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.

Current Realities of Wilms Tumor Burden and Therapy in Ghana.

BACKGROUND: Between 2005 and 2014, Ghana's Wilms tumor (WT) 2-year disease-free survival of 44% trailed behind that of high-income countries. This study aimed to uncover social determinants of health leading to preventable WT death in Ghana. METHODS: WT patient records (2014-2022) at Korle-Bu Teaching Hospital (KBTH; Ghana) were reviewed retrospectively. Demographics, clinical course, tumor characteristics, and survival were evaluated using t-tests, Pearson Chi-square, and multivariate Cox logistic regression. RESULTS: Of 127 patients identified, 65 were female. Median age was 44 months [IQR 25-66]. Forty-eight patients (38%) presented with distant metastasis (75% lung, 25% liver), which associated with hypoalbuminemia (p = 0.009), caregiver informal employment (p = 0.04), and larger tumors (p = 0.002). Despite neoadjuvant chemotherapy shrinking 84% of tumors, larger initial size associated with incomplete resection (p = 0.046). Of 110 nephrectomies, 31 patients had residual disease, negatively impacting survival (p = 2.7 × 10-5). Twenty-two patients (17%) abandoned treatment (45% before nephrectomy; 55% after nephrectomy), with seven patients ultimately lost to follow-up (LTFU). Decedents represented 43% of stage IV patients compared to 28% in other stages. Event-free survival (EFS) was 60% at 4 years with overall survival (OS) at 67%. CONCLUSIONS: Although Ghana's WT survival has improved, informal employment and distance from KBTH predisposed patients to delayed referral, greater tumor burden, hypoalbuminemia, and lower survival. TYPE OF STUDY: Prognosis Study. LEVEL OF EVIDENCE: II.

Short-term chemotherapy-related complications and undernutrition in children diagnosed with cancer at Korle Bu Teaching Hospital, Accra, Ghana: A prospective cohort study.

Undernutrition in children with cancer is associated with complications during cancer therapy. The study objective was to determine the association between specific anthropometric parameters and short-term chemotherapy-related complications and mortality. This was a hospital-based, prospective cohort study of children, age ≤12 years, with a new cancer diagnosis at the Paediatric Oncology Unit, Korle Bu Teaching Hospital, Ghana. Socio-demographic information, cancer characteristics and anthropometric measurements were obtained at enrolment. Participants were followed up for twelve weeks from commencement of chemotherapy and selected treatment-related complications such as anaemia and thrombocytopenia requiring transfusions, prolonged neutropenia resulting in treatment delays, febrile neutropenia, mucositis and death were recorded. A total of 133 participants were recruited with a median age of 4.5 years. Eighty-one (60.9%) were diagnosed with solid tumours, 31 (23.3%) had leukaemias and 21 (15.8%) had lymphomas. Of the anthropometric parameters assessed, only arm anthropometry using upper arm muscle area (UAMA) and mid-upper arm circumference (MUAC) were associated with complications. Participants with wasting were more likely to develop anaemia and mucositis. However, the incidence of prolonged neutropenia was significantly higher among participants with average UAMA (p = 0.043) and low average UAMA (p = 0.049) compared to those with low UAMA. Risk of neutropenia was also significantly less among those with wasting by MUAC compared to those well-nourished (p = 0.045). Twenty-three participants (17.3%) died with a greater proportion (11/44; 25%) occurring in those who were wasted using MUAC. These findings underscore the need for nutritional surveillance at diagnosis and during chemotherapy, particularly where co-morbid disease is prevalent.

NUTRITIONAL STATUS AND RISK FACTORS ASSOCIATED WITH SEVERE ACUTE MALNUTRITION AMONG HIV-INFECTED CHILDREN ENROLLED IN THE PAEDIATRIC HIV CLINIC, KORLE BU TEACHING HOSPITAL, ACCRA, GHANA.

