Xpert Breast Cancer STRAT4 Assay using fine-needle aspiration biopsy samples in a resource-constrained setting: a prospective diagnostic accuracy study.

BACKGROUND: Use of fine-needle aspiration biopsy (FNAB) specimens on Xpert Breast Cancer STRAT4 Assay (STRAT4; Cepheid, Sunnyvale, CA, USA), a CE-marked in-vitro diagnostic medical device, could potentially increase access to breast cancer biomarker testing in resource-constrained settings. We aimed to assess the performance of a research use-only version of STRAT4 using FNAB specimens in Tanzania. METHODS: In this prospective diagnostic accuracy study, patients aged 18 years or older with palpable breast masses presenting to the FNAB Clinic at Muhimbili National Hospital (Dar es Salaam, Tanzania) were recruited consecutively. Patients who were pregnant, lactating, or had a previous diagnosis of breast cancer were excluded. STRAT4 testing was performed on off-label FNAB samples using four protocols: the 1 × protocol (using the standard lysate method) on FNAB smears (1 × FNAB), quick lysis and Maui protocols (both on FNAB smears), and the 1 × protocol on formalin-fixed paraffin-embedded (FFPE) cell block material (1 × cell block). For 1 × FNAB and 1 × cell block, tissue was processed using FFPE lysis reagent, incubated at 80°C with proteinase K, and followed by addition of 95% or higher ethanol. Quick lysis was processed using FFPE lysis reagent and 95% or higher ethanol, whereas Maui was processed using a proprietary research-use only lysis reagent. The primary outcomes were overall concordance, sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) of STRAT4 as compared with immunohistochemistry or immunohistochemistry plus fluorescence in-situ hybridisation performed on cell blocks using clinically validated protocols in a Clinical Laboratory Improvement Amendments-accredited laboratory at the University of California, San Francisco (San Francisco, CA, USA). FINDINGS: Between Nov 29, 2017, and Dec 17, 2020, 208 patients were enrolled. Of 208 cases, 51 (25%) were excluded from analysis because of insufficient tissue in the cell block or absent cell blocks, leaving 157 participants (all female) for analysis. For oestrogen receptor, 1 × FNAB had the best performance, with an overall concordance of 95% (95% CI 90-100), sensitivity of 94% (85-100), specificity of 97% (90-100), and AUC of 0·96 (0·81-1·00). For progesterone receptor, 1 × cell block had the best overall performance (overall concordance 89% [95% CI 84-95], sensitivity 91% [82-99], and specificity 89% [81-97], with an AUC of 0·93 [0·89-0·99]) and 1 × FNAB performed the best among the smear protocols, with a concordance of 84% (95% CI 74-93), sensitivity of 63% (43-82), specificity of 97% (92-100), and AUC of 0·91 (0·72-0·97). For HER2, Maui had the highest agreement, with an overall concordance of 93% (95% CI 89-98), sensitivity of 96% (88-100), specificity of 92% (87-98), and AUC of 0·95 (0·98-1·00). For Ki67, Maui had the best performance of smear protocols, with a concordance of 73% (95% CI 64-82), sensitivity of 70% (58-81), specificity of 81% (66-96), and AUC of 0·80 (0·54-0·82). INTERPRETATION: Processing FNAB samples with STRAT4 is feasible in Tanzania, and performance for the oestrogen receptor is robust. Further optimisation of STRAT4 for FNAB has the potential to improve timely access to breast cancer diagnostics in resource-constrained settings. FUNDING: US National Institutes of Health; UCSF Global Cancer Program, Helen Diller Family Comprehensive Cancer Center; UCSF Department of Pathology; and Cepheid.

Rapid Onsite Evaluation for Specimen Adequacy and Triage of Breast Masses in a Low-Resource Setting.

