Barriers to effective treatment of pediatric solid tumors in middle-income countries: can we make sense of the spectrum of nonbiologic factors that influence outcomes?

BACKGROUND: The delivery of effective treatment for pediatric solid tumors poses a particular challenge to centers in middle-income countries (MICs) that already are vigorously addressing pediatric cancer. The objective of this study was to improve the current understanding of barriers to effective treatment of pediatric solid tumors in MICs. METHODS: An ecologic model centered on pediatric sarcoma and expanded to country as the environment was used as a benchmark for studying the delivery of solid tumor care in MICs. Data on resources were gathered from 7 centers that were members of the Central American Association of Pediatric Hematologists and Oncologists (AHOPCA) using an infrastructure assessment tool. Pediatric sarcoma outcomes data were available, were retrieved from hospital-based cancer registries for 6 of the 7 centers, and were analyzed by country. Patients who were diagnosed from January 1, 2000 to December 31, 2009 with osteosarcoma, Ewing sarcoma, rhabdomyosarcoma, and other soft tissue sarcomas were included in the analysis. To explore correlations between resources and outcomes, a pilot performance index was created. RESULTS: The analyses identified specific deficits in human resources, communication, quality, and infrastructure. The treatment abandonment rate, the proportion of metastatic disease at diagnosis, the relapse rate, and the 4-year abandonment-sensitive overall survival (AOS) rate varied considerably by country, ranging from 1% to 38%, from 15% to 54%, from 24% to 52%, and from 21% to 51%, respectively. The treatment abandonment rate correlated inversely with health economic expenditure per capita (r = -0.86; P = .03) and life expectancy at birth (r = -0.93; P = .007). The 4-year AOS rate correlated inversely with the mortality rate among children aged <5 years (r = -0.80; P = 0.05) and correlated directly with the pilot performance index (r = 0.98; P = 0.005). CONCLUSIONS: Initiatives to improve the effectiveness of treatment for pediatric solid tumors in MICs are warranted, particularly for pediatric sarcomas. Building capacity and infrastructure, improving supportive care and communication, and fostering comprehensive, multidisciplinary teams are identified as keystones in Central America. A measure that meaningfully describes performance in delivering pediatric cancer care is feasible and needed to advance comparative, prospective analysis of pediatric cancer care and to define resource clusters internationally.

Asociación de Hemato-Oncología Pediátrica de Centro América (AHOPCA): a model for sustainable development in pediatric oncology.

Bridging the survival gap for children with cancer, between those (the great majority) in low and middle income countries (LMIC) and their economically advantaged counterparts, is a challenge that has been addressed by twinning institutions in high income countries with centers in LMIC. The long-established partnership between a Central American consortium--Asociación de Hemato-Oncología Pediátrica de Centro América (AHOPCA)--and institutions in Europe and North America provides a striking example of such a twinning program. The demonstrable success of this endeavor offers a model for improving the health outcomes of children with cancer worldwide. As this remarkable enterprise celebrates its 15th anniversary, it is appropriate to reflect on its origin, subsequent growth and development, and the lessons it provides for others embarking on or already engaged in similar journeys. Many challenges have been encountered and not all yet overcome. Commitment to the endeavor, collaboration in its achievements and determination to overcome obstacles collectively are the hallmarks that stamp AHOPCA as a particularly successful partnership in advancing pediatric oncology in the developing world.

Pediatric sarcoma in Central America: outcomes, challenges, and plans for improvement.

BACKGROUND: Children with cancer in middle-income countries have inferior outcomes compared with similar children in high-income countries. The magnitude and drivers of this survival gap are not well understood. In the current report, the authors sought to describe patterns of clinical presentation, magnitude of treatment abandonment, and survival in children with sarcoma in Central America. METHODS: A retrospective review was conducted of hospital-based registries from national pediatric oncology referral centers. Patients with newly diagnosed osteosarcoma, Ewing sarcoma, rhabdomyosarcoma (RMS), and soft tissue sarcoma (STS) between January 1, 2000 and December 31, 2009 were included. Survival analyses were performed first using standard definitions of overall survival (OS) and event-free survival (EFS) and then with abandonment included as an event (abandonment-sensitive OS and abandonment-sensitive EFS). RESULTS: In total, 785 new cases of pediatric sarcoma were reported (264 diagnoses of osteosarcoma, 175 diagnoses of Ewing sarcoma, 240 diagnoses of RMS, and 106 diagnoses of STS). The rate of metastatic disease at presentation was high (osteosarcoma, 38%; Ewing sarcoma, 39%; RMS, 29%; and STS, 21%). The treatment abandonment rate also was high, particularly among patients with extremity bone sarcomas (osteosarcoma, 30%; Ewing sarcoma, 15%; RMS, 25%; and STS, 15%). Of 559 patients who experienced a first event, 59% had either recurrent or progressive disease. The 4-year OS rate (±standard error) was 40% ± 3%, and the EFS rate was 30% ± 2%; however, these rates decreased further to 31% ± 2% and 24% ± 2%, respectively, when abandonment was taken into account. CONCLUSIONS: The current results indicated that high rates of metastases and treatment abandonment and difficulty with upfront treatment effectiveness are important contributors to the poor survival of children with pediatric sarcomas in Central America. Initiatives for early diagnosis, psychosocial support, quality improvement, and multidisciplinary care are warranted to improve outcomes.

Retinoblastoma in Central America: report from the Central American Association of Pediatric Hematology Oncology (AHOPCA).

