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

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

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

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

Safety, efficacy, and affordability of ABVD for Hodgkin lymphoma in Malawi: a prospective cohort study.

Background: ABVD (doxorubicin, bleomycin, vinblastine, and dexamethasone) is a proven, curative regimen for Hodgkin lymphoma (HL). Prospective data describing HL treatment in sub-Saharan Africa are limited. We aimed to fill this knowledge gap, using data from Malawi. Methods: We report a prospective observational cohort of HL (aged ≥ 15) from a single, tertiary referral centre in Malawi. We enrolled patients with pathologicially confirmed Hodgkin lymphoma between June 1, 2013, and Dec 31, 2021 with follow-up censored on May 31, 2022. Patients were treated with ABVD and concurrent antiretroviral therapy if HIV-positive and were followed up for 5 years. The primary outcome was overall survival; secondary outcomes included progression-free survival, response assessment, and adverse events. Microcosting of HL diagnosis, treatment, and follow-up was embedded. Findings: We enrolled 38 patients with a median age of 27 years (interquartile range 19-46); eleven (28%) were HIV-positive. Of 35 patients treated with ABVD, 24 (71%) had stage III/IV, nine (26%) unfavourable limited stage, and two (6%) favourable limited stage. Among HIV-infected individuals, mean CD4 count at HL diagnosis was 179 cells/uL and ten (91%) had HIV RNA < 400 copies/mL. Grade 3/4 neutropenia occurred in 24 (68%) patients and caused treatment delay in 16 (46%). Of ten deaths, seven were due to HL, two possible treatment-related toxicity, and one uncertain. 2-year overall survival was 82% (95% CI 70-96%) and 2-year progression-free survival was 64% (95% CI 50-83%). PFS appeared better for HIV-positive patients (HR 0.23 (95% CI 0.05-1.02)) after controlling for stage and performance status (p = 0.05). We estimated $2708 (2022 USD) for HL diagnosis, treatment, and follow-up in our cohort. Interpretation: Our findings suggest that treatment with ABVD is safe, efficacious, and affordable for HL in Malawi. Outcomes are worse than in high-income countries due to HL progression. Future studies are needed to understand outcome inequities and to assess efficacy of therapies for patients with relapsed or refractory HL in Malawi. Funding: National Institutes of Health, Lineberger Comprehensive Cancer Center.

Effectiveness of an intervention to increase uptake of voluntary medical male circumcision among men with sexually transmitted infections in Malawi: a preinterventional and postinterventional study.

OBJECTIVE: To evaluate the effect a multistrategy demand-creation and linkage intervention on voluntary medical male circumcision (VMMC) uptake, time to VMMC and predictors of VMMC uptake among men with sexually transmitted infections (STIs). DESIGN: Pragmatic preinterventional and postinterventional quasi-experimental study combined with a prospective observational design. SETTING: A public and specialised STI clinic in Lilongwe, Malawi. POPULATION: Uncircumcised men who presented to the STI clinic. METHODS AND INTERVENTION: The intervention consisted of transport reimbursement ('R'), intensified health education ('I') and short-messaging services/telephonic tracing ('Te'), abbreviated (RITe). A preintervention phase was conducted at baseline while RITe was rolled-out in the intervention phase in a sequential manner called implementation blocks: 'I' only-block 1; 'I+Te'-block 2 and RITe-block 3. MAIN OUTCOME MEASURES: Primary: VMMC uptake and time to VMMC for the full intervention and for each block. Secondary: predictors of VMMC uptake. RESULTS: A total of 2230 uncircumcised men presented to the STI clinic. The mean age was 29 years (SD±9), 58% were married/cohabiting, HIV prevalence was 6.4% and 43% had urethral discharge. Compared with standard of care (8/514, 1.6%), uptake increased by 100% during the intervention period (55/1716, 3.2%) (p=0.048). 'I' (25/731, 113%, p=0.044) and RITe (17/477, 125%, p=0.044) significantly increased VMMC uptake. The median time to VMMC was shorter during the intervention period (6 days, IQR: 0, 13) compared with standard of care (15 days, IQR: 9, 18). There was no significant incremental effect on VMMC uptake and time to VMMC between blocks. Men with genital warts were 18 times more likely to receive VMMC (adjusted relative risk=18.74, 95% CI: 2.041 to 172.453). CONCLUSIONS: Our intervention addressing barriers to VMMC improved VMMC uptake and time to VMMC among uncircumcised men with STIs, an important subpopulation for VMMC prioritisation. TRIAL REGISTRATION NUMBER: NCT04677374.

A prospective cohort study identifies two types of HIV+ Kaposi Sarcoma lesions: proliferative and inflammatory.

