Cognition, Functioning Deficits in Survivors of Pediatric Extracranial Solid Tumors and Lymphomas

Surviving childhood cancer is fraught with difficulty, both immediate and long-term. Some cancers and their treatments cause cognitive and other chronic health concerns that may have lasting outcomes. Oncology nurses should be aware of them. Nina S. Kadan-Lottick, MD, MSPH, associate professor of pediatrics (hematology and oncology) at Yale Cancer Center in New Haven, Connecticut, believes these sequelae reach far into the patient’s future, where they affect education, employment, and even income.

Dr Kadan-Lottick and colleagues sought to understand the sequelae that affected survivors of pediatric cancers. For this review, the researchers focused on studies on patients’ cognitive functioning after diagnosis of specific extracranial solid tumors and lymphomas. The researchers also focused on gaps in research and considered possible comorbidities and other related risk factors.

The researchers organized their review by cancer diagnosis because of the wide variation in patients and treatments. They searched PubMed and PsycINFO for studies that investigated long-term cognitive outcomes in survivors of childhood extracranial solid tumors and lymphomas going back to 1990. Long-term survival was described as off therapy for more than 2 years and/or 5 years from diagnosis. Their study population included at least 10 patients in each subcategory and were younger than 21 years at diagnosis.

Findings from their analysis of the studies on several extracranial solid tumors and lymphomas commonly diagnosed in children follows.

Osteosarcoma Survivors in the St Jude Lifetime Cohort (median age at diagnosis, 12.3 years) had significantly worse scores in attention, memory, reading, and processing speed. The diminished cognitive performance correlated with low rates of graduation from college, poor success in full-time employment, and low income.  

Ewing sarcoma Studies demonstrated inconsistent findings. In the largest sample of survivors (median age at diagnosis, 12.3 years), self-reported task efficiency and emotional dysregulation were worse compared to their siblings. Diminished task efficiency was associated with being unemployed as adults. However, when compared to a community control groups, survivors had no increased impairment in attention, memory, or executive functioning.

Neuroblastoma Significant inattention and learning problems were reported among this group (median age at diagnosis, 1.4 years). Studies found discrepancies in general cognition, concentration, memory, and executive functioning. Dr Kadan-Lottick and colleagues found a number of risk factors associated with problems in these survivors, such as hearing loss and chronic health burden, as well as lower household income and lower maternal education.

Wilms tumor Data are conflicting for cognitive outcomes among survivors (mean age at diagnosis, 3.6 years). Early study results found that when compared to control groups, survivors have similar cognition, attention, and visual motor functioning. However, more recent studies demonstrate that Wilms tumor survivors have worse memory, attention, and cognitive functioning than community control groups. Survivors also have at least 1 academic difficulty, are more likely to be in special education programs and/or unemployed, and are less likely to graduate community college than their siblings.

Hodgkin lymphoma Survivor (mean age at diagnosis, 15.1 years) cognition studies are sparse. In one study, these survivors had difficulty with short- and long-term memory, working memory, lower sustained attention, and cognitive fluency. In another study comparing survivors to their siblings, Hodgkin lymphoma survivors had more difficulty with task efficiency, memory, and emotional regulation.

Non-Hodgkin lymphoma Survivors (mean age at diagnosis, 10.4 years) often received intrathecal chemotherapy. Eighty-one percent of those patients had deficits in executive function, processing speed, memory and academic achievement. Unexpectedly high rates of cognitive dysfunction also were noted.

Langerhans cell histiocytosis (LCH) Pediatric patients with central nervous system disease and/or are treated with chemotherapy have the most significant risk of cognitive impairment. The likelihood of neurologic, cognitive, or psychiatric problems is 10% to 50% for LCH survivors. Little is known about the neuropathophysiology, and results varied among different studies. These researchers found that 25% of survivors (mean age at diagnosis, 3.4 years) used special education programs. The researchers found that cognitive impairment could be the result of certain brain structures having been affected by chemotherapy or central nervous system disease.  

“Given the older age at diagnosis of many childhood extracranial solid tumors and lymphomas as well as toxicities associated with certain therapies, patients may benefit from vocational services, occupational therapy, physical therapy, and/or hearing or visual rehabilitation in addition to surveillance for cognitive difficulties,” the researchers concluded.

However, most studies are limited by small sample sizes and/or self-report rather than neuropsychological testing. “Larger prospective studies are needed that better delineate the severity of cognitive impairment, contributory risk factors, and effective interventions to reduce impairment.”

Reference

Foster R, Zheng DJ, Netson-Amore KL, Kadan-Lottick NS. Cognitive impairment in survivors of pediatric extracranial solid tumors and lymphomas. J Clin Oncol. Published online April 22, 2021. doi:10.1200/JCO.20.02358