In high-income countries (HICs), the annual incidence of childhood cancer is approximately 140 per 1 million children younger than age 15 years, although estimates vary between and within countries (Parkin and others 1998). Incidence rates from low- and middle-income country (LMIC) registries are generally significantly lower, as annual rates per 1 million children of 45.6 in Namibia and 64.4 in India, respectively, illustrate (Parkin and others 1998). Some of this variation may relate to differences in environmental exposures or to biologic susceptibility. However, deficiencies in diagnosis and registration likely contribute significantly to differences in the reported incidence of cancer, both overall and of particular subtypes, such as acute leukemias (Howard and others 2008).

Treating Childhood Cancer in Low- and Middle-Income Countries

Background 
Treatment abandonment (TxA) is recognized as a leading cause of treatment failure for children with cancer in low-and-middle-income countries (LMC). However, its global frequency and burden have remained elusive due to lack of global data. This study aimed to obtain an estimate using survey and population data.


Methods 
Childhood cancer clinicians (medical oncologists, surgeons, and radiation therapists), nurses, social workers, and psychologists involved in care of children with cancer were approached through an online survey February-May 2012. Incidence and population data were obtained from public sources. Descriptive, univariable, and multivariable analyses were conducted.


Results 
602 responses from 101 countries were obtained from physicians (84%), practicing pediatric hematology/oncology (83%) in general or children’s hospitals (79%). Results suggested, 23,854 (15%) of 155,088 children 6% were outside the capital. Lower national income category, higher reliance on out-of-pocket payments, and high prevalence of economic hardship at the center were independent contextual predictors for TxA ≥6% (p<0.001). Global survival data available for more developed and less developed regions suggests TxA may account for at least a third of the survival gap between HIC and LMC.


Conclusion 
Results show TxA is prevalent (compromising cancer survival for 1 in 7 children globally), confirm the suspected high burden of TxA in LMC, and illustrate the negative impact of poverty on its occurrence. The present estimates may appear small compared to the global burden of child death from malnutrition and infection (measured in millions). However, absolute numbers suggest the burden of TxA in LMC is nearly equivalent to annually losing all kids diagnosed with cancer in HIC just to TxA, without even considering deaths from disease progression, relapse or toxicity–the main causes of childhood cancer mortality in HIC. Results document the importance of monitoring and addressing TxA as part of childhood cancer outcomes in at-risk settings.

/pdf/magnitude-of-treatment-abandonment-in-childhood-cancer-2vyx5qffhj.pdf

Magnitude of Treatment Abandonment in Childhood Cancer.

Background Understanding and addressing treatment abandonment (TxA) is crucial for bridging the pediatric cancer survival gap between high-income (HIC) and low-and middle-income countries (LMC). In childhood cancer, TxA is defined as failure to start or complete curative cancer therapy and known to be a complex phenomenon. With rising interest on causes and consequences of TxA in LMC, this study aimed to establish the lay-of-the-land regarding determinants of TxA globally, perform and promote comparative research, and raise awareness on this subject. Methods Physicians (medical oncologists, surgeons, and radiation therapists), nurses, social workers, and psychologists involved in care of children with cancer were approached through an online survey February-May 2012. Queries addressed social, economic, and treatment-related determinants of TxA. Free-text comments were collected. Descriptive and qualitative analyses were performed. Appraisal of overall frequency, burden, and predictors of TxA has been reported separately. Results 581 responses from 101 countries were obtained (contact rate = 26%, cooperation rate = 70%). Most respondents were physicians (86%), practicing pediatric hematology/oncology (86%) for >10 years (54%). Providers from LMC considered social/economic factors (families' low socioeconomic status, low education, and long travel time), as most influential in increasing risk of TxA. Treatment-related considerations such as preference for complementary and alternative medicine and concerns about treatment adverse effects and toxicity, were perceived to play an important role in both LMC and HIC. Perceived prognosis seemed to mediate the role of other determinants such as diagnosis and treatment phase on TxA risk. For example, high-risk of TxA was most frequently reported when prognosis clearly worsened (i.e. lack of response to therapy, relapse), or conversely when the patient appeared improved (i.e. induction completed, mass removed), as well as before aggressive/mutilating surgery. Provider responses allowed development of an expanded conceptual model of determinants of TxA; one which illustrates established and emerging individual, family, center, and context specific factors to be considered in order to tackle this problem. Emerging factors included vulnerability, family dynamics, perceptions, center capacity, public awareness, and governmental healthcare financing, among others. Conclusion TxA is a complex and multifactorial phenomenon. With increased recognition of the role of TxA on global pediatric cancer outcomes, factors beyond social/economic status and beliefs have emerged. Our results provide insights regarding the role of established determinants of TxA in different geographical and economic contexts, allow probing of key determinants by deliberating their mechanisms, and allow building an expanded conceptual model of established and emerging determinants TxA.

/pdf/determinants-of-treatment-abandonment-in-childhood-cancer-17rd73g9cd.pdf

Determinants of Treatment Abandonment in Childhood Cancer: Results from a Global Survey.

