title: Intensified external-beam radiation therapy improves the outcome of stage 4 neuroblastoma in children > 1 year with residual local disease.
abstract: OBJECTIVE
  In neuroblastoma, the value of radiation therapy in high-intensive first-line treatment protocols is still not exactly known but radiation-associated long-term effects need to be considered. The impact of external-beam radiation therapy (EBRT) on event-free (EFS) and overall survival (OS) of stage 4 neuroblastoma patients of the NB97 trial was analyzed.
  
  
  METHODS
  The authors retrospectively analyzed data of 110 stage 4 neuroblastoma patients > or = 1 year who underwent induction therapy and high-dose chemotherapy with stem cell transplantation without relapse. Intensified local EBRT (36 Gy) of the residual tumor volume was reserved for patients with residual viable tumor documented by MRI and corresponding metaiodobenzylguanidine (MIBG) uptake.
  
  
  RESULTS
  13 patients who received EBRT for local residual disease had similar outcome (3-year EFS 85 +/- 10%, 3-year OS 92 +/- 7%) as 74 patients without any MIBG residual (3-year EFS 61 +/- 6%, 3-year OS 75 +/- 6%). Outcome was worse in 23 children without EBRT to residual primary (3-year EFS 25 +/- 10%, 3-year OS 51 +/- 11%). Separate analysis of 14 patients with isolated localized residual disease found far better outcome of eight patients with EBRT (3-year EFS 100%, 3-year OS 100%) compared to six patients without EBRT (3-year EFS 20 +/- 18%, 3-year OS 20 +/- 18%). Multivariate analysis identified EBRT as influential on EFS (hazard ratio 0.27) and OS (hazard ratio 0.17) in addition to MYCN amplification and presence of primary tumor site MIBG residual.
  
  
  CONCLUSIONS
  EBRT appeared effective in high-intensive treatment of stage 4 neuroblastoma. It seems to compensate the disadvantage of incomplete response to induction chemotherapy. These retrospective results need confirmation by a prospective randomized trial.
authors.affiliation: Children's Hospital, University of Cologne, Germany. thorsten.simon@uk-koeln.de
authors.forename: Thorsten
authors.initials: T
authors.lastname: Simon
authors.forename: Barbara
authors.initials: B
authors.lastname: Hero
authors.forename: Rudolf
authors.initials: R
authors.lastname: Bongartz
authors.forename: Matthias
authors.initials: M
authors.lastname: Schmidt
authors.forename: Rolf Peter
authors.initials: RP
authors.lastname: Müller
authors.forename: Frank
authors.initials: F
authors.lastname: Berthold
mesh_terms: D002648:Child; D002675:Child, Preschool; D018849:Controlled Clinical Trials as Topic; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000473:pathology* / Q000532:radiotherapy*; D016017:Odds Ratio; D011879:Radiotherapy Dosage; D050397:Radiotherapy, Intensity-Modulated / Q000379:methods*; D012074:Remission Induction; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome