Biology and management of ependymomas

Abstract

Ependymomas are rare primary tumors of the central nervous system in children and adults that comprise histologically similar but genetically distinct subgroups. The tumor biology is typically more associated with the site of origin rather than being age-specific. Genetically distinct subgroups have been identified by genomic studies based on locations in classic grade II and III ependymomas. They are supratentorial ependymomas with C11orf95-RELA fusion or YAP1 fusion, infratentorial ependymomas with or without a hypermethylated phenotype (CIMP), and spinal cord ependymomas. Myxopapillary ependymomas and subependymomas have different biology than ependymomas with typical WHO grade II or III histology. Surgery and radiotherapy are the mainstays of treatment, while the role of chemotherapy has not yet been established. An in-depth understanding of tumor biology, developing reliable animal models that accurately reflect tumor molecule features, and high throughput drug screening are essential for developing new therapies. Collaborative efforts between scientists, physicians, and advocacy groups will enhance the translation of laboratory findings into clinical trials. Improvements in disease control underscore the need to incorporate assessment and management of patients' symptoms to ensure that treatment advances translate into improvement in quality of life.

Keywords: Collaborative Ependymoma Research Network; ependymoma; management; molecular classification; rare disease.

Fig. 1.

Histological features of (A) myxopapillary ependymoma, (B) subependymoma, (C) ependymoma, and (D) anaplastic ependymoma. (E) Description of histological characteristics of ependymomas of all grades. Red * indicates perivascular pseudorosettes, and red solid triangle indicates ependymal rosettes. Scale bar = 50 microns.

Fig. 2.

MRI with gadolinium showing a myxopapillary ependymoma of the filum terminale presenting as a contrast-enhanced spinal mass.

Fig. 3.

Progression-free survival distributions according to tumor location (A) and tumor grade (B). (Adapted from Vera-Bolanos et al, 2015, and used with permission of Oxford University Press).

Fig. 4.

Progression-free survival distributions by age at diagnosis (A) and initial treatment (B). (Adapted from Vera-Bolanos et al, 2015, and used with permission of Oxford University Press).

Fig. 5.

Genetically distinct subgroups in supratentorial, infratentorial and spinal cord ependymomas of WHO grades II and III. Abbreviations: PFA: CIMP+, posterior fossa group A: CpG island methylator phenotype positive; PFB: CIMP-, posterior fossa group B: CpG island methylator phenotype negative.

Fig. 6.

The core research projects are built around and support the development of new treatments through clinical trials.