Racial Differences in the Phenotype of Colorectal Cancer: A Prospective Comparison Between Nigeria and South Africa.

INTRODUCTION: There are significant differences in the phenotype of CRC by race in the U.S. A similar CRC phenotype-race relationship also appears to exist in South Africa (SA). However, there is a paucity of comparative data on the presentation and survival of CRC in sub-Saharan African by country of origin or race. This study compares clinicopathologic variables between CRC patients in Nigeria and SA. METHODS: From a prospective CRC database, consecutive patients diagnosed between September, 2013 and October, 2018 from the African Research Group for Oncology in South West Nigeria were compared to consecutive patients diagnosed from January, 2016 to October, 2018 from the Colorectal Cancer in South Africa database. Patients with histologically confirmed adenocarcinoma were included. Patients were excluded if they had in-situ disease or no histological diagnosis. Clinical outcomes were calculated from the date of presentation. National census categories were used to define self-reported race in SA. RESULTS: The mean age at presentation in Nigeria (n = 347) was 54.1 years (SD 15.5) compared to 56.8 (SD 13.7) in SA (n = 534). The median age among Black SA (BSA) patients was significantly lower than the median age among White SA (WSA) patients (55 vs. 63, p < 0.001). Right-sided colon cancer was more common in Nigerian (27.4%) and BSA (21.2%) patients compared to WSA patients (15.2%, p < 0.001). Nigerian (39.1%) and BSA (16.7%) patients were also more likely to present with mucinous histology than WSA patients (4.9%, p < 0.001). There was a significant difference in the stage-at-presentation between the cohorts, with a large burden of stage IV disease in the Nigerian cohort (52.6%). Adjusting for stage-at-presentation, there was a significant difference in the median overall survival between country and racial cohorts. CONCLUSION: There are significant differences in the phenotype of CRC between Nigeria and SA. Nigerian and BSA patients, appear to share characteristics that are different than those of WSA patients. Larger series with tissue banking and next-generation sequencing are needed to better delineate these observed differences.

Contemporary management of breast cancer in Nigeria: Insights from an institutional database.

High-quality data are needed to guide interventions aimed at improving breast cancer outcomes in sub-Saharan Africa. We present data from an institutional breast cancer database to create a framework for cancer policy and development in Nigeria. An institutional database was queried for consecutive patients diagnosed with breast cancer between January 2010 and December 2018. Sociodemographic, diagnostic, histopathologic, treatment and outcome variables were analyzed. Of 607 patients, there were 597 females with a mean age of 49.8 ± 12.2 years. Most patients presented with a palpable mass (97%) and advanced disease (80.2% ≥ Stage III). Immunohistochemistry was performed on 21.6% (131/607) of specimens. Forty percent were estrogen receptor positive, 32.8% were positive for HER-2 and 43.5% were triple negative. Surgery was performed on 49.9% (303/607) of patients, while 72% received chemotherapy and 7.9% had radiotherapy. At a median follow-up period of 20.5 months, the overall survival was 43.6% (95% CI -37.7 to 49.5). Among patients with resectable disease, 18.8% (57/303) experienced a recurrence. Survival was significantly better for early-stage disease (I and II) compared to late-stage disease (III or IV) (78.6% vs 33.3%, P < .001). Receipt of adjuvant radiotherapy after systemic chemotherapy was associated with improved survival in patients with locally advanced disease (68.5%, CI -46.3 to 86 vs 51%, CI 38.6 to 61.9, P < .001). This large cohort highlights the dual burden of advanced disease and inadequate access to comprehensive breast cancer care in Nigeria. There is a significant potential for improving outcomes by promoting early diagnosis and facilitating access to multimodality treatment.

Opportunities for Improvement in the Administration of Neoadjuvant Chemotherapy for T4 Breast Cancer: A Comparison of the U.S. and Nigeria.