Background: Malnutrition remains a common problem among Human Immunodeficiency Virus (HIV)-infected children even while receiving antiretroviral therapy leading to disease progression and reduced survival. Aim: To assess the nutritional status and risk factors associated with severe acute malnutrition (SAM) among HIV-infected children aged 1 to 15 years attending the Paediatric HIV Clinic at Korle Bu Teaching Hospital (KBTH), Accra. Methods: A cross-sectional study was conducted from October 2018 to January 2019 at the Clinic during which 150 participants aged 15 to 179 months were systematically recruited. A structured interview, physical examination, including anthropometric measurements, data extraction from hospital records, and laboratory investigations were conducted. Weight-for- age, weight-for-length/height, length/height-for-age, body mass index Z scores, and mid-upper arm circumference-for-age were obtained. Logistic regression models were used to assess the crude and adjusted odds of the nutritional status on the socio-demographic, clinical, and HIV-related characteristics of the participants at alpha= 0.05. Results: The prevalence of SAM, moderate acute malnutrition and normal nutrition were 4.0% (6/149), 13.4% (20/149) and 80.5% (120/149), respectively, whilst 1.3% (2/149) were overweight and 0.7% (1/149) obese. Stunting and severe stunting were 18.1% (27/149) and 6.7% (10/149) prevalent, respectively. SAM was significantly associated with oral thrush among participants in the adjusted model. The prevalence of mild-, moderate- and severe-anaemia were 23.7% (33/139), 38.8% (54/139) and 1.4% (2/139), respectively. Conclusion: Malnutrition is prevalent among HIV-infected children on antiretroviral therapy at KBTH. SAM is associated with oral thrush.

Pediatric HIV Disclosure Intervention Improves Immunologic Outcome at 48 Weeks: The Sankofa Trial Experience.

BACKGROUND: The World Health Organization recommends disclosure of HIV status to children and adolescents living with HIV (CALWH). HIV disclosure improves adherence to antiretroviral therapy and immunologic and virologic outcomes. However, the prevalence of HIV disclosure is low in sub-Saharan Africa. We assessed the longitudinal effect of the Sankofa Pediatric HIV disclosure intervention on immunologic and virologic outcomes among CALWH in Ghana. METHODS: We conducted a secondary analysis of a two-arm site-randomized clinical trial among CALWH aged 7-18 years. Data were collected at baseline, 24, and 48 weeks. Generalized linear mixed models were used to compare immunologic (CD4) and virologic (viral load) outcomes as both continuous and categorical variables by disclosure status and by intervention group. RESULTS: Among participants who had their HIV status disclosed during this study, the proportion with CD4 percent >25% increased from 56.5% at baseline to 75.4% at week 48 ( P = 0.03), with a slight increase in the undisclosed group (69.5% vs. 74.3%, P = 0.56). In the intervention arm, there was a steady increase in proportion with CD4 percent >25% from 47.1% at baseline to 67.8% at week 48 ( P = 0.01) while it remained unchanged in the control arm (80.5% vs. 81.3% [ P = 0.89]). Concurrently, declines in detectable viral load were observed in both disclosed (63.3% vs. 51.5%, P = 0.16) and undisclosed (69.9% vs. 62.0%, P = 0.17) groups while the intervention group experienced a meaningful drop from 72.9% to 57.6% at 24 weeks ( P = 0.04), which was maintained at 48 weeks. CONCLUSIONS: A structured, culturally relevant disclosure intervention can improve clinical outcomes.

Enhancing information on stage at diagnosis for childhood cancer in Africa.

BACKGROUND/PURPOSE: Stage at diagnosis is an important metric in treatment and prognosis of cancer, and also in planning and evaluation of cancer control. In sub-Saharan Africa (SSA), for the latter, the only data source is the population-based cancer registry (PBCR). For childhood cancers, the 'Toronto Staging Guidelines' have been developed to facilitate abstraction of stage by cancer registry personnel. Although the feasibility of staging using this system has been shown, there is limited information on the accuracy of staging. METHODS: A panel of case records of six common childhood cancers was established. A total of 51 cancer registrars from 20 SSA countries staged these records, using Tier 1 of the Toronto guidelines. The stage that they assigned was compared with that decided by two expert clinicians. RESULTS: The registrars assigned the correct stage for 53%-83% of cases (71% overall), with the lowest values for acute lymphocytic leukaemia (ALL), retinoblastoma and non-Hodgkin lymphoma (NHL), and the highest for osteosarcoma (81%) and Wilms tumour (83%). For ALL and NHL, many unstageable cases were mis-staged, probably due to confusion over the rules for dealing with missing data; for the cases with adequate information, accuracy was 73%-75%. Some confusion was observed over the precise definition of three stage levels of retinoblastomas. CONCLUSIONS: A single training in staging resulted in an accuracy, for solid tumours, that was not much inferior to what has been observed in high-income settings. Nevertheless, some lessons were learned on how to improve both the guidelines and the training course.

