Predictors of Cognitive Performance Among Infants Treated for Brain Tumors: Findings From a Multisite, Prospective, Longitudinal Trial

Abstract

PURPOSE Infants treated for CNS malignancies experience a significantly poorer response to treatment and are particularly at risk for neuropsychological deficits. The literature is limited and inconsistent regarding cognitive outcomes among this group. We investigated predictors of cognitive outcomes in children treated for brain tumors during infancy as part of a large, prospective, multisite, longitudinal trial. PATIENTS AND METHODS One hundred thirty-nine infants with a newly diagnosed CNS tumor were treated with chemotherapy, with or without focal proton or photon radiation therapy (RT). Cognitive assessments were conducted at baseline, 6 months, 1 year, and then annually for 5 years. The median length of follow-up was 816 days (26.8 months). Neurocognitive testing included assessment of intellectual functioning (intellectual quotient [IQ]), parent ratings of executive functioning and emotional and behavioral functioning, and socioeconomic status. RESULTS At baseline, IQ, parent-reported working memory, and parent-reported adaptive functioning were worse than normative expectations. Baseline cognitive difficulties were associated with younger age at diagnosis and lower socioeconomic status. Linear mixed models did not demonstrate a decline in IQ over time. There were increased parent-reported attention and executive problems over time. Increased concerns were related to supratentorial tumor location and CSF diversion. There were no differences in cognitive outcomes based on treatment exposure (chemotherapy-only v chemotherapy with RT and proton v photon focal RT). CONCLUSION Even before adjuvant therapy, young children with brain tumors experience cognitive difficulties that can affect quality of life. Changes in cognitive functioning over time were dependent on tumor location and surgical factors rather than adjuvant therapy. These findings may serve to guide treatment planning and indicate targets for cognitive monitoring and intervention.

Survivors of infant atypical teratoid/rhabdoid tumors present with severely impaired cognitive functions especially for fluid intelligence and visual processing: data from the German brain tumor studies

“…Intensive treatment was associated with relevant impairments in fluid intelligence and visual processing, the latter previously described as visual‐spatial performance problems by Lafay‐Cousin et al 13 . In a recent study of infant survivors of various pediatric brain tumors, estimated IQ and attentional functions were found below the expected population score, 11 but were rather related to tumor location and just surgery than subsequent treatment. As full‐scale or estimated IQ is highly dependent on processing speed and visuomotor coordination, our findings suggest that simply evaluating the IQ score does not reflect all possible impairments associated with multimodal treatment 26 .…”

“…Their sequelae included attentional performance and psychomotor speed as described before for this histologic group, even if patients just received surgical resection. 18,20,37 Such deficits are probably associated with tumor location, 11,18 white matter volume reduction, 38 and impaired cerebello-thalamo-cerebral pathways 39 in both ATRT and…”

“…QoL has been assessed solely after proton therapy with no significant abnormalities shortly after treatment 10 . A recent study by Ali et al 11 . investigated cognitive performance, as well as executive, behavioral, and adaptive functioning in infants with various central nervous system (CNS) tumors, including ATRT.…”

Molecular Landscape in Infant High-Grade Gliomas: A Single Center Experience

“…Therefore, the poor prognosis is intricate with a higher incidence of early and late toxicities, experienced by long-term survivors [ 28 ]. Ali et al investigated 132 children with CSN tumors, identifying several factors as predictors of neurocognitive outcome such as lower baseline QI, supratentorial tumor location, and younger age at diagnosis; however, the authors did not report any negative impact of adjuvant treatment (chemotherapy and/or focal RT) [ 29 ].…”

Patients With Pediatric Brain Tumor: When Do Their Delays Begin?

“…There are well-documented neuropsychologic risk factors of treatment for a pediatric brain tumor including young age. [3][4][5][6][7][8][9][10][11] In the current study by Ali et al, 12 the authors investigated predictors of neurocognitive outcomes of infants treated for pediatric brain tumors at a mean age of 1.7 years (standard deviation [SD] 5 1 year) at diagnosis. They present serial estimated intelligence quotient (IQ) data and parent-report questionnaires for 139 of 293 (47%) infants with a newly diagnosed CNS tumor who were treated on a St Jude Children's Research Hospital phase II consortium study (SJYC07) between 2007 and 2017.…”