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Keywords:

  • high income countries;
  • middle income countries;
  • low income countries;
  • cancer epidemiology;
  • developing countries;
  • tumor registries

Abstract

  1. Top of page
  2. Abstract
  3. Sources and Quality of Childhood Cancer Epidemiology Data
  4. Acknowledgements
  5. REFERENCES

Global studies of childhood cancer provide clues to cancer etiology, facilitate prevention and early diagnosis, identify biologic differences, improve survival rates in low-income countries (LIC) by facilitating quality improvement initiatives, and improve outcomes in high-income countries (HIC) through studies of tumor biology and collaborative clinical trials. Incidence rates of cancer differ between various ethnic groups within a single country and between various countries with similar ethnic compositions. Such differences may be the result of genetic predisposition, early or delayed exposure to infectious diseases, and other environmental factors. The reported incidence of childhood leukemia is lower in LIC than in more prosperous countries. Registration of childhood leukemia requires recognition of symptoms, rapid access to primary and tertiary medical care (a pediatric cancer unit), a correct diagnosis, and a data management infrastructure. In LIC, where these services are lacking, some children with leukemia may die before diagnosis and registration. In this environment, epidemiologic studies would seem to be an unaffordable luxury, but in reality represent a key element for progress. Hospital-based registries are both feasible and essential in LIC, and can be developed using available training programs for data managers and the free online Pediatric Oncology Networked Data Base (www.POND4kids.org), which allows collection, analysis, and sharing of data. Cancer 2008. © 2007 American Cancer Society.

The 5-year event-free survival for children with cancer is 75% to 79% in high-income countries (HIC).1–3 However, 80% of the world's children live in middle- and low-income countries (MIC and LIC), where poverty, lack of public health infrastructure, high mortality rates in children under the age of 5 years (under 5-year mortality rates), and low childhood cancer cure rates are pervasive. In such settings, studies of cancer epidemiology may seem to be an unaffordable luxury, but analysis of the global epidemiology of childhood cancer and differences between LIC, MIC, and HIC is not merely an academic exercise. Studies of childhood cancer in different regions provide clues to cancer etiology, facilitate improvements in public health through prevention and early diagnosis, identify biologic differences that may require different therapeutic strategies, improve survival rates in LIC by identification of causes of treatment failure so that quality improvement initiatives can focus on these causes, and improve outcomes in HIC through studies of tumor biology and collaborative clinical trials (Table 1). Geographic differences in incidence may suggest unique genetic or environmental exposures that affect cancer risk. In this report we review the incidence rates of childhood cancer in MIC and LIC, discuss possible reasons for different reported incidence rates, provide examples of the importance of epidemiologic studies in LIC and their practical importance to patients and society, and propose the universal implementation of hospital-based cancer registries in pediatric cancer units as a feasible next step to improve childhood cancer care and global epidemiologic research.

Table 1. Importance of Childhood Cancer Epidemiology in Low-Income Countries
 Use of epidemiologic dataDescriptionExamples and references
  1. HIC indicates high-income countries; MIC, middle-income countries; LIC, low-income countries; BFM, Berlin-Frankfurt-Munster cooperative study group; ALL, acute lymphoblastic leukemia; NHL, non-Hodgkin lymphoma.

