Neurocognitive and psychosocial outcomes in adult survivors of childhood soft‐tissue sarcoma: A report from the St. Jude Lifetime Cohort

Abstract

Background To the authors' knowledge, few studies to date have examined long‐term neurocognitive outcomes in survivors of childhood soft‐tissue sarcoma. Methods A total of 150 survivors (41% of whom were female with a mean current age of 33 years [SD, 8.9 years] and a time since diagnosis of 24 years [SD, 8.7 years]) and 349 community controls (56% of whom were female with a mean current age of 35 years [SD, 10.2 years]) completed comprehensive neuropsychological testing, echocardiography, electrocardiography, pulmonary function tests, endocrine evaluation, and physical examination. Patient‐reported outcomes of health‐related quality of life (HRQOL) and social attainment were collected. Survivors were compared with norms and controls on neurocognitive outcomes using general linear models, and on HRQOL and social attainment using modified Poisson models. The impacts of treatment and chronic health conditions on outcomes were examined using multivariable general linear models (effect size was expressed as unstandardized β estimates that reflected the unit of change from a mean of 0 and an SD of 1) and modified Poisson models (effect size expressed as relative risks). Results Compared with controls and population norms, survivors demonstrated lower performance on measures of verbal reasoning (mean z score, −0.45 [SD, 1.15]; P < .001) mathematics (mean z score, −0.63 [SD, 1.07]; P < .001), and long‐term memory (mean z score, −0.37 [SD, 1.14]; P < .001). Cumulative anthracycline exposure (per 100 mg/m2) was found to be associated with poorer verbal reasoning (β = −0.14 z scores; P = .04), reading (β = −0.09 z score; P = .04), and patient‐reported vitality (relative risk, 1.32; 95% CI, 1.09‐1.59). Neurologic and neurosensory chronic conditions were associated with poorer mathematics (neurologic conditions: β = −0.63 z score [P = 0.02]; and hearing impairment: β = −0.75 z scores [P < 0.01]). Better cognitive performance was associated with higher social attainment. Conclusions Long‐term survivors of soft‐tissue sarcoma are at risk of neurocognitive problems and poor HRQOL associated with anthracycline treatment and chronic health conditions.

Cognition, psychosocial functioning, and health-related quality of life among childhood cancer survivors

“…Interestingly, our data confirm previous findings (Ehrhardt et al, 2018;Hocking et al, 2015;Puhr et al, 2019;Tonning Olsson et al, 2020): executive functions, processing speed, and fluid intelligence were correlated with peer problems, and this was associated with poorer health-related quality of life in CC survivors. This finding underscores the importance of good executive functions and other cognitive functions for age-appropriate social behaviour and good quality of life (Ehrhardt et al, 2018;Puhr et al, 2019;Tonning Olsson et al, 2020;Wolfe et al, 2013). Our data extend the previous findings by Ehrhardt et al (2018) on adult CC survivors for the first time in children and adolescents.…”

“…Even though cancer treatment protocols are continuously modified to reduce long-term sequelae (Mucci & Torno, 2015), cognitive late effects are often reported (Krull et al, 2018;van der Linden et al, 2020). Cognitive problems likely affect psychosocial behaviour and health-related quality of life (Ehrhardt et al, 2018;Tonning Olsson et al, 2020). For instance, 29% to 59% of longterm survivors who have been treated for leukemia (Krull et al, 2013) and approximately 15% to 85% of adult survivors of childhood brain tumours demonstrate cognitive impairment (Brinkman et al, 2016).…”

“…Indeed, some studies have found that survivors' health-related quality of life tends to be worse than that of their healthy peers, whereas others have found that they report comparable or even better health-related quality of life than their healthy counterparts (Vetsch et al, 2018). Ehrhardt et al (2018) and Tonning Olsson et al (2020) have examined the relationship between cognition, psychosocial functioning, and quality of life in adult survivors of CC and demonstrated that cognitive impairment is associated with lower social attainment (e.g., educational attainment, unemployment) and poorer health-related quality of life. The findings of Puhr et al (2019) highlight that in particular lower executive functioning is associated with poorer social outcome (e.g., educational adjustments, government support) in young adults after childhood cancer.…”

Pediatric sarcoma survivorship: A call for a developmental cascades approach

“…Compared to more common childhood cancers, overall survivability is worse (Lim et al, 2015) and subsequent limitations on survivors' physical functions and daily activities are greater (Ness et al, 2005(Ness et al, , 2008. Moreover, cognitive and psychosocial outcomes for sarcoma survivors are less than ideal (Tonning Olsson et al, 2020;Storey et al, 2019). These compromised outcomes in turn raise additional challenges, the sum of which can prove overwhelminga recent analysis (Siracuse, Gorgy, Ruskin, & Beebe, 2017) of survivors ranging 0 and 30 years since their diagnosis indicated that they were twice as likely to die by suicide than the national average.…”

“…Sarcoma survivors trying to create a social identity post-treatment may be "damned if they do, damned if they don't"few peers want to be around someone consumed by health concerns; yet if such concerns are hidden from close others, one experiences a different type of loneliness and isolation (Fantozzi, personal communication, 2019). In other words, loneliness and isolation may result from coping (Patenaude & Kupst, 2005;Wiener et al, 2006;Schultz et al, 2007;Schwarzer, 2008;Gurney et al, 2009;de la Haye et al, 2011;Quesada et al, 2012;Cassidy, 2016;Edelmann et al, 2016;Moran, 2016;Shields et al, 2016;McLachlan & Gale, 2018;Olsson et al, 2020). mechanisms aimed at protecting the survivor from social rejection rooted in compromised physical functioning and aimed at protecting close others from worry or harm.…”