BACKGROUND: Cellular senescence, measured by expression of the cell cycle kinase inhibitor p16 INK4a , may contribute to accelerated aging in survivors of childhood, adolescent, and young adult cancer. The authors measured peripheral blood T-lymphocyte p16 INK4a expression among pediatric and young adult cancer survivors, hypothesizing that p16 INK4a expression is higher after chemotherapy and among frail survivors. METHODS: A cross-sectional cohort of young adult survivors and age-matched, cancer-free controls were assessed for p16 INK4a expression and frailty. Newly diagnosed pediatric patients underwent prospective measurements of p16 INK4a expression before and after cancer therapy. Frailty was measured with a modified Fried frailty phenotype evaluating sarcopenia, weakness, slowness, energy expenditure, and exhaustion. RESULTS: The cross-sectional cohort enrolled 60 survivors and 29 age-matched controls with a median age of 21 years (range, 17-29 years). The prospective cohort enrolled 9 newly diagnosed patients (age range, 1-18 years). Expression of p16 INK4a was higher among survivors compared with controls (9.6 vs 8.9 log 2 p16 units; 2-sided P = .005, representing a 25-year age acceleration in survivors) and increased among newly diagnosed patients from matched pretreatment to posttreatment samples (7.3-8.9 log 2 p16 units; 2-sided P = .002). Nine survivors (16%) were frail and had higher p16 INK4a expression compared with robust survivors (10.5 [frail] vs 9.5 [robust] log 2 p16 units; 2-sided P = .055), representing a 35-year age acceleration among frail survivors. CONCLUSIONS: Chemotherapy is associated with increased cellular senescence and molecular age in pediatric and young adult cancer survivors. Frail survivors, compared with robust survivors, exhibit higher levels of p16 INK4a , suggesting that cellular senescence may be associated with early aging in survivors. Cancer 2020;126:4975-4983.
Compared with peers without cancer, survivors of childhood cancer have greater rates of prescription use across many drug classes, suggesting greater medical morbidity. Survivors were more likely to use opioid, psychoactive, hormone, and cardiovascular medications. All general pediatricians and subspecialists should be aware of potentially emerging morbidities during the early post-therapy period to guide risk-based surveillance and survivorship care.
We observed a lower incidence rate of catheter-associated venous thrombosis than in most previous reports. No modifiable characteristics altered the risk of thrombosis. Additional investigation of measures to prevent thrombosis is warranted in higher-risk populations, such as patients undergoing dialysis or patients with inflammatory bowel disease.
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