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Cited by 55Childhood Cancer Survivors' Quality of LifeCancer-related cognitive impairment studiesCancer survivorship and care

Neurocognitive and Patient-Reported Outcomes in Adult Survivors of Childhood Osteosarcoma

Open access
Edelmann, Michelle N., Daryani, Vinay M., Bishop, Michael W., Liu, Wei, Brinkman, Tara M., Stewart, Clinton F., Mulrooney, Daniel A., Kimberg, Cara +6 more·2016·JAMA Oncology
DOI 10.1001/jamaoncol.2015.4398PMC PMC4752424
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Abstract

IMPORTANCE: This study provides the first objective data documenting neurocognitive impairment in long-term survivors of childhood osteosarcoma. OBJECTIVE: To examine neurocognitive, neurobehavioral, emotional, and quality-of-life outcomes in long-term survivors of childhood osteosarcoma. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional cohort study at an academic research hospital, with prospective treatment and chronic health predictors. Outcome data were collected from June 2008 to August 2014. Data analysis was completed in April 2015. Survivors of osteosarcoma recruited from the St Jude Lifetime Cohort Study were compared with community controls. MAIN OUTCOMES AND MEASURES: Neurocognitive function, neurobehavioral symptoms, emotional distress, and quality of life. Outcomes were examined in relation to pharmacokinetic indices of methotrexate exposure and current chronic health conditions, which were assessed through medical examination and coded according to Common Terminology Criteria for Adverse Events, Version 4.03. RESULTS: Eighty survivors of osteosarcoma (mean [SD] age, 38.9 [7.6] years; time since diagnosis, 24.7 [6.6] years; 42% female) were compared with 39 community controls (age, 39.0 [11.7] years; 56% female). Survivors demonstrated lower mean scores in reading skills (-0.21 [95% CI, -0.32 to -0.10] vs 0.05 [95% CI, -0.13 to 0.23]; P = .01), attention (-0.78 [95% CI, -1.32 to -0.24] vs 0.24 [95% CI, -0.07 to 0.55]; P = .002), memory (-0.24 [95% CI, -0.48 to 0] vs 0.27 [95% CI, -0.08 to 0.62]; P = .01), and processing speed (-0.15 [95% CI, -0.35 to 0.05] vs 0.74 [95% CI, 0.44 to 1.03]; P < .001). Results of pharmacokinetic analysis showed that high-dose methotrexate maximum plasma concentration (estimate = 0; P = .48), median clearance (estimate = -0.11; P = .76), and median/cumulative exposure (estimate = 0; P = .45) were not associated with neurocognitive outcomes. Any grade 3 or 4 Common Terminology Criteria for Adverse Events cardiac, pulmonary, or endocrine condition was associated with poorer memory (t = 2.93; P = .006) and slower processing speed (t = 3.03; P = .002). Survivor-reported poor general health was associated with decreased sustained attention (estimate = 0.24; P = .05) and processing speed (estimate = 0.34; P = .005). CONCLUSIONS AND RELEVANCE: Long-term survivors of osteosarcoma are at risk for neurocognitive impairment, which is related to current chronic health conditions and not to original treatment with high-dose methotrexate. Prospective longitudinal studies are needed to identify onset and progression of impairment to inform optimal interventions.

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  • Having a grade 3 or grade 4 cardiac, pulmonary or endocrine toxic effect on chart review was associated with an increased risk of neurocognitive impairment.

    “Having a grade 3 or grade 4 cardiac, pulmonary or endocrine toxic effect on chart review was associated with an increased risk of neurocognitive impairment 178 .”

    From Osteosarcoma (2022) · cites this paper as [178]

  • A single institution study evaluating HRQoL in 80 survivors at least 10 years after initial diagnosis of osteosarcoma revealed neurocognitive impairment, with significantly lower mean scores in reading skills (P = 0.01), sustained attention (P = 0.002), short-term memory (P = 0.01) and physical processing speed (P < 0.001) compared with matched controls.

    “A single institution study evaluating HRQoL in 80 survivors at least 10 years after the initial diagnosis of osteosarcoma revealed that individuals had neurocognitive impairment, with significantly lower mean scores in reading skills (P = 0.01), sustained attention (P = 0.002), short-term memory (P = 0.01) and physical processing speed (P < 0.001) compared with matched controls 178 .”

    From Osteosarcoma (2022) · cites this paper as [178]

  • In this group of osteosarcoma survivors, the burden of physical health conditions was high, with 32% self-reporting impaired physical functioning and 16% reporting impaired general health, considerably worse than matched controls.

    “In this group of patients, the burden of physical health conditions was high, with 32% of osteosarcoma survivors self-reporting impaired physical functioning and 16% reporting impaired general health, which is considerably worse than in matched controls.”

    From Osteosarcoma (2022) · cites this paper as [178]

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  1. [25]Derogatis LR Brief Symptoms Inventory 18: Administration, scoring, and procedures manual 2001 Minneapolis, MN NCS Pearson Inc.

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Authors
Edelmann, M. N., Daryani, V. M., Bishop, M. W., Liu, W., Brinkman, T. M., Stewart, C. F., Mulrooney, D. A., Kimberg, C., Ness, K. K., Cheung, Y. T., Srivastava, D. K., Robison, L. L., Hudson, M. M., & Krull, K. R.
Affiliations
St. Jude Children's Research Hospital (US)
Corresponding author
Krull, Kevin R.
ORCID
Venue
JAMA Oncology
Publisher
American Medical Association (AMA)
Published
2016-02-01
Volume
2
Issue
2
Pages
201
ISSN
2374-2437 (ISSN-L)
DOI
10.1001/jamaoncol.2015.4398
PMC
PMC4752424
OpenAlex
W2175113758
Cited by
55
References
31
Citations by year
2026: 4 · 2025: 5 · 2024: 2 · 2023: 9 · 2022: 6 · 2021: 7 · 2020: 4 · 2019: 5 · 2018: 6 · 2017: 5 · 2016: 1 · 2015: 1
FWCI
4.33
Type
journal article
Language
en
Open access
Locations
  • JAMA Oncology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • American Lebanese Syrian Associated Charities
  • National Institutes of Health (UL1TR001425)
  • National Cancer Institute (U01CA195547, CA21765, P30CA021765)
  • National Center for Advancing Translational Sciences
Topics
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Childhood Cancer Survivors' Quality of Life
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cancer-related cognitive impairment studies
  • Health Sciences › Medicine › Oncology › Cancer survivorship and care
Keywords
long-term cancer survivors, neurocognitive impairment, attention deficits, memory impairment, processing speed, reading skills, quality of life, emotional distress, neurobehavioral symptoms, methotrexate pharmacokinetics, chronic disease, late effects of cancer treatment, St. Jude Lifetime Cohort Study, childhood cancer survivors
MeSH terms
Adult, Antimetabolites, Antineoplastic, Attention, Bone Neoplasms, Cognition, Cognition Disorders, Cross-Sectional Studies, Emotions, Female, Humans, Male, Memory, Methotrexate, Middle Aged, Quality of Life, Risk Factors, Osteosarcoma, Time Factors, United States, Case-Control Studies, Treatment Outcome, Survivors, Risk Assessment, Neurotoxicity Syndromes, Executive Function

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