title: Low-stage medulloblastoma: final analysis of trial comparing standard-dose with reduced-dose neuraxis irradiation.
abstract: OBJECTIVE
  To evaluate prospectively the effects on survival, relapse-free survival, and patterns of relapse of reduced-dose (23.4 Gy in 13 fractions) compared with standard-dose (36 Gy in 20 fractions) neuraxis irradiation in patients 3 to 21 years of age with low-stage medulloblastoma, minimal postoperative residual disease, and no evidence of neuraxis disease.
  
  
  METHODS
  The Pediatric Oncology Group and Children's Cancer Group randomized 126 patients to the study. All patients received posterior fossa irradiation to a total dose of 54 Gy in addition to the neuraxis treatment. Patients were staged postoperatively with contrast-enhanced cranial computed tomography, myelography, and CSF cytology. Of the registered patients, 38 were ineligible.
  
  
  RESULTS
  The planned interim analysis that resulted in closure of the protocol showed that patients randomized to the reduced neuraxis treatment had increased frequency of relapse. In the final analysis, eligible patients receiving standard-dose neuraxis irradiation had 67% event-free survival (EFS) at 5 years (SE = 7.4%), whereas eligible patients receiving reduced-dose neuraxis irradiation had 52% event-free survival at 5 years (SE = 7.7%) (P =.080). At 8 years, the respective EFS proportions were also 67% (SE = 8.8%) and 52% (SE = 11%) (P =.141). These data confirm the original one-sided conclusions but suggest that differences are less marked with time.
  
  
  CONCLUSIONS
  Reduced-dose neuraxis irradiation (23.4 Gy) is associated with increased risk of early relapse, early isolated neuraxis relapse, and lower 5-year EFS and overall survival than standard irradiation (36 Gy). The 5-year EFS for patients receiving standard-dose irradiation is suboptimal, and improved techniques and/or therapies are needed to improve ultimate outcome. Chemotherapy may contribute to this improvement.
authors.affiliation: Pediatric Oncology Group, Chicago, IL 60611, USA. pthomasmd@aol.com
authors.forename: P R
authors.initials: PR
authors.lastname: Thomas
authors.forename: M
authors.initials: M
authors.lastname: Deutsch
authors.forename: J L
authors.initials: JL
authors.lastname: Kepner
authors.forename: J M
authors.initials: JM
authors.lastname: Boyett
authors.forename: J
authors.initials: J
authors.lastname: Krischer
authors.forename: P
authors.initials: P
authors.lastname: Aronin
authors.forename: L
authors.initials: L
authors.lastname: Albright
authors.forename: J C
authors.initials: JC
authors.lastname: Allen
authors.forename: R J
authors.initials: RJ
authors.lastname: Packer
authors.forename: R
authors.initials: R
authors.lastname: Linggood
authors.forename: R
authors.initials: R
authors.lastname: Mulhern
authors.forename: J A
authors.initials: JA
authors.lastname: Stehbens
authors.forename: J
authors.initials: J
authors.lastname: Langston
authors.forename: P
authors.initials: P
authors.lastname: Stanley
authors.forename: P
authors.initials: P
authors.lastname: Duffner
authors.forename: L
authors.initials: L
authors.lastname: Rorke
authors.forename: J
authors.initials: J
authors.lastname: Cherlow
authors.forename: H S
authors.initials: HS
authors.lastname: Friedman
authors.forename: J L
authors.initials: JL
authors.lastname: Finlay
authors.forename: T J
authors.initials: TJ
authors.lastname: Vietti
authors.forename: L E
authors.initials: LE
authors.lastname: Kun
mesh_terms: D000293:Adolescent; D000328:Adult; D002490:Central Nervous System / Q000528:radiation effects*; D016543:Central Nervous System Neoplasms / Q000556:secondary; D002648:Child; D002675:Child, Preschool; D003388:Cranial Fossa, Posterior; D018572:Disease-Free Survival; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D015192:Infratentorial Neoplasms / Q000532:radiotherapy* / Q000601:surgery; D008297:Male; D008527:Medulloblastoma / Q000532:radiotherapy* / Q000601:surgery; D009367:Neoplasm Staging; D018365:Neoplasm, Residual / Q000532:radiotherapy; D011446:Prospective Studies; D011879:Radiotherapy Dosage; D018714:Radiotherapy, Adjuvant; D012008:Recurrence; D019292:Skull Base Neoplasms / Q000532:radiotherapy* / Q000601:surgery; D018709:Statistics, Nonparametric; D017211:Treatment Failure