Germline Testing Around the Globe: Challenges in Different Practice Settings.

Cancer is an increasing global public health burden. Lately, more emphasis has emerged on the importance of heredity in cancer, mostly driven by the introduction of germline genetic variants-directed therapeutics. It is true that 40% of cancer risk is attributed to modifiable environmental and lifestyle factors; still, 16% of cancers could be heritable, accounting for 2.9 of the 18.1 million cases diagnosed worldwide. At least two third of those will be diagnosed in countries with limited resources-low- and middle-income countries, especially where high rates of consanguine marriage and early age at diagnosis are already prevalent. Both are hallmarks of hereditary cancer. This creates a new opportunity for prevention, early detection, and recently therapeutic intervention. However, this opportunity is challenged by many obstacles along the path to addressing germline testing in patients with cancer in the clinic worldwide. Global collaboration and expertise exchange are important to bridge the knowledge gap and facilitate practical implementation. Adapting existing guidelines and prioritization according to local resources are essential to address the unique needs and overcome the unique barriers of each society.

Geographic Accessibility of Radiation Therapy Facilities in Sub-Saharan Africa.

PURPOSE: Access to radiation therapy in Sub-Saharan Africa (SSA) remains unacceptably low. Prior studies have focused on how many radiation therapy machines a country has but have not accounted for geographic accessibility, which is a known barrier to radiation therapy compliance. In this study, we describe accessibility measured as travel time by road to radiation therapy in SSA. METHODS AND MATERIALS: This study used geographic information systems modeling techniques. A list of radiation therapy facilities was obtained from the Directory of Radiotherapy Centres. We obtained a 1 km2 surface of travel times using a least-cost-path algorithm implemented in Google Earth Engine (Google, Mountain View, CA). AccessMod 5 (World Health Organization, Geneva, Switzerland) was used to compute the percentage of each country's population with access to a radiation therapy facility within prespecified one-way travel time intervals. We then ranked countries using 3 measures of access: 2-hour geographic access, units per capita, and units per cancer case. RESULTS: Only 24.4% of the population of SSA can access a radiation therapy facility within 2 hours of travel by road; access was 14.6% and 42.5% within 1 and 4 hours, respectively. More than 80% of Rwandans and South Africans were within 2 hours of radiation therapy, the highest in the region. Although countries with more radiation therapy units per capita tended to have higher 2-hour access, there was notable discordance between the 2 measures. Mauritania, Zambia, Sudan, and Namibia were among the top 10 countries ranked by machines per capita, but none ranked in the top 10 by 2-hour geographic access. There was similar discordance between 2-hour access and radiation therapy units per cancer case; Rwanda, Nigeria, Senegal, and Cote d'Ivoire ranked in the top 10 for the former but ranked worse using units per cancer case. CONCLUSIONS: Prior measures of radiation therapy access provide an incomplete picture. Geographic location of radiation therapy centers is a crucial component of access that should be considered for future planning in SSA.

Breast cancer molecular diagnostics in Rwanda: a cost-minimization study of immunohistochemistry versus a novel GeneXpert® mRNA expression assay.

Objective: To compare the financial and time cost of breast cancer biomarker analysis by immunohistochemistry with that by the Xpert® STRAT4 assay. Methods: We estimated costs (personnel, location, consumables and indirect) and time involved in breast cancer diagnosis at the Butaro Cancer Centre of Excellence, Rwanda, using time-driven activity-based costing. We performed a cost-minimization analysis to compare the cost of biomarker analysis for estrogen receptor, progesterone receptor and human epidermal growth factor receptor-2 status with immunohistochemistry versus STRAT4. We performed sensitivity analyses by altering laboratory-specific parameters for the two methods. Findings: We estimated that breast cancer diagnosis in Rwanda costs 138.29 United States dollars (US$) per patient when conducting biomarker analysis by immunohistochemistry. At a realistic immunohistochemistry antibody utilization efficiency of 70%, biomarker analysis comprises 48.7% (US$ 67.33) of diagnostic costs and takes 33 min. We determined that biomarker analysis with STRAT4 yields a reduction in diagnosis cost of US$ 7.33 (10.9%; 7.33/67.33), and in pathologist and technician time of 20 min (60.6%; 20/33), per patient. Our sensitivity analysis revealed that no cost savings would be made in laboratories with antibody utilization efficiencies over 90%, or where only estrogen and/or progesterone receptor status are assessed; however, such operational efficiencies are unlikely, and more laboratories are pursuing human epidermal growth factor receptor-2 analysis as targeted therapies become increasingly available. Conclusion: Breast cancer biomarker analysis with STRAT4 has the potential to reduce the required human and capital resources in sub-Saharan African laboratories, leading to improved treatment selection and better clinical outcomes.