Retinoblastoma seeds: impact on American Joint Committee on Cancer clinical staging.

AIM: To investigate whether the American Joint Committee on Cancer (AJCC) clinical category cT2b needs to be subclassified by the type and distribution of retinoblastoma (RB) seeding. METHODS: Multicentre, international registry-based data were collected from RB centres enrolled between January 2001 and December 2013. 1054 RB eyes with vitreous or subretinal seeds from 18 ophthalmic oncology centres, in 13 countries within six continents were analysed. Local treatment failure was defined as the use of secondary enucleation or external beam radiation therapy (EBRT) and was estimated with the Kaplan-Meier method. RESULTS: Clinical category cT2b included 1054 eyes. Median age at presentation was 16.0 months. Of these, 428 (40.6%) eyes were salvaged, and 430 (40.8%) were treated with primary and 196 (18.6%) with secondary enucleation. Of the 592 eyes that had complete data for globe salvage analysis, the distribution of seeds was focal in 143 (24.2%) and diffuse in 449 (75.8%). The 5-year Kaplan-Meier cumulative globe-salvage (without EBRT) was 78% and 49% for eyes with focal and diffuse RB seeding, respectively. Cox proportional hazards regression analysis confirmed a higher local treatment failure risk with diffuse seeds as compared with focal seeds (hazard rate: 2.8; p<0.001). There was insufficient evidence to prove or disprove an association between vitreous seed type and local treatment failure risk(p=0.06). CONCLUSION: This international, multicentre, registry-based analysis of RB eyes affirmed that eyes with diffuse intraocular distribution of RB seeds at diagnosis had a higher risk of local treatment failure when compared with focal seeds. Subclassification of AJCC RB category cT2b into focal vs diffuse seeds will improve prognostication for eye salvage.

Evaluation of a Health Care Worker Training Intervention to Improve the Early Diagnosis and Referral of Childhood Cancers in Ghana: A Qualitative Descriptive Study.

PURPOSE: This study sought to (1) evaluate the perceived effectiveness of an early childhood cancer warning signs and symptoms (EWSS) training intervention on health care worker (HCW) knowledge, attitudes, and clinical practice; (2) evaluate the ease of implementation of training received, including potential barriers and facilitators; and (3) provide insights into program improvements for future iterations of the intervention. METHOD: Using a qualitative descriptive study design, we conducted in-depth, semistructured interviews with 23 purposively sampled Ghanaian HCW recipients of the EWSS training intervention. We undertook iterative thematic analysis of data concurrently with interviews and used a modified version of the theoretical framework of acceptability to guide the evaluation of the training intervention. RESULTS: We identified six themes-affective attitude, burden, intervention coherence, perceived effectiveness, self-efficacy, and quality improvement-that structure participant perceptions of the effectiveness of the EWSS training. Participants generally had a positive attitude to the training intervention, found the content relatively easy to understand, and communicated the positive impacts of the training on their day-to-day practice. However, they also identified patient- and system-level challenges to the real-world implementation of intervention components, including patients' cultural and religious beliefs about illnesses, patients' financial constraints, and inadequately funded health systems. CONCLUSION: Our findings suggest that although an HCW-focused training intervention has the potential to improve timely diagnosis and referral for childhood cancers in Ghana and comparable health system contexts, complementary interventions to address patient- and system-level implementation challenges are required to translate improvements in HCW knowledge to sustained impact on health outcomes for children with cancer.

Cancer in sub-Saharan Africa: a Lancet Oncology Commission.

