ALDH1A3 promotes invasion and metastasis in triple-negative breast cancer by regulating the plasminogen activation pathway.

Aldehyde dehydrogenase 1A3 (ALDH1A3) is a cancer stem cell marker that promotes metastasis. Triple-negative breast cancer (TNBC) progression has been linked to ALDH1A3-induced gene expression changes. To investigate the mechanism of ALDH1A3-mediated breast cancer metastasis, we assessed the effect of ALDH1A3 on the expression of proteases and the regulators of proteases that degrade the extracellular matrix, a process that is essential for invasion and metastasis. This revealed that ALDH1A3 regulates the plasminogen activation pathway; it increased the levels and activity of tissue plasminogen activator (tPA) and urokinase plasminogen activator (uPA). This resulted in a corresponding increase in the activity of serine protease plasmin, the enzymatic product of tPA and uPA. The ALDH1A3 product all-trans-retinoic acid similarly increased tPA and plasmin activity. The increased invasion of TNBC cells by ALDH1A3 was plasminogen-dependent. In patient tumours, ALDH1A3 and tPA are co-expressed and their combined expression correlated with the TNBC subtype, high tumour grade and recurrent metastatic disease. Knockdown of tPA in TNBC cells inhibited plasmin generation and lymph node metastasis. These results identify the ALDH1A3-tPA-plasmin axis as a key contributor to breast cancer progression.

Population-Level Access to Breast Cancer Early Detection and Diagnosis in Nigeria.

PURPOSE: Mammography, breast ultrasound (US), and US-guided breast biopsy are essential services for breast cancer early detection and diagnosis. This study undertook a comprehensive evaluation to determine population-level access to these services for breast cancer early detection and diagnosis in Nigeria using a previously validated geographic information system (GIS) model. METHODS: A comprehensive list of public and private facilities offering mammography, breast US, and US-guided breast biopsy was compiled using publicly available facility data and a survey administered nationally to Nigerian radiologists. All facilities were geolocated. A cost-distance model using open-source population density (GeoData Institute) and road network data (OpenStreetMap) was used to estimate population-level travel time to the nearest facility for mammography, breast US, and US-guided biopsy using GIS software (ArcMAP). RESULTS: In total, 1,336 facilities in Nigeria provide breast US, of which 47.8% (639 of 1,336) are public facilities, and 218 provide mammography, of which 45.4% (99 of 218) are public facilities. Of the facilities that provide breast US, only 2.5% (33 of 1,336) also provide US-guided breast biopsy. At the national level, 83.1% have access to either US or mammography and 61.7% have access to US-guided breast biopsy within 120 minutes of a continuous one-way travel. There are differences in access to mammography (64.8% v 80.6% with access at 120 minutes) and US-guided breast biopsy (49.0% v 77.1% with access at 120 minutes) between the northern and southern Nigeria and between geopolitical zones. CONCLUSION: To our knowledge, this is the first comprehensive evaluation of breast cancer detection and diagnostic services in Nigeria, which demonstrates geospatial inequalities in access to mammography and US-guided biopsy. Targeted investment is needed to improve access to these essential cancer care services in the northern region and the North East geopolitical zone.

The African Research Group for Oncology: A decade fostering colorectal cancer research in Nigeria.

The African Research Group for Oncology (ARGO) was formed in 2013 to undertake methodologically rigorous cancer research in Nigeria, and to strengthen cancer research capacity in the country through training and mentorship of physicians, scientists, and other healthcare workers. Here, we describe how ARGO's work in colorectal cancer (CRC) has evolved over the past decade. This includes the consortium's scientific contributions to the understanding of CRC in Nigeria and globally and its research capacity-building program.

Cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) for peritoneal mesothelioma: Canadian practices and outcomes.

