title: Microbleeds and cavernomas after radiotherapy for paediatric primary brain tumours.
abstract: BACKGROUND
  With the expected growth and aging of the population of primary central nervous system tumours (PCNST) survivors, attention to the radiation-induced late brain injury is fundamental. Late focal hemosiderin deposition (FHD) lesions, namely microbleeds and cavernomas, are among the presumable late cerebrovascular complications associated with radiotherapy for PCNST.
  
  
  OBJECTIVE
  To explore association between PCNST radiotherapy and the occurrence FHD lesions and to address the correlation between the topographic location of these microvascular lesions with the focal radiotherapy location.
  
  
  METHODS
  Retrospective cohort study of 190 paediatric patients being followed for PCNST in a single referral oncological centre. The frequency of FHD lesions was compared between paediatric PCNST treated (n=132) and not treated (n=58) with brain radiation. Microbleed Anatomical Rating Scale (MARS) was used for systematic identification of these cerebrovascular lesions and to address the consistency between the topographic location of each lesion and the location of the focal radiotherapy area. Univariate analysis to address the role of variables such as tumour histology, location, gender and age of children at the beginning of radiotherapy, duration of follow-up and chemotherapy was performed.
  
  
  RESULTS
  FHD lesions (microbleeds and cavernomas) occurred exclusively and in a high percentage (41.6%) in PCNST survivors treated with brain radiation. Younger age at the diagnosis (p=0.031), duration of follow-up (p=0.010) and embryonal histology (p=0.003) positively correlated with the occurrence FHD lesions. FHD lesions were topographically concordant with the brain focal irradiation area in 3/19 (15.8%) patients from the focal RT subgroup and in 22/111 (19.8%) patients from the WBRT plus focal RT subgroup.
  
  
  CONCLUSIONS
  Our study, which is one of the largest to date on the topic, shows that FHD lesions are a common complication after radiotherapy for childhood PCNST. The young brain is probably more susceptible to radiation-induced late cerebrovascular injury. Diffuse small vessel disease and ceiling effect may account for the low topographic concordance we found. The clinical implications of FHD lesions in this specific population are yet to be clarified.
authors.affiliation: Neurology Department, Instituto Português de Oncologia de Lisboa Francisco Gentil, Portugal.
authors.forename: João
authors.initials: J
authors.lastname: Passos
authors.affiliation: Biomedical Science and Medicine Department, Universidade do Algarve, Portugal. Electronic address: nzwalo@gmail.com.
authors.forename: Hipólito
authors.initials: H
authors.lastname: Nzwalo
authors.affiliation: Neurology Department, Instituto Português de Oncologia de Lisboa Francisco Gentil, Portugal.
authors.forename: Mariana
authors.initials: M
authors.lastname: Valente
authors.affiliation: Neurology Department, Instituto Português de Oncologia de Lisboa Francisco Gentil, Portugal.
authors.forename: Joana
authors.initials: J
authors.lastname: Marques
authors.affiliation: Neurology Department, Instituto Português de Oncologia de Lisboa Francisco Gentil, Portugal.
authors.forename: Ana
authors.initials: A
authors.lastname: Azevedo
authors.affiliation: Radiotherapy Department, Instituto Português de Oncologia de Lisboa Francisco Gentil, Portugal.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Netto
authors.affiliation: Radiotherapy Department, Instituto Português de Oncologia de Lisboa Francisco Gentil, Portugal.
authors.forename: António
authors.initials: A
authors.lastname: Mota
authors.affiliation: Radiology Department, Instituto Português de Oncologia de Lisboa Francisco Gentil, Portugal.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Borges
authors.affiliation: Paediatric Department, Instituto Português de Oncologia de Lisboa Francisco Gentil, Portugal; Paediatric Neuro-Oncology Unit, Instituto Português de Oncologia de Lisboa Francisco Gentil, Portugal.
authors.forename: Sofia
authors.initials: S
authors.lastname: Nunes
authors.affiliation: Neurology Department, Instituto Português de Oncologia de Lisboa Francisco Gentil, Portugal; Paediatric Department, Instituto Português de Oncologia de Lisboa Francisco Gentil, Portugal.
authors.forename: Duarte
authors.initials: D
authors.lastname: Salgado
mesh_terms: D000293:Adolescent; D001932:Brain Neoplasms / Q000401:mortality / Q000532:radiotherapy*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D006392:Hemangioma, Cavernous / Q000000981:diagnostic imaging / Q000209:etiology*; D006470:Hemorrhage / Q000000981:diagnostic imaging / Q000209:etiology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008279:Magnetic Resonance Imaging; D008297:Male; D011878:Radiotherapy / Q000009:adverse effects*
keywords: Cavernomas; Focal hemosiderin deposition; Microbleeds; Radiotherapy; Tumor