Search

The incidence of esophageal squamous cell carcinoma (ESCC) is disproportionately high in the eastern corridor of Africa and parts of Asia. Emerging research has identified a potential association between poor oral health and ESCC. One possible link between poor oral health and ESCC involves the alteration of the microbiome. We performed an integrated analysis of four independent sequencing efforts of ESCC tumors from patients from high- and low-incidence regions of the world. Using whole genome sequencing (WGS) and RNA sequencing (RNAseq) of ESCC tumors from 61 patients in Tanzania, we identified a community of bacteria, including members of the genera Fusobacterium, Selenomonas, Prevotella, Streptococcus, Porphyromonas, Veillonella and Campylobacter, present at high abundance in ESCC tumors. We then characterized the microbiome of 238 ESCC tumor specimens collected in two additional independent sequencing efforts consisting of patients from other high-ESCC incidence regions (Tanzania, Malawi, Kenya, Iran, China). This analysis revealed similar ESCC-associated bacterial communities in these cancers. Because these genera are traditionally considered members of the oral microbiota, we next explored whether there was a relationship between the synchronous saliva and tumor microbiomes of ESCC patients in Tanzania. Comparative analyses revealed that paired saliva and tumor microbiomes were significantly similar with a specific enrichment of Fusobacterium and Prevotella in the tumor microbiome. Together, these data indicate that cancer-associated oral bacteria are associated with ESCC tumors at the time of diagnosis and support a model in which oral bacteria are present in high abundance in both saliva and tumors of some ESCC patients.

The incidence of esophageal squamous cell carcinoma (ESCC) is disproportionately high in the eastern corridor of Africa and parts of Asia. Emerging research has identified a potential association between poor oral health and ESCC. One proposed biological pathway linking poor oral health and ESCC involves the alteration of the microbiome. Thus, we performed an integrated analysis of four independent sequencing efforts of ESCC tumors from patients from high- and low-incidence regions of the world. Using whole genome sequencing (WGS) and RNA sequencing (RNAseq) of ESCC tumors and WGS of synchronous collections of saliva specimens from 61 patients in Tanzania, we identified a community of bacteria, including members of the genera Fusobacterium, Selenomonas, Prevotella, Streptococcus, Porphyromonas, Veillonella, and Campylobacter, present at high abundance in ESCC tumors. We then characterized the microbiome of 238 ESCC tumor specimens collected in two additional independent sequencing efforts consisting of patients from other high-ESCC incidence regions (Tanzania, Malawi, Kenya, Iran, China). This analysis revealed a similar tumor enrichment of the ESCC-associated bacterial community in these cancers. Because these genera are traditionally considered members of the oral microbiota, we explored if there is a relationship between the synchronous saliva and tumor microbiomes of ESCC patients in Tanzania. Comparative analyses revealed that paired saliva and tumor microbiomes are significantly similar with a specific enrichment of Fusobacterium and Prevotella in the tumor microbiome. Together, these data indicate that cancer-associated oral bacteria are associated with ESCC tumors at the time of diagnosis and support a model in which oral bacteria are present in high abundance in both saliva and tumors of ESCC patients. Longitudinal studies of the pre-diagnostic oral microbiome are needed to investigate whether these cross-sectional similarities reflect temporal associations.