Public healthPrograms for prevention and screeningEducation efforts can be targeted at the populations at highest risk; programs can raise awareness at a societal level so that families and healthcare professionals work together to implement screening and promote early diagnosisRetinoblastoma in Honduras27
 Health planningMeasurement of the geographic distribution and total number of cases of each cancer type allows planning of the location where pediatric cancer units and satellite clinics should be established and determination of services needed at each siteHonduras satellite clinics; development of a regional flow cytometry center45
 Quality improvementMeasuring outcomes of treatment and cancer-specific mortality identifies services that need to be improved and facilitates assessment of the efficacy of interventionsDevelopment of a pediatric cancer center of excellence in Recife, Brazil34
Clinical researchAdaptation of pediatric oncology treatment regimensConducting clinical trials of therapy in LIC that use less toxic, less expensive, or otherwise modified versions of published treatment regimens can evaluate the feasibility and outcomes in the local settingALL and lymphoma in Recife, Brazil,33, 34 Indonesia,35 and India46–48
 Clinical research that can only be performed in LICEvaluation of clinical problems unique to children with cancer in LIC, including abandonment of therapy, the effects of extreme poverty on compliance and toxicity, and the effects of comorbid illnesses (e.g. malnutrition, parasitic infection) on outcomes can lead to specific mitigation strategiesAbandonment risk factors for children with ALL23, 34, 35; telemedicine in Jordan to improve treatment of central nervous system cancer49
 Comparative clinical researchEvaluation of specific aspects of care in diverse settings, such as the effects on outcome of culture, language, socioeconomic status, and other variables that differ greatly between countriesPerceptions of pain in children with cancer in Jordan50
 Clinical trials for patients with advanced disease at diagnosisEvaluation of treatment regimens in patients with high-stage disease at diagnosis to determine the optimal treatment strategy in the local setting, where intense chemotherapy and stem cell transplantation may not be feasible. Trials of new agents are also appropriate in such settings, where the event-free survival without novel therapy is close to 0%. Indeed, the patients that stand to gain most from novel therapies are those in LIC, where late diagnosis increases the proportion of patients with incurable cancerExtraocular retinoblastoma27
 Collaborative trials with global participationMulti-center, multi-national research on rare tumors with participation of centers in HIC, MIC and LIC allow sufficient sample size to perform randomized controlled trials of therapy. Global collaboration permits more rapid progress in therapeutics than if clinical trials are performed only in HIC, where only 20% of children with cancer liveInternational study of infant ALL (Interfant), haploidentical stem cell transplantation in Chile51
Epidemiology researchCancer etiologyAssessment of differences in genetics, lifestyle, and environmental exposures between LIC and MIC that correlate with different cancer incidenceAdrenocortical carcinoma in southern Brazil11
 Cancer diagnosisAssessment of relative incidences of each type of childhood cancer to determine whether these reflect genetic or environmental differences, or bias based on the differential probability of survival until diagnosis among different cancersALL in Honduras23
Basic researchDiscovery of new causes of childhood cancerObservation of unusual patterns of disease presentation or clusters of cancer within families or regions may elucidate novel genetic and environmental risk factors for childhood cancerAdrenocortical carcinoma in southern Brazil11, 24, 25
 Biology research with primary tumor samplesPatients with advanced disease have large tumors sufficient for a variety of biologic studies. In HIC, less than 5% of retinoblastoma is extraocular, and the majority of tumors are not biopsied. In contrast, 43% to 73% of retinoblastomas in LIC are extraocular and biopsy material is available27, 52Extraocular retinoblastoma27, 52; Adrenocortical carcinoma in Southeast Brazil11, 24, 25
 Comparative cancer biology researchComparison of clinical and biologic features of the same cancer in distinct regions may help identify unique clinical features, causes, and possibly therapiesBurkitt lymphoma in North America, Latin America, and Africa9

Sources and Quality of Childhood Cancer Epidemiology Data

  1. Top of page
  2. Abstract
  3. Sources and Quality of Childhood Cancer Epidemiology Data
  4. Acknowledgements
  5. REFERENCES

Information about childhood cancer incidence in LIC comes from hospital-based registries, population-based registries, international organizations, and specific research projects. The International Agency for Cancer Research (IARC) has conducted extensive studies of childhood cancer incidence throughout the world by combining information from multiple population-based tumor registries, and its publications provide a comprehensive source of information about cancer epidemiology in selected LIC (Table 2).4, 5