INTRODUCTION: Peritoneal mesothelioma (PM) is a rare malignancy originating from the peritoneal lining. Cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) is the standard-of-care for patients with isolated PM. Due to a paucity of prospective data there are several different HIPEC protocols. The aims of this study are to describe the CRS and HIPEC protocols for PM and patient outcomes across Canada. METHODS: A multicenter retrospective study was performed on patients diagnosed and treated for PM with CRS and HIPEC in four major peritoneal disease centers in Canada between 2000 and 2021. Data on patient characteristics, treatment patterns, postoperative morbidity, recurrence, and survival were collected. RESULTS: A total of 72 patients were identified. Mean age was 52 years (17-75) and 37.5% were male. Epithelioid (70.1%) and multicystic (13%) mesothelioma were the most common subtypes. Twenty-one patients (30%) were treated with neoadjuvant chemotherapy. CRS and HIPEC was performed in 64 patients (91.4%). Of these, the mean PCI was 22 (2-39) and cisplatin+doxorubicin was the most common HIPEC regimen (n = 33, 51.6%). A semi-closed coliseum technique was used in 68.8% of HIPECs and the mean duration of surgery was 486 min (90-1052). Clavien-Dindo III or IV complications occurred in 12 patients (16.9%). With a median follow-up of 24 months (0.2-104.4), we found a 5-year overall survival of 61% and a 5-year recurrence-free survival of 35%. CONCLUSION: CRS and HIPEC is a safe and effective treatment modality for well-selected patients with PM, with some achieving prolonged survival.

Prevalence and determinants of lymphedema in newly diagnosed Nigerian breast cancer patients using bioimpedance estimations.

Background: Breast cancer-related lymphedema (BCRL) is common and has significant impact on quality of life. Very little is known about BCRL in sub-Saharan Africa. Generally, BCRL has been mostly evaluated post treatment, with very limited data on the prevalence of pre-treatment BCRL at baseline. This study presents the prevalence and clinical associations of lymphedema among newly diagnosed, treatment-naive breast cancer patients in a Nigerian cohort using bioimpedance estimations. Methods: Consecutively consenting, newly diagnosed, treatment-naive breast cancer patients were assessed for upper limb lymphedema using bioimpedance measurements of the extracellular fluid and the single-frequency bioelectrical impedance analysis value at 5 kHz. Patients were classified as having lymphedema if there was >10% difference in arm measurements or if the ratios of the arm measurements were >3 SD above a normative mean generated from representative controls. Regression analysis was performed to determine clinical variables associated with lymphedema. Results: There were 154 breast cancer patients with a median age of 47 (40.0-56.8) years and a body mass index of 27 (23.5-30.9) kg/m2. The majority (70%) had stage III disease. All measurements were significantly higher in cases than controls. Using various definitions, the prevalence of lymphedema was between 11.7% and 14.3%. Various clinical variables relating to clinical stage were significantly associated with lymphedema. Conclusion: The predominance of locally advanced disease in the Nigerian setting is associated with high pre-treatment lymphedema rates. This may set the stage for higher rates in the post-operative setting. Management of lymphedema should be incorporated into the treatment planning.

Improving Safety During Transitions of Care Through the Use of Electronic Referral Loops to Receive and Reconcile Health Information.

BACKGROUND: Medicare's Promoting Interoperability Program evaluates how often organizations completely reconcile differences between the internal medical record with problems, medications, and allergies received from outside electronic health records (EHRs) during hospitalizations. This quality improvement project sought to increase rates of complete reconciliation of patient problems, medications, and allergies to 80% of hospitalizations for 90 consecutive days at all eight hospitals in an academic medical system by December 31, 2021. METHODS: Baseline characteristics were determined using monthly reconciliation performance from October 2019 to October 2020. The intervention period occurred from November 2020 to December 2021 and consisted of 26 Plan-Do-Study-Act cycles. Performance was monitored from January 2022 to June 2022 to observe the sustainability of the initiative. Statistical process control charts were used to identify special cause variation in system-level performance. RESULTS: All eight hospitals successfully recorded 90 consecutive days of complete reconciliation above 80% in 2021, and seven of eight hospitals maintained this goal in the sustainability period. Average baseline reconciliation was 22.1%. System-level performance satisfied criteria for baseline shift after PDSA 17, when the average performance was recalculated as 52.4%. Criteria for a second baseline shift were satisfied during the sustainability period, when the average performance was recalculated at 79.9%. Overall performance has remained within the recalculated control limits throughout the sustainability period. CONCLUSION: An intervention that included enhancing EHR workflows, training medical providers, and communicating division performance was successful in increasing and sustaining complete reconciliation of clinical information in a multihospital medical system.

The out-of-pocket cost of breast cancer care at a public tertiary care hospital in Nigeria: an exploratory analysis.

