Pediatric Sarcoma Survivors Research Articles

Educational and occupational outcomes in Swedish children treated for sarcomas: A nationwide registry-based study.

Many children treated for cancer experience a negative impact on their academic performance; however, most studies of children treated for sarcomas have not investigated academic performance. Our aim was to explore how Swedish children treated for sarcomas perform academically, as well as how they adjust to life afterwards. We compared 167 pediatric sarcoma survivors with 776 matched, non-sibling controls without a history of cancer, in a retrospective cohort study using data from nationwide registries. Primary outcomes were grades at the end of compulsory education, high school eligibility, post-compulsory education (i.e., education after school Year 9), employment, and sickness or activity compensation. Pediatric sarcoma survivors were more likely to be ineligible for high school (odds ratio [OR] 1.76; p=.045) and more likely to fail Swedish (OR 2.12; p=.046), mathematics (OR 2.27; p=.011), and/or physical education (OR 2.24; p=.004), compared with controls. Survivors were less likely to have been employed (OR 0.58; p=.027) and received sickness or activity compensation more often (OR 2.49; p=.008) compared with controls. Pediatric sarcoma survivors have poorer academic performance compared to peers without cancer in multiple school subjects. Survivors seem to catch up during post-compulsory education, but might struggle to find employment.

Pediatric sarcoma survivorship: A call for a developmental cascades approach.

Survivors of pediatric sarcomas often experience greater psychological and psychosocial difficulties than their non-afflicted peers. We consider findings related to poorer outcomes from a developmental cascade perspective. Specifically, we discuss how physical, neurocognitive, psychological, and psychosocial costs associated with pediatric sarcomas and their treatment function transactionally to degrade well-being in long-term pediatric sarcoma survivors. We situate the sarcoma experience as a broad developmental threat - one stemming from both the presence and treatment of a life-imperiling disease, and the absence of typical childhood experiences. Ways in which degradation in one developmental domain spills over and effects other domains are highlighted. We argue that the aggregate effect of these cascades is two-fold: first, it adds to the typical stress involved in meeting developmental milestones and navigating developmental transitions; and second, it deprives survivors of crucial coping strategies that mitigate these stressors. This position suggests specific moments of intervention and raises specific hypotheses for investigators to explore.

Considerations for the Long Term Treatment of Pediatric Sarcoma Survivors.

Sarcomas are primary malignancies of the connective tissues. They are exceedingly rare in adults, but much more common in children. The historically recent advent of cytotoxic chemotherapy for pediatric sarcomas has revolutionized the treatment of these diseases and dramatically improved their prognoses. There is thus a population of pediatric sarcoma survivors that are “coming of age” as adults. However, this progress is not without consequences. Due to aggressive treatment protocols that include various combinations of surgery, chemotherapy, and radiation therapy, pediatric sarcoma survivors are at risk of myriad physical, medical, and psychological difficulties as they enter adulthood. These include but are not limited to physical disabilities, chemotherapy-induced cardiac issues, second malignancies, and anxiety. These patients pose unique challenges to their adult primary care physicians. One possible solution to these challenges is multidisciplinary sarcoma survivorship clinics. By paying greater attention to the unique issues of pediatric sarcoma survivors, involved physicians can maximize the physical and emotional health of pediatric sarcoma survivors.

Establishing Guidelines for Safe and Effective Treatment of Pediatric Sarcoma Survivors: A Mission of the Pediatric Oncology Special Interest Group

Physical therapists have long been involved in the postoperative care of children with a diagnosis of bone and soft-tissue sarcoma. The International Classification of Functioning, Disability and Health model provides a guide to identify impairments, performance limitations, and participation restrictions in this population. The Pediatric Oncology Special Interest Group of the APTA Oncology Section is determined to use this information to facilitate improvements in the treatment of these children. Specifically, a Limb Sparing Committee has been formed to more clearly develop and define the role of physical therapy in the management of pediatric patients with sarcoma.