Approximately 90% of children with cancer reside in low-income and middle-income countries (LMIC) where healthcare resources are scarce and allocation decisions difficult. The cost effectiveness of treating childhood cancers in these settings is unknown. The objective of the present work was to determine cost-effectiveness thresholds for common paediatric cancers using acute lymphoblastic leukaemia (ALL) in Brazil and Burkitt lymphoma (BL) in Malawi as examples. Disability-adjusted life years (DALYs) prevented by treatment were compared to the gross domestic product (GDP) per capita of each country to define cost-effectiveness thresholds using WHO-CHOICE ('CHOosing Interventions that are Cost-Effective') guidelines. The case examples were selected due to the data available and because ALL and BL both have the potential to yield significant health gains at a low cost per patient treated. The key findings were as follows: the 3:1 cost/DALY prevented to GDP/capita ratio for ALL in Brazil was US $771,225; expenditures below this threshold were cost effective. Costs below US $257,075 (1:1 ratio) were considered very cost effective. Analogous thresholds for BL in Malawi were US $42,729 and US $14,243. Actual costs were far less. In Brazil, US $16,700 was spent to treat each patient while in Malawi total drug costs were less than US $50 per child. In summary, treatment of certain paediatric cancers in LMIC is very cost effective. Future research should evaluate actual treatment and infrastructure expenditures to help guide policymakers.

https://adc.bmj.com/content/archdischild/early/2012/11/29/archdischild-2011-301419.full.pdf

The cost effectiveness of treating paediatric cancer in low-income and middle-income countries: a case-study approach using acute lymphocytic leukaemia in Brazil and Burkitt lymphoma in Malawi

In developing countries, BL has a strong association with EBV infection during childhood In South America, the data have shown an EBV association intermediate between that reported in the United States (30%) and that in equatorial Africa (95%) Early age at EBV infection and lower socioeconomic status have been related to increased EBV-associated BL in developing countries In Brazil, there are not enough data on childhood BL related to EBV infection Our aim was to evaluate the clinicopathologic features and EBV association of 44 children with NHL from the state of Rio de Janeiro, situated in the southeast of Brazil EBV was detected using RNA in situ hybridization in 36 biopsy specimens DNA from fresh tumor samples and from paraffin-embedded tissues of patients were analyzed by PCR, in which the first reaction included primers for an EBNA-2 common region while the nested reaction amplified the region discriminating between EBV types 1 and 2 in separate reactions EBV was detected in 21 of 29 BLs (72%), and type 1 virus infected the majority of EBV-positive BLs (18/21) There was a trend for younger age in children with EBV-positive BL compared to EBV-negative BL (median age 4 compared to 6 years, respectively; p = 0056) Our study confirmed that in the southeast of Brazil BL had an intermediate association with EBV A higher rate of EBV-associated BL was described in the northeast of Brazil These differences are probably related to regional socioeconomic status In conclusion, our study suggests that early infection with EBV in the background of a low socioeconomic condition associated with other environmental factors could contribute to BL in Brazil

Geographic variation in Epstein-Barr virus-associated Burkitt's lymphoma in children from Brazil.

The purpose of this paper was to define the histologic distribution, clinical features, and treatment response of childhood non-Hodgkin lymphoma (NHL) in northeastern Brazil. We reviewed medical records and histopathologic studies of 98 children treated for NHL from 1980 to 1987 at a major pediatric cancer center in Recife, Brazil. Treatment outcome was evaluated in relation to tumor burden (stage and serum LDH) and type of therapy (LSA2L2 vs other multiagent chemotherapy). There was a striking predominance of the small noncleaved cell (Burkitt) subtype, which occurred in 92 of the 98 children and adolescents diagnosed with NHL. Subsequent analyses focused on these patients. The majority (n = 84) had advanced (stage III/IV) disease at diagnosis. The abdomen was the most common site of disease (84 cases); jaw involvement was rare (three cases). Five-year event-free survival (excluding treatment refusals) was significantly better for patients with limited vs advanced stage disease (75 +/- 14% vs 42 +/- 6%; P 500 U/l) was associated with a poorer outcome (P = 0.008). The type of chemotherapy did not affect EFS (P = 0.95). Only 39% of patients are long-term survivors, reflecting the high rate of septic deaths (25% of patients) and parental refusal/abandonment of therapy (10%). Epstein-Barr virus (EBV) was detected in tumor cells from eight of the 11 cases studied. In clinical presentation, these cases resemble sporadic Burkitt lymphoma, yet in their apparent responsiveness to LSA2L2 therapy and association with EBV, they do not. Childhood NHL in northeastern Brazil is predominantly of the Burkitt subtype, and is associated with clinical features that appear to distinguish it from the endemic and sporadic forms of this tumor. These cases may represent a third or intermediate subtype of Burkitt lymphoma.

Predominance and characteristics of Burkitt lymphoma among children with non-Hodgkin lymphoma in northeastern Brazil

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Predominance and characteristics of Burkitt lymphoma among children with non-Hodgkin lymphoma in northeastern Brazil