Is health status impaired in childhood cancer survivors? A systematic review and meta-analysis

Highlights

• Childhood cancer survivors (CCS) have a lower left ventricular function.

• CCS also present with lower HDL-cholesterol and higher adiposity.

• There is thus a need to monitor the cardiometabolic health status of CCS.

Abstract

Background

: An increase in survival rates of childhood cancer is associated with long-term health issues in survivors.

Methods

: We conducted a systematic review and meta-analysis comparing health status-related endpoints in childhood cancer survivors (CCS) versus controls.

Results

: Eighty-six studies (n = 98,480 participants, 62% CCS) were included in the review. Of these, 73 studies (n = 96,550, 63% CCS) could be meta-analyzed. CCS showed a lower left ventricular ejection and fractional shortening (SMD=-0.59 and -0.55, respectively, both p < 0.01 [n=1,824 and 1,880]), a lower HDL-cholesterol concentration (SMD=-0.48, p<0.001, n=1,378) and a higher waist-to-hip ratio (SMD=0.61, p < 0.01, n=229) than their healthy peers. No significant differences were found for the remaining endpoints.

Conclusions

: CCS is associated with a lower left ventricular function and HDL-cholesterol level, and a higher waist-to-hip ratio than healthy controls. These findings support the need to closely monitor the cardiometabolic health status of CCS and to implement preventive lifestyle interventions for this population.

Introduction

Treatment advances for childhood cancer have improved considerably over the last decades, with an overall 5-year survival of ˜80% (Ward et al., 2014). The prevalence of childhood cancer survivors (CCS) is therefore increasing, with the total number of CCS estimated to reach 500,000 in the United States by 2020 (Robison and Hudson, 2014). However, the increase in survival rates is not necessarily associated with a good health status after disease recovery, and can impose significant medical burdens. Indeed, conventional anti-cancer treatments (chemotherapy and/or radiotherapy) can induce late effects in adult survivors of childhood cancer and thus be associated with long-term health issues (Lipshultz et al., 1991; Oeffinger et al., 2000), which need to be monitored (Ward et al., 2014). Further, intensification of traditional treatments is likely to induce marginal benefits while further aggravating adverse effects, which drives the development of new targeted therapy strategies (e.g., immunotherapy) (Burdach et al., 2018).

Approximately 62% of CCS will have at least one chronic disease 30 years after the first diagnosis (Oeffinger et al., 2006), and a higher incidence of a severe, disabling, life-threatening, or fatal health condition has been reported in CCS as compared with their siblings (Armstrong et al., 2014). Notably, cardiac abnormalities (Adams et al., 2004; Landy et al., 2013; Lipshultz et al., 2012), pulmonary complications (Dietz et al., 2016), diabetes (Meacham et al., 2009; van Nimwegen et al., 2014), obesity,(Guler et al., 2018; Nam et al., 2015), poor bone health (Gilsanz et al., 1990; Mostoufi-Moab et al., 2012; Petryk et al., 2006), impaired muscular and cardiorespiratory fitness (CRF) (Söntgerath and Eckert, 2015; van Brussel et al., 2005), or mental disorders, especially depression (Brinkman et al., 2016), have all been found to be higher among CCS than among healthy peers. However, no meta-analysis has yet compared the global health status of CCS and their controls.

Our objective was to conduct a systematic review and meta-analysis of case (CCS)-control studies to compare, from an integrative perspective, the health status of cancer-free CCS with their healthy counterparts. To this end, we studied those health-related parameters likely to be most affected by disease or its treatment considering the aforementioned health conditions more prevalent in CCS, including cardiovascular and pulmonary function, body composition, metabolic and inflammatory markers, physical capacity phenotypes (e.g., CRF, muscular strength), physical activity levels, fatigue, and mental health.