Treatment and Survival Among Patients With Colorectal Cancer in Sub-Saharan Africa: A Multicentric Population-Based Follow-Up Study.

BACKGROUND: The burden of colorectal cancer (CRC) is increasing in Sub-Saharan Africa (SSA). However, little is known about CRC treatment and survival in the region. METHODS: A random sample of 653 patients with CRC diagnosed from 2011 to 2015 was obtained from 11 population-based cancer registries in SSA. Information on clinical characteristics, treatment, and/or vital status was obtained from medical records in treating hospitals for 356 (54%) of the patients ("traced cohort"). Concordance of CRC treatment with NCCN Harmonized Guidelines for SSA was assessed. A Cox proportional hazards model was used to examine the association between survival and human development index (HDI). RESULTS: Of the 356 traced patients with CRC, 51.7% were male, 52.8% were from countries with a low HDI, 55.1% had colon cancer, and 73.6% were diagnosed with nonmetastatic (M0) disease. Among the patients with M0 disease, however, only 3.1% received guideline-concordant treatment, 20.6% received treatment with minor deviations, 31.7% received treatment with major deviations, and 35.1% received no treatment. The risk of death in patients who received no cancer-directed therapy was 3.49 (95% CI, 1.83-6.66) times higher than in patients who received standard treatment or treatment with minor deviations. Similarly, the risk of death in patients from countries with a low HDI was 1.67 (95% CI, 1.07-2.62) times higher than in those from countries with a medium HDI. Overall survival at 1 and 3 years was 70.9% (95% CI, 65.5%-76.3%) and 45.3% (95% CI, 38.9%-51.7%), respectively. CONCLUSIONS: Fewer than 1 in 20 patients diagnosed with potentially curable CRC received standard of care in SSA, reinforcing the need to improve healthcare infrastructure, including the oncology and surgical workforce.

Decrease in liver cancer incidence rates in Bamako, Mali over 28 years of population-based cancer registration (1987-2015).

BACKGROUND: Primary liver cancer is common in West Africa due to endemic risk factors. However, epidemiological studies of the global burden and trends of liver cancer are limited. We report changes in trends of the incidence of liver cancer over a period of 28 years using the population-based cancer registry of Bamako, Mali. AIM: To assess the trends and patterns of liver cancer by gender and age groups by analyzing the cancer registration data accumulated over 28 years (1987-2015) of activity of the population-based registry of the Bamako district. METHODS: Data obtained since the inception of the registry in 1987 through 2015 were stratified into three periods (1987-1996, 1997-2006, and 2007-2015). Age-standardized rates were estimated by direct standardization using the world population. Incidence rate ratios and the corresponding 95% confidence intervals (CI) were estimated using the early period as the reference (1987-1996). Joinpoint regression models were used to assess the annual percentage change and highlight trends over the entire period (from 1987 to 2015). RESULTS: Among males, the age-standardized incidence rates significantly decreased from 19.41 (1987-1996) to 13.12 (1997-2006) to 8.15 (2007-2015) per 105 person-years. The incidence rate ratio over 28 years was 0.42 (95%CI: 0.34-0.50), and the annual percentage change was -4.59 [95%CI: (-6.4)-(-2.7)]. Among females, rates dropped continuously from 7.02 (1987-1996) to 2.57 (2007-2015) per 105 person-years, with an incidence rate ratio of 0.37 (95%CI: 0.28-0.45) and an annual percentage change of -5.63 [95%CI: (-8.9)-(-2.3)]. CONCLUSION: The population-based registration showed that the incidence of primary liver cancer has steadily decreased in the Bamako district over 28 years. This trend does not appear to result from biases or changes in registration practices. This is the first report of such a decrease in an area of high incidence of liver cancer in Africa. This decrease may be explained by the changes and diversity of diet that could reduce exposure to aflatoxins through dietary contamination in this population.

Association of caspase 8 polymorphisms -652 6N InsDel and Asp302His with progression-free survival and tumor infiltrating lymphocytes in early breast cancer.

