Using Patient Navigation to Reduce Time to Diagnosis of Breast Cancer in Uganda.

PURPOSE: The Ugandan Ministry of Health adopted BI-RADS as standard of care in 2016. The authors performed a medical audit of breast ultrasound practices at four tertiary-level hospitals to assess interpretive performance. The authors also determined the effect of a low-cost navigation program linking breast imaging and pathology on the percentage of patients completing diagnostic care. METHODS: The authors retrieved 966 consecutive diagnostic breast ultrasound reports, with complete data, for studies performed on women aged >18 years presenting with symptoms of breast cancer between 2018 and 2020 from participating hospitals. Ultrasound results were linked to tumor registries and patient follow-up. A medical audit was performed according to the ACR's BI-RADS Atlas, fifth edition, and results were compared with those of a prior audit performed in 2013. At Mulago Hospital, an intervention was piloted on the basis of patient navigation, cost sharing, and same-day imaging, tissue sampling, and pathology. RESULTS: In total, 888 breast ultrasound examinations (91.9%) were eligible for inclusion. Compared with 2013, the postintervention cancer detection rate increased from 38 to 148.7 cancers per 1,000 examinations, positive predictive value 2 from 29.6% to 48.9%, and positive predictive value 3 from 62.7% to 79.9%. Specificity decreased from 90.5% to 87.7% and sensitivity from 92.3% to 81.1%. The mean time from tissue sampling to receipt of a diagnosis decreased from 60 to 7 days. The intervention increased the percentage of patients completing diagnostic care from 0% to 100%. CONCLUSIONS: Efforts to establish a culture of continuous quality improvement in breast ultrasound require robust data collection that links imaging results to pathology and patient follow-up. Interpretive performance met BI-RADS benchmarks for palpable masses, except sensitivity. This resource-appropriate strategy linking imaging, tissue sampling, and pathology interpretation decreased time to diagnosis and rates of loss to follow-up and improved the precision of the audit.

HIV-related lung cancer in Uganda: a cohort study.

BACKGROUND: There are few reports on lung cancer among people with HIV (PWH) in Sub-Saharan Africa. In this report, we describe a cohort of PWH and lung cancer at the Uganda Cancer Institute. METHODS: This retrospective cohort of PWH and lung cancer was managed at the Uganda Cancer Institute between 2008 and 2018. Sociodemographic and clinical data were abstracted from the patient charts. The median survival from diagnosis to death, loss-to-follow up or 31st December 2018, was estimated. RESULTS: There were 18 people with HIV and lung cancer. The median (interquartile range, IQR) age was 49.5 (38.8-56.0) years, 11 (61.1%) were women and 5 (27.8%) were smokers. Of the 18 PWH, 13 (72.2%) were on antiretroviral therapy and the median (IQR) CD4 count (n = 13) was 380 (243.5-595) cells per mm3. Difficulty in breathing (88.9%), chest pain (78.6%, n = 11), cough (76.5%, n = 17) and weight loss (72.2%) were the commonest symptoms while pleural effusions were observed in 12 (66.7%). In this cohort, 8 (44.4%) were presumptively treated for tuberculosis before the diagnosis of lung cancer. Seven (38.9%) had an Eastern Cooperative Oncology Group performance status of 3. Non-small cell lung cancer was the predominant histological type observed in 17 (94.4%) of whom 14 (82.4%) had adenocarcinoma. Majority of PWH had stage IV disease (88.9%). The median (IQR) survival was 3.3 (1.1-13.2) months and all were either dead (72.2%) or lost-to-follow up (27.8%) at five years from diagnosis. CONCLUSION: People with HIV and lung cancer in Uganda report low rates of smoking, present with advanced disease and post very poor survival rates. There is need for biomarkers for early detection of lung cancer in HIV.

A 10-year retrospective study of lung cancer in Uganda.