CONTEXT.­: Rapid onsite evaluation (ROSE) is critical in determining sample adequacy and triaging cytology samples. Although fine-needle aspiration biopsy (FNAB) is the primary method of initial tissue sampling in Tanzania, ROSE is not practiced. OBJECTIVE.­: To investigate the performance of ROSE in determining cellular adequacy and providing preliminary diagnoses in breast FNAB in a low-resource setting. DESIGN.­: Patients with breast masses were recruited prospectively from the FNAB clinic at Muhimbili National Hospital. Each FNAB was evaluated by ROSE for overall specimen adequacy, cellularity, and preliminary diagnosis. The preliminary interpretation was compared to the final cytologic diagnosis and histologic diagnosis, when available. RESULTS.­: Fifty FNAB cases were evaluated, and all were adequate for diagnosis on ROSE and final interpretation. Overall percentage of agreement (OPA) between preliminary and final cytologic diagnosis was 84%, positive percentage of agreement (PPA) was 33%, and negative percentage of agreement (NPA) was 100% (κ = 0.4, P < .001). Twenty-one cases had correlating surgical resections. OPA between preliminary cytologic and histologic diagnoses was 67%, PPA was 22%, and NPA was 100% (κ = 0.2, P = .09). OPA between final cytologic and histologic diagnoses was 95%, PPA was 89%, and NPA was 100% (κ = 0.9, P = <.001). CONCLUSIONS.­: False-positive rates of ROSE diagnoses for breast FNAB are low. While preliminary cytologic diagnoses had a high false-negative rate, final cytologic diagnoses had overall high concordance with histologic diagnoses. Therefore, the role of ROSE for preliminary diagnosis should be considered carefully in low-resource settings, and it may need to be paired with additional interventions to improve pathologic diagnosis.

Tracheostomy care quality improvement in low- and middle-income countries: A scoping review.

Tracheostomy is a lifesaving, essential procedure performed for airway obstruction in the case of head and neck cancers, prolonged ventilator use, and for long-term pulmonary care. While successful quality improvement interventions in high-income countries such as through the Global Tracheostomy Collaborative significantly reduced length of hospital stay and decreased levels of anxiety among patients, limited literature exists regarding tracheostomy care and practices in low and middle-income countries (LMIC), where most of the world resides. Given limited literature, this scoping review aims to summarize published tracheostomy studies in LMICs and highlight areas in need of quality improvement and clinical research efforts. Based on the PRISMA guidelines, a scoping review of the literature was performed through MEDLINE/PubMed and Embase using terms related to tracheostomy, educational and quality improvement interventions, and LMICs. Publications from 2000-2022 in English were included. Eighteen publications representing 10 countries were included in the final analysis. Seven studies described baseline needs assessments, 3 development of training programs for caregivers, 6 trialed home-based or hospital-based interventions, and finally 2 articles discussed development of standardized protocols. Overall, studies highlighted the unique challenges to tracheostomy care in LMICs including language, literacy barriers, resource availability (running water and electricity in patient homes), and health system access (financial costs of travel and follow-up). There is currently limited published literature on tracheostomy quality improvement and care in LMICs. Opportunities to improve quality of care include increased efforts to measure complications and outcomes, implementing evidence-based interventions tailored to LMIC settings, and using an implementation science framework to study tracheostomy care in LMICs.

Feasibility and Clinical Acceptability of Automation-Assisted 3D Conformal Radiotherapy Planning for Patients With Cervical Cancer in a Resource-Constrained Setting.

PURPOSE: The Ocean Road Cancer Institute (ORCI) in Tanzania began offering 3D conformal radiation therapy (3DCRT) in 2018. Steep learning curves, high patient volume, and a limited workforce resulted in long radiation therapy (RT) planning workflows. We aimed to establish the feasibility of implementing an automation-assisted cervical cancer 3DCRT planning system. MATERIALS AND METHODS: We performed chart abstractions on 30 patients with cervical cancer treated with 3DCRT at ORCI. The Radiation Planning Assistant (RPA) generated a new automated set of contours and plans on the basis of anonymized computed tomography images. Each were assessed for edit time requirements, dose-volume safety metrics, and clinical acceptability by two ORCI physician investigators. Dice similarity coefficient (DSC) agreement analysis was conducted between original and new contour sets. RESULTS: The average time to manually develop treatment plans was 7 days. Applying RPA, automated same-day contours and plans were developed for 29 of 30 patients (97%). Of the 29 evaluable contours, all were approved with <2 minutes of edit time. Agreement between clinical and RPA contours was highest for the rectum (median DSC, 0.72) and bladder (DSC, 0.90). Agreement was lower with the primary tumor clinical target volume (CTVp; DSC, 0.69) and elective nodal clinical target volume (CTVn; DSC, 0.63). All RPA plans were approved with <4 minutes of edit time. RPA target coverage was excellent, covering the CTVp with median V45 Gy 100% and CTVn with median V45 Gy 99.9%. CONCLUSION: Automation-assisted 3DCRT contouring yielded high levels of agreement for normal structures. The RPA met all planning safety metrics and sustained high levels of clinical acceptability with minimal edit times. This tool offers the potential to significantly decrease RT planning timelines while maintaining high-quality RT delivery in resource-constrained settings.