A Systematic Review of Patient Education Strategies for Oncology Patients in Low- and Middle-Income Countries.

INTRODUCTION: Patient education can facilitate early cancer diagnosis, enhance treatment adherence, and improve outcomes. While there is increasing cancer burden in low- and middle-income countries (LMICs), there is little research to inform successful patient education in these regions. This systematic review summarizes the existing literature on oncology education and evaluation strategies in LMICs, identifies best practices, and highlights areas which require further investigation. METHODS: The review was conducted using PRISMA guidelines and an a priori protocol. Four databases (Ovid Medline, Cochrane Libraries, Embase, and Cabi) were searched in December 2021. Two independent reviewers evaluated studies for inclusion. Using a coded data extraction form, information was collected about the study site, intervention characteristics, and evaluation methods. RESULTS: Of the 2047 articles generated in the search, 77 met the inclusion criteria. Twenty-four countries were represented; only 6 studies (8%) were in low-income countries. The most common education methods included technology-based interventions (31, 40%) and visual pamphlets or posters (20, 26%). More than one education method was used in 57 (74%) studies. Nurses were the most frequent educators (25, 33%). An evaluation was included in 74 (96%) studies, though only 41 (55%) studies used a validated tool. Patient knowledge was the most common measured outcome in 35 (47%) studies. CONCLUSIONS: There is limited empiric research on oncology patient education in LMICs. The available data show heterogeneity in education approaches and gaps in evaluation. Further research to determine successful patient education and evaluation strategies is urgently needed to improve treatment cancer outcomes in LMICs.

The utility of procalcitonin for diagnosing bacteremia and bacterial pneumonia in hospitalized oncology patients.

PURPOSE: Procalcitonin (PCT) is an inflammatory marker elevated in bacteremia and bacterial pneumonia. We aimed to assess the real-world diagnostic accuracy of PCT in hospitalized patients with malignancy. METHODS: A retrospective cohort of 715 patients with cancer who had PCT measured during 750 admissions was analyzed. Diagnosis of bacteremia was determined using blood culture data. Diagnosis of bacterial pneumonia was based on radiographic infiltrate and/or sputum culture. PCT's performance was assessed using receiver operating characteristic (ROC) curves, sensitivity, and specificity. RESULTS: Patients had bacteremia, bacterial pneumonia, or both during 210 admissions (28%). PCT elevation above 0.5 ng/mL was significantly associated with diagnosed infection in the overall population (p < 0.0001) and in subgroups with solid tumor malignancies (p < 0.0001) and hematologic malignancies (p = 0.008). PCT was associated with infectious status in patients with any metastases, but not those with primary lung cancer, lung metastases, neuroendocrine tumors, febrile neutropenia, or history of bone marrow transplant (BMT). The area under the ROC curve for PCT in the overall population was 0.655. An ideal cutoff of 0.21 ng/mL led to a sensitivity of 60% and specificity of 59%. At cutoffs of 0.5 ng/mL and 0.05 ng/mL, PCT's sensitivity was 39% and 94%, while specificity was 79% and 17%, respectively. CONCLUSION: In this large cohort of hospitalized oncology patients, PCT elevation was associated with diagnosed bacteremia and/or bacterial pneumonia. However, specificity was limited, and PCT elevation was not associated with diagnosed infection in some subpopulations. While PCT may have some diagnostic utility for hospitalized oncology patients, values must be interpreted cautiously and considering clinical context.

