Cumulative Burden of Chronic Health Conditions in Adult Survivors of Osteosarcoma and Ewing Sarcoma: A Report from the St. Jude Lifetime Cohort Study

Abstract

Background: Adult survivors of childhood osteosarcoma and Ewing sarcoma are at risk of developing therapy-related chronic health conditions. We characterized the cumulative burden of chronic conditions and health status of survivors of childhood bone sarcomas.Methods: Survivors (n ¼ 207) treated between 1964 and 2002 underwent comprehensive clinical assessments (history/ physical examination, laboratory analysis, and physical and neurocognitive testing) and were compared with community controls (n ¼ 272). Health conditions were defined and graded according to a modified version of the NCI's Common Terminology Criteria for Adverse Events and the cumulative burden estimated.Results: Osteosarcoma and Ewing sarcoma survivors [median age 13.6 years at diagnosis (range 1.7-24.8); age at evaluation 36.6 years (20.7-66.4)] demonstrated an increased prevalence of cardiomyopathy (14.5%; P < 0.005) compared with controls.Nearly 30% of osteosarcoma survivors had evidence of hypertension. By age 35 years, osteosarcoma and Ewing sarcoma survivors had, on average, 12.0 (95% confidence interval, 10.2-14.2) and 10.6 (8.9-12.6) grade 1-4 conditions and 4.0 (3.2-5.1) and 3.5 (2.7-4.5) grade 3-4 conditions, respectively, compared with controls [3.3 (2.9-3.7) grade 1-4 and 0.9 (0.7-1.0) grade 3-4]. Both survivor cohorts exhibited impaired 6-minute walk test, walking efficiency, mobility, strength, and endurance (P < 0.0001). Accumulation of ≥4 grade 3-4 chronic conditions was associated with deficits in executive function [RR: osteosarcoma 1.6 (1.0-2.4), P ¼ 0.049; Ewing sarcoma 2.0 (1.2-3.3), P ¼ 0.01] and attention [RR: osteosarcoma 2.3 (1.2-4.2); P ¼ 0.008].Conclusions: Survivors of osteosarcoma and Ewing sarcoma experience a high cumulative burden of chronic health conditions, with impairments of physical function and neurocognition.Impact: Early intervention strategies may ameliorate the risk of comorbidities in bone sarcoma survivors.

Neurocognitive Outcomes of Children with Osteosarcoma Treated with High-dose Intravenous Methotrexate

“…Collectively, cognitive development was not adversely affected in this cohort of childhood osteosarcoma survivors treated with HD-MTX. However, chronic health conditions have been reported to affect neurocognitive functions in adults treated for osteosarcoma during childhood [9,10]. Since patients in this study were younger than 17 years of age and in an early phase of survivorship (mean follow-up time of 66 months, range, 25-144 months), these results may not be generalizable to older survivors with longer elapsed time from treatment.…”

Prevalence of low bone mineral density and risk of fractures in osteosarcoma and Ewing’s sarcoma survivors: A scoping review

“…The number of patients included in each study ranged from nine to 207 (median, 47). BMD evaluation and laboratory tests were performed during treatment or within 1 month of treatment completion in four studies [15] , [16] , [17] , [18] and at least 1 year after treatment completion in seven studies [12] , [19] , [20] , [21] , [22] , [23] , [24] . In the former publications, the mean/median age of patients ranged from 12.8 to 15.0 year, and in the latter, from 26 to 37.6 year.…”

“…Diagnosis of osteoporosis and osteopenia in OS/ES survivors (at least 1 year after the completion of therapy) was described in six studies [12] , [19] , [20] , [21] , [23] , [24] . In three studies [19] , [20] , [24] , osteoporosis and osteopenia in adults were determined according to the WHO osteoporosis definition [25] , where a T -score < −2.5 was diagnosed as osteoporosis, −2.5 ≤ T -score < −1 as osteopenia, and −1.0 ≤ T -score as normal.…”

“…In three studies [19] , [20] , [24] , osteoporosis and osteopenia in adults were determined according to the WHO osteoporosis definition [25] , where a T -score < −2.5 was diagnosed as osteoporosis, −2.5 ≤ T -score < −1 as osteopenia, and −1.0 ≤ T -score as normal. One study [12] used the Common Terminology Criteria for Adverse Events, ver. 4.03 (the Division of Cancer Treatment and Diagnosis, National Cancer Institute), in which grade 1 and grade 2 bone loss correspond to the WHO definition of osteopenia and osteoporosis, respectively.…”

“…In either case, patients with OS or ES have to undergo not only intensive chemotherapy but also musculoskeletal surgery, which can result in a lasting disability in daily activity and mobility. Therefore, it is possible that chronic musculoskeletal complications and conditions in OS/ES survivors are different from those in other types of childhood cancer, as they do not involve musculoskeletal surgery [12] . However, most studies investigating chronic health conditions in CCS have focused on acute lymphoblastic leukemia (ALL), the most common malignancy in childhood [1] , [13] , indicating that there is an underappreciated knowledge gap regarding chronic health conditions in OS/ES survivors.…”