EPCO-01. MOLECULAR PROFILING OF SPINAL CORD EPENDYMOMA

BACKGROUND Ependymomas are currently classified into 9 subgroups by DNA methylation profiles. Although spinal cord ependymoma (SP-EPN) is distinct from other tumors, diversity within SP-EPN is still unclear. Here, we used transcriptomic and epigenomic profiles to investigate the diversity among Japanese SP-EPN cases. MATERIALS AND METHODS We analyzed 57 SP-EPN patients (32 males and 25 females, aged from 18 to 78 years, median: 52), including two cases of neurofibromatosis type 2, five cases of grade 3 (WHO grade). We obtained transcriptome (RNA-seq) and DNA methylation (Infinium Methylation EPIC array) data from fresh frozen specimens of SP-EPN resected at the University of Tokyo Hospital and our collaborative groups. RESULTS Three cases had a previous intracranial ependymoma operation. Hierarchical clustering of the DNA methylation data showed that these three cases of intracranial origin as a different cluster from spinal origin. The 45 grade 2 spinal ependymoma showed a relatively homogenous methylation pattern. However, the methylation status of HOX gene cluster regions is compatible with the segment of origin, which reflects the cells of origins are derived after the determination of segment identity. RNA sequencing of 57 cases revealed two subgroups within grade 2. Gene ontology analysis of differentially expressed genes suggested the difference in metabolic state such as rRNA translation and mitochondrial respiration between the two expression subgroups. CONCLUSION Epigenetic analysis indicated the accurate body segment origin of SP-EPN. We observed that metabolic states could divide grade 2 spinal cord ependymoma into 2 subgroups and will present the relationship to clinicopathological information.

Multisegmental Versus Monosegmental Intramedullary Spinal Cord Ependymomas: Perioperative Neurological Functions and Surgical Outcomes

Objectives: Multiple factors, such as tumor size, lateralization, tumor location, accompanying syringomyelia, and regional spinal cord atrophy, may affect the resectability and clinical prognosis of intramedullary spinal cord ependymomas. However, whether long-segmental involvement of the spinal cord may impair functional outcomes remains unclear. This study was aimed to compare perioperative neurological functions and long-term surgical outcomes between multisegmental ependymomas and their monosegmental counterparts.Methods: A total of 54 patients with intramedullary spinal cord ependymoma (WHO Grade II) were enrolled, and all of them underwent surgical resection. The patients were classified into the multisegmental group (n=40) and the monosegmental group (n=14). Perioperative and long-term (average follow-up period, 53.5 ± 18.2 months) neurological functions were evaluated using the modified McCormick (mMC) scale and the modified Japanese Orthopaedic Association (mJOA) scoring system.Results: Preoperative neurological functions in the multisegmental group were significantly worse than those in the monosegmental group (P < 0.05). However, postoperative short-term neurological functions, as well as long-term functional outcomes, were similar between the two groups (P > 0.05). Logistic regression analysis showed that only preoperative mMC and mJOA scores were significantly correlated with neurological improvement during the follow-up period (P < 0.05).Conclusion: Multisegmental involvement of the spinal cord is associated with worse neurological functions in patients with intramedullary spinal cord ependymoma, while the long-term prognosis is not affected. The preoperative neurological status of the patient is the only predictor of long-term functional improvement.

Surgical outcome and prognostic factors in spinal cord ependymoma: a single-center, long-term follow-up study