Table 2. Incidence of Childhood Cancer per Million Children Less Than 15 Years Old in Selected Countries Categorized by Mean per Capita Gross National Income
CountryCancer incidenceLeukemia incidenceNonleukemia incidenceGross National income*Total healthcare spending*Under 5-y mortality rates
  • Incidence data are from the International Agency for Research on Cancer.5

  • Low-income country (LIC) is defined as a country in which the mean per capita annual income in 2005 is less than US $825; middle-income country (MIC) is a country in which the mean per capita annual income is $825 to $10,065. MIC are divided into lower middle-income country (mean per capita annual income of $825 to $3255) and upper middle-income country (mean per capita annual income of $3256 to $10,065); high-income country (HIC) is a country in which the mean per capita annual income is more than $10,065.

  • *

    Annual per capita figures in US dollars. Gross national incomes were taken from the world development indicators database of the World Bank for 2005.

  • Kaposi sarcoma accounted for 68.5 nonleukemia cancers per million per year in Uganda and 10.7 in Zimbabwe.

Low-income countries (n = 9)102168549121128
 Malawi100.01.198.916013175
 Uganda183.510.3173.228018138
 Zimbabwe111.222.888.434040129
 Mali77.44.073.43809219
 Nigeria71.28.662.656022197
 Vietnam108.433.475.06202619
 Papua New Guinea100.08.191.96602393
 Pakistan100.040.559.569013101
 India64.419.245.27302785
Middle-income countries (n = 18)1073770453724125
 Lower middle-income countries (n = 8)93375623249333
  Philippines100.447.952.513003133
  China104.840.264.617406131
  Ecuador124.455.469.0218010926
  Colombia121.841.780.1229013821
  Peru104.435.668.826109829
  Algeria69.637.332.327308940
  Thailand70.128.142.027507621
  Namibia45.66.239.4299014563
 Upper middle-income countries (n = 10)1183781630735818
  Bulgaria98.632.066.6345019115
  Brazil100.027.872.2346021234
  Uruguay117.443.274.2436032314
  Costa Rica134.056.577.5459030513
  South Africa100.022.078.0496029567
  Poland111.035.076.071103548
  Slovakia125.635.090.679503609
  Croatia162.641.5121.180604947
  Estonia123.535.687.991003668
  Hungary103.436.566.9100306846
High-income countries (n=25)13041893287225165
 Korea106.436.969.5158307056
 Portugal146.736.0110.71617013485
 Slovenia113.536.377.21735012184
 Israel131.025.2105.81862015146
 United Arab Emirates100.043.756.3237706618
 Kuwait109.732.377.42404058012
 Spain132.340.891.52536015415
 New Zealand147.639.5108.12596016186
 Germany125.934.291.72622032045
 Singapore125.348.277.1274909643
 Hong Kong128.952.476.527670.3
 Italy134.144.389.83001021395
 Australia137.046.790.33222025196
 Canada144.248.196.13260026696
 France129.838.291.63481029815
 Netherlands132.838.694.23662030885
 Finland148.647.3101.33746023074
 United Kingdom118.238.679.63760024286
 Japan107.635.572.13898026624
 Sweden149.445.6103.84106031494
 USA137.943.194.84374057118
 Iceland109.037.271.84632038213
 Denmark149.347.2102.14739035345
 Switzerland139.543.895.75493050355
 Norway143.244.099.25959049764

