title: Sequencing of local therapy affects the pattern of treatment failure and survival in children with atypical teratoid rhabdoid tumors of the central nervous system.
abstract: OBJECTIVE
  To assess the pattern of treatment failure associated with current therapeutic paradigms for childhood atypical teratoid rhabdoid tumors (AT/RT).
  
  
  METHODS
  Pediatric patients with AT/RT of the central nervous system treated at our institution between 1987 and 2007 were retrospectively evaluated. Overall survival (OS), progression-free survival, and cumulative incidence of local failure were correlated with age, sex, tumor location, extent of disease, and extent of surgical resection. Radiotherapy (RT) sequencing, chemotherapy, dose, timing, and volume administered after resection were also evaluated.
  
  
  RESULTS
  Thirty-one patients at a median age of 2.3 years at diagnosis (range, 0.45-16.87 years) were enrolled into protocols that included risk- and age-stratified RT. Craniospinal irradiation with focal tumor bed boost (median dose, 54 Gy) was administered to 18 patients. Gross total resection was achieved in 16. Ten patients presented with metastases at diagnosis. RT was delayed more than 3 months in 20 patients and between 1 and 3 months in 4; 7 patients received immediate postoperative irradiation preceding high-dose alkylator-based chemotherapy. At a median follow-up of 48 months, the cumulative incidence of local treatment failure was 37.5% ± 9%; progression-free survival was 33.2% ± 10%; and OS was 53.5% ± 10%. Children receiving delayed RT (≥1 month postoperatively) were more likely to experience local failure (hazard ratio [HR] 1.23, p = 0.007); the development of distant metastases before RT increased the risk of progression (HR 3.49, p = 0.006); and any evidence of disease progressionbefore RT decreased OS (HR 20.78, p = 0.004). Disease progression occurred in 52% (11/21) of children with initially localized tumors who underwent gross total resection, and the progression rate increased proportionally with increasing delay from surgery to RT.
  
  
  CONCLUSIONS
  Delayed RT is associated with a higher rate of local and metastatic disease progression in children with AT/RT. Current treatment regimens for pediatric patients with AT/RT are distinctly age stratified; novel protocols investigating RT volumes and sequencing are needed.
authors: Department of Radiological Sciences, St. Jude Children's Research Hospital, Memphis, TN, USA. atmaram.pai-panandiker@stjude.org
authors: Atmaram S
authors: AS
authors: Pai Panandiker
authors: Thomas E
authors: TE
authors: Merchant
authors: Chris
authors: C
authors: Beltran
authors: Shengjie
authors: S
authors: Wu
authors: Shelly
authors: S
authors: Sharma
authors: Frederick A
authors: FA
authors: Boop
authors: Jesse J
authors: JJ
authors: Jenkins
authors: Kathleen J
authors: KJ
authors: Helton
authors: Karen D
authors: KD
authors: Wright
authors: Alberto
authors: A
authors: Broniscer
authors: Larry E
authors: LE
authors: Kun
authors: Amar
authors: A
authors: Gajjar
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