An Assessment of the Knowledge and Perceptions of Precision Medicine (PM) in the Rwandan Healthcare Setting.

INTRODUCTION: Precision medicine (PM) or personalized medicine is an innovative approach that aims to tailor disease prevention and treatment to consider the differences in people's genes, environments, and lifestyles. Although many efforts have been made to accelerate the universal adoption of PM, several challenges need to be addressed in order to advance PM in Africa. Therefore, our study aimed to establish baseline data on the knowledge and perceptions of the implementation of PM in the Rwandan healthcare setting. METHOD: A descriptive qualitative study was conducted in five hospitals offering diagnostics and oncology services to cancer patients in Rwanda. To understand the existing policies regarding PM implementation in the country, two additional institutions were surveyed: the Ministry of Health (MOH), which creates and sets policies for the overall vision of the health sector, and the Rwanda Biomedical Center (RBC), which coordinates the implementation of health sector policies in the country. The researchers conducted 32 key informant interviews and assessed the functionality of available PM equipment in the 5 selected health facilities. The data were thematically categorized and analyzed. RESULTS: The study revealed that PM is perceived as a complex and expensive program by most health managers and health providers. The most cited challenges to implementing PM included the following: the lack of policies and guidelines; the lack of supportive infrastructures and limited suppliers of required equipment and laboratory consumables; financial constraints; cultural, behavioral, and religious beliefs; and limited trained, motivated, and specialized healthcare providers. Regarding access to health services for cancer treatment, patients with health insurance pay 10% of their medical costs, which is still too expensive for Rwandans. CONCLUSION: The study participants highlighted the importance of PM to enhance healthcare delivery if the identified barriers are addressed. For instance, Rwandan health sector leadership might consider the creation of specialized oncology centers in all or some referral hospitals with all the necessary genomic equipment and trained staff to serve the needs of the country and implement a PM program.

Clinicopathological Characteristics and Mutational Landscape of APC, HOXB13, and KRAS among Rwandan Patients with Colorectal Cancer.

Cancer research in Rwanda is estimated to be less than 1% of the total African cancer research output with limited research on colorectal cancer (CRC). Rwandan patients with CRC are young, with more females being affected than males, and most patients present with advanced disease. Considering the paucity of oncological genetic studies in this population, we investigated the mutational status of CRC tissues, focusing on the Adenomatous polyposis coli (APC), Kirsten rat sarcoma (KRAS), and Homeobox B13 (HOXB13) genes. Our aim was to determine whether there were any differences between Rwandan patients and other populations. To do so, we performed Sanger sequencing of the DNA extracted from formalin-fixed paraffin-embedded adenocarcinoma samples from 54 patients (mean age: 60 years). Most tumors were located in the rectum (83.3%), and 92.6% of the tumors were low-grade. Most patients (70.4%) reported never smoking, and 61.1% of patients had consumed alcohol. We identified 27 variants of APC, including 3 novel mutations (c.4310_4319delAAACACCTCC, c.4463_4470delinsA, and c.4506_4507delT). All three novel mutations are classified as deleterious by MutationTaster2021. We found four synonymous variants (c.330C>A, c.366C>T, c.513T>C, and c.735G>A) of HOXB13. For KRAS, we found six variants (Asp173, Gly13Asp, Gly12Ala, Gly12Asp, Gly12Val, and Gln61His), the last four of which are pathogenic. In conclusion, here we contribute new genetic variation data and provide clinicopathological information pertinent to CRC in Rwanda.

Breast cancer molecular diagnostics in Rwanda: a cost-minimization study of immunohistochemistry versus a novel GeneXpert® mRNA expression assay.

