- More than 500,000 childhood cancer survivors will be living in the United States by 2020.
- Childhood cancer survivors age 35 and older are 5 times more likely to develop a severe, disabling, life-threatening, or fatal chronic condition compared to siblings.
- As this population continues to expand, it is essential that knowledgeable, multidisciplinary teams of providers are available and prepared to meet the unique needs of survivors.
- Studies seeking to understand the impact of temporal changes in cancer treatments on psychosocial outcomes, physical function, and neurocognitive performance are needed in order to maintain cost-effective surveillance strategies and to provide targeted interventions to those survivors at risk for adverse outcomes.
Advances in treatment and supportive care have led to dramatic improvement in the overall survival for children with cancer. As a result, more than 84% of children (ages 0-19) newly diagnosed with a malignancy will be 5-year survivors and go on to live many decades beyond completion of cancer therapy.1 By 2020, it is estimated that more than 500,000 childhood cancer survivors will be living in the United States,2 reinforcing past and ongoing efforts to better characterize the health care needs of this aging population.
Improved survival has led to better characterization of the many potential late effects of cancer and its curative treatments. We now recognize that childhood cancer survivors age 35 and older are 5 times more likely to develop a severe, disabling, life-threatening, or fatal chronic condition compared to siblings.3 The spectrum of cancer- and cancer treatment–related late-occurring health events extends beyond the development of chronic conditions, impacting physical performance,4 neurocognition,5 health status,6 psychosocial outcomes,7,8 and educational and occupational status.9 Moreover, we recognize that this number likely underestimates the true burden of disease in survivors because of the limitations of retrospective cohort studies and self-reported outcomes.10,11 Even more concerning is the recognition that compared to siblings, long-term survivors incur significantly increased mortality from chronic health conditions.12 Additionally, the costs associated with increasing survival duration and excess lifetime morbidity, as well as risks from novel treatment agents, remain uncertain (Fig. 1).2 A key question that remains unanswered is whether interventions that prevent or reduce risk for chronic conditions will mitigate these mortality risks. There is good news for survivors from more modern eras, however, as reductions in cancer treatment have recently been shown to have directly affected reductions in late mortality (Fig. 2) and risk for subsequent neoplasms.13,14
Much of the improvement in overall survival attained in pediatric oncology can be attributed to the establishment of treatment consortia and high rates of enrollment and treatment of children on cooperative clinical trials.15 A parallel paradigm has occurred in pediatric cancer survivorship over the past 3 decades, wherein a number of cohort studies were developed in order to systematically assess survivors throughout various stages of long-term follow-up.16 Among others, the Childhood Cancer Survivor Study, a multi-institutional retrospective cohort established in 1994, has grown to include 35,923 survivors and more than 5,000 siblings for comparison.17,18 Rigorous abstraction of treatment exposure data, combined with self-reported outcomes, have resulted in almost 300 scientific publications that have identified increased risk for late mortality, chronic health conditions, subsequent neoplasms, and behavioral outcomes.7,13,14,19
Similar cohorts have since been established internationally, validating and extending results.20 In many cases, investigators have pooled cohort data, affording opportunities to perform critical studies that would otherwise have been underpowered in each individual cohort.21,22 More recently, the St. Jude Lifetime Cohort Study (SJLIFE), a prospectively evaluated cohort designed to facilitate longitudinal, direct clinical assessment of survivors, was established to address limitations inherent to retrospective cohorts with self-reported outcomes, including identification of subclinical and undiagnosed health effects, potentially affording opportunities for early and effective intervention. SJLIFE has been actively enrolling survivors since 2007 and, at the time of this writing, has accrued 4,983 survivors and 419 community controls. These cohorts, along with numerous single-institution investigations, have shaped the development of survivorship care as we know it today.16
Clinical Practice Guidelines
As this population continues to expand, it is essential that knowledgeable, multidisciplinary teams of providers are available and prepared to meet the unique needs of survivors. Availability of clinicians with robust exposure to childhood cancer survivors is limited in many regions. Thus, for many survivors, their primary caregiver will be on the front line of providing clinical care. To facilitate the care of these complex cases across a variety of clinical settings, leading organizations have developed national clinical practice guidelines.23 In the United States, for example, the Children’s Oncology Group Long-term Follow-up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers provide evidence-based recommendations regarding risk-based surveillance strategies.17,24 Included in the guidelines are several “Health Links” that provide patient-directed health information that can be tailored toward individuals at risk for a given outcome.
These guidelines have capitalized on previous research by evaluating the strength of the evidence linking specific therapeutic exposures with observed late effects. In regard to recommendations for screening and early detection of late effects, the evidence for efficacy is more sparse. Thus, these guidelines rely on consensus-based surveillance recommendations from late-effects experts that align the intensity of screening with the magnitude of risk. In many cases, data to support screening recommendations are limited by the long latency period for development of late effects, such as cardiomyopathy, and, in some cases, low incidences of the late outcome in question. However, recent reports have demonstrated the utility of simulation models with regard to both testing existing and potentially informing the development of future cost-effective surveillance strategies.25,26 This will undoubtedly strengthen existing recommendations and enhance future iterations of pediatric survivorship guidelines.
