Childhood Cancer Survivor with congenital anomalies: the potential of physical activity to improve health-related outcomes

Pediatric cancer patients are living longer. The 5-year overall survival rate for childhood cancer survivors (CCS) has improved from approximately 30% in the 1960s (1) to more than 85% today (2). However, improved survival often comes at the cost of therapy-related late effects and chronic health conditions in adulthood. These conditions are classified according to the Common Terminology Criteria for Adverse Events (CTCAE) as mild/asymptomatic (grade 1), moderate (grade 2), severe/disabling (grade 3), life-threatening (grade 4), or fatal (grade 5) (3,4). Data from the Childhood Cancer Survivor Study (CCSS) indicate that more than 25% of CCS treated in the 1990s will develop at least one severe chronic health condition (grades 3–5) (3,4). Furthermore, nearly all CCS will experience at least one chronic health condition of any grade during their lifetime and 96% will develop a severe, life-threatening, or fatal condition by the age of 50 years (5). By comparison, in the general population, it is estimated that over 75% of US adults will live with at least one chronic health condition and more than 50% will have multiple chronic conditions during their lifetime (6,7). On average, CCS experience 17 chronic health conditions across their lifespan, approximately five of which are severe, life-threatening or fatal chronic health conditions (5). Chronic health conditions ultimately affect long-term morbidity and mortality among CCS (8). And while late effects in CCS have been characterized, the impact of cancer and its treatments, specifically on survivors with congenital anomalies remains largely unknown.

It is in this research context that Janitz and colleagues recently reported health outcomes in 22,247 CCS (median age at diagnosis: 6 years; median age at follow-up: 31 years) (9). Among these CCS, 3,880 (16.9%) self-reported a congenital anomaly, with congenital heart defects being the second most common (N=693; 18.4%), after large/multiple birthmarks (N=1,540; 40.4%). The authors reported that CCS with self-reported congenital anomalies demonstrated a higher cumulative incidence of chronic health conditions compared with those without congenital anomalies (9). Specifically, CCS who self-reported congenital anomalies have an elevated risk of developing any chronic health conditions (e.g., digestive, renal, neurologic) of any grade across multiple systems, including cardiovascular conditions (9). Importantly, CCS with congenital anomalies were 24% more likely to develop a severe, disabling, life-threatening, or fatal chronic health condition than CCS without congenital anomalies (9).

This study represents an important contribution to pediatric oncology, particularly given that children with congenital anomalies have a five-fold higher risk of developing cancer compared with children without congenital anomalies (10). The findings reinforce that the consequences of cancer extend well beyond treatment completion, with chronic health conditions emerging or worsening as survivors age (11). A similar age-related pattern is also observed in the general population. In fact, approximately 60% of young adults, 80% of middle-aged adults and 93% of older adults live with at least one chronic health condition (6,7). Nevertheless, exposure to cancer therapies during critical developmental periods may further exacerbate underlying vulnerabilities. Janitz et al. reported stronger associations after adjustment for age at cancer diagnosis and treatment exposures (9). Notably, CCS with self-reported congenital anomalies were 28% more likely to develop a cardiovascular condition of any grade, compared with CCS without congenital anomalies (9). Consistent with these findings, cumulative incidence estimates showed a greater overall burden of chronic health conditions among CCS with self-reported congenital anomalies than among those without congenital anomalies (9). Hence, these findings support the authors’ assertion that “children with congenital heart defects are at increased risk of cardiovascular disease, thus the cardiotoxic effects of chemotherapy may further exacerbate this risk” (9). This concern is underscored by the literature reporting that CCS have a 15-fold increased risk of heart failure and seven-fold increased risk of premature cardiac death compared with the general population, making cardiovascular disease the leading cause of non-cancer-related death in this unique population (3,8). However, Janitz et al. found similar mortality rates for CCS with and without congenital anomalies (9). For cardiac-related deaths, CCS with self-reported congenital anomalies had very similar mortality rate compared to CCS without congenital anomalies (0.37 vs. 0.36 per 1,000 person-years) (9). These findings suggest that although congenital anomalies are associated with a higher incidence of chronic health conditions, including cardiovascular conditions among CCS, this increased risk was not associated with a statistically significant difference in cardiac mortality (9). However, these findings must be interpreted in the context of limitations. As Janitz et al. reported in their discussion section, early mortality among CCS was not evaluated because the cohort was restricted to 5-year survivors, thereby excluding those who died earlier. Consequently, cardiac mortality in this population may have been underestimated

