Conquering the Cancer Care Continuum – Series Three: Fifth Issue

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Conquering Cancer Everywhere: A Physician’s Perspective

Scott Howard, MD, MSc 

Cure rates for children with cancer now exceed 80% in high-income countries (HIC), but several challenges remain.1 Curing the remaining 20% requires new drugs, better combination regimens, and improved risk stratification to avoid undertreatment, and the 80% who are event-free survivors after frontline therapy often must deal with significant late toxicities of treatment. Unfortunately, cure rates in low- and middle-income countries (LMIC) fall far short of the 80% achieved in HIC.2 Addressing the first 2 challenges is a central focus of academic centers and clinical research groups in HIC, but achieving high cure rates in LMIC requires the combined efforts of academia, professional societies, nongovernmental organizations (NGOs), government, and industry. The potential rewards of such efforts for children with cancer worldwide cannot be overestimated, since 90% of children with cancer live in LMIC and can be treated in a local setting at very low cost.3 Furthermore, lessons learned in LMIC often have implications for children with cancer everywhere, including HIC, and because some clinical trials require large numbers of patients, their feasibility depends on inclusion of children in LMIC.

Several strategies have proven effective for curing more children with cancer in LMIC. Three essential strategies are discussed here: (1) addressing preventable causes of treatment failure, (2) adapting treatment regimens to local conditions, and (3) international collaboration via “twinning programs,” defined as long-term relationships between institutions to exchange knowledge and improve care for patients on both sides of the relationship.

Implementing programs to address preventable causes of treatment failure, which include treatment abandonment (ie, failure to start or complete medically indicated curative therapy) and excess toxicity-related death, has been shown to increase survival for acute lymphoblastic leukemia by ≥30%.2,4-7 For example, the Instituto Materno Infantil of Recife, in the relatively poor northeast region of Brazil, reduced the rate of treatment abandonment from 16% to less than 1% by providing subsidized transportation, free oncology care, free housing and food for patients from out of town, and an intensive education and follow-up program.2 Similar programs have subsequently been deployed in many LMIC centers, where they are extremely cost-effective, since helping a child complete all treatment greatly increases the odds of event-free survival and reduces the need for salvage therapy after relapse, which is associated with increased morbidity and cost.

Adapting treatment regimens for use in LMIC is necessary because cancer centers in these countries often lack certain diagnostic capabilities, risk-stratification tools, chemotherapeutic agents, and, in some cases, radiation therapy. Nevertheless, many children can be cured even in cancer centers with a basic infrastructure, and curing the curable allows such centers to build on their success as resources become available. The International Society of Paediatric Oncology (SIOP, for the initials in French) has a very active Committee on Developing Countries (PODC Committee) that includes working groups focused on adapting treatment regimens, preventing treatment abandonment, improving nursing, facilitating access to essential medications, providing education and training, and addressing many other areas necessary to improve cancer care in LMIC. The SIOP-PODC Committee’s working group for adapted treatment regimens comprises healthcare providers from all continents, including disease experts, global health experts, and people practicing in both LMIC and HIC. To date, the working group has developed, published, and deployed adapted regimens for 8 common childhood cancers, and others are in the pipeline. Even more important, the working group provides a forum in which to optimize the implementation and further refinement of each regimen to cure the maximum number of children possible in every setting. Regular online meetings are held via www.Cure4Kids.org, developed and supported by St. Jude Children’s Research Hospital (St. Jude) to provide educational materials and online conferencing at no cost to users. Besides SIOP, other professional societies, such as the American Society of Hematology and The American Society of Pediatric Hematology/Oncology, also have programs to promote education, training, infrastructure development, and clinical research in LMIC.

In addition to activities under the auspices of professional societies, international collaboration includes twinning programs between academic centers in HIC and LMIC (Figure). For example, St. Jude has 21 such partnerships with centers in Latin America, Africa, Asia, and the Middle East; Texas Children’s Hospital supports several programs in Africa; and Boston Children’s Hospital collaborates with centers in Latin America, Asia, and Africa.6,8,9 A number of factors have proven critical to the success of twinning programs (see the essential “C”s in the Table), such that, in addition to support from professional societies and academic centers, support from NGOs, government, and industry is also needed and obtained. For example, World Child Cancer (www.WorldChildCancer.org) and Cure2Children (www.Cure2Children.org) are 2 NGOs specifically dedicated to improving care for children with cancer and blood disorders in LMIC, and between them they have funded and implemented twinning projects on all continents except Antarctica.10-12 Nevertheless, a great deal remains to be done, since, at present, approximately 950 cancer centers in LMIC lack twinning partnerships.

In summary, cure rates for children with cancer in HIC continue to rise, and reducing the late toxicities of treatment is the subject of very active research. Although extending these cures to LMIC is complex, requiring collaboration of many stakeholders in HIC and LMIC, twinning programs have already improved the lives of countless children with cancer and have laid the foundation to help even more in the future.

References

  1. Magrath I, Steliarova-Foucher E, Epelman S, et al. Paediatric cancer in low-income and middle-income countries. Lancet Oncol. 2013;14:e104-e116.
  2. Howard SC, Pedrosa M, Lins M, et al. Establishment of a pediatric oncology program and outcomes of childhood acute lymphoblastic leukemia in a resource-poor area. JAMA. 2004;291:2471-2475.
  3. Bhakta N, Martiniuk ALC, Gupta S, et al. 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. Arch Dis Child. 2013;98:155-160.
  4. Weaver MS, Arora RS, Howard SC, et al. A practical approach to reporting treatment abandonment in pediatric chronic conditions. Pediatr Blood Cancer. 2015;62:565-570.
  5. Weaver MS, Howard SC, Lam CG. Defining and distinguishing treatment abandonment in patients with cancer [published online ahead of print March 6, 2015]. J Pediatr Hematol Oncol. doi:10.1097/MPH.0000000000000319.
  6. Metzger ML, Howard SC, Fu LC, et al. Outcome of childhood acute lymphoblastic leukaemia in resource-poor countries. Lancet. 2003;362:706-708.
  7. Gavidia R, Fuentes SL, Vasquez R, et al. Low socioeconomic status is associated with prolonged times to assessment and treatment, sepsis and infectious death in pediatric fever in El Salvador. PLOS ONE. 2012;7:e43639.
  8. Cox CM, El-Mallawany NK, Kabue M, et al. Clinical characteristics and outcomes of HIV-infected children diagnosed with Kaposi sarcoma in Malawi and Botswana. Pediatr Blood Cancer. 2013;60:1274-1280.
  9. Friedrich P, Ortiz R, Strait K, et al. Pediatric sarcoma in Central America: outcomes, challenges, and plans for improvement. Cancer. 2013;119:871-879.
  10. Faulkner LB, Uderzo C, Masera G. International cooperation for the cure and prevention of severe hemoglobinopathies. J Pediatr Hematol Oncol. 2013;35:419-423.
  11. Paintsil V, David H, Kambugu J, et al. The Collaborative Wilms Tumour Africa Project; baseline evaluation of Wilms tumour treatment and outcome in eight institutes in sub-Saharan Africa. Eur J Cancer. 2015;51:84-91.
  12. Islam A, Eden T. Brief report on pediatric oncology in Bangladesh. South Asian J Cancer. 2013;2:105-106.
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