Metabolic syndrome traits in long‐term survivors of pediatric sarcoma

The metabolic syndrome (MS), a cluster of central obesity, dyslipidemia, hyperglycemia, and hypertension, conveys an increased risk of type 2 diabetes and cardiovascular disease. This cross-sectional study investigated the prevalence of metabolic syndrome traits (MST) in long-term survivors of pediatric sarcoma (SARC) who received multi-modality therapy (MMT). Thirty-two SARC survivors (predominantly Ewings; median age 36.5; median age at MMT 15) underwent body composition, activity, and psychosocial analysis. Serum endocrine and inflammatory parameters and urine beta(2)-microglobulin (B2M) were evaluated. The prevalence of MST was compared to age- and gender-matched U.S. population data. SARC survivors were more likely to have two or more MST (OR 2.38 95% CI: [1.14, 5.04]). Analysis of individual MST demonstrated higher prevalence of hypertension (OR 2.61 95% CI: [1.20, 5.59]), hypertriglyceridemia (OR 3.63 95% CI: [1.75, 7.60]), and male visceral abdominal obesity (20-39 years old OR 4.63 95% CI: [0.91, 21.63], 40-59 years old OR infinity). Survivors 18-39 years old had a higher prevalence of the MS (OR 4.29 95% CI: [1.50, 11.21]), defined as three or more MST. Plasminogen activator inhibitory activity (P = 0.016) and B2M (P = 0.027) increased with increasing numbers of MST. In males, total testosterone declined (P = 0.0027) as the number of MST increased. Average (P = 0.014) and maximum (P = 0.021) activity levels decreased as the number of MST increased. After a median follow up of 17 years, adult SARC survivors of MMT had an increased prevalence of MST, especially those less than 40 years old. The development of MST in this population was associated with decreased testosterone and activity levels.

Functional Outcomes and Life Satisfaction in Long-Term Survivors of Pediatric Sarcomas

Gerber LH, Hoffman K, Chaudhry U, Augustine E, Parks R, Bernad M, Mackall C, Steinberg S, Mansky P. Functional outcomes and life satisfaction in long-term survivors of pediatric sarcomas. Objectives To describe the inter-relationships among impairments, performance, and disabilities in survivors of pediatric sarcoma and to identify measurements that profile survivors at risk for functional loss. Design Prospective, cross-sectional. Setting Research facility. Participants Thirty-two participants in National Cancer Institute clinical trials. Interventions Not applicable. Main Outcome Measures Range of motion (ROM), strength, limb volume, grip strength, walk velocity, Assessment of Motor and Process Skills (AMPS); Human Activity Profile (HAP), Sickness Impact Profile (SIP), standard form of the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36); and vocational attitudes and leisure satisfaction. Results Twenty of 30 survivors tested had moderate or severe loss of ROM; 13 of 31 tested had 90% or less of predicted walk velocity; all of whom had trunk or lower-extremity lesions. Women with decreased ROM ( r=.50, P=.06) or strength ( r=.74, P=.002) had slow gait velocity. Sixteen of 31 tested were more than 1 standard deviation below normal grip strength. Eighteen had increased limb volume. These 18 had low physical competence (SF-36) ( r=−.70, P=.001) and high SIP scores ( r=.73, P=.005). AMPS scores were lower than those of the matched normed sample ( P<.001). HAP identified 15 of 30 who had moderately or severely reduced activity. Leisure satisfaction was higher in the subjects ( P<.001). Eight reported cancer had negatively impacted work and 17 reported that it negatively impacted vocational plans. Conclusions Survivors with lower-extremity or truncal lesions and women with decreased ROM and strength likely have slow walk velocity, low exercise tolerance, and high risk for functional loss. They should be identified using ROM, strength, limb volume, and walk time measures.

Risk factors for low bone mineral density (BMD) in pediatric sarcoma survivors

9059 Background: The incidence of and risk factors for low BMD in patients treated for sarcoma in childhood is unknown. Methods: Retrospective medical record review of 99 patients with pediatric sarcoma diagnosed between 12/82 and 2/03 who had undergone QCT evaluation more than 1 year after completion of treatment. Low BMD was defined as &gt;1.5 standard deviations below the mean. A Z-test was used to assess whether BMD was lower in our patient population than in the normal reference population. Logistic regression was used to examine factors predictive of low BMD. Risk factors analyzed included demographic variables, tumor features, treatment exposures, endocrine/renal dysfunction, and health habits. Results: Twenty-six of the 99 sarcoma survivors (26%) had low BMD. The mean (−0.8) and median (−0.75) QCT Z-scores were significantly lower than those of the normal reference population (mean and median = 0, p&lt;0.0001). Factors associated with lower BMD included young age at sarcoma diagnosis (p=0.044) or at QCT measurement (p=0.001), greater weight at diagnosis (p=0.045), non-lower extremity tumor site (p=0.023), higher cumulative cyclophosphamide dose (p=0.007), smaller size at QCT measurement [height (p=0.018), weight (p=0.012)], and low serum creatinine [at diagnosis (p=0.033), at QCT measurement (p=0.014)]. Gender, race, ifosfamide/methotrexate/etoposide exposure, radiotherapy, endocrinopathy, and health habits were not predictive of low BMD. Conclusions: Survivors of childhood sarcoma are at high risk for low BMD. Risk factors include young age, non-lower extremity tumor site, and high cumulative cyclophosphamide exposure. Prospective studies are needed to confirm these risk factors, and to guide implementation of effective screening guidelines and therapeutic measures. No significant financial relationships to disclose.

