Ischemic Stroke and Transient Ischemic Attack After Head and Neck Radiotherapy

Plummer, Chris; Henderson, Robert D.; O’Sullivan, John D.; Read, Stephen

doi:10.1161/strokeaha.111.615203

Cited by 229 publications

(194 citation statements)

References 79 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: 99%

“…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%

“…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: 99%

Section: Methodsmentioning

confidence: 99%

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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“…Cerebrovascular mortality, in contrast to cardiovascular mortality, remained elevated in GH-treated patients, but to a lower level (SMR, 1.88; 95% CI, 1.44-2.41) than the respective SMR of 3.39 (95% CI, 2.27-4.99) (3), 2.44 (95% CI, 1.58-4.18) (4), 2.74 (95% CI, 2.21-3.35) (6) and 2.4 (95% CI, 1.2-4.7) (8) reported in the literature in non-GH-treated patients with GHD. Whereas the relationship between radiotherapy and cerebrovascular disease was not specifically examined, the observed differences in cardiovascular compared with cerebrovascular SMR may indicate that stroke resulting from radiation vasculopathy is less effectively influenced by GH replacement (33).…”

Section: Discussionmentioning

confidence: 99%

Overall and cause-specific mortality in GH-deficient adults on GH replacement

Gaillard

Mattsson²,

Åkerblad³

et al. 2012

European Journal of Endocrinology

120

108

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Objective: Hypopituitarism is associated with an increased mortality rate but the reasons underlying this have not been fully elucidated. The purpose of this study was to evaluate mortality and associated factors within a large GH-replaced population of hypopituitary patients. Design: In KIMS (Pfizer International Metabolic Database) 13 983 GH-deficient patients with 69 056 patient-years of follow-up were available. Methods: This study analysed standardised mortality ratios (SMRs) by Poisson regression. IGF1 SDS was used as an indicator of adequacy of GH replacement. Statistical significance was set to P!0.05. Results: All-cause mortality was 13% higher compared with normal population rates (SMR, 1.13; 95% confidence interval, 1.04-1.24). Significant associations were female gender, younger age at followup, underlying diagnosis of Cushing's disease, craniopharyngioma and aggressive tumour and presence of diabetes insipidus. After controlling for confounding factors, there were statistically significant negative associations between IGF1 SDS after 1, 2 and 3 years of GH replacement and SMR. For cause-specific mortality there was a negative association between 1-year IGF1 SDS and SMR for deaths from cardiovascular diseases (PZ0.017) and malignancies (PZ0.044). Conclusions: GH-replaced patients with hypopituitarism demonstrated a modest increase in mortality rate; this appears lower than that previously published in GH-deficient patients. Factors associated with increased mortality included female gender, younger attained age, aetiology and lower IGF1 SDS during therapy. These data indicate that GH replacement in hypopituitary adults with GH deficiency may be considered a safe treatment.

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Apixaban vs Aspirin in Patients With Cancer and Cryptogenic Stroke

Navi,

Zhang,

Miller

et al. 2024

JAMA Neurol

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ImportanceApproximately 10% to 15% of ischemic strokes are associated with cancer; cancer-associated stroke, particularly when cryptogenic, is associated with high rates of recurrent stroke and major bleeding. Limited data exist on the safety and efficacy of different antithrombotic strategies in patients with cancer and cryptogenic stroke.ObjectiveTo compare apixaban vs aspirin for the prevention of adverse clinical outcomes in patients with history of cancer and cryptogenic stroke.Design, Setting, and ParticipantsPost hoc analysis of data from 1015 patients with a recent cryptogenic stroke and biomarker evidence of atrial cardiopathy in the Atrial Cardiopathy and Antithrombotic Drugs in Prevention After Cryptogenic Stroke (ARCADIA) trial, a multicenter, randomized, double-blind clinical trial conducted from 2018 to 2023 at 185 stroke centers in North America. Data analysis was performed from October 15, 2023, to May 23, 2024.ExposuresOral apixaban, 5 mg (or 2.5 mg if criteria met), twice daily vs oral aspirin, 81 mg, once daily. Subgroups of patients with and without cancer at baseline were examined.Main Outcomes and MeasuresThe primary outcome for this post hoc analysis was a composite of major ischemic or major hemorrhagic events. Major ischemic events were recurrent ischemic stroke, myocardial infarction, systemic embolism, and symptomatic deep vein thrombosis or pulmonary embolism. Major hemorrhagic events included symptomatic intracranial hemorrhage and any major extracranial hemorrhage.ResultsAmong 1015 participants (median [IQR] age, 68 [60-76] years; 551 [54.3%] female), 137 (13.5%) had a history of cancer. The median (IQR) follow-up was 1.5 (0.6-2.5) years for patients with history of cancer and 1.5 (0.6-3.0) years for those without history of cancer. Participants with history of cancer, compared with those without history of cancer, had a higher risk of major ischemic or major hemorrhagic events (hazard ratio [HR], 1.73; 95% CI, 1.10-2.71). Among those with history of cancer, 8 of 61 participants (13.1%) randomized to apixaban and 16 of 76 participants (21.1%) randomized to aspirin had a major ischemic or major hemorrhagic event; however, the risk was not significantly different between groups (HR, 0.61; 95% CI, 0.26-1.43). Comparing participants randomized to apixaban vs aspirin among those with cancer, events included recurrent stroke (5 [8.2%] vs 9 [11.8%]), major ischemic events (7 [11.5%] vs 14 [18.4%]), and major hemorrhagic events (1 [1.6%] vs 2 [2.6%]).Conclusions and RelevanceAmong participants in the ARCADIA trial with history of cancer, the risk of major ischemic and hemorrhagic events did not differ significantly with apixaban compared with aspirin.Trial RegistrationClinicalTrials.gov Identifier: NCT03192215

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Ischemic Stroke and Transient Ischemic Attack After Head and Neck Radiotherapy

Cited by 229 publications

References 79 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

Overall and cause-specific mortality in GH-deficient adults on GH replacement

Apixaban vs Aspirin in Patients With Cancer and Cryptogenic Stroke

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