In an analysis reported in JAMA Network Open, Phillips et al found that adult survivors of childhood cancer were at an increased risk of new-onset memory impairment vs their siblings. Modifiable factors associated with increased risk of impairment among survivors were identified.
Study Details
The study involved a cohort of adult survivors from the Childhood Cancer Survivor Study (CCSS), with their siblings serving as a control group. The survivor cohort consisted of patients who had received a cancer diagnosis between January 1970 and December 1986 who had available longitudinal neurocognitive assessments.
The prevalence of new-onset neurocognitive impairment between baseline (23.4 years after diagnosis) and follow-up (35.0 years after diagnosis) was identified. Neurocognitive impairment was defined as score in the worst 10% of the sibling cohort using the CCSS neurocognitive questionnaire. The current analysis focused on new-onset memory impairment.
Key Findings
The analysis included 2,375 survivors (mean [standard deviation, SD] age at evaluation = 31.8 [7.5] years) and 232 siblings (mean [SD] age at evaluation = 34.2 [8.4] years). Childhood cancers included acute lymphoblastic leukemia (ALL; n = 1,316), central nervous system (CNS) tumors (n = 488), and Hodgkin lymphoma (n = 571).
New-onset memory impairment at follow-up was found in 7.8% (95% confidence interval [CI] = 4.3%–11.4%) of siblings vs 14.0% (95% CI = 10.7%–17.4%) of ALL survivors who received chemotherapy only, 25.8% (95% CI = 22.6%–29.0%) of ALL survivors treated with cranial radiation, 34.7% (95% CI = 30.0%–39.5%) of CNS tumor survivors, and 16.6% (95% CI = 13.4%–19.8%) of Hodgkin lymphoma survivors.
New-onset memory impairment was associated with cranial radiation in CNS tumor survivors (relative risk [RR] = 1.97, 95% CI = 1.33–2.90) and with alkylator chemotherapy dose > 8,000 mg/m2 in ALL survivors who did not receive cranial radiotherapy (RR = 2.80, 95% CI = 1.28–6.12).
New onset of grade 3 or 4 neurologic conditions after baseline was associated with impaired memory in ALL survivors (RR = 3.68, 95% CI = 1.30–10.4), CNS tumor survivors (RR = 2.32, 95% CI = 1.64–3.28), and Hodgkin lymphoma survivors (RR = 2.67, 95% CI = 1.64–4.35).
Patient characteristics associated with increased risk of new-onset memory impairment included smoking at baseline in ALL survivors treated with cranial radiation (RR = 1.56, 95% CI = 1.11–2.18), low baseline physical activity in CNS tumor survivors (RR = 1.43, 95% CI = 1.09–1.89), and obesity at baseline in Hodgkin lymphoma survivors (RR = 1.72, 95% CI = 1.11–2.65).
The investigators concluded, “These findings suggest that adult survivors of childhood cancer are at elevated risk for late-onset memory impairment related to modifiable risk factors identified early in survivorship.”
Nicholas S. Phillips, MD, PhD, of the Department of Epidemiology and Cancer Control, St. Jude Children’s Research Hospital, Memphis, is the corresponding author for the JAMA Network Open article.
Disclosure: The study was supported by the National Cancer Institute and American Lebanese Syrian Associated Charities. For full disclosures of the study authors, visit jamanetwork.com.
