Assessing the utilization of cancer medicines in Rwanda: an analysis of treatment patterns.

Introduction: Cancer is a growing public health concern in Africa, especially in low- and middle-income countries (LMICs) like Rwanda. Increased cancer incidences translate into increased utilisation of cancer medicine. Access to affordable cancer medicines in Rwanda is a pressing issue as the National Health Insurance plan does not provide coverage for cancer medicines. In this study, we investigated the utilisation patterns of cancer medicines in Rwanda. Methods: This retrospective cross-sectional study was conducted at all referral hospitals (n = 3) capable of delivering chemotherapy in Rwanda. The data collection was over a period of 6 months, during which a team of trained research assistants reviewed a convenience sample of selected patient charts. Both paper charts and electronic medical records were used to collect patients' data, including cancer type, stage, treatment setting, type of drugs or regimen used and completed cycles. Data were analysed using descriptive statistics. Results: A total of 630 patients received chemotherapy during the study period and were included. Seventy-seven percent (n = 486) were female and mean age was 51 (SD ± 13). Among all patients receiving chemotherapy, 43% (n = 270) had breast cancer, 22% (n = 140) had cervical cancer and 19% (n = 121) had colorectal cancer. The majority of patients (71%) had a community-based insurance. Butaro Cancer Centre treated the most patients (48%, n = 303). Thirty-six percent (221/630) had stage III cancer. The most common regimens within the cohort were adriamycin, cyclophosphamide and taxane, capecitabine and oxaliplatin (CAPOX), paclitaxel + carboplatin and a single agent cisplatin given concurrently with radiotherapy. The proportion of chemotherapy that was given in the curative and palliative setting was 72% and 28% respectively. Conclusion: Access to affordable cancer medicines remains a challenge in Rwanda. The study's findings provide valuable information on the utilisation patterns of cancer medicines in Rwanda, which can be used to guide policy decisions and improve cancer care in the country.

Screening of germline mutations in young Rwandan patients with breast cancers.

BACKGROUND: In Sub-Saharan Africa breast cancer is commonly detected at younger age and the profile is more aggressive with a high mortality rate compared to the European countries. It is suggested that African-specific genetic background plays a key role in this matter. The present study aimed at understanding the role of genetic factors in breast cancer development in young Rwandan. METHODS: We performed a massive parallel sequencing on Illumina MiSeq NGS system for the screening of 26 genes associated with hereditary breast cancer from 40 patients under 35 years old from two University Teaching Hospitals in Kigali, Rwanda. Sanger sequencing was used to confirm pathogenic and likely pathogenic mutations. RESULTS: Five patients out of 40 (12.5%) presented with pathogenic mutations including four patients (10%) carrying BRCA1 or BRCA2 pathogenic variants. One patient showed a missense likely pathogenic TP53 variant. We have also detected additional missense, intronic, and 3'UTR variants of unknown significance in all study participants. CONCLUSION: This preliminary study suggests that the frequency of germline mutations in young Rwandan patients with breast cancer is similar to the observations made in Caucasians. However, further large studies including patients and controls are needed to better understand the impact of genetic factors as well as the environmental risk factors in the development of breast cancer in young Rwandans.

State of Cancer Control in Rwanda: Past, Present, and Future Opportunities.

Rwanda is a densely populated low-income country in East Africa. Previously considered a failed state after the genocide against the Tutsi in 1994, Rwanda has seen remarkable growth over the past 2 decades. Health care in Rwanda is predominantly delivered through public hospitals and is emerging in the private sector. More than 80% of patients are covered by community-based health insurance (Mutuelle de Santé). The cancer unit at the Rwanda Biomedical Center (a branch of the Ministry of Health) is responsible for setting and implementing cancer care policy. Rwanda has made progress with human papillomavirus (HPV) and hepatitis B vaccination. Recently, the cancer unit at the Rwanda Biomedical Center launched the country's 5-year National Cancer Control Plan. Over the past decade, patients with cancer have been able to receive chemotherapy at Butaro Cancer Center, and recently, the Rwanda Cancer Center was launched with 2 linear accelerator radiotherapy machines, which greatly reduced the number of referrals for treatment abroad. Palliative care services are increasing in Rwanda. A cancer registry has now been strengthened, and more clinicians are becoming active in cancer research. Despite these advances, there is still substantial work to be done and there are many outstanding challenges, including the need to build capacity in cancer awareness among the general population (and shift toward earlier diagnosis), cancer care workforce (more in-country training programs are needed), and research.

