title: Population-based risks of CNS tumors in survivors of childhood cancer: the British Childhood Cancer Survivor Study.
abstract: OBJECTIVE
  CNS tumors are the most common second primary neoplasm (SPN) observed after childhood cancer in Britain, but the relationship of risk to doses of previous radiotherapy and chemotherapy is uncertain.
  
  
  METHODS
  The British Childhood Cancer Survivor Study is a national, population-based, cohort study of 17,980 individuals surviving at least 5 years after diagnosis of childhood cancer. Linkage to national, population-based cancer registries identified 247 SPNs of the CNS. Cohort and nested case-control studies were undertaken.
  
  
  RESULTS
  There were 137 meningiomas, 73 gliomas, and 37 other CNS neoplasms included in the analysis. The risk of meningioma increased strongly, linearly, and independently with each of dose of radiation to meningeal tissue and dose of intrathecal methotrexate. Those whose meningeal tissue received 0.01 to 9.99, 10.00 to 19.99, 20.00 to 29.99, 30.00 to 39.99 and≥40 Gy had risks that were two-fold, eight-fold, 52-fold, 568-fold, and 479-fold, respectively, the risks experienced by those whose meningeal tissue was unexposed. The risk of meningioma among individuals receiving 1 to 39,40 to 69, and at least 70 mg/m2 of intrathecal methotrexate was 15-fold, 11-fold, and 36-fold, respectively, the risk experienced by those unexposed. The standardized incidence ratio for gliomas was 10.8 (95% CI, 8.5 to 13.6). The risk of glioma/primitive neuroectodermal tumors increased linearly with dose of radiation, and those who had CNS tissue exposed to at least 40 Gy experienced a risk four-fold that experienced by those who had CNS tissue unexposed.
  
  
  CONCLUSIONS
  The largest-ever study, to our knowledge, of CNS tumors in survivors of childhood cancer indicates that the risk of meningioma increases rapidly with increased dose of radiation to meningeal tissue and with increased dose of intrathecal methotrexate.
authors.affiliation: Centre for Childhood Cancer Survivor Studies, School of Health and Population Sciences, University of Birmingham, Public Health Building, Edgbaston, Birmingham, B15 2TT, United Kingdom.
authors.forename: Aliki J
authors.initials: AJ
authors.lastname: Taylor
authors.forename: Mark P
authors.initials: MP
authors.lastname: Little
authors.forename: David L
authors.initials: DL
authors.lastname: Winter
authors.forename: Elaine
authors.initials: E
authors.lastname: Sugden
authors.forename: David W
authors.initials: DW
authors.lastname: Ellison
authors.forename: Charles A
authors.initials: CA
authors.lastname: Stiller
authors.forename: Marilyn
authors.initials: M
authors.lastname: Stovall
authors.forename: Clare
authors.initials: C
authors.lastname: Frobisher
authors.forename: Emma R
authors.initials: ER
authors.lastname: Lancashire
authors.forename: Raoul C
authors.initials: RC
authors.lastname: Reulen
authors.forename: Michael M
authors.initials: MM
authors.lastname: Hawkins
mesh_terms: D000328:Adult; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects*; D016022:Case-Control Studies; D016543:Central Nervous System Neoplasms / Q000453:epidemiology* / Q000209:etiology / Q000235:genetics; D002648:Child; D015331:Cohort Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007278:Injections, Spinal; D008579:Meningioma / Q000453:epidemiology / Q000209:etiology / Q000235:genetics; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects*; D009381:Neoplasms, Radiation-Induced / Q000453:epidemiology* / Q000209:etiology / Q000235:genetics; D016609:Neoplasms, Second Primary / Q000453:epidemiology* / Q000209:etiology / Q000235:genetics; D011878:Radiotherapy / Q000009:adverse effects; D012307:Risk Factors; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D000964:Antimetabolites, Antineoplastic; D008727:Methotrexate