Expanding radiotherapy access in Sub-Saharan Africa: an analysis of travel burdens and patient-related benefits of hypofractionation.

Purpose: The purpose of this project was to examine the travel burdens for radiotherapy patients in Nigeria, Tanzania, and South Africa, and to assess the patient-related benefits of hypofractionated radiotherapy (HFRT) for breast and prostate cancer patients in these countries. The outcomes can inform the implementation of the recent Lancet Oncology Commission recommendations on increasing the adoption of HFRT in Sub-Saharan Africa (SSA) to enhance radiotherapy access in the region. Methods: Data were extracted from electronic patient records at the NSIA-LUTH Cancer Center (NLCC) in Lagos, Nigeria and the Inkosi Albert Luthuli Central Hospital (IALCH) in Durban, South Africa, from written records at the University of Nigeria Teaching Hospital (UNTH) Oncology Center in Enugu, Nigeria, and from phone interviews at Ocean Road Cancer Institute (ORCI) in Dar Es Salaam, Tanzania. Google Maps was used to calculate the shortest driving distance between a patient's home address and their respective radiotherapy center. QGIS was used to map the straight-line distances to each center. Descriptive statistics were used to compare transportation costs, time expenditures, and lost wages when using HFRT versus conventionally fractionated radiotherapy (CFRT) for breast and prostate cancer. Results: Patients in Nigeria (n=390) traveled a median distance of 23.1 km to NLCC and 86.7 km to UNTH, patients in Tanzania (n=23) traveled a median distance of 537.0 km to ORCI, and patients in South Africa (n=412) traveled a median distance of 18.0 km to IALCH. Estimated transportation cost savings for breast cancer patients in Lagos and Enugu were 12,895 Naira and 7,369 Naira, respectively and for prostate cancer patients were 25,329 and 14,276 Naira, respectively. Prostate cancer patients in Tanzania saved a median of 137,765 Shillings in transportation costs and 80.0 hours (includes travel, treatment, and wait times). Mean transportation cost savings for patients in South Africa were 4,777 Rand for breast cancer and 9,486 Rand for prostate cancer. Conclusion: Cancer patients in SSA travel considerable distances to access radiotherapy services. HFRT decreases patient-related costs and time expenditures, which may increase radiotherapy access and alleviate the growing burden of cancer in the region.

Challenges and opportunities for implementing hypofractionated radiotherapy in Africa: lessons from the HypoAfrica clinical trial.

The rising cancer incidence and mortality in sub-Saharan Africa (SSA) warrants an increased focus on adopting or developing approaches that can significantly increase access to treatment in the region. One such approach recommended by the recent Lancet Oncology Commission for sub-Saharan Africa is hypofractionated radiotherapy (HFRT), which can substantially increase access to radiotherapy by reducing the overall duration of time (in days) each person spends being treated. Here we highlight challenges in adopting such an approach identified during the implementation of the HypoAfrica clinical trial. The HypoAfrica clinical trial is a longitudinal, multicentre study exploring the feasibility of applying HFRT for prostate cancer in SSA. This study has presented an opportunity for a pragmatic assessment of potential barriers and facilitators to adopting HFRT. Our results highlight three key challenges: quality assurance, study harmonisation and machine maintenance. We describe solutions employed to resolve these challenges and opportunities for longer term solutions that can facilitate scaling-up use of HFRT in SSA in clinical care and multicentre clinical trials. This report provides a valuable reference for the utilisation of radiotherapy approaches that increase access to treatment and the conduct of high-quality large-scale/multi-centre clinical trials involving radiotherapy. Trial registration: Not available yet.

Utilization of cancer immunotherapy in sub-Saharan Africa.

Introduction: The Lancet Oncology Commission for sub-Saharan Africa (SSA) predicts that cancer deaths will double from 520,158 per year to more than 1 million per year by the year 2040. These striking figures indicate a need to urgently evaluate cancer treatment infrastructure and resources in the region. Studies have found immunotherapy to be effective for the treatment of advanced-stage cancer, which almost 70% of patients in SSA present with. Despite immunotherapy's significant therapeutic potential, its utilization in SSA is not well documented. The purpose of this study was to evaluate the landscape of immunotherapy in SSA. Methods: A Qualtrics survey assessing the existing infrastructure and training for safe immunotherapy administration was developed and distributed online via email and WhatsApp to 3,231 healthcare providers across SSA, with a target audience of healthcare providers serving patients with cancer. The survey contained 22 questions evaluating the accessibility, use, knowledge, and training on immunotherapy in SSA. Responses were collected between January and February 2023. Microsoft Excel was used to summarize and visually present the distribution of responses as counts and proportions. Results: 292 responses were included from 28 countries in SSA. 29% of all respondents indicated their clinic has easy access to cancer immunotherapy and 46% indicated their clinic currently practices it. Of clinics that practiced immunotherapy (n = 133), 12% used genomic sequencing to assess the tumor mutational burden biomarker, and 44% assessed expression of the PD-L1 biomarker prior to immunotherapy administration. 46% of all respondents were familiar with immunotherapy. 11% indicated being adequately trained to administer it. Of these (n=33), 52% indicated also being trained to manage immune-related adverse events related to immunotherapy administration. Conclusion: Immunotherapy utilization and training is low in SSA and insufficient for the rising cancer burden. Increased accessibility and usage of biomarker testing to predict immunotherapy response, incorporation of immunotherapy training into continuous medical education, and increased access to immunotherapy drugs may be prerequisites for expanded utilization of immunotherapy in SSA.

