title: Early clinical outcomes demonstrate preserved cognitive function in children with average-risk medulloblastoma when treated with hyperfractionated radiation therapy.
abstract: OBJECTIVE
  To report on acute toxicity, longitudinal cognitive function, and early clinical outcomes in children with average-risk medulloblastoma.
  
  
  METHODS
  Twenty children ≥ 5 years of age classified as having average-risk medulloblastoma were accrued on a prospective protocol of hyperfractionated radiation therapy (HFRT) alone. Radiotherapy was delivered with two daily fractions (1 Gy/fraction, 6 to 8 hours apart, 5 days/week), initially to the neuraxis (36 Gy/36 fractions), followed by conformal tumor bed boost (32 Gy/32 fractions) for a total tumor bed dose of 68 Gy/68 fractions over 6 to 7 weeks. Cognitive function was prospectively assessed longitudinally (pretreatment and at specified posttreatment follow-up visits) with the Wechsler Intelligence Scale for Children to give verbal quotient, performance quotient, and full-scale intelligence quotient (FSIQ).
  
  
  RESULTS
  The median age of the study cohort was 8 years (range, 5-14 years), representing a slightly older cohort. Acute hematologic toxicity was mild and self-limiting. Eight (40%) children had subnormal intelligence (FSIQ <85), including 3 (15%) with mild mental retardation (FSIQ 56-70) even before radiotherapy. Cognitive functioning for all tested domains was preserved in children evaluable at 3 months, 1 year, and 2 years after completion of HFRT, with no significant decline over time. Age at diagnosis or baseline FSIQ did not have a significant impact on longitudinal cognitive function. At a median follow-up time of 33 months (range, 16-58 months), 3 patients had died (2 of relapse and 1 of accidental burns), resulting in 3-year relapse-free survival and overall survival of 83.5% and 83.2%, respectively.
  
  
  CONCLUSIONS
  HFRT without upfront chemotherapy has an acceptable acute toxicity profile, without an unduly increased risk of relapse, with preserved cognitive functioning in children with average-risk medulloblastoma.
authors.affiliation: Department of Radiation Oncology, Advanced Centre for Treatment Research and Education in Cancer and Tata Memorial Hospital, Mumbai, India. tejpalgupta@rediffmail.com
authors.forename: Tejpal
authors.initials: T
authors.lastname: Gupta
authors.forename: Rakesh
authors.initials: R
authors.lastname: Jalali
authors.forename: Savita
authors.initials: S
authors.lastname: Goswami
authors.forename: Vimoj
authors.initials: V
authors.lastname: Nair
authors.forename: Aliasgar
authors.initials: A
authors.lastname: Moiyadi
authors.forename: Sridhar
authors.initials: S
authors.lastname: Epari
authors.forename: Rajiv
authors.initials: R
authors.lastname: Sarin
mesh_terms: D000293:Adolescent; D000367:Age Factors; D002528:Cerebellar Neoplasms / Q000401:mortality / Q000532:radiotherapy* / Q000601:surgery; D002648:Child; D002675:Child, Preschool; D003071:Cognition / Q000502:physiology / Q000528:radiation effects*; D019583:Dose Fractionation, Radiation; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007360:Intelligence; D007361:Intelligence Tests; D008297:Male; D008527:Medulloblastoma / Q000401:mortality / Q000532:radiotherapy* / Q000601:surgery; D009364:Neoplasm Recurrence, Local; D011446:Prospective Studies; D016019:Survival Analysis