Social contexts as mediator of risk behaviors in Rwandan men who have sex with men (MSM): Implications for HIV and STI transmission.

INTRODUCTION: Men who have sex with men (MSM) are disproportionately impacted by HIV/AIDS resulting from risky sexual behaviors. Social and contextual factors are known to mediate risk behaviors, but there is limited information about the prevalence of risky sexual practices of Rwandan MSM and the concomitant socio-contextual determinants making it difficult to assess implications for preventing HIV/STI transmission in this key population. METHODS: Using exploratory qualitative design, we obtained socio-contextual information regarding prevalence of risky sexual behavior and assessed implications for HIV/ STIs transmission and preventive measures taken by MSM to improve sexual health and wellbeing. Thirty MSM were recruited to participate in in-depth interviews using respondent-driven sampling from LGBT associations in Kigali. Data were analyzed using standard qualitative data analysis procedures. RESULTS: Respondents' were between 18-40 years old; all completed primary education and are mostly low-socioeconomic status. Risky sexual practices were common, but differed by peculiar individual and contextual factors. Older MSM often reported occasional sexual relations with women to avoid suspicion and social stigma. Younger MSM's risky sexual practices are mostly transactional and mediated by the need for social acceptance and support. Knowledge of STIs was poor, but prevalence, especially of HPV was high. The options for improving sexual wellbeing are limited and mostly clandestine. CONCLUSION: Risky sexual behavior of Rwandan MSM has major implications for HIV/STI transmission. An environment of intense social stigma and social isolation makes it difficult to obtain information or services to improve sexual health. Effective interventions that address individual and contextual determinants of risk and access to health services are urgently needed to limit the consequence of MSM as a bridge for HIV transmission to the general population.

Cancer Control at the District Hospital Level in Sub-Saharan Africa: An Educational and Resource Needs Assessment of General Practitioners.

PURPOSE: The WHO framework for early cancer diagnosis highlights the need to improve health care capacity among primary care providers. In Rwanda, general practitioners (GPs) at district hospitals (DHs) play key roles in diagnosing, initiating management, and referring suspected patients with cancer. We sought to ascertain educational and resource needs of GPs to provide a blueprint that can inform future early cancer diagnosis capacity-building efforts. METHODS: We administered a cross-sectional survey study to GPs practicing in 42 Rwandan DHs to assess gaps in cancer-focused knowledge, skills, and resources, as well as delays in the referral process. Responses were aggregated and descriptive analysis was performed to identify trends. RESULTS: Survey response rate was 76% (73 of 96 GPs). Most responders were 25 to 29 years of age (n = 64 [88%]) and 100% had been practicing between 3 and 12 months. Significant gaps in cancer knowledge and physical exam skills were identified-88% of respondents were comfortable performing breast exams, but less than 10 (15%) GPs reported confidence in performing pelvic exams. The main educational resource requested by responders (n = 59 [81%]) was algorithms to guide clinical decision-making. Gaps in resource availability were identified, with only 39% of responders reporting breast ultrasound availability and 5.8% reporting core needle biopsy availability in DHs. Radiology and pathology resources were limited, with 52 (71%) reporting no availability of pathology services at the DH level. CONCLUSION: The current study reveals significant basic oncologic educational and resource gaps in Rwanda, such as physical examination skills and diagnostic tools. Capacity building for GPs in low- and middle-income countries should be a core component of national cancer control plans to improve accurate and timely diagnosis of cancer. Continuing professional development activities should address and focus on context-specific educational gaps, resource availability, and referral practice guidelines.

Impact of delayed care on surgical management of patients with gastric cancer in a low-resource setting.

