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The immune system plays an important role in protecting the body against malignancy. During cancer immunoediting, the immune system can recognize and keep checking the tumor cells by down-expression of some self-molecules or by increasing expression of some novel molecules. However, the microenvironment created in the course of cancer development hampers the immune ability to recognize and destroy the transforming cells. Human Leukocyte Antigen G (HLA-G) is emerging as immune checkpoint molecule produced more by cancer cells to weaken the immune response against them. HLA-G is a non-classical HLA class I molecule which is normally expressed in immune privileged tissues as a soluble or membrane-bound protein. HLA-G locus is highly polymorphic in the non-coding 3′ untranslated region (UTR) and in the 5′ upstream regulatory region (5′ URR). HLA-G expression is controlled by polymorphisms located in these regions, and several association studies between these polymorphic sites and disease predisposition, response to therapy, and/or HLA-G protein expression have been reported. Various polymorphisms are demonstrated to modulate its expression and this is increasingly finding more significance in cancer biology. This review focuses on the relevance of the HLA-G gene and its polymorphisms in cancer development. We highlight population genetics of HLA-G as evidence to espouse the need and importance of exploring potential utility of HLA-G in cancer diagnosis, prognosis and immunotherapy in the currently understudied African population.

Reproductive history and genetics are well-known risk factors of breast cancer (BC). Little is known about how these factors interact to effect BC. This study investigated the association of ten polymorphisms in DNA repair genes with BC susceptibility in the Tanzanian samples and further analyzed the association between reproductive risk factors and disease risk METHODS: A hospital-based case-control study in 263 histopathological confirmed BC patients and 250 age-matched cancer-free controls was carried out. Allelic, genotypic, and haplotype association analyses were executed. Also, multifactor dimensionality reduction (MDR), and interaction dendrogram approaches were performed.The frequency of genotypic and allelic variants of XRCC1-Arg399Gln (rs25487), XRCC2-Arg188His (rs3218536), XRCC3-Thr241Met (rs861539), XPG-Asp1104His (rs17655), and MSH2-Gly322Asp (rs4987188) were significantly different between the groups (p 0.05). Moreover, XRCC1-Arg399Gln (rs25487), XRCC3-Thr241Met (rs861539), and XPG-Asp1104His (rs17655) were associated with the increased risk of BC in co-dominant, dominant, recessive, and additive genetic-inheritance models (p 0.05). XRCC1-Arg/Gln genotype indicated a 3.1-fold increased risk of BC in pre-menopausal patients (p = 0.001) while XPG-His/His genotype showed a 1.2-fold increased risk in younger BC patients (40 years) (p = 0.028). Asp/His+His/His genotypes indicated a 1.3-fold increased risk of BC in PR+ patients and a 1.1-fold decreased risk of BC in luminal-A patients (p = 0.014, p = 0.020, respectively). MDR analysis revealed a positive interaction between BC and the XPG-Asp1104His (rs17655) together with family history of cancer in the first-degree relatives. Dendrogram analysis indicated that the XPG-Asp1104His (rs17655) and family history of cancer in first-degree relatives were significantly synergistic and might be associated with an elevated risk of BC in Tanzania.The XPG-Asp1104His (rs17655) might exert both independent and interactive effects on BC development in the Tanzanian women.

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), Tanzania

Growing prevalence and aggressiveness of breast cancer (BC) among East African women strongly indicate that the genetic risk factor implicated in the etiology of the disease may have a key role. Germline pathogenic variants in BRCA1 and BRCA2 (BRCA1/2) are known to increase the lifetime risk of BC. This study investigated the prevalence and spectrum of germline single nucleotide variant/insertion and deletion (SNV/indel), and copy number variations (CNVs) in BRCA1/2 among Tanzanian BC patients, and evaluated the associations of identified variants with patient's socio-demographic and histopathological characteristics.One hundred BC patients were examined for BRCA1/2 variants using next-generation sequencing (NGS). Sanger sequencing and multiplex ligation-dependent probe amplification (MLPA) assay were performed for the confirmation of SNV/indel and CNVs, respectively.Six germline SNV/indel pathogenic variants were detected from six unrelated patients. Five of these variants were identified in BRCA1, and one in BRCA2. We also identified, in one patient, one variant of uncertain clinical significance (VUS). CNV was not detected in any of the BC patients. Furthermore, we found that in our cohort, BRCA1/2 variant carriers were triple-negative BC patients (p = 0.019).Our study provides first insight into BC genetic landscape by the use of NGS in the under-represented East African Tanzanian populations. Our findings support the importance of genetic risk factors in BC etiology in Tanzania and showed a relatively high overall prevalence (6%) of germline BRCA1/2 pathogenic variants in BC patients. Therefore, our results indicate that BRCA1/2 pathogenic variants may well contribute to BC incidence in Tanzania. Thus, the identification of frequent variants in BRCA1/2 genes will enable implementation of rapid, inexpensive population-specific BRCA1/2 genetic testing, particularly for triple-negative BC patients known for their high prevalence in Tanzania. This will, in turn, greatly contributes to provide effective therapeutic strategies.

