Five-year survival for many childhood cancers approaches 80%, and there is a growing number of long-term survivors in the United States. These survivors are at risk for developing adverse health-related complications. We highlight recently published studies that provide new insight into the association between specific therapeutic exposures and late-occurring complications such as second malignant neoplasms, cardiovascular disease, endocrinopathies, and neurocognitive impairment.
The incidence for many long-term complications continues to increase with longer follow-up. Investigators have begun to explore the impact of aging and the role of genetic susceptibility as modifiers of risk in diseases wherein there is a clear association between therapeutic exposure and adverse outcome. Increased awareness of the importance of screening has set the stage for assessment of the impact of early detection for reduction of long-term morbidity and mortality among childhood cancer survivors at highest risk for therapy-related complications.
The long-term health-related burden in childhood cancer survivors is substantial. Recent studies exploring the etiopathogenesis of treatment-related late effects have provided important information that will assist in ongoing efforts to develop personalized cancer care. Efficacious medical interventions are needed to help mitigate treatment-related complications in high-risk survivors.
"Over the past five decades, there has been remarkable overall success in terms of improved survival among children with cancer (Armenian et al., 2013). However, the survival rates for some cancers—such as brain tumors—have not improved to the same degree, and over the past decade it has become increasingly clear that long-term adverse effects of therapy are impacting on the health and well-being of the survivors of childhood cancer (Rosoff, 2006; Armenian and Robinson, 2013). The rate of adverse drug reactions in children with cancer is high and many of the most dreaded complications of childhood cancer are adverse events directly related to drug therapy. "
[Show abstract][Hide abstract] ABSTRACT: Adverse drug reactions are a common and important complication of drug therapy in children. Over the past decade it has become increasingly apparent that genetically controlled variations in drug disposition and response are important determinants of adverse events for many important adverse events associated with drug therapy in children. While this research has been difficult to conduct over the past decade technical and ethical evolution has greatly facilitated the ability of investigators to conduct pharmacogenomic studies in children. Some of this research has already resulted in changes in public policy and clinical practice, for example in the case of codeine use by mothers and children. It is likely that the use of pharmacogenomics to enhance drug safety will first be realized among selected groups of children with high rates of drug use such as children with cancer, but it also likely that this research will be extended to other groups of children who have high rates of drug utilization and as well as providing insights into the mechanisms and pathophysiology of adverse drug reactions in children.
Frontiers in Genetics 04/2014; 5:78. DOI:10.3389/fgene.2014.00078
[Show abstract][Hide abstract] ABSTRACT: There is an increasing recognition of the healthcare needs of long-term childhood and adolescent cancer survivors, but less information is known about the education and training needs of healthcare professionals.
The need for the provision of late effects care for this cohort of patients is now universally accepted by the paediatric cancer community in the western world. As evidence of healthcare needs become known, internationally agreed evidence-based screening practices are emerging.
The next clear step is to ensure that clinical staff, medical and nursing alike, are sufficiently prepared to provide safe, compassionate, patient-centred, contemporaneous and clinically effective late effects care. This review considers evidence for existing educational approaches and considers how we may prepare the workforce.
Current opinion in supportive and palliative care 09/2013; 7(3):296-302. DOI:10.1097/SPC.0b013e3283640f87 · 1.66 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Future advances in childhood cancer treatment will pivot on developing biology-driven new drug development pathways that build on current knowledge of oncogenic pathways; however, we need to address major barriers to accessing new drugs for clinical evaluation in childhood cancers.
Through legislative change, substantial incentives to the pharmaceutical industry to invest in the ultra-rare diseases, such as childhood cancers, have encouraged greater engagement with paediatric oncology drug development consortia. Disappointingly, this has not translated into paediatric-focussed drug development. Adult disease-driven drug development will continue to dominate until biology/target-driven approaches prevail.There are specific challenges to undertaking early drug development trials in children with incurable disease. The balance between risk and benefit for a child participating in trials wherein the chance of clinical benefit is indeterminate has the potential for unrealistic optimism by both physicians and families. Importantly, innovative trial designs that assess safety and maximize information on potential efficacy from small patient numbers are needed.
International collaboration in early phase trial consortia addresses these challenges. Academic networks concentrating early phase trials expertise and delivery of innovative trial designs will maximize appropriate selection of drugs that can translate into therapeutic advantage when incorporated into standard care.
Current opinion in pediatrics 12/2013; 26(1). DOI:10.1097/MOP.0000000000000054 · 2.53 Impact Factor
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