Absence of Germline BRCA1 c.68_69delAG and c.5266dupC Mutations among Hormone Receptor-negative Breast Cancer Patients: A First Impression at a Tertiary Cancer-care Facility in Tanzania

The germline BRCA1 c.68_69delAG (185delAG) and c.5266dupC (5382insC) mutations are associated with hormone receptor-negative breast cancer (BC).  Limited studies have examined their contribution to alarming BC incidence in Sub Saharan Africa (SSA). Our study aimed to examine the contribution of  germline BRCA1 c.68_69delAG and c.5266dupC mutations to BC incidence among hormone receptor-negative BC patients admitted to Ocean Road Cancer Institute in Tanzania. Face-to-face interviews were conducted to capture socio-demographic characteristics, anthropometric measurements, family history of cancer and reproductive information from each patient. Their  histopathological data were extracted from the hospital medical records. The germline BRCA1 founder mutations were analyzed on blood samples using Sanger sequencing technology. The patients mean age at diagnosis was 47.05 ± 12.82 years. A family history of cancer was observed in 13.6% of patients. The germline BRCA1 c.68_69delAG and c.5266dupC mutations were not detected in the study group. Our findings indicate that the germline BRCA1 c.68_69delAG and c.5266dupC mutations do not contribute to BC manifestation in hormone receptor-negative BC patients in Tanzania. Thus, screening BC patients for these mutations has no clinical relevance. Our data further suggest that the c.68_69delAG and the c.5266dupC mutations should not be considered when developing genetic testing guidelines in Tanzania. Keywords: Breast cancer, germline BRCA1 mutation, c.68_69delAG (185delAG), c.5266dupC (5382insC), Tanzani

Mutational spectrum of DNA damage and mismatch repair genes in prostate cancer

Over the past few years, a number of studies have revealed that a significant number of men with prostate cancer had genetic defects in the DNA damage repair gene response and mismatch repair genes. Certain of these modifications, notably gene alterations known as homologous recombination (HRR) genes; PALB2, CHEK2 BRCA1, BRCA2, ATM, and genes for DNA mismatch repair (MMR); MLH1, MSH2, MSH6, and PMS2 are connected to a higher risk of prostate cancer and more severe types of the disease. The DNA damage repair (DDR) is essential for constructing and diversifying the antigen receptor genes required for T and B cell development. But this DDR imbalance results in stress on DNA replication and transcription, accumulation of mutations, and even cell death, which compromises tissue homeostasis. Due to these impacts of DDR anomalies, tumor immunity may be impacted, which may encourage the growth of tumors, the release of inflammatory cytokines, and aberrant immune reactions. In a similar vein, people who have altered MMR gene may benefit greatly from immunotherapy. Therefore, for these treatments, mutational genetic testing is indicated. Mismatch repair gene (MMR) defects are also more prevalent than previously thought, especially in patients with metastatic disease, high Gleason scores, and diverse histologies. This review summarizes the current information on the mutation spectrum and clinical significance of DDR mechanisms, such as HRR and MMR abnormalities in prostate cancer, and explains how patient management is evolving as a result of this understanding

The distribution of reproductive risk factors disclosed the heterogeneity of receptor-defined breast cancer subtypes among Tanzanian women

BACKGROUND: Recent epidemiological studies suggest that reproductive factors are associated with breast cancer (BC) molecular subtypes. However, these associations have not been thoroughly studied in the African populations. The present study aimed to investigate the prevalence of BC molecular subtypes and assess their association with reproductive factors in Tanzanian BC patients. METHODS: This hospital-based case-only cross-sectional study consisted of 263 histologically confirmed BC patients in Tanzania. Clinico-pathological data, socio-demographic characteristics, anthropometric measurements, and reproductive risk factors were examined using the Chi-square test and one-way ANOVA. The association among reproductive factors and BC molecular subtypes was analyzed using multinomial logistic regression. The heterogeneity of the associations was assessed using the Wald test. RESULTS: We found evident subtype heterogeneity for reproductive factors. We observed that post-menopausal status was more prevalent in luminal-A subtype, while compared to luminal-A subtype, luminal-B and HER-2 enriched subtypes were less likely to be found in post-menopausal women (OR: 0.21, 95%CI 0.10–0.41, p = 0.001; OR: 0.39, 95%CI 0.17–0.89, p = 0.026, respectively). Also, the luminal-B subtype was more likely to be diagnosed in patients aged ≤ 40 years than the luminal-A subtype (OR: 2.80, 95%CI 1.46–5.32, p = 0.002). Women who had their first full-term pregnancy at < 30 years were more likely to be of luminal-B (OR: 2.71, 95%CI 1.18–4.17, p = 0.018), and triple-negative (OR: 2.28, 95%CI 1.02–4.07, p = 0.044) subtypes relative to luminal-A subtype. Furthermore, we observed that breastfeeding might have reduced odds of developing luminal-A, luminal-B and triple-negative subtypes. Women who never breastfed were more likely to be diagnosed with luminal-B and triple-negative subtypes when compared to luminal-A subtype (OR: 0.46, 95%CI 0.22–0.95, p = 0.035; OR: 0.41, 95%CI 0.20–0.85, p = 0.017, respectively). . CONCLUSION: Our results are the first data reporting reproductive factors heterogeneity among BC molecular subtypes in Tanzania. Our findings suggest that breast-feeding may reduce the likelihood of developing luminal-A, luminal-B, and triple-negative subtypes. Meanwhile, the first full-term pregnancy after 30 years of age could increase the chance of developing luminal-A subtype, a highly prevalent subtype in Tanzania. More interventions to promote modifiable risk factors across multiple levels may most successfully reduce BC incidence in Africa. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12905-021-01536-6

