OC14 - Brain metastasis in differentiated thyroid cancer: an international multicentric retrospective analysis

Background Brain metastases (BM) from Differentiated Thyroid Cancer (DTC) occur in 0.9–1.5% of all DTC cases and in up to 18% of patients with distant metastases. Given their rarity, disease features and optimal management are unclear. Purpose To describe the clinical, biochemical, and radiological features of BM from DTC, and to identify prognostic factors and effective treatment strategies. Methods Multicentric retrospective study including 18 international referral centres for thyroid cancer management. Results We included 189 patients (102 females, 87 males) with BM from DTC. Most (92.6%) had additional distant metastases, and 98 patients (52.1%) had a single BM, while 23 patients (12.4%) had ≥4 BMs. Neurological symptoms prompted diagnosis in 50.8% of the patients. Initial treatments included stereotactic radiosurgery (SRS, 27.0%), neurosurgery (23.8%), whole-brain radiotherapy (WBRT, 18.5%), best supportive care (BSC, 10.6%), tyrosine kinase inhibitors (6.9%), radioiodine therapy (3.2%) and chemotherapy (1.1%). Objective-response rate (ORR) and disease-control rate (DCR) were highest with neurosurgery and neurosurgery + SRS and lowest with WBRT or BSC (p<0.001; Cramer’s V = 0.54 for ORR and 0.40 for DCR). The median overall survival (OS) from BM diagnosis was 15 months (25-75 IQR: 4.0–38.4). Multivariate Cox regression identified age >75 years (HR: 2.38, p=0.028), performance status (ECOG) [2 (HR: 2.30; p=0.018), 3 (HR: 2.59; p=0.034), 4 (HR: 8.97; p<0.001)], PTC histology (HR: 2.00, p=0.007), presence of extracranial metastases (HR: 2.28, p=0.028), and BM>4 (HR: 2.28, p=0.035) as independent predictors of worse OS. Based on these factors, we developed a disease-specific Graded Prognostic Assessment (GPA) system assigning scores from 0 to 2 for every feature; patients were stratified into four prognostic groups: Group 1 (GPA 0–1, n=31): median OS = 72.6 months, Group 2 (GPA 1.5–2, n=101): median OS = 33.1 months, Group 3 (GPA 2.5–3, n=45): median OS = 15.9 months and Group 4 (GPA 3.5–4, n=11): median OS = 1.2 month (log-rank p value <0.001). Conclusion(s) In this international, real-world study, we documented the disease features of the largest cohort of patients with BM from DTC. Surgery offers the best outcomes in selected cases. The proposed GPA model effectively stratifies prognosis and may guide clinical decision-making.