Background In response to the increasing burden of cancer in Tanzania, the Ministry of Health, Community Development, Gender, Elderly and Children launched National Cancer Treatment Guidelines (TNCTG) in February 2020. The guidelines aimed to improve and standardize oncology care in the country. At Ocean Road Cancer Institute (ORCI), we developed a theory‐informed implementation strategy to promote guideline‐concordant care. As part of the situation analysis for implementation strategy development, we conducted focus group discussions to evaluate clinical systems and contextual factors that influence guideline‐based practice prior to the launch of the TNCTG. Materials and Methods In June 2019, three focus group discussions were conducted with a total of 21 oncology clinicians at ORCI, stratified by profession. A discussion guide was used to stimulate dialogue about facilitators and barriers to delivery of guideline‐concordant care. Discussions were audio recorded, transcribed, translated, and analyzed using thematic framework analysis. Results Participants identified factors both within the inner context of ORCI clinical systems and outside of ORCI. Themes within the clinical systems included capacity and infrastructure, information technology, communication, efficiency, and quality of services provided. Contextual factors external to ORCI included interinstitutional coordination, oncology capacity in peripheral hospitals, public awareness and beliefs, and financial barriers. Participants provided pragmatic suggestions for strengthening cancer care delivery in Tanzania. Conclusion Our results highlight several barriers and facilitators within and outside of the clinical systems at ORCI that may affect uptake of the TNCTG. Our findings were used to inform a broader guideline implementation strategy, in an effort to improve uptake of the TNCTGs at ORCI. Implications for Practice This study provides an assessment of cancer care delivery systems in a low resource setting from the unique perspectives of local multidisciplinary oncology clinicians. Situational analysis of contextual factors that are likely to influence guideline implementation outcomes is the first step of developing an implementation strategy for cancer treatment guidelines. Many of the barriers identified in this study represent actionable targets that will inform the next phases of our implementation strategy for guideline‐concordant cancer care in Tanzania and comparable settings., Guidelines to improve and standardize oncology care in Tanzania were developed in 2020. This study utilized focus group discussions to assess the barriers and facilitators to guideline implementation at Ocean Road Cancer Institute.

PURPOSE The eastern corridor of Africa is affected by a high burden of esophageal cancer (EC), with > 90% of patients presenting with advanced disease. Self-expanding metal stents (SEMS) have been previously reported as safe and effective for palliation of malignant dysphagia in resource-limited settings; however, access is limited throughout Eastern Africa. METHODS In response to demand for palliative interventions for patients with dysphagia because of EC, the African Esophageal Cancer Consortium (AfrECC) partnered with the Clinton Health Access Initiative to improve access to SEMS in Eastern Africa. We undertook a stepwise implementation approach to (1) identify barriers to SEMS access, (2) conduct a market analysis, (3) select an industry partner, (4) establish regulatory and procurement processes, (5) develop endoscopic training resources, (6) create a medical device registry, and (7) establish principles of accountability. RESULTS Following an evaluation of market demand and potential SEMS manufacturers, Boston Scientific Corporation announced its commitment to launch an access program to provide esophageal SEMS to patients in Tanzania, Kenya, Malawi, and Zambia at a subsidized price. Parallel regulatory and procurement processes were established in each participating country. Endoscopy training courses were designed and conducted, using the Training-of-Trainers model. A device registry was created to centralize data for quality control and to monitor channels of SEMS distribution. Principles of accountability were developed to guide the sustainability of this endeavor. CONCLUSION The AfrECC Stent Access Initiative is an example of a multisector partnership formed to provide an innovative solution to align regional needs with a supply chain for a high-priority medical device.

