Vascular Late Effects of Cranial Radiation

  • Christine Hill-KayserEmail author
  • Louis Constine


Many pediatric cancer survivors have received cranial radiation as part of multimodality treatment, most commonly those with leukemia and primary tumors of the central nervous system. The effects of radiotherapy on the developing vascular system may be significant, in summary causing the vessels to appear prematurely aged and fragile. As a result of these changes, survivors are at risk for vascular pathologies that include ischemic stroke, vascular malformations such as Moyamoya, aneurysm, and cavernoma, hemorrhage, necrosis, complicated migraines, and other, rarer, syndromes. Certain factors including age, genetic predisposition, and radiation dose and volume may contribute to risk of such pathologies. There is an increasing role for prevention through modifiable risk factors including metabolic factors. Treatment of vascular pathologies arising after radiotherapy remains similar to that recommended for de novo vascular disease.


  1. Aoiki S et al (2002) Radiation-induced arteritis: thickened wall with prominent enhancement on cranial MR images—report of five cases and comparison with 18 cases of moyamoya disease. Radiology 223:683–688CrossRefGoogle Scholar
  2. Bartleson JD et al (2003) Reversible, strokelike migraine attacks in patients with previous radiation therapy. Neuro-Oncology 5(2):121–127CrossRefPubMedPubMedCentralGoogle Scholar
  3. Bowers DC et al (2005) Stroke as a late treatment effect of Hodgkin’s disease: a report from the Childhood Cancer Survivor Study. J Clin Oncol 23:6508–6515CrossRefPubMedGoogle Scholar
  4. Bowers DC et al (2006) Late-occurring stroke among long-term survivors of childhood leukemia and brain tumors: a report from the Childhood Cancer Survivor Study. J Clin Oncol 24:5277–5282CrossRefPubMedGoogle Scholar
  5. Burn S et al (2007) Incidence of cavernoma development in children after radiotherapy for brain tumors. J Neurosurg 106:379–383PubMedGoogle Scholar
  6. Campen C et al (2010) Late neurovascular events in pediatric brain tumor patients. Stroke 43(11):3035–3040CrossRefGoogle Scholar
  7. Children’s Oncology Group (2013) Long-term follow-up guidelines for survivors of childhood, adolescent and young adult cancers, version 4.0. Children’s Oncology Group, Monrovia, CA. Available on-line: Scholar
  8. Coderre JA et al (2006) Late effects of radiation on the central nervous system: role of vascular endothelial damage and glial stem cell survival. Radiat Res 166:495–503CrossRefPubMedGoogle Scholar
  9. Desai SS et al (2006) Radiation-induced moyamoya syndrome. Int J Radiat Oncol Biol Phys 65:1222–1227CrossRefPubMedGoogle Scholar
  10. Farjam R et al (2015) Radiation-induced hippocampal vascular injury surrogate marker predicts late neurocognitive dysfunction. Int J Radiat Oncol Biol Phys 93(4):908–915CrossRefPubMedPubMedCentralGoogle Scholar
  11. Fearnley JM, Stevens JM, Rudge P (1995) Superficial siderosis of the central nervous system. Brain 118:1051–1066CrossRefPubMedGoogle Scholar
  12. Freund D et al (2015) Predictive risk of radiation induced cerebral necrosis in pediatric brain cancer patients after VMAT versus proton therapy. Cancers (Basel) 7(2):617–630CrossRefGoogle Scholar
  13. Fung LW, Thompson D, Ganesan V (2005) Revascularisation surgery for paediatric moyamoya: a review of the literature. Childs Nerv Syst 21:358–364CrossRefPubMedGoogle Scholar
  14. Hersh JH (2008) American Academy of Pediatrics Committee on genetics: health supervision for children with neurofibromatosis. Pediatrics 121:633–642CrossRefPubMedGoogle Scholar
  15. Indelicato DJ et al (2014) Incidence and dosimetric parameters of pediatric brainstem toxicity following proton therapy. Acta Oncol 53(10):1298–1304CrossRefPubMedGoogle Scholar
  16. Kestle JR, Hoffman HJ, Mock AR (1993) Moyamoya phenomenon after radiation for optic glioma. J Neurosurg 79:32–35CrossRefPubMedGoogle Scholar
  17. Kikuchi A et al (2007) Moyamoya syndrome following childhood acute lymphoblastic leukemia. Pediatr Blood Cancer 48:268–272CrossRefPubMedGoogle Scholar
  18. Koeppen AH et al (1993) Pathogenesis of superficial siderosis of the central nervous system. Ann Neurol 34:646–653CrossRefPubMedGoogle Scholar
  19. Koike S et al (2004) Asyptomatic radiation-induced telangiectasia in children after cranial radiation: frequency, latency, and dose relation. Radiology 230:93–99CrossRefPubMedGoogle Scholar
