Effectiveness of a Wilms tumour treatment guideline adapted to local circumstances in sub-Saharan Africa: A report from Wilms Africa Phase II-CANCaRe Africa.

BACKGROUND: Wilms tumour (WT) is one of the cancer types targeted by the Global Initiative for Childhood Cancer (GICC). The objective of this study was to describe the outcomes of Wilms Africa Phase II in sub-Saharan Africa. METHODS: Wilms Africa Phase II used a comprehensive WT treatment protocol in a multi-centre, prospective study conducted in eight hospitals in Ethiopia (2), Ghana (2), Malawi, Cameroon, Zimbabwe and Uganda. Eligibility criteria were: age younger than 16 years, unilateral WT, diagnosed between 1 January 2021 and 31 December 2022. RESULTS: We included 230 WT patients, median age 3 years, 53% male. Median maximum tumour diameter at diagnosis was 13.6 cm and 33% of patients had metastatic disease. Nephrectomy was performed in 71% of patients, of whom 21% had a tumour rupture. Two-year event-free survival (EFS) was 41.3% ± 3.9% after a median follow-up of 17 months (range: 1-33 months), with treatment abandonment considered an event. Treatment abandonment occurred in 26% and death during treatment in 14%. Disease relapse occurred in 10%. Two-year EFS of the 26 patients who received radiotherapy was 64.5% ± 9.7% with no reported disease relapse. CONCLUSION: Patients continue to present late with advanced WT in sub-Saharan Africa, and their survival is below the 60% GICC target. Prevention of treatment abandonment and treatment-related mortality remain important. Earlier diagnosis and access to radiotherapy are expected to decrease disease-related mortality.

Local evidence in sub-Saharan Africa; the CANCaRe Africa experience-Lessons learned and shared thoughts about the way forward.

Collaborative research generating local evidence is key to closing the research and survival gap between sub-Saharan Africa and high-income countries. Lessons learned by CANCaRe Africa, the Collaborative African Network for Childhood Cancer Care and Research while pioneering such research are being discussed together with recommendations for the future.

Surgical aspects and outcomes after nephrectomy for Wilms tumour in sub-Saharan Africa: A report from Wilms Africa Phase II-CANCaRe Africa.

BACKGROUND: Wilms tumour (WT) is one of the common and curable cancer types targeted by the Global Initiative for Childhood Cancer. Tumour excision is essential for cure. This analysis focuses on surgical outcomes of patients with WT in sub-Saharan Africa. METHODS: We implemented a risk-stratified WT treatment guideline as a multicentre, prospective study across eight hospitals and six countries. Eligibility criteria were age 6 months to 16 years, unilateral WT, surgery performed after preoperative chemotherapy and diagnosed between 1 January 2021 and 31 December 2022. Data collection included a specific surgical case report form (CRF). RESULTS: The study registered 230 patients, among whom 164 (71.3%) had a nephrectomy. Ninety-eight percent of patients had a completed surgical CRF. Out 164 patients, 50 (30.5%) had distant metastases. Median tumour diameter at surgery was 11.0 cm. Lymph node sampling was done in 122 (74.3%) patients, 34 (20.7%) had intraoperative tumour rupture, and for 18 (10.9%), tumour resection involved en bloc resection of another organ. Tumour size at surgery was significantly correlated with tumour rupture (p < .01). With a median follow-up of 17 months (range: 2-33), 23 (14.0%) patients have relapsed. Twenty-two (13.4%) patients abandoned treatment post nephrectomy. Two-year event-free survival was 60.4% ± 4.7% with treatment abandonment as an event. CONCLUSION: Survival post nephrectomy is challenged by treatment abandonment, treatment-related mortality and relapse. Large tumours after preoperative chemotherapy were associated with a higher risk of tumour rupture. Earlier diagnosis and access to radiotherapy are expected to improve survival.

Prevention of treatment abandonment remains an important challenge to increase survival of Wilms tumor in sub-Saharan Africa: A report from Wilms Africa-CANCaRe Africa.

