Nina S Kadan-Lottick1, Daniel J Zheng2, Mingjuan Wang3, Michael W Bishop4, Deo Kumar Srivastava3, Wilhelmenia L Ross5, Rozalyn L Rodwin5, Kirsten K Ness6, Todd M Gibson6, Sheri L Spunt7, Mehmet Fatih Okcu8, Wendy M Leisenring9, Leslie L Robison6, Gregory T Armstrong6, Kevin R Krull6,10. 1. Cancer Prevention and Control Program, Georgetown Lombardi Comprehensive Cancer Center, 2115 Wisconsin Ave., NW - 3Rd Floor, Washington, DC, 20007, USA. nina.kadanlottick@georgetown.edu. 2. Divisions of Hematology and Oncology, Children's Hospital of Philadelphia, Philadelphia, PA, USA. 3. Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, TN, USA. 4. Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA. 5. Section of Pediatric Hematology-Oncology, Yale University School of Medicine, New Haven, CT, USA. 6. Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, TN, USA. 7. Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA. 8. Department of Pediatrics, Section of Hematology-Oncology, Baylor College of Medicine, Houston, TX, USA. 9. Fred Hutchinson Cancer Research Center, Seattle, WA, USA. 10. Department of Psychology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Abstract
PURPOSE: Little is known regarding long-term neurocognitive outcomes in osteosarcoma and Ewing sarcoma (EWS) survivors despite potential risk factors. We evaluated associations among treatment exposures, chronic health conditions, and patient-reported neurocognitive outcomes in adult survivors of childhood osteosarcoma and EWS. METHODS: Five-year survivors of osteosarcoma (N = 604; median age 37.0 years) and EWS (N = 356; median age 35.0 years) diagnosed at < 21 years from 1970 to 1999, and 697 siblings completed the Childhood Cancer Survivor Study Neurocognitive Questionnaire and reported chronic health conditions, education, and employment. Prevalence of reported neurocognitive difficulties were compared between diagnostic groups and siblings. Modified Poisson regression identified factors associated with neurocognitive difficulties. RESULTS: Osteosarcoma and EWS survivors, vs. siblings, reported higher prevalences of difficulties with task efficiency (15.4% [P = 0.03] and 14.0% [P = 0.04] vs. 9.6%, respectively) and emotional regulation (18.0% [P < 0.0001] and 15.2% [P = 0.03] vs. 11.3%, respectively), adjusted for age, sex, and ethnicity/race. Osteosarcoma survivors reported greater memory difficulties vs. siblings (23.5% vs. 16.4% [P = 0.01]). Comorbid impairment (i.e., ≥ 2 neurocognitive domains) was more prevalent in osteosarcoma (20.0% [P < 0.001]) and EWS survivors (16.3% [P = 0.02]) vs. siblings (10.9%). Neurological conditions were associated with worse task efficiency (RR = 2.17; 95% CI = 1.21-3.88) and emotional regulation (RR = 1.88; 95% CI = 1.01-3.52), and respiratory conditions were associated with worse organization (RR = 2.60; 95% CI = 1.05-6.39) for EWS. Hearing impairment was associated with emotional regulation difficulties for osteosarcoma (RR = 1.98; 95% CI = 1.22-3.20). Patient report of cognitive difficulties was associated with employment but not educational attainment. CONCLUSIONS: Survivors of childhood osteosarcoma and EWS are at increased risk for reporting neurocognitive difficulties, which are associated with employment status and appear related to chronic health conditions that develop over time. IMPLICATIONS FOR CANCER SURVIVORS: Early screening, prevention, and treatment of chronic health conditions may improve/prevent long-term neurocognitive outcomes.
PURPOSE: Little is known regarding long-term neurocognitive outcomes in osteosarcoma and Ewing sarcoma (EWS) survivors despite potential risk factors. We evaluated associations among treatment exposures, chronic health conditions, and patient-reported neurocognitive outcomes in adult survivors of childhood osteosarcoma and EWS. METHODS: Five-year survivors of osteosarcoma (N = 604; median age 37.0 years) and EWS (N = 356; median age 35.0 years) diagnosed at < 21 years from 1970 to 1999, and 697 siblings completed the Childhood Cancer Survivor Study Neurocognitive Questionnaire and reported chronic health conditions, education, and employment. Prevalence of reported neurocognitive difficulties were compared between diagnostic groups and siblings. Modified Poisson regression identified factors associated with neurocognitive difficulties. RESULTS: Osteosarcoma and EWS survivors, vs. siblings, reported higher prevalences of difficulties with task efficiency (15.4% [P = 0.03] and 14.0% [P = 0.04] vs. 9.6%, respectively) and emotional regulation (18.0% [P < 0.0001] and 15.2% [P = 0.03] vs. 11.3%, respectively), adjusted for age, sex, and ethnicity/race. Osteosarcoma survivors reported greater memory difficulties vs. siblings (23.5% vs. 16.4% [P = 0.01]). Comorbid impairment (i.e., ≥ 2 neurocognitive domains) was more prevalent in osteosarcoma (20.0% [P < 0.001]) and EWS survivors (16.3% [P = 0.02]) vs. siblings (10.9%). Neurological conditions were associated with worse task efficiency (RR = 2.17; 95% CI = 1.21-3.88) and emotional regulation (RR = 1.88; 95% CI = 1.01-3.52), and respiratory conditions were associated with worse organization (RR = 2.60; 95% CI = 1.05-6.39) for EWS. Hearing impairment was associated with emotional regulation difficulties for osteosarcoma (RR = 1.98; 95% CI = 1.22-3.20). Patient report of cognitive difficulties was associated with employment but not educational attainment. CONCLUSIONS: Survivors of childhood osteosarcoma and EWS are at increased risk for reporting neurocognitive difficulties, which are associated with employment status and appear related to chronic health conditions that develop over time. IMPLICATIONS FOR CANCER SURVIVORS: Early screening, prevention, and treatment of chronic health conditions may improve/prevent long-term neurocognitive outcomes.
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