A Genomic Analysis of Esophageal Squamous Cell Carcinoma in Eastern Africa.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) comprises 90% of all esophageal cancer cases globally and is the most common histology in low-resource settings. Eastern Africa has a disproportionately high incidence of ESCC. METHODS: We describe the genomic profiles of 61 ESCC cases from Tanzania and compare them to profiles from an existing cohort of ESCC cases from Malawi. We also provide a comparison to ESCC tumors in The Cancer Genome Atlas (TCGA). RESULTS: We observed substantial transcriptional overlap with other squamous histologies via comparison with TCGA PanCan dataset. DNA analysis revealed known mutational patterns, both genome-wide as well as in genes known to be commonly mutated in ESCC. TP53 mutations were the most common somatic mutation in tumors from both Tanzania and Malawi but were detected at lower frequencies than previously reported in ESCC cases from other settings. In a combined analysis, two unique transcriptional clusters were identified: a proliferative/epithelial cluster and an invasive/migrative/mesenchymal cluster. Mutational signature analysis of the Tanzanian cohort revealed common signatures associated with aging and cytidine deaminase activity (APOBEC) and an absence of signature 29, which was previously reported in the Malawi cohort. CONCLUSIONS: This study defines the molecular characteristics of ESCC in Tanzania, and enriches the Eastern African dataset, with findings of overall similarities but also some heterogeneity across two unique sites. IMPACT: Despite a high burden of ESCC in Eastern Africa, investigations into the genomics in this region are nascent. This represents the largest comprehensive genomic analysis ESCC from sub-Saharan Africa to date.

How a Digital Case Management Platform Affects Community-Based Palliative Care of Sub-Saharan African Cancer Patients: Clinician-Users' Perspectives.

BACKGROUND: Symptom control among cancer patients is a Tanzanian public health priority impacted by limited access to palliative care (PC) specialists and resources. Mobile Palliative Care Link (mPCL), a mobile/web application, aims to extend specialist access via shared care with local health workers (LHWs) with the African Palliative care Outcome Scale (POS) adapted for regular, automated symptom assessment as a core feature. OBJECTIVE: The aim of the study is to assess clinicians' attitudes, beliefs, and perceptions regarding mPCL usability and utility with their patients within a government-supported, urban Tanzanian cancer hospital setting. METHODS: We used a mixed methods approach including surveys, qualitative interviews, and system usage data to assess clinicians' experience with mPCL in a field study where discharged, untreatable cancer patients were randomized to mPCL or phone-contact POS collection. RESULTS: All six specialists and 10 LHWs expressed overall satisfaction with mPCL among 49 intervention arm patients. They perceived mPCL as a way to stay connected with patients and support remote symptom control. Timely access to POS responses and medical records were identified as key benefits. Some differences in perceptions of mPCL use and utility were seen between clinician groups; however, both expressed strong interest in continuing app use, recommending it to colleagues, and extending use throughout Tanzania. Primary use was for clinical status communication and care coordination. Pain and other symptom progression were the most frequently reported reasons for provider-patient interactions accounting for 34% (n = 44) and 12% (n = 15) of reasons, respectively. Usage barriers included time required to create a new clinical record, perceived need for response to non-urgent reminders or alerts, and training. necessary for competent use. System-level implementation barriers included variable patient access to smartphones and SIM cards and unreliable Internet access. CONCLUSION: This work demonstrates broad clinician desire for digital health tools to support remote community-based PC among cancer patients, particularly pain management.

Delayed diagnostic evaluation of symptomatic breast cancer in sub-Saharan Africa: A qualitative study of Tanzanian women.

