Cerebrovascular disease risk in older head and neck cancer patients after radiotherapy.

PURPOSE Cerebrovascular disease is common in head and neck cancer patients, but it is unknown whether radiotherapy increases the cerebrovascular disease risk in this population. PATIENTS AND METHODS We identified 6,862 patients (age > 65 years) from the Surveillance, Epidemiology, and End Results (SEER) -Medicare cohort diagnosed with nonmetastatic head and neck cancer between 1992 and 2002. Using proportional hazards regression, we compared risk of cerebrovascular events (stroke, carotid revascularization, or stroke death) after treatment with radiotherapy alone, surgery plus radiotherapy, or surgery alone. To further validate whether treatment groups had equivalent baseline risk of vascular disease, we compared the risks of developing a control diagnosis, cardiac events (myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft, or cardiac death). Unlike cerebrovascular risk, no difference in cardiac risk was hypothesized. RESULTS Mean age was 76 +/- 7 years. Ten-year incidence of cerebrovascular events was 34% in patients treated with radiotherapy alone compared with 25% in patients treated with surgery plus radiotherapy and 26% in patients treated with surgery alone (P < .001). After adjusting for covariates, patients treated with radiotherapy alone had increased cerebrovascular risk compared with surgery plus radiotherapy (hazard ratio [HR] = 1.42; 95% CI, 1.14 to 1.77) and surgery alone (HR = 1.50; 95% CI, 1.18 to 1.90). However, no difference was found for surgery plus radiotherapy versus surgery alone (P = .60). As expected, patients treated with radiotherapy alone had no increased cardiac risk compared with the other treatment groups (P = .63 and P = .81). CONCLUSION Definitive radiotherapy for head and neck cancer, but not postoperative radiotherapy, was associated with excess cerebrovascular disease risk in older patients.

[1]  K. Furie,et al.  Heart disease and stroke statistics--2007 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. , 2008, Circulation.

[2]  H. Bartelink,et al.  Long-term risk of cardiovascular disease in 10-year survivors of breast cancer. , 2007, Journal of the National Cancer Institute.

[3]  J. Klijn,et al.  Decreased risk of stroke among 10-year survivors of breast cancer. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[4]  Yan Liu,et al.  Late-occurring stroke among long-term survivors of childhood leukemia and brain tumors: a report from the Childhood Cancer Survivor Study. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[5]  C. Gross,et al.  Effectiveness of radiation therapy in older women with ductal carcinoma in situ. , 2006, Journal of the National Cancer Institute.

[6]  Brian O'Sullivan,et al.  Hyperfractionated or accelerated radiotherapy in head and neck cancer: a meta-analysis , 2006, The Lancet.

[7]  D. Chang,et al.  Trends in the in-hospital stroke rate following carotid endarterectomy in California and Maryland. , 2006, Journal of vascular surgery.

[8]  W. Woodward,et al.  Supraclavicular radiation for breast cancer does not increase the 10‐year risk of stroke , 2006, Cancer.

[9]  C. Gross,et al.  Effectiveness of radiation therapy for older women with early breast cancer. , 2006, Journal of the National Cancer Institute.

[10]  Steven L Hancock,et al.  Clinical manifestations of noncoronary atherosclerotic vascular disease after moderate dose irradiation , 2006, Cancer.

[11]  P. Brown,et al.  A historical prospective cohort study of carotid artery stenosis after radiotherapy for head and neck malignancies. , 2005, International journal of radiation oncology, biology, physics.

[12]  J. Goodwin,et al.  Cardiac morbidity of adjuvant radiotherapy for breast cancer. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[13]  Yan Liu,et al.  Stroke as a late treatment effect of Hodgkin's Disease: a report from the Childhood Cancer Survivor Study. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[14]  James S Goodwin,et al.  Risk of cardiac death after adjuvant radiotherapy for breast cancer. , 2005, Journal of the National Cancer Institute.

[15]  L. Holmberg,et al.  Increased incidence of stroke in women with breast cancer. , 2005, European journal of cancer.

[16]  J. Jacobs,et al.  Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. , 2004, The New England journal of medicine.

[17]  C. Pepine,et al.  Valvular dysfunction and carotid, subclavian, and coronary artery disease in survivors of hodgkin lymphoma treated with radiation therapy. , 2003, JAMA.

[18]  J. Horiot,et al.  Compliance to the prescribed dose and overall treatment time in five randomized clinical trials of altered fractionation in radiotherapy for head-and-neck carcinomas. , 2003, International journal of radiation oncology, biology, physics.

[19]  G. Weinstein,et al.  Relative Risk of Stroke in Head and Neck Carcinoma Patients Treated With External Cervical Irradiation , 2002, The Laryngoscope.

[20]  A. Garden,et al.  Randomized trial addressing risk features and time factors of surgery plus radiotherapy in advanced head-and-neck cancer. , 2002, International journal of radiation oncology, biology, physics.

[21]  S. Leung,et al.  Incidence of carotid stenosis in nasopharyngeal carcinoma patients after radiotherapy , 2001, Cancer.

[22]  A. Garden,et al.  Randomized trial addressing risk features and time factors of surgery plus radiotherapy in advanced head-and-neck cancer , 2001 .

[23]  J L Warren,et al.  Development of a comorbidity index using physician claims data. , 2000, Journal of clinical epidemiology.

[24]  S. Ashley,et al.  The incidence of cerebrovascular accidents in patients with pituitary adenoma. , 1999, International journal of radiation oncology, biology, physics.

[25]  W. Powers,et al.  Cost-effectiveness of screening for asymptomatic carotid atherosclerotic disease. , 1997, Stroke.

[26]  S L Hancock,et al.  Factors affecting late mortality from heart disease after treatment of Hodgkin's disease. , 1993, JAMA.

[27]  E. Hall,et al.  Radiosensitivity and sublethal damage repair in human umbilical cord vein endothelial cells. , 1987, International journal of radiation oncology, biology, physics.

[28]  H. Bartelink,et al.  Increased risk of ischemic stroke after radiotherapy on the neck in patients younger than 60 years. , 2002, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[29]  Jay S. Cooper,et al.  A radiation therapy oncology group (RTOG) phase III randomized study to compare hyperfractionation and two variants of accelerated fractionation to standard fractionation radiotherapy for head and neck squamous cell carcinomas: first report of RTOG 9003 , 1999 .