BACKGROUND: Lung cancer is a leading cause of cancer-related deaths in Uganda. In this study, we aimed to describe the baseline characteristics and survival of patients with lung cancer at the Uganda Cancer Institute (UCI). METHODS: We retrospectively reviewed medical records of all patients with a histological diagnosis of lung cancer registered at UCI between January 2008 and August 2018. Data on demographic, clinical, and treatment characteristics, and vital status were abstracted and analyzed. Patients with undocumented vital status on the medical records were contacted through phone calls. We determined survival as time from histological diagnosis to death. The Kaplan-Meier survival analysis was performed to estimate the median survival time and the 5-year overall survival rate. RESULTS: Of the 207 patients enrolled, 56.5% (n = 117) were female, median age was 60 years (range: 20-94), 78.7% (n = 163) were never-smokers and 18 (8.7%) were living with HIV. Presumptive anti-tuberculosis treatment was given to 23.2% (n = 48). Majority had non-small cell lung cancer (96.6%, n = 200) with 74.5% (n = 149) adenocarcinoma and 19% (n = 38) squamous cell carcinoma. All had advanced (stage III or IV) disease with 96.1% (n = 199) in stage IV. Chemotherapy (44.9%, n = 93) and biological therapy (34.8%, n = 72) were the commonest treatments used. Overall survival at 6 months, 1-, 2- and 5-years was 41.7, 29.7, 11.8, and 1.7%, respectively. The median survival time of 4.4 months was not statistically significantly different between participants with NSCLC or SCLC (4.5 versus 3.9 months, p = .335). CONCLUSION: In Uganda, adenocarcinoma is the predominant histologic subtype of lung cancer and patients are predominantly females, and non-smokers. Patients present late with advanced disease and poor overall survival. Public awareness should be heightened to facilitate early detection and improve outcomes.

Rational and design of SATRACD study: detecting subclinical anthracycline therapy related cardiac dysfunction in low income country.

BACKGROUND: Anthracycline therapy-related cardiac dysfunction (ATRCD) is the most notorious adverse side-effect of chemotherapy. It has become a significant cardiovascular health concern for long-term cancer survivors. With the emerging concept of subclinical ATRCD and newer diagnostictools (Speckle Tracking Echocardiography (STE) and biomarkers), detecting anthracycline cardiac toxicity at an early stage has become an important step to prevent severe cardiac dysfunction and improve the cardiovascular outcome in cancer survivors. Despite the increasing population at risk in sub-Saharan Africa (SSA), there is no contemporary data in Uganda to address the burden, pathogenesis and risk factors of subclinical ATRCD. This big gap in knowledge has led to a lack of local guidelines for monitoring and management of ATRCD. METHODS: SATRACD (Detecting Subclinical Anthracycline Therapy Related Cardiac Dysfunction In Low Income Country) study is an observational prospective cohort study. Three hundred and fifty-three anthracycline naïve cancer patients will be recruited at baseline. Patients are followed up on completion of anthracycline-based chemotherapy and at 6 months after completion of anthracycline therapy. Data on demographics, cancer profile and clinical presentation will be collected at baseline. Comprehensive cardiac assessment will be performed at each visit, including electrocardiogram, conventional echocardiography, STE, cardiac and oxidative stress markers. We will be able to determine the incidence of subclinical and clinical ATRCD at 6 months after completion of anthracycline therapy, determine whether hypertension is a major risk factor for ATRCD, evaluate the role of conventional echocardiography parameters, and biomarkers for detecting subclinical ATRCD. CONCLUSION: This SATRACD study will provide contemporary data on Ugandan cancer patients who have subclinical and clinical ATRCD, help in the development of local strategies to prevent and manage ATRCD, and improve cardiovascular outcome for Ugandan cancer survivors.

Clinical characterization, cardiovascular risk factor profile and cardiac strain analysis in a Uganda cancer population: The SATRACD study.

BACKGROUND: The link between cancer and cardiovascular disease is firmly established. We sought to investigate the prevalence of cardiovascular disease (CVD) risk factors in Uganda cancer patients, their pre-chemotherapy left ventricular strain echocardiographic pattern and its associations with the CVD risk factors. METHODS AND RESULTS: Baseline pre-chemotherapy data of patients who were enrolled in the SATRACD study (a cancer cohort, who were planned for anthracycline therapy), were analyzed. The prevalence of cardiovascular risk factors and baseline strain echocardiographic images were assessed. Among the 355 patients who were recruited over a period of 15 months, 283 (79.7%) were female, with a mean age of 43 years. The types of cancer of the study patients included breast cancer (70.6%), lymphomas, sarcomas, leukemias and hepatocellular carcinoma. Hypertension was the most common comorbidity (27.0%). The prevalence of obesity was 12.1% and that of HIV was 18.3%. All patients had a normal left ventricular ejection fraction (LVEF). The mean global longitudinal strain (GLS) was -20.92 ±2.43%, with females having a significantly higher GLS than males (-21.09±2.42 vs -20.25±2.39, p = 0.008). Fifty-three patients (14.9%) had suboptimal GLS (absolute GLS≤18.00%), which was associated with obesity (POR = 3.07; 95% CI, 1.31-6.98; p = 0.003), alcohol use (POR = 1.94; 95% CI, 1.01-3.74; p = 0.044), long QTc interval in electrocardiogram (POR = 2.54; 95% CI, 1.06-5.74; p = 0.015,) and impaired left ventricular relaxation (POR = 2.24; 95% CI, 1.17-4.25; p = 0.007). On multivariable logistic regression analysis, obesity (POR = 2.95; 95% CI, 1.24-7.03; p = 0.014) was the only independent factor associated with suboptimal GLS. CONCLUSION: There is high prevalence and a unique pattern of cardiovascular risk factors in Uganda cancer patients. In cancer patients with cardiovascular risk conditions, there is reduction in GLS despite preserved LVEF. Longitudinal research is needed to study the predictive value of cardiovascular risk factors and baseline GLS for post chemotherapy cardiac dysfunction.

