Quality indicators for evaluating cancer care in low-income and middle-income country settings: a multinational modified Delphi study.

This Policy Review sourced opinions from experts in cancer care across low-income and middle-income countries (LMICs) to build consensus around high-priority measures of care quality. A comprehensive list of quality indicators in medical, radiation, and surgical oncology was identified from systematic literature reviews. A modified Delphi study consisting of three 90-min workshops and two international electronic surveys integrating a global range of key clinical, policy, and research leaders was used to derive consensus on cancer quality indicators that would be both feasible to collect and were high priority for cancer care systems in LMICs. Workshop participants narrowed the list of 216 quality indicators from the literature review to 34 for inclusion in the subsequent surveys. Experts' responses to the surveys showed consensus around nine high-priority quality indicators for measuring the quality of hospital-based cancer care in LMICs. These quality indicators focus on important processes of care delivery from accurate diagnosis (eg, histologic diagnosis via biopsy and TNM staging) to adequate, timely, and appropriate treatment (eg, completion of radiotherapy and appropriate surgical intervention). The core indicators selected could be used to implement systems of feedback and quality improvement.

Addressing challenges in low-income and middle-income countries through novel radiotherapy research opportunities.

Although radiotherapy continues to evolve as a mainstay of the oncological armamentarium, research and innovation in radiotherapy in low-income and middle-income countries (LMICs) faces challenges. This third Series paper examines the current state of LMIC radiotherapy research and provides new data from a 2022 survey undertaken by the International Atomic Energy Agency and new data on funding. In the context of LMIC-related challenges and impediments, we explore several developments and advances-such as deep phenotyping, real-time targeting, and artificial intelligence-to flag specific opportunities with applicability and relevance for resource-constrained settings. Given the pressing nature of cancer in LMICs, we also highlight some best practices and address the broader need to develop the research workforce of the future. This Series paper thereby serves as a resource for radiation professionals.

Pharmaceutical industry relationships with oncologists in sub-Saharan Africa.

Health-care systems in sub-Saharan Africa are considered to be new markets for pharmaceutical companies. This perception is particularly relevant within oncology, as the pharmaceutical industry has changed strategic priorities in the past 10 years to focus on cancer. Since the 1930s, pharmaceutical companies have used advertisements, sample drugs, gifts, paid speaking engagements, advisory boards, and trips to conferences to influence clinical practice and policy. A large amount of literature describes the commonness of these practices and their effects on the behaviour of doctors. However, these data come almost exclusively from high-income countries. Industry-doctor relationships are increasingly common in sub-Saharan Africa and other low-income and middle-income countries. Although there are undoubtedly risks of industry engagement in low-income and middle-income countries, many programmes with educational, research, and clinical value would not occur in these countries without industry support. Thus, what is known about these relationships in high-income countries will not necessarily apply in low-income and middle-income countries. There is a need for widespread discussion about industry-oncologist interactions across the African continent and context-specific data to understand the potential risks and benefits of these relationships.

Mosquito control exposures and breast cancer risk: analysis of 1071 cases and 2096 controls from the Ghana Breast Health Study.

Epidemiologic data on insecticide exposures and breast cancer risk are inconclusive and mostly from high-income countries. Using data from 1071 invasive pathologically confirmed breast cancer cases and 2096 controls from the Ghana Breast Health Study conducted from 2013 to 2015, we investigated associations with mosquito control products to reduce the spread of mosquito-borne diseases, such as malaria. These mosquito control products were insecticide-treated nets, mosquito coils, repellent room sprays, and skin creams for personal protection against mosquitos. Multivariable and polytomous logistic regression models were used to estimate odds ratios (ORadj) and 95% confidence intervals (CI) with breast cancer risk-adjusted for potential confounders and known risk factors. Among controls, the reported use of mosquito control products were mosquito coils (65%), followed by insecticide-treated nets (56%), repellent room sprays (53%), and repellent skin creams (15%). Compared to a referent group of participants unexposed to mosquito control products, there was no significant association between breast cancer risk and mosquito coils. There was an association in breast cancer risk with reported use of insecticide-treated nets; however, that association was weak and not statistically significant. Participants who reported using repellent sprays were at elevated risks compared to women who did not use any mosquito control products, even after adjustment for all other mosquito control products (OR = 1.42, 95% CI=1.15-1.75). We had limited power to detect an association with repellent skin creams. Although only a few participants reported using repellent room sprays weekly/daily or < month-monthly, no trends were evident with increased frequency of use of repellent sprays, and there was no statistical evidence of heterogeneity by estrogen receptor (ER) status (p-het > 0.25). Our analysis was limited when determining if an association existed with repellent skin creams; therefore, we cannot conclude an association. We found limited evidence of risk associations with widely used mosquito coils and insecticide-treated nets, which are reassuring given their importance for malaria prevention. Our findings regarding specific breast cancer risk associations, specifically those observed between repellent sprays, require further study.

Measured body size and serum estrogen metabolism in postmenopausal women: the Ghana Breast Health Study.

BACKGROUND: Several anthropometric measures have been associated with hormone-related cancers, and it has been shown that estrogen metabolism in postmenopausal women plays an important role in these relationships. However, little is known about circulating estrogen levels in African women, and the relevance to breast cancer or breast cancer risk factors. To shed further light on the relationship of anthropometric factors and estrogen levels in African women, we examined whether measured body mass index (BMI), waist-to-hip ratio (WHR), height, and self-reported body size were associated with serum estrogens/estrogen metabolites in a cross-sectional analysis among postmenopausal population-based controls of the Ghana Breast Health Study. METHODS: Fifteen estrogens/estrogen metabolites were quantified using liquid chromatography-tandem mass spectrometry in serum samples collected from postmenopausal female controls enrolled in the Ghana Breast Health Study, a population-based case-control study conducted in Accra and Kumasi. Geometric means (GMs) of estrogens/estrogen metabolites were estimated using linear regression, adjusting for potential confounders. RESULTS: Measured BMI (≥ 30 vs. 18.5-24.9 kg/m2) was positively associated with parent estrogens (multivariable adjusted GM for unconjugated estrone: 78.90 (66.57-93.53) vs. 50.89 (43.47-59.59), p-value < 0.0001; and unconjugated estradiol: 27.83 (21.47-36.07) vs. 13.26 (10.37-16.95), p-value < 0.0001). Independent of unconjugated estradiol, measured BMI was associated with lower levels of 2-pathway metabolites and higher levels of 16-ketoestradriol. Similar patterns of association were found with WHR; however, the associations were not entirely independent of BMI. Height was not associated with postmenopausal estrogens/estrogen metabolite levels in African women. CONCLUSIONS: We observed strong associations between measured BMI and parent estrogens and estrogen metabolite patterns that largely mirrored relations that have previously been associated with higher breast cancer risk in postmenopausal White women. The consistency of the BMI-estrogen metabolism associations in our study with those previously noted among White women suggests that estrogens likely explain part of the BMI-postmenopausal breast cancer risk in both groups. These findings merit evaluation in Black women, including prospective studies.

The oral microbiome and breast cancer and nonmalignant breast disease, and its relationship with the fecal microbiome in the Ghana Breast Health Study.

The oral microbiome, like the fecal microbiome, may be related to breast cancer risk. Therefore, we investigated whether the oral microbiome was associated with breast cancer and nonmalignant breast disease, and its relationship with the fecal microbiome in a case-control study in Ghana. A total of 881 women were included (369 breast cancers, 93 nonmalignant cases and 419 population-based controls). The V4 region of the 16S rRNA gene was sequenced from oral and fecal samples. Alpha-diversity (observed amplicon sequence variants [ASVs], Shannon index and Faith's Phylogenetic Diversity) and beta-diversity (Bray-Curtis, Jaccard and weighted and unweighted UniFrac) metrics were computed. MiRKAT and logistic regression models were used to investigate the case-control associations. Oral sample alpha-diversity was inversely associated with breast cancer and nonmalignant breast disease with odds ratios (95% CIs) per every 10 observed ASVs of 0.86 (0.83-0.89) and 0.79 (0.73-0.85), respectively, compared to controls. Beta-diversity was also associated with breast cancer and nonmalignant breast disease compared to controls (P ≤ .001). The relative abundances of Porphyromonas and Fusobacterium were lower for breast cancer cases compared to controls. Alpha-diversity and presence/relative abundance of specific genera from the oral and fecal microbiome were strongly correlated among breast cancer cases, but weakly correlated among controls. Particularly, the relative abundance of oral Porphyromonas was strongly, inversely correlated with fecal Bacteroides among breast cancer cases (r = -.37, P ≤ .001). Many oral microbial metrics were strongly associated with breast cancer and nonmalignant breast disease, and strongly correlated with fecal microbiome among breast cancer cases, but not controls.

