Neuropsychological outcomes on Head Start III: a prospective, multi-institutional clinical trial for young children diagnosed with malignant brain tumors

Abstract

Background Current pediatric brain tumor treatment focuses on titrating toxicity based on risk factors while simultaneously improving survivorship. The Head Start (HS) protocols I to IV (1991-present) use high-dose chemotherapy (HDCTx) with an aim of reducing or eliminating cranial irradiation in very young children, the most vulnerable to its effects. Methods We examined estimated Full Scale IQ, overall Adaptive Functioning, Working Memory, Processing Speed, and Verbal and Nonverbal Memory outcome data for 43 HS III patients diagnosed between ages 2 months and 7 years from 15 institutions in the United States and Canada. Results At a mean of 5.12 years postdiagnosis, the HS III patients performed within the average to low-average ranges across these variables; however, individual variability was noted with scores ranging from superior to impaired, and the sample as a whole performed lower than age expectations. Performance did not significantly differ by sex or ethnicity, diagnosis, or for those treated with an intravenous methotrexate dose of 400 mg/kg vs 270 mg/kg. Additionally, performance did not significantly differ by age at diagnosis or length of follow-up. Conclusions The results, indicating overall average to low-average neurocognitive functioning, are encouraging, though significant individual variability was noted. Those who were younger at diagnosis, received more intensive methotrexate, and were further out from treatment were not at significantly increased risk of cognitive decline within our sample, suggesting a strategy of using HDCTx and autologous hematopoietic progenitor cell rescue to reduce or eliminate irradiation may allow for continued CNS development in young children treated for a brain tumor.

High-Dose Chemotherapy in Children with Newly Diagnosed Medulloblastoma

“…Twenty-four patients (56%) had MB and 12 (28%) received radiation therapy. As a group, the Headstart III patients per-formed within average to low-average range across all tested variables and no significant difference were found by diagnosis (MB, PNET and others) [45]. Fay McClymont et al, also reported the neurocognitive profile of 24 survivors of MB treated with HDC according to the protocol 99703.…”

Neuropsychological Outcomes of Children Treated for Brain Tumors

“…For these reasons, cognitive and neuropsychological outcomes have been included as endpoints in recent trials with the aim of reducing or eliminating radiotherapy, when possible, without affecting prognosis. Headstart trials focused on intensive chemotherapy followed by hematopoietic stem cell rescue with the goal of avoiding or postponing radiotherapy; results published from Headstart II and III showed stable neuro-cognitive functioning over time, suggesting this approach to be effective in sparing CNS development in young children [ 74 ].…”

Educational Pain Points for Pediatric Brain Tumor Survivors: Review of Risks and Remedies

“…Cranial radiation therapy (CRT) is often identified as the most impactful and deleterious treatment-related risk factor to neurocognitive outcomes for PBT survivors due to white matter changes that associate with neurocognitive dysfunction and persisting late effects [ 21 ]. Chemotherapy, while thought to be less toxic relative to radiation treatment, has been associated with cognitive impairment [ 22 , 23 ], as well as hearing impairments [ 24 ] thus, magnifying the functional impact of neurocognitive late effects. Independent of other treatment modalities, neurosurgical resection of tumors is associated with neurocognitive morbidity [ 25 , 26 ] and in some cases results in the post-surgical complication of posterior fossa syndrome (also known as cerebellar mutism) characterized by diminished speech, ataxia, emotional and behavior lability, and apathy [ 27 ] which may lead to worse long term neurocognitive outcomes for PBT survivors [ 28 ].…”