BACKGROUND: The Wilms Africa studies implemented an adapted Wilm's tumor (WT) treatment protocol in sub-Saharan Africa in two phases. Phase I began with four sites and provided out-of-pocket costs. Phase II expanded the number of sites, but lost funding provision. Objective is to describe the outcomes of Phase II and compare with Phase I. METHODS: Wilms Africa Phase I (n = 4 sites; 2014-2018) and Phase II (n = 8 sites; 2021-2022) used adapted treatment protocols. Funding for families' out-of-pocket costs was provided during Phase I but not Phase II. Eligibility criteria were age less than 16 years and newly diagnosed unilateral WT. We documented patients' outcome at the end of planned first-line treatment categorized as treatment abandonment, death during treatment, and disease-related events (death before treatment, persistent disease, relapse, or progressive disease). Sensitivity analysis compared outcomes in the same four sites. RESULTS: We included 431 patients in Phase I (n = 201) and Phase II (n = 230). The proportion alive without evidence of disease decreased from 69% in Phase I to 54% in Phase II at all sites (p = .002) and 58% at the original four sites (p = .04). Treatment abandonment increased overall from 12% to 26% (p < .001), and was 20% (p = .04) at the original four sites. Disease-related events (5% vs. 6% vs. 6%) and deaths during treatment (14% vs. 14% vs. 17%) were similar. CONCLUSION: Provision of out-of-pocket costs was important to improve patient outcomes at the end of planned first-line treatment in WT. Prevention of treatment abandonment remains an important challenge.

Evaluating the baseline survival outcomes of the "six Global Initiative for Childhood Cancer index cancers" in Africa.

Limited survival data for the six Global Initiative for Childhood Cancer (GICC) priority cancers are available in Africa. Management of pediatric malignancies in Africa is challenging due to lack of resources, setting-specific comorbidities, high rates of late presentation and treatment abandonment. Reporting of outcome data is problematic due to the lack of registries. With the aim of evaluating the feasibility of baseline outcomes for the six index cancers, we present a descriptive analysis of respective survival rates in Africa. The survival rates were between 18% (lower middle-income countries) to 82.3% (upper middle-income countries) for acute lymphoblastic leukemia, between 26.9% (low-income countries) to 77.9% (upper middle-income countries) for nephroblastoma, between 23% (low-income countries) to 100% (upper middle-income countries), for retinoblastoma, 45% (low-income countries) to 95% (upper middle-income countries) for Hodgkin lymphoma and 28% (low-income countries) to 76% (upper middle-income countries) for Burkitt lymphoma. Solutions to improve survival rates and reported outcomes include establishing and funding sustainable registries, training and to actively include all countries in consortia from different African regions.HighlightsContinental differences in childhood cancer management such lack of resources, setting-specific comorbidities, high rates of late presentation and treatment abandonment, present challenges to the achievement of Global Initiative for Childhood Cancer goals.The available data registries do not adequately inform on the true incidences and outcomes of childhood cancers in Africa.The pathophysiology of some childhood cancers in Africa are associated with high-risk prognostic factors.Outcomes can be improved by greater regional collaboration to manage childhood cancer based on local resources and tumor characteristics.Some individual countries have reached the Global Initiative for Childhood Cancer goals for single cancers and it should be possible for more African countries to follow suit.

Conference report on the 14th International Society of Paediatric Oncology African Continental Meeting, 16-18 March 2022, Kampala, Uganda.

Together with the Africa Continental Branch of the International Society of Paediatric Oncology (SIOP Africa), the Uganda Cancer Institute, a tertiary governmental institution for specialised cancer care services, research and training, hosted the 14th continental meeting of SIOP Africa from the 16-18 March 2022. Under the conference theme, 'Innovate for Africa', the hybrid conference brought together close to 400 international delegates to discuss innovations and experiences, as well as share the latest research in the field of paediatric oncology. The World Health Organisation 2030 Global Initiative for Childhood Cancer provided the main starting point for the conference with a comprehensive pre-conference workshop programme, from multiple stakeholders and organisations and the themes for the plenaries towards improving survival to the main breakout sessions. Delegates discussed various ways of improving outcomes in Africa, despite the challenges faced individually and collectively ranging from education, management systems and treatment guidelines to future governmental and NGO involvement in African cancer care. The main achievements of the conference were various commitments for collaboration, investing in junior investigators, development of registries and systems for improved childhood care on the African continent, while working towards greater access to advanced management options such as targeted therapies and bone marrow transplant services.

Towards zero percent treatment abandonment of patients with common and curable childhood cancer types in Blantyre, Malawi.

