Skip to main content

Advertisement

Log in

Radiotherapy and death from cerebrovascular disease in patients with primary brain tumors

  • Clinical Study
  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

Abstract

Radiotherapy is often used in the management of primary brain tumors, but late cerebrovascular risks remain incompletely characterized. We examined the relationship between radiotherapy and the risk of death from cerebrovascular disease (CVD) in this population. We used the Surveillance, Epidemiology, and End Results Program to identify 19,565 patients of any age diagnosed with a primary brain tumor between 1983–2002. Multivariable competing risks analysis and an interaction model were used to determine whether receipt of radiotherapy was associated with an increased risk of CVD-specific death, adjusting for tumor proximity to central arterial circulations of the brain. The median follow up in surviving patients was 12.75 years. Baseline characteristics were similar in patients who did and did not receive radiotherapy. Ten-year CVD-specific mortality in patients with tumors near central arterial circulations who did and did not receive radiotherapy were 0.64 % (95 % CI 0.42–0.93 %) versus 0.16 % (95 % CI 0.055–0.40 %), p = 0.01. After adjustment for demographic, tumor-related, and treatment-related covariates, patients with tumors near central arterial circulations were significantly more likely to experience CVD-specific mortality after radiotherapy (HR 2.81; 95 % CI 1.25–6.31; p = 0.01); no association was observed among patients with more distant tumors (HR 0.77; 95 % CI 0.50–1.16; p = 0.21). The interaction model showed that tumor location was a key predictor of the risk of radiotherapy-associated, CVD-specific mortality (p-interaction = 0.004). Patients receiving radiotherapy for tumors near but not distant from the central vasculature of the brain are at increased risk for death secondary to CVD, which should be considered when counseling patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Darby SC, Ewertz M, McGale P, Bennet AM, Blom-Goldman U, Bronnum D, Correa C, Cutter D, Gagliardi G, Gigante B, Jensen MB, Nisbet A, Peto R, Rahimi K, Taylor C, Hall P (2013) Risk of ischemic heart disease in women after radiotherapy for breast cancer. N Engl J Med 368:987–998. doi:10.1056/NEJMoa1209825

    Article  CAS  PubMed  Google Scholar 

  2. Giordano SH, Kuo YF, Freeman JL, Buchholz TA, Hortobagyi GN, Goodwin JS (2005) Risk of cardiac death after adjuvant radiotherapy for breast cancer. J Natl Cancer Inst 97:419–424. doi:10.1093/jnci/dji067

    Article  PubMed Central  PubMed  Google Scholar 

  3. Harris EE, Correa C, Hwang WT, Liao J, Litt HI, Ferrari VA, Solin LJ (2006) Late cardiac mortality and morbidity in early-stage breast cancer patients after breast-conservation treatment. J Clin Oncol 24:4100–4106. doi:10.1200/JCO.2005.05.1037

    Article  PubMed  Google Scholar 

  4. Correa CR, Litt HI, Hwang WT, Ferrari VA, Solin LJ, Harris EE (2007) Coronary artery findings after left-sided compared with right-sided radiation treatment for early-stage breast cancer. J Clin Oncol 25:3031–3037. doi:10.1200/JCO.2006.08.6595

    Article  PubMed  Google Scholar 

  5. Mueller S, Sear K, Hills NK, Chettout N, Afghani S, Gastelum E, Haas-Kogan D, Fullerton HJ (2013) Risk of first and recurrent stroke in childhood cancer survivors treated with cranial and cervical radiation therapy. Int J Radiat Oncol Biol Phys 86:643–648. doi:10.1016/j.ijrobp.2013.03.004

    Article  PubMed Central  PubMed  Google Scholar 

  6. Bowers DC, Liu Y, Leisenring W, McNeil E, Stovall M, Gurney JG, Robison LL, Packer RJ, Oeffinger KC (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 24:5277–5282. doi:10.1200/JCO.2006.07.2884

    Article  PubMed  Google Scholar 

  7. Bowers DC, McNeil DE, Liu Y, Yasui Y, Stovall M, Gurney JG, Hudson MM, Donaldson SS, Packer RJ, Mitby PA, Kasper CE, Robison LL, Oeffinger KC (2005) Stroke as a late treatment effect of Hodgkin’s Disease: a report from the Childhood Cancer Survivor Study. J Clin Oncol 23:6508–6515. doi:10.1200/JCO.2005.15.107

    Article  PubMed  Google Scholar 

  8. Mueller S, Fullerton HJ, Stratton K, Leisenring W, Weathers RE, Stovall M, Armstrong GT, Goldsby RE, Packer RJ, Sklar CA, Bowers DC, Robison LL, Krull KR (2013) 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 86:649–655. doi:10.1016/j.ijrobp.2013.03.034