Breast cancer molecular diagnostics in Rwanda: a cost-minimization study of immunohistochemistry versus a novel GeneXpert® mRNA expression assay

Objective To compare the financial and time cost of breast cancer biomarker analysis by immunohistochemistry with that by the Xpert® STRAT4 assay. Methods We estimated costs (personnel, location, consumables and indirect) and time involved in breast cancer diagnosis at the Butaro Cancer Centre of Excellence, Rwanda, using time-driven activity-based costing. We performed a cost-minimization analysis to compare the cost of biomarker analysis for estrogen receptor, progesterone receptor and human epidermal growth factor receptor-2 status with immunohistochemistry versus STRAT4. We performed sensitivity analyses by altering laboratory-specific parameters for the two methods. Findings We estimated that breast cancer diagnosis in Rwanda costs 138.29 United States dollars (US$) per patient when conducting biomarker analysis by immunohistochemistry. At a realistic immunohistochemistry antibody utilization efficiency of 70%, biomarker analysis comprises 48.7% (US$ 67.33) of diagnostic costs and takes 33 min. We determined that biomarker analysis with STRAT4 yields a reduction in diagnosis cost of US$ 7.33 (10.9%; 7.33/67.33), and in pathologist and technician time of 20 min (60.6%; 20/33), per patient. Our sensitivity analysis revealed that no cost savings would be made in laboratories with antibody utilization efficiencies over 90%, or where only estrogen and/or progesterone receptor status are assessed; however, such operational efficiencies are unlikely, and more laboratories are pursuing human epidermal growth factor receptor-2 analysis as targeted therapies become increasingly available. Conclusion Breast cancer biomarker analysis with STRAT4 has the potential to reduce the required human and capital resources in subSaharan African laboratories, leading to improved treatment selection and better clinical outcomes.

Authorship Distribution and Under-Representation of Sub-Saharan African Authors in Global Oncology Publications.

PURPOSE: Local researchers must be engaged in research conducted in their populations. However, local authors from low- and middle-income countries are often under-represented in global health journals. This report aims to assess and describe the representation of authors in the Journal of Clinical Oncology Global Oncology (JCO GO). METHODS: This retrospective cross-sectional study describes data from JCO GO articles published between October 2015 and March 2020. Data were collected on studied countries, authorship position, classified as first, middle, or last, and country of authors' institutional affiliations. Countries were then categorized on the basis of their World Bank region and income classifications. We describe aggregate authorship distribution and distribution by region and income classification. Additionally, we explore the relationships between author's country and studied country. RESULTS: Of the 608 articles identified, 420 (69.1%) studied a single country population. Although articles represented studies from all World Bank regions, the sub-Saharan Africa (SSA) region accounted for the highest number (n = 145; 34.5%). In all other regions except SSA, most of the first (66.7%-100%) and last authors (56.6%-95.2%) had primary institutional affiliations based in the same region as the studied country. However, among articles about SSA countries, SSA first authors (n = 65; 44.8%) and last authors (n = 59; 40.7%) were under-represented. In fact, there were more North American first (n = 74; 51.0%) and last authors (n = 72; 49.6%) than SSA authors. There was higher SSA representation among middle authors (n = 97; 68.8%) in studies from the region. A similar trend was also noted with the under-representation of authors from low-income compared with high-income countries. CONCLUSION: SSA authors are under-represented in global oncology articles. Concerted strategies are needed to build local capacity, promote meaningful engagement, and foster equity.

Toward Equitable Access to Tertiary Cancer Care in Rwanda: A Geospatial Analysis.

PURPOSE: Geographic access to care is an important measure of health equity. In this study, we describe geographic access to cancer care centers (CCCs) in Rwanda with the current facilities providing care and examine how access could change with expanded care infrastructure. METHODS: Health facilities included are public hospitals administered by the Rwanda Ministry of Health. The WorldPop Project was used to estimate population distribution, and OpenStreetMap was used to determine travel routes. On the basis of geolocations of the facilities, AccessMod 5 was used to estimate the percentage of the population that live within 1 hour, 2 hours, and 4 hours of CCCs under the current (two facilities) and expanded care (seven facilities) scenarios. Variations in access by region, poverty, and level of urbanization were described. RESULTS: Currently, 13%, 41%, and 85% of Rwandans can access CCCs within one, two, and 4 hours of travel, respectively. With expansion of CCCs to seven facilities, access increases to 37%, 84%, and 99%, respectively. There is a substantial variation in current geographic access by province, with 1-hour access in Kigali at 98%, whereas access in the Western Province is 0%; care expansion could increase 2-hour access in the Western Province from 1% to 71%. Variation in access is also seen across the level of urbanization, with current 1-hour access in urban versus rural areas of 45% and 8%, respectively. Expanded care results in improvement of 1-hour access to 67% and 33%, respectively. Similar trends were also noted across poverty levels. CONCLUSION: Geographical access to CCCs varies substantially by province, level of urbanization, and poverty. These disparities can be alleviated by strategic care expansion to other tertiary care facilities across Rwanda.