Introduction: in Nigeria, the incidence of breast cancer has increased by over 80% in the last four decades. This study quantifies the out-of-pocket (OOP) cost of breast cancer management and the associated rate of catastrophic healthcare expenditure (CHE) at a public tertiary care facility in Ile-Ife, Nigeria. Methods: patients treated between December 2017 - August 2018 were identified from a prospective breast cancer database. A questionnaire was developed to capture the total cost of care, including direct and indirect expenses. Three commonly used thresholds for a CHE were used in this analysis. The cost of radiotherapy and targeted therapy were captured separately. Results: data was collected from 22 eligible patients. Sixty-eight percent had no form of health insurance. The mean cost of diagnosis and treatment was $2,049 (SD $1,854). At a threshold of 10% and 25% of annual income, 95% and 86% of households experienced a CHE. Based on a household´s capacity-to-pay, 90% experienced a CHE. The mean cost of radiotherapy was $462 (SD $223) and the mean cost of trastuzumab was $6,568 (SD $2,766). Cost precluded surgery in 14% of patients with resectable disease. As a result of accessing treatment, 72% of households had to borrow money and 9% of households interrupted a child´s education. Conclusion: the out-of-pocket cost of breast cancer care in Nigeria is significant. This results in a CHE for 68-95% of households, which has significant health and economic sequelae. Greater financial protection is essential as the burden of breast cancer increases in Nigeria.

Colorectal cancer screening with fecal immunochemical testing: a community-based, cross-sectional study in average-risk individuals in Nigeria.

BACKGROUND: The estimated incidence of colorectal cancer is rising in Nigeria, where most patients present with advanced disease. Earlier detection of colorectal cancer is a goal of the Nigerian National Cancer Control Plan, but the utility of fecal-based screening is unclear. This study aimed to assess the fecal immunochemical test as a colorectal cancer screening modality in average-risk individualS in Nigeria. METHODS: A population-based, cross-sectional study of qualitative fecal immunochemical test-based colorectal cancer screening was done in asymptomatic, average-risk participants aged 45-75 years in three states in Nigeria (Osun, Kwara, and Lagos). Participants were invited to enrol using age-stratified and sex-stratified convenience sampling following community outreach. Exclusion criteria included a personal history of colorectal cancer or rectal bleeding in the previous 6 months, a first-degree relative with a known diagnosis of colorectal cancer, or a comorbidity that would preclude conscious sedation or general anesthesia. Participants with positive fecal immunochemical test results underwent colonoscopy, and the positive predictive value of fecal immunochemical testing for colorectal cancer and advanced adenomas (≥10 mm, tubulovillous or villous or high-grade dysplasia) was calculated. Data on demographics and acceptability of fecal immunochemical testing and colonoscopy were collected. FINDINGS: Between January and April 2021, 2330 participants were enrolled in the study and received a fecal immunochemical test, which was returned by 2109 participants. 1677 participants tested negative and 432 tested positive. Of these 432 participants, 285 underwent a colonoscopy (235 showed no polyps or cancer, 47 had polyps identified, and three had colorectal cancer identified). Of the 47 participants who had polyps identified, 20 had advanced adenomas diagnosed. The median age was 57 years (IQR 50-63), 958 (41%) were male and 1372 (59%) were female, and 68% had at least a secondary-level education. Participants were evenly spread across wealth quintiles. The positivity rate of the fecal immunochemical test was 21% overall (432 of 2109; 95% CI 20-21%), 11% (51 of 455; 95% CI 10-12) in Lagos, 20% (215 of 1052; 95% CI 20-21) in Osun, and 28% (166 of 597; 95% CI 27-29) in Kwara. Among the patients with a positive fecal immunochemical test who completed colonoscopy, the positive predictive value for invasive colorectal cancer was 1·1% (95% CI 0·3-3·3), and 7·0% (4·5-10·8) for advanced adenoma. The acceptability of fecal immunochemical screening among participants was very high. INTERPRETATION: Colorectal cancer screening with qualitative fecal immunochemical tests in Nigeria is feasible and acceptable to average-risk asymptomatic participants. However, the low positive predictive value for advanced neoplasia and high endoscopy burden investigating false positives suggests it might not be an appropriate screening tool in this setting. FUNDING: Thompson Family Foundation, Prevent Cancer Foundation, National Institutes of Health/National Cancer Institute Program Cancer Center.

The iBreastExam versus clinical breast examination for breast evaluation in high risk and symptomatic Nigerian women: a prospective study.