Causes of variation in cancer incidence rates

Differences in cancer incidence rates between HIC and many LIC have been documented for childhood cancer as a whole,5–7 and for a variety of specific cancers, including Burkitt and Hodgkin lymphomas,8–10 adrenocortical carcinoma,11, 12 and acute lymphoblastic leukemia (ALL), the most common childhood cancer worldwide. International variation in the incidence of ALL is well recognized.13 Observations of a markedly increased incidence rate of ALL in children between 2 and 5 years old in affluent societies, the lack of such an age peak age in LIC, and occasional clustering of childhood ALL cases (especially in new towns) have fueled 2 parallel infection-based theories of leukemogenesis: the delayed-infection hypothesis14 and the population-mixing hypothesis.15 Both hypotheses attribute the peak incidence in industrialized countries to early infectious insulation that predisposes the immune system of susceptible individuals to aberrant or pathologic responses after subsequent or delayed exposure to common infections at an age commensurate with increased lymphoid cell proliferation.14, 15 Some other cases of childhood ALL can be attributed to maternal exposures during pregnancy,16, 17 in which risk may be modulated by genetic polymorphisms of enzyme systems responsible for the metabolism of drugs or environmental xenobiotics.18–21 However, variations in environmental exposures and genetic susceptibility can only account for small differences in childhood leukemia incidence rates, and do not explain the large differences (up to 10-fold) between HIC and some LIC (Table 2). Hence, the role of underdiagnosis and underreporting must be investigated.

Sources of error in estimating childhood cancer incidence in LIC

Determination of cancer incidence requires both an accurate estimate of the population of interest (eg, younger than 15 years old) and an accurate count of cancer cases within the population. Population estimates depend on the accuracy and frequency of censuses. Age-specific population estimates between censuses are calculated by interpolation. However, this approach does not provide valid estimates if the accuracy of the most recent census is poor or when there are large shifts in the population due to migration, refugees, or rapid changes in birth or death rates. In such instances the age-specific population may be over- or underestimated, and even determination of the most likely direction of error may not be possible. Compounding the problem of inaccurate population estimates are potential errors in ascertainment and characterization of cancer cases within the population of interest. Cancer cases can only be considered if a diagnosis is made and the case registered—a chain of care that comprises several links (Fig. 1). In LIC, barriers occur at all steps. Patients and parents may not be aware of signs and symptoms of childhood cancer, may rely on nonmedical forms of treatment, and may not have the transportation or money to travel to a primary care facility. If the patient arrives to primary care, personnel may not be trained to recognize childhood cancer, laboratory and diagnostic imaging equipment may not be available to screen for cancer, and the patient or clinic may lack money to pay for necessary testing and treatment. Similar barriers make access to tertiary care and correct diagnosis problematic, and even when correct diagnoses of cancer are made they may not be documented systematically in a cancer registry.

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Figure 1. Links in the chain of childhood cancer diagnosis and registration. Many steps are required for a child with cancer to be diagnosed and registered. In low-income countries, barriers occur at all steps. SES indicates socioeconomic status.

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Any missing link in the chain of cancer diagnosis can prevent ascertainment of the case, and cause the reported cancer incidence rate to be lower than the actual incidence rate—assuming an accurate population census. The degree of underestimation depends on many social, economic, and medical factors. In countries like Jordan, with a total population of 5,900,000, a few major hospitals treat almost all children in the country who develop cancer. It can be argued that combining hospital registries of these cancer centers approximates a population-based registry; however, even in Jordan there is a higher measured incidence rate in the capital city, which suggests that children with cancer in rural or distant areas may have less access to diagnosis and treatment.22 We observed a similar pattern in Honduras (population 7,500,000), where the measured annual incidence of ALL in the capital city was 20 per million versus 10 per million in distant and rural provinces.23 These problems are probably even more significant in larger countries, where changes in referral patterns may not respect boundaries established for the population used as the denominator for incidence calculations.