BACKGROUND: Treatment abandonment is a common cause of treatment failure in low-income countries (LIC). We implemented a comprehensive package of interventions aiming to enable all families to complete the treatment of their child. The objective of this study was to evaluate the impact of those interventions. PROCEDURE: In this prospective and historically controlled study, we included all children younger than 16 years with a newly diagnosed common and curable cancer type (acute lymphoblastic leukaemia [ALL], Hodgkin disease, Wilms tumour, retinoblastoma and Burkitt lymphoma) admitted to the Queen Elizabeth Central Hospital in Blantyre, Malawi, between 1 June 1 2019 and 1 June 1 2020. Interventions to enable treatment completion included full funding of costs to the family (treatment, transport, accommodation and food in the hospital) and tracking of patients if they did not attend treatment appointments. The outcomes of patients were compared with those of a similar historical cohort. RESULTS: The intervention cohort of 150 patients were compared to 264 historical control patients. Treatment abandonment decreased significantly from 19% (49/264) to 7% (10/150) (p < .001). The proportion of patients with Wilms tumour, retinoblastoma or ALL alive without evidence of disease at the end of treatment increased from 38% (57/149) to 53% (44/83) (p = .03). CONCLUSION: A simple and relatively low-cost comprehensive intervention package with no costs for families, significantly decreased treatment abandonment. This strategy may increase survival of children with common and curable cancers in LIC, especially when coupled with improvements in access to treatment and quality of treatment, including supportive care.

Treatment abandonment: A report from the collaborative African network for childhood cancer care and research-CANCaRe Africa.

BACKGROUND: 'Treatmentabandonment' is a common and preventable cause of childhood cancer treatment failure in low- and middle-income countries (LMIC). Risk factors and effective interventions in LMIC are reported. Poverty and costs of treatment are perceived as overriding causes in sub-Saharan Africa. The objective of this study was to study potential determinants of treatment abandonment, including aspects of treatment costs in sub-Saharan Africa, to be better informed for planned future interventions. METHODS: A multicentre, prospective, observational, cohort study was conducted in five hospitals in sub-Saharan Africa. Children younger than 16 years with newly diagnosed cancer treated as inpatient with curative intent were included. The occurrence of treatment abandonment and potential determinants including aspects of treatment costs were documented during the first 3 months of treatment. RESULTS: We included 252 patients (median age 6.0, range 0.2-15.0 years, 54% male). The most common cancer was Burkitt lymphoma (63/252, 25%). Seven percent of patients (18 of 252) abandoned treatment. Two thirds (65%, 163/252) of patients had to borrow money to reach the hospital for the diagnosis and start of treatment. Treatment abandonment occurred more frequently in families who had to borrow money (16/163, 10%) versus those who did not (2/89, 2%; p = .026). CONCLUSIONS: Limiting costs for families and improved counselling may reduce treatment abandonment. Development and implementation of interventions to reduce treatment abandonment are required in sub-Saharan Africa.

Fever and neutropenia outcomes and areas for intervention: A report from SUCCOUR - Supportive Care for Children with Cancer in Africa.

BACKGROUND: Death during paediatric cancer treatment is common in sub-Saharan Africa. Using the infrastructure of Supportive Care for Children with Cancer in Africa (SUCCOUR), our objective was to describe fever and neutropenia (FN) characteristics and outcomes in order to identify potential areas for future intervention. METHODS: A multicentre prospective, observational cohort study was conducted in sub-Saharan Africa. Data were collected from September 2019 to March 2020. Children below 16 years with newly diagnosed cancer treated with curative intent were included. Data were abstracted in real time using standardised case report forms by trained personnel. Characteristics and outcomes of FN during the first 3 months of treatment were documented. RESULTS: A total of 252 patients were included (median age 6.0, range 0.2-15.0 years, 54% male). The most common cancer was Burkitt lymphoma (63/252, 25%). Among 104 FN episodes, 21 (21%) were associated with prolonged neutropenia (>1 week) and 32 (31%) were associated with profound neutropenia (absolute neutrophil count <0.1 × 109 /L). In 10/104 (10%) episodes, empiric antibiotics were started within 1 hour following fever onset and in 16/104 (15%) episodes, a blood culture was obtained before starting antibiotics. Malaria parasitaemia was detected in four of 104 (4%). A total of 11/104 (11%) patients died in the FN episodes. CONCLUSIONS: Although in most, FN was not associated with prolonged or profound neutropenia, 11% resulted in death. Areas to target include blood cultures prior to antibiotics and earlier initiation of empiric antibiotics. Future efforts should modify FN practices to reduce treatment-related mortality.