Kaposi sarcoma (KS) is the most common cancer in people living with HIV (PLWH) in many countries where KS-associated herpesvirus is endemic. Treatment has changed little in 20 years, but the disease presentation has. This prospective cohort study enrolled 122 human immunodeficiency virus (HIV) positive KS patients between 2017 and 2019 in Malawi. Participants were treated with bleomycin, vincristine and combination antiretroviral therapy, the local standard of care. One-year overall survival was 61%, and progression-free survival was 58%. The 48-week complete response rate was 35%. RNAseq (n = 78) differentiated two types of KS lesions, those with marked endothelial characteristics and those enriched in inflammatory transcripts. This suggests that different KS lesions are in different disease states consistent with the known heterogeneous clinical response to treatment. In contrast to earlier cohorts, the plasma HIV viral load of KS patients in our study was highly variable. A total of 25% of participants had no detectable HIV; all had detectable KSHV viral load. Our study affirms that many KS cases today develop in PLWH with well-controlled HIV infection and that different KS lesions have differing molecular compositions. Further studies are needed to develop predictive biomarkers for this disease.

Comparison of baseline lymphoma and HIV characteristics in Malawi before and after implementation of universal antiretroviral therapy.

Access to antiretroviral therapy (ART) led to epidemiological changes in human immunodeficiency virus (HIV) associated lymphoma in high-income countries such as reductions in diffuse large B-cell lymphoma (DLBCL) and stable or increased Hodgkin lymphoma (HL) and Burkitt lymphoma (BL). In 2016, Malawi implemented a universal ART (UART) policy, expanding ART eligibility to all persons living with HIV (PLWH). We compare the distribution of lymphoma subtypes and baseline HIV and prognostic characteristics for lymphoma patients in Malawi before and after implementation of UART. We enrolled patients with pathologically confirmed incident lymphoproliferative disorders into a observational clinical cohort. At diagnosis, a comprehensive clinicopathological evaluation was performed. Of 412 participants, 156 (38%) were pre-UART (2013-June 2016) and 256 (62%) post-UART (July 2016-2020). HIV prevalence was 50% in both groups. The most common pre-UART diagnoses were DLBCL [75 (48%)], low-grade non-Hodgkin lymphoma (NHL) [19 (12%)], HL [17 (11%)] and, BL [13 (8%)]. For post-UART they were DLBCL [111 (43%)], NHL [28 (11%)], BL [27 11%)] and, HL [20 (8%)]. Among PLWH, 44 (57%) pre-UART initiated ART prior to lymphoma diagnosis compared to 99 (78%) post-UART (p = 0.02). HIV-ribonucleic acid was suppressed <1000 copies/mL in 56% (33/59) pre-UART and 71% (73/103) post-UART (p = 0.05). CD4 T-cell counts were similar for both groups. We observed similar findings in the subset of participants with DLBCL. Overall, there were no significant changes in incident lymphoma subtypes (p = 0.61) after implementation of UART, but HIV was better controlled. Emerging trends bear monitoring and may have implications for prognosis and health system priority setting. Trial registration: ClinicalTrials.gov identifier: NCT02835911.

Outcomes and prognostic factors for women with breast cancer in Malawi.

BACKGROUND: Breast cancer incidence in sub-Saharan Africa (SSA) is increasing, and SSA has the highest age-standardized breast cancer mortality rate worldwide. However, high-quality breast cancer data are limited in SSA. MATERIALS AND METHODS: We examined breast cancer patient and tumor characteristics among women in Lilongwe, Malawi and evaluated risk factor associations with patient outcomes. We consecutively enrolled 100 women ≥ 18 years with newly diagnosed, pathologically confirmed breast cancer into a prospective longitudinal cohort with systematically assessed demographic data, HIV status, and clinical characteristics. Tumor subtypes were further determined by immunohistochemistry, overall survival (OS) was estimated using Kaplan-Meier methods, and hazards ratios (HR) were calculated by Cox proportional hazard analyses. RESULTS: Of the 100 participants, median age was 49 years, 19 were HIV-positive, and 75 presented with late stage (III/IV) disease. HER2-enriched and triple-negative/basal-like subtypes represented 17% and 25% tumors, respectively. One-year OS for the cohort was 74% (95% CI 62-83%). Multivariable analyses revealed mortality was associated with HIV (HR, 5.15; 95% CI 1.58-16.76; p = 0.006), stage IV disease (HR, 8.86; 95% CI 1.07-73.25; p = 0.043), and HER2-enriched (HR, 7.46; 95% CI 1.21-46.07; p = 0.031), and triple-negative subtypes (HR, 7.80; 95% CI 1.39-43.69; p = 0.020). CONCLUSION: Late stage presentation, HER2-enriched and triple-negative subtypes, and HIV coinfection were overrepresented in our cohort relative to resource-rich settings and were associated with mortality. These findings highlight robust opportunities for population- and patient-level interventions across the entire cascade of care to improve breast cancer outcomes in low-income countries in SSA.