Alt-RPL36 downregulates the PI3K-AKT-mTOR signaling pathway by interacting with TMEM24.

Thousands of human small and alternative open reading frames (smORFs and alt-ORFs, respectively) have recently been annotated. Many alt-ORFs are co-encoded with canonical proteins in multicistronic configurations, but few of their functions are known. Here, we report the detection of alt-RPL36, a protein co-encoded with human RPL36. Alt-RPL36 partially localizes to the endoplasmic reticulum, where it interacts with TMEM24, which transports the phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) precursor phosphatidylinositol from the endoplasmic reticulum to the plasma membrane. Knock-out of alt-RPL36 increases plasma membrane PI(4,5)P2 levels, upregulates PI3K-AKT-mTOR signaling, and increases cell size. Alt-RPL36 contains four phosphoserine residues, point mutations of which abolish interaction with TMEM24 and, consequently, alt-RPL36 effects on PI3K signaling and cell size. These results implicate alt-RPL36 as an upstream regulator of PI3K-AKT-mTOR signaling. More broadly, the RPL36 transcript encodes two sequence-independent polypeptides that co-regulate translation via different molecular mechanisms, expanding our knowledge of multicistronic human gene functions.

Cross-Sectional Association of Food Source with Food Insecurity, Dietary Diversity and Body Mass Index in Western Kenya.

The triple burden of malnutrition in many low- and middle-income countries (LMICs) is partly a result of changing food environments and a shift from traditional diets to high-calorie Western-style diets. Exploring the relationship between food sources and food- and nutrition-related outcomes is important to understanding how changes in food environments may affect nutrition in LMICs. This study examined associations of household food source with household food insecurity, individual dietary diversity and individual body mass index in Western Kenya. Interview-administered questionnaire and anthropometric data from 493 adults living in 376 randomly-selected households were collected in 2019. Adjusted regression analyses were used to assess the association of food source with measures of food insecurity, dietary diversity and body mass index. Notably, participants that reported rearing domesticated animals for consumption ('own livestock') had lower odds of moderate or severe household food insecurity (odds ratio (OR) = 0.29 (95% CI: 0.09, 0.96)) and those that reported buying food from supermarkets had lower odds of moderate or severe household food insecurity (borderline significant, OR = 0.37 (95% CI: 0.14, 1.00)), increased dietary diversity scores (Poisson coefficient = 0.17 (95% CI: 0.10, 0.24)) and higher odds of achieving minimum dietary diversity (OR = 2.84 (95% CI: 1.79, 4.49)). Our findings provide insight into the relationship between food environments, dietary patterns and nutrition in Kenya, and suggest that interventions that influence household food source may impact the malnutrition burden in this context.

Comparative Proteomic Profiling of Unannotated Microproteins and Alternative Proteins in Human Cell Lines.

Ribosome profiling and mass spectrometry have revealed thousands of small and alternative open reading frames (sm/alt-ORFs) that are translated into polypeptides variously termed as microproteins and alt-proteins in mammalian cells. Some micro-/alt-proteins exhibit stress-, cell-type-, and/or tissue-specific expression; understanding this regulated expression will be critical to elucidating their functions. While differential translation has been inferred by ribosome profiling, quantitative mass spectrometry-based proteomics is needed for direct comparison of microprotein and alt-protein expression between samples and conditions. However, while label-free quantitative proteomics has been applied to detect stress-dependent expression of bacterial microproteins, this approach has not yet been demonstrated for analysis of differential expression of unannotated ORFs in the more complex human proteome. Here, we present global micro-/alt-protein quantitation in two human leukemia cell lines, K562 and MOLT4. We identify 12 unannotated proteins that are differentially expressed in these cell lines. The expression of six micro/alt-proteins from cDNA was validated biochemically, and two were found to localize to the nucleus. Thus, we demonstrate that label-free comparative proteomics enables quantitation of micro-/alt-protein expression between human cell lines. We anticipate that this workflow will enable the discovery of regulated sm/alt-ORF products across many biological conditions in human cells.