Risk of cerebrovascular disease among 13,457 five-year survivors of childhood cancer: a population based cohort study

Raoul C. Reulen, Joyeeta Guha, Chloe J. Bright, Katherine E. Henson, Richard G. Feltbower, Marlous Hall, Julie S. Kelly, David L. Winter, Michelle Kwok‐williams, Roderick Skinner, David J. Cutter, Clare Frobisher, Mike M. Hawkins

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Survivors of childhood cancer treated with cranial irradiation are at risk of cerebrovascular disease (CVD), but the risks beyond age 50 are unknown. In all, 13457 survivors of childhood cancer included in the population‐based British Childhood Cancer Survivor Study cohort were linked to Hospital Episode Statistics data for England. Risk of CVD related hospitalisation was quantified by standardised hospitalisation ratios (SHRs), absolute excess risks and cumulative incidence. Overall, 315 (2.3%) survivors had been hospitalised at least once for CVD with a 4‐fold risk compared to that expected (95% confidence interval [CI]: 3.7‐4.3). Survivors of a central nervous system (CNS) tumour and leukaemia treated with cranial irradiation were at greatest risk of CVD (SHR = 15.6, 95% CI: 14.0‐17.4; SHR = 5.4; 95% CI: 4.5‐6.5, respectively). Beyond age 60, on average, 3.1% of CNS tumour survivors treated with cranial irradiation were hospitalised annually for CVD (0.4% general population). Cumulative incidence of CVD increased from 16.0% at age 50 to 26.0% at age 65 (general population: 1.4‐4.2%). In conclusion, among CNS tumour survivors treated with cranial irradiation, the risk of CVD continues to increase substantially beyond age 50 up to at least age 65. Such survivors should be: counselled regarding this risk; regularly monitored for hypertension, dyslipidaemia and diabetes; advised on life‐style risk behaviours. Future research should include the recall for counselling and brain MRI to identify subgroups that could benefit from pharmacological or surgical intervention and establishment of a case‐control study to comprehensively determine risk‐factors for CVD.
Original languageEnglish
Pages (from-to)572-583
Number of pages12
JournalInternational Journal of Cancer
Issue number3
Early online date19 Jul 2020
Publication statusPublished - 1 Feb 2021

Bibliographical note

Funding Information:
The British Childhood Cancer Survivor Study (BCCSS) is a national collaborative undertaking with close links with the Children's Cancer and Leukaemia Group (CCLG). In particular, the Late Effects Group of the CCLG provides clinical advice and support to the BCCSS. In addition, the BCCSS benefits from contributions from the Officers, Centres and individual members of the CCLG. The BCCSS collaborates with the Regional Paediatric Cancer Registries. The BCCSS acknowledges the collaboration of the Office for National Statistics, Public Health England, the National Cancer Registration and Analysis Service, NHS Digital, the National Records of Scotland and the Welsh Cancer Intelligence and Surveillance Unit. The BCCSS would not have been possible without the support of our funders: Cancer Research UK, Children with Cancer UK, the Brain Tumour Charity and Public Health England to whom we offer our profound thanks. The views expressed in this publication are those of the authors and not necessarily those of the funders or collaborators. Finally, thanks to all the cancer survivors whose experience has been used to try and understand the full consequences of childhood cancer and its treatment. This work was supported by Cancer Research UK [C386/A10422 & C8225/A21133] and Children with Cancer (20457). Raoul C. Reulen was supported by an Academy of Medical Sciences Springboard award. No funder had any role in the study design; collection, analysis, interpretation of the data; writing of the report; or in the decision to submit the article for publication.

Publisher Copyright:
© 2020 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of Union for International Cancer Control.


  • cancer survivorship
  • cohort
  • epidemiology
  • late effects

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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