  20. Kralik SF et al (2015) Radiation necrosis in pediatric patients with brain tumors treated with proton radiotherapy. AJNR Am J Neuroradiol 36(8):1572–1578. doi: 10.3174/ajnr.A4333. Epub 2015 Jul 2
  21. Kranick SM et al (2013) Headache as a risk factor for neurovascular events in pediatric brain tumor patients. Neurology 80(16):1452–1456CrossRefPubMedPubMedCentralGoogle Scholar
  22. Krystal JI et al (2015) Arterial stiffness in childhood cancer survivors. Pediatr Blood Cancer 62(10):1832–1837CrossRefPubMedGoogle Scholar
  23. LeFevre M, U.S. Preventive Services Task Force (2014) Screening for asymptomatic carotid artery Stenoisis: U.S. Preventive Services Task Force Recommendation Statement. Ann Intern Med 161(5):356–362CrossRefPubMedGoogle Scholar
  24. Lo AC et al (2016) A cross-sectional cohort study of cerebrovascular disease and late effects after radiation therapy for Craniopharyngioma. Pediatr Blood Cancer 63(5):786–793CrossRefPubMedGoogle Scholar
  25. Lucas J, Mack WJ (2014) Effects of ionizing radiation on cerebral vasculature. World Neurosurg 81(3–4):490–491CrossRefPubMedGoogle Scholar
  26. Moraldo MV et al (2013) Doses to carotid arteries after modern radiation therapy for Hodgkin Lymphoma: is stroke still a late effect of treatment? Int J Radiat Oncol Biol Phys 87(2):297–303CrossRefGoogle Scholar
  27. Morris B et al (2009) Cerebrovascular disease in childhood cancer survivors: a Children’s Oncology Group report. Neurology 73(22):1906–1913CrossRefPubMedPubMedCentralGoogle Scholar
  28. Mueller S et al (2013a) Risk of first and recurrent stroke in childhood cancer survivors treated with cranial and cervical radiation therapy. Int J Radiat Oncol Biol Phys 86(4):643–648CrossRefPubMedPubMedCentralGoogle Scholar
  29. Mueller S et al (2013b) Radiation, atherosclerotic risk factors, and stroke risk in survivors of pediatric cancer: a report from the Childhood Cancer Survivor Study. Int J Radiat Oncol Biol Phys 86(4):649–655CrossRefPubMedPubMedCentralGoogle Scholar
  30. Nanney AD et al (2014) Intracranial aneurysms. World Neurosurg 81(3–4):5–6Google Scholar
  31. Oeffinger KC et al (2006) Chronic health conditions in adult survivors of childhood cancer. N Engl J Med 355:1572–1582CrossRefPubMedGoogle Scholar
  32. Okuno T, Prensky AL, Gado M (1985) The moyamoya syndrome associated with irradiation of an optic glioma in children: report of two cases and review of the literature. Pediatr Neurol 1:311–316CrossRefPubMedGoogle Scholar
  33. Partap S (2012) Stroke and cerebrovascular complications in childhood cancer survivors. Semin Pediatr Neurol 19(1):18–24CrossRefPubMedGoogle Scholar
  34. Plimpton SR et al (2015) Cerebral radiation necrosis in pediatric patients. Pediatr Hematol Oncol 32(1):78–83CrossRefPubMedGoogle Scholar
  35. Pradhan K et al (2015) Differences in circulating endothelial progenitor cells among childhood cancer survivors treated with and without radiation. J Hematol Thromb 1(1):iiGoogle Scholar
  36. Rajakulasingam K, Cerullo LJ, Raimondi AJ (1979) Childhood moyamoya syndrome. Postradiation pathogenesis. Childs Brain 5:467–475PubMedGoogle Scholar
  37. Rogers LR (2003) Cerebrovascular complications in cancer patients. Neurol Clin 21:167–192CrossRefPubMedGoogle Scholar
  38. Rosser TL, Vezina G, Packer RJ (2005) Cerebrovascular abnormalities in a population of children with neurofibromatosis type 1. Neurology 64:553–555CrossRefPubMedGoogle Scholar
  39. Vatanen A et al (2015) Radiotherapy-related arterial intima thickening and plaque formation in childhood cancer survivors detected with very-high resolution ultrasound during young adulthood. Pediatr Blood Cancer 62(11):2000–2006CrossRefPubMedGoogle Scholar
  40. Wang C et al (2014) Delayed cerebral vasculopathy following cranial radiation therapy for pediatric tumors. Pediatr Neurol 50(6):549–556. doi: 10.1016/j.pediatrneurol.2013.09.018. Epub 2014 Jan 25. Review
  41. Warrington JP et al (2013) Whole brain radiation-induced vascular cognitive impairment: mechanisms and implications. J Vasc Res 50(6):445–457CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Department of Radiation OncologyUniversity of Pennsylvania Perelman School of Medicine, The Children’s Hospital of PhiladelphiaPhiladelphiaUSA
  2. 2.Department of Radiation OncologyUniversity of RochesterRochesterUSA

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