Late Effects of Treatment for Childhood Cancer (PDQ®): Treatment - Health Professional Information [NCI] - Late Effects of the Central Nervous System
Vinca alkaloid agents (vincristine and vinblastine) and cisplatin may cause peripheral neuropathy. This condition presents during treatment and appears to clinically resolve after completion of therapy. However, higher cumulative doses of vincristine and/or intrathecal methotrexate have been linked to neuromuscular impairments in long-term survivors of childhood ALL, which suggests that persistent effects of these agents may impact functional status in aging survivors.
In a report from the CCSS that compared 4,151 adult survivors of childhood ALL with their siblings, survivors were at an elevated risk for late-onset coordination problems, motor problems, seizures, and headaches. The overall cumulative incidence was 44% at 20 years. Serious headaches were most common, with a cumulative incidence of 25.8% at 20 years followed by focal neurologic dysfunction (21.2%) and seizures (7%). Children who were treated with regimens that included cranial radiation for ALL and those who suffer relapse were at increased risk for late-onset neurologic sequelae.
Table 3. Central Nervous System Late Effects
|Predisposing Therapy||Neurologic Effects||Health Screening|
|IQ = intelligence quotient; IT = intrathecal; IV = intravenous.|
|Platinum agents (carboplatin, cisplatin)||Peripheral sensory neuropathy||Neurologic exam|
|Plant alkaloid agents (vinblastine, vincristine)||Peripheral sensory or motor neuropathy (areflexia, weakness, foot drop, paresthesias)||Neurologic exam|
|Methotrexate (high dose IV or IT); cytarabine (high dose IV or IT); radiation impacting the brain||Clinical leukoencephalopathy (spasticity, ataxia, dysarthria, dysphagia, hemiparesis, seizures); headaches; seizures; sensory deficits||History: cognitive, motor, and/or sensory deficits, seizures|
|Radiation impacting cerebrovascular structures||Cerebrovascular complications (stroke, moyamoya, occlusive cerebral vasculopathy)||History: transient/permanent neurological events|
|Neurosurgery–brain||Motor and/or sensory deficits (paralysis, movement disorders, ataxia, eye problems [ocular nerve palsy, gaze paresis, nystagmus, papilledema, optic atrophy]); seizures||Neurologic exam|
|Neurosurgery–brain||Hydrocephalus; shunt malfunction||Abdominal x-ray|
|Neurosurgery–spine||Neurogenic bladder; urinary incontinence||History: hematuria, urinary urgency/frequency, urinary incontinence/retention, dysuria, nocturia, abnormal urinary stream|
|Neurosurgery–spine||Neurogenic bowel; fecal incontinence||History: chronic constipation, fecal soiling|
|Predisposing Therapy||Neuropsychological Effects||Health Screening|
|Methotrexate (high-dose IV or IT); cytarabine (high-dose IV or IT); radiation impacting the brain; neurosurgery–brain||Neurocognitive deficits (executive function, memory, attention, processing speed, etc.); learning deficits; diminished IQ; behavioral change||Assessment of educational and vocational progress|
|Formal neuropsychological evaluation|
Many childhood cancer survivors have adverse quality of life or other adverse psychological outcomes. Incorporation of psychological screening into clinical visits for childhood cancer survivors may be valuable; however, limiting such evaluations to those returning to long-term follow-up clinics may result in a biased subsample of those with more difficulties, and precise prevalence rates may be difficult to establish. A review of behavioral, emotional, and social adjustment among survivors of childhood brain tumors illustrates this point, in whom rates of psychological maladjustment range from 25% to 93%. In a series of CNS malignancy survivors (n = 802) reported from the CCSS, adverse outcome indicators of successful adult adaptation (educational attainment, income, employment, and marital status) were most likely in survivors who report neurocognitive dysfunction. Collectively, studies evaluating psychosocial outcomes among CNS tumor survivors indicate deficits in social competence in the level of social adjustment that worsen over time. In a CCSS study evaluating predictors of independent living status across diagnostic groups, adult survivors of childhood cancer with neurocognitive, psychological, or physical late effects were less likely to live independently as adults compared with a sibling control group. The presence of chronic health conditions can also impact other aspects of psychological health. In a study evaluating psychological outcomes among long-term survivors treated with hematopoietic cell transplantation (HCT), 22% of survivors reported adverse outcomes compared with 8% of sibling controls. Somatic distress was the most prevalent among the domains studied and affected 15% of HCT survivors, representing a threefold higher risk compared with siblings. HCT survivors with severe/life-threatening conditions and active chronic GVHD had a twofold increased risk for somatic distress.