BACKGROUND: Women with breast cancer in sub-Saharan Africa are commonly diagnosed at advanced stages. In Tanzania, more than 80% of women are diagnosed with stage III or IV disease, and mortality rates are high. This study explored factors contributing to delayed diagnostic evaluation among women with breast cancer in Tanzania. METHODS: A qualitative study was performed at Muhimbili National Hospital in Dar es Salaam, Tanzania. Twelve women with symptomatic pathologically proven breast cancer were recruited. In-depth, semi-structured interviews were conducted in Swahili. Interviews explored the women's journey from symptom recognition to diagnosis, including the influence of breast cancer knowledge and pre-conceptions, health seeking behaviors, psychosocial factors, preference for alternative treatments, and the contribution of culture and norms. Audio-recorded interviews were transcribed and translated into English. Thematic analysis was facilitated by a cloud-based qualitative analysis software. RESULTS: All women reported that their first breast symptom was a self-identified lump or swelling. Major themes for factors contributing to delayed diagnostic presentation of breast cancer included lack of basic knowledge and awareness of breast cancer and misconceptions about the disease. Participants faced barriers with their local primary healthcare providers, including symptom mismanagement and delayed referrals for diagnostic evaluation. Other barriers included financial hardships, fear and stigma of cancer, and use of traditional medicine. The advice and influence of family members and friends played key roles in healthcare-seeking behaviors, serving as both facilitators and barriers. CONCLUSION: Lack of basic knowledge and awareness of breast cancer, stigma, financial barriers, and local healthcare system barriers were common factors contributing to delayed diagnostic presentation of breast cancer. The influence of friends and family also played key roles as both facilitators and barriers. This information will inform the development of educational intervention strategies to address these barriers and improve earlier diagnosis of symptomatic breast cancer in Tanzania.

An international report on bacterial communities in esophageal squamous cell carcinoma.

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.

Risk Factors Associated With Early-Onset Esophageal Cancer in Tanzania.

PURPOSE: Eastern Africa is one of several regions affected by high incidence rates of esophageal squamous cell carcinoma (ESCC). A unique epidemiologic feature of ESCC in Eastern Africa is the high incidence in young people, with one-third of cases diagnosed at age < 45 years. This study aimed to investigate risk factors for early-onset ESCC in Tanzania through a secondary analysis of a matched case-control study. MATERIALS AND METHODS: From 2013 to 2015, ESCC cases were recruited at Muhimbili National Hospital and Ocean Road Cancer Institute in Dar es Salaam, Tanzania. Hospital controls were identified from patients with nonmalignant conditions and matched 1:1 for sex and age (± 10 years). Questionnaires were used to assess sociodemographic characteristics and environmental, dietary, and lifestyle risk exposures. Multivariate logistic regression models were used to estimate age-specific odds ratios of ESCC for exposures among participants age 30-44 and ≥ 45 years. RESULTS: A total of 471 cases and 471 controls were enrolled. Among cases, 100 (21%) were < 45 years. Multiple exposures were identified as risk factors for early-onset ESCC, several of which were unique to this age group, including infrequent teeth cleaning, secondhand tobacco smoke exposure, and pest infestation of grain and/or nuts. Lower socioeconomic status, family history of ESCC, tobacco smoking, home-brewed alcohol consumption, home storage of grain and/or nuts, and use of firewood for cooking were associated in the older but not the younger age group. Hot beverage intake was associated with increased ESCC risk in both age groups. CONCLUSION: Our results suggest that ESCC risk factors in Tanzania vary between age groups. With the data currently available, environmental and behavioral risk factors appear to play an important role in the high incidence of ESCC among young people.

