Browsing by Author "Casper, Corey"

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    A Population-Level Evaluation of the Effect of Antiretroviral Therapy on Cancer Incidence in Kyadondo County, Uganda, 1999–2008
    (JAIDS Journal of Acquired Immune Deficiency Syndromes, 2015-08-01) Mutyaba, Innocent; Krantz, Elizabeth M.; Nambooze, Sarah; Orem, Jackson; Wabinga, Henry R.; Casper, Corey
    The introduction of antiretroviral therapy (ART) in the United States and Europe has led to changes in the incidence of cancers among HIV-infected persons, including dramatic decreases in Kaposi sarcoma and non-Hodgkin lymphoma, and increases in Hodgkin lymphoma, liver, and anogenital malignancies. We sought to evaluate whether increasing availability of ART is associated with changing cancer incidence in Uganda. Incident cases of 10 malignancies were identified from Kampala Cancer Registry from 1999 to 2008. ART coverage rates for Uganda were abstracted from the Joint United Nations Program on HIV/AIDS reports. Negative binomial and Poisson regression modeled the association between ART coverage and age-adjusted cancer incidence. ART coverage in Uganda increased from 0% to 43% from 1999 to 2008. With each 10% increase in ART coverage, incidence of Kaposi sarcoma decreased by 5% [incidence rate ratio (IRR) = 0.95, 95% confidence interval: 0.91 to 0.99, P = 0.02] and stomach cancer decreased by 13% [IRR = 0.87 (95% CI: 0.80 to 0.95), P = 0.002]. Conversely, incidence of non-Hodgkin lymphoma increased by 6% [IRR = 1.06 (95% CI: 1 to 1.12), P = 0.05], liver cancer by 12% [IRR = 1.12 (95% CI: 1.04 to 1.21), P = 0.002], prostate cancer by 5% [IRR = 1.05 (95% CI: 1 to 1.10), P = 0.05], and breast cancer by 5% [IRR = 1.05 (95% CI: 1 to 1.11), P = 0.05]. ART coverage was not associated with incidence of invasive cervical cancer, lung, colon, and Hodgkin disease. These findings were similar when restricted to histologically confirmed cases. Our findings suggest that AIDS-defining malignancies and other malignancies are likely to remain significant public health burdens in sub-Saharan Africa even as ART availability increases.
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    Antiretroviral Therapy is Highly Effective Against Incident Hepatitis B Disease Acquisition Among HIV-Infected Adults in Rakai, Uganda
    (American Society of Clinical Oncology, 2016) Seremba, Emmanuel; Ssempijja, Victor; Kalibbala, Sarah; Gray, Ronald; Wawer, Maria; