- ALL —
- acute lymphoblastic leukemia
- HICs —
- high-income countries
- LMICs —
- low- and middle-income countries
Although morbidity from childhood cancer is second only to unintentional injuries in high-income countries, in low-income countries, it hardly hits the radar screen compared with death from pneumonia, diarrhea, malaria, neonatal sepsis, preterm birth, and neonatal asphyxia. Nevertheless, the extraordinary progress made in treating childhood cancer in high-income countries brings into harsh focus the mammoth disparities that exist in impoverished areas of the world. As the capacity to diagnose and treat childhood cancer improves in low- and middle-income countries, the ability to improve outcomes for the more common diseases benefits as well. The authors have summarized the issues related to childhood cancer care with thoughtful attention to how children everywhere can gain from the advances in medical science in high-income nations.
Jay E. Berkelhamer
Childhood cancer is a relatively rare disease, and most cases occur in the low- and middle-income countries (LMICs) where nearly 90% of the world’s children live.1,2 In low-income countries, childhood cancer mortality is low compared with childhood mortality from other causes (eg, infectious disease). However, as mortality rates from other causes decreased by 49% worldwide from 1990 to 2013 for children aged under 5 years, so the relative importance of childhood cancer has increased.2,3
Although no etiologic agent or trigger is identifiable for most childhood cancers, there are some well-described associations with infectious diseases. The incidence of Burkitt lymphoma is much higher in malaria-endemic regions, Kaposi sarcoma is almost always associated with HIV infection, and hepatocellular carcinoma is more frequent in areas with a high prevalence of hepatitis B infection.1,2 Public health measures to reduce these infectious diseases will also lower childhood cancer mortality.
There are 3 standard modalities to treat a child with cancer: chemotherapy, surgery, and radiotherapy. Each cancer requires a specific combination of modalities and a defined treatment protocol feasible in the patient’s environment. Ideally, a multidisciplinary team includes a pediatrician, pediatric oncologist, surgeon, radiologist, radiotherapist, pathologist, nurses, social workers, and providers of psychological and spiritual support.
Some cancers are more difficult to cure than others and require more intensive treatment. The relatively common and curable tumors include acute lymphoblastic leukemia (ALL), Wilms tumor, retinoblastoma, Hodgkin lymphoma, and germ cell cancers. Burkitt lymphoma is often the most common malignancy in areas with endemic malaria.
Childhood cancer survival in high-income countries (HICs) has improved dramatically over the past half century. Collaborative groups and scientifically sound research along with improved supportive care have played essential roles in this progress. Five-year overall survival in the 1960s was <30% and is now nearly 80%.4,5 Survival rates for Wilms tumor, Burkitt lymphoma, and ALL in HICs are higher than 85%, 90%, and 85%, respectively.4–6 With significant improvement of survival in HICs, the rate of progress has slowed and plateaued. The focus in several childhood cancers has now shifted to decreasing short- and long-term morbidities while maintaining or improving survival rates.
Challenges in LMICs
In contrast to the heartening progress in HICs, childhood cancer survival remains low in many LMICs. The reasons are multiple and interrelated. Many children with cancer in LMICs remain undiagnosed and have no access to treatment.7 Population-based survival data are extremely rare. Reported survival rates of children treated for Wilms tumor in sub-Saharan Africa range from 11% in Sudan (where only 11% completed treatment), to 46% in Malawi.8–10 Event-free survival was 61% for children treated for Burkitt lymphoma in Cameroon 11 and 56% for ALL in El Salvador.12 Those who do access care often present with an advanced stage of disease and lower probability of cure.7 Children in LMICs are often severely malnourished at diagnosis, reducing their tolerance for chemotherapy and increasing the risk of life-threatening infections during treatment.
Facilities to treat children with cancer and provide concomitant supportive care are rare in low-income countries. Multidisciplinary staff is limited and not always well trained, chemotherapy supplies may be intermittent, and radiotherapy is not available in many centers in sub-Saharan Africa. Severe nursing shortages and a lack of specialty training also result in diminished supportive care.13
Late presentation with advanced disease necessitates more intense treatment, resulting in a greater risk for treatment toxicity. These factors and other comorbidities, such as malnutrition, lead to increased disease- and treatment-related mortality. Adequate palliative care is essential when caring for children with cancer but is often not available in LMICs.14 One critical component is adequate pain assessment and treatment; however, in LMICs, there are often barriers to morphine access.15 These challenging circumstances contribute to the phenomenon of “abandonment” of treatment, a common cause of treatment failure in many LMICs.16 Abandonment of treatment is caused by several factors, generally related to poverty. Treatment and associated costs (eg, travel and loss of income) are important factors. Other contributors include inadequate counseling and parents’ lack of hope that their child can be cured.
