A prospective study of cognitive function in children receiving whole-brain radiotherapy and chemotherapy: 2-year results

Abstract

As survival rates have risen for children with malignant primary brain tumors, so has the concern that many survivors have significant permanent cognitive deficits. Cranial irradiation (CRT) has been implicated as the major cause for cognitive dysfunction. To clarify the etiology, incidence, and severity of intellectual compromise in children with brain tumors after CRT, a prospective study was undertaken comparing the neuropsychological outcome in 18 consecutive children with malignant brain tumors treated with CRT to outcome in 14 children harboring brain tumors in similar sites in the nervous system who had not received CRT. Children with cortical or subcortical brain tumors were not eligible for study. Neuropsychological testing was performed after surgery prior to radiotherapy, after radiotherapy, and at 1- and 2-year intervals thereafter. Children who had received CRT had a mean full-scale intelligence quotient (FSIQ) of 105 at diagnosis which fell to 91 by Year 2. Similar declines were noted in their performance intelligence quotient (IQ) and verbal IQ. After CRT, patients demonstrated a statistically significant decline from baseline in FSIQ (p less than 0.02) and verbal IQ (p less than 0.04). Children who had not received CRT did not demonstrate a fall in any cognitive parameter over time. The decline between baseline testing and testing performed at Year 2 in patients who had CRT was inversely correlated with age (p less than 0.02), as younger children demonstrated the greatest loss of intelligence. Children less than 7 years of age at diagnosis had a mean decline in FSIQ of 25 points 2 years posttreatment. No other clinical parameter correlated with the overall IQ or decline in IQ. After CRT, children demonstrated a wide range of dysfunction including deficits in fine motor, visual-motor, and visual-spatial skills and memory difficulties. After CRT, children with brain tumors also demonstrated a fall in a wide range of achievement scores and an increased need, over time, for special help in school. The 2-year results of this study suggest that children with brain tumors treated with CRT are cognitively impaired and that these deficits worsen over time. The younger the child is at the time of treatment, the greater is the likelihood and severity of damage. These children, although not retarded, have a multitude of neurocognitive deficits which detrimentally affects school performance. New treatment strategies are needed for children with malignant brain tumors.

Pre‐radiation chemotherapy with response‐based radiation therapy in children with central nervous system germ cell tumors: A report from the Children's Oncology Group

“…While patients with germ cell tumors may present with permanent hormone deficiencies, brain and ventricular RT may cause neurocognitive impairment [47][48][49][50][51][52][53], as well as additional hormonal dysfunction. Neuraxis RT also causes growth retardation.…”

Detection and characterization of neurotoxicity in cancer patients using proton MR spectroscopy

“…Cognitive deficits documented by neuropsychological (NP) testing involve attention and concentration, processing speed, memory, general intelligence, language, and academic achievement [29,26,13]. Risk factors identified from studies of patients with acute lymphoblastic leukemia and brain tumors include young age at treatment [13,23,3,1], dose and type of treatment, particularly cranial irradiation and high-dose chemotherapy [13,15,25], increased time since treatment [26,23], and female gender [3]. Structural changes, including subacute leukoencephalopathy, mineralizing microangiopathy, and cortical atrophy, have been observed on CT or MRI during and after treatment [5], but associations between NP deficits and structural abnormalities are inconsistent and yield mixed results [18,28].…”

Role of diffusion tensor imaging in resection of thalamic juvenile pilocytic astrocytoma

“…Furthermore, the potential long-term adverse ef- fects of such therapies raise important concerns in young children. 37 The techniques for stereotactic volumetric resection of JPAs located in the thalamus have been previously described with good functional neurological outcomes and long-term disease-free survival. 24,25,32,34,35 With the aid of the preoperative imaging database, operative trajectories are planned that minimally disrupt normal eloquent brain tissue en route to the tumor.…”