Metabolic syndrome traits in long-term survivors of pediatric sarcoma at a single institution

9041 Multi-modality therapy (MMT) for pediatric sarcoma (SARC) may result in late endocrine abnormalities and increased cardiovascular morbidity. Metabolic syndrome (MS; NCEP ATPIII definition), a cluster of obesity, dyslipidemia, hyperglycemia and hypertension, conveys an increased risk of type 2 diabetes and cardiovascular disease. This cross-sectional study investigated the prevalence of the MS traits (MST) in long-term survivors of MMT for SARC. 32 survivors of SARC (predominantly Ewing’s; median age 36.5 years, range 17–54; f:m = 15:17; median age at MMT of 15 years, range 7–34; median time since completion of MMT 18 years, range 3–33) completed CT evaluation of abdominal obesity, DEXA scan for body mass composition, fasting serum lipid profile (FLP), the Human Activity Profile (HAP) and PAI and beta 2 microglobulin (B2M) analysis. Results, compared to appropriate controls were considered statistically significant if the p-value &lt; 0.01. SARC survivors were more likely to have one or more MST (common OR 4.04, CI:[1.52, 13.55], p=0.0045). Subjects aged 20–39 had a higher pooled prevalence of the MS (common OR 4.29 [1.50, 11.21], p=0.0077), defined as 3 or more traits, compared to controls stratified by gender. Analysis of individual MST demonstrated higher prevalence of hypertension (common OR 2.61,[1.20, 5.59], p=0.015), hypertriglyceridemia (common OR 3.63, [1.75, 7.60], p=0.0006), and male abdominal obesity (common OR 4.52, [1.57, 13.39], p=0.0046). SARC survivors had a higher prevalence of hypercholesterolemia than healthy adults (p=0.012). PAI antigen (p=0.043), PAI activity (p=0.018) and B2M levels (p=0.043) increased with an increasing number of MST. In male subjects, total testosterone declined (p=0.008) as the number of MST increased. Average (p=0.028) and maximum (p=0.041) activity levels decreased as the number of MST increased. After a median follow up of 18 years, adult SARC survivors of MMT have an increased prevalence of MST, especially between ages 20–39 years. The development of MST may be associated with decreased testosterone and decreased activity level. Younger male adult SARC survivors may be at particular risk for type 2 diabetes and cardiovascular disease and should be monitored. No significant financial relationships to disclose.

Treatment late effects in long‐term survivors of pediatric sarcoma

To assess health and musculoskeletal function in survivors of pediatric sarcomas. Thirty-two individuals treated for Ewing sarcoma family of tumors (ESFT), rhabdomyosarcoma (RMS), or non-rhabdomyosarcoma soft tissue sarcomas (NR-STS) with multi-modality therapy were enrolled on this cross-sectional study. Median age at the time of therapy was 15.4 years (range 7.1-34.2), median age at the time of analysis was 37.4 years (17.5-55.4), and median duration of time elapsed from completion of therapy was 17.3 years (2.9-32.6). Participants underwent assessments of musculoskeletal functioning, cardiac function, metabolic and lipid analyses, renal and gonadal function, and psychological evaluation. This cohort of sarcoma survivors shows expected locoregional limitations in function of the area affected by sarcoma, and impaired global musculoskeletal functioning as evidenced by limited endurance and limited overall activity levels. The cohort also demonstrated substantial rates of cardiac dysfunction, elevated body fat index, hyperlipidemia, chronic psychological distress, and infertility in men (76%) and premature menopause (49%) in women. Sarcoma survivors demonstrate diminished locoregional and global musculoskeletal functioning which likely limit occupational opportunities and socioeconomic health. In addition, the combination of diminished cardiac reserve, limited activity levels, and lipid dysregulation in sarcoma survivors suggests that this population is at increased risk for cardiovascular disease, even many years following completion of sarcoma therapy. Sarcoma survivors may benefit from life long follow-up for cardiovascular disease and from occupational counseling upon completion of therapy.

Persistent psychological distress in long-term survivors of pediatric sarcoma: the experience at a single institution.

