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.

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.

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.

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.

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.

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.

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.

Triple therapy of vincristine, bleomycin and etoposide for children with Kaposi sarcoma: Results of a study in Malawian children.

BACKGROUND: Kaposi sarcoma (KS) is the most common paediatric cancer in human immunodeficiency virus (HIV) endemic countries of sub-Saharan Africa, but there is little research on management and outcomes. METHODS: Children with KS at Queen Elizabeth Central Hospital, Blantyre, Malawi treated between August 2012 and March 2015 with six courses of vincristine, bleomycin and etoposide combination chemotherapy, including antiretroviral therapy (ART) if HIV infected, were studied and outcomes compared with previously reported results. FINDINGS: Fifty-six children were included; 38 (68%) were male; and 48 (86%) were HIV positive, of whom 36 (77%) were on ART at diagnosis. Median age at diagnosis was 8 years (interquartile range [IQR] 3-12) and median follow-up was 16.9 months (IQR 3.4-36.4). Quality of life improved in 45 (80%) children; the median Lansky Score increased from 80% pre-treatment to 100% post-treatment. Eighteen (32%) children had complete response to treatment. At 12 months, overall survival was 71% (95% confidence interval [CI] 56-82) and event-free survival (event = death, loss to follow-up or relapse) was 50% (95% CI 36-63). At 1 year, the risk of loss to follow-up was 13.4%. In a previous, same-site, randomized controlled study of vincristine monotherapy, vincristine and bleomycin, or oral etoposide, oral etoposide monotherapy had the best outcome with survival at 12 month of 66% (95% CI 46-80) and event-free survival of 52% (95% CI 33-68); however, loss to follow-up was not reported. CONCLUSION: Overall survival, event-free survival and quality of life appear to have improved with this three-agent combination chemotherapy; however larger, randomized studies are needed to determine optimal management.

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.

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.

The use of anthracyclines in the treatment of endemic Burkitt lymphoma.

Burkitt lymphoma is the most common malignancy in children in Malawi, the world's poorest country, where there is a long history of treating this disease using a 28-day cyclophosphamide-based protocol. Stage III/IV disease has had poor outcomes. In an attempt to improve the outcome for higher stage disease, anthracyclines were added to the existing protocol. The disease-free (DFS) and overall survival (OS) of 58 children with cytologically confirmed Burkitt lymphoma admitted during 2012-2014 and treated using this protocol were calculated. Six (10%) children had stage I disease, ten (17%) stage II and 42 stage III or IV (73%). Overall 12-month DFS (OS) was 68·5% (72·9%); for stage I disease 100% (100%), stage II 56·2% (60%), stage III/IV 66·3% (72·2%). The DFS was significantly improved from the previous protocol (P = 8 × 10-4 ). The addition of doxorubicin to stage III and IV disease resulted in a markedly improved DFS. Anthracyclines are deliverable in resource-poor settings and possibly improve the survival of children with Burkitt lymphoma.

A framework to develop adapted treatment regimens to manage pediatric cancer in low- and middle-income countries: The Pediatric Oncology in Developing Countries (PODC) Committee of the International Pediatric Oncology Society (SIOP).

Many children with cancer in low- and middle-income countries are treated in hospitals lacking key infrastructure, including diagnostic capabilities, imaging modalities, treatment components, supportive care, and personnel. Childhood cancer treatment regimens adapted to local conditions provide an opportunity to cure as many children as possible with the available resources, while working to improve services and supportive care. This paper from the Adapted Treatment Regimens Working Group of the Pediatric Oncology in Developing Countries committee of the International Society of Pediatric Oncology outlines the design, development, implementation, and evaluation of adapted regimens and specifies levels of services needed to deliver them.

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

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.

Outcome is unchanged by adding vincristine upfront to the Malawi 28-day protocol for endemic Burkitt lymphoma.

BACKGROUND: We previously reported a 28-day treatment protocol for children with endemic Burkitt lymphoma (BL) which included four doses of cyclophosphamide (CPM), intrathecal methotrexate and hydrocortisone (IT MTX/HC) at Queen Elizabeth Central Hospital (QECH) in Malawi which resulted in an Event-Free Survival (EFS) of 50% at 1 year. METHODS: In an attempt to improve survival whilst maintaining acceptable toxicity, brevity, low-cost and a standard treatment for all patients, four doses of vincristine (VCR) at 1.5 mg/m(2) were added to the backbone of CPM 40 mg/kg on day 1 and 60 mg/kg on days 8,18 and 28 and IT MTX /HC 12.5 mg on days 1,8,18 and 28. RESULTS: Seventy cytology confirmed cases of BL, 42 males and 28 females with a median age of 80 years, were treated with this protocol between January 2010 and April 2012. Four percent had St Jude Stage I disease; 29% Stage II; 30% Stage III and 37% Stage IV. Disease site in order of frequency was face (64%); abdomen (47%); CSF (26%) and paraspinal (17%). There were two on-treatment deaths. Sixty-three percent required antibiotics and 19% required blood transfusion. Eighty-one percent of patients achieved complete clinical remission at day 28. Overall predicted EFS at 1 year was 48%; 100% in Stage I, 83% in Stage II, 24% in Stage III and 32% in Stage IV disease. EFS was significantly worse in patients with Stage III/IV disease (P = 0.002) and paraplegia (P = 0.002). CONCLUSION: The addition of vincristine to the Malawi 28 day BL treatment protocol did not improve survival.

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

Neuroblastoma is the most common extracranial solid tumor in childhood in high-income countries (HIC), where consistent treatment approaches based on clinical and tumor biological risk stratification have steadily improved outcomes. However, in low- and middle- income countries (LMIC), suboptimal diagnosis, risk stratification, and treatment may occur due to limited resources and unavailable infrastructure. The clinical practice guidelines outlined in this manuscript are based on current published evidence and expert opinions. Standard risk stratification and treatment explicitly adapted to graduated resource settings can improve outcomes for children with neuroblastoma by reducing preventable toxic death and relapse.