Trijn Israels

Toward the Cure of All Children With Cancer Through Collaborative Efforts: Pediatric Oncology As a Global Challenge

Advances in the treatment of childhood cancers have resulted in part from the development of national and international collaborative initiatives that have defined biologic determinants and generated risk-adapted therapies that maximize cure while minimizing acute and long-term effects. Currently, more than 80% of children with cancer who are treated with modern multidisciplinary treatments in developed countries are cured; however, of the approximately 160,000 children and adolescents who are diagnosed with cancer every year worldwide, 80% live in low- and middle-income countries (LMICs), where access to quality care is limited and chances of cure are low. In addition, the disease burden is not fully known because of the lack of population-based cancer registries in low-resource countries. Regional and ethnic variations in the incidence of the different childhood cancers suggest unique interactions between genetic and environmental factors that could provide opportunities for etiologic research. Regional collaborative initiatives have been developed in Central and South America and the Caribbean, Africa, the Middle East, Asia, and Oceania. These initiatives integrate regional capacity building, education of health care providers, implementation of intensity-graduated treatments, and establishment of research programs that are adjusted to local capacity and local needs. Together, the existing consortia and regional networks operating in LMICs have the potential to reach out to almost 60% of all children with cancer worldwide. In summary, childhood cancer burden has been shifted toward LMICs and, for that reason, global initiatives directed at pediatric cancer care and control are needed. Regional networks aiming to build capacity while incorporating research on epidemiology, health services, and outcomes should be supported.

Practical recommendations for the management of children with Endemic Burkitt Lymphoma (BL) in a resource limited setting

Treatment recommendations for endemic Burkitt lymphoma (BL) in settings with only minimum requirements for curative treatment (PODC setting 1) are described. The reported cure rate for endemic BL is usually <50%. Facilities within setting 1 differ. Three treatment schedules are proposed based on: (1) when accurate staging is not possible, (2) when staging is possible and for (3) relapses and poor responders to primary therapy. A literature review and personal experience were used to formulate the recommendations. Recorded 1‐year event free survival was 48% for treatment 1, 61% for treatment 2, and 35% for the rescue treatment. Pediatr Blood Cancer 2013; 60: 357–362.

SIOP PODC: Recommendations for supportive care of children with cancer in a low-income setting†

These supportive care recommendations were prepared to guide doctors who practice in areas with significantly limited resources but who have sufficient infrastructure and training to treat children with cancer with curative intent. The success of any cancer treatment regimen depends largely on the availability and quality of supportive care and this also determines the intensity of treatment that can be delivered. We present practical recommendations on how to prevent infections, general nursing care, management of febrile neutropenia, nutritional assessment and support, treatment of co‐infections and the social support to help prevent failure to complete treatment in resource poor settings. Pediatr Blood Cancer 2013; 60: 899–904.

SIOP-PODC recommendations for graduated-intensity treatment of retinoblastoma in developing countries.

Retinoblastoma remains incurable in many regions of the world. The major obstacles to cure are delayed diagnosis, poor treatment compliance, and lack of evidence‐based recommendations for clinical management. Although enucleation is curative for intraocular disease, in developing countries retinoblastoma is often diagnosed after the disease has disseminated beyond the eye. A SIOP‐PODC committee generated guidelines for the clinical management of retinoblastoma in developing countries and developed a classification system based on the resources available in those settings. Recommendations are provided for staging and treatment of unilateral and bilateral retinoblastoma and counseling of families for whom compliance is an issue. Pediatr Blood Cancer 2013; 60: 719–727.

The management of children with Kaposi sarcoma in resource limited settings

Kaposi sarcoma (KS) is common where HIV infection is endemic. Antiretroviral therapy (ART) has reduced the incidence in well‐resourced settings but in some parts of the world access to ART is delayed. These recommendations are for use where only minimal requirements for treatment are available. Consensus was sought for the management of childhood HIV‐associated KS in this setting. There are no randomised controlled studies of chemotherapy for KS in children and these recommendations have drawn on consensus of a group of experts and published reports from studies in adults. Pediatr Blood Cancer 2013; 60: 538–542.