Breast cancer screening in sub-Saharan Africa: a systematic review and ethical appraisal.

BACKGROUND: The aim of this systematic review was to evaluate the evidence and clinical outcomes of screening interventions and implementation trials in sub-Saharan Africa (SSA) and also appraise some ethical issues related to screening in the region through quantitative and qualitative narrative synthesis of the literature. METHODS: We searched Pubmed, OvidMEDLINE, Embase, and Web of Science to identify studies published on breast cancer screening interventions and outcomes in SSA. Descriptive statistics were used to summarize the frequency and proportions of extracted variables, and narrative syntheses was used to evaluate the clinical outcomes of the different screening modalities. The mixed methods appraisal tool was used to assess the quality of studies included in the review. RESULTS: Fifteen studies were included, which consisted of 72,572 women in ten countries in SSA. 63% (8/15) of the included publications evaluated Clinical Breast Examination (CBE), 47% (7/15) evaluated mammography and 7% (1/15) evaluated ultrasound screening. The cancer detection rate was < 1/1000 to 3.3/1000 and 3.3/100 to 56/1000 for CBE and mammography screening respectively. There was a lot of heterogeneity in CBE methods, target age for screening and no clear documentation of screening interval. Cost-effective analyses showed that CBE screening linked to comprehensive cancer care is most cost effective. There was limited discussion of the ethics of screening, including the possible harms of screening in the absence of linkage to care. The gap between conducting good screening program and the appropriate follow-up with diagnosis and treatment remains one of the major challenges of screening in SSA. DISCUSSION: There is insufficient real-world data to support the systematic implementation of national breast cancer screening in SSA. Further research is needed to answer important questions about screening, and national and international partnerships are needed to ensure that appropriate diagnostic and treatment modalities are available to patients who screen positive.

Financial toxicity of cancer care in low- and middle-income countries: a systematic review and meta-analysis.

INTRODUCTION: The costs associated with cancer diagnosis, treatment and care present enormous financial toxicity. However, evidence of financial toxicity associated with cancer in low- and middle-income countries (LMICs) is scarce. AIM: To determine the prevalence, determinants and how financial toxicity has been measured among cancer patients in LMICs. METHODS: Four electronic databases were searched to identify studies of any design that reported financial toxicity among cancer patients in LMICs. Random-effects meta-analysis was used to derive the pooled prevalence of financial toxicity. Sub-group analyses were performed according to costs and determinants of financial toxicity. RESULTS: A total of 31 studies were included in this systematic review and meta-analysis. The pooled prevalence of objective financial toxicity was 56.96% (95% CI, 30.51, 106.32). In sub-group meta-analyses, the objective financial toxicity was higher among cancer patients with household size of more than four (1.17% [95% CI, 1.03, 1.32]; p = 0.02; I2 = 0%), multiple cycles of chemotherapy (1.94% [95% CI, 1.00, 3.75]; p = 0.05; I2 = 43%) and private health facilities (2.87% [95% CI, 1.89, 4.35]; p < 0.00001; I2 = 26%). Included studies hardly focused primarily on subjective measures of financial toxicity, such as material, behavioural and psychosocial. One study reported that 35.4% (n = 152 of 429) of cancer patients experienced high subjective financial toxicity. CONCLUSIONS: This study indicates that cancer diagnosis, treatment and care impose high financial toxicity on cancer patients in LMICs. Further rigorous research on cancer-related financial toxicity is needed.

Outcomes of patients with cervical cancer treated with low- or high-dose rate brachytherapy after concurrent chemoradiation.