In sub-Saharan Africa (SSA), urgent action is needed to curb a growing crisis in cancer incidence and mortality. Without rapid interventions, data estimates show a major increase in cancer mortality from 520 348 in 2020 to about 1 million deaths per year by 2030. Here, we detail the state of cancer in SSA, recommend key actions on the basis of analysis, and highlight case studies and successful models that can be emulated, adapted, or improved across the region to reduce the growing cancer crises. Recommended actions begin with the need to develop or update national cancer control plans in each country. Plans must include childhood cancer plans, managing comorbidities such as HIV and malnutrition, a reliable and predictable supply of medication, and the provision of psychosocial, supportive, and palliative care. Plans should also engage traditional, complementary, and alternative medical practices employed by more than 80% of SSA populations and pathways to reduce missed diagnoses and late referrals. More substantial investment is needed in developing cancer registries and cancer diagnostics for core cancer tests. We show that investments in, and increased adoption of, some approaches used during the COVID-19 pandemic, such as hypofractionated radiotherapy and telehealth, can substantially increase access to cancer care in Africa, accelerate cancer prevention and control efforts, increase survival, and save billions of US dollars over the next decade. The involvement of African First Ladies in cancer prevention efforts represents one practical approach that should be amplified across SSA. Moreover, investments in workforce training are crucial to prevent millions of avoidable deaths by 2030. We present a framework that can be used to strategically plan cancer research enhancement in SSA, with investments in research that can produce a return on investment and help drive policy and effective collaborations. Expansion of universal health coverage to incorporate cancer into essential benefits packages is also vital. Implementation of the recommended actions in this Commission will be crucial for reducing the growing cancer crises in SSA and achieving political commitments to the UN Sustainable Development Goals to reduce premature mortality from non-communicable diseases by a third by 2030.

Metastatic Death Based on Presenting Features and Treatment for Advanced Intraocular Retinoblastoma: A Multicenter Registry-Based Study.

PURPOSE: To evaluate presenting features, tumor size, and treatment methods for risk of metastatic death due to advanced intraocular retinoblastoma (RB). DESIGN: International, multicenter, registry-based retrospective case series. PARTICIPANTS: A total of 1841 patients with advanced RB. METHODS: Advanced RB was defined by 8th edition American Joint Committee on Cancer (AJCC) categories cT2 and cT3 and new AJCC-Ophthalmic Oncology Task Force (OOTF) Size Groups (1: < 50% of globe volume, 2: > 50% but < 2/3, 3: > 2/3, and 4: diffuse infiltrating RB). Treatments were primary enucleation, systemic chemotherapy with secondary enucleation, and systemic chemotherapy with eye salvage. MAIN OUTCOME MEASURES: Metastatic death. RESULTS: The 5-year Kaplan-Meier cumulative survival estimates by patient-level AJCC clinical subcategories were 98% for cT2a, 96% for cT2b, 88% for cT3a, 95% for cT3b, 92% for cT3c, 84% for cT3d, and 75% for cT3e RB. Survival estimates by treatment modality were 96% for primary enucleation, 89% for systemic chemotherapy and secondary enucleation, and 90% for systemic chemotherapy with eye salvage. Risk of metastatic mortality increased with increasing cT subcategory (P < 0.001). Cox proportional hazards regression analysis confirmed a higher risk of metastatic mortality in categories cT3c (glaucoma, hazard ratio [HR], 4.9; P = 0.011), cT3d (intraocular hemorrhage, HR, 14.0; P < 0.001), and cT3e (orbital cellulitis, HR, 19.6; P < 0.001) than in category cT2a and with systemic chemotherapy with secondary enucleation (HR, 3.3; P < 0.001) and eye salvage (HR, 4.9; P < 0.001) than with primary enucleation. The 5-year Kaplan-Meier cumulative survival estimates by AJCC-OOTF Size Groups 1 to 4 were 99%, 96%, 94%, and 83%, respectively. Mortality from metastatic RB increased with increasing Size Group (P < 0.001). Cox proportional hazards regression analysis revealed that patients with Size Group 3 (HR, 10.0; P = 0.002) and 4 (HR, 41.1; P < 0.001) had a greater risk of metastatic mortality than Size Group 1. CONCLUSIONS: The AJCC-RB cT2 and cT3 subcategories and size-based AJCC-OOTF Groups 3 (> 2/3 globe volume) and 4 (diffuse infiltrating RB) provided a robust stratification of clinical risk for metastatic death in advanced intraocular RB. Primary enucleation offered the highest survival rates for patients with advanced intraocular RB.

High-risk Pathologic Features Based on Presenting Findings in Advanced Intraocular Retinoblastoma: A Multicenter, International Data-Sharing American Joint Committee on Cancer Study.