The caspase 8 variants CASP8 -652 6N InsDel and Asp302His have previously been identified to promote survival of T-lymphocytes and to indicate reduced breast cancer susceptibility. Besides some preliminary findings, prognostic relevance of these polymorphisms in patients with existing breast cancer has not been investigated. Considering an immunomodulatory role of these polymorphisms, we genotyped 785 early breast cancer patients and correlated caspase 8 variants with disease-free survival (DFS) and the presence of tumor infiltrating lymphocytes (TILs). Early breast cancer specimens were collected as part of the multicenter prospective PiA study. Genotyping was performed by pyrosequencing, TILs status was assessed using hematoxylin & eosin staining. The CASP8 -652Del variant was significantly associated with improved DFS in an allele-dose dependent manner (p = 0.027). Homozygosity for the -652Del variant was an independent predictor for improved DFS (HR = 0.36; 95% CI = 0.174-0.726; p = 0.005). In patients with the 302HisHis genotype, there was no event of recurrence during observation time. Combined analysis of diplotypes revealed an influence of both polymorphisms on DFS (p = 0.029). Interestingly, patients with the 302HisHis variant among the unstratified patient cohort (and among the luminal-like subtype, by trend) had tumors with lower lymphocyte infiltration (p = 0.025). We propose a prognostically favorable role of the -652Del and the 302His variant in primary breast cancer and suggest for the first time an association between polymorphisms in apoptosis-related genes and the immunophenotype in breast cancer. Our findings encourage further investigation of caspase 8 polymorphisms as biomarkers for prognostic and immunotherapeutic considerations.

Health system organisation and patient pathways: breast care patients' trajectories and medical doctors' practice in Mali.

BACKGROUND: Information on pathways of women seeking diagnostic services due to breast- related symptoms can help highlight challenges related to the healthcare system in improving early diagnosis of breast cancer. METHODS: We retrospectively analysed the entire patient pathway, from first symptom recognition via initial healthcare visit up to final diagnosis at the pathology service in Mali. Data from questionnaire-based structured patient interviews (n = 124) were used to calculate time to first healthcare visit (median 91 days) and consecutive time to diagnosis (median 21 days) and to extract information on type of initially visited healthcare facility (community healthcare centre, referral hospital, tertiary hospital, private clinic). Median time to first healthcare visit and time to diagnosis and type of initially-visited healthcare facility were cross-tabulated with patient characteristics. An additional survey among (n = 30) medical doctors in the community healthcare centres and referral hospitals in Bamako was conducted to understand current knowledge and referral practice with respect to female patients with breast-related symptoms. RESULTS: Patients who initially visited private clinics had the shortest time to first healthcare visit (median 44 days), but the longest time to diagnosis (median 170 days). Patients visiting community healthcare centres and referral hospitals took longest for a first healthcare visit (median 153 and 206 days, respectively), but the time to diagnosis was shorter (median 95 and 7 days, respectively). The majority of patients (45%) initially visited a tertiary hospital; these patients had shortest total time to diagnosis (median 56 days health seeking and 8 days diagnostic time), but did not follow the recommended pathway for patients in the pyramidal healthcare system in Mali. The doctors' survey showed lower breast cancer knowledge in the community healthcare centres than in the referral hospitals. However, most doctors felt able to recognise suspected cases of cancer and referred patients directly to a hospital. CONCLUSIONS: The role of different healthcare facilities in ensuring triage of patients with breast-related symptoms needs to be defined before any early detection initiatives are implemented. Especially at the entry level of the healthcare system, the access and quality of health services need to be strengthened.

Factors associated with time to first healthcare visit, diagnosis and treatment, and their impact on survival among breast cancer patients in Mali.

