Radiotherapy and death from cerebrovascular disease in patients with primary brain tumors
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.
KeywordsCancer Stroke Death Location Radiation
The authors have no acknowledgments to report. This study has not been presented elsewhere.
The authors have no financial disclosures to report.
No funding was required for this study.
- 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 CrossRefPubMedGoogle 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 PubMedCentralCrossRefPubMedGoogle 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 CrossRefPubMedGoogle 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 CrossRefPubMedGoogle 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 PubMedCentralCrossRefPubMedGoogle 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 PubMedCentralCrossRefPubMedGoogle 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 CrossRefPubMedGoogle 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 CrossRefPubMedGoogle 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 CrossRefPubMedGoogle 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
- 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 CrossRefPubMedGoogle 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 PubMedCentralCrossRefPubMedGoogle 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 CrossRefPubMedGoogle Scholar