Comparing absolute and relative distance and time travel measures of geographic access to healthcare facilities in rural Haiti.

INTRODUCTION: While travel distance and time are important proxies of physical access to health facilities, obtaining valid measures with an appropriate modelling method remains challenging in many settings. We compared five measures of geographic accessibility in Haiti, producing recommendations that consider available analytic resources and geospatial goals. METHODS: Eight public hospitals within the ministry of public health and population were included. We estimated distance and time between hospitals and geographic centroids of Haiti's section communes and population-level accessibility. Geographic feature data were obtained from public administrative databases, academic research databases and government satellites. We used validated geographic information system methods to produce five geographic access measures: (1) Euclidean distance (ED), (2) network distance (ND), (3) network travel time (NTT), (4) AccessMod 5 (AM5) distance (AM5D) and (5) AM5 travel time (AM5TT). Relative ranking of section communes across the measures was assessed using Pearson correlation coefficients, while mean differences were assessed using analysis of variance (ANOVA) and pairwise t-tests. RESULTS: All five geographic access measures were highly correlated (range: 0.78-0.99). Of the distance measures, ED values were consistently the shortest, followed by AM5D values, while ND values were the longest. ND values were as high as 2.3 times ED values. NTT models generally produced longer travel time estimates compared with AM5TT models. ED consistently overestimated population coverage within a given threshold compared with ND and AM5D. For example, population-level accessibility within 15 km of the nearest studied hospital in the Center department was estimated at 68% for ED, 50% for AM5D and 34% for ND. CONCLUSION: While the access measures were highly correlated, there were significant differences in the absolute measures. Consideration of the benefits and limitations of each geospatial measure together with the intended purpose of the estimates, such as relative proximity of patients or service coverage, are key to guiding appropriate use.

Gaps in completion and timeliness of breast surgery and adjuvant therapy: a retrospective cohort of Haitian patients with nonmetastatic breast cancer.

BACKGROUND: There are limited data on breast surgery completion rates and prevalence of care-continuum delays in breast cancer treatment programs in low-income countries. METHODS: This study analyzes treatment data in a retrospective cohort of 312 female patients with non-metastatic breast cancer in Haiti. Descriptive statistics were used to summarize patient characteristics; treatments received; and treatment delays of > 12 weeks. Multivariate logistic regressions were performed to identify factors associated with receiving surgery and with treatment delays. Exploratory multivariate survival analysis examined the association between surgery delays and disease-free survival (DFS). RESULTS: Of 312 patients, 249 (80%) completed breast surgery. The odds ratio (OR) for surgery completion for urban vs. rural dwellers was 2.15 (95% confidence interval [CI]: 1.19-3.88) and for those with locally advanced vs. early-stage disease was 0.34 (95%CI: 0.16-0.73). Among the 223 patients with evaluable surgery completion timelines, 96 (43%) experienced delays. Of the 221 patients eligible for adjuvant chemotherapy, 141 (64%) received adjuvant chemotherapy, 66 of whom (47%) experienced delays in chemotherapy initiation. Presentation in the later years of the cohort (2015-2016) was associated with lower rates of surgery completion (75% vs. 85%) and with delays in adjuvant chemotherapy initiation (OR [95%CI]: 3.25 [1.50-7.06]). Exploratory analysis revealed no association between surgical delays and DFS. CONCLUSION: While majority of patients obtained curative-intent surgery, nearly half experienced delays in surgery and adjuvant chemotherapy initiation. Although our study was not powered to identify an association between surgical delays and DFS, these delays may negatively impact long-term outcomes.

Authorship Equity and Gender Representation in Global Oncology Publications.

