title: Necrosis after craniospinal irradiation: results from a prospective series of children with central nervous system embryonal tumors.
abstract: OBJECTIVE
  Necrosis of the central nervous system (CNS) is a known complication of craniospinal irradiation (CSI) in children with medulloblastoma and similar tumors. We reviewed the incidence of necrosis in our prospective treatment series.
  
  
  METHODS
  Between 1996 and 2009, 236 children with medulloblastoma (n = 185) or other CNS embryonal tumors (n = 51) received postoperative CSI followed by dose-intense cyclophosphamide, vincristine, and cisplatin. Average risk cases (n = 148) received 23.4 Gy CSI, 36 Gy to the posterior fossa, and 55.8 Gy to the primary; after 2003, the treatment was 23.4 Gy CSI and 55.8 Gy to the primary. All high-risk cases (n = 88) received 36-39.6 Gy CSI and 55.8 Gy primary. The primary site clinical target volume margin was 2 cm (pre-2003) or 1 cm (post-2003). With competing risk of death by any cause, we determined the cumulative incidence of necrosis.
  
  
  RESULTS
  With a median follow-up of 52 months (range, 4-163 months), eight cases of necrosis were documented. One death was attributed. The median time to the imaging evidence was 4.8 months and to symptoms 6.0 months. The cumulative incidence at 5 years was 3.7% ± 1.3% (n = 236) for the entire cohort and 4.4% ± 1.5% (n = 196) for infratentorial tumor location. The mean relative volume of infratentorial brain receiving high-dose irradiation was significantly greater for patients with necrosis than for those without: ≥ 50 Gy (92.12% ± 4.58% vs 72.89% ± 1.96%; P=.0337), ≥ 52 Gy (88.95% ± 5.50% vs 69.16% ± 1.97%; P=.0275), and ≥ 54 Gy (82.28% ± 7.06% vs 63.37% ± 1.96%; P=.0488), respectively.
  
  
  CONCLUSIONS
  Necrosis in patients with CNS embryonal tumors is uncommon. When competing risks are considered, the incidence is 3.7% at 5 years. The volume of infratentorial brain receiving greater than 50, 52, and 54 Gy, respectively, is predictive for necrosis.
authors: Cleveland Clinic, Cleveland, OH, USA.
authors: Erin S
authors: ES
authors: Murphy
authors: Thomas E
authors: TE
authors: Merchant
authors: Shengjie
authors: S
authors: Wu
authors: Xiaoping
authors: X
authors: Xiong
authors: Renin
authors: R
authors: Lukose
authors: Karen D
authors: KD
authors: Wright
authors: Ibrahim
authors: I
authors: Qaddoumi
authors: Gregory T
authors: GT
authors: Armstrong
authors: Alberto
authors: A
authors: Broniscer
authors: Amar
authors: A
authors: Gajjar
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001921:Brain / Q000473:pathology / Q000528:radiation effects*; D016543:Central Nervous System Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy*; D002528:Cerebellar Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy; D002648:Child; D002675:Child, Preschool; D002945:Cisplatin / Q000008:administration & dosage; D016371:Cranial Irradiation / Q000009:adverse effects*; D003520:Cyclophosphamide / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008297:Male; D008527:Medulloblastoma / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy*; D009336:Necrosis / Q000453:epidemiology / Q000209:etiology / Q000473:pathology; D009373:Neoplasms, Germ Cell and Embryonal / Q000188:drug therapy / Q000532:radiotherapy*; D011446:Prospective Studies; D011832:Radiation Injuries / Q000150:complications* / Q000473:pathology; D011879:Radiotherapy Dosage; D014750:Vincristine / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D014750:Vincristine; D003520:Cyclophosphamide; D002945:Cisplatin