Incidence, Characteristics, and Risk Factors of Post-Radiosurgery Headaches: A Prospective Observational Study

This prospective observational study aimed to characterize the incidence, clinical features, and risk factors of headaches following CyberKnife radiosurgery (CKRS) in patients with intracranial pathologies.

In a prospective observational study conducted from January 2022 to January 2023, we enrolled consecutive patients who underwent CKRS. Patients completed headache-related questionnaires developed based on the International Classification of Headache Disorders (ICHD-3) guidelines at 24 h, 1 week, and 3 months post-radiosurgery. The incidence of CKRS-related headaches was determined, and the link between risk factors and outcomes was analyzed.

Of 153 patients (female 58.2%; mean age 47.7 ± 14.8 years), all completed a 3-month follow-up. Among 153 patients, 61 (39.9%) developed post-CKRS headaches, with 83.6% reporting peak intensity within 2 weeks post-procedure. Fifty (32.7%) developed headaches within 2 weeks, resolving within 3 months. A strong temporal association between headache onset and CKRS supports a causal relationship. Multivariate Cox regression analysis identified female sex (HR = 2.16, 95% CI = 1.14-4.11, p = 0.019), younger age (HR = 0.97 per year, p = 0.006), absence of prior craniocerebral surgery (HR = 0.55, p = 0.046), and multiple lesions (HR = 2.28, p = 0.047) as independent risk factors. Although headaches were more frequently observed following radiation targeting the basal ganglia and thalamus, this association lacked statistical significance (p > 0.05).

Headaches attributed to brain radiosurgery constitute a significant yet overlooked clinical issue, warranting increased focus from surgical teams to deliver improved and tailored treatment.