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.