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.

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.

A retrospective evaluation of the presentation, prognostic factors and outcomes of neuroblastoma in Ugandan children.

Neuroblastoma (NB) is the most common extracranial solid tumor of childhood. The complete burden and outcomes in Uganda are unknown. The study was a multicenter retrospective chart review of children aged between 0 to 15 years diagnosed with NB from 2010 to 2020. Demographic, clinical and tumor-related characteristics were extracted for analysis. Kaplan-Meier survival curves and Cox regression models were used to determine the one-year overall survival (OS) and identify prognostic factors. Seventy-five patients were evaluated, with a median age at diagnosis of 48 months (IQR 26-108 months). Fever (74.7%), weight loss (74.7%), high blood pressure (70.3%) and abdominal swelling/mass (65.3%) were the most common features at diagnosis. Suprarenal tumors (52%) and stage 4 disease (70.7%) were also common. The one-year OS was 60.0% (95%CI 56.8%; 64.3%) with a median survival time of 12.6 months (95% CI: 8.1; 20.8). The one-year OS for non-metastatic and metastatic disease was 67.3% and 42.6% (p = 0.11) respectively. Leukocytosis (p < 0.001) at diagnosis was of prognostic significance while clinical remission after induction chemotherapy (p < 0.001) provided survival advantages. Children who received maintenance chemotherapy had a longer median survival time of 38.5 months (range 10.8-69.5). Age (p = 0.001), lung metastasis (p < 0.001), and leukocytosis (p < 0.001) remained significant on multivariate analysis. In this Ugandan study, leukocytosis was a clinical predictor of prognosis, metastatic disease had management challenges and maintenance chemotherapy prolonged the survival time but not OS.

Ugandan children diagnosed with neuroblastoma present with advanced disease.Surgery and radiotherapy are under-utilized in the management of neuroblastoma, but have prognostic value in neuroblastoma outcomes.Children under the age of 12 months are under-diagnosed in Uganda, but those that do present for treatment fare poorer than older age groups.The overall survival is poor but the survival time can be increased with maintenance chemotherapy.

Frequency, severity, and factors associated with clinically significant drug-drug interactions among patients with cancer attending Mbarara Regional Referral Hospital Cancer Unit, Uganda.

BACKGROUND: Cancer is a major public health problem with pharmacotherapy being the cornerstone of its management. Cancer patients receive multiple drugs concurrently risking Drug-Drug Interactions (DDIs). DDIs, though avoidable, can significantly contribute to morbidity, mortality, and increased healthcare costs in this population of patients. Currently, there is no published study from Uganda on clinically significant DDIs (cs-DDIs) among cancer patients. This study identifies frequency, severity, and factors associated with cs-DDIs at Mbarara Regional Referral Hospital Cancer Unit (MRRHCU). METHOD: A cross-sectional study was conducted among 300 cancer patients receiving chemotherapy from a tertiary care hospital in western Uganda from January-February 2022. A questionnaire and data collection form were used to collect patient data. Lexicomp® Drug interaction software was used to screen the patient drug information for DDIs and assess their severity. Predictors of DDIs were identified using logistic regression using SPSS (Statistical Package for Social Sciences). RESULT: Three hundred participants were enrolled with a mean age of 48 ± 23.3 years. One hundred eighty-one patients experienced 495 cs-DDIs; with a mean of 1.7 ± 2.2. The prevalence of cs-DDI was 60.3% (55.0-66.0% at 95% CI). Digestive organ neoplasms were the most commonly (80, 26.7%) diagnosed category, and 'plant alkaloids and other natural products were the most frequently (143, 47.7%) used chemotherapeutic drug classes. About three-quarters of cs-DDIs were rated as category C risk (367, 74.1%) whereas over two-thirds (355, 71.7%) were moderate in severity.. Being female (aOR = 2.43 [1.23-4.48 at 95% CI]; P-value = 0.011) and use of ≥ 6 drugs concurrently (aOR = 18.82 [9.58-36.95 at 95% CI]; P-value < 0.001)) were significantly associated with cs-DDIs. CONCLUSION: More than half of the participants experienced at-least one cs-DDI which is generally higher than what was reported in high-income settings. About three-quarters were category C and moderate in severity, and require enhanced monitoring for safety and treatment outcome. Being female and using ≥ 6 drugs were significantly associated with cs-DDIs.

"Money was the problem": Caregivers' self-reported reasons for abandoning their children's cancer treatment in southwest Uganda.

INTRODUCTION: Treatment abandonment contributes significantly to poor survival of children with cancer in low- and middle-income countries (LMIC). In order to inform an approach to this problem, we investigated why caregivers withdraw their children from treatment. METHODS: In a qualitative study, carried out in October and November 2020, in-depth interviews were conducted with caregivers of children who had abandoned cancer treatment at the Pediatric Cancer Unit of Mbarara Regional Referral Hospital in south-western Uganda. Recorded in-depth interviews were transcribed and analyzed to identify themes of caregivers' self-reported reasons for treatment abandonment. The study was approved by the Review and Ethics Committee of Mbarara University of Science and Technology. RESULTS: Seventy-seven out of 343 (22.4%) children diagnosed with cancer abandoned treatment during the study period; 20 contactable and consenting caregivers participated in the study. The median age of the caregivers was 37 years and most (65%) were mothers. At the time of this study, eight (40%) children were alive and five (62.5%) were males; with a median age of 6.5 years. Financial difficulty, other obligations, the child falsely appearing cured, preference for alternative treatments, belief that cancer was incurable, fear that the child's death was imminent and chemotherapy side effects were the caregivers' reasons for treatment abandonment. CONCLUSIONS AND RECOMMENDATION: Seeking cancer treatment for children in Uganda is an expensive venture and treatment abandonment is mainly caused by caregivers' difficult socio-economic circumstances. This problem needs to be approached with empathy and support rather than blame.

