title: Cerebrovascular Diseases in Childhood Cancer Survivors: Role of the Radiation Dose to Willis Circle Arteries.
abstract: The aim of this study was to investigate the role of radiation dose received to the circle of Willis (WC) during radiation therapy (RT) and of potential dose-response modifiers on the risk of stroke after treatment of childhood cancer.
  
  
  
  We evaluated the risk factors for stroke in a cohort of 3172 5-year survivors of childhood cancer who were followed up for a median time of 26 years. Radiation doses to the WC and brain structures were estimated for each of the 2202 children who received RT.
  
  
  
  Fifty-four patients experienced a confirmed stroke; 39 were ischemic. Patients not receiving RT had a stroke risk similar to that of the general population, whereas those who received RT had an 8.5-fold increased risk (95% confidence interval [CI]: 6.3-11.0). The excess of incidence of stroke increased yearly. The dose of radiation to the WC, rather than to other brain structures, was found to be the best predictor of stroke. The relative risk was 15.7 (95% CI: 4.9-50.2) for doses of 40 Gy or more. At 45 years of age, the cumulative stroke incidence was 11.3% (95% CI: 7.1%-17.7%) in patients who received 10 Gy or more to the WC, compared with 1% expected from general population data. Radiation doses received to the heart and neck also increased the risk. Surgery for childhood brain cancer was linked to hemorrhagic strokes in these patients.
  
  
  
  The WC should be considered as a major organ at risk during RT for childhood brain cancers. The incidence of radiation-induced ischemic stroke strongly increases with long-term follow-up.
authors.affiliation: Inserm U1018, Villejuif, France; Gustave Roussy, Villejuif, France; University of Paris XI, Villejuif, France.
authors.forename: Chiraz
authors.initials: C
authors.lastname: El-Fayech
authors.affiliation: Inserm U1018, Villejuif, France; Gustave Roussy, Villejuif, France; University of Paris XI, Villejuif, France.
authors.forename: Nadia
authors.initials: N
authors.lastname: Haddy
authors.affiliation: Inserm U1018, Villejuif, France; Gustave Roussy, Villejuif, France; University of Paris XI, Villejuif, France.
authors.forename: Rodrigue Sètchéou
authors.initials: RS
authors.lastname: Allodji
authors.affiliation: Inserm U1018, Villejuif, France; Gustave Roussy, Villejuif, France; University of Paris XI, Villejuif, France.
authors.forename: Cristina
authors.initials: C
authors.lastname: Veres
authors.affiliation: Inserm U1018, Villejuif, France; Gustave Roussy, Villejuif, France; University of Paris XI, Villejuif, France.
authors.forename: Fara
authors.initials: F
authors.lastname: Diop
authors.affiliation: Inserm U1018, Villejuif, France; Gustave Roussy, Villejuif, France; University of Paris XI, Villejuif, France.
authors.forename: Amar
authors.initials: A
authors.lastname: Kahlouche
authors.affiliation: Inserm U1018, Villejuif, France; Gustave Roussy, Villejuif, France; University of Paris XI, Villejuif, France.
authors.forename: Damien
authors.initials: D
authors.lastname: Llanas
authors.affiliation: Inserm U1018, Villejuif, France; Gustave Roussy, Villejuif, France; University of Paris XI, Villejuif, France.
authors.forename: Angela
authors.initials: A
authors.lastname: Jackson
authors.affiliation: Inserm U1018, Villejuif, France; Gustave Roussy, Villejuif, France; University of Paris XI, Villejuif, France.
authors.forename: Carole
authors.initials: C
authors.lastname: Rubino
authors.affiliation: Inserm U1018, Villejuif, France; Gustave Roussy, Villejuif, France; University of Paris XI, Villejuif, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Guibout
authors.affiliation: Institut Curie, Paris, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Pacquement
authors.affiliation: Gustave Roussy, Villejuif, France.
authors.forename: Odile
authors.initials: O
authors.lastname: Oberlin
authors.affiliation: Inserm U1018, Villejuif, France; Hôpital Bicêtre, Le Kremlin Bicêtre, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Thomas-Teinturier
authors.affiliation: Inserm U1018, Villejuif, France.
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Scarabin
authors.affiliation: Gustave Roussy, Villejuif, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Chavaudra
authors.affiliation: Gustave Roussy, Villejuif, France.
authors.forename: Dimitry
authors.initials: D
authors.lastname: Lefkopoulos
authors.affiliation: Registre Dijonnais des accidents vasculaires cérébraux, Dijon, France.
authors.forename: Maurice
authors.initials: M
authors.lastname: Giroud
authors.affiliation: Registre Dijonnais des accidents vasculaires cérébraux, Dijon, France.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Bejot
authors.affiliation: Centre Alexis Vautrin, Vandœuvre-lès-Nancy, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Bernier
authors.affiliation: Centre Léon Bérard, Lyon, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Carrie
authors.affiliation: Inserm U1018, Villejuif, France; Gustave Roussy, Villejuif, France; University of Paris XI, Villejuif, France.
authors.forename: Ibrahima
authors.initials: I
authors.lastname: Diallo
authors.affiliation: Inserm U1018, Villejuif, France; Gustave Roussy, Villejuif, France; University of Paris XI, Villejuif, France. Electronic address: florent.devathaire@gustaveroussy.fr.
authors.forename: Florent
authors.initials: F
authors.lastname: de Vathaire
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000145:classification; D002545:Brain Ischemia / Q000453:epidemiology / Q000209:etiology; D001932:Brain Neoplasms / Q000517:prevention & control / Q000532:radiotherapy; D002423:Cause of Death; D002543:Cerebral Hemorrhage / Q000453:epidemiology / Q000209:etiology; D002561:Cerebrovascular Disorders / Q000209:etiology; D002648:Child; D002675:Child, Preschool; D002941:Circle of Willis / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005500:Follow-Up Studies; D005602:France; D006321:Heart / Q000528:radiation effects; D006689:Hodgkin Disease / Q000532:radiotherapy; D006801:Humans; D015994:Incidence; D007223:Infant; D008297:Male; D008875:Middle Aged; D009333:Neck / Q000528:radiation effects; D058958:Organs at Risk / Q000528:radiation effects*; D011829:Radiation Dosage; D012189:Retrospective Studies; D020521:Stroke / Q000453:epidemiology / Q000209:etiology*; D017741:Survivors / Q000706:statistics & numerical data; D013997:Time Factors; D006113:United Kingdom
chemical_list: D000970:Antineoplastic Agents