BACKGROUND: Gastric cancer is the fifth most common cancer in Eastern Africa. Diagnostic delays in low-resource countries result in advanced disease presentation. We describe perioperative management of gastric cancer in Rwanda. METHODS: A retrospective review of records at three hospitals was performed to identify gastric adenocarcinoma cases from January 2012 to June 2016. Multiple perioperative and tumor-related variables were collected. Descriptive and bivariate analyses were performed. RESULTS: The final analysis included 229 patients with gastric cancer. Median age was 58 years (interquartile range [IQR] 49-65) and 49.6% were female (n = 114). Patients reported symptoms (ie, weight loss, epigastric pain) for a median time of 12 months (IQR 7.5-24). On presentation, 18.8% ( n = 43) had gastric outlet obstruction; 13.5% ( n = 31) had a palpable mass. Fifty-one percent ( n = 117) underwent an operation; of these, 74% ( n = 86) received gastrojejunostomy or were inoperable; and 29% ( n = 34) underwent curative resection. Palliative care referrals were made for 9% ( n = 20). Pathology reports were available for 190 patients (83.0%). Only 11.3% ( n = 26) had Helicobacter pylori ( H. pylori) testing of which 65.4% tested positive ( n = 17). CONCLUSIONS: A majority of patients presented with advanced disease. Very few patients had a curative resection. Significant advances in diagnosis and treatment are needed to improve the care of gastric cancer patients in Rwanda.

Protocol for the study of cervical cancer screening technologies in HIV-infected women living in Rwanda.

INTRODUCTION: The optimal method(s) for screening HIV-infected women, especially for those living in sub-Saharan Africa, for cervical precancer and early cancer has yet to be established. METHODS AND ANALYSIS: A convenience sample of >5000 Rwandan women, ages 30-54 years and living with HIV infection, is being consented and enroled into a cross-sectional study of cervical cancer screening strategies. Participants are completing an administered short risk factor questionnaire and being screened for high-risk human papillomavirus (hrHPV) using the Xpert HPV assay (Cepheid, Sunnyvale, California, USA), unaided visual inspection after acetic acid (VIA) and aided VIA using the Enhanced Visual Assessment (EVA) system (Mobile ODT, Tel Aviv, Israel). Women positive for hrHPV and/or by unaided VIA undergo colposcopy, which includes the collection of two cervical specimens prior to undergoing a four-quadrant microbiopsy protocol. The colposcopy-collected specimens are being tested by dual immunocytochemical staining for p16INK4a and Ki-67 (CINtec PLUS Cytology, Ventana, Tucson, Arizona, USA) and for E6 or E7 oncoprotein for 8 hrHPV genotypes (HPV16, 18, 31, 33, 35, 45, 52 and 58) using the next-generation AV Avantage hrHPV E6/E7 test (Arbor Vita Corporation, Freemont, California, USA). Women with a local pathology diagnosis of cervical intraepithelial neoplasia grade 2 (CIN2) or more severe (CIN2+) or pathology review diagnosis of CIN grade three or more severe (CIN3+) will receive treatment. Clinical performance and cost-effectiveness (eg, sensitivity, specificity and predictive values) of different screening strategies and algorithms will be evaluated. ETHICS AND DISSEMINATION: The protocol was approved by local and institutional review boards for human subjects research. At the completion of the study, results will be disseminated to the scientific community through peer-reviewed publication and to the Rwandan stakeholders through an external advisory panel.

Association between glutathione peroxidase 1 codon 198 variant and the occurrence of breast cancer in Rwanda.

BACKGROUND: Glutathione peroxidase 1 gene (GPX1) is one of the antioxidant enzyme that remove the reactive oxygen species in a continuous process. Since the identification of a well-characterized functional polymorphism named p.Pro198Leu (rs1050450 C>T) in GPX1 gene, abundant studies have evaluated the association between p.Pro198Leu polymorphism and tumor risk in diverse population. But, the available results related to breast cancer are conflicting and absent in Africa. The present case-control study was planned to assess the presence of GPX1 Pro198Leu polymorphism in Rwanda population to determine whether it is associated with the risk of developing breast cancer. METHODS: Genomic DNA from peripheral blood leukocytes of 41 patients with breast cancer and 42 healthy controls were enrolled and genotyped GPX1 Pro198Leu polymorphism by PCR amplification and DNA sequencing. RESULTS: No significant difference in the frequencies of Pro/Pro (49%) and Pro/Leu (51%) genotypes in cancer cases and in controls (50% each) were found. The allelic frequencies of Pro and Leu were 74% versus 26% and 75% versus 25% in breast cancer cases and controls respectively. No association was observed in allele frequencies of Pro and Leu, and familial history. Only an overall association of GPX1 Pro198Leu with grade of cancer (Pro/Leu vs. Pro/Pro: p = .0200) was detected. CONCLUSION: The result of this study suggested that GPX1 Pro198Leu polymorphism could not be a risk factor for breast cancer in Rwanda. However, large-scale studies on the effect of this polymorphism on the factors disturbing the redox homeostasis are needed for conclusive understanding.