Objective: To compare the financial and time cost of breast cancer biomarker analysis by immunohistochemistry with that by the Xpert® STRAT4 assay. Methods: We estimated costs (personnel, location, consumables and indirect) and time involved in breast cancer diagnosis at the Butaro Cancer Centre of Excellence, Rwanda, using time-driven activity-based costing. We performed a cost-minimization analysis to compare the cost of biomarker analysis for estrogen receptor, progesterone receptor and human epidermal growth factor receptor-2 status with immunohistochemistry versus STRAT4. We performed sensitivity analyses by altering laboratory-specific parameters for the two methods. Findings: We estimated that breast cancer diagnosis in Rwanda costs 138.29 United States dollars (US$) per patient when conducting biomarker analysis by immunohistochemistry. At a realistic immunohistochemistry antibody utilization efficiency of 70%, biomarker analysis comprises 48.7% (US$ 67.33) of diagnostic costs and takes 33 min. We determined that biomarker analysis with STRAT4 yields a reduction in diagnosis cost of US$ 7.33 (10.9%; 7.33/67.33), and in pathologist and technician time of 20 min (60.6%; 20/33), per patient. Our sensitivity analysis revealed that no cost savings would be made in laboratories with antibody utilization efficiencies over 90%, or where only estrogen and/or progesterone receptor status are assessed; however, such operational efficiencies are unlikely, and more laboratories are pursuing human epidermal growth factor receptor-2 analysis as targeted therapies become increasingly available. Conclusion: Breast cancer biomarker analysis with STRAT4 has the potential to reduce the required human and capital resources in sub-Saharan African laboratories, leading to improved treatment selection and better clinical outcomes.

Breast cancer molecular diagnostics in Rwanda: a cost-minimization study of immunohistochemistry versus a novel GeneXpert® mRNA expression assay

Objective To compare the financial and time cost of breast cancer biomarker analysis by immunohistochemistry with that by the Xpert® STRAT4 assay. Methods We estimated costs (personnel, location, consumables and indirect) and time involved in breast cancer diagnosis at the Butaro Cancer Centre of Excellence, Rwanda, using time-driven activity-based costing. We performed a cost-minimization analysis to compare the cost of biomarker analysis for estrogen receptor, progesterone receptor and human epidermal growth factor receptor-2 status with immunohistochemistry versus STRAT4. We performed sensitivity analyses by altering laboratory-specific parameters for the two methods. Findings We estimated that breast cancer diagnosis in Rwanda costs 138.29 United States dollars (US$) per patient when conducting biomarker analysis by immunohistochemistry. At a realistic immunohistochemistry antibody utilization efficiency of 70%, biomarker analysis comprises 48.7% (US$ 67.33) of diagnostic costs and takes 33 min. We determined that biomarker analysis with STRAT4 yields a reduction in diagnosis cost of US$ 7.33 (10.9%; 7.33/67.33), and in pathologist and technician time of 20 min (60.6%; 20/33), per patient. Our sensitivity analysis revealed that no cost savings would be made in laboratories with antibody utilization efficiencies over 90%, or where only estrogen and/or progesterone receptor status are assessed; however, such operational efficiencies are unlikely, and more laboratories are pursuing human epidermal growth factor receptor-2 analysis as targeted therapies become increasingly available. Conclusion Breast cancer biomarker analysis with STRAT4 has the potential to reduce the required human and capital resources in subSaharan African laboratories, leading to improved treatment selection and better clinical outcomes.

Pathological Characteristics, Prognostic Determinants and the Outcome of Patients Diagnosed with Colorectal Adenocarcinoma at the University Teaching Hospital of Kigali.

Worldwide, colorectal cancer (CRC) is the second most diagnosed cancer in female and the third in men, arising from the epithelium of the colorectum. It is known that colorectal cancer is common in developed countries than in developing countries which may be due to inaccurate data on the existence of the disease in that region combined with embracing western lifestyle expressed by the current trend of changes in cultural, social, and lifestyle practices playing a major part in the etiology of CRC. The aim of this study was to document epidemiological, pathological characteristics, and prognostics determinants of patients diagnosed with CRC in Rwanda. The data from patients' files and reviewed glass slides for 101 cases all from Kigali University Teaching Hospital (CHUK) were statistically analyzed and patient characteristics were described as mean and frequency accordingly. Comparisons were performed using chi square tests, Fisher's exact test and odds ratio with 95% confidence interval (CI). Survival curves were plotted using the Kaplan-Meier method, and log-rank test was used to assess the statistical differences in the observed survival curves by each categorical variable. A P value < 0.05 was considered statistically significant. Statistical analyses were performed using Statistical Product and Service Solutions (SPSS), GraphPad Prism, and MedCalc, accordingly. Mean age of the participants was 54.26 years, the main symptom was rectal bleeding (46.5%), rectal adenocarcinoma NOS represented 40.6%, conventional adenocarcinoma was 60.4%, most tumors were of Grade II (54.5%), most common stage was pT3N0 (20.8%), resection margins were free at 71.3%, lympho-vascular invasion was 49.5% of cases, a high immune response was in 71.3% of cases and of 101cases, and 55.4% were still alive at the end of the data collection, with 29.3% of patients have overall survival of 5 years. Prognostic determinants also affect the outcome in this study and overall survival period was 3 years for CRC diagnosed in Rwanda.