PURPOSE: To determine the value of clinical features for advanced intraocular retinoblastoma as defined by the eighth edition of the American Joint Committee on Cancer (AJCC) cT3 category and AJCC Ophthalmic Oncology Task Force (OOTF) Size Groups to predict the high-risk pathologic features. DESIGN: International, multicenter, registry-based retrospective case series. PARTICIPANTS: Eighteen ophthalmic oncology centers from 13 countries over 6 continents shared evaluations of 942 eyes enucleated as primary treatment for AJCC cT3 and, for comparison, cT2 retinoblastoma. METHODS: International, multicenter, registry-based data were pooled from patients enrolled between 2001 and 2013. High-risk pathologic features were defined as AJCC categories pT3 and pT4. In addition, AJCC OOTF Size Groups were defined as follows: (1) less than half, (2) more than half but less than two thirds, (3) more than two thirds of globe volume involved, and (4) diffuse infiltrating retinoblastoma. MAIN OUTCOME MEASURES: Statistical risk of high-risk pathologic features corresponding to AJCC cT3 subcategories and AJCC OOTF Size Groups. RESULTS: Of 942 retinoblastoma eyes treated by primary enucleation, 282 (30%) showed high-risk pathologic features. Both cT subcategories and AJCC OOTF Size Groups (P < 0.001 for both) were associated with high-risk pathologic features. On logistic regression analysis, cT3c (iris neovascularization with glaucoma), cT3d (intraocular hemorrhage), and cT3e (aseptic orbital cellulitis) were predictive factors for high-risk pathologic features when compared with cT2a with an odds ratio of 2.3 (P = 0.002), 2.5 (P = 0.002), and 3.3 (P = 0.019), respectively. Size Group 3 (more than two-thirds globe volume) and 4 (diffuse infiltrative retinoblastoma) were the best predictive factors with an odds ratio of 3.3 and 4.1 (P < 0.001 for both), respectively, for high-risk pathologic features when compared with Size Groups 1 (i.e., < 50% of globe volume). CONCLUSIONS: The AJCC retinoblastoma staging clinical cT3c-e subcategories (glaucoma, intraocular hemorrhage, and aseptic orbital cellulitis, respectively) as well as the AJCC OOTF Size Groups 3 (tumor more than two thirds of globe volume) and 4 (diffuse infiltrative retinoblastoma) both allowed stratification of clinical risk factors that can be used to predict the presence of high-risk pathologic features and thus facilitate treatment decisions.

Performance of a Histidine Rich Protein-2 Based (First Response) and a p-Lactate Dehydrogenase-based (Optimal) Rapid Diagnostic Test for Diagnosis of Malaria in Patients With Pediatric Sickle Cell Disease.

BACKGROUND: Rapid diagnostic tests (RDTs) have been extensively evaluated and play an important role in malaria diagnosis. However, the accuracy of RDTs for malaria diagnosis in patients with sickle cell disease (SCD) is unknown. METHODS: We compared the performance of a histidine rich protein 2 (HRP-2)-based RDT (First Response) and a lactate dehydrogenase (LDH)-based RDT (Optimal) with routine microscopy as reference standard in 445 children with SCD and an acute febrile illness in Accra, Ghana. RESULTS: The overall sensitivity, specificity, and positive and negative predictive values of the HRP-2-based RDTs were 100%, 95.7%, 73.8%, and 100%, respectively. Comparable values for the LDH-based RDTs were 91.7%, 99.5%, 95.7%, and 99.0%, respectively. A total of 423 results were true in both tests, 1 result was false in both tests, 16 results were false in the HRP-2 test only, and 5 were false in the LDH test only (McNemar test, P = .03). At follow-up, 73.7% (28/38), 52.6% (20/38), 48.6% (17/35), and 13.2% (5/38) of study participants were HRP-2 positive on days 14, 28, 35, and 42, respectively, compared with 0%, 2.6% (1/38), 2.9% (1/35), and 2.6% (1/38) for LDH. CONCLUSION: The HRP2-based RDT fulfilled World Health Organization criteria for malaria diagnosis in patients with SCD and may provide diagnostic evidence for treatment to begin in cases in which treatment would otherwise have begun presumptively based on symptoms, whereas LDH-based RDTs may be more suitable as a confirmatory test in low-parasitemic subgroups, such as patients with SCD.

HIV virological non-suppression and its associated factors in children on antiretroviral therapy at a major treatment centre in Southern Ghana: a cross-sectional study.