Understanding the role of age in HIV disclosure rates and patterns for HIV-infected children in southwestern Uganda.

Highly active antiretroviral therapy has enabled HIV-infected children to survive into adolescence and adulthood, creating need for their own HIV diagnosis disclosure. Disclosure has numerous social and medical benefits for the child and family; however, disclosure rates tend to be low, especially in developing countries, and further understanding of the barriers is needed. This study describes the patterns and correlates of disclosure among HIV-infected children in southwestern Uganda. A cross-sectional study was conducted in a referral hospital pediatric HIV clinic between February and April 2012. Interviews were administered to caregivers of HIV-infected children aged 5-17 years. Data collected included socio-demographic characteristics of the child and caregiver, reported disclosure status, and caregivers' reasons for full disclosure or non-full disclosure of HIV status to their children. Bivariate and multivariate analysis was done to establish the socio-demographic correlates of disclosure. Caregivers provided data for 307 children; the median age was eight years (interquartile range [IQR] 7-11) and 52% were males. Ninety-five (31%) children had received full disclosure (48% of whom were >12 years), 22 children (7%) had received partial disclosure, 39 (13%) misinformation, and 151 (49%) no disclosure. Full disclosure was significantly more prevalent among the 9-11 and 12- to 17-year-olds compared to 5- to 8-year-olds (p-value < 0.001). The most frequently stated reason for disclosure was the hope that disclosure would improve medication adherence; the most frequently stated reason for nondisclosure was the belief that the child was too young to understand his/her illness. There was an inverse relationship between age and full disclosure and partial disclosure was rare across all age groups, suggesting a pattern of rapid, late disclosure. Disclosure programs should emphasize the importance of gradual disclosure, starting at younger ages, to maximize the benefits to the child and caregiver.

High Expression of WT1 and Low Expression of p53 in Archived Blocks of Children with Wilms Tumor in South Western Uganda.

Purpose: The determination of the presence or absence of anaplasia in Wilms tumor is difficult sometimes creating diagnostic errors and is worsened by the use of neoadjuvant chemotherapy, which causes cellular alterations that may mimic anaplasia. This study described the histological features of Wilms tumor and their association with WT1 and p53 expression in archived specimens in South Western Uganda. Patients and Methods: A series of 308 formalin-fixed paraffin-embedded tissue blocks belonging to 85 children were retrospectively recruited in the only public Histopathology laboratory in South Western Uganda. Rabbit monoclonal Anti-Wilms tumor protein antibody [(CAN-R9) IHC-56-2] ab89901 and rabbit monoclonal Anti-p53 antibody [E26] ab32389 were used to assess the expression of WT1 and p53, respectively. The expression of WT1 and p53 were reported as proportions, Chi-square was also performed to assess for associations and statistical significance was considered when the p-value was less than 0.05. Results: The median age was 3.5 with an interquartile range of (2-6) years. Mixed histology was the most common at 35.29% (95% CI:25.77-46.14). Anaplasia was present in 5.88% (95% CI:2.44-13.52) of the specimens. p53 and WT1 expressions were 13.0% (95% CI:7.25-22.04), and 41.0% (95% CI: 31.11-52.04), respectively. Conclusion: Mixed-type histology is the most common histologic feature of Wilms tumor with high expression of WT1 and a low expression of p53 implying that these can be used routinely to confirm the diagnosis as well as anaplasia in South Western Uganda.

Prevalence and Risk Factors of Nephrotoxicity Among Adult Cancer Patients at Mbarara Regional Referral Hospital.

BACKGROUND: Nephrotoxicity is common among cancer patients, yet some anti-cancer drugs, for example, platinum derivatives, are nephrotoxic and have narrow therapeutic indices. If nephrotoxicity is not managed, it can progress to kidney injury, which results in unregulated blood pressure, hormonal imbalance, electrolyte imbalance, body fluid imbalance and death. However, the burden of nephrotoxicity among adult cancer patients in Uganda is not documented in the literature. OBJECTIVE: This study assessed the prevalence and risk factors of nephrotoxicity among cancer patients receiving chemotherapy at Mbarara Regional Referral Hospital Cancer Unit (MRRHCU). METHODS: The study was a cross-sectional study carried out at the MRRHCU, Uganda. All the 206 adult cancer patients who received at least three cycles of chemotherapy and fulfilled the inclusion criteria were included. A data collection form was used to collect data, which was recorded into Microsoft Excel version 2013. Data were analyzed using Stata version 12.1. RESULTS: Of the 206 participants, 74 (35.9%) developed nephrotoxicity with majority in stage 1 (n = 83, 40.3%) and stage 2 (n = 55, 26.7%). In the multivariate logistic regression of risk factors for nephrotoxicity, age >50 years old (aOR: 1.80, 95% CI: 1.06, 1.91; p > 0.001), hypertension (aOR: 1.71, 95% CI: 1.74, 1.94; p = 0.011) and use of platinum agents (aOR: 2.04, 95% CI: 1.82, 3.34; p = 0.002) were significant independent risk factors of nephrotoxicity. CONCLUSION: About one-third (1/3) of the adult cancer patients at MRRHCU develop nephrotoxicity, which indicates a high burden of nephrotoxicity. The prevention of progression of nephrotoxicity from grades 0, 1 or 2 to grade 3 or 4 is therefore necessary, especially among the patients with risk factors, such as hypertension and age >50 years old and use of platinum agents.