Outcomes of Wilms tumor therapy in Lilongwe, Malawi, 2016-2021: Successes and ongoing research priorities.

INTRODUCTION: Wilms tumor therapy in low- and middle-income countries (LMICs) relies on treatment protocols adapted to resource limitations, but these protocols have rarely been evaluated in real-world settings. Such evaluations are necessary to identify high-impact research priorities for clinical and implementation trials in LMICs. The purpose of this study was to identify highest priority targets for future clinical and implementation trials in sub-Saharan Africa by assessing outcomes of a resource-adapted treatment protocol in Malawi. METHODS: We conducted a retrospective cohort study of children treated for Wilms tumor with an adapted SIOP-backbone protocol in Lilongwe, Malawi between 2016 and 2021. Survival analysis assessed variables associated with poor outcome with high potential for future research and intervention. RESULTS: We identified 136 patients, most commonly with stage III (n = 35; 25.7%) or IV disease (n = 35; 25.7%). Two-year event-free survival (EFS) was 54% for stage I/II, 51% for stage III, and 13% for stage IV. A single patient with stage V disease survived to 1 year. Treatment abandonment occurred in 36 (26.5%) patients. Radiotherapy was indicated for 55 (40.4%), among whom three received it. Of these 55 patients, 2-year EFS was 31%. Of 14 patients with persistent metastatic pulmonary disease at the time of nephrectomy, none survived to 2 years. Notable variables independently associated with survival were severe acute malnutrition (hazard ratio [HR]: 1.9), increasing tumor stage (HR: 1.5), and vena cava involvement (HR: 3.1). CONCLUSION: High-impact targets for clinical and implementation trials in low-resource settings include treatment abandonment, late presentation, and approaches optimized for healthcare systems with persistently unavailable radiotherapy.

The Burden of Malnutrition in Childhood Cancer in Malawi - Risk Regardless of Age.

Malnutrion among children with childhood cancer in low and middle income countries (LMICs) is prevelant. While national nutrition programs focus on children under 5 years, childhood cancer can occur regardless of their age. Through a single-center retrospective cohort in Lilongwe, Malawi, we aim to characterize the burden of age-related malnutrition among children diagnosed with cancer in Lilongwe, Malawi, and evaluate them for any associations with mortality. Four hundred and sixty-three children (63.5% ≥5 years and 58.3% males) were identified.The majority of children (63.3%) were malnourished; 23.1% had moderate acute malnutrition (MAM) and 40.2% had severe acute malnutrition (SAM). Malnutrition was more common in children ≥5 years (70.0%) compared to children <5 years (51.8%); p < 0.0001. Age <5 years (HR 1.6; 95%CI 1.1-2.3, p = 0.016) and presence of sever acute malnutrition (HR 1.6, 95%CI 1.1-2.3, p = 0.012) were both associated with increased mortality risk. Acute malnutrition was highly prevalent among children with cancer above 5 years of age. This age group is not prioritized among malnutrition programs in LMICs, hence there is a direct need to include children with cancer regardless of age in national nutrition guidelines in LMICs to give them acces to adequate nutritional support.

Pediatric lymphoma patients in Malawi present with poor health-related quality of life at diagnosis and improve throughout treatment and follow-up across all Pediatric PROMIS-25 domains.

BACKGROUND: Patient-reportedoutcomes (PROs) that assess health-related quality of life (HRQoL) are increasingly important components of cancer care and research that are infrequently used in sub-Saharan Africa (SSA). METHODS: We administered the Chichewa Pediatric Patient-Reported Outcome Measurement Information System Pediatric (PROMIS)-25 at diagnosis, active treatment, and follow-up among pediatric lymphoma patients in Lilongwe, Malawi. Mean scores were calculated for the six PROMIS-25 HRQoL domains (Mobility, Anxiety, Depressive Symptoms, Fatigue, Peer Relationships, Pain Interference). Differences in HRQoL throughout treatment were compared using the minimally important difference (MID) and an ANOVA analysis. Kaplan-Meier survival estimates and Cox hazard ratios for mortality are reported. RESULTS: Seventy-five children completed PROMIS-25 surveys at diagnosis, 35 (47%) during active treatment, and 24 (32%) at follow-up. The majority of patients died (n = 37, 49%) or were lost to follow-up (n = 6, 8%). Most (n = 51, 68%) were male, median age was 10 (interquartile range [IQR] 8-12), 48/73 (66%) presented with advanced stage III/IV, 61 (81%) were diagnosed with Burkitt lymphoma and 14 (19%) Hodgkin lymphoma. At diagnosis, HRQoL was poor across all domains, except for Peer Relationships. Improvements in HRQoL during active treatment and follow-up exceeded the MID. On exploratory analysis, fair-poor PROMIS Mobility <40 and severe Pain Intensity = 10 at diagnosis were associated with increased mortality risk and worse survival, but were not statistically significant. CONCLUSIONS: Pediatric lymphoma patients in Malawi present with poor HRQoL that improves throughout treatment and survivorship. Baseline PROMIS scores may provide important prognostic information. PROs offer an opportunity to include patient voices and prioritize holistic patient-centered care in low-resource settings.