Treatment outcomes of esophageal cancer in Eastern Africa: protocol of a multi-center, prospective, observational, open cohort study.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a major cause of cancer morbidity and mortality in Eastern Africa. The majority of patients with ESCC in Eastern Africa present with advanced disease at the time of diagnosis. Several palliative interventions for ESCC are currently in use within the region, including chemotherapy, radiation therapy with and without chemotherapy, and esophageal stenting with self-expandable metallic stents; however, the comparative effectiveness of these interventions in a low resource setting has yet to be examined. METHODS: This prospective, observational, multi-center, open cohort study aims to describe the therapeutic landscape of ESCC in Eastern Africa and investigate the outcomes of different treatment strategies within the region. The 4.5-year study will recruit at a total of six sites in Kenya, Malawi and Tanzania (Ocean Road Cancer Institute and Muhimbili National Hospital in Dar es Salaam, Tanzania; Kilimanjaro Christian Medical Center in Moshi, Tanzania; Tenwek Hospital in Bomet, Kenya; Moi Teaching and Referral Hospital in Eldoret, Kenya; and Kamuzu Central Hospital in Lilongwe, Malawi). Treatment outcomes that will be evaluated include overall survival, quality of life (QOL) and safety. All patients (≥18 years old) who present to participating sites with a histopathologically-confirmed or presumptive clinical diagnosis of ESCC based on endoscopy or barium swallow will be recruited to participate. Key clinical and treatment-related data including standardized QOL metrics will be collected at study enrollment, 1 month following treatment, 3 months following treatment, and thereafter at 3-month intervals until death. Vital status and QOL data will be collected through mobile phone outreach. DISCUSSION: This study will be the first study to prospectively compare ESCC treatment strategies in Eastern Africa, and the first to investigate QOL benefits associated with different treatments in sub-Saharan Africa. Findings from this study will help define optimal management strategies for ESCC in Eastern Africa and other resource-limited settings and will serve as a benchmark for future research. TRIAL REGISTRATION: This study was retrospectively registered with the ClinicalTrials.gov database on December 15, 2021,  NCT05177393 .

A mixed methods needs assessment and gap analysis for establishment of a cancer research training program in East Africa.

BACKGROUND: The burden of non-communicable diseases (NCDs), including cancer, in Africa is rising. Policymakers are charged with formulating evidence-based cancer control plans; however, there is a paucity of data on cancers generated from within Africa. As part of efforts to enhance cancer research training in East Africa, we performed a needs assessment and gap analysis of cancer-related research training resources in Tanzania. METHODS: A mixed-methods study to evaluate existing individual, institutional, and national resources supporting cancer research training in Tanzania was conducted. Qualitative data were collected using in-depth interviews while quantitative data were collected using self-administered questionnaires and online surveys. The study also included a desk-review of policy and guidelines related to NCD research and training. Study participants were selected to represent five groups: (i) policymakers; (ii) established researchers; (iii) research support personnel; (iv) faculty members in degree training programs; and (v) post-graduate trainees. RESULTS: Our results identified challenges in four thematic areas. First, there is a need for coordination and monitoring of the cancer research agenda at the national level. Second, both faculty and trainees identified the need for incorporation of rigorous training to improve research competencies. Third, sustained mentoring and institutional investment in development of mentorship resources is critical to empowering early career investigators. Finally, academic institutions can enhance research outputs by providing adequate research infrastructure, prioritizing protected time for research, and recognizing research accomplishments by trainees and faculty. CONCLUSIONS: As we look towards establishment of cancer research training programs in East Africa, investment in the development of rigorous research training, mentorship resources, and research infrastructure will be critical to empowering local health professionals to engage in cancer research activities.

mPalliative Care Link: Examination of a Mobile Solution to Palliative Care Coordination Among Tanzanian Patients With Cancer.

PURPOSE: Late-stage cancer patient symptom control is a national priority in Tanzania. Mobile health promises to improve the reach of a limited pool of palliative care specialists through interprofessional, community-based care coordination. This work assessed the effectiveness of a smartphone- or Web-based app, mPalliative Care Link (mPCL), to extend specialist access via shared data and communication with local health workers. Central to mPCL is the African Palliative care Outcome Scale (POS), adapted for automated mobile symptom assessment and response. METHODS: Adult patients with incurable cancer were randomly assigned at hospital discharge to mPCL versus phone-contact POS collection. Sociodemographic, clinical, and POS data were obtained at baseline. Twice-weekly POS responses were collected and managed via mPCL or phone contact with clinician study personnel for up to 4 months, on the basis of study arm assignment. Patient end-of-study care satisfaction was assessed via phone survey. RESULTS: Forty-nine patients per arm participated. Comparison of baseline characteristics showed an insignificant trend toward more women (P = .07) and higher discharge morphine use (P = .09) in the mPCL group compared with phone-contact and significant between-group differences in cancer types (P = .003). Proportions of deaths were near equal between groups (mPCL: 27%; phone-contact: 29%). Overall symptom severity was significantly lower in the phone-contact group (P < .0001), and symptom severity decreased over time in both groups (P = .0001); however, between-group change in overall symptoms over time did not vary significantly (P = .34). Care satisfaction was generally high in both groups. CONCLUSION: Higher symptom severity scores in the mPCL arm likely reflect between-group sociodemographic and clinical differences and clinical support of phone-contact arm participants. Similar rates of care satisfaction in both groups suggest that mPCL may support symptom-focused care coordination in a more efficient and scalable manner than phone contact. A broader study of mPCL's cost efficiency and utility in Tanzania is needed.