Interventions to Address Challenges in LMICs
Some progress has been achieved in improving outcomes for children with cancer in LMICs although many challenges remain. A significant achievement has been the result of advocacy efforts that have moved LMICs issues to the forefront of pediatric oncology. Advocacy and education of health workers on the early warning signs of childhood cancer will promote early referral and early diagnosis, which are essential to improve survival.
Many centers in LMICs have formed long-term “twinning” partnerships with HICs centers to improve care and survival.17 These partnerships generally include mentoring, education, and some form of funding. Mentoring often includes regular (eg weekly) online conferences where individual cases are discussed.
Several regional collaborative groups of childhood cancer treatment centers have been established (eg, in Central America and North Africa), similar to the cooperative groups that have driven progress in Europe and North America in recent decades.18,19 These LMICs groups share similar challenges in caring for children with cancer in their regions and join forces to find sustainable solutions that improve care.
Treatment guidelines are needed that are adapted to local conditions, including local unavailability of certain drugs or treatment modalities (radiotherapy, certain surgical techniques). Equally important is treatment intensity, which must be reduced to avoid unacceptable rates of deaths from toxicity because supportive care measures are less comprehensive. Furthermore, malnourished children require less intensive treatment.
The Pediatric Oncology in Developing Countries committee of the International Society of Pediatric Oncology has published several adapted treatment guidelines with broad input from professionals in HICs and LMICs.20–25 These adapted regimens are intended for children with common and curable cancers.
It is crucial to develop interventions that are sustainable in local settings and to give priority to interventions that benefit all children, not just children with cancer. For example, improving supportive care resources such as blood transfusion services, infection control programs, access to antibiotics, and nutritional support benefits all pediatric patients. By contrast, stem cell transplantation, a highly specialized intervention, may benefit only a few selected children at a high cost but is cost-effective for certain hematologic disorders, even in middle-income countries.26
Capacity building is key to improve care and treatment of children with cancer in LMICs. Locally relevant research and clinical trials build capacity and improve care, while answering important local research questions.27 For this approach to childhood cancer to be successful, the local LMIC team has to set the priorities because they know best what is needed and feasible.
Although giant strides have been made over the past half-century in curing children with cancer in high-income settings, global progress has been sadly unequal, and the lack of resources is critical in this. However, over the past decade, there has been a remarkable demonstration of progress and examples of good practice, where a holistic approach to managing childhood cancer (medical, social, and economic) with collaboration and partnership has had a tremendous impact on outcomes in LMICs. The challenge for us lies in translating these experiences, ideas, and knowledge into practice and policy to benefit the most children worldwide.
- Accepted April 21, 2015.
- Address correspondence to Trijn Israels, MD, PhD, Pediatric Oncology, VU University Medical Center, De Boelelaan 1117, Amsterdam, The Netherlands 1081 HV. E-mail:
Dr Israels drafted the initial manuscript and revised the manuscript; Drs Challinor, Howard, and Arora helped conceptualize the article and critically reviewed the manuscript; and all authors approved the final manuscript as submitted.
The authors each served as International Society for Paediatric Oncology Committee on Developing Countries cochair in different periods between 2010 and 2015.
FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose.
FUNDING: No external funding.
POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.
- Ferlay J,
- Shin HR,
- Bray F,
- Forman D,
- Mathers C,
- Parkin DM
- 3.↵World Health Organization Global Health Observatory (GHO) Under-five mortality. 2014. Available at: http://www.who.int/gho/child_health/mortality/mortality_under_five/en. Accessed December 20, 2014
- Smith MA,
- Seibel NL,
- Altekruse SF,
- et al
- Stiller CA,
- Kroll ME,
- Pritchard-Jones K
- Lebaron V,
- Beck SL,
- Maurer M,
- Black F,
- Palat G
- Copyright © 2015 by the American Academy of Pediatrics