Objective Effective cancer treatment involves aggressive chemo-radiotherapy protocols that alter survivors’ quality of life (QOL). This has recently aroused the attention not only to focus on clinical care but rather to be holistic and client-centered, looking beyond morbidity and mortality. The study assessed the QOL and associated factors among patients with cervical cancer (CC) after the completion of chemoradiotherapy. Methods A cross-sectional analytical study was conducted at Ocean Road Cancer Institute (ORCI) from September to November 2020. A total of 323 CC patients were interviewed with a structured questionnaire of QOL, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), and its cervical cancer module (EORTC QLQ-CX24). The QOL domains, socio-demographic and clinical variables were analyzed with Mann–Whitney and Kruskal–Wallis on SPSS version 23, and a P Results More than half (54.8%) of the CC patients had a good overall QOL. Overall, QOL was affected by education (P = 0.019), smoking (0.044), sexual partner (P = 0.000), treatment modality (P = 0.018), and time since completion of treatment (P = 0.021). Patients who underwent external beam radiation suffered from significant side effect symptoms (P P Conclusions A significant improvement in QOL was observed after chemoradiotherapy and was affected by socio-demographic and clinical variables. Thus, calls for individualized care in addressing these distressing symptoms.

PURPOSE Albinism affects some facets of the eye’s function and coloration, as well as hair and skin color. The prevalence of albinism is estimated to be one in 2,000-5,000 people in sub-Saharan Africa and one in 270 in Tanzania. People in Tanzania with albinism experience sociocultural and economic disparities. Because of stigma related to albinism, they present to hospitals with advanced disease, including skin cancers. Mobile health (mHealth) can help to bridge some of the gaps in detection and treatment of skin cancers affecting this population. METHODS We assessed the feasibility of using a mobile application (app) for detection of skin cancers among people with albinism. The study was approved by the Ocean Road Cancer Institute institutional review board. Data, including pictures of the lesions, were collected using a mobile smartphone and submitted to expert reviewers. Expert reviewers’ diagnosis options were benign, malignant, or unevaluable. RESULTS A total of 77 lesions from different body locations of 69 participants were captured by the NgoziYangu mobile app. Sixty-two lesions (81%) were considered malignant via the app and referred for biopsy and histologic diagnosis. Of those referred, 55 lesions (89%) were biopsied, and 47 lesions (85%) were confirmed as skin malignancies, whereas eight (15%) were benign. CONCLUSION With an increasing Internet coverage in Africa, there is potential for smartphone apps to improve health care delivery channels. It is important that mobile apps like NgoziYangu be explored to reduce diagnostic delay and improve the accuracy of detection of skin cancer, especially in stigmatized groups.

Background: Colorectal carcinoma usually arises from an adenomatous polyp and observational studies suggest that the adenoma-to-carcinoma sequence takes approximately 10 to 15 years. Risk factors are adoption of westernized diets, obesity, cigarette smoking, and alcohol and reduced physical activity. Clinical Presentations are blood per rectum, abdominal pain, Anemia, change in bowel habits and bowel obstructive symptoms. The treatment of colorectal cancer is a dependent stage which includes chemotherapy, radiotherapy, surgery or both. Objective: This study aims at describing the clinical pathological characteristics of colorectal carcinoma and factors influencing survival among patients treated at Ocean Road Cancer Institute. Methods: This was a cross sectional study that involved histological confirmed colorectal carcinoma treated at Ocean Road Cancer Institute from 2010-2015. Results: Among 100 files extracted, 63% were males and 37% females. 21% were below 40 years of age. Left-sided tumor accounted for 46%. Abdominal pain, rectal bleeding and constipation were 72%, 68% and 55% respectively. Moderately differentiated adenocarcinoma accounted for 80%. Patients presented at stage III and IV were 37% and 56% respectively. Colostomy was the most surgical procedures performed. Folinic acid, Fluorouracil and Oxaliplatin were the most common chemotherapies used. Median overall survival was estimated to be 9.4 months. Conclusion: A significant proportion of patients in this study population are young. Survival from colorectal cancer is poor owing largely to the late presentation seen in this study group.