BACKGROUND: Children living with human immunodeficiency virus (HIV) infection require lifelong effective antiretroviral therapy (ART). The goal of ART in HIV-infected persons is sustained viral suppression. There is limited information on virological non-suppression or failure and its associated factors in children in resource limited countries, particularly Ghana. METHODS: A cross-sectional study of 250 children aged 8 months to 15 years who had been on ART for at least 6 months attending the Paediatric HIV clinic at Korle Bu Teaching hospital in Ghana was performed. Socio-demographic, clinical, laboratory and ART Adherence related data were collected using questionnaires as well as medical records review. Blood samples were obtained for viral load and CD4+ count determination. Viral load levels > 1000 copies/ml on ART was considered virological non-suppression. Logistic regression was used to identify factors associated with virological non-suppression. RESULTS: The mean (±SD) age of the study participants was 11.4 ± 2.4 years and the proportion of males was 53.2%. Of the 250 study participants, 96 (38.4%) had virological non-suppression. After adjustment for significant variables, the factors associated with non-suppressed viral load were female gender (AOR 2.51 [95% CI 1.04-6.07], p = 0.041), having a previous history of treatment of tuberculosis (AOR 4.95 [95% CI 1.58-15.5], p = 0.006), severe CD4 immune suppression status at study recruitment (AOR 24.93 [95% CI 4.92-126.31], p < 0.001) and being on a nevirapine (NVP) based regimen (AOR 7.93 [95% CI 1.58-1.15], p = 0.005). CONCLUSION: The prevelance of virological non-suppression was high. Virological non-suppression was associated with a previous history of TB treatment, female gender, severe CD4 immune suppression status at study recruitment and being on a NVP based regimen. Early initiation of ART and phasing out NVP-based regimen might improve viral load suppression in children. In addition, children with a history of TB may need focused measures to maximize virological suppression.

Phylogeography and resistome of pneumococcal meningitis in West Africa before and after vaccine introduction.

Despite contributing to the large disease burden in West Africa, little is known about the genomic epidemiology of Streptococcus pneumoniae which cause meningitis among children under 5 years old in the region. We analysed whole-genome sequencing data from 185 S. pneumoniae isolates recovered from suspected paediatric meningitis cases as part of the World Health Organization (WHO) invasive bacterial diseases surveillance from 2010 to 2016. The phylogeny was reconstructed, accessory genome similarity was computed and antimicrobial-resistance patterns were inferred from the genome data and compared to phenotypic resistance from disc diffusion. We studied the changes in the distribution of serotypes pre- and post-pneumococcal conjugate vaccine (PCV) introduction in the Central and Western sub-regions separately. The overall distribution of non-vaccine, PCV7 (4, 6B, 9V, 14, 18C, 19F and 23F) and additional PCV13 serotypes (1, 3, 5, 6A, 19A and 7F) did not change significantly before and after PCV introduction in the Central region (Fisher's test P value 0.27) despite an increase in the proportion of non-vaccine serotypes to 40 % (n=6) in the post-PCV introduction period compared to 21.9 % (n=14). In the Western sub-region, PCV13 serotypes were more dominant among isolates from The Gambia following the introduction of PCV7, 81 % (n=17), compared to the pre-PCV period in neighbouring Senegal, 51 % (n=27). The phylogeny illustrated the diversity of strains associated with paediatric meningitis in West Africa and highlighted the existence of phylogeographical clustering, with isolates from the same sub-region clustering and sharing similar accessory genome content. Antibiotic-resistance genotypes known to confer resistance to penicillin, chloramphenicol, co-trimoxazole and tetracycline were detected across all sub-regions. However, there was no discernible trend linking the presence of resistance genotypes with the vaccine introduction period or whether the strain was a vaccine or non-vaccine serotype. Resistance genotypes appeared to be conserved within selected sub-clades of the phylogenetic tree, suggesting clonal inheritance. Our data underscore the need for continued surveillance on the emergence of non-vaccine serotypes as well as chloramphenicol and penicillin resistance, as these antibiotics are likely still being used for empirical treatment in low-resource settings. This article contains data hosted by Microreact.

The cost-effectiveness of treating childhood cancer in 4 centers across sub-Saharan Africa.