Views from Multidisciplinary Oncology Clinicians on Strengthening Cancer Care Delivery Systems in Tanzania.

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.

A Mobile App to Improve Symptom Control and Information Exchange Among Specialists and Local Health Workers Treating Tanzanian Cancer Patients: Human-Centered Design Approach.

BACKGROUND: Improving access to end-of-life symptom control interventions among cancer patients is a public health priority in Tanzania, and innovative community-based solutions are needed. Mobile health technology holds promise; however, existing resources are limited, and outpatient access to palliative care specialists is poor. A mobile platform that extends palliative care specialist access via shared care with community-based local health workers (LHWs) and provides remote support for pain and other symptom management can address this care gap. OBJECTIVE: The aim of this study is to design and develop mobile-Palliative Care Link (mPCL), a web and mobile app to support outpatient symptom assessment and care coordination and control, with a focus on pain. METHODS: A human-centered iterative design framework was used to develop the mPCL prototype for use by Tanzanian palliative care specialists (physicians and nurses trained in palliative care), poor-prognosis cancer patients and their lay caregivers (patients and caregivers), and LHWs. Central to mPCL is the validated African Palliative Care Outcome Scale (POS), which was adapted for automated, twice-weekly collection of quality of life-focused patient and caregiver responses and timely review, reaction, and tracking by specialists and LHWs. Prototype usability testing sessions were conducted in person with 21 key informants representing target end users. Sessions consisted of direct observations and qualitative and quantitative feedback on app ease of use and recommendations for improvement. Results were applied to optimize the prototype for subsequent real-world testing. Early pilot testing was conducted by deploying the app among 10 patients and caregivers, randomized to mPCL use versus phone-contact POS collection, and then gathering specialist and study team feedback to further optimize the prototype for a broader randomized field study to examine the app's effectiveness in symptom control among cancer patients. RESULTS: mPCL functionalities include the ability to create and update a synoptic clinical record, regular real-time symptom assessment, patient or caregiver and care team communication and care coordination, symptom-focused educational resources, and ready access to emergency phone contact with a care team member. Results from the usability and pilot testing demonstrated that all users were able to successfully navigate the app, and feedback suggests that mPCL has clinical utility. User-informed recommendations included further improvement in app navigation, simplification of patient and caregiver components and language, and delineation of user roles. CONCLUSIONS: We designed, built, and tested a usable, functional mobile app prototype that supports outpatient palliative care for Tanzanian patients with cancer. mPCL is expressly designed to facilitate coordinated care via customized interfaces supporting core users-patients or caregivers, LHWs, and members of the palliative care team-and their respective roles. Future work is needed to demonstrate the effectiveness and sustainability of mPCL to remotely support the symptom control needs of Tanzanian cancer patients, particularly in harder-to-reach areas.

Improving Access to Self-Expanding Metal Stents for Patients With Esophageal Cancer in Eastern Africa: A Stepwise Implementation Strategy.

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.

A Case-Control Study to Evaluate Environmental and Lifestyle Risk Factors for Esophageal Cancer in Tanzania.