Background: Accurate and reproducible patient positioning is fundamental to the success of fractionated radiotherapy. To achieve accurate daily treatment delivery, various immobilization devices are used in radiotherapy departments. At ORCI the mostly used immobilization devices for radiotherapy treatment of head and neck cancer patients are thermoplastic mask and LS-2000. However, the effectiveness and accuracy of these immobilization devices in daily set-up is not known. This study was performed to evaluate accuracy and reproducibility of patient setup for both thermoplastic mask and LS-2000 devices, during irradiation of head and neck tumors.

Background East Africa is one of the fastest growing regions in the world and faces a rising burden of cancer; however, few people are equipped to effectively conduct research in this area. Materials and Methods A 31-item questionnaire was distributed to current trainees and recent graduates of the Master in Medicine in Clinical Oncology Program at Muhimbili University of Health and Allied Sciences in Tanzania. Areas that were assessed included (a) demographic information, (b) prior research training, (c) prior and current research activities, (d) attitudes toward the importance of research, and (e) supports and barriers to inclusion of research in an oncology career path. Results A total of 30 individuals responded to the survey, of whom 53% (n = 16) were male and 70% (n = 21) identified as current trainees. Among the majority of respondents, attitudes toward research were strongly favorable. Although only 37% (n = 11) reported receiving any formal training in research methodology, 87% (n = 26) reported intentions to incorporate research into their careers. The absence of protected time for research and lack of access to research funding opportunities were identified by a majority of respondents as critical barriers. Conclusion A majority of current or recent oncology trainees in Tanzania desire to incorporate research into their careers, but most also lack adequate training in research methodology and longitudinal mentorship. Our future collaboration will focus on creation of appropriate research training curriculums and fostering an environment that catalyzes interprofessional development and transforms and extends context-specific cancer research in East Africa. Implications for Practice Current and recent oncology trainees in East Africa expressed a high enthusiasm for research, driven by a sense of urgency related to the burden from cancer that the region faces. This highlights the need for cancer research training and mentorship in this setting. This work hypothesizes that African principal investigators can operate effectively if proper attention is given to selection and provision of high-quality foundational didactic training to learn the theory and implementation of research as well as to the development of an environment conducive to mentoring.

Background Pediatric sarcomas represent an important group of childhood tumors who require treatment at Muhimbili National Hospital (MNH), the largest pediatric oncology center in Tanzania. Treatment is often adapted from established childhood protocols validated in clinical trials from the United States and United Kingdom. There are no studies describing the outcomes of treatment in Tanzania to understand similarities and disparities with other countries. The objective of this study was to describe the treatment outcomes including the overall survival for children seen at MNH. Methods Data on treatment outcome was collected on all children seen at MNH pediatric oncology unit between 2011 and 2016 with a confirmed histological diagnosis of either bone or soft tissue sarcoma. Results A total of 135 cases were analyzed; 89 (66%) were Soft tissue sarcoma (STS) and 46 (34%) were bone sarcomas. In the STS group, 37 (41.6%) achieved a complete response, 12 (13.5%) achieved a partial response and 40 (44.9%) had no response. Factors found to be significantly associated with a higher complete response rate included early stage disease (stage I or II), embryonal histology, tumor in favorable sites and tumor size of

Background: During cancer growth, immunosuppressive microenvironment is created that enables tumour cells to evade an eliminative immune response and hence manage to grow into malignancy. HLA-G, existing as either membrane-bound (mHLA-G) or soluble (sHLA-G) molecule is thought to be immunosuppressive and produced more by tumor cells. The +3142G/C polymorphism in HLA-G gene affects its expression, and G allele is considered to be a protective mutant allele associated with less expression of HLA-G. The implication of HLA-G in cancer development has been reported in different cancers and populations. But, its implication in most African populations has not yet been investigated. The aim of this study was to determine the possible associations of soluble HLA-G and HLA-G +3142G/C SNP with breast cancer. Materials and Methods: 75 breast cancer patients and 84 normal controls were recruited in this study. The genotyping of HLA-G +3142G/C polymorphism was determined by LightSNiP typing assay using quantitative Real-Time PCR and sHLA-G levels were determined by ELISA. Results: The sHLA-G levels were significantly lower in breast cancer patients than in controls (p0.05) and was neither associated with sHLA-G levels. Conclusion: While the +3142G/C SNP was found not to be relevant to breast cancer, the changes of sHLA-G levels in response to medical interventions such as mastectomy may be translated into its potential prognostic utility for breast cancer. More studies are needed to provide clear evidence of sHLA-G as a diagnostic and prognostic marker of breast cancer in Tanzania.