CHEK2 Germ Line Mutations are Lacking among Familial and Sporadic Breast Cancer Patients in Rwanda

Worldwide, breast cancer is the most frequent neoplasm and the second leading cause of cancer death among females. It dominates in both developed and developing countries and represents a major public health problem. The etiology is multifactorial and involves exogenous agents as well as endogenous factors. Although they account for only a small fraction of the breast cancer burden, mutations in the BRCA1 and BRCA2 genes are known to confer a high risk predisposition. Mutations in moderate/low-penetrance genes may also contribute to breast cancer risk. Previous studies have shown that mutations in the CHEK2 gene are involved in breast cancer susceptibility due to its impact on DNA repair processes and replication checkpoints. This study was conducted to evaluate the frequencies of three germline mutations in CHEK2 gene (c.1100delC, R145W and I157T) in breast cancers in Rwanda. Using direct DNA sequencing, we analyzed 41 breast cancer patients and 42 normal breast controls but could not detect any positives. CHEK2 mutations may be a rare event in Rwandan population and may only play a minor if an role in breast cancer predisposition among familial and sporadic cases.

Association of p53 Codon 72 Polymorphism with Breast Cancer in a Rwandese Population.

BACKGROUND AND AIMS: A common polymorphism in the tumor suppressor gene p53 at codon 72 has been suggested to play a role in the development of a number of cancers. This polymorphism has been studied in many populations worldwide, with conflicting results. The present study was planned to assess the association of p53 codon 72 polymorphism with breast cancer development in a Rwandese population. METHODS: In this study, the polymorphism was examined by allele-specific PCR analysis in 40 patients with breast cancer and 39 healthy controls. RESULTS: The heterozygous genotype Pro/Arg prevailed in both breast cancer patients and controls, and was present in 80% (32/40) and 92.3% (36/39) of cases, respectively. No statistically significant association was observed between p53 codon 72 polymorphism and breast cancer risk. Distribution of p53 genotypes was also studied according to familial history, tumor grade, and clinical stage, and results clearly showed no statistically significant difference. CONCLUSION: These results suggest that p53 codon 72 polymorphism could not be assessed as a risk factor marker for predisposition to breast cancer in Rwanda. However, further studies using larger sample sizes are needed to provide more conclusive results and to investigate other genetic mutations affecting the activity of p53.

PrePex Male Circumcision: Follow-Up and Outcomes during the First Two Years of Implementation at the Rwanda Military Hospital.

BACKGROUND: PrePex Male Circumcision (MC) has been demonstrated as an effective and scalable strategy to prevent HIV infection in low- and middle-income countries. This study describes the follow-up and outcomes of clients who underwent PrePex MC between January 2011 and December 2012 with weekly follow-up at the Rwanda Military Hospital, the first national hospital in Rwanda to adopt PrePex. METHODS: Data on 570 clients age 21 to 54 were extracted from patient records. We compared socio-demographic and clinical characteristics, the operator's qualification, HIV status, pain before and after device removal, urological status, device size and follow-up time between clients who were formally discharged and those who defaulted. We reported bivariate associations between each covariate and discharge status, number of people with adverse events by discharge status, and time to formal discharge or defaulting using life table methods. Data were entered into Epidata and analyzed with Stata v 13. RESULTS: Among study participants, 96.5% were circumcised by non-physician operators, 85.4%were under 30 years, 98.9% were HIV-negative and 97.9% were without any urological problems that could delay the healing time. Most (70.7%) defaulted before formal discharge. Pain before (p<0.001) and after PrePex device removal (p = 0.001) were associated with discharge status, although very few cases were reported, and pain was more commonly missing among defaulters. Twenty-seven adverse events were reported (7 formally discharged, 20 defaulters). Median follow-up time was seven weeks among formally discharged and six weeks among defaulters (p<0.001). CONCLUSION: Given that all socio-demographic and most clinical characteristics were not associated with defaulting, we hypothesize that clients stopped returning once they determined they were healed. We recommend less frequent follow-up protocols to encourage clinical visits until formal discharge. Based on these results and recommendations, we believe PrePex MC is a practical circumcision strategy in Rwanda and in sub-Saharan Africa.