Nephroblastoma Treatment and Outcomes in a Low-Income Setting.

PURPOSE: Nephroblastoma is a highly curable pediatric cancer that requires multidisciplinary care. Few reports have assessed long-term treatment outcomes in low-resource settings using a task-shifting model of care. We report outcomes of a large cohort and factors associated with survival. METHODS: We performed a retrospective chart review of all patients with nephroblastoma presenting to the Butaro Cancer Center of Excellence in Rwanda between July 2012 and June 2018. RESULTS: In total, 136 patients were identified and treated according to International Society of Pediatric Oncology guidelines for low-income settings. Median age at diagnosis was 39.7 months (interquartile range, 25.3-61.8 months); 56.6% were female. Sixty-one (44.9%) patients presented with stage I-III disease, 35 (25.7%) with stage IV disease, and 6 (4.4%) with stage V disease; the remainder were unstaged (n = 34; 25.0%). Most patients completed surgery (n = 97; 71.3%) and postoperative chemotherapy (n = 82; 60.2%); 17 patients received radiotherapy. With a median follow-up time of 18.1 months, 44.9% of patients were alive, 41.9% had died, 8.8% were lost to follow-up, and 4.4% were referred for palliative care or declined further care at the end of the study. Three-year overall survival was 57.5% (95% CI, 48.1 to 65.8) for the entire cohort, and 80.1% (95% CI, 66.8 to 88.5) and 44.0% (95% CI, 26.8 to 60.0) for stages I-III and IV-V, respectively. CONCLUSION: We demonstrate that patients with nephroblastoma can be successfully treated in a low-resource setting. Survival remains lower than in high-income countries, in part due to early deaths, contributing to approximately 30% of patients not being medically able to receive surgical intervention. Next steps include the development of strategies that focus on earlier diagnosis, supportive care during the early phases of therapy, and efficient and timely transitions between specialties for multimodal care.

A Ten-Year Experience of Treating Chronic Myeloid Leukemia in Rural Rwanda: Outcomes and Insights for a Changing Landscape.

PURPOSE: In describing our ten-year experience with treating chronic myeloid leukemia (CML) as part of the Glivec Patient Assistance Program (GIPAP) in rural Rwanda, we evaluate (1) patient characteristics and treatment outcomes, (2) resource-adapted management strategies, and (3) the impact of diagnostic capacity development. METHODS: We retrospectively reviewed all patients with BCR-ABL-positive CML enrolled in this GIPAP program between 2009 and 2018. Clinical data were analyzed using descriptive statistics, Kaplan-Meier methods, proportional hazards regression, and the Kruskal-Wallis test. RESULTS: One hundred twenty-four patients were included. The median age at diagnosis was 34 (range 8-81) years. On imatinib, 91% achieved complete hematologic response (CHR) after a median of 49 days. Seven (6%) and 12 (11%) patients had primary and secondary imatinib resistance, respectively. The 3-year overall survival was 80% (95% CI, 72 to 87) for the cohort, with superior survival in imatinib responders compared with those with primary and secondary resistance. The median time from imatinib initiation to CHR was 59 versus 38 days (P = .040) before and after in-country diagnostic testing, whereas the median time to diagnosis (P = .056) and imatinib initiation (P = .170) was not significantly different. CONCLUSION: Coupling molecular diagnostics with affordable access to imatinib within a comprehensive cancer care delivery program is a successful long-term strategy to treat CML in resource-constrained settings. Our patients are younger and have higher rates of imatinib resistance compared with historic cohorts in high-income countries. High imatinib resistance rates highlight the need for access to molecular monitoring, resistance testing, and second-generation tyrosine kinase inhibitors, as well as systems to support drug adherence. Hematologic response is an accurate resource-adapted predictor of survival in this setting. Local diagnostic capacity development has allowed for continuous, timely CML care delivery in Rwanda.

Cervical cancer treatment in Rwanda: Resource-driven adaptations, quality indicators, and patient outcomes.

