Clinical and Molecular Features Associated with the Presence of Brain Metastases and Survival in Patients with Advanced Thyroid Cancer

Abstract Background Brain metastases in advanced thyroid cancer may be underrecognized due to lack of routine brain imaging. We characterized the clinical and molecular features, risk factors, and survival outcomes of patients with non-anaplastic follicular cell-derived thyroid carcinoma (FCDTC) with brain metastases. Methods This retrospective cohort study included patients with advanced non-anaplastic FCDTC treated in the Medical Oncology department at Princess Margaret Cancer Centre from 2007–2022. Clinicopathologic and treatment data were extracted from electronic records, and all tumors underwent targeted next-generation sequencing. Risk factors for brain metastasis were assessed using logistic regression, and overall survival was analyzed with Kaplan-Meier and Cox proportional hazards models. Results Of 187 patients with advanced non-anaplastic FCDTC, 32 (17%) were diagnosed with brain metastases. Dedicated brain imaging was performed in 56% of patients, and most metastases (78%) were asymptomatic and incidentally detected. Lung metastases were associated with higher risk of developing brain metastases (aOR 8.27, 95% CI 1.87-36.46). ARID2 mutations were enriched in patients with brain metastases (9% vs 1%, p = 0.02). Survival did not differ between patients with and without brain metastases. Patients with brain metastases who had an ECOG performance status ≥2 (aHR 8.42, 95% 1.96-36.11) or ≥ 4 brain metastases (aHR 5.43, 95% CI 1.51-19.48) had worse survival. Molecular alterations were not predictive of survival. Conclusion Brain metastases occurred more frequently than previously reported. Lung metastases were associated with higher risk of developing brain metastases, and performance status and lesion number were associated with survival. These findings support consideration of brain metastasis screening in advanced thyroid cancer and may inform future prognostic and treatment strategies.