Prognostic Stratification of Brain Metastases from Nonanaplastic Follicular Cell–Derived Thyroid Carcinoma: Results of an International Multicenter Retrospective Study

Background: Brain metastases (BMs) from nonanaplastic follicular cell–derived thyroid carcinoma (hereinafter referred to as non-ATC) are rare and not well characterized, with limited evidence guiding treatment and prognostic stratification. We aimed to describe clinical features, treatment patterns, and outcomes of patients with BMs from non-ATC and to develop and validate a disease-specific prognostic score. Methods: This retrospective international multicenter study included adults with histologically confirmed non-ATC and radiologically documented BMs treated at 19 tertiary referral centers. Clinical, radiological, treatment, and outcome data were collected. Independent predictors of progression-free survival (PFS) and overall survival (OS) were analyzed using Cox regression, and variables identified were used to develop a disease-specific Graded Prognostic Assessment (non-ATC GPA), exploratorily assessed in an independent SEER cohort. Results: A total of 189 patients were included; median age at BM diagnosis was 59 years (interquartile range [IQR] 48–67). First-line BM treatments included stereotactic radiosurgery (27.0%), neurosurgery (23.8%), whole-brain radiotherapy (18.5%), and best supportive care (10.6%). Median PFS was 7.0 months (IQR: 2.9–22.4), and median OS was 15.0 months (IQR: 4.0–38.4). Independent predictors of shorter OS were age >75 years, Eastern Cooperative Oncology Group performance status ≥2, papillary histology, extracranial metastases, and ≥4 BM. The GPA stratified patients into four prognostic groups with median OS ranging from 72.6 months in the highest-score group to 3.7 months in the lowest. An exploratory SEER-based assessment showed survival differences across adapted prognostic groups ( p = 0.036), although this analysis was limited by the absence of all key GPA variables. Conclusions: BMs from non-ATC are associated with poor survival and marked prognostic heterogeneity. The proposed GPA may provide a useful framework for prognostic stratification, pending further validation in independent datasets to support individualized management.

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Journal
Thyroid
Published
2026-08-03
DOI
https://doi.org/10.1177/10507256261473771
Primary Topic
Thyroid Cancer Diagnosis and Treatment
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article
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article

Prognostic Stratification of Brain Metastases from Nonanaplastic Follicular Cell–Derived Thyroid Carcinoma: Results of an International Multicenter Retrospective Study

Evert F S van Velsen, B. Kiesewetter, Roman Liščák, Pasqualino Malandrino et al.
Thyroid
Thyroid Cancer Diagnosis and Treatment
article

Prognostic Stratification of Brain Metastases from Nonanaplastic Follicular Cell–Derived Thyroid Carcinoma: Results of an International Multicenter Retrospective Study

Evert F S van Velsen, B. Kiesewetter, Roman Liščák, Pasqualino Malandrino, Liyona Kampel, Merel T Stegenga, Rafael Selbach Scheffel, Mouhammed Amir Habra, Inbar Finkel, Antonio Prinzi, Wouter T. Zandee, Fabián Pitoia, Jan Jiskra, Ladislaia Wolff, Ali Saeed Alzahrani, Thera P. Links, Christine Spitzweg, Viktoria Florentine Koehler, Rajeev Parameswaran, Francesco Frasca, Won Gu Kim, Vania Balderrama-Brondani, W. Edward Visser, Matti L. Gild, Ana Luiza Maia, Ralf Paschke, Chae A. Kim, Jolanta Krajewska, Jonathan Wadsley, Magdalena Kolton, Jason Sheehan
article en

Abstract

Background: Brain metastases (BMs) from nonanaplastic follicular cell–derived thyroid carcinoma (hereinafter referred to as non-ATC) are rare and not well characterized, with limited evidence guiding treatment and prognostic stratification. We aimed to describe clinical features, treatment patterns, and outcomes of patients with BMs from non-ATC and to develop and validate a disease-specific prognostic score. Methods: This retrospective international multicenter study included adults with histologically confirmed non-ATC and radiologically documented BMs treated at 19 tertiary referral centers. Clinical, radiological, treatment, and outcome data were collected. Independent predictors of progression-free survival (PFS) and overall survival (OS) were analyzed using Cox regression, and variables identified were used to develop a disease-specific Graded Prognostic Assessment (non-ATC GPA), exploratorily assessed in an independent SEER cohort. Results: A total of 189 patients were included; median age at BM diagnosis was 59 years (interquartile range [IQR] 48–67). First-line BM treatments included stereotactic radiosurgery (27.0%), neurosurgery (23.8%), whole-brain radiotherapy (18.5%), and best supportive care (10.6%). Median PFS was 7.0 months (IQR: 2.9–22.4), and median OS was 15.0 months (IQR: 4.0–38.4). Independent predictors of shorter OS were age >75 years, Eastern Cooperative Oncology Group performance status ≥2, papillary histology, extracranial metastases, and ≥4 BM. The GPA stratified patients into four prognostic groups with median OS ranging from 72.6 months in the highest-score group to 3.7 months in the lowest. An exploratory SEER-based assessment showed survival differences across adapted prognostic groups ( p = 0.036), although this analysis was limited by the absence of all key GPA variables. Conclusions: BMs from non-ATC are associated with poor survival and marked prognostic heterogeneity. The proposed GPA may provide a useful framework for prognostic stratification, pending further validation in independent datasets to support individualized management.

Thyroid
Ulsan College (KR), The University of Sydney (AU), Universidade Federal do Rio Grande do Sul (BR), University Medical Center Groningen (NL), The University of Texas MD Anderson Cancer Center (US), National University of Singapore (SG), University of Calgary (CA), University of Groningen (NL), Inha University (KR), Charles University (CZ), Tel Aviv Sourasky Medical Center (IL), Royal North Shore Hospital (AU), King Faisal Specialist Hospital & Research Centre (SA), Asan Medical Center (KR), Erasmus MC (NL), Weston Park Cancer Centre (GB), LMU Klinikum (DE), University of Ulsan (KR), Hospital de Clínicas de Porto Alegre (BR), Na Homolce Hospital (CZ), Ospedale Garibaldi (IT), Hospital de Clínicas "José de San Martín" (AR), The Maria Sklodowska-Curie National Research Institute of Oncology (PL), University of Virginia (US), Medical University of Vienna (AT), Ludwig-Maximilians-Universität München (DE), University of Palermo (IT), Erasmus University Rotterdam (NL)
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Thyroid Cancer Diagnosis and Treatment
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