Clinical and genomic characterization of brain metastasis in thyroid cancer

Brain metastasis (BrM) resulting from thyroid cancer remains poorly characterized despite its significant impact on patient outcomes. The current study aims to combine clinical features with genomic sequencing data to identify potential prognostic variables in thyroid cancer BrM.

A single-center retrospective cohort study consisting of 1,606 patients who were diagnosed with thyroid cancer and seen at an NCI-designated Comprehensive Cancer Center for a brain magnetic resonance imaging (MRI) between January 1, 2000 and December 31, 2024 was performed, and patients with BrM were identified. Clinical and genomic data were collected, with the latter obtained from the Memorial Sloan Kettering-Integrating Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) clinical sequencing platform.

154 patients (median age at BrM diagnosis = 62.4 years [range 18.9-92.5], 69 [45%] male, 85 [55%] female) participated in the study. The median OS from BrM diagnosis was 1.53 years (95%CI = 1.05-1.95 years). 1- and 3-year OS rates were 59.28% (95%CI = 51.02-66.61%) and 33.27% (95%CI = 25.54-41.17%), respectively. In multivariable analysis, Eastern Cooperative Oncology Group performance status ≥ 2, presence of leptomeningeal or dural-based metastasis, whole-brain radiotherapy treatment, pre-BrM diagnosis tyrosine kinase inhibitor treatment, and histological subtypes of poorly-differentiated and anaplastic thyroid cancer were associated with increased risk of mortality. Genomic analysis of matched primary and BrM samples revealed universal conservation of BRAF and NRAS mutations between samples.

Contemporary thyroid cancer BrM outcomes are dependent on primary malignancy histology and may benefit from further molecular profiling.