BACKGROUND: The iBreastExam electronically palpates the breast to identify possible abnormalities. We assessed the iBreastExam performance compared with clinical breast examination for breast lesion detection in high risk and symptomatic Nigerian women. METHODS: This prospective study was done at the Obafemi Awolowo University Teaching Hospital Complex (OAUTHC) in Nigeria. Participants were Nigerian women aged 40 years or older who were symptomatic and presented with breast cancer symptoms or those at high risk with a first-degree relative who had a history of breast cancer. Participants underwent four breast examinations: clinical breast examination (by an experienced surgeon), the iBreastExam (performed by recent nursing school graduates, who finished nursing school within the previous year), ultrasound, and mammography. Sensitivity, specificity, positive predictive values (PPV), and negative predictive values (NPV) of the iBreastExam and clinical breast examination for detecting any breast lesion and suspicious breast lesions were calculated, using mammography and ultrasound as the reference standard. FINDINGS: Between June 19 and Dec 5, 2019, 424 Nigerian women were enrolled (151 [36%] at high risk of breast cancer and 273 [64%] symptomatic women). The median age of participants was 46 years (IQR 42-52). 419 (99%) women had a breast imaging-reporting and data system (BI-RADS) assessment and were included in the analysis. For any breast finding, the iBreastExam showed significantly better sensitivity than clinical breast examination (63%, 95% CI 57-69 vs 31%, 25-37; p<0·0001), and clinical breast examination showed significantly better specificity (94%, 90-97 vs 59%, 52-66; p<0·0001). For suspicious breast findings, the iBreastExam showed similar sensitivity to clinical breast examination (86%, 95% CI 70-95 vs 83%, 67-94; p=0·65), and clinical breast examination showed significantly better specificity (50%, 45-55 vs 86%, 83-90; p<0·0001). The iBreastExam and clinical breast examination showed similar NPVs for any breast finding (56%, 49-63 vs 52%, 46-57; p=0·080) and suspicious findings (98%, 94-99 vs 98%, 96-99; p=0·42), whereas the PPV was significantly higher for clinical breast examination in any breast finding (87%, 77-93 vs 66%, 59-72; p<0·0001) and suspicious findings (37%, 26-48 vs 14%, 10-19; p=0·0020). Of 15 biopsy-confirmed cancers, clinical breast examination and the iBreastExam detected an ipsilateral breast abnormality in 13 (87%) women and missed the same two cancers (both <2 cm). INTERPRETATION: The iBreastExam by nurses showed a high sensitivity and NPV, but lower specificity than surgeon's clinical breast examination for identifying suspicious breast lesions. In locations with few experienced practitioners, the iBreastExam might provide a high sensitivity breast evaluation tool. Further research into improved specificity with device updates and cost feasibility in low-resource settings is warranted. FUNDING: Prevent Cancer Foundation Global Community Grant Award with additional support from the P30 Cancer Center Support Grant (P30 CA008748).

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.

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.

High-burden Cancers in Middle-income Countries: A Review of Prevention and Early Detection Strategies Targeting At-risk Populations.

Cancer incidence is rising in low- and especially middle-income countries (MIC), driven primarily by four high-burden cancers (breast, cervix, lung, colorectal). By 2030, more than two-thirds of all cancer deaths will occur in MICs. Prevention and early detection are required alongside efforts to improve access to cancer treatment. Successful strategies for decreasing cancer mortality in high-income countries are not always effective, feasible or affordable in other countries. In this review, we evaluate strategies for prevention and early detection of breast, cervix, lung, and colorectal cancers, focusing on modifiable risk factors and high-risk subpopulations. Tobacco taxation, human papilloma virus vaccination, cervical cancer screen-and-treat strategies, and efforts to reduce patient and health system-related delays in the early detection of breast and colorectal cancer represent the highest yield strategies for advancing cancer control in many MICs. An initial focus on high-risk populations is appropriate, with increasing population coverage as resources allow. These strategies can deliver significant cancer mortality gains, and serve as a foundation from which countries can develop comprehensive cancer control programs. Investment in national cancer surveillance infrastructure is needed; the absence of national cancer data to identify at-risk groups remains a barrier to the development of context-specific cancer control strategies.

Cancer-Specific Outcomes in the Elderly with Triple-Negative Breast Cancer: A Systematic Review.