OBJECTIVE: The majority of patients with cervical cancer in Ghana present with locally advanced disease. In October 2014, high-dose rate (HDR) brachytherapy was introduced at the National Center for Radiotherapy, Accra after years of using low-dose rate (LDR) brachytherapy. The aim of this study was to compare the treatment outcomes of patients treated with LDR versus HDR brachytherapy. METHODS: Patients with cervical cancer treated from January 2008 to December 2017 were reviewed. Those with stage IB-IIIB who received chemoradiation plus brachytherapy were included in the study. Post-operative patients and those with stage IV were excluded. The study end points were local control, disease-free survival, and overall survival at 2 years. Endpoints were estimated using the Kaplan-Meier method. Comparisons between treatment groups were performed using the log-rank test and Cox proportional hazards model. RESULTS: We included 284 LDR and 136 HDR brachytherapy patients. For stages IB, IIA, IIB, IIIA and IIIB disease, the 2-year local control for LDR versus HDR brachytherapy was 63% and 61% (p=0.35), 86% and 90% (p=0.68), 86% and 88% (p=0.83), 66% and 60% (p=0.56), and 77% and 40% (p=0.005), respectively. The 2-year disease-free survival for LDR versus HDR brachytherapy was 64% and 61% (p=0.50), 81% and 69% (p=0.18), 81% and 80% (p=0.54), 62% and 33% (p=0.82), and 71% and 30% (p=0.001) for stages IB, IIA, IIB, IIIA, and IIIB, respectively. The 2-year overall survival for LDR versus HDR brachytherapy was 94% and 93% (p=0.92), 98% and 68% (p=0.21), 89% and 88% (p=0.60), and 88% and 82% (p=0.34) for stages IB, IIA, IIB, and IIIB disease, respectively. CONCLUSION: There was no difference between LDR and HDR brachytherapy in local control and disease-free survival for all stages of disease, except in stage IIIB. These findings highlight the need to refine this brachytherapy technique for this group of patients.

Development of the 'REadiness SElf-assessment (RESEA) guide' to assist low and middle-income countries with establishing safe and sustainable radiotherapy services: a pragmatic sequential mixed qualitative methods project.

BACKGROUND: Improving access to radiotherapy services in low and middle-income countries (LMICs) is challenging. Many LMICs' radiotherapy initiatives fail because of multi-faceted barriers leading to significant wastage of scarce resources. Supporting LMICs to self-assess their readiness for establishing radiotherapy services will help to improve cancer outcomes by ensuring safe, effective and sustainable evidenced-based cancer care. The aim of the study was to develop practical guidance for LMICs on self-assessing their readiness to establish safe and sustainable radiotherapy services. METHODS: The Access to Radiotherapy for Cancer treatment (ARC) Project was a pragmatic sequential mixed qualitative methods design underpinned by the World Health Organisation's 'Innovative Care for Chronic Conditions Framework' and 'Health System Building Blocks Framework for Action' conceptual frameworks. This paper reports on the process of overall data integration and meta-inference from previously published components comprising a systematic review and two-part qualitative study (semi-structured interviews and a participant validation process). The meta-inferences enabled a series of radiotherapy readiness self-assessment requirements to be generated, formalised as a REadiness SElf-Assessment (RESEA) Guide' for use by LMICs. FINDINGS: The meta-inferences identified a large number of factors that acted as facilitators and/or barriers, depending on the situation, which include: awareness and advocacy; political leadership; epidemiological data; financial resources; basic physical infrastructure; radiation safety legislative and regulatory framework; project management; and radiotherapy workforce training and education. 'Commitment', 'cooperation', 'capacity' and 'catalyst' were identified as the key domains enabling development of radiotherapy services. Across these four domains, the RESEA Guide included 37 requirements and 120 readiness questions that LMICs need to consider and answer as part of establishing a new radiotherapy service. CONCLUSIONS: The RESEA Guide provides a new resource for LMICs to self-assess their capacity to establish safe and sustainable radiotherapy services. Future evaluation of the acceptability and feasibility of the RESEA Guide is needed to inform its validity. Further work, including field study, is needed to inform further refinements. Exploratory and confirmatory factor analyses are required to reduce the data set and test the fit of the four-factor structure (commitment, cooperation, capacity and catalyst) found in the current study.

Breast cancer early detection: A phased approach to implementation.