Reported Versus Actual Incidence Rates of Childhood Cancers

The difference in reported versus actual incidence rates of childhood cancer is most extreme for leukemia, a disease with protean signs and symptoms that resemble those of infection, in which early death can occur before cancer is suspected or diagnosed. By contrast, lymphomas and solid tumors typically present with a visible mass or other manifestation that prompts parents to seek medical care. Furthermore, early death due to lymphomas and solid tumors is less common, even when the disease reaches an advanced stage. The mean annual leukemia incidence per million children was 16.4 (standard deviation [SD] 13.6) in LIC, 36.5 (SD 11.6) in MIC, and 40.9 (SD 6.1) in HIC (Table 2), an observation that supports the contention that leukemia incidence is systematically underestimated in LIC (Fig. 2). In contrast, the incidence of nonleukemia cancers was 85 (SD 37) in LIC, 70 (SD 20.5) in MIC, and 89 (SD 14) in HIC (Table 2), which does not support a pattern of systematic underestimation of nonleukemias in LIC (Fig. 3). After exclusion of Kaposi sarcoma, which is common in Uganda and Zimbabwe, the incidence rates of nonleukemia cancers in LIC decreases to 76. LIC with the lowest reported incidence rates of leukemia have a very high incidence of malaria (>200 cases per 1000 population per year), suggesting that patients with leukemia may die with anemia and fever that is attributed to malaria, which is 10,000 times more common than leukemia in endemic areas.

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Figure 2. Relation of the reported incidence rate of childhood leukemia to gross national income. The reported incidence of childhood leukemia (all types combined) varies significantly according to mean annual per capita gross national income (GNI). In low-income countries there is a wide range of recorded leukemia incidence. This range is much narrower in upper middle-income countries, which report an average of 37 cases per million children per year, and high-income countries, which report an average of 41 cases per million per year. In low-income countries, the reported incidence rate of leukemia correlates with GNI (r = 0.56, P = .12), but less so in middle- (r = −0.05, P = .83) and high-income countries (r = 0.38, P = .06).

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Figure 3. Relation of the reported incidence rate of childhood nonleukemia cancers to gross national income (GNI). The reported incidence of nonleukemia childhood cancers does not vary consistently according to the category of mean annual per capita GNI, although there is a weak positive correlation of GNI with nonleukemia cancer incidence when all groups are combined (r = 0.31, P = .02). Uganda, which has an annual incidence of 173.2 nonleukemia childhood cancers per million and a GNI of $280, is not shown.

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Competing causes of death in LIC

One proposed cause of lower reported incidence of childhood cancer in LIC is the high mortality rate among children younger than 5 years of age in some countries, which may lead to death of a child before development of cancer. However, premature death of children due to infection and malnutrition does not change the incidence rate very much, because such deaths are presumed to occur in equal proportion in children who would have later developed cancer as in those who would not have done so. In other words, if 10% of children die before reaching the age of 5 years, there will be 10% fewer cancer cases among children aged 6 to 15 years, but there will also be 10% fewer children without cancer in this age group, so the incidence rate will remain unchanged. Of the 52 countries reported in Table 2, Mali has the highest under 5-year mortality: 219 per 1000 children (21.9%). Most of these children die of infection, whose symptoms resemble those of leukemia. For this reason, a high under 5-year mortality correlates strongly with a lower reported incidence of leukemia (Fig. 4, P < .001), because regions in which young children die from infection are the same as those in which children with leukemia will die before diagnosis. In contrast, the reported incidence rate of nonleukemia cancers does not correlate with under 5-year mortality (Fig. 5, P = .89), because children with solid tumors do not die of infection before diagnosis.

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Figure 4. Relation of the reported incidence rate of childhood leukemia to under 5-year mortality in low- and middle-income countries. In low- and middle-income countries the reported incidence of childhood leukemia (all types combined) rises as the under 5-year mortality decreases (r = −0.78, P < .001). This inverse correlation reflects improved survival until diagnosis and registration as under 5 mortality decreases.

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Figure 5. Relation of the reported incidence rate of childhood nonleukemia cancers to under 5-year mortality in low- and middle-income countries. In low- and middle-income countries the reported incidence of nonleukemia cancers does not correlate with under 5-year mortality (r = −0.02, P = .89).