Experiences of women receiving high dose rate brachytherapy for cervical cancer at ocean road cancer institute Dar-es-salaam Tanzania

The objective of this study was to present a descriptive summary of the experiences of women treated with high dose rate brachytherapy for cervical cancer. A qualitative descriptive study design was used and 50 women who undergo high dose rate brachytherapy at Ocean Road Cancer Institute (ORCI) in Dar-es-salaam were selected. Qualitative interviewer administered questionnaire was used for data collection from cervical cancer patients treated between April 2019 to July 2019 for descriptive and thematic analysis of data. Qualitative interviewer administered questioning was done from which three themes arose: the patient perception, expectation and impressions, informational need, and psychological experiences. Many patients had good perception about brachytherapy although their first impression was bad. The study found the importance of provision of procedure information to patient which seems to improve their treatment experiences. The psychological experiences faced by patients before and during treatment included pain, distress, fear, humiliation and anxiety Pain was a major problem, as the preventative medication participants received had low efficiency in pain prevention hence did not protect them from experiencing pain. Opening and hanging their legs was a humiliating experience aggravated by the presence of doctors and nurses. Their belief that brachytherapy can cure their disease comforted them and gave them courage to endure the treatment, whilst caring staff comforted and supported them. In addition to individualized patient education, nurses should assess the level of pain women experience before, during and after receiving brachytherapy and advice the revision of pain management protocols.&nbsp;</p

Assessing Concordance to an Intensified Upendo Ward Wilms Tumor Treatment Protocol in Tanzania: An Institutional Review

Background: In Tanzania Wilms tumor (WT) ranks second among the most frequently diagnosed childhood cancer. Due to late presentation an intensified treatment protocol was established aiming for tumor reduction before surgery for achieving better surgical outcomes. We used two indicators for measuring the protocol concordance. First indicator was assessing the number of patients that received radiotherapy and second was number of patients treated with the high-risk regimen as per the protocol indications.Methodology: This was a cross sectional study. Data was collected using a retrospective chart review of all children with WT at Muhimbili National Hospital Pediatric Oncology Unit for a period between April 2016 to May 2017 who were treated using the intensified treatment protocol (combination of two WT protocols with neoadjuvant as per SIOP-PODC and adjuvant as per modified SIOP International). Analysis was conducted using excel sheet and SPSS v20.Results: A total of 74 children were eligible. The median age was 3 years ranging from 6 months to 17 years with small female predisposition of 57% (n=42). On clinical presentation all patients presented with history of abdominal swelling. In terms of clinical stage; 45% (n= 33) and 43% (n= 32) presented with stage 4 and 3 disease, respectively. Radiotherapy treatment was administered to 30% (n=22). As per protocol stage III and IV disease require radiotherapy thus only 34% of eligible candidates received radiotherapy. On histology report; 34% (n = 25) reports were never found and 66% (n=49) were available. High-risk cases were 27% (n = 20). We noted high-risk regimen was given to 12% (n=9) of study participants; thus only 45% of eligible candidates received high-risk regimen. All patient had intention to treat on admission with noted 19% (n = 14) default rate.Conclusion: Measuring concordance with guidelines allows for identification of best practices, which in turn inform on quality improvements. This snapshot identified opportunities for improvement in protocol uptake in our unit. Key words: Wilms Tumor, low income country, pediatric malignancy

Radiation therapists' perceptions of thermoplastic mask use for head and neck cancer patients undergoing radiotherapy at Ocean Road Cancer Institute in Tanzania: A qualitative study.

