title: Acute Toxicity Grade 3 and 4 After Irradiation in Children and Adolescents: Results From the IPPARCA Collaboration.
abstract: OBJECTIVE
  In the context of oncologic therapy for children, radiation therapy is frequently indicated. This study identified the frequency of and reasons for the development of high-grade acute toxicity and possible sequelae.
  
  
  METHODS
  Irradiated children have been prospectively documented since 2001 in the Registry for the Evaluation of Side Effects After Radiation in Childhood and Adolescence (RiSK) database in Germany and since 2008 in the registry for radiation therapy toxicity (RADTOX) in Sweden. Data were collected using standardized, published forms. Toxicity classification was based on Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria.
  
  
  RESULTS
  As of June 2013, 1500 children have been recruited into the RiSK database and 485 into the RADTOX registry leading to an analysis population of 1359 patients (age range 0-18). A total of 18.9% (n=257) of all investigated patients developed high-grade acute toxicity (grades 3/4). High-grade toxicity of the bone marrow was documented for 63.8% (n=201) of those patients, oral mucositis for 7.6% (n=24), and dermatitis for 7.6% (n=24). Patients with high-grade acute toxicity received concomitant chemotherapy more frequently (56%) than patients with no or lower acute toxicity (31.5%). In multivariate analyses, concomitant chemotherapy, diagnosis of Ewing sarcoma, and total radiation dose showed a statistically noticeable effect (P≤.05) on acute toxicity, whereas age, concomitant chemotherapy, Hodgkin lymphoma, Ewing sarcoma, total radiation dose, and acute toxicity influenced the time until maximal late toxicity.
  
  
  CONCLUSIONS
  Generally, high-grade acute toxicity after irradiation in children and adolescence occurs in a moderate proportion of patients (18.9%). As anticipated, the probability of acute toxicity appeared to depend on the prescribed dose as well as concomitant chemotherapy. The occurrence of chronic toxicity correlates with the prior acute toxicity grade. Age seems to influence the time until maximal late toxicity but not the development of acute toxicity.
authors.affiliation: Department of Radiation Oncology, University Hospital of Muenster, Muenster, Germany.
authors.forename: Caroline
authors.initials: C
authors.lastname: Pixberg
authors.affiliation: Institute of Biostatistics and Clinical Research, University of Muenster, Muenster, Germany.
authors.forename: Raphael
authors.initials: R
authors.lastname: Koch
authors.affiliation: Department of Radiation Oncology, University Hospital of Muenster, Muenster, Germany; Department of Radiation Oncology, University of Koeln, Koeln, Germany. Electronic address: Hans.Eich@ukmuenster.de.
authors.forename: Hans Theodor
authors.initials: HT
authors.lastname: Eich
authors.affiliation: Department of Oncology, University Hospital, Uppsala, Sweden.
authors.forename: Ulla
authors.initials: U
authors.lastname: Martinsson
authors.affiliation: Department of Radiation Physics, Skåne University Hospital, Lund, Sweden.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Kristensen
authors.affiliation: Department of Radiation Oncology, University Hospital of Duesseldorf, Duesseldorf, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Matuschek
authors.affiliation: Department of Radiation Oncology, University Hospital of Leipzig, Leipzig, Germany.
authors.forename: Rolf-Dieter
authors.initials: RD
authors.lastname: Kortmann
authors.affiliation: Department of Radiation Oncology, University of Regensburg, Regensburg, Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Pohl
authors.affiliation: Department of Radiation Oncology, University Hospital of Muenster, Muenster, Germany.
authors.forename: Khaled
authors.initials: K
authors.lastname: Elsayad
authors.affiliation: Department of Radiation Oncology, Medical School Hannover, Hannover, Germany.
authors.forename: Hans
authors.initials: H
authors.lastname: Christiansen
authors.affiliation: Department of Radiation Oncology, University Hospital of Muenster, Muenster, Germany.
authors.forename: Normann
authors.initials: N
authors.lastname: Willich
authors.affiliation: Department of Radiation Sciences, Umeå University, Umeå, Sweden.
authors.forename: Jack
authors.initials: J
authors.lastname: Lindh
authors.affiliation: Department of Radiation Oncology, University Hospital of Muenster, Muenster, Germany; Department of Radiation Oncology, Medical School Hannover, Hannover, Germany.
authors.forename: Diana
authors.initials: D
authors.lastname: Steinmann
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000367:Age Factors; D001853:Bone Marrow / Q000528:radiation effects*; D059248:Chemoradiotherapy / Q000009:adverse effects* / Q000706:statistics & numerical data; D002648:Child; D002675:Child, Preschool; D005260:Female; D005858:Germany; D006689:Hodgkin Disease / Q000532:radiotherapy; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008527:Medulloblastoma / Q000532:radiotherapy; D011446:Prospective Studies; D011832:Radiation Injuries / Q000453:epidemiology / Q000209:etiology* / Q000473:pathology; D011855:Radiodermatitis / Q000453:epidemiology / Q000209:etiology* / Q000473:pathology; D011879:Radiotherapy Dosage; D012042:Registries / Q000706:statistics & numerical data; D012208:Rhabdomyosarcoma / Q000532:radiotherapy; D012512:Sarcoma, Ewing / Q000532:radiotherapy; D013280:Stomatitis / Q000453:epidemiology / Q000209:etiology* / Q000473:pathology; D013548:Sweden