CNS Tumors
Children treated for brain tumors are at greatest cognitive risk given tumor mass effect and CNS-directed therapy.34Accordingly, many of the current trials emerging from the COG CNS committee center around modifying front-line therapy to maintain high survival rates (e.g., non-inferiority trials) while improving QOL. Since ALTE07C1 was discontinued as a free-standing protocol, there have been more than 10 new studies developed within the CNS committee that include cognitive and/or QOL assessments, highlighting the importance of collaborations with the BSC.
BSC members are also actively involved in intervention trials that seek to mitigate the emergence of cognitive late effects. ACCL2031 is a prime example whereby memantine, a glutamatergic NMDA receptor antagonist, is being investigated as a neuroprotectant in a randomized, placebo-controlled trial. Memantine has been shown to be neuroprotective in preclinical models35,36 and resulted in less cognitive decline among adults receiving whole brain radiation therapy for brain metastases.37 ACCL2031 randomizes children with primary CNS tumors, initiating cranial radiation therapy, to memantine or placebo. Change in cognitive functioning is the primary outcome for this trial. Cogstate and parent-reported executive function are required assessments for monitoring outcomes; the COG Standardized Neurocognitive Assessment Battery is recommended but not required. Trial enrollment is underway for this NCI-funded study. Notably, positive study findings would suggest cognitive late effects can be prophylactically ameliorated or even prevented.