Background Sub-Saharan Africa is simultaneously facing a rising incidence of cancer and a dearth of medical professionals because of insufficient training numbers and emigration, creating a growing shortage of cancer care. To combat this, Massachusetts General Hospital and Beth Israel Deaconess Medical Center partnered with institutions in South Africa, Tanzania, and Rwanda to develop a fellowship exchange program to supplement the training of African oncologists practicing in their home countries. Methods In its initial year, 2018, the Program for Enhanced Training in Cancer (POETIC) hosted a pilot cohort of seven fellows for 3-week observerships in their areas of interest. Researchers distributed questionnaires for program evaluation to participants prior to arrival and upon departure; additionally, three participated in semistructured interviews. Results Five themes emerged from the qualitative data: expectations of POETIC, differences between oncology in the U.S. and in sub-Saharan Africa, positive elements of the program, areas for improvement, and potential impact. Fellows identified several elements of Western health care that will inform their practice: patient-centered care; clinical trials; and collaboration among medical, radiation, and surgical oncologists. From the quantitative data, feedback was primarily around logistical areas for improvement. Conclusion POETIC was found to be feasible and valuable. The results from the pilot year justify the program's continuation in hopes of strengthening global health partnerships to support oncology training in Africa. One weakness is the small number of fellows, which will limit the impact of the study and the relevance of its conclusions. Future research will report on the expansion of the program and follow-up with former participants. Implications for Practice This work presents a novel model for fellowship exchange between lower- and higher-resourced areas. The program is a short-term observership with tumor boards and didactic teaching sessions incorporated. By attracting oncologists who aim to practice in their home countries, it facilitates international collaboration without contributing to the preexisting lack of medical professionals in low- and middle-income countries.

PURPOSE Sub-Saharan Africa is simultaneously facing a rising incidence of cancer and a dearth of medical professionals as a result of insufficient training numbers and emigration, creating a growing shortage of cancer care. To combat this, Massachusetts General Hospital and Beth Israel Deaconess Medical Center partnered with institutions in South Africa, Tanzania, and Rwanda to develop a fellowship exchange program to supplement the training of African oncologists practicing in their home countries. METHODS In its initial 2 years (2018 and 2019), the Program for Enhanced Training in Cancer (POETIC) hosted a pilot cohort of 14 fellows for 3-week observerships in their areas of interest. Researchers distributed questionnaires for program evaluation to participants before arrival and upon departure, and 8 participated in semistructured interviews. RESULTS Five themes emerged from the qualitative data: expectations of POETIC, differences in oncology between the United States and sub-Saharan Africa, positive elements of the program, areas for improvement, and potential impact. Fellows identified several elements of Western health care that will inform their practice: patient-centered care, research development, and collaboration among medical, radiation, and surgical oncologists. The time in Boston modeled a research infrastructure that participants expressed interest in emulating at their home hospitals. In addition, the fellowship inspired some participants to address prevention and survivorship efforts in their home countries. From the quantitative data, feedback was primarily around logistical areas for improvement. CONCLUSION POETIC was found to be feasible and valuable. The results from the first years justify the program’s continuation in hopes of strengthening global health partnerships to support oncology training in Africa. One weakness is the small number of fellows, which will limit the impact of the study and the relevance of its conclusions. Future work will involve long-term follow up with participants and the development of an alumni network.

