Radiotherapy Exposure in Cancer Patients and Subsequent Risk of Stroke: A Systematic Review and Meta-Analysis

Background: Cancer patients who have undergone radiotherapy may have an increased risk of subsequent stroke. A clear and detailed understanding of this risk has not been established. Methods: A search for research articles published from January 1990 to November 2017 in the English language was conducted. Subsequent stroke risk in cancer survivors was compared using relative risk (RR) and 95% confidence intervals (CI) according to whether or not radiotherapy was given. Results: A total of 12 eligible studies were identified including 57,881 total patients. All studies were retrospective, as no prospective studies were identified. The meta-analysis revealed a higher overall risk of subsequent stroke in cancer survivors/patients given radiotherapy compared to those not given radiotherapy (RR: 2.09, 95% CI: 1.45, 3.16). In addition, compared to patients not given radiotherapy, there was an increased risk of subsequent stroke for radiotherapy treated patients with Hodgkin's lymphoma (RR: 2.81, 95% CI: 0.69, 4.93) or head/neck/brain/nasopharyngeal cancer (RR: 2.16, 95% CI: 1.16, 3.16), for patients younger than 40 years (RR: 3.53, 95% CI: 2.51, 4.97) or aged 40–49 years (RR: 1.23, 95% CI: 1.09, 1.45) and for patients treated in Asia (RR: 1.88, 95% CI: 1.48, 2.29), the United States (RR: 1.62, 95% CI: 1.01, 2.23), or in Europe (RR: 4.11, 95% CI 2.62, 6.45). Conclusions: The available literature indicates an approximate overall doubling of the subsequent stroke risk in cancer patients given radiotherapy. The elevated risk was generally statistically significant according to cancer type, baseline patient age and region or country where treatment was given. Caution is required in interpreting these findings due to the heterogeneity of populations represented and lack of standardization and completeness across published studies. Further, if real, we cannot conclude the extent to which patient, treatment and/or investigational factors are responsible for this apparent elevated risk. An objective and more detailed understanding of the risks of radiotherapy, and how to prevent them, is urgently required. It is the responsibility of all who provide cancer services to ensure that the experience of all their patients is documented and analyzed using quality registries.