An overview of childhood cancer care and outcomes in Egypt: a narrative review.

Childhood cancer is an urgent priority in Egypt, owing to a large number of children with cancer, the great need and demand for paediatric oncology services, limited resources/funds and inferior survival outcomes. Therefore, an overview of the status of childhood cancer care in Egypt and an evidence-based approach towards optimal utilisation of resources/funds to improve this care are needed. This paper summarises key evidence about childhood cancer care and outcomes in Egypt. We conducted a narrative literature review using a structured search strategy of the MEDLINE database through the PubMed interface. All relevant evidence was summarised under five main sub-topics: (1) burden of childhood cancer in Egypt; (2) treatment approaches; (3) health outcomes; (4) costs and cost-effectiveness of treatment; and (5) barriers and facilitators to optimal childhood cancer care. We found high estimates of disease burden of childhood cancer in Egypt. Furthermore, childhood cancer treatment in Egypt is based on either implementing intensity-regulated protocols or adopting international protocols with or without adaptations to local contexts, leading to varying standards of care among the different treating centres. Limited data about the survival outcomes, costs and cost-effectiveness of treatment exist, although high-quality data from retrospective cohort studies were published from a large paediatric oncology centre (Children's Cancer Hospital Egypt-57357). As Egypt joins the WHO Global Initiative for Childhood Cancers as a focus country, it is prepared to move towards streamlining national efforts to implement a national childhood cancer plan to advance care, improve health outcomes and optimise resource use. Through these efforts, Egypt could become a beacon of hope and a role model to other low- and middle-income countries seeking to improve their childhood cancer care.

Barriers and Facilitators to Implementing Cost-Effective Evidence-Based Childhood Cancer Treatment in a Resource-Limited Setting in Egypt: A Qualitative Interview Study.

PURPOSE: Childhood cancer treatment is complex, resource-intensive, and expensive, and resource-limited settings would benefit from providing cost-effective treatment approaches on the basis of evidence. Effective implementation of cost-effective evidence-based treatment requires knowledge about factors influencing its use. In this study, we determined the clinicians' perceptions of the barriers and facilitators to implementing cost-effective evidence-based treatment for children with cancer in a resource-limited pediatric oncology setting in Egypt. METHODS: We conducted a qualitative study on the basis of semistructured interviews with senior clinicians who make high-level decisions on treatment protocols and tailored decisions for the atypically complicated group of patients. Purposive sampling was used to recruit the participants. Thematic analysis was conducted semantically to develop themes of barriers and facilitators. RESULTS: Fourteen participants agreed to participate in the study: nine pediatric oncologists; three surgeons; and two radiation oncologists. We identified four main themes of barriers and facilitators: awareness and orientation; knowledge, skills, and attitudes; system, resources, and context; and clinical practice. The main barriers included absence of easily available costs/cost-effectiveness data, limited resources and inability to pay for expensive novel (cost-effective) drugs, and gap between evidence and practice. The main facilitators included adopting standard treatment protocols on the basis of clinical effectiveness, leadership support, availability of patients' clinical and cost data from local context, and existing knowledge and skills in clinical research and health economic evaluation. The interview participants also provided suggestions to promote the implementation of cost-effective evidence-based treatment in priority areas. CONCLUSION: Our study findings provide an understanding of the barriers and facilitators affecting the implementation of cost-effective evidence-based treatment for childhood cancers in Egypt. We provide practical recommendations to address the implementation gaps with implications on practice, policy, and research.

Cost-effectiveness of childhood cancer treatment in Egypt: Lessons to promote high-value care in a resource-limited setting based on real-world evidence.

