Increased Risk of Ischemic Stroke After Radiotherapy on the Neck in Patients Younger Than 60 Years

Dorresteijn, Lucille D.A.; Kappelle, A.C.; Boogerd, Willem; Klokman, Willem J.; Balm, Alfons J. M.; Keus, Ronald B.; Leeuwen, Flora E. van; Bartelink, Harry

doi:10.1200/jco.2002.20.1.282

Cited by 234 publications

(176 citation statements)

References 23 publications

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“…Relative quantities of alcohol consumption were not consistently available across participants. Although the number of persons included in this analysis was small, the annual CVE rate was significant, consistent with previous neck RT reports 3, 4…”

Section: Discussionsupporting

confidence: 84%

“…In contrast, in an analysis of >50 000 RT‐treated HNCA patients, traditional risk factors (hypertension and diabetes mellitus) were observed in only 30% of stroke events 22. Consequently, there are likely other risk factors that may at least partially explain the >500% increased risk of stroke events faced by HNCA patients treated with RT 3, 4. In this study, we found that HPV status was predictive of stroke and TIA following RT, even after adjustment for traditional risk factors and RT dose.…”

Section: Discussionmentioning

confidence: 92%

“…This was specifically defined as a composite of ischemic stroke and TIA. We chose this outcome based on data showing an increase in the combination of stroke and TIA after neck RT 3, 4, 18. Death was also reported but was not the focus of this study 19.…”

Section: Methodsmentioning

confidence: 99%

“…We used Cox regression models to examine associations between the independent variables and the development of CVEs. Covariates included in the model were variables significant on univariate analysis as well as known predictors and confounders of CVEs 3, 20. Hazard ratios (HRs) for the association of HPV status with events were estimated using Cox proportional hazards.…”

Section: Methodsmentioning

confidence: 99%

“…Radiation therapy (RT) to the neck is a standard primary treatment for HNCA2; however, RT that involves the neck is associated with a 5‐ to 17‐fold increased risk of cerebrovascular events (CVEs; stroke or transient ischemic attack [TIA]) 3, 4. The mechanisms for this increase in CVEs after RT that involves the neck are not completely understood but likely are related to inflammation and accelerated atherosclerosis in the carotid artery 4…”

Section: Introductionmentioning

confidence: 99%

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Human Papillomavirus Status and the Risk of Cerebrovascular Events Following Radiation Therapy for Head and Neck Cancer

Seidelmann

Janjua

Emami

et al. 2017

JAHA

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BackgroundRadiation therapy (RT) is a standard treatment for head and neck cancer; however, it is associated with inflammation, accelerated atherosclerosis, and cerebrovascular events (CVEs; stroke or transient ischemic attack). Human papillomavirus (HPV) is found in nearly half of head and neck cancers and is associated with inflammation and atherosclerosis. Whether HPV confers an increased risk of CVEs after RT is unknown.Methods and ResultsUsing an institutional database, we identified all consecutive patients treated with RT from 2002 to 2012 for head and neck cancer who were tested for HPV. The outcome of interest was the composite of ischemic stroke and transient ischemic attack, and the association between HPV and CVEs was assessed using Cox proportional hazard models, competing risk analysis, and inverse probability weighting. Overall, 326 participants who underwent RT for head and neck cancer were tested for HPV (age 59±12 years, 75% were male, 9% had diabetes mellitus, 45% had hypertension, and 61% were smokers), of which 191 (59%) were tumor HPV positive. Traditional risk factors for CVEs were similar between HPV‐positive and ‐negative patients. Over a median follow‐up of 3.4 years, there were 18 ischemic strokes and 5 transient ischemic attacks (event rate of 1.8% per year). The annual event rate was higher in the HPV‐positive patients compared with the HPV‐negative patients (2.6% versus 0.9%, P=0.002). In a multivariable model, HPV‐positive status was associated with a >4 times increased risk of CVEs (hazard ratio: 4.4; 95% confidence interval, 1.5–13.2; P=0.008).ConclusionsIn this study, HPV‐positive status is associated with an increased risk of stroke or transient ischemic attack following RT for head and neck cancer.