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Adrenocortical Carcinoma and Retinoblastoma as Models of the Usefulness of International Childhood Cancer Epidemiology

Adrenocortical carcinoma (ACC)

The estimated annual incidence of ACC in the US is 0.3 per million children younger than 15 years of age.5 The disease often occurs in association with the Li-Fraumeni familial cancer syndrome, in which mutations in the germline p53 gene predispose to a variety of cancers, including ACC. However, in the Parana and Sao Paulo states of southern Brazil the incidence of ACC is 10–15 times greater, but no endemic infections, environmental or occupational exposures, ethnic predisposition, or kindreds with Li-Fraumeni syndrome could be identified.12 From 1996 to 1999 a subset of 92 children with ACC treated at a single institution in southern Brazil underwent genotyping of p53 and were found to have an identical point mutation in exon 10 encoding an arginine-to-histidine amino acid substitution at codon 337 of p53.24 Although half of first-degree and a third of second-degree relatives had a similar point mutation, there was no family history of cancers to suggest Li-Fraumeni syndrome.11 Functional studies of the protein derived from the mutated p53 gene revealed that p53 in these patients had normal activity except at high pH, which can be found in the adrenal cortex in its physiologic state, a finding that partially explained the tissue-specific cancer predisposition.25 A tumor registry for ACC has now been established to facilitate continued clinical and biologic studies and to prepare an infrastructure for subsequent clinical trials of prevention and early detection.26

Retinoblastoma

Similarly, recognition of the apparent high incidence and advanced stage of presentation of retinoblastoma in Honduras led to development of programs to promote universal screening, early diagnosis, improvements in treatment, collaborative studies of tumor biology with scientists at St. Jude Children's Research Hospital, and a multinational clinical trial of therapy in Central America.27, 28 In Honduras from 1995 to 2003, 73% of children presented with extraocular disease. A national retinoblastoma education campaign was undertaken in concert with a national vaccination effort, and the rate of extraocular disease decreased to 35% in the subsequent 2 years (P = .002).27

Extended educational programs are under way to further reduce diagnostic delays, but new treatments are needed for children who present with extraocular disease. To develop such treatments an improved understanding of retinoblastoma biology is needed. Studies in cell lines and mice have been very promising in this regard,29–32 but clinical trials in humans will be needed to definitively test any new drug or combination. In the US an estimated 200 children per year develop retinoblastoma, but only about 10 of these (5%) have extraocular disease at diagnosis. Clinical trials of new agents will require large-scale international cooperation, and the participation of centers in LIC will be critical (Table 1). Such trials should be performed in concert with community education programs to promote early diagnosis, in pediatric cancer centers with expertise in both chemotherapy administration and ocular local control measures, such as those being developed in Panama, Honduras, and Guatemala.27, 28

The Way Forward

Improving survival rates in LIC

The only way to know with certainty the optimal treatment strategy in a particular LIC setting is to implement uniform, protocol-based care for each childhood cancer and to carefully monitor rates of toxic death, abandonment of treatment, and recurrence.28, 33–35 In some cases adjustment of the chemotherapy regimen will be required to maximize the probability of cure; in all cases, improvements in supportive care and efforts to reduce abandonment will be required.35 A hospital-based cancer registry and active data management program are essential to successfully monitor outcomes and measure the effect of specific interventions.36 Such registries must always be developed in the context of a pediatric cancer unit, which serves as the focal point for efforts to improve the quality of care.

Hospital cancer registries are feasible everywhere

In light of the difficulties and costs associated with accurate population-based cancer registries and significant uncertainties in estimates of both cancer cases and the populations from which they derive, how can LIC obtain accurate epidemiologic information and take advantage of its many benefits to patients and society? The logical first step is the implementation of a pediatric cancer unit coupled with a registry in all hospitals where children with cancer are treated. Such registries can be maintained at low cost and comprise a key component of a pediatric oncology data management program that includes a data manager, database, and data analysis. They also serve as a practical first step toward a possible population-based assessment of cancer incidence rates. Finally, an excessively high or low incidence rate for a particular cancer may serve as an indicator of systematic misdiagnosis of certain types of cancer, particularly among cancers that are difficult to distinguish from each other without expertise and infrastructure for pathologic diagnosis. For example, if Ewing sarcoma were frequently misdiagnosed as rhabdomyosarcoma, the registry would reveal an unrealistically low rate of Ewing sarcoma and an excessively high incidence of rhabdomyosarcoma, and would suggest a need for further investigation.