Early death and treatment-related mortality: A report from SUCCOUR - Supportive Care for Children with Cancer in Africa.

BACKGROUND: Deaths during paediatric cancer treatment are common in Africa. It is often difficult to distinguish between treatment-related and disease-related causes. To prevent these deaths, it is important to study them and identify the cause. The Supportive Care for Children with Cancer in Africa (SUCCOUR) programme enabled a study with the objective to identify the reasons for early death during treatment. METHODS: We conducted a multicentre prospective, observational cohort study in sub-Saharan Africa. Children younger than 16 years with newly diagnosed cancer treated with curative intent were included from 1 September 2019 until 30 March 2020. Data were abstracted in real time by trained personnel using standardised case report forms. The treating clinician's assessment of the cause of death and signs, symptoms and laboratory values of patients who died during the first 3 months of treatment (early death) were documented. RESULTS: We included 252 patients (median age 6.0, range 0.2-15.0 years, 54% male). The most common cancer was Burkitt lymphoma (63/252, 25%). Fifteen percent of patients (37/252) died during the first 3 months of treatment. Of these 37 patients, 33 (89%) died of a treatment-related cause. Treatment-related mortality of all patients in the first 3 months of treatment was 13% (33/252). CONCLUSION: Fifteen percent of patients had an early death during treatment and 13% had a treatment-related death. This suggests the need to improve supportive care. Implementation of supportive care pathways adapted to local circumstances may be helpful.

Outcome at the end of treatment of patients with common and curable childhood cancer types in Blantyre, Malawi.

BACKGROUND: The WHO Global Initiative for Childhood Cancer aims to increase survival to at least 60% for all children with cancer globally, with initial focus on six common curable cancer types. Frequent causes of treatment failure in low income countries (LICs) are treatment abandonment and death during treatment. Here, we report on the outcome at the end of treatment of patients with newly diagnosed common and curable cancer types, admitted in the Queen Elizabeth Central Hospital, Blantyre, Malawi. PROCEDURE: Outcome at end of treatment was documented and analyzed retrospectively for all children with a working diagnosis of a common and curable cancer type (ALL, Hodgkin disease, Wilms tumor, retinoblastoma, and Burkitt lymphoma) admitted over a 2-year period. Patients with a misdiagnosis were excluded. Outcomes were categorized as alive without evidence of disease, treatment abandonment, death during treatment, or persistent disease. RESULTS: We included 264 patients. Seven patients with a misdiagnosis were excluded. At the end of treatment, 53% (139 of 264) of patients were alive without evidence of disease, 19% (49 of 264) had abandoned treatment, 23% (61 of 264) had died during treatment, and 6% (15 of 264) had persistent disease. CONCLUSION: Survival of children with common and curable cancers is (significantly) below 50%. Almost half (42%) of the patients either abandoned treatment or died during treatment. Strategies to enable parents to complete treatment of their child and improved supportive care are needed. Such interventions may need to be given priority to improve the currently poor survival.

Improvement of overall survival in the Collaborative Wilms Tumour Africa Project.

INTRODUCTION: The Collaborative Wilms Tumour (WT) Africa Project implemented an adapted WT treatment guideline in six centres in sub-Saharan Africa. The primary objectives were to describe abandonment of treatment, death during treatment, event-free survival (EFS) and relapse following implementation. An exploratory objective was to compare outcomes with the baseline evaluation, a historical cohort preceding implementation. METHODS: The Collaborative WT Africa Project is a multi-centre prospective clinical trial that began in 2014. Funding was distributed to all participating centres and used to cover treatment, travel and other associated costs for patients. Patient characteristics, tumour characteristics and events were described. RESULTS: In total, 201 WT patients were included. Two-year EFS was 49.9 ± 3.8% when abandonment of treatment was considered an event. Relapse of disease occurred in 21% (42 of 201) of all included patients and in 26% (42 of 161) of those who had a nephrectomy. Programme implementation was associated with significantly higher survival without evidence of disease at the end of treatment (52% vs 68.5%, P = .002), significantly reduced abandonment of treatment (23% vs 12%, P = .009) and fewer deaths during treatment (21% vs 13%, P = .06). CONCLUSION: This collaborative implementation of an adapted WT treatment guideline, using relatively simple and low-cost interventions, was feasible. Two-year EFS was almost 50%. In addition, a significant decrease in treatment abandonment and an increase in survival at the end of treatment were observed compared to a pre-implementation cohort. Future work should focus on decreasing deaths during treatment and will include enhancing supportive care.