Effect of fatty acid profiles in varying recipes of ready-to-use therapeutic foods on neurodevelopmental and clinical outcomes of children (6-59 months) with severe wasting: a systematic review.

CONTEXT: In 2020, 13.6 million children under 5 years suffered from severe acute malnutrition (SAM)/wasting. Standard ready-to-use therapeutic foods (RUTFs) improve polyunsaturated fatty acid (PUFA) status but contain suboptimal amounts of omega-3 (n-3) PUFAs with unbalanced n-6-to-n-3 PUFA ratios. OBJECTIVES: The aim was to compare the effects of RUTFs with different essential fatty acid contents on PUFA status, neurodevelopmental, and clinical outcomes (mortality, comorbidities, and recovery) of children with severe wasting. DATA SOURCES: Twelve databases, trial repositories, and article references with no publication limitations. DATA EXTRACTION: Ten studies from randomized, quasi, and cluster-randomized controlled trials providing RUTFs as home treatment to children 6-59 months with SAM/wasting were included. DATA ANALYSIS: Plasma phospholipid eicosapentaenoic acid content was higher in children receiving RUTF with altered essential fatty acid contents compared with standard RUTF (0.20 [0.15-0.25], P < 0.00001). Docosahexaenoic acid (DHA) status only improved in children receiving RUTF with added fish oil (0.33 [0.15-0.50], P = 0.0003). The Malawi Developmental Assessment tool (MDAT) global development and problem-solving assessment scores were higher in global assessment and gross motor domains in children receiving added fish oil compared with standard formulation (0.19 [0.0-0.38] and 0.29 [0.03-0.55], respectively). Children receiving high-oleic-acid RUTF (lowering the n-6:n-3 PUFA ratio of the RUTF) with or without fish oil had significantly higher scores in social domains compared with those receiving the standard formulation (0.16 [0.00-0.31] and 0.24 [0.09-0.40]). Significantly higher mortality risk was found in children receiving a standard formulation compared with RUTF with a lower n-6:n-3 PUFA ratio (0.79 [0.67-0.94], P = 0.008). CONCLUSION: Although lowering n-6:n-3 PUFA ratios did not increase plasma DHA, it improved specific neurodevelopmental scores and mortality due to lower linoleic acid (high-oleic-acid peanuts), higher alpha-linolenic acid (altered oil), or both. Additional preformed n-3 long-chain PUFAs (fish oil) with RUTF improved the children's DHA status, neurodevelopmental outcomes, and weight-for-height z score. More research is needed regarding cost, availability, stability, acceptability, and the appropriate amount of n-3 long-chain PUFAs required in RUTFs for the best clinical outcomes. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42022303694.

Palliative Care Services within a Pediatric Hematology-Oncology Program in a Low-Resource Setting.

