title: Impact of cranial radiotherapy on central nervous system prophylaxis in children and adolescents with central nervous system-negative stage III or IV lymphoblastic lymphoma.
abstract: OBJECTIVE
  In the Non-Hodgkin's Lymphoma-Berlin-Frankfurt-Munster (NHL-BFM) 95 trial, we tested, against the historical control of the combined trials NHL-BFM90 and NHL-BFM86, whether prophylactic cranial radiotherapy (PCRT) can be omitted for CNS-negative patients with stage III or IV lymphoblastic lymphoma (LBL) with sufficient early response.
  
  
  METHODS
  Apart from the removal of PCRT in NHL-BFM95, the chemotherapy of the three trials was identical except for the amount of l-asparaginase and daunorubicin during induction. The therapy in NHL-BFM95 was accepted to be noninferior when compared with trials NHL-BFM90/86 if the lower limit of the one-sided 95% CI for the difference in the 2-year probability of event-free-survival (pEFS) between target patients of NHL-BFM95 and the historical controls of NHL-BFM90/86 did not exceed -14%. The target patient group consisted of stage III and IV patients who were CNS negative and responded well to induction therapy.
  
  
  RESULTS
  The number of target patients was 156 in NHL-BFM95 (median age, 8.6 years; range, 0.2 to 19.5 years) and 163 in NHL-BFM90/86 (median age, 8.4 years; range, 0.6 to 16.6 years). For the target group, the pEFS rates at 2 and 5 years were 86% +/- 3% and 82% +/- 3%, respectively, in NHL-BFM95 (median follow-up time, 5.1 years; range, 2.1 to 9.1 years) compared with 91% +/- 2% and 88% +/- 3%, respectively in NHL-BFM90/86 (median follow-up time, 10.7 years; range, 5 to 15.4 years). The lower limit of the one-sided 95% CI for the difference in pEFS was -11% at 2 years and -13% at 5 years. In NHL-BFM95, one isolated and two combined CNS relapses occurred compared with one combined CNS relapse in NHL-BFM90/86. Five-year disease-free-survival rate was 88% +/- 3% in NHL-BFM95 compared with 91% +/- 2% in NHL-BFM90/86.
  
  
  CONCLUSIONS
  For CNS-negative patients with stage III or IV LBL and sufficient response to induction therapy, treatment without PCRT may be noninferior to treatment including PCRT.
authors.affiliation: Department of Pediatric Hematology and Oncology, Children's University Hospital, Giessen, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Burkhardt
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Woessmann
authors.forename: Martin
authors.initials: M
authors.lastname: Zimmermann
authors.forename: Udo
authors.initials: U
authors.lastname: Kontny
authors.forename: Josef
authors.initials: J
authors.lastname: Vormoor
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Doerffel
authors.forename: Georg
authors.initials: G
authors.lastname: Mann
authors.forename: Guenter
authors.initials: G
authors.lastname: Henze
authors.forename: Felix
authors.initials: F
authors.lastname: Niggli
authors.forename: Wolf-Dieter
authors.initials: WD
authors.lastname: Ludwig
authors.forename: Dirk
authors.initials: D
authors.lastname: Janssen
authors.forename: Hansjoerg
authors.initials: H
authors.lastname: Riehm
authors.forename: Martin
authors.initials: M
authors.lastname: Schrappe
authors.forename: Alfred
authors.initials: A
authors.lastname: Reiter
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001215:Asparaginase / Q000008:administration & dosage; D001932:Brain Neoplasms / Q000517:prevention & control* / Q000556:secondary; D002648:Child; D016371:Cranial Irradiation; D003630:Daunorubicin / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D009367:Neoplasm Staging; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000473:pathology*; D012074:Remission Induction; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D001215:Asparaginase; D003630:Daunorubicin