Global Incidence, Mortality, and Risk Factors of Stroke in Multi‐Modality Head and Neck Cancer Treatment—A Systematic Review and Meta‐Analysis

BACKGROUND: Head and neck cancer (HNC) due to its nature and proximity to essential vasculature, along with different treatments, can lead to stroke, significantly contributing to morbidity and mortality. Our aim is to systematically evaluate the association of stroke incidence, mortality, and predictors with HNC treatment. METHODS: Pubmed, Web of Science, Embase, and ScienceDirect were searched from inception to July 2024 for articles reporting stroke incidences, mortality, or associated risk factors following treatment in HNC patients. A random-effects meta-analysis assessed cumulative incidence and mortality rates with proportional analysis and risk factors using hazard ratios (HRs) associated with HNC treatment. Subgroup analyses of incidence and mortality were conducted for pre- and post-2010 periods, reflecting changes in stroke protocols. RESULTS: Out of 1561 studies, 69 studies with 258 850 HNC patients were included. The global cumulative incidence of stroke in HNC was 4.1% (95% CI: 3.3%-5.0%), with similar rates before and after 2010 (4.4% vs. 4.0%). In patients undergoing chemoradiotherapy (CRT), stroke incidence was 4.9% (95% CI: 3.5%-6.7%) with a median time to first stroke of 45 months (range: 14-51.7 months). Following radiation therapy (RT), stroke incidence was 3.8% (95% CI: 2.7%-5.3%) with a median time to stroke of 36 months (range: 6.8-130 months). The incidence rates of stroke in HNC patients were higher compared to the general population (HR: 1.69, 95% CI: 1.24-2.31, p = 0.001). Stroke mortality decreased from 28.5% (95% CI: 11.6%-54.9%) pre-2010 to 14.5% (95% CI: 11.6%-17.9%) 2010-2024. Stroke mortality was 39.3% (95% CI: 17.8%-66.0%) post-CRT and 21% (95% CI: 7.2%-47.7%) post-RT. Hypertension (HR = 1.75), diabetes (HR = 1.71), and age > 65 (HR = 2.17) increased stroke risk (p < 0.0001 for all). Geographically, South Korea (6.6%) had the highest incidence of stroke. CONCLUSION: This is the first systematic review to analyze the association between stroke and HNC treatment. Stroke mortality decreased from 28.5% to 14.5% (pre-2010 vs. 2010-2024), with the highest mortality in the CRT group (39.3%). Given that stroke occurs 36-45 months after CRT, a screening protocol within 3-4 years is crucial.