The European Society of Paediatric Oncology Ependymoma-II program Core-Plus model: Development and initial implementation of a cognitive test protocol for an international brain tumour trial

Abstract

It is increasingly accepted that survival alone is an inadequate measure of the success of childhood brain tumour treatments. Consequently, there is increasing emphasis on capturing quality of survival.Ependymomas are the third most frequently occurring brain tumours in childhood and present significant clinical challenges. European Society of Paediatric Oncology Ependymoma II is a comprehensive international program aiming to evaluate outcomes under different treatment regimens and improve diagnostic accuracy. Importantly, there has been agreement to lower the age at which children with posterior fossa ependymoma undergo focal irradiation from three years to either eighteen months or one year of age. Hitherto radiotherapy in Europe had been reserved for children over three years due to concerns over adverse cognitive outcomes following irradiation of the developing brain. There is therefore a duty of care to include longitudinal cognitive follow-up and this has been agreed as an essential trial outcome. Discussions between representatives of 18 participating European countries over 10 years have yielded European consensus for an internationally accepted test battery for follow-up of childhood ependymoma survivors. The 'Core-Plus' model incorporates a two-tier approach to assessment by specifiying core tests to establish a minimum dataset where resources are limited, whilst maintaining scope for comprehensive assessment where feasible. The challenges leading to the development of the Core-Plus model are presented alongside learning from the initial stages of the trial. We propose that this model provides a solution for future international trials addressing both childhood brain tumours and other conditions associated with cognitive morbidity.

Limited Research Investigating the Value of MRI in Predicting Future Cognitive Morbidity in Survivors of Paediatric Brain Tumours: A Call to Action for Clinical Neuroimaging Researchers

“…In the absence of a common outcome measure for these children (for instance a common data elements set as proposed by the National Institute of Neurological Disorders and Stroke (NINDS) for other neurological disease [84]) broad composite measures should be used that can capture multiple aspects of the neurocognitive morbidity experienced by these patients (for example the Wechsler Intelligence Scale for Children [46] or the NIH Toolbox Cognition Battery [85]. Neurocognitive assessment protocols are being developed for specific tumour groups (for instance in childhood ependymomas [86]) which will provide practical approaches to "strongly support the routine incorporation of neuropsychology assessments as key outcomes" to "facilitate successful global collaborations" [87]. These should be adopted wherever possible.…”

Transatlantic progress in measurement of cognitive outcomes in paediatric oncology trials

“…The first prospective application of the ‘Core Plus’ cognitive test battery 10 took place within the SIOP‐Europe Ependymoma II trial which remains in progress 11 . The protocol mandates assessments at post‐surgical baseline, 2 and 5 years from diagnosis and at age 18 years.…”

“…Similarly, on the SIOPE Ependymoma II trial, co-ordinators for each country were established, with evident improvement in adherence within those countries where charitable funding was obtained for a dedicated co-ordinator. In the UK, ascertainment in this trial was increased from 54% in the first year to 87% in the second year once a dedicated co-ordinator was employed to liaise with and support national centres 10. Feedback from local clinical psychologists has indicated the guidance provided is helpful and valued.There continue to be resource discrepancies between individual centres and 25% of COG sites were not able to open the ALTE7C1 study, many of which have limited psychological care.…”

Toward Improved Diagnosis Accuracy and Treatment of Children, Adolescents, and Young Adults With Ependymoma: The International SIOP Ependymoma II Protocol

“…Neurocognitive development and other aspects of quality of survival are captured through the SIOPE Core Plus model ( 26 ). This comprehensive battery of cognitive tests and quality of survival measures is implemented at postsurgical baseline, 2- and 5-year follow-up, and at age 18 years, as recently reported ( 27 ). The Core Plus model circumvents resource discrepancies within and between participating countries by mandating a minimum Core battery of measures augmented by more comprehensive measures where feasible.…”