OBJECTIVE: Most cervical cancer cases and deaths occur in low- and middle-income countries, yet clinical research from these contexts is significantly underrepresented. We aimed to describe the treatment quality, resource-driven adaptations, and outcomes of cervical cancer patients in Rwanda. METHODS: A retrospective cohort study was conducted of all patients with newly diagnosed cervical cancer enrolled between April 2016 and June 2018. Data were abstracted from medical records and analyzed using descriptive statistics, Kaplan Meier methods, and Cox proportional hazards regression. RESULTS: A total of 379 patients were included; median age 54 years, 21% HIV-infected. A majority (55%) had stage III or IV disease. Thirty-four early-stage patients underwent radical hysterectomy. Of 254 patients added to a waiting list for chemoradiation, 114 ultimately received chemoradiation. Of these, 30 (26%) received upfront chemoradiation after median 126 days from diagnosis, and 83 (73%) received carboplatin/paclitaxel while waiting, with a median 56 days from diagnosis to chemotherapy and 207 days to chemoradiation. There was no survival difference between the upfront chemoradiation and prior chemotherapy subgroups. Most chemotherapy recipients (77%) reported improvement in symptoms. Three-year event-free survival was 90% with radical hysterectomy (95% CI 72-97%), 66% with chemoradiation (95% CI 55-75%), and 12% with chemotherapy only (95% CI 6-20%). CONCLUSIONS: Multi-modality treatment of cervical cancer is effective in low resource settings through coordinated care and pragmatic approaches. Our data support a role for temporizing chemotherapy if delays to chemoradiation are anticipated. Sustainable access to gynecologic oncology surgery and expanded access to radiotherapy are urgently needed.

Actinomycetoma of the colon presenting as abdominal wall abscess. Case report and review of the literature.

INTRODUCTION AND IMPORTANCE: Abdominal actinomycetoma is a rare and often a missed diagnosis by most of clinicians due to its rarity and different clinical presentations. It is caused by Actinomyces speces which are gram positive bacilli and normal commensal inhabitants of the human bronchial and gastrointestinal tracts. A.Israelli is responsible for disease in humans once the mucosal barrier is broken. CASE PRESENTATION: This case report presents an adult female patient who consulted for a localized abdominal wall mass of 3 weeks duration and the clinical exam was in favor of an abdominal wall abscess, but later found to be an actinomycotoma of the colon invading the abdominal wall and forming an abdominal wall abscess. Transverse colectomy and drainage of abscess was done and she improved well. CLINICAL DISCUSSION: Actinomycosis is common in the tropical and subtropical area. However, this is the first case reported in Rwanda and prompt surgical treatment and antibiotherapy have led to a good clinical outcome. CONCLUSION: Abdominal actinomycetoma should be considered as a differential diagnosis of any abdominal wall mass for patients with known risk factors and surgery and antibiotics are the only curative treatment.

Pathology Characteristics of Lymphomas in Rwanda: A Retrospective Study.

BACKGROUND: Lymphomas have been a global challenge for many decades and despite measures for prevention and management, the incidence continues to increase. There are two main categories, which are Non-Hodgkin's Lymphomas and Hodgkin's Lymphomas and most common etiologies are environmental, genetic alteration, radiation and some viruses. OBJECTIVE: To describe pathology characteristics of lymphomas in Rwanda based on Hematoxylin and Eosin stained glass slides and immuno histo chemistry, and classify them according to clinical aggressiveness. PATIENTS AND METHODS: We conducted a retrospective observational and descriptive study from January 2013 to December 2019. Lymphoma cases were retrieved together with relevant clinical and pathological information, and reviewed by independent pathologists. Histological diagnosis was classified according to the 2008 World Health Organization system in order to assign clinical aggressiveness of the lymphoma. RESULTS: Three hundred and six lymphoma cases were enrolled. Males contributed to 57% of all reviewed case, and slightly over 50% were young aged ≤35 years. Approximately 191 (62%) of cases were nodal lymphomas. Approximately one fifth (18%) of lymphoma cases were HIV positive. Most 213(70%) cases were Non-Hodgkin's Lymphomas of aggressive forms 164(77%). Among 164 cases of aggressive Non-Hodgkin's Lymphomas, diffuse large B cell lymphoma was the leading subtype 91(55.5%), followed by solid lymphoblastic lymphoma 32(19.5%) and Burkitt lymphoma 17(10.4%). Among all Hodgkin lymphoma cases, 90(97%) were classical Hodgkin lymphomaof nodular sclerosis subtype. Hodgkin lymphoma patients were younger compared to Non-Hodgkin's Lymphomas patients (mean age of 24.78±16.3 years versus 38.6±22. 5years, p=.000). CONCLUSION: Substantial proportion of Lymphomapatients in Rwanda were also HIV positive. Interestingly, Non-Hodgkin's Lymphomas in Rwanda are predominated by the most aggressive forms, and these mostly affect a younger population. Optimal characterisation of such cases, using advanced methods, is recommended.