Triple-negative breast cancer (TNBC) is more common among young women, although it frequently presents in older patients. Despite an aging population, there remains a paucity of data on the treatment of TNBC in elderly women. We conducted a systematic review of the peer-reviewed and unpublished literature that captures the management and breast-cancer-specific survival (BCSS) of women ≥70 years old with TNBC. Out of 739 papers, five studies met our inclusion criteria. In total, 2037 patients with TNBC treated between 1973 and 2014 were captured in the analysis. Women ≥70 years old were less likely to undergo surgical resection compared to those <70 (92.8% vs. 94.6%, p = 0.002). Adjuvant therapy, including radiation and chemotherapy, was also less likely to be utilized in women ≥70 years of age. These treatment differences were associated with more than a doubling of cancer-specific mortality in the elderly cohort (5.9% vs. 2.7% in ≤70 years old, p < 0.0001). Two of the five studies showed improved BCSS with adjuvant treatment while others showed no difference. Our systemic review questions the appropriateness of therapeutic de-escalation in this cohort and highlights the significant gap in our understanding of the optimal management for elderly patients with TNBC. Until more data are available, multidisciplinary treatment decision-making should carefully balance the available clinical evidence as well as the patient's predicted life expectancy and goals-of-care preferences.

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.

Durability of Complete Response to Intralesional Interleukin-2 for In-Transit Melanoma.

BACKGROUND: Intralesional injection of interleukin-2 (IL-2) for in-transit melanoma (ITM) is associated with a high rate of complete response. However, there is a paucity of data on treatment durability and long-term outcomes. OBJECTIVES: To provide long-term data on patients with a complete response to IL-2 therapy for ITM. METHODS: Consecutive patients with ITM, treated with intralesional IL-2 therapy, at the Tom Baker Cancer Center were identified from April 2009 to August 2019. All patients received at least 4 cycles (every 2 weeks) of IL-2 (5 MIU/mL). Complete response was defined as sustained (ie, 3 months) clinical complete remission of all known in-transit disease. RESULTS: Sixty-five patients were treated with curative intent for in-transit disease with intralesional IL-2. Complete clinical response was identified in 44.6% (29/65). In this subset of patients, the median number of lesions per patient was 9 (range 1-40). The median total dose of IL-2 was 0.8 mL (IQR 0.4-1.5) per lesion. One patient received isolated limb infusion and 13.8% (4/29) received systemic immunotherapy as part of their initial management. At a median follow-up of 27 months (IQR 16-59), 34.5% (10/29) developed recurrent disease. Of these patients, 50.0% (5/10) presented with synchronous in-transit and distant metastases. The median time to recurrence was 10.5 months (IQR 5.8-16.3). CONCLUSION: With long-term follow-up, 65.5% of complete responders have a durable response to intralesional IL-2 therapy. In this cohort of patients, local in-transit recurrence is most likely to occur within 12 months and is often associated with concomitant distant disease.

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.

Feasibility and performance of the fecal immunochemical test (FIT) for average-risk colorectal cancer screening in Nigeria.

INTRODUCTION: There is a paucity of prospective data on the performance of the fecal immunochemical test (FIT) for colorectal cancer (CRC) screening in sub-Saharan Africa. The aim of this exploratory analysis was to evaluate the feasibility and performance of FIT in Nigeria. METHODS: This was a prospective, single-arm study. A convenience sample of asymptomatic, average-risk individuals between 40-75 years of age were enrolled at Obafemi Awolowo University Teaching Hospital. Study participants returned in 48 hours with a specimen for ova and parasite (O&P) and qualitative FIT (50ug/g) testing. Participants with a positive FIT had follow-up colonoscopy and those with intestinal parasites were provided treatment. RESULTS: Between May-June 2019, 379 individuals enrolled with a median age of 51 years (IQR 46-58). In total, 87.6% (n = 332) returned for FIT testing. FIT positivity was 20.5% (95% CI = 16.3%-25.2%). Sixty-one (89.7%) of participants with a positive FIT had a follow-up colonoscopy (n = 61), of whom 9.8% (95%CI:3.7-20.2%) had an adenoma and 4.9% (95%CI:1.0-13.7%) had advanced adenomas. Presence of intestinal parasites was inversely related to FIT positivity (6.5% with vs. 21.1% without parasites, p = 0.05). Eighty-two percent of participants found the FIT easy to use and 100% would recommend the test to eligible family or friends if available. CONCLUSIONS: Asymptomatic, FIT-based CRC screening was feasible and well tolerated in this exploratory analysis. However, the high FIT positivity and low positive predictive value for advanced neoplasia raises concerns about its practicality and cost effectiveness in a low-resource setting such as Nigeria.

Geospatial access predicts cancer stage at presentation and outcomes for patients with breast cancer in southwest Nigeria: A population-based study.