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Section: Discussionsupporting

confidence: 84%

Section: Discussionmentioning

confidence: 92%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Human Papillomavirus Status and the Risk of Cerebrovascular Events Following Radiation Therapy for Head and Neck Cancer

Seidelmann

Janjua

Emami

et al. 2017

JAHA

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Non–Cancer-Related Deaths From Suicide, Cardiovascular Disease, and Pneumonia in Patients With Oral Cavity and Oropharyngeal Squamous Carcinoma

Gao

Mehta

Branovan

et al. 2012

Arch Otolaryngol Head Neck Surg

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Suicide rates have significantly increased in patients with OC/OP cancer since 1980 to 1984. Although cardiovascular disease-and pneumonia-related deaths have significantly decreased over time, they remain higher than the general US population. Increased knowledge of risk factors associated with non-cancer-related mortality in OC/OP cancer may lead to early intervention and enhanced overall survival.

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Stroke Risk in Survivors of Head and Neck Cancer

Yip,

Zheng,

Cheo

et al. 2024

JAMA Netw Open

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ImportanceSurvivors of head and neck cancers (HNC) have increased risk of stroke. A comprehensive report using standardized methods is warranted to characterize the risk and to inform on survivorship strategy.ObjectiveTo determine the stroke risk in subpopulations of survivors of HNC in Singapore.Design, Setting, and ParticipantsThis national, registry-based, cross-sectional study aimed to estimate stroke risk in subgroups of the HNC population between January 2005 and December 2020. Participants were identified from the Singapore Cancer Registry, the Singapore Stroke Registry, and the Registry of Birth and Deaths using relevant International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, Australian Modification (ICD-10-AM) codes. HNC subgroups were defined based on patient demographic, disease, and treatment factors. Data were analyzed from September 2022 to September 2023.ExposureDiagnosis of HNC.Main Outcomes and MeasuresBoth ischemic and hemorrhagic stroke were studied. The age-standardized incidence rate ratio (SIRR) and age-standardized incidence rate difference (SIRD) were reported. The Singapore general population (approximately 4 million) served as the reference group for these estimations.ResultsA total of 9803 survivors of HNC (median [IQR] age at diagnosis, 58 [49-68] years; 7166 [73.1%] male) were identified. The most common HNC subsites were nasopharynx (4680 individuals [47.7%]), larynx (1228 individuals [12.5%]), and tongue (1059 individuals [10.8%]). A total of 337 individuals (3.4%) developed stroke over a median (IQR) follow-up of 42.5 (15.0-94.5) months. The overall SIRR was 2.46 (95% CI, 2.21-2.74), and the overall SIRD was 4.11 (95% CI, 3.37-4.85) strokes per 1000 person-years (PY). The cumulative incidence of stroke was 3% at 5 years and 7% at 10 years after HNC diagnosis. The SIRR was highest among individuals diagnosed at younger than 40 years (SIRR, 30.55 [95% CI, 16.24-52.35]). All population subsets defined by age, sex, race and ethnicity, HNC subsites (except tongue), stage, histology, and treatment modalities had increased risk of stroke compared with the general population. The SIRR and SIRD were significantly higher among individuals who had a primary radiation treatment approach (SIRR, 3.01 [95% CI, 2.64-3.43]; SIRD, 5.12 [95% CI, 4.18-6.29] strokes per 1000 PY) compared with a primary surgery approach (SIRR, 1.64 [95% CI, 1.31-2.05]; SIRD, 1.84 [95% CI, 0.923.67] strokes per 1000 PY).Conclusions and RelevanceIn this cross-sectional study of survivors of HNC, elevated stroke risks were observed across different age, subsites, and treatment modalities, underscoring the importance of early screening and intervention.

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Increased Risk of Ischemic Stroke After Radiotherapy on the Neck in Patients Younger Than 60 Years

Abstract: This is the first study to demonstrate an increased risk of stroke after RT on the neck. During medical follow-up, preventive measures should be taken to reduce the impact of the risk factors for cerebrovascular disease, to decrease stroke in these patients.

Cited by 234 publications

References 23 publications

Human Papillomavirus Status and the Risk of Cerebrovascular Events Following Radiation Therapy for Head and Neck Cancer

Human Papillomavirus Status and the Risk of Cerebrovascular Events Following Radiation Therapy for Head and Neck Cancer

Non–Cancer-Related Deaths From Suicide, Cardiovascular Disease, and Pneumonia in Patients With Oral Cavity and Oropharyngeal Squamous Carcinoma

Stroke Risk in Survivors of Head and Neck Cancer

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