OBJECTIVE: To analyse patient and healthcare system related factors influencing the time to first healthcare visit, diagnosis and treatment of breast cancer patients in sub-Saharan Africa and the impact on survival in order to advise on early detection strategies. METHODS: A prospective hospital cohort study was conducted at the only pathology department in Mali, at the University Hospital in Bamako. All the female patients with a breast cancer diagnosis between January and April 2016 were interviewed with a structured questionnaire (N = 64) to gather information about breast symptom recognition and first healthcare visit. Information on beginning of treatment and survival were collected at 18-months follow-up. Simple Cox regression analyses were performed. RESULTS: The median time to first healthcare visit was 4.8 months, from first healthcare visit to diagnosis was 0.9 months and for the patients who started treatment (N = 46) the time from diagnosis to treatment was 1.3 months. Knowledge of breast-self-examination and correct symptom interpretation increased the chance of an earlier healthcare visit. Prolonged time to diagnosis was found with shorter duration to first healthcare visit, for working women compared to housewives and for those living within Bamako. Living outside Bamako and smaller tumour size (T1/T2) prolonged time to treatment. Visit of a traditional healer and larger tumour size (T3/T4) shortened survival time, whereas time to first healthcare visit and subsequent time to diagnosis had no influence on survival. CONCLUSIONS: Down-staging strategies are only useful if the continuum of breast cancer care is warranted for the majority of patients.

Why Do Women with Breast Cancer Get Diagnosed and Treated Late in Sub-Saharan Africa? Perspectives from Women and Patients in Bamako, Mali.

BACKGROUND: Breast cancer, the most common cancer among women worldwide, has a high mortality rate in low-income countries. In sub-Saharan Africa, most breast cancer patients are diagnosed with advanced disease. Some studies have quantified the time delay to diagnosis in sub-Saharan Africa, but very few have used qualitative methods to understand barriers leading to delay. This study analyses barriers throughout a breast cancer patient's pathway from symptom recognition to treatment in Mali. METHOD: Three focus group discussions were conducted. The model of pathways to treatment was used to structure the results into 4 time intervals: appraisal, help-seeking, diagnosis, and treatment, with a focus on barriers during each interval. RESULTS: The main barriers during the appraisal interval were a low level of breast cancer knowledge among women, their families, and medical professionals, and during the help-seeking interval, mistrust in the community health care centers and economic hardship. Barriers during the diagnosis interval were low quality of health care services and lack of social support, and during the pretreatment interval high costs and lack of specialized services. CONCLUSION: Multilevel interventions are needed to ensure access, availability, and affordability of a minimum standard of care for breast cancer patients in sub-Saharan Africa.

Breast cancer in pre-menopausal women in West Africa: analysis of temporal trends and evaluation of risk factors associated with reproductive life.

BACKGROUND: In West Africa, trends and risk factors for breast cancer (BC) have been rarely studied. METHODS: Here we have analyzed trends of BC over two periods in two population-based cancer registries, in Mali-Bamako (1987-1997; 1998-2009) and in The Gambia (1988-1997; 1998-2006). We have conducted a case-control study (n = 253 cases, 249 controls) on risk factors associated with reproductive life stratified by menopausal status in Bamako. RESULTS: Between the two periods, BC incidence rates increased by 20% (incidence rate ratio (IRR) 1.20 (95% CI [1.07-1.35])) in Bamako, with an annual percentage change of 2% (95% CI [0.4-3.6]). The increase was of 30% in women under 55 years (IRR 1.30 (95% CI [1.14-1.60])). A similar pattern was observed in The Gambia for women under 50 years (IRR 1.47 (95% CI [1.07-2.01])). Overall, pre-menopausal breast cancer was predominant in both countries. In contrary to what is well established, case-control study showed that late age at menarche (>14 years) increased the risk of BC among pre-menopausal women (OR: 2.02 (95% CI [1.08-3.78])) while it tended to be protective in post-menopausal women (OR: 0.61 (95% CI [0.29-1.29])). Later age at a first pregnancy (>20 years) was associated with a reduction of risk in pre-menopausal women (OR: 0.41 (95% CI [0.18-0.89])). CONCLUSION: These results indicate that the burden of pre-menopausal BC is increasing in West African countries. These cancers appear to be associated with distinct reproductive risk factors, highlighting the need for better understanding the biological bases of early BC in African populations.