BACKGROUND: The treatment of childhood cancer often is assumed to be costly in African settings, thereby limiting advocacy and policy efforts. The authors determined the cost and cost-effectiveness of maintaining childhood cancer centers across 4 hospitals throughout sub-Saharan Africa. METHODS: Within hospitals representing 4 countries (Kenya, Nigeria, Tanzania, and Zimbabwe), cost was determined either retrospectively or prospectively for all inputs related to operating a pediatric cancer unit (eg, laboratory costs, medications, and salaries). Cost-effectiveness was calculated based on the annual number of newly diagnosed patients, survival rates, and life expectancy. RESULTS: Cost per new diagnosis ranged from $2400 to $31,000, attributable to variances with regard to center size, case mix, drug prices, admission practices, and the treatment abandonment rate, which also affected survival. The most expensive cost input was found to be associated with medication in Kenya, and medical personnel in the other 3 centers. The cost per disability-adjusted life-year averted ranged from 0.3 to 3.6 times the per capita gross national income. Childhood cancer treatment therefore was considered to be very cost-effective by World Health Organization standards in 2 countries and cost-effective in 1 additional country. In all centers, abandonment of treatment was common; modeling exercises suggested that public funding of treatment, additional psychosocial personnel, and modifications of inpatient policies would increase survival rates while maintaining or even improving cost-effectiveness. CONCLUSIONS: Across various African countries, childhood cancer treatment units represent cost-effective interventions. Cost-effectiveness can be increased through the control of drug prices, appropriate policy environments, and decreasing the rate of treatment abandonment. These results will inform national childhood cancer strategies across Africa.

Global Retinoblastoma Treatment Outcomes: Association with National Income Level.

PURPOSE: To compare metastasis-related mortality, local treatment failure, and globe salvage after retinoblastoma in countries with different national income levels. DESIGN: International, multicenter, registry-based retrospective case series. PARTICIPANTS: Two thousand one hundred ninety patients, 18 ophthalmic oncology centers, and 13 countries on 6 continents. METHODS: Multicenter registry-based data were pooled from retinoblastoma patients enrolled between January 2001 and December 2013. Adequate data to allow American Joint Committee on Cancer staging, eighth edition, and analysis for the main outcome measures were available for 2085 patients. Each country was classified by national income level, as defined by the 2017 United Nations World Population Prospects, and included high-income countries (HICs), upper middle-income countries (UMICs), and lower middle-income countries (LMICs). Patient survival was estimated with the Kaplan-Meier method. Logistic and Cox proportional hazards regression models were used to determine associations between national income and treatment outcomes. MAIN OUTCOME MEASURES: Metastasis-related mortality and local treatment failure (defined as use of secondary enucleation or external beam radiation therapy). RESULTS: Most (60%) study patients resided in UMICs and LMICs. The global median age at diagnosis was 17.0 months and higher in UMICs (20.0 months) and LMICs (20.0 months) than HICs (14.0 months; P < 0.001). Patients in UMICs and LMICs reported higher rates of disease-specific metastasis-related mortality and local treatment failure. As compared with HICs, metastasis-related mortality was 10.3-fold higher for UMICs and 9.3-fold higher for LMICs, and the risk for local treatment failure was 2.2-fold and 1.6-fold higher, respectively (all P < 0.001). CONCLUSIONS: This international, multicenter, registry-based analysis of retinoblastoma management revealed that lower national income levels were associated with significantly higher rates of metastasis-related mortality, local treatment failure, and lower globe salvage.

Health system determinants of access to essential medicines for children with cancer in Ghana.

BACKGROUND: Evidence of the context-specific challenges related to childhood cancer drug (CCD) access is vital to improving outcomes for children with cancer in low- and middle-income countries, such as Ghana. We sought to determine the availability and cost of essential CCD in Ghana and identify the underlying determinants of access. METHODS: Our study integrated quantitative data on drug prices and availability with qualitative insights into health system and sociopolitical determinants of CCD access in Ghana. We analysed retrospective monthly price and stock data for 41 cancer and supportive care drugs on the WHO Essential Medicines List (EML) from private retail and public institutional pharmacies. Non-parametric analyses evaluated relationships between drug price and availability, and impacts of drug class and formulation on availability and procurement efficiency. We assessed the determinants of drug access through thematic analysis of policy documents and semi-structured interviews (n=21) with key health system stakeholders. RESULTS: Ghana lists only 47% of essential CCD on its National EML, revealing gaps in domestic formulary inclusion. Stock-outs occurred for 88% of essential CCD, with a 70-day median stock-out duration; 32% had median price ratios above internationally-accepted efficiency thresholds. Drugs procured inefficiently were more susceptible to stock-outs (p=0.0003). Principal determinants of drug access included: (1) lack of sociopolitical priority afforded childhood cancer and (2) the impact of policy and regulatory environments on drug affordability, availability and quality. Establishment of a population-based cancer registry, a nationally-coordinated procurement strategy for CCD, public financing for childhood cancer care and policies to control drug costs emerged as priority interventions to improve drug access in Ghana. CONCLUSION: Our study provides context-specific evidence to enable responsive policy development for efficient drug procurement and supply management in Ghana and establishes a rigorous approach to the analysis of childhood cancer drug access in similar health system settings.