    Article  PubMed Central  PubMed  Google Scholar 

  9. Campen CJ, Kranick SM, Kasner SE, Kessler SK, Zimmerman RA, Lustig R, Phillips PC, Storm PB, Smith SE, Ichord R, Fisher MJ (2012) Cranial irradiation increases risk of stroke in pediatric brain tumor survivors. Stroke 43:3035–3040. doi:10.1161/STROKEAHA.112.661561

    Article  PubMed Central  PubMed  Google Scholar 

  10. Hong JC, Kruser TJ, Gondi V, Mohindra P, Cannon DM, Harari PM, Bentzen SM (2013) Risk of cerebrovascular events in elderly patients after radiation therapy versus surgery for early-stage glottic cancer. Int J Radiat Oncol Biol Phys 87:290–296. doi:10.1016/j.ijrobp.2013.06.009

    Article  PubMed  Google Scholar 

  11. Smith GL, Smith BD, Buchholz TA, Giordano SH, Garden AS, Woodward WA, Krumholz HM, Weber RS, Ang KK, Rosenthal DI (2008) Cerebrovascular disease risk in older head and neck cancer patients after radiotherapy. J Clin Oncol 26:5119–5125. doi:10.1200/JCO.2008.16.6546

    Article  PubMed  Google Scholar 

  12. Haynes JC, Machtay M, Weber RS, Weinstein GS, Chalian AA, Rosenthal DI (2002) Relative risk of stroke in head and neck carcinoma patients treated with external cervical irradiation. Laryngoscope 112:1883–1887. doi:10.1097/00005537-200210000-00034

    Article  PubMed  Google Scholar 

  13. Flickinger JC, Nelson PB, Taylor FH, Robinson A (1989) Incidence of cerebral infarction after radiotherapy for pituitary adenoma. Cancer 63:2404–2408

    Article  CAS  PubMed  Google Scholar 

  14. Brada M, Ashley S, Ford D, Traish D, Burchell L, Rajan B (2002) Cerebrovascular mortality in patients with pituitary adenoma. Clin Endocrinol (Oxf) 57:713–717

    Article  CAS  Google Scholar 

  15. Brada M, Burchell L, Ashley S, Traish D (1999) The incidence of cerebrovascular accidents in patients with pituitary adenoma. Int J Radiat Oncol Biol Phys 45:693–698

    Article  CAS  PubMed  Google Scholar 

  16. Erfurth EM, Bulow B, Svahn-Tapper G, Norrving B, Odh K, Mikoczy Z, Bjork J, Hagmar L (2002) Risk factors for cerebrovascular deaths in patients operated and irradiated for pituitary tumors. J Clin Endocrinol Metab 87:4892–4899. doi:10.1210/jc.2002-020526

    Article  CAS  PubMed  Google Scholar 

  17. Sattler MG, Vroomen PC, Sluiter WJ, Schers HJ, van den Berg G, Langendijk JA, Wolffenbuttel BH, van den Bergh AC, van Beek AP (2013) Incidence, causative mechanisms, and anatomic localization of stroke in pituitary adenoma patients treated with postoperative radiation therapy versus surgery alone. Int J Radiat Oncol Biol Phys 87:53–59. doi:10.1016/j.ijrobp.2013.05.006

    Article  PubMed  Google Scholar 

  18. Surveillance, Epidemiology, and End Results (SEER) Program (www.seer.cancer.gov) Research Data (1973–2011), National Cancer Institute, DCCPS, Surveillance Research Program, Surveillance Systems Branch, released April 2014, based on the November 2013 submission

  19. Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987–996. doi:10.1056/NEJMoa043330

    Article  CAS  PubMed  Google Scholar 

  20. Iezzoni LI, Ngo LH, Li D, Roetzheim RG, Drews RE, McCarthy EP (2008) Early stage breast cancer treatments for younger Medicare beneficiaries with different disabilities. Health Serv Res 43:1752–1767. doi:10.1111/j.1475-6773.2008.00853.x

    Article  PubMed Central  PubMed  Google Scholar 

  21. Gray RJ (1988) A Class of K-Sample Tests for Comparing the Cumulative Incidence of a Competing Risk. Ann Stat 16:1141–1154

    Article  Google Scholar 

  22. Fine JP, Gray RJ (1999) A proportional hazards model for the sub distribution of a competing risk. J Am Stat Assoc 94:496–509