The long-term psychological impact of pediatric sarcoma is largely unknown. As part of a cross-sectional study examining the late effects of pediatric sarcoma therapy, we examined whether psychological distress or posttraumatic stress symptoms are present in an adult cohort of pediatric sarcoma survivors. Thirty-four patients participated in the study, an average of 17 years after their treatment ended, each completing the SCID module for Posttraumatic Stress Disorder, Impact of Events Scale, Brief Symptom Inventory (BSI) and a questionnaire assessing sociodemographic variables and psychosocial issues. Significant persistent psychological distress characterized this cohort of patients. Seventy-seven percent scored in the clinical range on the BSI. Twelve percent met diagnostic criteria for PTSD. Current psychological distress was associated with intrusive thoughts and avoidant behaviors, male gender, employment, difficulty readjusting to work/school after treatment, and enduring worries about health. No differences were found based on age, presence of metastatic disease or time since diagnosis. This is the first report of a clinical evaluation of psychological distress in a cohort of pediatric sarcoma survivors treated with intensive multimodal cancer therapy. The results suggest that survivors of pediatric sarcoma might be at high risk for adverse psychological outcomes. Appropriate interventions are proposed.

Poster 34 physical performance and perceived psychosocial stress in pediatric sarcoma survivors. Usha G. Chaudhry, MD (Natl Inst Health, Bethesda, MD); Lynn Gerber, MD; Gloria Furst, OTRL, MPH; Lori Wiener, PhD, DCSW; Patrick Mansky, MD; Elizabeth Augustine, MSPT, e-mail: uchaudhry@nih.gov

Poster 34 physical performance and perceived psychosocial stress in pediatric sarcoma survivors. Usha G. Chaudhry, MD (Natl Inst Health, Bethesda, MD); Lynn Gerber, MD; Gloria Furst, OTRL, MPH; Lori Wiener, PhD, DCSW; Patrick Mansky, MD; Elizabeth Augustine, MSPT, e-mail: uchaudhry@nih.gov

Rehabilitation assessments of pediatric sarcoma survivors

8528 Background: Improved diagnosis and comprehensive treatment of childhood cancers has increased the overall survival rate. This study assesses physical impairments, functional limitations, health status and behaviors; and vocational and occupational histories of adult survivors of pediatric sarcomas. Methods: Physical impairment assessment: Joint range of motion (ROM); manual muscle testing (MMT); hand grip strength (HGS). Functional limitations: Assessment of motor and process skills (AMPS); 6-minute walk (6MWT); and human activity performance (HAP) questionnaire. Health status and behaviors: Leisure satisfaction measure (LSM); SF-36; sickness impact profile (SIP). Vocational and occupational histories: The Goldberg Scale (GS). Statistics: Standardized measures compared patients with norms. The results were evaluated by Wilcoxon signed rank two-sided p-values, unadjusted for multiple comparisons. Results: 32 survivors were diagnosed at median age 15.4 years (male:female=17:15, Ewing's sarcoma in 24/32). ROM of 22 subjects tested was >40% reduced in 12/13 with lower extremity (LE) lesions. HGS equaled matched norms. 28 /32 performed the 6MWT. 3/4 non-ambulatory subjects were LE amputees. Velocity in 9 was <90% predicted. HAP maximum score/maximum adjusted scores were lower than matched norms (p=0.015 and p=0.043 respectively). Motor and process scores for performance of routine daily tasks were lower than normal matched controls (p<0.0001). SF36 physical competency subscale trended lower (p=0.065), mental competency scores trended higher (p=0.058) than normal, respectively. Overall LSM was higher than the control group (p<0.001). Preliminary GS evaluation suggests higher work satisfaction. Conclusion: Survivors of childhood sarcoma have residual impairment of strength and motion, more likely of the lower extremity. Performance(mobility and daily routines), was reduced. Leisure satisfaction and self-reported mental competency higher than matched normal subjects, despite significant physical limitations, may reflect an augmented sense of well-being. Vocational drive and occupational behaviors were above average compared to people with disabilities. No significant financial relationships to disclose.

Rehabilitation assessments of pediatric sarcoma survivors

8528 Background: Improved diagnosis and comprehensive treatment of childhood cancers has increased the overall survival rate. This study assesses physical impairments, functional limitations, health status and behaviors; and vocational and occupational histories of adult survivors of pediatric sarcomas. Methods: Physical impairment assessment: Joint range of motion (ROM); manual muscle testing (MMT); hand grip strength (HGS). Functional limitations: Assessment of motor and process skills (AMPS); 6-minute walk (6MWT); and human activity performance (HAP) questionnaire. Health status and behaviors: Leisure satisfaction measure (LSM); SF-36; sickness impact profile (SIP). Vocational and occupational histories: The Goldberg Scale (GS). Statistics: Standardized measures compared patients with norms. The results were evaluated by Wilcoxon signed rank two-sided p-values, unadjusted for multiple comparisons. Results: 32 survivors were diagnosed at median age 15.4 years (male:female=17:15, Ewing's sarcoma in 24/32...