Spinal ependymal tumors form a histologically and molecularly heterogeneous group of tumors with generally good prognosis. However, their treatment can be challenging if infiltration of the spinal cord or dissemination throughout the central nervous system (CNS) occurs and, in these cases, clinical outcome remains poor. Here, we describe a new and relatively rare subgroup of spinal ependymal tumors identified using DNA methylation profiling that is distinct from other molecular subgroups of ependymoma. Copy number variation plots derived from DNA methylation arrays showed MYCN amplification as a characteristic genetic alteration in all cases of our cohort (n = 13), which was subsequently validated using fluorescence in situ hybridization. The histological diagnosis was anaplastic ependymoma (WHO Grade III) in ten cases and classic ependymoma (WHO Grade II) in three cases. Histological re-evaluation in five primary tumors and seven relapses showed characteristic histological features of ependymoma, namely pseudorosettes, GFAP- and EMA positivity. Electron microscopy revealed cilia, complex intercellular junctions and intermediate filaments in a representative sample. Taking these findings into account, we suggest to designate this molecular subgroup spinal ependymoma with MYCN amplification, SP-EPN-MYCN. SP-EPN-MYCN tumors showed distinct growth patterns with intradural, extramedullary localization mostly within the thoracic and cervical spine, diffuse leptomeningeal spread throughout the whole CNS and infiltrative invasion of the spinal cord. Dissemination was observed in 100% of cases. Despite high-intensity treatment, SP-EPN-MYCN showed significantly worse median progression free survival (PFS) (17 months) and median overall survival (OS) (87 months) than all other previously described molecular spinal ependymoma subgroups. OS and PFS were similar to supratentorial ependymoma with RELA-fusion (ST-EPN-RELA) and posterior fossa ependymoma A (PF-EPN-A), further highlighting the aggressiveness of this distinct new subgroup. We, therefore, propose to establish SP-EPN-MYCN as a new molecular subgroup in ependymoma and advocate for testing newly diagnosed spinal ependymal tumors for MYCN amplification.Electronic supplementary materialThe online version of this article (10.1007/s00401-019-02056-2) contains supplementary material, which is available to authorized users.

IntroductionThis study aimed to assess psychological distress (PD) as scored by the Distress Thermometer (DT) in adult primary brain tumor patients and caregivers (CGs) in a clinic setting and ascertain if any high-risk subgroups for PD exist.Material and methodsFrom May 2012 to August 2013, n = 96 patients and n = 32 CG underwent DT screening at diagnosis, and a differing cohort of n = 12 patients and n = 14 CGs at first recurrence. Groups were described by diagnosis (high grade, low grade, and benign) and English versus non English speaking. Those with DT score ≥4 met caseness criteria for referral to psycho-oncology services. One-way ANOVA tests were conducted to test for between-group differences where appropriate.ResultsAt diagnosis and first recurrence, 37.5 and 75.0% (respectively) of patients had DT scores above the cutoff for distress. At diagnosis, 78.1% of CGs met caseness criteria for distress. All CGs at recurrence met distress criterion. Patients with high-grade glioma had significantly higher scores than those with a benign tumor. For patients at diagnosis, non English speaking participants did not report significantly higher DT scores than English speaking participants.DiscussionPsychological distress is particularly elevated in CGs and in patients with high-grade glioma at diagnosis. Effective PD screening, triage, and referral by skilled care coordinators are vital to enable timely needs assessment, psychological support, and effective intervention.

No abstract

Return to work following treatment does occur but it is not a common outcome.

To determine the outcome of elderly patients with glioblastoma managed with hypofractionated [40 Gray (Gy)] or long-course (60 Gy) radiation therapy (RT). Patients aged >60 years diagnosed with WHO grade IV glioma managed with RT between October 2006 and July 2012 were retrospectively identified. Baseline data including ECOG performance status, RT dose and use of temozolomide (TMZ) were recorded. Overall survival was calculated in months from date of diagnosis. 109 patients were included with age distribution from 61 to 88 years (13 % <65, 63 % 65-75, and 24 % >75). Median survival (MS) of total group was 12 months (95 % CI 11-13) with 12 % surviving beyond 2 years. For age groups <65, 65-75, >75 the survival was 17, 12, and 9 months respectively (p = 0.001). Near total resection (p = 0.027), but not ECOG 0-1 (p = 0.34) was associated with improved MS. For the 69 patients aged 65-75, 55 % were managed with 40 Gy and 45 % 60 Gy. Longer survival was associated with the use of 60 Gy (15 vs. 9 months, p < 0.0001), and use of TMZ (13 vs. 7 months, p < 0.0001). In the 48 patients (70 %) managed with TMZ, the MS was 15 months with 60 Gy (95 % CI 13-17) compared with 11 months (95 % CI 9-13) in those with 40 Gy. Performance status with ECOG 0-1 was not associated with improved survival (p = 0.25). Within the limitations of a retrospective study, we demonstrate improved MS in the elderly population when TMZ is added to RT. Those in the age group 65-75 may benefit from long-course RT with TMZ.