BACKGROUND: The majority of women in Nigeria present with advanced-stage breast cancer. To address the role of geospatial access, we constructed a geographic information-system-based model to evaluate the relationship between modeled travel time, stage at presentation, and overall survival among patients with breast cancer in Nigeria. METHODS: Consecutive patients were identified from a single-institution, prospective breast cancer database (May 2009-January 2019). Patients were geographically located, and travel time to the hospital was generated using a cost-distance model that utilized open-source data. The relationships between travel time, stage at presentation, and overall survival were evaluated with logistic regression and survival analyses. Models were adjusted for age, level of education, and socioeconomic status. RESULTS: From 635 patients, 609 were successfully geographically located. The median age of the cohort was 49 years (interquartile range [IQR], 40-58 years); 84% presented with ≥stage III disease. Overall, 46.5% underwent surgery; 70.8% received systemic chemotherapy. The median estimated travel time for the cohort was 45 minutes (IQR, 7.9-79.3 minutes). Patients in the highest travel-time quintile had a 2.8-fold increase in the odds of presenting with stage III or IV disease relative to patients in the lowest travel-time quintile (P = .006). Travel time ≥30 minutes was associated with an increased risk of death (HR, 1.65; P = .004). CONCLUSIONS: Geospatial access to a tertiary care facility is independently associated with stage at presentation and overall survival among patients with breast cancer in Nigeria. Addressing disparities in access will be essential to ensure the development of an equitable health policy.

Mapping Geospatial Access to Comprehensive Cancer Care in Nigeria.

PURPOSE: To address the increasing burden of cancer in Nigeria, the National Cancer Control Plan outlines the development of 8 public comprehensive cancer centers. We map population-level geospatial access to these eight centers and explore equity of access and the impact of future development. METHODS: Geospatial methods were used to estimate population-level travel times to the 8 cancer centers. A cost distance model was built using open source road infrastructure data with verified speed limits. Geolocated population estimates were amalgamated with this model to calculate travel times to cancer centers at a national and regional level for both the entire population and the population living on < US$2 per day. RESULTS: Overall, 68.9% of Nigerians have access to a comprehensive cancer center at 4 hours of continuous vehicular travel. However, there is significant variability in access between geopolitical zones (P < .001). The North East has the lowest access at 4 hours (31.4%) and the highest mean travel times (268 minutes); this is significantly lower than the proportion with 4-hour access in the South East (31.4% v 85.0%, respectively; P < .001). The addition of a second comprehensive cancer center in the North East, in either Bauchi or Gombe, would significantly improve access to this underserved region. CONCLUSION: The Federal Ministry of Health endorses investment in 8 public comprehensive cancer centers. Strengthening these centers will allow the majority of Nigerians to access the full complement of multidisciplinary care within a reasonable time frame. However, geospatial access remains inequitable, and the impact on outcomes is unclear. This must be considered as the cancer control system matures and expands.

An Exploratory Analysis of Fecal Immunochemical Test Performance for Colorectal Cancer Screening in Nigeria.

INTRODUCTION: The fecal immunochemical test (FIT) for hemoglobin is recommended for colorectal cancer (CRC) screening in resource-limited environments. However, there are several unique variables that may alter FIT performance in this setting, including endemic intestinal parasites and high ambient temperature. This prospective study evaluated the performance of FIT in asymptomatic, average-risk individuals of screening age in rural Nigeria. METHODS: Three hundred and twenty-four community volunteers completed a questionnaire and provided stool specimens for parasitology and microbiome analysis. Specimens were frozen and stored at -80 °C. Of 324 subjects, 139 met criteria for average-risk CRC screening and had a stool sample for analysis. These were thawed and tested with a qualitative FIT. Specimens positive for occult blood were retested every two days to evaluate the impact of time and temperature on test performance. RESULTS: Of 139 individuals, 69 (49.6%) were positive for intestinal parasites and 10 (7.2%) were positive for occult blood. The most common pathogen was Cryptosporidium (40.6%). Among patients with intestinal parasites, 10.1% (7/69) had a positive FIT. Only 4.3% (3/70) of patients without parasites had a positive FIT (p = 0.208). On bivariate analysis, sociodemographic variables were not associated with a positive FIT result. Thirty percent (3/10) of the FIT-positive specimens became FIT-negative with routine storage. CONCLUSION: Although a positive FIT result was more common in those with parasitic infection, the relationship was not significant in this small cohort. The impact of high ambient temperature on test positivity may necessitate shorter processing time guidelines for equatorial countries. Additional prospective studies are needed to validate FIT performance in Nigeria.