CONTEXT: Outcomes for children with cancer in sub-Saharan Africa (SAA) are dismal due to delayed diagnosis and limited access to curative therapy. When establishing a pediatric hematology-oncology (PHO) program in low-resource settings, early integration of palliative care services becomes essential. While palliative care is a human right, equitable distribution is lacking. OBJECTIVES: We aim to describe our experience establishing a palliative care program, the services offered, and the distribution of patients served. METHODS: This is a brief description of our PHO palliative care program in Lilongwe, Malawi at a tertiary care center and a three-year retrospective review of activities (2017-2020). Services offered include inpatient, outpatient, home visits, end of life care, and strengthening of referral systems. RESULTS: Over the three-year period, 315 patients were enrolled. 57% (n=179) were male. The median age was seven years (5 months-22 years). Patients served were from 17 of 28 districts within Malawi. Diagnoses of patients included 43% solid tumors (n=135), 22% lymphoma (n=68), 15% leukemia (n=47), and 21% hematologic disease (n=65). 40% of patients have died (n=125), with 53% of deaths occurring at home (n=66), 22% in the hospital (n=28), and 25% at unknown locations (n=31). CONCLUSION: Palliative care is a critical component of PHO programs worldwide. Programs must leverage existing networks to ensure optimal care to children and families. We demonstrate the feasibility of integrating palliative care services within a PHO program in a low-resource setting, which could serve as a model for other countries in SSA.

Household Air Pollution and Acute Lower Respiratory Infections in Adults: A Systematic Review.

INTRODUCTION: Household air pollution from solid fuel burning kills over 4 million people every year including half a million children from acute lower respiratory infections. Although biologically plausible, it is not clear whether household air pollution is also associated with acute lower respiratory infections in adults. We systematically reviewed the literature on household air pollution and acute lower respiratory infection in adults to identify knowledge gaps and research opportunities. METHODS: Ten bibliographic databases were searched to identify studies of household air pollution and adult acute lower respiratory infection. Data were extracted from eligible studies using standardised forms. RESULTS: From 4617 titles, 513 abstracts and 72 full-text articles were reviewed. Eight studies met the inclusion criteria of which 2 found a significant adjusted increased risk of acute lower respiratory infection, 2 identified a univariate association whilst 4 found no significant association. Study quality was generally limited. Heterogeneity in methods and findings precluded meta-analysis. DISCUSSION: A systematic review of the literature found limited evidence for an association between household air pollution and risk of acute lower respiratory infection in adults. Additional research, with carefully defined exposure and outcome measures, is required to complete the risk profile caused by household air pollution in adults. REGISTRATION NUMBER: CRD42015028042.

Cancer survival in Malawi: a retrospective cohort study.

INTRODUCTION: Cancer is a leading cause of morbidity and mortality worldwide with the burden in sub-Saharan Africa projected to double by year 2030 from 715,000 new cases and 542,000 deaths in 2008. However, cancer survival data to inform interventions for early detection, diagnosis and treatment are lacking. METHODS: Cancer survival analysis was conducted on 842 cancer patients registered and followed-up from 2006 to 2013 at NdiMoyo Palliative Care Centre in Salima District, central Malawi. Cancer survival was measured from the time of diagnosis. RESULTS: In both sexes, the common types of cancer were; Kaposi's sarcoma (KS) (48.0%), cervical cancer (21.1%), cancer of oesophagus (14.8%), liver cancer (3.1%) and breast cancer (2.5%). In Males; KS, cancer of the oesophagus, cancer of the liver, bone cancer and non-Hodgkin's lymphoma were the commonest accounting for 67.4%, 19.4%, 3.9%, 1.0% and 1.0% respectively. In females; cancer of the cervix, KS, cancer of the oesophagus, cancer of the breast and cancer of the liver were the top five cancers accounting for 41.6%, 29.2%, 10.3%, 4.9% and 2.3% respectively. Of the 830 cancer patients with complete 5-year follow-up data, the overall median survival time was 9 months. Absolute survival rates at 1, 2, 3, 4 and 5 years or more were 31.8%, 18.0%, 12.5%, 7.8% and 6.0% respectively. The survival rates for top five cancers at 1, 2, 3, and 4 years or more were; KS (n= 397): 47.1%, 30.2%, 21.4% and 13.1%; cancer of the cervix (n = 174): 31.0%, 10.3%, 5.2% and 2.9%; cancer of the oesophagus (n = 124): 4.0%, 2.4%, 1.6% and 1.6%; liver cancer (n = 26): 19.2%, 3.8%, 3.8% and 3.8% and breast cancer (n = 21): 9.5%, 0%, 0%, 0% respectively. The risk of death was high in females than males, in those aged 50 years or more than in those aged less than 50 (p < 0.05). CONCLUSION: This study demonstrated that cancer survival from the time of diagnosis in Malawi was poor with median survival time of about 9 months and only 6% of patients survived for 5 years or more. Improvement of early detection, diagnostic capability, access to treatment and palliative care services could improve cancer survival.