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Purpose: The objective of this study is to document the prevalence of traditional, complementary, and alternative medicine (TCAM) use by adult cancer patients at a national teaching hospital in Malawi. We aim to document the products/therapies used, the reason for use, as well as patient-reported satisfaction with TCAM practitioners and modalities., Methods: We conducted investigator-administered interviews with adult cancer patients presenting to the Kamuzu Central Hospital (KCH) Cancer Clinic in Lilongwe, Malawi between January and July 2018. The KCH is a national teaching hospital in the capital of Lilongwe, which serves patients with cancer from the northern half of Malawi. Descriptive statistics were used to describe TCAM use and logistic regression was applied to identify predictors of TCAM., Results: A total of 263 participants completed the survey, of which 70% (n = 183) were female and average age was 45 (SD 14) years old. The prevalence of overall TCAM use was 84% (n = 222), and 60% (n = 157) of participants reported combining TCAM with conventional cancer treatment. The majority of patients used TCAM to directly treat their cancer versus for symptom management. Patients reported using faith-based healing (64%, n = 168), herbal medicine (56%, n = 148), diet change (46%, n = 120), and vitamins/minerals (23%, n = 61). Participants reported the highest satisfaction for physicians among practitioners and diet change for modalities. Female gender was found to be a predictor of TCAM with conventional treatment use, no other significant predictors were observed., Conclusion: There is a high prevalence of TCAM use among an adult population with cancer in Malawi, and a wide variety in the TCAM modalities used among patients. Additional studies are needed to identify risks and benefits of TCAM use to assist with policy and public health, patient safety, and holistically address the global burden of cancer., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Purpose: There are limited data on treatment and outcomes for acute lymphoblastic leukemia (ALL) among adolescents and young adults in sub-Saharan Africa. We describe a prospective observational cohort in Malawi., Methods: Patients age 15-39 years with newly diagnosed ALL at Kamuzu Central Hospital, Malawi, were enrolled from 2013 to 2019; follow-up was censored on December 2020. ALL diagnosis was confirmed on-site using immunohistochemistry and telepathology consultation involving pathologists in Malawi and the United States. All but four patients were treated with a modified pediatric-inspired regimen (Cancer and Leukemia Group B 10403 protocol). Key modifications included omission of asparaginase and no dose escalation for methotrexate., Results: Of 19 participants, the median age was 22 (range 15-36) years. Of the 15 patients who initiated treatment, 11 (73%) achieved remission after induction, one (7%) died during induction, two (13%) had refractory disease, and one (7%) absconded. No patients were lost to follow-up. Eventually, 10 of 11 patients (91%) with confirmed remission relapsed. The median duration of first remission was 10 (range 3-22) months. Twelve of 15 treated patients (80%) had died at the time of censoring. Among treated patients, the 12- and 24-month overall survival was 50% (95% CI, 23 to 72) and 17% (95% CI, 3 to 42), respectively. CNS involvement was associated with worse survival., Conclusion: It is possible to treat adolescents and young adults with ALL in low-resource settings using a low-cost, pediatric-inspired regimen; however, outcomes are poor. Both cost and limitations in supportive care infrastructure limit intensive cytotoxic approaches such as asparaginase. Patient-reported outcomes are needed to understand the quality of life and cost-effectiveness. Critically, innovative, leap-frog therapies, such as monoclonal or bispecific antibodies, and feasible economic models for resource-limited settings are urgently needed.

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., (© 2021 Wiley Periodicals LLC.)

