In a prospective longitudinal trial reported in the Journal of Clinical Oncology, Ali et al found that infants treated for central nervous system (CNS) malignancies had baseline intellectual quotient (IQ) and parent-reported working memory and adaptive functioning worse than normative expectations; IQ remained stable over follow-up, whereas there appeared to be worsening attention and executive function over time. Potential predictive factors in outcomes were also identified.
Study Details
In the St. Jude Children’s Research Hospital–initiated phase II multicenter trial, a total of 293 patients were enrolled between November 2007 and May 2017. The current analysis includes 139 infants with newly diagnosed CNS tumors who underwent surgical resection and were treated with chemotherapy with or without focal proton or photon radiation therapy. Cognitive assessments were performed at baseline (postsurgery; early in adjuvant therapy from time of enrollment up to 60 days), 6 months, 1 year, and then annually for 5 years.
Neurocognitive testing included assessment of IQ; parent ratings of executive, emotional, and behavioral functioning; and socioeconomic status. Emerging executive functions, including working memory, were evaluated by parent report on the Behavior Rating Inventory of Executive Functioning–Preschool Version (BRIEF-P). Attention and adaptive skills were evaluated by parent report on the Behavior Assessment System for Children, Second Edition (BASC-2) and the Bayley-III Adaptive Behavior Composite.
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.— Ali et al
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Key Findings
Median length of follow-up was 816 days (26.8 months) among the 139 patients. At baseline, IQ (P < .001), adaptive functioning (Bayley-III Adaptive Skills Composite score; P < .001), and working memory (BRIEF-P Working Memory; P < .001) were below normative expectations, whereas BRIEF-P Global Executive Composite and BASC-2 Attention Problems were within age expectations.
Patients with higher socioeconomic status had higher IQ scores at baseline (P = .004), and a trend toward lower scores was found for younger age at diagnosis (P = .067). Poorer adaptive function was also associated with younger age at diagnosis (P = .009). No demographic or clinical factors predicted baseline values for the BRIEF-P Global Executive Composite, BRIEF-P Working Memory, or BASC-2 Attention Problems.
Longitudinal analysis showed that slopes for IQ, BRIEF-P Working Memory, BASC-2 Adaptive Skills, and Bayley-III Adaptive Behavior Composite did not significantly change over time. Slopes for BRIEF-P Global Executive Composite (P = .010) and BASC-2 Attention Problems showed worsening over time (P = .003). Tumor location was the sole significant predictor of change in IQ over time (P < .001), with supratentorial tumors being associated with greater IQ decline vs infratentorial tumors. Shunt placement was associated with increased parental concerns on BRIEF-P Working Memory (P = .002) and BRIEF-P Global Executive Composite scores (P = .008).
Treatment type (chemotherapy only vs chemotherapy plus focal radiotherapy and focal photon vs focal proton radiotherapy) did not affect IQ, BRIEF-P Working Memory, BASC-2 Adaptive Skills, or Bayley-III Adaptive Behavior Composite over time.
The investigators concluded, “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.”
Heather M. Conklin, PhD, of the Department of Psychology, St. Jude Children’s Research Hospital, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported in part by the National Cancer Institute and American Lebanese Syrian Associated Charities. For full disclosures of the study authors, visit ascopubs.org.
