title: Hepatotoxicity after liver irradiation in children and adolescents : results from the RiSK.
abstract: OBJECTIVE
  The aim of this study was to evaluate acute and late radiotherapy-associated hepatotoxicity in consideration of dose-volume effects and liver function in childhood and adolescence.
  
  
  METHODS
  Since 2001, irradiated children and adolescents in Germany have been prospectively documented in the "Register of Treatment-Associated Late Effects After Radiotherapy of Malignant Diseases in Childhood and Adolescence (RiSK)" using standardized forms. Toxicity was graded according to the Radiation Therapy Oncology Group (RTOG) criteria.
  
  
  RESULTS
  Until April 2012, 1,392 children and adolescents from 62 radiotherapy centers were recruited. In all, 216 patients underwent irradiation of the liver (median age 9 years, range 1-18 years, 70 patients with total-body irradiation, TBI). For 75 % of patients without TBI, information on acute toxicity of the liver was available: 24 patients had acute toxicity of grade 1-4 (grade 1, 2, and 4, in 20, 3, and 1 patient, respectively), including five patients receiving simultaneous hepatotoxic chemotherapy. Information on late toxicity was documented in 465 forms from 216 patients, with a median follow-up of 2 years. A maximum grade of toxicity of ≥ 0 occurred in 18 patients over time (with grade 1, 2, and 3 toxicity occurring in 15, 2, and 1 patient, respectively), including three patients (17 %) with TBI. One of them received simultaneous hepatotoxic chemotherapy. In multivariable analysis, volume-dose correlations showed no statistically noticeable effect on acute or chronic toxicity.
  
  
  CONCLUSIONS
  Only low hepatotoxicity developed in children after irradiation of various abdominal and thoracic tumors. Due to the low radiation doses to the liver (median liver dose = 5 Gy) and the low toxicities that were consecutively observed, dose-volume curves for liver toxicity could not be established. These findings reflect the cautious attitude of radiation oncologists in terms of attributable liver doses in the treatment of the investigated tumor entities. It offers the option of increasing these conservative doses if tumor control is necessary.
authors.affiliation: Department of Radiotherapy and Special Oncology, Medical School Hannover, Hannover, Germany.
authors.forename: Pascal
authors.initials: P
authors.lastname: Rösler
authors.forename: Hans
authors.initials: H
authors.lastname: Christiansen
authors.forename: Rolf-Dieter
authors.initials: RD
authors.lastname: Kortmann
authors.forename: Carmen
authors.initials: C
authors.lastname: Martini
authors.forename: Christiane
authors.initials: C
authors.lastname: Matuschek
authors.forename: Frank
authors.initials: F
authors.lastname: Meyer
authors.forename: Christian
authors.initials: C
authors.lastname: Rübe
authors.forename: Thorsten
authors.initials: T
authors.lastname: Langer
authors.forename: Raphael
authors.initials: R
authors.lastname: Koch
authors.forename: Hans Theodor
authors.initials: HT
authors.lastname: Eich
authors.forename: Normann
authors.initials: N
authors.lastname: Willich
authors.forename: Diana
authors.initials: D
authors.lastname: Steinmann
mesh_terms: D000293:Adolescent; D000970:Antineoplastic Agents / Q000009:adverse effects; D059248:Chemoradiotherapy / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D008099:Liver / Q000528:radiation effects*; D008111:Liver Function Tests; D008297:Male; D011446:Prospective Studies; D011832:Radiation Injuries / Q000175:diagnosis / Q000209:etiology*; D014916:Whole-Body Irradiation
chemical_list: D000970:Antineoplastic Agents