Malignant Extracranial Germ Cell Tumours: A First Report by the South African Children’s Cancer Study Group

OBJECTIVE To determine the overall survival (OS) and prognostic factors influencing outcomes in children and adolescents with malignant extracranial germ cell tumours (MEGCTs) in preparation for the development of a harmonised national treatment protocol. METHODS A retrospective folder review was undertaken at nine South African paediatric oncology units to document patient profiles, tumour and treatment-related data and outcomes. RESULTS Between 1 January 2000 and 31 December 2015, 218 patients were diagnosed with MEGCTs. Female sex (OR 2.26; p=0.037) and higher socio-economic status (SES) (HR 0.071; p=0.039) were associated with a significantly lower risk of death. Advanced clinical stage at diagnosis significantly affected 5-year OS: stage I -96%; stage II – 94.3%; stage III -75.5%; (p=0.017) and stage IV (60.1%; p<0.001). There was a significant association between earlier stage at presentation and higher SES (p=0.03). Patients with a serum AFP level of more than 33,000 ng/ml at diagnosis had significantly poorer outcomes (p=0.002). The use of chemotherapy significantly improved survival, irrespective of the regimen used (p33,000ng/ml were independently predictive of outcome. The relationship between SES and outcome is important as the implementation of a new national protocol aims to standardise care across the socio-economic divide.

Effect of COVID-19 pandemic lockdowns on planned cancer surgery for 15 tumour types in 61 countries: an international, prospective, cohort study

Background
Surgery is the main modality of cure for solid cancers and was prioritised to continue during COVID-19 outbreaks. This study aimed to identify immediate areas for system strengthening by comparing the delivery of elective cancer surgery during the COVID-19 pandemic in periods of lockdown versus light restriction.

Methods
This international, prospective, cohort study enrolled 20 006 adult (≥18 years) patients from 466 hospitals in 61 countries with 15 cancer types, who had a decision for curative surgery during the COVID-19 pandemic and were followed up until the point of surgery or cessation of follow-up (Aug 31, 2020). Average national Oxford COVID-19 Stringency Index scores were calculated to define the government response to COVID-19 for each patient for the period they awaited surgery, and classified into light restrictions (index 60). The primary outcome was the non-operation rate (defined as the proportion of patients who did not undergo planned surgery). Cox proportional-hazards regression models were used to explore the associations between lockdowns and non-operation. Intervals from diagnosis to surgery were compared across COVID-19 government response index groups. This study was registered at ClinicalTrials.gov, NCT04384926.

Findings
Of eligible patients awaiting surgery, 2003 (10·0%) of 20 006 did not receive surgery after a median follow-up of 23 weeks (IQR 16–30), all of whom had a COVID-19-related reason given for non-operation. Light restrictions were associated with a 0·6% non-operation rate (26 of 4521), moderate lockdowns with a 5·5% rate (201 of 3646; adjusted hazard ratio [HR] 0·81, 95% CI 0·77–0·84; p<0·0001), and full lockdowns with a 15·0% rate (1775 of 11 827; HR 0·51, 0·50–0·53; p<0·0001). In sensitivity analyses, including adjustment for SARS-CoV-2 case notification rates, moderate lockdowns (HR 0·84, 95% CI 0·80–0·88; p<0·001), and full lockdowns (0·57, 0·54–0·60; p<0·001), remained independently associated with non-operation. Surgery beyond 12 weeks from diagnosis in patients without neoadjuvant therapy increased during lockdowns (374 [9·1%] of 4521 in light restrictions, 317 [10·4%] of 3646 in moderate lockdowns, 2001 [23·8%] of 11 827 in full lockdowns), although there were no differences in resectability rates observed with longer delays.

Interpretation
Cancer surgery systems worldwide were fragile to lockdowns, with one in seven patients who were in regions with full lockdowns not undergoing planned surgery and experiencing longer preoperative delays. Although short-term oncological outcomes were not compromised in those selected for surgery, delays and non-operations might lead to long-term reductions in survival. During current and future periods of societal restriction, the resilience of elective surgery systems requires strengthening, which might include protected elective surgical pathways and long-term investment in surge capacity for acute care during public health emergencies to protect elective staff and services.

Funding
National Institute for Health Research Global Health Research Unit, Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, Medtronic, Sarcoma UK, The Urology Foundation, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research.

Late Diagnosis of Breast Cancer and Associated Factors Among Women Attending Hawassa University Comprehensive and Specialized Hospital Southern Ethiopia

Background; Breast cancer is a significant public health issue in sub-Saharan Africa and the second commonest cancer overall. In Ethiopia, most women present at the late-stage presentation. This is because Ethiopian government gives less attention, and is not well-studied as well. Therefore, it is important to assess delays in diagnosis and treating breast cancer that has been associated with a more advanced stage of the disease and a decrease in patient survival rates.

