Each year, globally, about 400,000 children and adolescents aged between 0 and 19 years are diagnosed with cancer; over 100,000 die from the disease, with most of those cases, over 80%, and deaths occurring in low- and middle-income countries.1 Delays in obtaining an accurate diagnosis, inaccessibility to effective therapy, abandonment of treatment, death from treatment toxicities, and avoidable relapse are all contributing factors to making cancer a leading cause of death for children and adolescents worldwide.
Where a child lives can also influence whether that child survives cancer. According to the World Health Organization (WHO), whereas more than 80% of children with cancer living in high-income countries are cured of their disease, that percentage drops to less than 30% for young patients living in low- and middle-income countries.1 And these figures likely do not capture the full scale of burden of disease because population-based cancer registries in many low- and middle-income countries do not exist, and research in childhood cancer survivorship is scarce.
To better understand the global distribution of research conducted in childhood cancer outcomes, including country of origin and study focus, Melissa Martos, MD, a pediatric oncologist at Seattle Children’s Hospital and her colleagues, including contributing author Matthew J. Ehrhardt, MD, MS, Associate Member in the Departments of Oncology and Epidemiology and Cancer Control at St. Jude Children’s Research Hospital, launched a systematic review of 1,558 studies in childhood cancer survivorship research conducted in 43 countries and territories from 1980 to 2021.
The results from the study show that the overwhelming majority (> 90%) of research published was based on studies conducted in high-income countries and in the combined WHO American and European regions, despite the greater cancer burden occurring in low- and middle-income countries. In addition, the review found that the primary focus of the research was on the physical effects of cancer and its treatment, especially in low- and middle-income countries compared with research in high-income countries, and often did not address other issues, such as mental health, health promotion, and disease prevention.2
Ten years ago, researchers were understandably focused on improving the cure rate and, therefore, in many cases weren’t able to commit adequate time to thinking about the long-term effects from cancer and its treatment on children.— MATTHEW J. EHRHARDT, MD, MS
Tweet this quote
“It shouldn’t come as a surprise that the bulk of research is being conducted in high-income regions, but I don’t think any of us would have predicted 95%,” said Dr. Ehrhardt. “There is just a huge disparity between the amount of research being done in high- vs low- and middle-income countries. There are about 1.2 million childhood cancer survivors in the United States and Europe, where many of these studies have been performed. However, that’s just a small fraction of the global number of survivors and patients transitioning into survivorship whose health needs may not be represented by these existing research studies.”
In this interview with The ASCO Post, Dr. Ehrhardt discussed why research in childhood cancer survivorship in low-resource countries is limited, what is needed to improve childhood survivorship rates in these countries, and the importance of developing resource-adapted childhood cancer treatment guidelines.
Understanding the Gaps in Survivorship Care in Low-Resource Settings
The results from this study are particularly disturbing because about 90% of children expected to develop cancer live in low- and middle-income countries. Yet, nearly all survivorship research is conducted in high-income countries, leaving gaps in survivorship care for children with cancer worldwide. Please talk about the importance of your finding; and why isn’t more research on childhood cancers being conducted in lower-income countries?
Part of the reason most of the [survivorship] research is conducted in high-income countries is because childhood cancer survival rates are so high in North America and Europe, about 85%, whereas they have been historically much lower in low-resource regions, in some cases 30% or less. The WHO’s Global Initiative for Childhood Cancer has set a goal of increasing the global survival rate of children with cancer to at least 60% by 2030, while simultaneously reducing their suffering and improving their quality of life.3
If we can come anywhere close to that percentage of children surviving cancer in low- and middle-income countries, and can also begin to perform more research in these countries, it will help tell us where the gaps in survivorship care are and how to close those gaps. We know that survivorship looks very different in different regions, and there are certainly local contextual issues that have to be considered when conducting research in different parts of the world. For example, variation in health-care delivery infrastructures, regional life expectancy, and cultural differences may play huge roles in how survivorship care practices are prioritized in specific regions. So, understanding these differences will be critical to implementing contextually appropriate care.
There are myriad other challenges to doing childhood cancer survivorship-related research, including lack of research infrastructure and mentors and limited opportunities for funding, training, and attending scientific conferences. Another important factor is identifying and reengaging survivors to enroll in these studies. Ten years ago, researchers were understandably focused on improving the cure rate and, therefore, in many cases weren’t able to commit adequate time to thinking about the long-term effects from cancer and its treatment on children. Today, there is a greater understanding of the importance of conducting survivorship research. However, often many survivors and their families just want to move on after their treatment and not talk about cancer anymore.
This used to be an issue in the United States and in other high-income countries as well. But efforts to educate patients and providers about the importance and benefits of proactive health screening and maintenance have helped to address this barrier to providing comprehensive survivorship care. We need to be proactive in determining how to overcome these challenges in different parts of the world, so that we can meet this challenge head-on for this emerging population.