BACKGROUND: Neoadjuvant chemotherapy (NAC) is an integral component of T4 breast cancer (BCa) treatment. We compared response to NAC for T4 BCa in the U.S. and Nigeria to direct future interventions. MATERIALS AND METHODS: Cross-sectional retrospective analysis included all patients with non-metastatic T4 BCa treated from 2010 to 2016 at Memorial Sloan Kettering Cancer Center (New York, New York) and Obafemi Awolowo University Teaching Hospitals Complex (Ile Ife, Nigeria). Pathologic complete response (pCR) and survival were compared and factors contributing to disparities evaluated. RESULTS: Three hundred and eight patients met inclusion criteria: 157 (51%) in the U.S. and 151 (49%) in Nigeria. All U.S. patients received NAC and surgery compared with 93 (62%) Nigerian patients. Fifty-six out of ninety-three (60%) Nigerian patients completed their prescribed course of NAC. In Nigeria, older age and higher socioeconomic status were associated with treatment receipt. Fewer patients in Nigeria had immunohistochemistry performed (100% U.S. vs. 18% Nigeria). Of those with available receptor subtype, 18% (28/157) of U.S. patients were triple negative versus 39% (9/23) of Nigerian patients. Overall pCR was seen in 27% (42/155) of U.S. patients and 5% (4/76) of Nigerian patients. Five-year survival was significantly shorter in Nigeria versus the U.S. (61% vs. 72%). However, among the subset of patients who received multimodality therapy, including NAC and surgery with curative intent, 5-year survival (67% vs. 72%) and 5-year recurrence-free survival (48% vs. 61%) did not significantly differ between countries. CONCLUSION: Addressing health system, socioeconomic, and psychosocial barriers is necessary for administration of complete NAC to improve BCa outcomes in Nigeria. IMPLICATIONS FOR PRACTICE: This cross-sectional retrospective analysis of patients with T4 breast cancer in Nigeria and the U.S. found a significant difference in pathologic complete response to neoadjuvant chemotherapy (5% Nigeria vs. 27% U.S.). Five-year survival was shorter in Nigeria, but in patients receiving multimodality treatment, including neoadjuvant chemotherapy and surgery with curative intent, 5-year overall and recurrence-free survival did not differ between countries. Capacity-building efforts in Nigeria should focus on access to pathology services to direct systemic therapy and promoting receipt of complete chemotherapy to improve outcomes.

Treatment of colorectal cancer in Sub-Saharan Africa: Results from a prospective Nigerian hospital registry.

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer worldwide. Mortality for CRC is improving in high income countries, but in low and middle income countries, rates of disease and death from disease are rising. In Sub-Saharan Africa, the ratio of CRC mortality to incidence is the highest in the world. This study investigated the nature of CRC treatment currently being offered and received in Nigeria. METHODS: Between April 2013 and October 2017, a prospective study of consecutively diagnosed cases of CRC was conducted. Patient demographics, clinical features, and treatment recommended and received was recorded for each case. Patients were followed during the study period every 3 months or until death. RESULTS: Three hundred patients were included in our analysis. Seventy-one percent of patients received a recommended surgical operation. Of those that didn't undergo surgery as recommended, 37% cited cost as the main reason, 30% declined due to personal reasons, and less than 5% absconded or were lost to follow up. Approximately half of patients (50.5%) received a chemotherapy regimen when it was recommended, and 4.1% received radiotherapy when this was advised as optimal treatment. With therapy, the median overall survival for patients diagnosed with stage III and stage IV CRC was 24 and 10.5 months respectively. Overall, we found significantly better median survival for patients that received the recommended treatment (25 vs 7 months; P < .01). CONCLUSIONS: A number of patients were unable to receive the recommended treatment, reflecting some of the burden of untreated CRC in the region. Receiving the recommended treatment was associated with a significant difference in outcome. Improved healthcare financing, literacy, training, access, and a better understanding of tumor biology will be necessary to address this discrepancy.

The Development of a Text Messaging Platform to Enhance a Youth Diabetes Prevention Program: Observational Process Study.

BACKGROUND: Approximately 1 in 5 adolescents in the United States has prediabetes, and racially and ethnically minoritized youths are disproportionately impacted. Unfortunately, there are few effective youth diabetes prevention programs, and in-person interventions are challenging because of barriers to access and engagement. OBJECTIVE: We aimed to develop and assess the preliminary feasibility and acceptability of a youth-informed SMS text messaging platform to provide additional support and motivation to adolescents with prediabetes participating in a diabetes prevention workshop in East Harlem, New York City, New York, United States. We collaborated with our youth action board and a technology partner (mPulse Mobile) to develop and pilot-test the novel interactive platform. METHODS: The technology subcommittee of our community action board (comprising youths and young adults) used the results from focus groups that we had previously conducted with youths from our community to develop 5 message types focused on healthy eating and active living: goal setting, behavior tracking, individually tailored guidance, motivational messages, and photo diary. We used an iterative process to develop and pilot the program with our internal study team, including youths from our community action board and mPulse Mobile developers. We then conducted a pilot of the 12-week SMS text messaging program with 13 youths with prediabetes. RESULTS: Participants (aged 15-21 years; 10/13, 77% female; 3/10, 23% Black and 10/13, 77% Hispanic or Latinx) received an average of 2 automated messages per day. The system correctly sent 84% (2231/2656) of the messages at the time intended; the remaining 16% (425/2656) of the messages were either sent at the incorrect time, or the system did not recognize a participant response to provide the appropriate reply. The level of engagement with the program ranged from 1 (little to no response) to 5 (highly responsive) based on how frequently participants responded to the interactive (2-way) messages. Highly responsive participants (6/13, 46%) responded >75% (1154/1538) of the time to interactive messages sent over 12 weeks, and 69% (9/13) of the participants were still engaged with the program at week 12. During a focus group conducted after program completion, the participants remarked that the message frequency was appropriate, and those who had participated in our in-person workshops reflected that the messages were reminiscent of the workshop content. Participants rated goal setting, behavior tracking, and tailored messages most highly and informed planned adaptations to the platform. Participants described the program as: "interactive, informative, enjoyable, very convenient, reliable, motivational, productive, and reflective." CONCLUSIONS: We partnered with youths in the initial content development and pilot testing of a novel SMS text messaging platform to support diabetes prevention. This study is unique in the triple partnership we formed among researchers, technology experts, and diverse youths to develop a mobile health platform to address diabetes-related disparities.