Development of paediatric non-stage prognosticator guidelines for population-based cancer registries and updates to the 2014 Toronto Paediatric Cancer Stage Guidelines.

Population-based cancer registries (PBCRs) generate measures of cancer incidence and survival that are essential for cancer surveillance, research, and cancer control strategies. In 2014, the Toronto Paediatric Cancer Stage Guidelines were developed to standardise how PBCRs collect data on the stage at diagnosis for childhood cancer cases. These guidelines have been implemented in multiple jurisdictions worldwide to facilitate international comparative studies of incidence and outcome. Robust stratification by risk also requires data on key non-stage prognosticators (NSPs). Key experts and stakeholders used a modified Delphi approach to establish principles guiding paediatric cancer NSP data collection. With the use of these principles, recommendations were made on which NSPs should be collected for the major malignancies in children. The 2014 Toronto Stage Guidelines were also reviewed and updated where necessary. Wide adoption of the resultant Paediatric NSP Guidelines and updated Toronto Stage Guidelines will enhance the harmonisation and use of childhood cancer data provided by PBCRs.

A Multicenter, International Collaborative Study for American Joint Committee on Cancer Staging of Retinoblastoma: Part II: Treatment Success and Globe Salvage.

PURPOSE: To evaluate the ability of the American Joint Committee on Cancer (AJCC) 8th edition to predict local tumor control and globe salvage for children with retinoblastoma (RB). DESIGN: International, multicenter, registry-based retrospective case series. PARTICIPANTS: A total of 2854 eyes of 2097 patients from 18 ophthalmic oncology centers from 13 countries over 6 continents. METHODS: International, multicenter, registry-based data were pooled from patients enrolled between January 2001 and December 2013. All RB eyes with adequate records to allow tumor staging by the AJCC 8th edition criteria and follow-up to ascertain treatment outcomes were included. MAIN OUTCOME MEASURES: Globe-salvage rates were estimated by AJCC clinical (cTNMH) categories and tumor laterality. Local treatment failure was defined as use of enucleation or external beam radiation therapy (EBRT), with or without plaque brachytherapy or intra-arterial chemotherapy (IAC). RESULTS: Unilateral RB occurred in 1340 eyes (47%). Among the 2854 eyes, tumor categories were cT1 to cT4 in 696 eyes (24%), 1334 eyes (47%), 802 eyes (28%), and 22 eyes (1%), respectively. Of these, 1275 eyes (45%) were salvaged, and 1179 eyes (41%) and 400 eyes (14%) underwent primary and secondary enucleation, respectively. The 2- and 5-year Kaplan-Meier cumulative globe-salvage rates without the use of EBRT by cTNMH categories were 97% and 96% for category cT1a tumors, 94% and 88% for cT1b tumors, 68% and 60% for cT2a tumors, 66% and 57% for cT2b tumors, and 32% and 25% for cT3 tumors, respectively. Risk of local treatment failure increased with increasing cT category (P < 0.001). Cox proportional hazards regression analysis confirmed a higher risk of local treatment failure in categories cT1b (hazard ratio [HR], 3.5; P = 0.004), cT2a (HR, 15.1; P < 0.001), cT2b (HR, 16.4; P < 0.001), and cT3 (HR, 45.0; P < 0.001) compared with category cT1a. Use of plaque brachytherapy and IAC improved local tumor control in categories cT1a (P = 0.031) and cT1b (P < 0.001). CONCLUSIONS: Multicenter, international, internet-based data sharing validated the 8th edition AJCC RB staging to predict globe-salvage in a large, heterogeneous, real-world patient population with RB.