Highlights from the 13th African Continental Meeting of the International Society of Paediatric Oncology (SIOP), 6-9 March 2019, Cairo, Egypt.

The 13th African continental meeting of the international society of paediatric oncology, held on 6-9 March 2019 in Cairo, was organised in collaboration with the Children Cancer Hospital (57357) in Egypt and the global parents' organisation (Childhood Cancer International) and supported by a large international faculty. With 629 delegates from 37 countries (24 African), this was the largest forum of healthcare professionals focused on children and young people with cancer in Africa to showcase advances and discuss further improvements. Three targeted workshops, on nursing care, pharmacy and nutrition, attracted large numbers and catalysed new collaborative initiatives in supportive care studies, extended roles for pharmacists in quality control and care delivery and addressed malnutrition concurrently with cancer treatment. The Collaborative Wilms Tumour Africa Project, open in seven sub-Saharan countries, and the trials in Burkitt's lymphoma reported encouraging outcomes with further initiatives in supportive care (the supportive care for children with cancer in Africa project). While acknowledging deficits in radiotherapy provision, available in only 23 of 52 African countries, centres with facilities reported their technical advances that benefit patients. Of great importance for children with brain tumours, who are underdiagnosed in Africa, was the first announcement of African paediatric neuro-oncology society, whose 63 current members aim to tackle the shortage of neurosurgeons through training fellowships, workshops and a dedicated conference. The congress provided the opportunity to discuss how African countries will work with the WHO global initiative aiming to improve childhood cancer survival to 60% in all countries by 2030. This conference report is dedicated to the three Kenyan delegates who died tragically on the Ethiopian Airlines flight ET302 on their way home, full of new ideas and pride in what they had achieved so far. All those who heard their presentations are determined to continue their excellent work to improve cancer care for children in Africa.

Survival of children with a Wilms tumor in Blantyre, Malawi.

Wilms tumor (WT) has a survival rate above 90% in high income countries. Reported survival rates in sub-Saharan Africa are much lower and long-term outcome is not well known as follow-up is challenging. In Blantyre, Malawi, an adapted WT treatment guideline with preoperative chemotherapy, supportive care, and strategies to enable children and parents to complete treatment was introduced in 2006. Between 2006 and 2011, 73 children with a unilateral WT were treated. Follow-up, including home visits when needed, was done. Median follow-up time is 5 years (range 14-95 months). Two and five-year event free survivals are 46 and 42%. Causes of treatment failure are: 7% (5/73) abandonment of treatment, 15% (11/73) death during treatment and 30% (22/73) disease-related deaths (persistent disease and relapse). Long-term follow-up is challenging but necessary to be able to assess outcome and the true impact of interventions.

Improved outcome at end of treatment in the collaborative Wilms tumour Africa project.

BACKGROUND: The Collaborative Wilms Tumour (WT) Africa Project has implemented an adapted WT treatment guideline in sub-Saharan Africa as a multi-centre prospective clinical trial. A retrospective, baseline evaluation of end-of-treatment outcome was performed for a 2-year period prior to the introduction of this guideline. The collaborative project aims to reduce both treatment abandonment and death during treatment to less than 10% for improving survival. PROCEDURE: All participating centres obtained local Institutional Research Board (IRB) approval and implemented the adapted WT treatment guideline. End-of-treatment outcome was documented for 2 years. It was divided into alive without evidence of disease, treatment abandonment, death during treatment and persistent disease. The outcome of children enroled in the first 2 years of the prospective clinical trial has been compared to the outcome before the start of the project. RESULTS: One hundred twenty-two patients were included in the baseline evaluation (2011-2012) and 133 in the first 2 years of the collaborative clinical trial (2014-2015). The percentage of patients alive without evidence of disease at the end of treatment increased from 52% (63/122) to 68% (90/133; P = 0.01). Treatment abandonment decreased from 23% (28/122) to 13% (17/133; P = 0.03). Death during treatment decreased from 21% (26/122) to 13% (17/133; P = 0.07). CONCLUSION: This collaboration, using relatively simple and low-cost interventions, led to a significant decrease in treatment abandonment and increase in survival without evidence of disease at the end of treatment.