Identification of urinary biomarkers of colorectal cancer: Towards the development of a colorectal screening test in limited resource settings.

BACKGROUND: African colorectal cancer (CRC) rates are rising rapidly. A low-cost CRC screening approach is needed to identify CRC from non-CRC patients who should be sent for colonoscopy (a scarcity in Africa). OBJECTIVE: To identify urinary metabolite biomarkers that, combined with easy-to-measure clinical variables, would identify patients that should be further screened for CRC by colonoscopy. Ideal metabolites would be water-soluble and easily translated into a sensitive, low-cost point-of-care (POC) test. METHODS: Liquid-chromatography mass spectrometry (LC-MS/MS) was used to quantify 142 metabolites in spot urine samples from 514 Nigerian CRC patients and healthy controls. Metabolite concentration data and clinical characteristics were used to determine optimal sets of biomarkers for identifying CRC from non-CRC subjects. RESULTS: Our statistical analysis identified N1, N12-diacetylspermine, hippurate, p-hydroxyhippurate, and glutamate as the best metabolites to discriminate CRC patients via POC screening. Logistic regression modeling using these metabolites plus clinical data achieved an area under the receiver-operator characteristic (AUCs) curves of 89.2% for the discovery set, and 89.7% for a separate validation set. CONCLUSIONS: Effective urinary biomarkers for CRC screening do exist. These results could be transferred into a simple, POC urinary test for screening CRC patients in Africa.

Molecular and phenotypic profiling of colorectal cancer patients in West Africa reveals biological insights.

Understanding the molecular and phenotypic profile of colorectal cancer (CRC) in West Africa is vital to addressing the regions rising burden of disease. Tissue from unselected Nigerian patients was analyzed with a multigene, next-generation sequencing assay. The rate of microsatellite instability is significantly higher among Nigerian CRC patients (28.1%) than patients from The Cancer Genome Atlas (TCGA, 14.2%) and Memorial Sloan Kettering Cancer Center (MSKCC, 8.5%, P < 0.001). In microsatellite-stable cases, tumors from Nigerian patients are less likely to have APC mutations (39.1% vs. 76.0% MSKCC P < 0.001) and WNT pathway alterations (47.8% vs. 81.9% MSKCC, P < 0.001); whereas RAS pathway alteration is more prevalent (76.1% vs. 59.6%, P = 0.03). Nigerian CRC patients are also younger and more likely to present with rectal disease (50.8% vs. 33.7% MSKCC, P < 0.001). The findings suggest a unique biology of CRC in Nigeria, which emphasizes the need for regional data to guide diagnostic and treatment approaches for patients in West Africa.

Urinary Metabolomics to Identify a Unique Biomarker Panel for Detecting Colorectal Cancer: A Multicenter Study.

BACKGROUND: Population-based screening programs are credited with earlier colorectal cancer diagnoses and treatment initiation, which reduce mortality rates and improve patient health outcomes. However, recommended screening methods are unsatisfactory as they are invasive, are resource intensive, suffer from low uptake, or have poor diagnostic performance. Our goal was to identify a urine metabolomic-based biomarker panel for the detection of colorectal cancer that has the potential for global population-based screening. METHODS: Prospective urine samples were collected from study participants. Based upon colonoscopy and histopathology results, 342 participants (colorectal cancer, 171; healthy controls, 171) from two study sites (Canada, United States) were included in the analyses. Targeted liquid chromatography-mass spectrometry (LC-MS) was performed to quantify 140 highly valuable metabolites in each urine sample. Potential biomarkers for colorectal cancer were identified by comparing the metabolomic profiles from colorectal cancer versus controls. Multiple models were constructed leading to a good separation of colorectal cancer from controls. RESULTS: A panel of 17 metabolites was identified as possible biomarkers for colorectal cancer. Using only two of the selected metabolites, namely diacetylspermine and kynurenine, a predictor for detecting colorectal cancer was developed with an AUC of 0.864, a specificity of 80.0%, and a sensitivity of 80.0%. CONCLUSIONS: We present a potentially "universal" metabolomic biomarker panel for colorectal cancer independent of cohort clinical features based on a North American population. Further research is needed to confirm the utility of the profile in a prospective, population-based colorectal cancer screening trial. IMPACT: A urinary metabolomic biomarker panel was identified for colorectal cancer with the potential of clinical application.