Background Despite recent international efforts to develop resource-stratified clinical practice guidelines for cancer, there has been little research to evaluate the best strategies for dissemination and implementation in low- and middle-income countries (LMICs). Guideline publication alone is insufficient. Extensive research has shown that structured, multifaceted implementation strategies that target barriers to guideline use are most likely to improve adherence; however, most of this research has been conducted in high-income countries. There is a pressing need to develop and evaluate guideline implementation strategies for cancer management in LMICs in order to address stark disparities in cancer outcomes. Methods In preparation for the launch of Tanzania’s first National Cancer Treatment Guidelines, we developed a theory-driven implementation strategy for guideline-based practice at Ocean Road Cancer Institute (ORCI). Here, we use the Intervention Mapping framework to provide a detailed stepwise description of our process. First, we conducted a needs assessment to identify barriers and facilitators to guideline-based practice at ORCI. Second, we defined both proximal and performance objectives for our implementation strategy. Third, we used the Capability, Opportunity, Motivation and Behavior/Behavior Change Wheel (COM-B/BCW) framework to categorize the barriers and facilitators, choose behavior change techniques most likely to overcome targeted barriers and leverage facilitators, and select a feasible mode of delivery for each technique. Fourth, we organized these modes of delivery into a phased implementation strategy. Fifth, we operationalized each component of the strategy. Sixth, we identified the indicators of the process, outcome, and impact of our intervention and developed an evaluation plan to measure them using a mixed methods approach. Discussion We developed a robust, multifaceted guideline implementation strategy derived from a prominent behavior change theory for use in Tanzania. The barriers and strategies we generated are consistent with those well established in the literature, enhancing the validity and generalizability of our process and results. Through our rigorous evaluation plan and systematic account of modifications and adaptations, we will characterize the transferability of “proven” guideline implementation strategies to LMICs. We hope that by describing our process in detail, others may endeavor to replicate it, meeting a widespread need for dedicated efforts to implement cancer guidelines in LMICs.

PURPOSE In response to the increasing burden of cancer in Tanzania, the Tanzanian Ministry of Health Community Development, Gender, Elderly, and Children plans to launch their first National Cancer Treatment Guidelines. These guidelines will provide an opportunity to improve and standardize care at Ocean Road Cancer Institute (ORCI), the national cancer center, where previous data suggest that patients do not consistently receive standard treatment. A theory-informed implementation strategy will be conducted to facilitate the routine use of guidelines among health care providers at ORCI. As part of the needs assessment for this effort, this study explored the barriers to and facilitators of guideline-concordant care at ORCI. METHODS We conducted three focus groups with participants stratified by profession, which included oncologists, radiotherapists, oncology residents, and nurses. A discussion guide was used to generate discussion about multiple aspects of current clinical processes at ORCI. Audio recordings were transcribed and translated to English, and data were analyzed using the framework method. RESULTS A total of 21 participants helped identify institutional and systemic factors that were internal and external to the clinical systems at ORCI that may affect guideline-concordant care. These can be categorized into the following: strengths and facilitators, barriers, and suggestions for improvement. Internal facilitators include multidisciplinary patient management, government-sponsored free cancer care, community engagement, and providers’ motivation for continuous learning and improvement. Internal barriers include interdepartmental and interinstitutional communication gaps, resource limitations for specialized services, high patient volumes, and patient misconceptions and nonadherence. Participants offered many practical suggestions for improving clinical systems at ORCI. CONCLUSION Our results highlight several barriers and facilitators within and outside of the clinical systems at ORCI that may affect the uptake of the National Cancer Treatment Guidelines. Findings have been used to recommend quality improvement and environmental restructuring measures at ORCI that will inform the broader guideline implementation strategy.

Background Fine-needle aspiration biopsy (FNAB) is a minimally invasive, cost-effective diagnostic tool that can be used in low-resource settings. However, adequacy and accuracy of FNAB is highly dependent on the skills of the operator and requires specialized training. Poor technique can preclude definitive diagnoses because of insufficient quality or quantity of FNAB samples. We evaluated the efficacy of an intensive training experience in Tanzania on improving ultrasound-guided FNAB techniques. Methods A 2-day workshop offered didactic lectures, demonstrations, and hands-on practicum on fundamentals of ultrasound imaging and FNAB technique. A prospective interventional study design was used with pre- and postintervention surveys and assessments to measure the effect of the workshop on specific skills related to slide smearing and ultrasound-guidance among participants. Results Twenty-six pathologists and radiologists, including trainees in each specialty, participated in the workshop. Pre- and postworkshop assessments demonstrated that most participants improved significantly in nearly all technical skills for slide smearing and ultrasound-guided FNAB. After the workshop, most participants demonstrated substantial improvements in ability to prepare the ultrasound equipment, measure the lesion in three dimensions by ultrasound, target lesions in one pass using both parallel and perpendicular approaches, and prepare high-quality aspirate smears. Conclusion An in-country 2-day workshop in Tanzania was efficacious in transferring basic skills in FNAB smear preparation and ultrasound-guided FNAB, resulting in skills enhancement among participating pathologists and radiologists. Although mastery of skills was not the goal of this short workshop, participants demonstrated proficiency in most technical elements after workshop completion, and the workshop generated interest among select participants to pursue additional intensive training in cytopathology.