Background: Childhood cancer in low-and middle-income countries is a global health priority, however, the perception that treatment is unaffordable has potentially led to scarce investment in resources, contributing to inferior survival. In this study, we analysed real-world data about the cost-effectiveness of treating 8886 children with cancer at a large resource-limited paediatric oncology setting in Egypt, between 2013 and 2017, stratified by cancer type, stage/risk, and disease status. Methods: Childhood cancer costs (USD 2019) were calculated from a health-system perspective, and 5-year overall survival was used to represent clinical effectiveness. We estimated cost-effectiveness as the cost per disability-adjusted life-year (cost/DALY) averted, adjusted for utility decrement for late-effect morbidity and mortality. Findings: For all cancers combined, cost/DALY averted was $1384 (0.5 × GDP/capita), which is very cost-effective according to WHO-CHOICE thresholds. Ratio of cost/DALY averted to GDP/capita varied by cancer type/sub-type and disease severity (range: 0.1-1.6), where it was lowest for Hodgkin lymphoma, and retinoblastoma, and highest for high-risk acute leukaemia, and high-risk neuroblastoma. Treatment was cost-effective (ratio <3 × GDP/capita) for all cancer types/subtypes and risk/stage groups, except for relapsed/refractory acute leukaemia, and relapsed/progressive patients with brain tumours, hepatoblastoma, Ewing sarcoma, and neuroblastoma. Treatment cost-effectiveness was affected by the high costs and inferior survival of advanced-stage/high-risk and relapsed/progressive cancers. Interpretation: Childhood cancer treatment is cost-effective in a resource-limited setting in Egypt, except for some relapsed/progressive cancer groups. We present evidence-based recommendations and lessons to promote high-value in care delivery, with implications on practice and policy. Funding: Egypt Cancer Network; NIHR School for Primary Care Research; ALSAC.

Estimated incidence, prevalence, mortality, and registration of childhood cancer (ages 0-14 years) in the WHO Eastern Mediterranean region: an analysis of GLOBOCAN 2020 data.

BACKGROUND: There is little evidence about childhood cancer burden in the WHO Eastern Mediterranean region (EMR). We aimed to provide an estimate of childhood cancer burden in the EMR, examine the connection between age-standardised mortality rate and level of income (gross domestic product [GDP] per capita), and reflect on the current status of childhood cancer registration in the EMR. METHODS: Using the GLOBOCAN 2020 data from the Cancer Surveillance Unit of the International Agency for Research on Cancer, we extracted data for childhood cancer (at ages 0-14 years) incidence, prevalence, and mortality for 22 countries in the EMR, the EMR as a whole, and other WHO regions, and categorised by main cancer types. Childhood cancers were classified according to the 10th revision of the International Classification of Diseases. We also searched MEDLINE, Google Scholar, and the grey literature between May 17 and Aug 2, 2021, for English-language articles and reports about the status of childhood cancer registration in the EMR. We further examined the connection between age-standardised mortality rate and GDP per capita for the 22 countries in the EMR. FINDINGS: The total estimated number of incident childhood cancer cases in the EMR was 23 847 in 2020, with an age-standardised incidence rate of 10·1 per 100 000 children at risk, ranging from 7·3 per 100 000 children at risk in Pakistan to 13·8 per 100 000 children at risk in Iran. The estimated number of incident cases was 7451 (age-standardised incidence rate 3·10 per 100 000 children at risk) for leukaemia, 3006 (1·30 per 100 000 children at risk) for brain and CNS tumours, 2222 (0·92 per 100 000 children at risk) for non-Hodgkin lymphoma, 1569 (0·67 per 100 000 children at risk) for kidney cancers, and 1420 (0·58 per 100 000 children at risk) for Hodgkin lymphoma. In 2020, the number of total estimated childhood cancer deaths in the EMR was 10 535, with an age-standardised mortality rate of 4·4 (per 100 000 children at risk, ranging from 0·8 per 100 000 children at risk in Qatar to 7·2 per 100 000 children at risk in Somalia. A negative correlation was found between countries' GDP per capita (income level) and mortality rates (r=-0·77, p<0·0001). The scarcity of data and quality of cancer registries in EMR countries prevented further analysis. INTERPRETATION: Given the variable quality and coverage of cancer registries in EMR countries, these findings are likely to be underestimates. Nevertheless, these data, especially the high mortality rates, reflect a need for effective national childhood cancer plans in line with the WHO Global Initiative for Childhood Cancer to improve survival. FUNDING: Friends of Cancer Patients.