PURPOSE: Authorship gender disparities persist across academic disciplines, including oncology. However, little is known about global variation in authorship gender distribution. METHODS: This retrospective cross-sectional study describes the distribution of author gender as determined from the first name across variables such as authorship position (first, middle, and last), country region, and country income level. The 608 articles with 5,302 authors included in this analysis were published in the Journal of Clinical Oncology Global Oncology, from its inception in October 2015 through March 2020. Primary outcome measure was author gender on the basis of first name probabilities assessed by genderize.io. World Bank classification was used to categorize the country region and income level. Odds ratios were used to describe associations between female last authorship and representation in other authorship positions. RESULTS: Although female authors were in the minority across all authorship positions, they were more under-represented in the last author position with 190 (32.1%) female, compared with 252 (41.4%) female first authors and 1,564 (38.1%) female middle authors. Female authors were most under-represented among authors from low-income countries, where they made up 21.6% of first authors and 9.1% of last authors. Of all the regions, sub-Saharan Africa and South Asia had the lowest percentage of female authors. Compared with articles with male last authors, those with female last authors had odds ratios (95% CI) of 2.2 (1.6 to 3.2) of having female first authors and 1.4 (0.9 to 2.1) of having 50% or more female middle authors. CONCLUSION: There are wide regional variations in author gender distribution in global oncology. Female authors remain markedly under-represented, especially in lower-income countries, sub-Saharan Africa, and South Asia. Future interventions should be tailored to mitigate these disparities.

Global challenges and policy solutions in breast cancer control.

Breast cancer is the leading cause of cancer morbidity, disability and mortality in women, worldwide. Overall, in 2020, it was the most diagnosed malignancy. Differences in breast cancer mortality have been historically evidenced, as a result of disparities in access to diagnosis, treatment and palliative care. Epidemiologic trends in the last decades display three main patterns of breast cancer mortality: some high-income countries report continuous substantial improvements exceeding 2% annual mortality reduction; however, many low- and middle-income countries (LMICs) have stagnant or even increasing mortality rates. Population-based studies show that investing in breast cancer control, based on a primary health care approach, and expanding the cancer treatment capacity can portend population health benefits, with positive changes of the epidemiological adverse trajectories. Framed as part of the political commitment to the Sustainable Development Goals Agenda, World Health Organization (WHO) has recently launched a global initiative to tackle disparities in breast cancer mortality. The WHO-led Global Breast Cancer Initiative (GBCI) is framed across 3 pillars, to address key determinants of the cancer-related outcomes: health promotion and early detection, timely access to diagnosis and treatment, comprehensive breast cancer treatment, palliative and survivorship care. GBCI is a systematized approach, with the goal to (i) increase the fraction of newly diagnosed invasive cancers being stage 1 or 2 at diagnosis (60% or more), (ii) ensure diagnostic work-up to be completed within 60 days from the first connection with the primary healthcare providers to avoid delays in diagnosis and treatment and (iii) assure 80% or more women with breast cancer to undergo and complete multimodal treatments. GBCI will pursue a comprehensive and multisectoral approach, to deliver population health, social and economic benefits, ultimately intended as an entry point for health system strengthening and for the broader cancer control.

Economic Evaluations of Breast Cancer Care in Low- and Middle-Income Countries: A Scoping Review.

