Wilms tumor treatment protocol compliance and the influence on outcomes for children in Tanzania.

BACKGROUND: Standardized Wilms tumor treatment protocols exist for low- and middle-income countries, but outcomes equivalent to high-income countries are not achieved outside of clinical trials. As Wilms tumor treatment protocols in Africa shift with increasing resource capacity, it is not known how treatment compliance to each stage of therapy affects outcomes and where the critical breakpoints are for protocol adherence in clinical practice. PROCEDURE: We describe both treatment outcomes and treatment protocol adherence in a retrospective single-center cohort study of pediatric Wilms tumor patients at a zonal cancer referral hospital in Tanzania from 2016 to 2019, treated per the International Society of Paediatric Oncology standard (2016-2017) or Tanzania adapted (2018-2019) therapy protocols. RESULTS: A total of 69 patients were evaluated. The two-year overall survival and event-free survival rates were 40% and 29%, respectively. Only 29% of patients completed recommended chemotherapy per protocol, and completion of preoperative and postoperative chemotherapy was predictive of two-year overall survival (odds ratio [OR] 14.4, p < .001). There were delays at almost every stage of treatment, especially time from preoperative chemotherapy to surgery (56 days), from surgery to pathology report (30 days), and from surgery to initiation of postoperative chemotherapy (38 days). CONCLUSIONS: Nonadherence with recommended Wilms tumor treatment guidelines due to key health system delays correlated to reduced overall survival rates, with chemotherapy nonadherence due to abandonment, lack of surgery, and deaths on therapy as the strongest contributors. Future interventions targeting health system delays and reducing deaths during therapy are critical to improving protocol compliance and increasing overall survival for pediatric Wilms tumor patients in low-resource settings.

Stroke Prevention with Hydroxyurea Enabled through Research and Education: A Phase 2 Primary Stroke Prevention Trial in Sub-Saharan Africa.

INTRODUCTION: Stroke is a severe complication of sickle cell anemia (SCA), with devastating sequelae. Transcranial Doppler (TCD) ultrasonography predicts stroke risk, but implementing TCD screening with suitable treatment for primary stroke prevention in low-resource environments remains challenging. SPHERE (NCT03948867) is a prospective phase 2 open-label hydroxyurea trial for SCA in Tanzania. METHODS: After formal training and certification, local personnel screened children 2-16 years old; those with conditional (170-199 cm/s) or abnormal (≥200 cm/s) time-averaged mean velocities (TAMVs) received hydroxyurea at 20 mg/kg/day with dose escalation to maximum tolerated dose (MTD). The primary study endpoint is change in TAMV after 12 months of hydroxyurea; secondary endpoints include SCA-related clinical events, splenic volume and function, renal function, infections, hydroxyurea pharmacokinetics, and genetic modifiers. RESULTS: Between April 2019 and April 2020, 202 children (average 6.8 ± 3.5 years, 53% female) enrolled and underwent TCD screening; 196 were deemed eligible by DNA testing. Most had numerous previous hospitalizations and transfusions, with low baseline hemoglobin (7.7 ± 1.1 g/dL) and %HbF (9.3 ± 5.4%). Palpable splenomegaly was present at enrollment in 49 (25%); average sonographic splenic volume was 103 mL (range 8-1,045 mL). TCD screening identified 22% conditional and 2% abnormal velocities, with hydroxyurea treatment initiated in 96% (45/47) eligible children. CONCLUSION: SPHERE has built local capacity with high-quality research infrastructure and TCD screening for SCA in Tanzania. Fully enrolled participants have a high prevalence of elevated baseline TCD velocities and splenomegaly. SPHERE will prospectively determine the benefits of hydroxyurea at MTD for primary stroke prevention, anticipating expanded access to hydroxyurea treatment across Tanzania.