The Collaborative Wilms Tumour Africa Project; baseline evaluation of Wilms tumour treatment and outcome in eight institutes in sub-Saharan Africa.

AIM Reported survival of Wilms tumour in sub-Saharan Africa is below 50%. A published International Society of Pediatric Oncology (SIOP) Pediatric Oncology in Developing Countries (PODC) consensus adapted treatment guideline is implemented as a multi-centre prospective clinical trial at eight centres in sub-Saharan Africa. A baseline evaluation has been done to help decide on priorities to improve outcome and to assess improvements over time. METHODS A retrospective chart review was performed of patients admitted with Wilms tumour in the three years (2011-2013) preceding the collaborative trial. Patient outcome at the end of treatment was documented for all patients diagnosed in 2011 and 2012. Outcome was classified as (1) alive, no evidence of disease; (2) alive with disease; (3) died during treatment and (4) incomplete treatment. Details on treatment facilities, staff and estimated cost of treatment are documented. RESULTS Every year 114-130 patients are diagnosed. The mean survival at end of treatment is 39% (69/176) ranging from 11% to 61%. Incomplete treatment is the most common cause of treatment failure with 31% (54/176), ranging from 14% to 48% between centres. Twenty-six percent (46/176) of patients died during treatment, ranging from 13% to 37%. Estimated cost of treatment for parents ranged from 100 US

Kaposi’s sarcoma in children: An open randomised trial of vincristine, oral etoposide and a combination of vincristine and bleomycin

to 1100 US

Improving Care for Children With Cancer in Low- and Middle-Income Countries-A SIOP PODC Initiative

and was considered an important cause of failure to complete treatment. CONCLUSION Overall two year survival is estimated at 25%. Prevention of incomplete treatment is possible and will positively affect outcome. Sharing similar local challenges in this regional collaborative project helps to identify and implement feasible, sustainable and successful strategies.

SIOP‐PODC adapted risk stratification and treatment guidelines: Recommendations for neuroblastoma in low‐ and middle‐income settings

INTRODUCTION Kaposis sarcoma (KS) is a common childhood cancer in places where HIV is endemic and access to antiretroviral therapy (ART) is delayed. Despite this there are no randomised trials to compare and assess chemotherapeutic regimens. METHOD An open label, randomised trial comparing intravenous vincristine alone, vincristine and bleomycin and oral etoposide, was carried out in children with Kaposis sarcoma in the Queen Elizabeth Central Hospital, Blantyre, Malawi. HIV infected children were given ART after 2-3 courses of chemotherapy if they were not already on treatment. Neither HIV nor widespread KS are curable and treatment is aimed at disease reduction and improved quality of life. Tumour reduction was assessed by measuring the size of sentinel KS nodules and quality of life (QoL) by using the Lansky score. Follow up was until death or for one year. FINDINGS 92 children were enrolled of whom 46% were naïve to ART; 10 (11%) were HIV negative. Survival was not influenced by age or gender but was better in the oral etoposide and the vincristine and bleomycin groups. P=0.0045. The group receiving oral etoposide had a better quality of life. Toxicity was not significant, and any drop in haemoglobin or white cell count could have been causally related to HIV infection rather than cytotoxic therapy. CONCLUSION Oral etoposide is a safe, effective treatment to contain KS and improve QoL which can be achieved without many visits to the hospital and intravenous injections.

Treating Children With Cancer Worldwide--Challenges and Interventions.

The Paediatric Oncology in Developing Countries (PODC) committee of International Society of Paediatric Oncology (SIOP) has 10 working groups that provide a forum for individuals to engage, network, and implement improvements in the care of children with cancer in low‐ and middle‐income countries. The development of adapted guidelines (medulloblastoma, retinoblastoma, Wilms tumor, neuroblastoma, retinoblastoma, Burkitt lymphoma, supportive care), advocacy and awareness (on hospital detention and essential drugs), education and training, and global mapping (nutritional practice, abandonment rates, and twinning collaborations) have been the initial areas of focus, and the impact of some of these activities is evident, for example, in the SIOP Africa PODC Collaborative Wilms tumor project.