Objective: To assess the magnitude and associated factors for late diagnosis of breast cancer among women attending Hawassa University Comprehensive Specialized Hospital in Southern Ethiopia.

Methodology: A facility-based cross-sectional study was conducted from December to January 2019. Data were collected from 261 consecutively selected clients based on the arrival of their hospital visit by using a pretested structured questionnaire and checklist. Physicians performed physical examinations and diagnoses. Data was checked for completeness and consistency, and entered into epi data, then exported to SPSS for analysis. Descriptive, Bivariate, and multivariable logistic regression analyses were performed using SPSS Version 25 Statistical Software.

Results: The magnitude of late diagnosis of breast cancer was 86.3%. The woman who had no initial advice for breast biopsy [AOR=5.1, 95% (CI=1.4-18.9)], not sharing the problem to others [AOR=4.7, 95% (CI=1.8-12.2)] and using traditional and faith healers as a first treatment choice [AOR=3.3, 95% (CI=1.2 – 8.8)] were associated with late diagnosis of breast cancer.

Conclusions: The majority of women having breast cancer were diagnosed at a late stage. It needs attention to provide better options of the modern health service, and providing accessible initial advice for breast biopsy, and creating awareness about the benefit of sharing problems with family to improve the health of mothers by early diagnosing and managing the breast cancer.

Improving knowledge about breast cancer and breast self examination in female Nigerian adolescents using peer education: a pre-post interventional study

Background
Prevention of BC of which the cornerstone is creating awareness and early detection is important in adolescents and young women because of their worse outcomes. Early detection strategies such as mammography are currently beyond the reach of most women in sub-Saharan Africa.. Lack of awareness and late presentation contribute to the poor outcomes. Awareness creation among adolescents may result in modification of some risk factors for BC with adoption of healthy life styles including accessing early detection activities. This study determined the effect of peer education as a strategy to create awareness on BC and breast self examination (BSE) among in-school female adolescents in Benin City.

Methods
This was a pre-post interventional study carried out in October –December 2016 on female students of four secondary schools in Benin City. Pre-peer training, using a pre-tested self-administered questionnaire, knowledge about BC and BSE was assessed in about 30% of each school population. This was followed by training of 124 students selected from the schools (one student per class) as peer trainers. The peer trainers provided training on BC and BSE (the intervention) for their classmates. Within two weeks of peer training knowledge about BC and BSE was reassessed in 30% of each school population. Selection of students for assessment pre and post intervention was by systematic sampling. Correct knowledge was scored and presented as percentages. Chi square test, student t test and ANOVA were used to assess associations and test differences with level of significance set at p < 0.05.

Results
There were 1337 and 1201 students who responded to the pre and post-training questionnaires respectively. The mean BC knowledge score (20.61 ± 13.4) prior to training was low and it statistically significantly improved to 55.93 ± 10.86 following training p < 0.0001 Following peer training, statistically significant improvement (p 0.037- < 0.001) occurred in most knowledge domains apart from symptomatology. Pre-peer training 906(67.8%) students knew about BSE but only 67(4.8%). Significantly more students 1134(94.7%) knew about BSE following peer training.

Conclusions
Peer education strategy can be used to improve BC and BSE knowledge in adolescents. This strategy is low cost and could be very useful in low resource settings.

Duration of intervals in the care seeking pathway for lung cancer in Bangladesh: A journey from symptoms triggering consultation to receipt of treatment

Timeliness in seeking care is critical for lung cancer patients’ survival and better prognosis. The care seeking trajectory of patients with lung cancer in Bangladesh has not been explored, despite the differences in health systems and structures compared to high income countries. This study investigated the symptoms triggering healthcare seeking, preferred healthcare providers (including informal healthcare providers such as pharmacy retailers, village doctors, and “traditional healers”), and the duration of intervals in the lung cancer care pathway of patients in Bangladesh. A cross-sectional study was conducted in three tertiary care hospitals in Bangladesh among diagnosed lung cancer patients through face-to-face interview and medical record review. Time intervals from onset of symptom and care seeking events were calculated and compared between those who sought initial care from different providers using Wilcoxon rank sum tests. Among 418 study participants, the majority (90%) of whom were males, with a mean age of 57 ±9.86 years, cough and chest pain were the most common (23%) combination of symptoms triggering healthcare seeking. About two-thirds of the total respondents (60%) went to informal healthcare providers as their first point of contact. Living in rural areas, lower levels of education and lower income were associated with seeking care from such providers. The median duration between onset of symptom to confirmation of diagnosis was 121 days, between confirmation of diagnosis and initiation of treatment was 22 days, and between onset of symptom and initiation of treatment was 151 days. Pre-diagnosis durations were longer for those who had sought initial care from an informal provider (p<0.05). Time to first contact with a health provider was shorter in this study compared to other developed and developing countries but utilizing informal healthcare providers caused delays in diagnosis and initiation of treatment. Encouraging people to seek care from a formal healthcare provider may reduce the overall duration of the care seeking pathway.