Clinical profile and initial treatment of non-small cell lung cancer: a retrospective cohort study at the Uganda Cancer Institute.

Introduction: Lung cancer is a major global public health burden constituting 11.6% of all new cancer diagnoses and 18.4% of all cancer-related mortality. Purpose: To describe the clinical profile and initial treatment of non-small cell lung cancer in Uganda. Methods: We reviewed charts of a cohort of patients with a histologically confirmed diagnosis of non-small cell lung cancer, treated between January 2013 and November 2015 at the Uganda Cancer Institute. Results: A total of 74 patients met the inclusion criteria. The median age was 56 years (IQR 47-70), with 16.2% below the age 45 years, and 51% were female. Only 10 percent were active smokers and the most frequent histological subtype was adenocarcinoma (71%). The majority (91.9%) had stage IV disease at diagnosis and frequent metastases to contralateral lung, liver, and bones. Twenty-seven (27) patients received platinum-based chemotherapy, while 27 patients received erlotinib, and only 4 patients received palliative thoracic radiotherapy. The median survival time was 12.4 months, and the overall response rate was 32.7%. There was no survival difference by type of systemic treatment, and on multivariate analysis, poor performance status was predictive of adverse outcomes (p < 0.001). Conclusions: Patients with non-small cell lung cancer in Uganda frequently presented with late-stage disease at diagnosis. The majority of patients were female, never-smokers, and had predominantly adenocarcinoma subtype.

Anthracycline induced cardiotoxicity in adult cancer patients: a prospective cohort study from a specialized oncology treatment centre in Uganda.

PURPOSE: To determine the cumulative incidence of anthracycline induced cardiotoxicity (AIC), its predictors, and associated electrocardiographic and echocardiographic manifestations in adult cancer patients at Uganda Cancer Institute (UCI). METHODS: We enrolled 160 participants between June 2013 and April 2014 and followed them up for a median of 146 days. Data on clinical, electrocardiographic and echocardiographic findings was obtained at baseline, and at completion of chemotherapy. The Pearson chi square test was used to identify the predictors associated with cardiotoxicity. RESULTS: Of the 64 patients who were accessible for follow-up electrocardiography (ECG) and echocardiography (ECHO), fourteen participants developed cardiotoxicity hence a cumulative incidence rate of 21.9% with 95% CI 13.5%-33.43%. The predictors of AIC were female gender (p=0.025), LVEF (p=0.014) and LVFS (P=0.019). Anthracycline therapy was associated with shortening of the QRS duration (84.3±7.9 Vs 82.1±11.8 ms, p=0.005), prolongation of the QTc interval (411.9±30.7 Vs 447.2±39.4 ms, p=<0.001) and reduction in the LVEF (66.4±7.7 Vs 63.9±8.4%, p=0.026) and LVFS (36.9±6.2 Vs 35.1±6.6%, p=0.03). CONCLUSION: The cumulative incidence of AIC in this study cohort was high. Our findings emphasize the need for early monitoring for AIC.

The Kynurenine Pathway of Tryptophan Catabolism and AIDS-Associated Kaposi Sarcoma in Africa.

BACKGROUND: Other than Kaposi sarcoma (KS)-associated herpesvirus and CD4 T-cell lymphopenia, the mechanisms responsible for KS in the context of HIV are poorly understood. One recently explored pathway of HIV pathogenesis involves induction of the enzyme indoleamine 2,3-dioxygenase-1 (IDO), which catabolizes tryptophan into kynurenine and several other immunologically active metabolites that suppress T-cell proliferation. We investigated the role of IDO in the development of KS in HIV disease. METHODS: In a case-control study among untreated HIV-infected Ugandans, cases were adults with KS and controls were without KS. IDO activity was assessed by the ratio of plasma kynurenine to tryptophan levels (KT ratio), measured by liquid chromatography-tandem mass spectrometry. RESULTS: We studied 631 HIV-infected subjects: 222 KS cases and 409 controls. Non-KS controls had a higher median plasma KT ratio (130, interquartile range: 90 to 190 nM/µM) than KS cases (110, interquartile range: 90 to 150 nM/µM) (P = 0.004). After adjustment for age, sex, CD4 count, and plasma HIV RNA level, subjects with the highest (fourth quartile) plasma KT ratios had a 59% reduction (95% confidence interval: 27% to 77%) in the odds of KS compared with those with the lowest (first quartile) levels. KS was also independently associated with lower CD4 count, higher plasma HIV RNA, and men. CONCLUSIONS: Among HIV-infected individuals, greater activity of the kynurenine pathway of tryptophan catabolism, as evidenced by higher levels of plasma KT ratio, was associated with lower occurrence of KS. Some consequences of immune activation in HIV infection might actually suppress certain cancers.