    Article  Google Scholar 

  23. United States Department of Agriculture Rural-Urban Continuum Codes. http://www.ers.usda.gov/data-products/rural-urban-continuum-codes.aspx. Accessed 13 Jan 2013

  24. United States Census Bureau. Census 2000 Gateway. http://www.census.gov/main/www/cen2000.html. Accessed 12 Dec 2012

  25. United States Census. Small Area Income and Poverty Estimates. http://www.census.gov/did/www/saipe/data/statecounty/data/2004.html. Accessed 12 Dec 2012

  26. Fouladi M, Langston J, Mulhern R, Jones D, Xiong X, Yang J, Thompson S, Walter A, Heideman R, Kun L, Gajjar A (2000) Silent lacunar lesions detected by magnetic resonance imaging of children with brain tumors: a late sequela of therapy. J Clin Oncol 18:824–831

    CAS  PubMed  Google Scholar 

  27. Gross BA, Ropper AE, Du R (2013) Vascular complications of stereotactic radiosurgery for arteriovenous malformations. Clin Neurol Neurosurg 115:713–717. doi:10.1016/j.clineuro.2012.08.008

    Article  PubMed  Google Scholar 

  28. Haddy N, Mousannif A, Tukenova M, Guibout C, Grill J, Dhermain F, Pacquement H, Oberlin O, El-Fayech C, Rubino C, Thomas-Teinturier C, Le-Deley MC, Hawkins M, Winter D, Chavaudra J, Diallo I, de Vathaire F (2011) Relationship between the brain radiation dose for the treatment of childhood cancer and the risk of long-term cerebrovascular mortality. Brain 134:1362–1372. doi:10.1093/brain/awr071

    Article  PubMed  Google Scholar 

  29. Caplan L, Chung CS, Wityk R, Glass T, Tapia J, Pazdera L, Chang HM, Dashe J, Chaves C, Vemmos K, Leary M, Dewitt L, Pessin M (2005) New England medical center posterior circulation stroke registry: I. Methods, data base, distribution of brain lesions, stroke mechanisms, and outcomes. J Clin Neurol 1:14–30. doi:10.3988/jcn.2005.1.1.14

    Article  PubMed Central  PubMed  Google Scholar 

  30. Nishizawa S, Ryu H, Yokoyama T, Ninchoji T, Shimoyama I, Yamamoto S, Uemura K (1991) Post-irradiation vasculopathy of intracranial major arteries in children–report of two cases. Neurol Med Chir (Tokyo) 31:336–341.

    Article  CAS  Google Scholar 

  31. Brant-Zawadzki M, Anderson M, DeArmond SJ, Conley FK, Jahnke RW (1980) Radiation-induced large intracranial vessel occlusive vasculopathy. AJR Am J Roentgenol 134:51–55. doi:10.2214/ajr.134.1.51

    Article  CAS  PubMed  Google Scholar 

  32. Omura M, Aida N, Sekido K, Kakehi M, Matsubara S (1997) Large intracranial vessel occlusive vasculopathy after radiation therapy in children: clinical features and usefulness of magnetic resonance imaging. Int J Radiat Oncol Biol Phys 38:241–249.

    Article  CAS  PubMed  Google Scholar 

  33. Schonewille WJ, Algra A, Serena J, Molina CA, Kappelle LJ (2005) Outcome in patients with basilar artery occlusion treated conventionally. J Neurol Neurosurg Psychiatry 76:1238–1241. doi:10.1136/jnnp.2004.049924

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  34. Lindsberg PJ, Mattle HP (2006) Therapy of basilar artery occlusion: a systematic analysis comparing intra-arterial and intravenous thrombolysis. Stroke 37:922–928. doi:10.1161/01.STR.0000202582.29510.6b

    Article  PubMed  Google Scholar 

  35. van den Bent MJ, Afra D, de Witte O, Ben Hassel M, Schraub S, Hoang-Xuan K, Malmstrom PO, Collette L, Pierart M, Mirimanoff R, Karim AB (2005) Long-term efficacy of early versus delayed radiotherapy for low-grade astrocytoma and oligodendroglioma in adults: the EORTC 22845 randomised trial. Lancet 366:985–990. doi:10.1016/S0140-6736(05)67070-5

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The authors have no acknowledgments to report. This study has not been presented elsewhere.

Disclosures

The authors have no financial disclosures to report.

Funding

No funding was required for this study.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Nils D. Arvold.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Aizer, A.A., Du, R., Wen, P.Y. et al. Radiotherapy and death from cerebrovascular disease in patients with primary brain tumors. J Neurooncol 124, 291–297 (2015). https://doi.org/10.1007/s11060-015-1839-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11060-015-1839-5

Keywords

Navigation