Systematic review of costs and cost-effectiveness of treatment for relapsed/refractory acute leukemia in children and young adults.

INTRODUCTION: Survival outcomes of children with relapsed/refractory (r/r) acute leukemia remain poor. Novel expensive treatments have been developed to improve their outcomes, yet, limited evidence exists about cost-effectiveness of alternative treatment strategies. AREAS COVERED: A systematic review was conducted to summarize health-economic evidence about costs/cost-effectiveness of treating r/r acute leukemia in children/young adults. We searched Medline, Embase, and Cochrane databases until August 13th, 2021. Eligible articles included peer-reviewed original studies addressing r/r pediatric/young-adult acute lymphoblastic leukemia (ALL), and acute myeloid leukemia (AML). Quality assessment was conducted using Consolidated Health Economics Evaluation Reporting Standards (CHEERS) checklist. EXPERT OPINION: The majority of papers focused on CAR-T cell therapy, which is still a novel treatment for r/r ALL, and was found to be cost-effective, yet, there remain concerns over its long-term effectiveness, affordability, and equity in access. The next best treatment option is Blinatumomab, followed by Clofarabine therapy, whereas FLA-IDA salvage chemotherapy provides least value for money. The quality of evidence is moderate to high, with limited generalizability of findings due to high variability in outcomes obtained from modeling studies. Limited studies evaluated r/r AML. We provide recommendations to deliver cost-effective treatments in real-world contexts, with implications for healthcare policy and practice.

Childhood cancer hospital resource utilization and costs in Egypt, 2013-2017; patterns, trends, and associated factors for 8886 patients from Children's Cancer Hospital, Egypt.

INTRODUCTION: There is a lack ofevidence about resource use and costs of childhood cancer care in Egypt. Knowledge about resource use/costs can help in better resource planning to improve care and outcomes efficiently. In this study, we estimated patterns and trends of hospital resource use and costs for children with cancer (n = 8886, aged 0-18 years) treated at Children's Cancer Hospital, Egypt (CCHE), between 2013 and 2017, by ICCC-3 groups, at one and three years post-diagnosis. METHODS: We estimated costs from the healthcare provider perspective, expressed in USD 2019. We also studied resource use/cost trends, and factors associated with inpatient days and costs. RESULTS: For all cancers combined, median costs were $14,774 (IQR: $6,559-$23,738) at one year and $19,799 (IQR: $8,921-$34,204) at three years post-diagnosis. Median inpatient days were 38 days (IQR: 17-60) at one year, and 43 days (IQR: 20-74) at three years post-diagnosis. Patients with acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and neuroblastoma imposed the greatest financial burden on CCHE, representing 53.1% of total costs. AML patients had the highest costs/resource use of all childhood cancers. Cost trends decreased by 2.9% (P < 0.001) for all cancers combined, due to economic instability in Egypt between 2013 and 2017. The use of IV supportive drugs increased by 24.3% (P < 0.001) over time for children with solid tumors. CONCLUSION: These findings will inform hospital resource planning and budgeting to promote value in care delivery, with implications for pediatric oncology practice and policy in Egypt/CCHE. Estimated costs provide the foundation for cost-effectiveness analysis.

Temporal trends in childhood cancer survival in Egypt, 2007 to 2017: A large retrospective study of 14 808 children with cancer from the Children's Cancer Hospital Egypt.