Intersectional social-economic inequalities in breast cancer screening in India: analysis of the National Family Health Survey

Background
Breast cancer incidence rates are increasing in developing countries including India. With 1.3 million new cases of cancer been diagnosed annually, breast cancer is the most common women’s cancer in India. India’s National Family Health Survey (NFHS-4) data 2015–2016 shows that only 9.8% of women between the ages of 15 and 49 had ever undergone breast examination (BE). Further, access to screening and treatment is unequally distributed, with inequalities by socio-economic status. It is unclear, however, if socio-economic inequalities in breast examination are similar across population subgroups.

Methods
We compared BE coverage in population sub-groups categorised by place of residence, religion, caste/tribal groups, education levels, age, marital status, and employment status in their intersection with economic status in India. We analysed data for 699,686 women aged 15–49 using the NFHS-4 data set conducted during 2015–2016. Descriptive (mean, standard errors, and confidence intervals) of women undergoing BE disaggregated by dimensions of inequality (education, caste/tribal groups, religion, place of residence) and their intersections with wealth were computed with national weights using STATA 12. Chi-square tests were performed to assess the association between socio-demographic factors and breast screening. Additionally, the World Health Organisation’s Health Equity Assessment Toolkit Plus was used to compute summary measures of inequality: Slope index for inequality (SII) and Relative Concentration Indices (RCI) for each intersecting dimension.

Results
BE coverage was concentrated among wealthier groups regardless of other intersecting population subgroups. Wealth-related inequalities in BE coverage were most pronounced among Christians (SII; 20.6, 95% CI: 18.5–22.7), married (SII; 14.1, 95% CI: 13.8–14.4), employed (SII: 14.6, 95%CI: 13.9, 15.3), and rural women (SII; 10.8, 95% CI: 10.5–11.1). Overall, relative summary measures (RCI) were consistent with our absolute summary measures (SII).

Conclusions
Breast examination coverage in India is concentrated among wealthier populations across population groups defined by place of residence, religion, age, employment, and marital status. Apart from this national analysis, subnational analyses may also help identify strategies for programme rollout and ensure equity in women’s cancer screening.

Procedural fairness for radiotherapy priority setting in a low resource context

Radiotherapy is an essential component of cancer treatment, yet many countries do not have adequate capacity to serve their populations. This mismatch between demand and supply creates the need for priority setting. There is no widely accepted system to guide patient prioritization for radiotherapy in a low resource context. In the absence of consensus on allocation principles, fair procedures for priority setting should be established. Research is needed to understand what elements of procedural fairness are important to decision makers in diverse settings, assess the feasibility of implementing fair procedures for priority setting in low resource contexts, and improve these processes. This study presents the views of decision makers engaged in everyday radiotherapy priority setting at a cancer center in Rwanda. Semi-structured interviews with 22 oncology physicians, nurses, program leaders, and advisors were conducted. Participants evaluated actual radiotherapy priority setting procedures at the program (meso) and patient (micro) levels, reporting facilitators, barriers, and recommendations. We discuss our findings in relation to the leading Accountability for Reasonableness (AFR) framework. Participants emphasized procedural elements that facilitate adherence to normative principles, such as objective criteria that maximize lives saved. They ascribed fairness to AFR’s substantive requirement of relevance more than transparency, appeals, and enforcement. They identified several challenges unresolved by AFR, such as conflicting relevant rationales and unintended consequences of publicity and appeals. Implementing fair procedure itself is resource intensive, a paradox that calls for innovative, context-appropriate solutions. Finally, socioeconomic and structural barriers to care that undermine procedural fairness must be addressed.

Incidence patterns, care continuum and impact of treatment on survival among women with breast cancer in Ghana and the United States

