Survivors of childhood osteosarcoma and Ewing sarcoma (EWS) have an elevated risk of neurocognitive impairment, according to study findings published in the Journal of Cancer Survivorship.

The neurocognitive difficulties among both groups of survivors were associated with employment status and chronic health conditions but not with educational attainment. 

Researchers conducted this large, retrospective cohort study to evaluate the associations among treatment exposures, chronic health conditions, and patient-reported neurocognitive outcomes in adult survivors of childhood osteosarcoma and EWS.

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The analysis included the Childhood Cancer Survivor Study (CCSS) cohort of 960 survivors; 604 were osteosarcoma survivors and 356 were EWS survivors. The study also included a comparison group of a random sample of 697 siblings.

All participants completed the CCSS Neurocognitive Questionnaire (NCQ), a scale that was developed for screening neurocognitive impairment in long-term survivors of childhood cancer in 4 cognitive domains (task efficiency, memory, organization, and emotional regulation). Patient-reported difficulties on the CCSS-NCQ were compared between osteosarcoma survivors, EWS survivors, and siblings.

Results showed a higher prevalence of difficulties with task efficiency among osteosarcoma (15.4%; P =.03) and EWS (14.0%; P =.04) survivors compared with the siblings (9.6%) after adjusting for age, sex, and ethnicity/race. 

Likewise, difficulties with emotional regulation were higher in both osteosarcoma (18.0%; P <.0001) and EWS (15.2%; P =.03) survivors compared with the siblings (11.3%). 

A higher proportion of both osteosarcoma (20.0%; P <.001) and EWS (16.3%; P =.02) survivors reported problems in 2 or more domains of neurocognitive function compared with siblings (10.9%).

Researchers noted that osteosarcoma survivors experienced greater problems with memory (23.5%) compared with the siblings (16.4%; P =.01). 

In a multivariate analysis in the osteosarcoma survivors, receiving a cumulative anthracycline dose of 300 mg/m2 or higher was independently associated with a lower risk of difficulties in emotional regulation (relative risk [RR], 0.64; 95% CI, 0.42-0.95). 

However, radiation to the chest or neck was associated with a greater risk of complaints in emotional regulation for osteosarcoma survivors (RR, 2.24; 95% CI, 1.11-4.54). Similarly, hearing impairment was associated with emotional regulation difficulties for osteosarcoma survivors (RR, 1.98; 95% CI, 1.22-3.20). 

Among EWS survivors, neurological conditions were independently 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), while respiratory conditions were associated with worse organization (RR, 2.60; 95% CI, 1.05-6.39). 

In the overall survivor population, less than full-time employment in the past 12 months was significantly associated with difficulties in task efficiency (RR, 1.97; 95% CI, 1.44-2.70), memory (RR, 1.76; 95% CI, 1.31-2.36), and emotional regulation (RR, 1.72; 95% CI, 1.25-2.36). Educational attainment was not associated with any of the 4 neurocognitive domains.

Taking these findings together, the researchers concluded that survivors of both childhood osteosarcoma and EWS are at increased risk of difficulties in neurocognitive function, which are associated with employment status and appear related to chronic health conditions that develop over time.

“Early screening, prevention, and treatment of chronic health conditions may improve/prevent long-term neurocognitive outcomes,” the researchers wrote. 


Kadan-Lottick NS, Zheng DJ, Wang M, et al. Patient-reported neurocognitive function in adult survivors of childhood and adolescent osteosarcoma and Ewing sarcoma. J Cancer Surviv. Published online January 21, 2022. doi:10.1007/s11764-021-01154-z

This article originally appeared on Cancer Therapy Advisor