Neuropsychological outcomes of patients with low-grade glioma diagnosed during the first year of life

Abstract

Purpose: Low-grade gliomas (LGG) are a heterogeneous group of brain tumors, which are often assumed to have a benign course. Yet, children diagnosed and treated for LGG in infancy are at increased risk for neurodevelopmental disruption. We sought to investigate neuropsychological outcomes of infants diagnosed with LGG. Methods: Between 1986 and 2013, 51 patients were diagnosed with LGG before 12 months of age and managed at St. Jude Children’s Research Hospital. Twenty-five of the 51 patients received a cognitive assessment (68% male; 6.8 ± 3.3 months at diagnosis; 10.5 ± 4.8 years at latest assessment). Approximately half the patients received radiation therapy (n = 12; aged 4.0 ± 3.0 years at radiation therapy), with a median of 2 chemotherapy regimens (range = 0 – 5) and 1 tumor directed surgery (range = 0 – 5). Results: The analyses revealed performance below age expectations on measures of IQ, memory, reading, mathematics, and fine motor functioning as well as parent-report of attention, executive, and adaptive functioning. Following correction for multiple comparisons, a greater number of chemotherapy regimens was associated with lower scores on measures of IQ and mathematics. More tumor directed surgeries and presence of visual field loss were associated with poorer dominant hand fine motor control. Radiation therapy exposure was not associated with decline in neuropsychological performance. Conclusions: Children diagnosed with LGG in infancy experience substantial neuropsychological deficits. Treatment factors, including number of chemotherapy regimens and tumor directed surgeries, may increase risk for neurodevelopmental disruption and need to be considered in treatment planning.

Cognitive and Psychosocial Development in Young Children with Brain Tumors: Observations from a Clinical Sample

“…Rates of impairment across domains were notable, with a significant proportion of patients in the impaired range (<10th percentile) across domains. However, in contrast to expectations and other studies [7,8], medical and demographic factors were largely unrelated to variability in functioning. The exception was younger age at diagnosis and longer time since diagnosis, which were both associated with worse performance on the cognitive composite.…”

“…Given these youth experience a significant neurological hit (e.g., presence of a brain tumor, surgery to remove, receipt of neurotoxic therapies) before entering school, understanding their early cognitive and psychosocial profile would allow for the development of effective early interventions that may prevent the emergence of later concerns (e.g., learning problems, reduced graduation rates). Unfortunately, the limited research that has been done with patients diagnosed at an early age has primarily documented the presence of impairments when these patients are school-aged (age 8 or older) and several years post-diagnosis and treatment [6,7]. There are few, if any, studies that explicitly evaluate the neurocognitive and psychosocial abilities of patients with brain tumors during early childhood (e.g., ages 0 to 6).…”

Treatment age and neurocognitive outcomes following proton beam radiotherapy for pediatric low‐ and intermediate‐grade gliomas

“…Diagnosis and treatment with XRT at a younger age increases cognitive risk for patients with pediatric LIGG. 5 To minimize neurocognitive late effects, radiotherapy is often delayed or avoided in younger patients, and chemotherapy is used as the preferred initial treatment. 6 In the current study, we prospectively assessed neurocognitive functioning following PRT in pediatric patients with LIGG.…”

“…In contrast, proton beam radiotherapy (PRT) allows for steep dose gradients and has superior dose profiles compared to XRT, 4 sparing healthy tissue. Diagnosis and treatment with XRT at a younger age increases cognitive risk for patients with pediatric LIGG 5 . To minimize neurocognitive late effects, radiotherapy is often delayed or avoided in younger patients, and chemotherapy is used as the preferred initial treatment 6 …”

Late effects after childhood brain tumor treatment: it’s not just about the radiation

“…The finding that neurocognitive and psychosocial functioning depend not only on the receipt of radiation but also on the combined burden of other anticancer therapies is an important point that is often neglected by patients and oncologists alike. Although part of an exploratory analysis, this finding adds to a growing body of literature that chemotherapy and surgery (including shunt placement) are not always benign interventions, and can cause long-standing toxicities that are cumulative over time in patients with primary brain tumors [5][6][7][8] as well as those with extracranial malignancies. 9,10 The state of pediatric late-effects research needs to move toward a state where the detriment to specific cognitive or psychosocial domains can be quantified on a granular, per-treatment level (Fig.…”