These findings highlight the need to prioritize effective pharmacological and non-pharmacological strategies to mitigate treatment-related cardiotoxicity during active therapy. Physical activity is a well-established non-pharmacological intervention with cardioprotective benefits. Growing evidence from the pediatric cardio-oncology field demonstrates that regular physical activity reduces treatment-related cardiotoxicity and improves long-term health outcomes in CCS (12). Physical activity may also extend survivorship, as CCS who increase their activity levels over an 8-year period experience a 40% reduction in all-cause mortality (13,14). Similarly, engaging in physical activity more than three days per week is associated with significantly lower all-cause mortality risk (15). Therefore, physical activity may play a key role for CCS with congenital anomalies.

Nevertheless, despite the well-established benefits of physical activity in CCS without congenital anomalies, physical activity benefits that pertain specifically to CCS with congenital anomalies remains limited. While evidence-based medicine strongly supports daily physical activity in pediatric oncology, interventions must be carefully designed to address patients’ needs and medical status. In a review focusing on children with congenital heart defects but without cancer, the authors reported that patients can be prescribed individualized physical activity programs; however, physical activity recommendations specific to this population remain scarce (16). Accounting for the presences of congenital anomalies is therefore essential when developing and implementing physical activity programs, especially when considering the frequency, intensity, duration and type of the physical activities. Future studies evaluating the safety and efficacy of physical activity interventions specifically in this subgroup of CCS with congenital heart defects are therefore warranted. Improved characterization of CCS health profiles, including medical history and chronic health conditions, as well continued monitoring of cardiac function, will support the integration of physical activity as a standard of care across the cancer care continuum. In this regard, the study by Janitz et al. provides valuable insight into long-term outcomes among CCS with self-reported congenital anomalies.

Early detection of chronic health conditions, coupled with the early integration of physical activity support in pediatric oncology is a cancer care priority. The International Pediatric Oncology Exercise Guidelines (iPOEG) (14,17) recognize the role of physical activity in managing long-term symptoms in children and adolescents diagnosed with cancer. This priority is also endorsed by the American Society of Clinical Oncology (ASCO) (18), the American College of Sports Medicine (ACSM) (19,20) and the Children’s Oncology Group (COG) (21). Beyond reducing cardiovascular risk in CCS, preventing sedentary behavior is critical in this population, as physical inactivity is associated with greater risk of chronic diseases and unfavorable physical and psychosocial outcomes.

As the field of pediatric oncology moves toward establishing physical activity as a standard of care, it is essential to better understand and address the needs of less-represented survivor subgroups. This study represents an important step forward and will be further strengthened by future investigations incorporating genetic data, as suggested by Janitz et al., to address potential misclassification related to self-reported congenital anomalies and chronic health conditions (9). The generalizability of their findings may still be limited, as the majority of the cohort is non-Hispanic White. Taken together, these efforts indicate that pediatric oncology is progressing toward more precise and inclusive survivorship care.

Acknowledgments

None.

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, Annals of Cancer Epidemiology. The article has undergone external peer review.

Peer Review File: Available at https://ace.amegroups.com/article/view/10.21037/ace-2026-1-0008/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://ace.amegroups.com/article/view/10.21037/ace-2026-1-0008/coif). M.C. is supported by the Four Diamonds Research Funds, Department of Pediatrics, Division of Hematology and Oncology, Penn State College of Medicine, Hershey, PA, USA. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

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