toxicity (thrombocytopenia) were seen. The 1-year local control rate was 71% (95 CI, 58% to 85%). The median overall survival was 17.6 months (95% CI, 10.4 to 38.1 months).
  
  
  CONCLUSIONS
  Individualized six-fraction liver metastases SBRT is safe, with sustained local control observed in the majority of patients.
authors.affiliation: Radiation Medicine Program, Department of Biostatistics and Medical Oncology, Princess Margaret Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Mark T
authors.initials: MT
authors.lastname: Lee
authors.forename: John J
authors.initials: JJ
authors.lastname: Kim
authors.forename: Robert
authors.initials: R
authors.lastname: Dinniwell
authors.forename: James
authors.initials: J
authors.lastname: Brierley
authors.forename: Gina
authors.initials: G
authors.lastname: Lockwood
authors.forename: Rebecca
authors.initials: R
authors.lastname: Wong
authors.forename: Bernard
authors.initials: B
authors.lastname: Cummings
authors.forename: Jolie
authors.initials: J
authors.lastname: Ringash
authors.forename: Regina V
authors.initials: RV
authors.lastname: Tse
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Knox
authors.forename: Laura A
authors.initials: LA
authors.lastname: Dawson
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D003131:Combined Modality Therapy; D019583:Dose Fractionation, Radiation; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000401:mortality / Q000556:secondary* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D016634:Radiosurgery / Q000009:adverse effects* / Q000379:methods*
chemical_list: D000970:Antineoplastic Agents