Originally published as JCO Early Release 10.1200/JCO.2008.16.6546 on August 25 2008

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Cerebrovascular Disease Risk in Older Head and Neck Cancer Patients After Radiotherapy

Grace L. Smith, Benjamin D. Smith, Thomas A. Buchholz, Sharon H. Giordano, Adam S. Garden, Wendy A. Woodward, Harlan M. Krumholz, Randal S. Weber, K.-Kian Ang, David I. Rosenthal

From the Departments of Radiation Oncology, Breast Medical Oncology, and Head and Neck Surgery, The University of Texas M. D. Anderson Cancer Center, Houston, TX; and the Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT

Corresponding author: David I. Rosenthal, MD, Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Unit 97, Houston, TX 77030; e-mail: dirosenthal{at}mdanderson.org

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.

published online ahead of print at www.jco.org on August 25, 2008.

Supported in part by the American Society of Clinical Oncology Young Investigator Award (B.D.S.) and by the Department of Scientific Publications, The University of Texas M. D. Anderson Cancer Center, Houston, TX.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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