BACKGROUND: Understanding the cost of delivering breast cancer (BC) care in low- and middle-income countries (LMICs) is critical to guide effective care delivery strategies. This scoping review summarizes the scope of literature on the costs of BC care in LMICs and characterizes the methodological approaches of these economic evaluations. MATERIALS AND METHODS: A systematic literature search was performed in five databases and gray literature up to March 2020. Studies were screened to identify original articles that included a cost outcome for BC diagnosis or treatment in an LMIC. Two independent reviewers assessed articles for eligibility. Data related to study characteristics and methodology were extracted. Study quality was assessed using the Drummond et al. checklist. RESULTS: Ninety-one articles across 38 countries were included. The majority (73%) of studies were published between 2013 and 2020. Low-income countries (2%) and countries in Sub-Saharan Africa (9%) were grossly underrepresented. The majority of studies (60%) used a health care system perspective. Time horizon was not reported in 30 studies (33%). Of the 33 studies that estimated the cost of multiple steps in the BC care pathway, the majority (73%) were of high quality, but studies varied in their inclusion of nonmedical direct and indirect costs. CONCLUSION: There has been substantial growth in the number of BC economic evaluations in LMICs in the past decade, but there remain limited data from low-income countries, especially those in Sub-Saharan Africa. BC economic evaluations should be prioritized in these countries. Use of existing frameworks for economic evaluations may help achieve comparable, transparent costing analyses. IMPLICATIONS FOR PRACTICE: There has been substantial growth in the number of breast cancer economic evaluations in low- and middle-income countries (LMICs) in the past decade, but there remain limited data from low-income countries. Breast cancer economic evaluations should be prioritized in low-income countries and in Sub-Saharan Africa. Researchers should strive to use and report a costing perspective and time horizon that captures all costs relevant to the study objective, including those such as direct nonmedical and indirect costs. Use of existing frameworks for economic evaluations in LMICs may help achieve comparable, transparent costing analyses in order to guide breast cancer control strategies.

Impact of COVID-19 on Cancer Care Delivery in Africa: A Cross-Sectional Survey of Oncology Providers in Africa.

PURPOSE: The COVID-19 pandemic has disrupted cancer care globally. There are limited data of its impact in Africa. This study aims to characterize COVID-19 response strategies and impact of COVID-19 on cancer care and explore misconceptions in Africa. METHODS: We conducted a web-based cross-sectional survey of oncology providers in Africa between June and August 2020. Descriptive statistics and comparative analysis by income groups were performed. RESULTS: One hundred twenty-two participants initiated the survey, of which 79 respondents from 18 African countries contributed data. Ninety-four percent (66 of 70) reported country mitigation and suppression strategies, similar across income groups. Unique strategies included courier service and drones for delivery of cancer medications (9 of 70 and 6 of 70, respectively). Most cancer centers remained open, but > 75% providers reported a decrease in patient volume. Not previously reported is the fear of infectivity leading to staff shortages and decrease in patient volumes. Approximately one third reported modifications of all cancer treatment modalities, resulting in treatment delays. A majority of participants reported ≤ 25 confirmed cases (44 of 68, 64%) and ≤ 5 deaths because of COVID-19 (26 of 45, 58%) among patients with cancer. Common misconceptions were that Africans were less susceptible to the virus (53 of 70, 75.7%) and decreased transmission of the virus in the African heat (44 of 70, 62.9%). CONCLUSION: Few COVID-19 cases and deaths were reported among patients with cancer. However, disruptions and delays in cancer care because of the pandemic were noted. The pandemic has inspired tailored innovative solutions in clinical care delivery for patients with cancer, which may serve as a blueprint for expanding care and preparing for future pandemics. Ongoing public education should address COVID-19 misconceptions. The results may not be generalizable to the entire African continent because of the small sample size.

Cost of breast cancer care in low- and middle-income countries: a scoping review protocol.

OBJECTIVE: This review will describe the scope of the literature on the cost of breast cancer care in low- and middle-income countries and summate the methodological characteristics and approaches of these economic evaluations. INTRODUCTION: In the past decade, there has been global momentum to improve capacity for breast cancer care in low- and middle-income countries, which have higher rates of breast cancer mortality compared to high-income countries. Understanding the cost of delivering breast cancer care in low- and middle-income countries is critical to guide effective cancer care delivery strategies and policy. INCLUSION CRITERIA: Studies that estimate the cost of breast cancer diagnosis and treatment in low- and middle-income countries will be included. Studies not available in English will be excluded. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Review guidelines will be utilized. The search strategy has been developed in consultation with a medical librarian and will be carried out on five electronic databases from their inception (MEDLINE, Embase, Web of Science, Global Health, WHO Global Index Medicus) as well as in gray literature sources. Two independent reviewers will review all abstracts and titles in the primary screen and full-text articles in the secondary screen. A third reviewer will adjudicate conflicts. One reviewer will perform data extraction. Study demographics, design, and methodological characteristics (such as costing perspective, time horizon, and included cost categories) will be summarized in narrative and tabular formats. The methodological quality of studies will be evaluated using a validated economic evaluation tool.