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

Objective: We propose to utilize tumor biospecimens from patients with esophageal squamous cell carcinoma (ESCC) to identify possible genetic, molecular, and infectious determinants of this high-incidence disease in East Africa. However, laboratory technologies in East Africa are not available to support DNA and RNA extraction and genome and transcriptome sequencing from patient specimens. In preparation for establishment of a biorepository for African ESCC specimens, we compared different fixation and preservation media for transportability over long distances and success in preserving the genetic integrity and expression profiles of ESCC. Methods: Patients with a suspected diagnosis of ESCC at Muhimbili National Hospital in Dar es Salaam, Tanzania were identified and consented prior to endoscopic evaluations. For patients with endoscopic findings consistent with ESCC, tumor biopsies were obtained and stored using two different fixation and preservation media: PAXgene® Tissue Container (n=2) and RNAlater® (n=2). All specimens were shipped at room temperature from Dar es Salaam to San Francisco. DNA and RNA quantity was measured by nanodrop method and DNA was further confirmed by picogreen method, yielding measures of total DNA and RNA acquired (ug). DNA quality was measured as percent of total DNA degradation to between 200-1000 bp. RNA quality measure was determined by bioanalyzer output measure RNA Integrity Number (RIN). Results: Specimens for our first 10 patients were analyzed. Average transit time of biopsy specimens in preservative at room temperature was 6.2 days (range 3.5-9.0). Tumor specimens preserved with PAXgene® yielded a mean of 7.7 ug total DNA and 8.6 ug total RNA. Tumor specimens preserved with RNAlater® yielded a mean 1.4 ug of DNA and 8.2 ug of RNA. DNA degradation products were 0% of total with PAXgene® versus 6% of total with RNAlater®. Specimens preserved with PAXgene® yielded a mean RIN of 4, while RNAlater® yielded a mean RIN of 9. DNA and RNA quality were not associated with length of time at room temperature, up to a maximum of 9 days. Conclusion: Tissue preserved using the PAXgene® Tissue Container yielded higher DNA quantity and quality than tissue preserved in RNAlater®. RNA quantity was comparable for both mediums, but RNAlater® resulted in superior RNA quality versus PAXgene®. Both mediums allowed for flexible transport of specimens at room temperature and merit further inquiry into their potential as cost-effective methods to facilitate molecular analyses for geographically isolated diseases in Africa. Based upon our pilot data, each medium offers unique advantages. Our expanded study will continue to utilize both mediums to optimize isolation of both DNA and RNA. We will plan to present data for an enriched sample size. Funding source: National Institutes of Health, National Cancer Institute Cancer Center Administrative Supplement to Promote Cancer Prevention and Control Research in Low and Middle Income Countries, A119617, [CA-0082629]. Citation Format: Beatrice Paul Mushi, John Greer, Charles William Cahalane, II, Msiba Selekwa, Ali Mwanga, Larry Akoko, Elia Mmbaga, Eric Collisson, Katherine Van Loon. A pilot study to establish procedures for DNA and RNA isolation from African esophageal tumor specimens [abstract]. In: Proceedings of the AACR International Conference: New Frontiers in Cancer Research; 2017 Jan 18-22; Cape Town, South Africa. Philadelphia (PA): AACR; Cancer Res 2017;77(22 Suppl):Abstract nr B39.