IntroductionA thermoplastic mask is the most widely used immobilization device for head and neck cancer patients undergoing radiotherapy. The radiation therapist is the staff responsible to prepare these masks and set-up the patients for treatment, a procedure that requires time, patience, and precision. An understanding of Radiation therapists' perceptions regarding thermoplastic mask use will help design interventions to address challenges encountered in its use. This study explored Radiation therapists' perceptions of thermoplastic mask use for head and neck cancer patients undergoing radiotherapy at Ocean Road Cancer Institute in Tanzania.Material and methodsAn exploratory qualitative study design was used to explore thermoplastic mask use for head and neck cancer patients undergoing radiotherapy. Semi-structured in-depth interviews were conducted, involving fifteen Radiation therapists from Ocean Road Cancer Institute in Tanzania between March and May 2021. A thematic analysis method was used to identify themes from data scripts.ResultsFour themes emerged that reflected radiation therapists' perceptions of thermoplastic mask use for head and neck cancer immobilization among patients undergoing radiotherapy. Emerged themes were (1) Perceived benefits and limitations of thermoplastic mask use, (2) Refresher training and supervision requirements for effective use, (3) Proper storage for quality maintenance, and (4) Increased financial support and proper budgeting.ConclusionParticipants perceived better patient immobilization with a thermoplastic mask use. However, too often recycling of thermoplastic masks and the long waiting time between thermoplastic mask preparation and treatment delivery limits their effective use. For efficient use of thermoplastic masks, there is a need for Radiation therapists' refresher training and proper supervision, improving the storage system and increasing financial support for procuring new thermoplastic masks

Clinicopathological Characteristics and Outcomes of Anal Squamous Cell Carcinoma Patients With and Without HIV Infection in Sub-Saharan Africa

PURPOSEIn the past 20 years, the burden of anal cancer (AC) increased by 60% in the United States and over three-fold in Africa. Rates of AC have increased by 20× in people living with HIV and the highest (50×) in men with HIV who have sex with men. However, in sub-Saharan Africa (SSA) where HIV is endemic, data on clinicopathological characteristics and outcomes of patients with AC are lacking. To address this, we have investigated AC disease presentation, treatment outcomes, and its predictors in a cohort of patients who were either HIV-infected or HIV-uninfected in SSA.METHODSWe conducted a retrospective cohort study of patients with anal squamous cell carcinoma (SCC) treated at Ocean Road Cancer Institute in Dar es Salaam, Tanzania from January 2014 to December 2019. Associations between the study outcomes and their predictors were analyzed using univariate and multivariate analysis models.RESULTSA total of 59 patients with anal SCC were retrieved and had at least 2-year follow-up. The mean age was 53.9 (standard deviation ±10.5) years. While none of the patients presented with stage I disease, 64.4% had locally advanced disease. HIV infection was the major comorbidity (64.4%). The rate of complete remission at the end of treatment was at 49% while the 2-year overall survival (OS) and local recurrence-free survival were 86.4% and 91.3%, respectively. Despite high HIV coinfection in the cohort, AC treatment outcomes were not significantly associated with HIV status. Disease stage (P = .012) and grade (P = .030) were significantly associated with 2-year OS.CONCLUSIONPatients with anal SCC in Tanzania present mainly with locally advanced disease associated with high HIV prevalence. In this cohort, the SCC grade was independently associated with treatment outcomes unlike other factors such as HIV coinfection

Radiation therapists’ perceptions of thermoplastic mask use for head and neck cancer patients undergoing radiotherapy at Ocean Road Cancer Institute in Tanzania: A qualitative study

Introduction A thermoplastic mask is the most widely used immobilization device for head and neck cancer patients undergoing radiotherapy. The radiation therapist is the staff responsible to prepare these masks and set-up the patients for treatment, a procedure that requires time, patience, and precision. An understanding of Radiation therapists’ perceptions regarding thermoplastic mask use will help design interventions to address challenges encountered in its use. This study explored Radiation therapists’ perceptions of thermoplastic mask use for head and neck cancer patients undergoing radiotherapy at Ocean Road Cancer Institute in Tanzania. Material and methods An exploratory qualitative study design was used to explore thermoplastic mask use for head and neck cancer patients undergoing radiotherapy. Semi-structured in-depth interviews were conducted, involving fifteen Radiation therapists from Ocean Road Cancer Institute in Tanzania between March and May 2021. A thematic analysis method was used to identify themes from data scripts. Results Four themes emerged that reflected radiation therapists’ perceptions of thermoplastic mask use for head and neck cancer immobilization among patients undergoing radiotherapy. Emerged themes were (1) Perceived benefits and limitations of thermoplastic mask use, (2) Refresher training and supervision requirements for effective use, (3) Proper storage for quality maintenance, and (4) Increased financial support and proper budgeting. Conclusion Participants perceived better patient immobilization with a thermoplastic mask use. However, too often recycling of thermoplastic masks and the long waiting time between thermoplastic mask preparation and treatment delivery limits their effective use. For efficient use of thermoplastic masks, there is a need for Radiation therapists’ refresher training and proper supervision, improving the storage system and increasing financial support for procuring new thermoplastic masks