When breast cancer is detected and treated early, the chances of survival are very high. However, women in many settings face complex barriers to early detection, including social, economic, geographic, and other interrelated factors, which can limit their access to timely, affordable, and effective breast health care services. Previously, the Breast Health Global Initiative (BHGI) developed resource-stratified guidelines for the early detection and diagnosis of breast cancer. In this consensus article from the sixth BHGI Global Summit held in October 2018, the authors describe phases of early detection program development, beginning with management strategies required for the diagnosis of clinically detectable disease based on awareness education and technical training, history and physical examination, and accurate tissue diagnosis. The core issues address include finance and governance, which pertain to successful planning, implementation, and the iterative process of program improvement and are needed for a breast cancer early detection program to succeed in any resource setting. Examples are presented of implementation, process, and clinical outcome metrics that assist in program implementation monitoring. Country case examples are presented to highlight the challenges and opportunities of implementing successful breast cancer early detection programs, and the complex interplay of barriers and facilitators to achieving early detection for breast cancer in real-world settings are considered.

Accreditation Improves Quality of Oncology Education in Low- and Middle-Income Countries: Perspectives of African Oncologists.

The purpose of this study is to understand the perspectives of African Oncologists on the role of accreditation and on global standards. We developed a survey that addressed African oncologists' opinions on the role of accreditation. The survey also included 187 standards from World Federation of Medical Education Postgraduate medical education (PGME) standards, American Council of Graduate Medical Education (ACGME)-I standards for hematology/oncology, and the Royal College of Physician and Surgeons of Canada Medical Oncology standards. A 3-point scale was employed for each standard: 1 = not important, 2 = important but not essential, 3 = essential. The survey was sent to 79 physicians, 38 responded. Eighty-seven percent agreed that accreditation ensures quality. Forty-five percent agreed it will not increase migration of qualified doctors. Twenty-two individuals who completed the entire survey were analyzed for the standards. Five standards received the highest ratings of 3 (essential) from all respondents. One standard received a rating of < 2.0. The majority of standards had ratings between 2.6 and 2.94 indicating African oncologists found most standards to be useful. Ratings < 2.6 were mostly related to resource constraints. Most African Oncologists believed that accreditation ensures quality of education, and most standards were considered important. This data is useful for developing and adapting accreditation standards in resource-constrained settings.

Skin lighteners and hair relaxers as risk factors for breast cancer: results from the Ghana breast health study.

Skin lighteners and hair relaxers, both common among women of African descent, have been suggested as possibly affecting breast cancer risk. In Accra and Kumasi, Ghana, we collected detailed information on usage patterns of both exposures among 1131 invasive breast cancer cases and 2106 population controls. Multivariate analyses estimated odds ratios (ORs) and 95% confidence intervals (CIs) after adjustment for breast cancer risk factors. Control usage was 25.8% for ever use of skin lighteners and 90.0% for use of hair relaxers for >1 year. The OR for skin lighteners was 1.10 (95% CI 0.93-1.32), with higher risks for former (1.21, 0.98-1.50) than current (0.96, 0.74-1.24) users. No significant dose-response relations were seen by duration, age at first use or frequency of use. In contrast, an OR of 1.58 (95% CI 1.15-2.18) was associated with use of hair relaxers, with higher risks for former (2.22, 1.56-3.16) than current (1.39, 1.00-1.93) users. Although numbers of burns were inconsistently related to risk, associations increased with duration of use, restricted to women who predominately used non-lye products (P for trend < 0.01). This was most pronounced among women with few children and those with smaller tumors, suggesting a possible role for other unmeasured lifestyle factors. This study does not implicate a substantial role for skin lighteners as breast cancer risk factors, but the findings regarding hair relaxers were less reassuring. The effects of skin lighteners and hair relaxers on breast cancer should continue to be monitored, especially given some biologic plausibility for their affecting risk.

The global burden of women's cancers: a grand challenge in global health.