In 2010, the International Late Effects of Childhood Cancer Guideline Harmonization Group was formed through the joint efforts of leading national guideline organizations with the aim of providing a unified vision and integrated strategy for chronic health condition surveillance in childhood cancer survivors.23 The group’s primary efforts centered on identification of discordances between existing guidelines, and ultimately, establishment of concordant, evidence-based (where possible) recommendations applicable across a variety of clinical settings. To date, harmonized screening guidelines regarding breast cancer,27 cardiomyopathy,28 and male and female gonadal dysfunction29,30 have been published, with a number of specific late-outcome harmonization efforts in progress. The results of these undertakings will not only strengthen existing recommendations but will identify knowledge gaps and prioritize future research initiatives. Most importantly, they will give clear guidance to the primary care community that will be providing the frontline care for this population that often has complex needs.
Translating Research Into Clinical Care
Critical to advancing cancer survivorship has been the translation of epidemiologic studies and structured clinical guidelines into meaningful medical care for survivors of all ages. Although efforts to optimize care delivery are ongoing, several models can be effective when used in the appropriate setting. Models vary considerably, from the resource-intense multidisciplinary approach to a less resource-dependent consultative strategy that offers single visits to survivors, subsequently transferring delivery of recommended care to the primary care provider.31 Alternatively, risk-stratified models provide specialty care only to those survivors whose risk for a given toxicity is considered high enough to merit long-term follow-up.31 Many have advocated for shared-care models, critically dependent upon open and effective communication between specialty and primary care providers.32 However, it is unclear which, if any, of these models is superior. Despite this uncertainty, it is generally felt that the best method is that which can be optimally supported by the available resources in a given institution.
So what can we really do? A recent survey of providers’ attitudes and knowledge regarding childhood cancer survivor care identified that despite a generalized willingness to be involved in the care of childhood cancer survivors, most were unfamiliar with recommended surveillance strategies and believed access to long-term follow-up guidelines and receipt of a concise treatment summary with surveillance recommendations would enhance the ability to care for survivors.33 Similarly, Oeffinger reported that incomplete knowledge of past exposures, treatment-related health risk, and surveillance recommendations were shared by survivors and health care providers.34 One commonly proposed solution to address these concerns has been the development of a comprehensive care summary or survivorship care plan. Survivorship care plans, as advocated for by the Institute of Medicine and National Research Council, should provide an overview of cancer type, treatments, and the potential consequences of both, in addition to patient-specific recommendations regarding preventive practices and surveillance/follow-up strategies.35 Despite this recommendation, most studies report that fewer than one-third of survivors and providers report ever having received of a care plan, identifying this breakdown in communication as a key area in which targeted intervention may improve delivery of care.33,36,37
Despite the long-term health implications identified in many childhood cancer survivors, there are ample reasons for optimism. The majority of survivors report psychological wellness and generalized satisfaction with their lives.7 In addition, studies suggest that a number of cancer survivors may, in fact, endorse more positive impacts of the cancer experience compared to siblings, and many are thriving, or experiencing positive life changes based upon the meaning that they derive from their own cancer narratives.38-40 Recent data provide welcome reassurance that not only are the treatments for childhood cancer curing more children, they are doing so at a reduced cost to long-term survivors.13 Studies seeking to understand the impact of temporal changes in cancer treatments on psychosocial outcomes, physical function, and neurocognitive performance are needed in order to maintain cost-effective surveillance strategies and to provide targeted interventions to those survivors at risk for adverse outcomes.
In summary, childhood cancer survivors are now a prevalent and aging population with unique health care requirements. These needs will undoubtedly continue to evolve in parallel with cancer therapies, reinforcing the role of cooperative studies designed to characterize the changing phenotypes in this population. Collaborative efforts of oncologists, generalists, subspecialty providers, and patients and their families are essential to advance knowledge related to survivorship care. Future investigations are needed to identify the most effective components of care and delivery mechanisms. Until these data are available, open and effective communication between providers and survivors remains critical to providing the best care to this medically complex cohort.
About the Authors: Dr. Ehrhardt is a pediatric oncologist with St. Jude Children’s Research Hospital. Dr. Hudson is a pediatric oncologist, director of the Cancer Survivorship Division, co-leader of the Cancer Prevention & Control Program, and the Charles E. Williams Endowed Chair of Oncology-Cancer Survivorship with St. Jude Children’s Research Hospital. Dr. Hudson is also the principal investigator of the SJLIFE study, and an associate editor for JCO. Dr. Armstrong is the Principal Investigator of the Childhood Cancer Survivors Study (CCSS), a full member of the Department of Epidemiology and Cancer Control, and a pediatric neuro-oncologist at St. Jude Children’s Research Hospital.