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Patient-reported neurocognitive function in adult survivors of childhood and adolescent osteosarcoma and Ewing sarcoma

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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.

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Funding

This work was supported by the National Cancer Institute at the National Institutes of Health [CA55727, G.T. Armstrong, Principal Investigator]. Support to St. Jude Children’s Research Hospital was also provided by the Cancer Center Support (CORE) grant [CA21765, C. Roberts, Principal Investigator] and the American Lebanese-Syrian Associated Charities (ALSAC).

National Cancer Institute,CA55727,Gregory T Armstrong,National Cancer Institute Core Center Grant,CA21765,American Lebanese Syrian Associated Charities

Author information

Authors and Affiliations

  1. Cancer Prevention and Control Program, Georgetown Lombardi Comprehensive Cancer Center, 2115 Wisconsin Ave., NW - 3Rd Floor, Washington, DC, 20007, USA

    Nina S. Kadan-Lottick

  2. Divisions of Hematology and Oncology, Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Daniel J. Zheng

  3. Department of Biostatistics, St. Jude Children’s Research Hospital, Memphis, TN, USA

    Mingjuan Wang & Deo Kumar Srivastava

  4. Department of Oncology, St. Jude Children’s Research Hospital, Memphis, TN, USA

    Michael W. Bishop

  5. Section of Pediatric Hematology-Oncology, Yale University School of Medicine, New Haven, CT, USA

    Wilhelmenia L. Ross & Rozalyn L. Rodwin

  6. Department of Epidemiology and Cancer Control, St. Jude Children’s Research Hospital, Memphis, TN, USA

    Kirsten K. Ness, Todd M. Gibson, Leslie L. Robison, Gregory T. Armstrong & Kevin R. Krull

  7. Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA

    Sheri L. Spunt

  8. Department of Pediatrics, Section of Hematology-Oncology, Baylor College of Medicine, Houston, TX, USA

    Mehmet Fatih Okcu

  9. Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    Wendy M. Leisenring

  10. Department of Psychology, St. Jude Children’s Research Hospital, Memphis, TN, USA

    Kevin R. Krull

Authors
  1. Nina S. Kadan-Lottick
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  2. Daniel J. Zheng
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  3. Mingjuan Wang
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  4. Michael W. Bishop
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  5. Deo Kumar Srivastava
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  6. Wilhelmenia L. Ross
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  7. Rozalyn L. Rodwin
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  8. Kirsten K. Ness
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  9. Todd M. Gibson
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  10. Sheri L. Spunt
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  11. Mehmet Fatih Okcu
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  12. Wendy M. Leisenring
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  13. Leslie L. Robison
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  14. Gregory T. Armstrong
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  15. Kevin R. Krull
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Contributions

Study concept and design: NKL, DJZ, MW, MWB, DKS, LLR, GTA, and KRK. Acquisition of the data: NKL, DJZ, MW, DKS, and WML. Statistical analysis: MW, DKS, and WML. Analysis and interpretation of the data: NKL, DJZ, MW, MWB, DKS, WLR, RLR, KKN, TMG, SLS, MFO, WML, LLR, GTA, and KRK. Drafting of the manuscript: NKL, DJZ, LLR, GTA, and KRK. Critical revision of the manuscript: NKL, DJZ, MW, MWB, DKS, WLR, RLR, KKN, TMG, SLS, MFO, WML, LLR, GTA, and KRK.

Corresponding author

Correspondence to Nina S. Kadan-Lottick.

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The Childhood Cancer Survivor Study was approved by the institutional review board at each institution.

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Kadan-Lottick, N.S., Zheng, D.J., Wang, M. et al. Patient-reported neurocognitive function in adult survivors of childhood and adolescent osteosarcoma and Ewing sarcoma. J Cancer Surviv 17, 1238–1250 (2023). https://doi.org/10.1007/s11764-021-01154-z

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