Childhood cancer is a priority in Egypt due to large numbers of children with cancer, suboptimal care and insufficient resources. It is difficult to evaluate progress in survival because of paucity of data in National Cancer Registry. In this study, we studied survival rates and trends in survival of the largest available cohort of children with cancer (n = 15 779, aged 0-18 years) from Egypt between 2007 and 2017, treated at Children's Cancer Hospital Egypt-(CCHE), representing 40% to 50% of all childhood cancers across Egypt. We estimated 5-year overall survival (OS) for 14 808 eligible patients using Kaplan-Meier method, and determined survival trends using Cox regression by single year of diagnosis and by diagnosis periods. We compared age-standardized rates to international benchmarks in England and the United States, identified cancers with inferior survival and provided recommendations for improvement. Five-year OS was 72.1% (95% CI 71.3-72.9) for all cancers combined, and survival trends increased significantly by single year of diagnosis (P < .001) and by calendar periods from 69.6% to 74.2% (P < .0001) between 2007-2012 and 2013-2017. Survival trends improved significantly for leukemias, lymphomas, CNS tumors, neuroblastoma, hepatoblastoma and Ewing Sarcoma. Survival was significantly lower by 9% and 11.2% (P < .001) than England and the United States, respectively. Significantly inferior survival was observed for the majority of cancers. Although survival trends are improving for childhood cancers in Egypt/CCHE, survival is still inferior in high-income countries. We provide evidence-based recommendations to improve survival in Egypt by reflecting on current obstacles in care, with further implications on practice and policy.

Outcome of resectable pediatric Ewing sarcoma of the ribs.

PURPOSE: Was to evaluate the outcome of multimodality treatment in resectable primary Ewing sarcoma/primitive neuroectodermal tumor ES/PNET of the ribs and role of thoracoscopy in facilitating resection of these tumors. PATIENTS AND METHODS: This was a retrospective study including 22 patients with primary ES/PNET of the ribs surgically treated at Children's Cancer Hospital Egypt (CCHE) between January 2008 until the end of December 2014. RESULTS: Median age was 8.5years (range 5months to 16years.). All patients received neoadjuvant chemotherapy. Thoracoscopic exploration was performed in 15 (68%) patients. Resection included 1,2,3 and 4 ribs in (7,4,8 and 3 patients) respectively, parts of the diaphragm (3 patients), wedge resection of the lung (10 patients) and pleural nodules (2 patients). Primary closure was feasible in 11 patients and rib transposition was done in one patient. Reconstruction by proline mesh covered by muscle flap was done in 10 patients. Margins were microscopically positive in 3 patients and close in 2 patients. Postoperative radiotherapy was given in 8 patients. With a median follow-up of 38.5months, the 3-year event -free survival (EFS) and overall survival(OS) rates were 31.6% and 55.6%, respectively. CONCLUSION: Multimodality treatment is essential in the management of ES-PNET of the ribs. Neoadjuvant chemotherapy facilitates adequate resection. The role of thoracoscopy and the indications of postoperative radiotherapy need further evaluation.

Risk stratification and pattern of cardiotoxicity in pediatric Ewing sarcoma.

INTRODUCTION: Anthracycline chemotherapy contributes to improved outcomes in Ewing sarcoma; however, the most feared complication is cardiotoxicity. Echocardiograms were routinely used to monitor cardiac function after anthracycline treatment. Nevertheless, indices chosen to assess cardiac toxicity vary significantly among different centers, and no uniform protocol has been accepted as ideal. METHODS: This retrospective study included children with Ewing sarcoma treated at Children's Cancer Hospital Egypt over 4years. All echocardiograms and related clinical assessments were reviewed. RESULTS: In total, 149 patients (median age 11years; range 1-18years) were included. Although all patients had a reduced ejection fraction compared with their baseline echocardiogram, only 39 patients developed cardiotoxicity (26%): 43% acute-onset, 36% chronic early-onset, and 21% chronic late-onset. There were no statistically significant association between the frequency of myocardial dysfunction and risk factors, including age, sex, follow-up duration, cumulative doxorubicin dose, and mediastinal irradiation. Over one-third (39%) of the patients with cardiac toxicity regained normal cardiac parameters, whereas seven patients died of acute cardiac toxicity. CONCLUSION: The routine use of echocardiography to screen for anthracycline-induced cardiac toxicity before and during chemotherapy identified myocardial dysfunction. Early medical intervention can improve cardiac parameters. Improved screening techniques with better sensitivity and predictability are needed.