Mitigating the Obstacles to Conducting Childhood Cancer Survivorship Research
The reasons for lower survival rates in low- and middle-income countries include delay in diagnosis, lack of access to essential medicines and technologies, treatment abandonment due to the high cost of care, death from side effects of cancer or its treatment, and relapse. How would focusing more on research in low-resource countries improve survival rates for childhood cancers in those regions? For example, would the development of guidelines specific to local priorities, resources, and culture mitigate some of the obstacles to conducting childhood cancer survivorship research?
There is a lot of research underway to answer that question. There definitely needs to be infrastructure in place to improve access to clinical care, in addition to educational outreach initiatives to help parents, children, community providers, and even community leaders to recognize the symptoms of cancer and to seek medical care immediately. Higher cure rates also require improved access to essential medicines, as well as greater awareness among local providers of the availability of curative treatment options for these cancers.
Childhood cancer is still a relatively rare condition both here and in low- and middle-income countries, and these patients represent a small fraction of the patients that a primary care physician sees on a daily basis. These clinicians are often the ones providing follow-up care, so determining the best ways to get them recommendations regarding surveillance care is an important challenge that we need to overcome.
We are doing a lot of qualitative research to get a better understanding of where these children are being treated in various regions. For example, are they being treated at a cancer center or at a community facility? Understanding more about the local context will help determine the best approaches to capturing data on these survivors and improving enrollment into clinical trials.
Increasing Survival for Children With Cancer
In 2018, the WHO, with support from St. Jude Children’s Research Hospital, launched the Global Initiative for Childhood Cancer to provide leadership and technical assistance to governments to support them in building and sustaining high-quality childhood cancer programs. The goal is to achieve at least 60% survival for all children with cancer by 2030. What progress are you seeing so far with this initiative?
Among the most promising approaches to increasing survival for these children is partnering with local hospitals or communities to develop the infrastructure, regional support, and access to local resources that are needed to improve childhood cancer survival rates. In many instances, it means developing cancer treatment and survivorship programs in individual low- and middle-income countries, which are challenging to do because they are labor intensive and difficult to sustain.
What our Department of Global Pediatric Medicine group has worked very hard to do is to facilitate development of local infrastructure that educates researchers on conducting research protocols, establish and maintain cancer data registries, and provide ongoing support as questions arise, so that local initiatives are not dependent on research facilities in high-income regions to conduct the studies directly.
Building those types of local infrastructure reinforcements and capacity is going to be critical to meet the ongoing health-care needs of the growing population of young survivors as they reach adulthood.
Developing Childhood Cancer Survivorship Care Plans
A major contributing factor to childhood cancer mortality in low- and middle-income countries is the lack of comprehensive cancer care plans and the associated resource limitations. Is St. Jude Children’s Research Hospital involved in helping low-resource countries develop cancer care plans, and how might greater attention to childhood cancer survivorship research in these countries potentially help accelerate the development of cancer care plans?
Several years ago, St. Jude and the International Society of Pediatric Oncology (SIOP) Congress developed the Adapted Resource and Implementation Application (ARIA) Guide to begin to address the global need for comprehensive, resource-adapted childhood cancer treatment guidance, including for supportive, palliative, and survivorship care, wherever clinicians practice.4 The guide is still in development, and we have recently begun to add survivorship recommendations to the available resources.
The idea behind the survivorship-specific aspect of ARIA is to co-develop a set of guidelines, in collaboration with our international partners, that can be delivered within the context of the available resources in a local community. We recognize that these recommendations may not align with survivorship guidelines developed in and largely for high-income countries, where substantial resources are needed to deliver care.
For example, the gold standard for subsequent breast cancer screening among survivors [of childhood cancers] who were treated with chest radiation is annual mammography and breast magnetic resonance imaging, but in many low-resource countries neither modality is available. We don’t want providers and survivors to be left without an alternative screening strategy, so we are preparing adapted guidelines that providers can use in the context of their local resource availability without having to develop them on their own. Where possible, these guidelines will be anchored in existing evidence. However, in many cases, these practices will likely open opportunities to evaluate existing practices through future research initiatives.
We’re excited about developing these guidelines and we are seeing tremendous enthusiasm from our global partners from all resource levels. We’re hoping to see improvement in childhood cancer survivorship research, and ultimately, improvement in global childhood cancer survivorship rates as the initiative gains momentum.
DISCLOSURE: Dr. Ehrhardt receives clinical trial support from Pfizer, speaker honorarium from Amgen, funding from the Children’s Oncology Group Foundation to support the Children’s Oncology Group Survivorship Guideline development, and funding from the National Institutes of Health.
REFERENCES
1. World Health Organization: Childhood Cancer. Available at www.who.int/news-room/fact-sheets/detail/cancer-in-children.
2. Martos M, George N, Arreguín-González FE, et al: Childhood cancer survivorship globally: A systematic review. JAMA Oncol (10):1231-1238, 2025.
3. World Health Organization: The Global Initiative for Childhood Cancer. Available at www.who.int/initiatives/the-global-initiative-for-childhood-cancer.
4. ARIA Guide: Comprehensive Management for Childhood Cancer. For Everyone. Available at https://aria.stjude.org.
