A systematic review and meta-analysis of outcomes in pediatric, recurrent ependymoma

Byer, Lennox; Kline, Cassie; Coleman, Christina; Allen, Isabel Elaine; Whitaker, Evans; Mueller, Sabine

doi:10.1007/s11060-019-03255-3

Cited by 19 publications

(24 citation statements)

References 31 publications

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“…The prognostic value of tumor WHO grade in ependymomas had been debated (28)(29)(30)(31)(32)(33). Our study found that tumor pathology grade was a significant prognostic factor regarding PFS and OS in CEs; WHO grade II CEs had longer PFS and OS compared with WHO grade III tumors.…”

Section: Discussionmentioning

confidence: 59%

The Survival and Prognostic Factors of Supratentorial Cortical Ependymomas: A Retrospective Cohort Study and Literature-Based Analysis

Wang

Cheng

et al. 2020

Front. Oncol.

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Aim: Survival rates and prognostic factors of cortical ependymomas (CEs) remain elusive. This study aimed to perform a comprehensive analysis of prognostic factors, treatment, and outcomes for patients with CEs based on institutional and literature case series. Materials and Methods: Thirty patients with CEs from our department were included in this study. Furthermore, a systemic review of the literature yielded an additional 106 patients with CEs. Clinical data including patient age, sex, symptoms, tumor location, World Health Organization (WHO) grade, extent of surgery, radiation, recurrence, and survival were recorded and statistically analyzed. Results: From January 2009 to October 2019, 30 (4.2%) cases were diagnosed as CEs in our department. These series consisted of 19 males and 11 females, 10 continuous patients after 2017 screened for C11orf95-RELA fusion, and 9 patients (90%) were RELA fusion positive. During the follow-up period, nine (30%) patients depicted tumor recurrence or progression; four (13.3%) patients died of tumor progression. The literature review yielded 106 CE cases, with additional 30 cases of our own collected for further analysis. Of these 136 cases, the frontal lobe (40%) was the most common location, and the average age was 22.6 ± 17.6 years. Anaplastic histology/WHO grade III tumors were identified in 68 (50%) patients. Statistically analysis demonstrated that extent of surgery and WHO tumor grade were significant prognostic factors in Kaplan-Meier logrank testing and Cox proportional hazards models. Gross total resection (GTR) predicted longer progression-free survival (PFS) [P = 0.013, hazard ratio (HR) = 3.012, 95% confidence interval (CI) = 1.257-7.213] and overall survival (OS)

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Section: Discussionmentioning

confidence: 59%

The Survival and Prognostic Factors of Supratentorial Cortical Ependymomas: A Retrospective Cohort Study and Literature-Based Analysis

Wang

Cheng

et al. 2020

Front. Oncol.

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“…If no local treatment is feasible, chemotherapy can be administered alone [55]. However, prognosis of children with recurrent ependymoma remains poor [68]. A recently published retrospective analysis reported an increased risk for recurrence in patients with tumors with gain of chromosome 1q and/or PFA-methylation profile, further demonstrating only little benefit from resurgery and reirradiation in case of relapse [69].…”

Section: Therapy Of Spinal Ependymomamentioning

confidence: 99%

Pediatric ependymoma: an overview of a complex disease

Jünger

Timmermann²,

Pietsch

2021

Childs Nerv Syst

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Pediatric ependymomas comprise biologically distinct tumor entities with different (epi)genetics, age distribution and localization, as well as a different prognosis. Regarding risk stratification within these biologically defined entities, histopathological features still seem to be relevant. The mainstay of treatment is gross total resection (GTR) if possible, achieved with intraoperative monitoring and neuronavigation—and if necessary second surgery—followed by adjuvant radiation therapy. However, there is growing evidence that some ependymal tumors may be cured by surgery alone, while others relapse despite adjuvant treatment. To date, the role of chemotherapy is not clear. Current therapy achieves reasonable survival rates for the majority of ependymoma patients. The next challenge is to go beyond initial tumor control and use risk-adapted therapy to reduce secondary effect and therapy-induced morbidity for low-risk patients and to intensify treatment for high-risk patients. With identification of specific alterations, targeted therapy may represent an option for individualized treatment modalities in the future.

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“…Ependymomas (EPN) are a molecularly and clinically heterogeneous group of neoplasms which occur throughout the nervous system [1]. In children, EPN represent the second most common malignant brain tumors, with a prognosis still dismal in approximately 50% of the patients [2,3]. The extensive molecular characterization and more indepth knowledge of the pathogenetic mechanisms of the disease have so far not translated into substantial improvement in clinical practice as treatment remains challenging because of high intratumor heterogeneity and intrinsic chemoresistance [4,5].…”

Section: Introductionmentioning

confidence: 99%

The BET Inhibitor OTX015 Exhibits In Vitro and In Vivo Antitumor Activity in Pediatric Ependymoma Stem Cell Models

Servidei

Meco

Martini

et al. 2021

IJMS

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Childhood ependymomas are heterogenous chemoresistant neoplasms arising from aberrant stem-like cells. Epigenome deregulation plays a pivotal role in ependymoma pathogenesis, suggesting that epigenetic modifiers hold therapeutic promise against this disease. Bromodomain and extraterminal domain (BET) proteins are epigenome readers of acetylated signals in histones and coactivators for oncogenic and stemness-related transcriptional networks, including MYC/MYCN (Proto-Oncogene, BHLH Transcritpion Factor)-regulated genes. We explored BET inhibition as an anticancer strategy in a panel of pediatric patient-derived ependymoma stem cell models by OTX015-mediated suppression of BET/acetylated histone binding. We found that ependymoma tissues and lines express BET proteins and their targets MYC and MYCN. In vitro, OTX015 reduced cell proliferation by inducing G0/G1-phase accumulation and apoptosis at clinically tolerable doses. Mechanistically, inhibitory p21 and p27 increased in a p53-independent manner, whereas the proliferative driver, phospho-signal transducer and activator of transcription 3 (STAT3), decreased. Upregulation of apoptosis-related proteins and survivin downregulation were correlated with cell line drug sensitivity. Minor alterations of MYC/MYCN expression were reported. In vivo, OTX015 significantly improved survival in 2/3 orthotopic ependymoma models. BET proteins represent promising targets for pharmaceutical intervention with OTX015 against ependymoma. The identification of predictive determinants of sensitivity may help identify ependymoma molecular subsets more likely to benefit from BET inhibitor therapies.

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A systematic review and meta-analysis of outcomes in pediatric, recurrent ependymoma

Cited by 19 publications

References 31 publications

The Survival and Prognostic Factors of Supratentorial Cortical Ependymomas: A Retrospective Cohort Study and Literature-Based Analysis

The Survival and Prognostic Factors of Supratentorial Cortical Ependymomas: A Retrospective Cohort Study and Literature-Based Analysis

Pediatric ependymoma: an overview of a complex disease

The BET Inhibitor OTX015 Exhibits In Vitro and In Vivo Antitumor Activity in Pediatric Ependymoma Stem Cell Models

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