Objective: Spinal cord ependymomas account for 3–6% of all central nervous system tumors and around 60% of all intramedullary tumors. The aim of this study was to analyze the neurological outcome after surgery and to determine prognostic factors for functional outcome. Patients and Methods: Patients treated surgically due to a spinal cord ependymoma between 1990 and 2018 were retrospectively included. Demographics, neurological symptoms, radiological parameters, histopathology, and neurological outcome (using McCormick Score [MCS]) were analyzed. Possible prognostic factors for neurological outcome were evaluated. Results: In total, 148 patients were included (76 males, 51.4%). The mean age was 46.7 ± 15.3 years. The median follow-up period was 6.8 ± 5.4 years. The prevalence was mostly in the lumbar spine (45.9%), followed by the thoracic spine (28.4%) and cervical spine (25.7%). Gross-total resection was achieved in 129 patients (87.2%). The recurrence rate was 8.1% and depended on the extent of tumor resection ( p = 0.001). Postoperative temporary neurological deterioration was observed in 63.2% of patients with ependymomas of the cervical spine, 50.0% of patients with ependymomas of the thoracic spine, and 7.4% of patients with ependymomas of the lumbosacral region. MCS 1–2 was detected in nearly two-thirds of patients with cervical and thoracic spinal cord ependymoma 36 months after surgery. Neurological recovery was superior in thoracic spine ependymomas compared with cervical spine ependymomas. Poor preoperative functional condition (MCS >2), cervical and thoracic spine location, and tumor extension >2 vertebrae were independent predictors of poor neurological outcome. Conclusion: Neurological deterioration was seen in the majority of cervical and thoracic spine ependymomas. Postoperative improvement was less in thoracic cervical spine ependymomas compared with thoracic spine ependymomas. Poor preoperative status and especially tumor extension >2 vertebrae are predictors of poor neurological outcome (MCS >2).

EPEN-50. THE MANAGEMENT AND TREATMENT OF PEDIATRIC SPINAL CORD EPENDYMOMA: RESULTS FROM A COLLABORATIVE INTERNATIONAL MULTI-INSTITUTIONAL REVIEW

PURPOSE Pediatric Spinal cord ependymoma (SCE) is rare, and the management is often heterogeneous across centers. We evaluated the impact of clinical, pathologic, and treatment-related factors on outcomes in a multi-institutional, international cohort. METHODS SCE patients age &lt;21 years were reviewed across 5 institutions. We utilized nonparametric descriptive statistics, survival, and recursive partitioning analysis (RPA) to examine patient, tumor, histopathologic and treatment characteristics, failure pattern, and cause of death. RESULTS 125 patients were identified, 18 (14.4%) with metastases. Initial surgery was GTR, and STR in 44, 56% of patients respectively. Histology was grade 1, 2, and 3 in 55, 17.7 and 23.2% respectively. 55 patients with initial GTR were observed (52.7%) or irradiated (43.6%); 60 patients had STR and were observed (40%) or irradiated (60%). The 7-year event-free (EFS) and overall survival (OS) was 60% (95% CI 51.5–71.4) and 79% (95% CI 71.1–87.8) respectively. STR and metastasis increased the hazard for death [HR 1.87, 95% CI 1.02–3.57, p=0.05 (vs. GTR)] and [HR 2.28, 95% CI 1.1–5.2, p=0.048 (vs. localized)] respectively. Across 43 failures, local failure predominated (48.8%). Distant and combined failure occurred in 30.2 and 13.9% respectively. Adjuvant RT offered a 20% absolute improvement (vs. observation) in EFS at 5 years regardless of extent of resection. RPA identified thoracic (vs. non-thoracic), grade (1 & 3 vs. 2), STR (vs. GTR) and metastases as determinants of inferior EFS. CONCLUSIONS Tumor and treatment-related factors are predictive of EFS. OS is favorable despite diverse schema and frequent distant failures.

PATH-33. EPIGENOMIC ANALYSIS OF SPINAL EPENDYMOMA

BACKGROUND Ependymomas commonly occur in the fourth ventricle and the spinal cord. Gross total resection, age and WHO grade are known prognostic factors. Ependymomas are currently classified into 9 distinct subgroups by DNA methylation profile analysis. Spinal cord ependymoma is distinct from other subgroups. To investigate heterogeneity within spinal cord ependymoma, we examined DNA methylation profiles. MATERIALS AND METHODS We used Infinium MethylationEPIC array (illumina) to obtain DNA methylation data from frozen specimens of spinal ependymoma resected at the University of Tokyo, Osaka City University, and Tokyo Metropolitan Neurological Hospital. Japan Pediatric Molecular Neuro-Oncology Group provided methylation data for 11 reported cases. Cluster analysis was performed using Cluster3.0. RESULTS We analyzed 34 patients, 21 male and 13 female, aged from 18 to 76 years (median 50.5 years), including 2 cases with neurofibromatosis type 2. WHO grade was grade_3 in 2 cases and grade_2 in others. Clustering of the DNA methylation data showed that WHO grade_3 cases tended to be classified into a subgroup distinct from other cases. CONCLUSION This is the largest DNA methylation profiling study on spinal cord ependymoma to date. The study may suggest a new subgroup correlated with higher WHO grade.