BACKGROUND: Retinoblastoma is highly curable in high income countries. Low income countries have poor results due to advanced disease and lack of resources. Central American Association of Pediatric Hematology Oncology (AHOPCA) aimed to standardize the approach and to improve outcomes of patients with retinoblastoma. PROCEDURE: One hundred seventy-one patients, age <18 years newly diagnosed with retinoblastoma were treated according to laterality and stage. Therapeutic modalities were: surgery (enucleation), local control (laser therapy, cryotherapy), chemotherapy, and radiation therapy. Chemotherapy consisted of vincristine, etoposide, and carboplatin (6 cycles). Outcomes were measured by overall survival. Events were abandonment of therapy and death. RESULTS: One hundred seventy-one patients (129 unilateral, 42 bilateral) were treated. Median age was 2 years 4 months; 112 (66%) were diagnosed before 3 years of age. 119 (92%) eyes in patients with unilateral disease were Reese-Ellsworth IV or V versus 52 (62%) eyes in patients with bilateral disease. Extraocular disease was more prevalent in unilateral disease (65% vs. 50%). Older age at diagnosis correlated with higher stage. Estimated overall survival at 60 months was 0.48 ± 0.04. Outcome of patients with bilateral disease was significantly better than unilateral (62% ± 0.09 vs. 42% ± 0.05, P = 0.0006). Thirty-eight patients (22%) refused or abandoned therapy. CONCLUSIONS: Protocol-directed therapy for retinoblastoma in Central America is possible. Patients present with advanced disease and outcome is significantly worse than in middle and high-income countries. Refusal and abandonment of therapy are societal events that affect outcome. Initiatives aimed at improving early diagnosis, while dedicated treatment centers are developed, are critical.

Measurement of health-related quality of life in survivors of cancer in childhood in Central America: feasibility, reliability, and validity.

Cancer is the commonest cause of disease-related death in children over 5 years of age in various parts of Latin America, but the survival rates are improving. This study assessed the health status and health-related quality of life (HRQL) of more than 200 survivors of cancer in childhood in the countries of a Central American consortium devoted to pediatric hematology-oncology. Patients' self-reports and parental proxy assessments were collected using interviewer-administered Spanish-language questionnaires, and physicians provided assessments using self-complete questionnaires, based on the complementary Health Utilities Index (HUI) Mark 2 (HUI2) and Mark 3 (HUI3) health status classification systems. Inter-rater agreement, measured by intra-class correlation (ICC), was fair to moderate (0.340.60) for all 3 pairs of assessors for readily assessable attributes: HUI2 sensation, HUI3 vision, HUI3 hearing, and HUI3 ambulation. Less than 40% of the patients reported being in perfect health. More than 20% reported being in health states with HRQL scores corresponding to moderate or severe disability, notably in the attributes of emotion and cognition. The results reflect a common profile in survivors of cancer in childhood, including those from industrialized societies. This study illustrates the feasibility of collecting reliable and valid information on HRQL in the developing country context, raising the prospect that such information could be used to influence clinical practice.

AMOR: a proposed cooperative effort to improve outcomes of childhood cancer in Central America.

The dramatic reduction of pediatric cancer mortality rates has been one of the greatest accomplishments of contemporary medicine. About 80% of children with cancer are now expected to be cured by current therapies. However, most of the world's children have no access to cancer treatment. The translation of effective pediatric cancer therapies to impoverished regions of the world presents an enormous challenge to the health care profession. Over the past 20 years, efforts have been under way to extend adequate cancer treatment to an increasing number of children in developing countries. These initiatives, collectively designated "twinning programs," consist essentially of a partnership between a pediatric cancer unit in a developing country and a group of health care providers in the developed world. Here we review the twinning programs that have been implemented in Central America, discuss their impact on the development of local resources and the outcome of childhood cancer, and propose a collaborative research initiative aimed at improving the international dissemination of progress in pediatric hematology-oncology.

Impact of hepatitis B and hepatitis C virus infections in a hematology-oncology unit at a children's hospital in Nicaragua, 1997 to 1999.

The risk of acquiring both hepatitis B virus (HBV) and hepatitis C virus (HCV) infections in patients with hematological-oncological disorders has been documented. However, the impact and risk factors for such infections from different geographical areas vary, and the use of both immunological and molecular assays to determine HCV infections has been our approach. Children from a hematology-oncology unit (HOU) in Nicaragua were studied for both HBV and HCV serological markers; studies for the latter used both immunological (anti-HCV) and molecular (HCV RNA) assays. The children from the HOU included patients with leukemia, lymphoma, other neoplasias, and anemia and a smaller group with other hematological diseases. As a control group, children from other units at the same hospital were enrolled, as well as health care workers attending both patient populations. Pertinent clinical and personal data for each child at the HOU were obtained for statistical analysis. Of the 625 children from the HOU enrolled in this study 53.3% were infected with HCV and 29.4% had a prior or present HBV infection. In the child patient control group 3.2% had HBV markers and all were negative for HCV. The group of children with leukemia had the highest infection rate for both HBV and HCV. However, the determination of anti-HCV was found to have an overall low sensitivity in children from HOU, and a retest consisting of a molecular assay to determine HCV RNA was performed to better establish the total number of HCV-infected subjects in this group. The highest independent risk factor for infection was hospitalization. The very high prevalence rates for both HBV and HCV infection in this patient group indicate an urgent need to implement better control of known risk factors and to consider the use of both immunological and molecular assays for HCV diagnostic purposes.