Data managers

Data managers in LIC can be hired and trained at low cost, with close supervision by local physicians and extensive use of internet communication via the free educational website www.Cure4Kids.org.36 In Honduras such a program was successfully implemented with a 2-day onsite training workshop followed by regular online communication and local supervision. In many LIC data manager salaries are less than US $600 per month plus the cost of a computer with internet access. All necessary software is available at no cost from the International Outreach Program of St. Jude Children's Research Hospital. Weekly data manager training sessions are held via www.Cure4Kids.org in both English and Spanish, and data managers from any country are welcome to participate at no cost.

POND Database

The Pediatric Oncology Networked Database (POND, www.Pond4kids.org) has been in use since 2004 and is currently in its second version.28, 36, 37 This multilingual, secure, online database was designed for data management programs in LIC, and is provided at no cost. In addition to standard tumor registry, cancer-specific, and toxicity information, POND can store nutrition, psychosocial, and socioeconomic information, which can be used to assess a patient's risk for abandonment of treatment. Chemotherapeutic regimens can be stored in POND with automatic generation of patient-specific treatment ‘roadmaps’ and calculation of chemotherapeutic drug doses. Protocols can be shared via a global library so that other sites can use them. POND allows sharing of automatically deidentified data with local and international collaborators, hospital administration, government agencies, and nongovernmental agencies for healthcare planning, outcomes assessment, quality improvement, and research. However, control of the data always remains with the site administrator. Sharing can be turned on or off at will, according to the site's needs, and a complete export of the data in the universal .xml format can be performed should the site decide that another software tool better meets its needs. The system currently supports English, Spanish, French, Portuguese, and Chinese, and is used at 33 sites in 16 countries, with more than 11,000 patients registered. POND is used as the database for the American Society of Hematology's international acute promyelocytic leukemia protocol and potentially could serve the needs of other international study groups.

Data analysis

Although a data manager and database are essential prerequisites, data analysis is the ultimate goal. Rapid adoption of POND occurred because physicians and hospital administrators saw immediate benefits to real-time data collection and periodic analysis of results. Analysis addresses local problems, such as abandonment of treatment, which is the most common cause of treatment failure in LIC.23, 38 Doctors in Guatemala generate the list of patients to be seen on a particular day and at the end of the day review all visits to make sure that patients who missed appointments can be contacted and encouraged to resume therapy the next day. Social workers store key socioeconomic information that helps determine eligibility for support programs, such as subsidized transportation for clinic visits. Hospital administrators use the data to assess personnel needs (nursing, laboratory, social work, etc) and in some cases the government is provided information from POND to determine funding needs for the pediatric oncology program.

Collaborators at 8 centers in 7 Central American countries who use shared treatment protocols implemented via POND can assess toxicity and event-free survival of protocol patients in real time using the sharing mechanism (which can be limited to a specific disease or protocol). Kaplan-Meier curves can be generated automatically by POND and other statistical analyses will be added in version 3 because many clinicians in LIC do not have access to statistical analysis programs and also lack resources to contract an epidemiologist or statistician to assist with analysis. Training in the conduct and analysis of clinical trials, and review of patients with difficulties are conducted via email and regular online conferences via www.Cure4kids.org. In this regard, statisticians and clinical researchers from the Monza International School of Pediatric Hematology/Oncology (MISPHO) and the Pediatric Oncology Group of Ontario (POGO) have been particularly helpful.28, 37, 39–41