BACKGROUND: East Africa is affected by a disproportionately high burden of esophageal squamous cell carcinoma (ESCC). METHODS: We conducted an incident case-control study in Dar es Salaam, Tanzania with 1:1 matching for gender and age. A questionnaire evaluated known and putative risk factors for ESCC. Cochran-Mantel-Haenszel and multivariable conditional logistic regression analyses were applied to evaluate associations with ESCC risk, with adjustment for geographic zone. RESULTS: Of 471 cases and 471 controls, the majority were male (69%); median ages were 59 and 55, respectively. In a multivariable logistic regression model, a low International Wealth Index (IWI) score [OR 2.57; 95% confidence interval (CI), 1.41-4.68], former smoking (OR 2.45; 95% CI, 1.46-4.13), second-hand smoke in the household (OR 1.67; 95% CI, 1.01-2.77), daily spicy chilies (OR 1.62; 1.04-2.52), and daily salted foods (OR 2.02; 95% CI, 1.06-3.85) were associated with increased risk of ESCC. Daily consumption of raw greens (OR 0.36; 95% CI, 0.16-0.80), fruit (OR 0.47; 95% CI, 0.27-0.82), and smoked fish (OR 0.31; 95% CI, 0.15-0.66) were protective. Permanent residence in the Central (OR 5.03; 95% CI, 2.16-11.73), Northern-Lake (OR 2.40; 95% CI, 1.46-3.94), or Southern Highlands zones (OR 3.18; 95% CI, 1.56-6.50) of Tanzania were associated with increased risk compared with residence in the Eastern zone. CONCLUSIONS: Low IWI score, smoke exposure(s), geographic zone, and dietary factors were associated with risk for ESCC in Tanzania. IMPACT: These findings will inform the development of future hypothesis-driven studies to examine risk factors for the high burden of ESCC in East Africa.See related commentary by McCormack et al., p. 248.

Development of a theory-driven implementation strategy for cancer management guidelines in sub-Saharan Africa.

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.

Efficacy of an Intensive, Ultrasound-Guided Fine-Needle Aspiration Biopsy Training Workshop in Tanzania.

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.

Characteristics of Esophageal Cancer Cases in Tanzania.

PURPOSE: Age-standardized incidence rates for esophageal cancer (EC) in East Africa have been reported as disproportionately high compared with the worldwide incidence of nine per 100,000 population. This study aimed to characterize EC cases seen at Muhimbili National Hospital and Ocean Road Cancer Institute in Dar es Salaam, Tanzania. METHODS: Demographic, clinical, and treatment variables were abstracted from charts of patients who received care for a diagnosis of EC at one or both institutions between 2011 and 2013. Categorical data were summarized as frequency counts and percentages. Continuous data were presented as medians and ranges. To compare men and women, Pearson's χ2 and two-sample t tests were applied. RESULTS: Seven hundred thirty-eight unique cases of EC were identified, of whom 68% were men and the median age was 60 years (range, 19 to 95 years). Notably, 93 cases (13%) were ≤ 40 years old at diagnosis. Squamous cell carcinoma was the dominant histology, comprising 90% of cases with documented histopathology. However, 34% of cases with a diagnosis of EC were not pathologically confirmed. The stage was documented as locoregional in 4% of cases, locally advanced in 20% of cases, metastatic in 14% of cases, and unknown in 63% of cases. Of 430 patients who received treatment at Ocean Road Cancer Institute, 76% were treated with radiation, 44% were treated with chemotherapy, 3% underwent a cancer-related surgical procedure, and 10% of cases received no cancer-directed therapy. The median overall survival for all patients was 6.9 months (95% CI, 5.0 to 12.8), regardless of stage at presentation. CONCLUSION: Between 2011 and 2013, cases of EC represented a large clinical burden at both institutions.

The African Esophageal Cancer Consortium: A Call to Action.

Esophageal cancer is the eighth most common cancer worldwide and the sixth most common cause of cancer-related death; however, worldwide incidence and mortality rates do not reflect the geographic variations in the occurrence of this disease. In recent years, increased attention has been focused on the high incidence of esophageal squamous cell carcinoma (ESCC) throughout the eastern corridor of Africa, extending from Ethiopia to South Africa. Nascent investigations are underway at a number of sites throughout the region in an effort to improve our understanding of the etiology behind the high incidence of ESCC in this region. In 2017, these sites established the African Esophageal Cancer Consortium. Here, we summarize the priorities of this newly established consortium: to implement coordinated multisite investigations into etiology and identify targets for primary prevention; to address the impact of the clinical burden of ESCC via capacity building and shared resources in treatment and palliative care; and to heighten awareness of ESCC among physicians, at-risk populations, policy makers, and funding agencies.