Pediatric ependymoma: an overview of a complex disease

Abstract

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.

Multifocal and Multiphasic Demyelinating Lesions After Radiation for Ependymoma in a Pediatric Population

“…They are stratified into ST-EPN-RELA, ST-EPN-YAP, and ST-SE. 14,15 The most common subgroup (70%) is the C11orf95-RELA translocation, resulting in pathologic activation in the NFκB pathway. 15 This controls cell proliferation, apoptosis, and vascularization.…”

“…13 Ependymomas are the third most common malignant neurologic tumor in children. 14 Most ependymomas are intracranial (90%). 15 The mean age at treatment is 3.8 years, with a 63.8% progression-free survival at 5 years.…”

Cell-of-Origin and Genetic, Epigenetic, and Microenvironmental Factors Contribute to the Intra-Tumoral Heterogeneity of Pediatric Intracranial Ependymoma

“…At present, 108 clinical trials are ongoing in pediatric EPN ( [ 224 ], accessed on 22 November 2021), however, they do not take into account EPN variants. Moving forward, the next challenge is to go beyond tumor control and to include EPN molecular classification in treatment decisions so as to adapt therapeutic strategies based on risk stratification, reducing therapy-induced morbidity in low-risk patients, while intensifying treatment for high-risk patients [ 225 ]. Development of new treatments for patients with EPN, especially in the pediatric cohort, meets several challenges, including low investment by pharmaceutical companies and low incidence of patients with rare cancers, that hamper testing of new compounds in prospective clinical trials [ 212 ].…”

Polish Multi-Institutional Study of Children with Ependymoma—Clinical Practice Outcomes in the Light of Prospective Trials

“…The goal of radical surgery could be achieved during the reoperation without compromising the benefit of R0 resection, which was confirmed in the ACNS0121 trial; however, this result concerns only patients with brain tumours [ 6 ]. Patients with brain tumors arising from the floor and the lateral aspect of the fourth ventricle were found to have worse outcome than those arising from the roof, possibly due to the more difficult surgery, if the rate of postoperative deficits is kept as low as possible [ 67 ]. The persistent lack of agreement is probably a result of the fact that the vast majority of failures occur inside the tumour bed or in the region treated with a high dose, especially when radical resection was not achieved [ 33 , 44 , 68 ].…”

“…The introduction of molecular grading into the diagnosis of ependymomas, combined with clinical and histological features, could be used for developing a risk-stratification model for patients and serves as a model for future treatment decisions [ 33 , 61 , 62 , 63 , 64 , 65 , 66 , 67 ]. The identification of those who could benefit from the treatment deintensification or, on the contrary, a more aggressive approach, should be the aim of future prospective trials.…”