Background: There are no clinical trials involving patients with diffuse large B-cell lymphoma (DLBCL) in sub-Saharan Africa since antiretroviral therapy (ART) for HIV became widely available in this region. We aimed to establish the safety and efficacy of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in patients with DLBCL in Malawi., Methods: This prospective, single-arm, non-randomised phase 1/2 clinical trial was done at Kamuzu Central Hospital Cancer Clinic (Lilongwe, Malawi). Eligible patients were adults (aged 18-60 years) with newly diagnosed DLBCL, an Eastern Cooperative Oncology Group performance status of 0-2, a CD4 count of 100 cells per μL or higher (if HIV-positive), measurable disease by physical examination, an absolute neutrophil count of 1000 × 10 9 cells per L or higher, a platelet count of 100 × 10 9 platelets per L or higher, a serum creatinine concentration of 132·60 μmol/L or less, a total bilirubin concentration of 34·21 μmol/L or less, a negative urine pregnancy test in women of childbearing potential, and no previous cytotoxic therapy. Pregnant or breastfeeding women, and individuals with CNS involvement from DLBCL, chronic hepatitis B infection (unless they were receiving tenofovir plus lamivudine), or any other comorbidities that would compromise the protocol objectives were excluded. Eligible patients received intravenous rituximab 375 mg/m 2 , cyclophosphamide 750 mg/m 2 , doxorubicin 50 mg/m 2 , and vincristine 1·4 mg/m 2 (maximum 2 mg/m 2 ), and oral prednisone 100 mg or an equivalent drug every 21 days for up to six cycles. HIV-positive patients received concurrent ART. The primary outcome was the proportion of patients with National Cancer Institute Common Terminology Criteria for Adverse Events grade 3 or 4 non-haematological toxic effects or treatment-related deaths after six cycles of treatment. Secondary efficacy outcomes included the proportion of patients with a complete response after six cycles of treatment, and progression-free survival and overall survival at 12 months and 24 months. This trial is registered with ClinicalTrials.gov, NCT02660710., Findings: Between Aug 1, 2016, and July 31, 2019, 76 patients were screened, of whom 37 were eligible for the study and received R-CHOP. The median age of patients was 44 years (IQR 39-49) and 16 (43%) were women. Of all 37 patients, 20 (54%) had stage III or IV DLBCL, and the age-adjusted international prognostic index was 2 or higher in 25 (68%) patients. 27 (73%) patients were HIV-positive, with a median CD4 count of 208 cells per μL (IQR 144-422), and 21 (78%) patients were receiving ART at enrolment. Patients completed a median of six cycles (IQR 4-6). Grade 3 or 4 non-haematological toxic effects were reported in 12 (32% [95% CI 19-49]) patients, the most common of which was infection (nine [24%] patients). Of 16 (43%) deaths, ten were due to progression of DLBCL, four were due to treatment-related complications, and two were due to other causes, yielding a treatment-related mortality of 11% (95% CI 4-26%). Grade 3 or 4 neutropenia was observed in 26 (70%) patients, and grade 3 or 4 anaemia was observed in 11 (29%) patients. A total of 22 (59%) patients had a complete response. Overall survival was 68% (95% CI 50-80) at 12 months and 55% (37-70) at 24 months, and progression-free survival was 59% (42-73) at 12 months and 53% (35-68) at 24 months., Interpretation: R-CHOP could be feasible, safe, and efficacious in patients with DLBCL in Malawi. This is the first completed clinical trial on DLBCL focused on sub-Saharan African populations. Given the paucity of data on treatment of DLBCL from this region, these results could inform emerging cancer treatment programmes in sub-Saharan Africa., Funding: The University of North Carolina Lineberger Comprehensive Cancer Center., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Cancer outcomes in sub-Saharan Africa (SSA) remain suboptimal, in part due to poor patient retention. Many patients travel long distances to receive care, and transportation costs are often prohibitively expensive. These are well-known and established causes of delayed treatment and care abandonment in Malawi and across SSA., Methods: We sent visit reminder texts and offered upfront money to cover transportation costs through a mobile money transfer (MMT) platform to lymphoma patients enrolled in a prospective cohort in Malawi. The primary aim was to test the feasibility of upfront MMTs., Results: We sent 1034 visit reminder texts to 189 participating patients. Of these texts, 614 (59%) were successfully delivered, with 536 (52%) responses. 320/536 (60%) MMTs were sent to interested patients and 312/320 (98%) came to their appointment on time. Of 189 total patients, 120 (63%) were reached via text and 84 (44%) received MMTs a median of three times (IQR 2-5). Median age of reachable patients was 41 (IQR 30-50), 75 (63%) were male, 62 (52%) were HIV+ and 79 (66%) resided outside of Lilongwe., Conclusion: MMTs were a feasible way to cover upfront transportation costs for patients reachable via text, however many of our patients were unreachable. Future studies exploring barriers to care, particularly among unreachable patients, may help improve the efficacy of MMT initiatives and guide retention strategies throughout SSA., (© The Author(s) 2020. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

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.

Plasma Epstein-Barr virus (EBV) DNA measurement has established prognostic utility in EBV-driven lymphomas, where it serves as a circulating tumor DNA marker. The value of plasma EBV measurement may be amplified in sub-Saharan Africa (SSA), where advanced imaging and molecular technologies for risk stratification are not typically available. However, its utility in diffuse large B-cell lymphoma (DLBCL) is less certain, given that only a subset of DLBCLs are EBV-positive. To explore this possibility, we measured plasma EBV DNA at diagnosis in a cohort of patients with DLBCL in Malawi. High plasma EBV DNA at diagnosis (≥3.0 log 10 copies/mL) was associated with decreased overall survival (OS) (P = .048). When stratified by HIV status, the prognostic utility of baseline plasma EBV DNA level was restricted to HIV-positive patients. Unexpectedly, most HIV-positive patients with high plasma EBV DNA at diagnosis had EBV-negative lymphomas, as confirmed by multiple methods. Even in these HIV-positive patients with EBV-negative DLBCL, high plasma EBV DNA remained associated with shorter OS (P = .014). These results suggest that EBV reactivation in nontumor cells is a poor prognostic finding even in HIV-positive patients with convincingly EBV-negative DLBCL, extending the potential utility of EBV measurement as a valuable and implementable prognostic marker in SSA., (© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Increasing access to conventional cancer treatment (CT) in low-income countries (LICs) is an important public health initiative to address the global burden of cancer. However, LICs have a high prevalence of use of traditional and complementary medicine (T&CM). It is important to consider the factors that influence a patient's choice to use T&CM, CT, or both for their cancer treatment., Methods: We conducted focus groups among adult cancer patients in Lilongwe, Malawi to identify facilitators and barriers of T&CM use. Focus groups were recorded, transcribed, translated, and underwent thematic content analysis., Results: Cultural norms, T&CM access, T&CM success, and CT failure were all identified as facilitators to T&CM use. CT success and T&CM failure were identified as barriers. Access and norms appear to determine initial treatment selection, while treatment outcomes dictate continued use of T&CM or CT., Conclusion: This study identified a pragmatic and experience-based treatment selection process that aligns with the social cognitive theory of behavior and assists in comprehending the factors that influence T&CM use among cancer patients in a low resource setting., Competing Interests: The authors have declared that no competing interests exist.