Abstract Purpose Comprehensive data on frequency, clinical characteristics and outcomes of primary metastatic ependymoma in children are limited. Methods Children with intracranial or spinal ependymoma registered between 2000 and 2025 in the “HIT-2000 trial, HIT-2000 interim-registry, I-HIT-MED-registry and SIOP-Ependymoma II study were analysed according to initial staging (postoperative residual tumor, metastases), tumour biology, treatment and outcome based on central neuropathological/-radiological review. Results Among 822 patients, lumbar cerebrospinal fluid (CSF) analysis was available in 763 patients, MRI in all. Metastatic disease was identified in 36 patients (4.4%; 22 males/14 females; median age 11.3 years (range, 0.4–17.1)). Primary tumor site was intracranial (20/766, 2.6%) in 20 patients (PF-EPN-A, n = 10; PF-EPN-B, n = 2; PF-EPN-NOS, n = 1; ZFTA–RELA, n = 3; not classifiable/unknown, n = 4) and spinal (16/56, 28.6%) in 16 (MPE, n = 13; SP-EPN, n = 3). Six intracranial cases showed microscopic CSF positivity only (M1; 0.8% of CSF-staged patients), five relapsed and one died. Intracranial metastases (M2) occurred in 13 patients (intracranial, n = 11; spinal, n = 2), and spinal metastases (M3) in 28 (intracranial, n = 12; spinal, n = 16). Median follow-up time was 5.9 years (SD ± 1.12). Residual tumor after initial surgery persisted in 18 patients (11≥1 re-surgery). First-line radiotherapy was administered to 16 patients (44.4%), most receiving craniospinal irradiation (CSI, n = 13; local radiotherapy only, n = 3). Chemotherapy was applied in 18 patients (50.0%; SKK/mSKK n = 13; high-dose chemotherapy n = 1; others n = 4) with measurable response in 16 patients (CR, n = 3, PR, n = 2, SD, n = 5, and PD, n = 6). Twenty-two tumors relapsed (intracranial, n = 17; spinal, n = 5) and 8 patients died (intracranial, n = 7, including 4 PF-EPN-A; spinal, n = 1). Intracranial primaries had inferior 5-year progression-free and overall survival vs. spinal (PFS, 14.4%±9.2% vs. 63.0%±17.7%, OS, 60.4%±11.7% vs. 100%, pPFS/pOS=0.02/0.12). Conclusion Primary metastatic pediatric ependymoma is rare and differs by primary site. Metastatic intracranial ependymoma is associated with a significantly worse progression-free survival and overall unfavourable outcome compared with metastatic spinal disease.
Fiedler et al. (Tue,) studied this question.