Clinical trials in pediatric neuro-oncology: what is missing and how we can improve

Abstract

Brain tumors are the most common solid tumor in childhood, yet outcomes vary dramatically. High-grade gliomas have dismal outcomes with poor survival. By contrast, low-grade gliomas, have high survival rates, but children suffer from morbidity of tumor burden and therapy-associated side effects. In this article, we discuss how current trial designs often miss the opportunity to include end points beyond tumor response and thus fail to offer complete assessments of therapeutic approaches. Quality of life, neurocognitive function and neurofunctional deficits need to be considered when assessing overall success of a therapy. Herein, we identify specific end points that should be included in the interpretation of clinical trial results and accordingly, offer a more comprehensive approach to treatment decision-making. • As a whole, treatment for pediatric brain tumors has greatly improved survival; however, patients can suffer from a myriad of treatment-related morbidities.• In particular, pediatric patients with low-grade tumors frequently go on to survive their tumor, but carry substantial burden related to prior treatments.• Quality of life (QoL), decreased neurocognitive ability and neurofunctional impairments are notable concerns for long-term survivors of pediatric brain tumors and these domains should be assessed when determining treatment strategies.• Historically, clinical trials have not adequately assessed QoL, neurocognition and neurofunctioning. These parameters deserve more attention and should be included as primary or secondary end points of clinical trials.• The Pediatric Quality of Life scales have been validated in the pediatric population and can effectively assess QoL in pediatric brain tumor patients.• Validated neurocognitive assessments such as CogState and the NIH Toolbox can play an important role in the evaluation of neurocognition in pediatric brain tumor patients.• Long-term motor, vision and hearing impairments may occur as a result of tumor and treatment in pediatric brain tumor patients and should be included in pediatric brain tumor clinical trial outcomes. BackgroundIn the USA, the number of adult survivors of pediatric brain tumors has been steadily increasing over recent years. The average 5-year survival rate for all-comers of pediatric brain cancers has risen to approximately 73% [1]. However, there is a broad range of survivorship depending on tumor type. Pure germinomas and pilocytic astrocytomas have 5-year survival rates greater than 90%; however, for diffuse intrinsic pontine glioma and other high-grade gliomas, outcomes remain extremely poor [2][3][4][5]. The main clinical trial objective for brain tumors with poor prognoses is to improve survival; however, quality of life (QoL) remains an important aspect for these children -especially if median survival is relatively short. Though, the current article is not focusing on explicit recommendations for highly aggressive tumors, QoL measures should still be addressed in trials for this group given the conceivably higher impor...

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