Identifying Breast Cancer Care Quality Measures for a Cancer Facility in Rural Sub-Saharan Africa: Results of a Systematic Literature Review and Modified Delphi Process.

PURPOSE: The burden of cancer is growing in low- and middle-income countries (LMICs), including sub-Saharan Africa. Ensuring the delivery of high-quality cancer care in such regions is a pressing concern. There is a need for strategies to identify meaningful and relevant quality measures that are applicable to and usable for quality measurement and improvement in resource-constrained settings. METHODS: To identify quality measures for breast cancer care at Butaro Cancer Center of Excellence (BCCOE) in Rwanda, we used a modified Delphi process engaging two panels of experts, one with expertise in breast cancer evidence and measures used in high-income countries and one with expertise in cancer care delivery in Rwanda. RESULTS: Our systematic review of the literature yielded no publications describing breast cancer quality measures developed in a low-income country, but it did provide 40 quality measures, which we adapted for relevance to our setting. After two surveys, one conference call, and one in-person meeting, 17 measures were identified as relevant to pathology, staging and treatment planning, surgery, chemotherapy, endocrine therapy, palliative care, and retention in care. Successes of the process included participation by a diverse set of global experts and engagement of the BCCOE community in quality measurement and improvement. Anticipated challenges include the need to continually refine these measures as resources, protocols, and measurement capacity rapidly evolve in Rwanda. CONCLUSION: A modified Delphi process engaging both global and local expertise was a promising strategy to identify quality measures for breast cancer in Rwanda. The process and resulting measures may also be relevant for other LMIC cancer facilities. Next steps include validation of these measures in a retrospective cohort of patients with breast cancer.

Treatment of Hodgkin Lymphoma With ABVD Chemotherapy in Rural Rwanda: A Model for Cancer Care Delivery Implementation.

PURPOSE: Hodgkin lymphoma (HL) is highly curable in high-income countries (HICs), yet many patients around the world do not have access to therapy. In 2012, cancer care was established at a rural district hospital in Rwanda through international collaboration, and a treatment protocol using doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) without radiotherapy was implemented. METHODS: We conducted a retrospective cohort study of all patients with confirmed HL seen at Butaro Hospital from 2012 to 2018 to evaluate quality indicators and clinical outcomes. RESULTS: Eighty-five patients were included (median age, 16.8 years; interquartile range, 11.0-30.5 years). Ten (12%) were HIV positive. Most had B symptoms (70%) and advanced stage (56%) on examination and limited imaging. Of 21 specimens evaluated for Epstein-Barr virus, 14 (67%) were positive. Median time from biopsy to treatment was 6.0 weeks. Of 73 patients who started ABVD, 54 (74%) completed 6 cycles; the leading reasons for discontinuation were treatment abandonment and death. Median dose intensity of ABVD was 92%. Of 77 evaluable patients, 33 (43%) are in clinical remission, 27 (36%) are deceased, and 17 (22%) were lost to follow-up; 3-year survival estimate is 63% (95% CI, 50% to 74%). Poorer performance status, advanced stage, B symptoms, anemia, dose intensity < 85%, and treatment discontinuation were associated with worse survival. CONCLUSION: Treating HL with standard chemotherapy in a low-resource setting is feasible. Most patients who completed treatment experienced a clinically significant remission with this approach. Late presentation, treatment abandonment, and loss to follow-up contribute to the discrepancy in survival compared with HICs. A strikingly younger age distribution in our cohort compared with HICs suggests biologic differences and warrants further investigation.

Building Laboratory Capacity to Strengthen Health Systems: The Partners In Health Experience.

The diagnostic laboratory is essential to patient care and to the achievement of health equity. Through the development of quality laboratories in settings burdened by poverty and weak health systems, Partners In Health has demonstrated the critical contributions of clinical laboratories to the care of patients with HIV, tuberculosis, and cancer, among other conditions. The lessons learned through the organization's experience include the importance of well-trained and well-supported staff; reliable access to supplies, reagents, and diagnostic equipment; adequate facilities to provide diagnostic services; the integration of laboratories into networks of care; and accompaniment of the public health sector.