Funding for data management programs in LIC

Data management programs in LIC are inexpensive, and many stakeholders benefit from the data collected.42 However, initiation and maintenance of a successful program does require some funding. In many cases, nonprofit foundations that support pediatric cancer units in LIC have used donated money to fund data management programs, just as they do to provide essential medications and subsidized transportation.34 The Central American program was initially funded by a 3-year grant from POGO, which paid for data manager training and salaries. As part of its My Child Matters program, Sanofi-Aventis and the International Union against Cancer (UICC) funded projects in LIC that included data management components. International research agencies are another potential source of support. An additional, as-yet untapped resource may be the pharmaceutical industry. One could even imagine branded data management programs, in which the supporting company is specifically recognized. Perhaps the most important source of ongoing support is that provided by nonprofit foundations in-country, which provides an opportunity for individuals to help fellow citizens and creates local capacity. This model has proved very successful in Recife, Brazil, and elsewhere.34

Objections

Although pediatric cancer unit-based registries, data management programs, and global epidemiology studies are feasible at modest cost, should they be a priority in LIC? Indeed, should cancer care be supported at all in a country like Mali, where 22% of children die before reaching 5 years of age, 47% of births occur with no prenatal visit, only 41% are vaccinated for measles in rural areas, and 43% have growth stunting from malnutrition (www.who.int/whosis/whostat2007)? Even if every child with cancer were cured of the disease, the under 5-year mortality would decrease by less than 1 per 1000, so in countries like Malawi, Nigeria, and Mali, where the under 5-year mortality is 175 to 219 per 1000, clean water, food, vaccines, antibiotics, oral rehydration programs, and malaria treatment remain the highest health priorities. However, in countries where an attempt is made to treat children with cancer, the diagnosis and outcome of these children should be recorded and analyzed so that use of limited resources can be optimized in the local setting. In this regard, 33% of 42 children with Burkitt lymphoma in Malawi were cured with a 42-day treatment regimen adapted to local conditions with a cost of US $250 per patient.43 These patients were cured (defined as remission for at least 12 months, after which recurrence is uncommon in Burkitt lymphoma) despite the finding that 52% presented malnourished and 39% with an active parasitic infection (usually malaria). Whether the funds used for cancer care would have saved more lives had they been spent on other health problems is an important question, but it is encouraging that even in the poorest regions some children with cancer can be cured with existing resources under local conditions. In the poorest LIC we do not advocate diversion of government health funds away from essential services such as vaccine and malaria control programs to treat childhood cancer; however, because treatment of curable illnesses is a fundamental right of children,44 we would propose that members of the healthcare system in LIC seek support for pediatric cancer care from every possible source, including international agencies and foundations, and that results be documented via the hospital-based registry.

Conclusions

In summary, the study of childhood cancer epidemiology in LIC may seem like a relatively low priority considering competing public health and medical demands. However, the large number of children with cancer in LIC, the need for health planning, clinical research to adapt treatment regimens to local conditions, and the opportunity for epidemiologic research make pediatric cancer unit (hospital)-based registries potentially cost-effective. Well-designed and maintained hospital registries can be established with modest financial support, represent an integral component of pediatric cancer care, and provide a potential platform for expansion to a population-based registry when feasible. As registries are established, the reported childhood leukemia incidence in LIC in all likelihood will increase, reflecting an improved healthcare infrastructure and providing an important marker of societal progress.

Acknowledgements

  1. Top of page
  2. Abstract
  3. Sources and Quality of Childhood Cancer Epidemiology Data
  4. Acknowledgements
  5. REFERENCES

We thank the Pediatric Oncology Group of Ontario (POGO) for supporting a data management program in Central America that served as the prototype for many of the ideas presented here and Hemalatha Kundurthi for invaluable assistance with data collection.

REFERENCES

  1. Top of page
  2. Abstract
  3. Sources and Quality of Childhood Cancer Epidemiology Data
  4. Acknowledgements
  5. REFERENCES