Every year, more than 2 million women worldwide are diagnosed with breast or cervical cancer, yet where a woman lives, her socioeconomic status, and agency largely determines whether she will develop one of these cancers and will ultimately survive. In regions with scarce resources, fragile or fragmented health systems, cancer contributes to the cycle of poverty. Proven and cost-effective interventions are available for both these common cancers, yet for so many women access to these is beyond reach. These inequities highlight the urgent need in low-income and middle-income countries for sustainable investments in the entire continuum of cancer control, from prevention to palliative care, and in the development of high-quality population-based cancer registries. In this first paper of the Series on health, equity, and women's cancers, we describe the burden of breast and cervical cancer, with an emphasis on global and regional trends in incidence, mortality, and survival, and the consequences, especially in socioeconomically disadvantaged women in different settings.

Fear of Mastectomy Associated with Delayed Breast Cancer Presentation Among Ghanaian Women.

BACKGROUND: Breast cancer is the leading cause of cancer mortality among women globally. Most women in Ghana present with advanced stage disease. The aim of this study is to characterize sociocultural factors associated with delayed presentation. MATERIALS AND METHODS: Qualitative study (grounded theory, constant comparative method) using individual in-depth interviews with breast cancer patients seen at the Korle Bu Teaching Hospital in Accra, Ghana. Interviews were conducted in English and three local languages. We achieved theoretical saturation with 31 participants. RESULTS: The mean length of delay reported by patients was approximately 1 year. Five recurrent themes were related to delayed presentation: (a) Women with a confirmed breast cancer diagnosis delay treatment because of the fear of mastectomy due to self and societal stigma; (b) role of the church as a social support system given the societal stigma associated with breast cancer; (c) study participants expressed some awareness of breast cancer, but with varying depths of breast cancer knowledge encompassing both myths and misconceptions about breast cancer; (d) most patients present late because they do not associate a "painless" breast lump with possible breast malignancy; and (e) delayed presentation linked to significant financial burden associated with breast cancer treatment. CONCLUSION: Despite current efforts to increase breast cancer awareness, the fear of mastectomy remains one of the main reasons for delayed presentation. Successful breast cancer education programs will need to be framed within the broader sociocultural dimensions of femininity that address some of the stigma associated with mastectomy reported in the Ghanaian context. IMPLICATIONS FOR PRACTICE: Most women in Ghana present with advanced-stage disease. The aim of this study was to characterize sociocultural factors associated with delayed presentation. Although several quantitative studies have been conducted on delays in presentation in sub-Saharan Africa (SSA), this study is one of the few to identify fear of mastectomy as a reason for delayed presentation. Anecdotal data from current clinical experiences in SSA suggest that this is still an issue that has not been adequately reported and addressed in most SSA countries. The research results presented here will hopefully guide health providers and national organizations in designing breast cancer education programs in Ghana and other parts of SSA.

Design considerations for identifying breast cancer risk factors in a population-based study in Africa.

Although breast cancer is becoming more prevalent in Africa, few epidemiologic studies have been undertaken and appropriate methodologic approaches remain uncertain. We therefore conducted a population-based case-control study in Accra and Kumasi, Ghana, enrolling 2,202 women with lesions suspicious for breast cancer and 2,161 population controls. Biopsy tissue for cases prior to neoadjuvant therapy (if given), blood, saliva and fecal samples were sought for study subjects. Response rates, risk factor prevalences and odds ratios for established breast cancer risk factors were calculated. A total of 54.5% of the recruited cases were diagnosed with malignancies, 36.0% with benign conditions and 9.5% with indeterminate diagnoses. Response rates to interviews were 99.2% in cases and 91.9% in controls, with the vast majority of interviewed subjects providing saliva (97.9% in cases vs. 98.8% in controls) and blood (91.8% vs. 82.5%) samples; lower proportions (58.1% vs. 46.1%) provided fecal samples. While risk factor prevalences were unique as compared to women in other countries (e.g., less education, higher parity), cancer risk factors resembled patterns identified elsewhere (elevated risks associated with higher levels of education, familial histories of breast cancer, low parity and larger body sizes). Subjects with benign conditions were younger and exhibited higher socioeconomic profiles (e.g., higher education and lower parity) than those with malignancies, suggesting selective referral influences. While further defining breast cancer risk factors in Africa, this study showed that successful population-based interdisciplinary studies of cancer in Africa are possible but require close attention to diagnostic referral biases and standardized and documented approaches for high-quality data collection, including biospecimens.