Background: Accurate and reproducible patient positioning is fundamental to the success of fractionated radiotherapy. To achieve accurate daily treatment delivery, various immobilization devices are used in radiotherapy departments. At ORCI the mostly used immobilization devices for radiotherapy treatment of head and neck cancer patients are thermoplastic mask and LS-2000. However, the effectiveness and accuracy of these immobilization devices in daily set-up is not known. This study was performed to evaluate accuracy and reproducibility of patient setup for both thermoplastic mask and LS-2000 devices, during irradiation of head and neck tumors.&nbsp

Background and context: Breast cancer is a common type of cancer among women worldwide, with about 2 million new cases diagnosed in the yearly. It is the second common cancer and leading cause of cancer mortality among women in Tanzania, after cervical cancer. More than 70% of breast cancer patients in developed countries are diagnosed at early stages, whereas in low and middle-income countries, only 20%–60% of patients are diagnosed early. Physician in developed countries consults on average 15-20 breast cancer patients daily, while in developing countries the number triples. This high load does not allow a treating physician to spend ample time with patients explaining hence leaving patients not informed about their diagnosis, side effects of treatments and even living with the physical, emotional and psychological challenges of their disease. Residents at the Ocean Road Cancer Institute (ORCI), initiated a patient support group targeting breast cancer patients for feasibility. Aim: Provide forum for patients with same diagnosis to share common challenges Provide peer emotional, psychosocial support and cancer education Organize activities that will help to spread awareness to the community Initiate projects to improve socioeconomic status of breast cancer survivors in Tanzania Strategy/Tactics: Involved the ORCI administration from the beginning Involved the academic and research unit of ORCI Residents prepared session curriculum and teaching materials Sessions took place once a month Sessions were two hours long divided into three components, where the first is introduction of participants, then survivors led discussions or lectures prepared by an expert in the topic and lastly closing remarks by a physician Breakfast was provided Program/Policy process: Open membership for all breast cancer patients Physician lead face to face peer discussions Institutional acknowledgment of the support group Provision of primary registry of patients for follow-up Provision of a link to other social organizations Outcomes: Increase knowledge of cancer in general and breast cancer in particular A total of seven sessions were held to date For each session, participation ranged from 30-50 breast cancer survivors, and on average attendance was 4 sessions out of 7 Topics covered over a period of seven months included Coping with a cancer diagnosis and treatment Living with cancer and its changes to daily life Exercise Nutrition Breast cancer general knowledge Collaboration with other stake holders including IST secondary school students who initiated breast prosthesis knitting club What was learned: A need to reach out and give psycho-social support to ORCI patients Through education we can improve treatment adherence Possible partners are available if we reach out Exist a need to address misconceptions in the community so as to avoid stigma to patients.

Purpose Low-income countries (LICs) face a growing cancer burden and a pressing need to strengthen cancer care delivery systems. Overall case fatality from cancer is estimated to be 30% higher in LICs than in high-income countries, and adherence to standard treatment guidelines is a critical component of addressing this disparity. Despite several recent international efforts to develop resource-stratified cancer treatment guidelines, little research has been done on their implementation. In 2018, Tanzania’s Ministry of Health will publish a new set of national cancer treatment guidelines for all cancers. The objective of this work is to evaluate the feasibility, adoption, and effectiveness of a theory-informed implementation strategy to facilitate the uptake of guideline-based clinical practice at the national referral center, Ocean Road Cancer Institute (ORCI). Our central hypothesis is that this implementation strategy will be undertaken with fidelity and context-appropriate adaptations and will effectively increase guideline-concordant treatment at ORCI. Methods Qualitative data demonstrate that major barriers to guideline-based practice at ORCI include a lack of familiarity with standard treatment guidelines and a culture that prioritizes experience-based expertise over guidelines. We developed a multifaceted intervention to target these barriers using the Capability, Opportunity, Motivation and Behavior/Behavior Change Wheel framework. Our intervention has three phases: distribution of national cancer treatment guidelines in hard and soft copy, with an accompanying publicity campaign; dedicated multidisciplinary trainings for oncology providers and implementation champions; and reinforcement strategies, such as environmental restructuring and point-of-care clinical forms, to promote guideline-based practice. We will use a pre–post design that uses a mixed-methods approach to measure process and outcomes, including clinical data collection, survey administration, and qualitative interviews, focus groups, and field observation. Conclusion In Tanzania and other LICs, shifting to guideline-based practice entails a change in clinical culture and behavior, and guideline publication alone is unlikely to result in meaningful change. A theory-informed implementation strategy is the optimal way to ensure the adoption and sustained use of guideline-based practice. Systematic evaluation will allow us to make necessary modifications, disseminate findings, and advance knowledge in the field of cancer treatment guideline implementation in LICs. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/site/ifc . Li Zhang Consulting or Advisory Role: Dendreon, Unity