Breast cancer is the most commonly diagnosed cancer among women worldwide. Of the five breast cancer subtypes, triple negative breast cancer (TNBC) is the most aggressive subtype. Black women in the US and Ghana are more likely to be diagnosed with TNBC, at young ages and advanced stages. Combining information from Ghana and the US, this project identified the breast cancer care continuum in Ghana, examined the breast cancer incidence patterns in Ghana and the US and assessed the optimal surgical treatment for TNBC. In the first manuscript, we examined how women in Ghana navigate the healthcare system and factors that influence their decisions and ability to seek and access breast cancer care. We interviewed thirty-one women diagnosed with breast cancer in Kumasi, Ghana. Based on the findings from the interviews, we presented a framework showing specific steps in the pathways and how women transition from one step to another. In the second manuscript, we assessed factors explaining the younger age at breast cancer diagnosis among Ghanaian women compared to women in the US. To achieve these aims we analyzed breast cancer data from the Kumasi Cancer Registry, the only population-based cancer registry in Ghana, and compared it to the US Surveillance, Epidemiology and End Results (SEER) data. Population age structure, screening and cohort effects explain the younger age at breast cancer diagnosis among women in Ghana In the third manuscript, we examined whether the poor prognosis of TNBC warrants a more aggressive surgical approach and whether there is value in expanded use of radiation therapy among women with TNBC who receive mastectomy. We found that breast conserving surgery followed by radiotherapy is an effective treatment for women with early-stage TNBC. Findings from this dissertation are timely due to the rapidly rising burden of breast cancer in sub-Saharan Africa and persistent disparities in the US.

Provider Barriers and Facilitators of Breast Cancer Guideline-Concordant Therapy Delivery in Botswana: A Consolidated Framework for Implementation Research Analysis

Introduction
Systemic treatment for breast cancer in Sub-Saharan Africa (SSA) is cost-effective. However, there is limited real-world data on the translation of breast cancer treatment guidelines into clinical practice in SSA. The study aimed to identify provider factors associated with adherence to breast cancer guideline-concordant care at Princess Marina Hospital (PMH) in Botswana.

Methods
The Consolidated Framework for Implementation Research was used to conduct one-on-one semi-structured interviews with breast cancer providers at PMH. Purposive sampling was used, and sample size determined by thematic saturation. Transcribed interviews were double-coded and analyzed in NVivo using an integrated analysis approach.

Results
Forty-one providers across eight departments were interviewed. There were variations in breast cancer guidelines used. Facilitators included a strong tension for change and a government-funded comprehensive cancer care plan. Common provider and health system barriers were lack of available resources, staff shortages and poor skills retention; lack of relative priority compared to HIV/AIDS, suboptimal interdepartmental communication and lack of a clearly defined national cancer control policy. Community-level barriers included accessibility and associated transportation costs. Participants recommended the formal implementation of future guidelines that involved key stakeholders in all phases of planning and implementation, strategic government buy-in, expansion of multidisciplinary tumor boards, leveraging non-governmental and academic partnerships, and setting-up monitoring, evaluation and feedback processes.

Discussion
The study identified complex, multi-level factors affecting breast cancer treatment delivery in Botswana. These results and recommendations will inform strategies to overcome specific barriers in order to promote standardized breast cancer care delivery and improve survival outcomes.

Implications for Practice
To address the increasing cancer burden in low- and middle-income countries, resource-stratified guidelines have been developed by multiple international organizations to promote high quality guideline-concordant care. However, these guidelines still require adaptation in order to be successfully translated into clinical practice in the countries where they intend to be used. This study highlights a systematic approach of evaluating important contextual factors associated with the successful adaptation and implementation of resource-stratified guidelines in sub-Saharan Africa. In Botswana, there is a critical need for local stakeholder input to inform country-level and facility-level resources, cancer care accessibility and community-level barriers and facilitators.

Data on histological characteristics, survival patterns and determinants of mortality among colorectal, esophageal and prostate cancer patients in Ethiopia

This article describes data collected retrospectively on a cohort of esophageal, colorectal and prostate cancer patients registered in the patient log book of Tikur Anbessa Specialized Hospital, Ethiopia, from January 1, 2012 to December 31, 2017. The key variables studied include histological characteristics of each type of cancer, clinical and TNM stages, baseline laboratory results (Carcinoembryonic antigen (CEA) for colorectal cancer, Prostate-Specific Antigen (PSA) for prostate cancer, hemoglobin level, etc.), clinical characteristics including sign and symptoms, family history of cancer, diagnostic and treatment modalities a patient received for each type of cancer. The event status (death) was also collected using death certificates (whenever available) and supplemented by telephone interviews with the patient or attendant. Furthermore, lifestyle characteristics of patients including tobacco use, alcohol consumption, khat (‘Catha edulis’) chewing, etc. and socioeconomic characteristics including age, sex, region of residence, marital status, and educational level were also collected. The aim that led to conduct the study that generated these data was to describe clinical presentation, histological characteristics, survival pattern, and to identify determinants of mortality among cancer patients in Ethiopia. Thus, independent survival analyzes were performed using Kaplan-Meier estimates and life table analysis. Furthermore, Cox’s proportional hazards regression was developed to investigate the survival pattern and determinants of cancer specific mortality among colorectal, esophageal and prostate cancer patients.