Cutaneous T-cell lymphoma in sub-Saharan Africa.

The incidence and economic burden of cancer in sub-Saharan Africa is increasing, and innovative strategies are needed to improve prevention and care in this population. This article uses a case of cutaneous T-cell lymphoma in Uganda to propose guidelines for the diagnosis and treatment of this disease in resource-limited settings. These guidelines were developed from the consensus opinion of specialists at the Uganda Cancer Institute and Fred Hutchinson Cancer Research Center as part of an established collaboration. Areas for future investigation that can improve the care of patients in this region are identified.

Infection-related cancers in sub-saharan Africa: a paradigm for cancer prevention and control.

There is much commonality between chronic noncommunicable and communicable diseases which is best exemplified by cancers of infectious origin. It provides the perfect opportunity for harnessing the advances that have been made in the control of communicable diseases to attempt the control of noncommunicable diseases. There are possibilities at various levels of intervention, at primary, secondary and tertiary levels, which fit well within a well-planned national cancer control strategy. Prevention should proceed through steps of disruption of transmission, improvement in disease recognition and diagnosis, as well as through prompt effective treatment. This principle should work for both infection and the resultant cancer. Research is very important in understanding how best to use the available knowledge and how best to sequentially implement strategies. Finally, policies that acknowledge infection-related cancers as a major problem in the region should be in place.

Burkitt lymphoma in Uganda, the legacy of Denis Burkitt and an update on the disease status.

Burkitt lymphoma (BL) was first described in Uganda in 1958 as a sarcoma of the jaw but later confirmed to be a distinct form of Non Hodgkin lymphoma (NHL). This discovery was the defining moment of cancer research in Uganda, which eventually led to the establishment of a dedicated cancer research institute, the Uganda Cancer Institute (UCI) in 1967. The centre was dedicated to Denis Burkitt in recognition of his contribution to cancer research in East Africa. BL is still the commonest NHL in childhood in Uganda. Its incidence has significantly increased recently due to yet unknown factors. Although the human immunodeficiency virus (HIV) was considered a possible reason for the increase, there is no evidence that it has substantially impacted on the epidemiology of the disease. However, for those patients with BL who are co infected with HIV there is a clear impact of the disease on clinical presentation and outcome. HIV-infected patients commonly present with extra facial sites and tend to have poor overall survival (median survival of 11·79 months). In summary, BL, as a disease entity in Uganda, has maintained the same clinical characteristics since its discovery, despite the emergence of HIV during the intervening period.

Clinical presentation and outcome of epidemic Kaposi sarcoma in Ugandan children.

BACKGROUND: Kaposi sarcoma (KS) is one of the most common pediatric cancers in sub-Saharan Africa. Few data are available about the clinical presentation or response to treatment of children with epidemic (HIV-associated) KS. METHODS: Medical records of all children with KS and HIV infection referred to the Uganda Cancer Institute in Kampala, Uganda from October 2004 to June 2007 were reviewed. Charts were abstracted for age, sex, location of KS lesions at presentation, biopsy results, CD4 T-cell count and percentage, and KS treatment and outcome. RESULTS: Seventy-three children with epidemic KS were identified, 37 males and 36 females. The median age was 10.1 years (range 2-18). KS presented with lymph node (LN) involvement in 60% of cases. The median absolute and percentage CD4 T-cells at presentation were 210 cells/microl and 7.4%, respectively. Those children with lymphadenopathic KS were younger (mean difference 3.7 years; P = 0.01) and had higher CD4 T-cell counts (mean difference 242 cells/microl; P = 0.03) than those without LN involvement. Of 32 patients for whom outcome data were available, a complete response to chemotherapy and/or antiretroviral therapy was documented in 20 (62.5%) patients. CONCLUSIONS: In comparison to cutaneous involvement, LN involvement of epidemic KS occurs at younger ages and at higher CD4 levels. This clinical presentation may reflect recent infection with human herpesvirus 8 followed by a rapid progression to malignancy. Favorable response to treatment was observed in the majority of cases, but prospective studies are needed to determine optimal management.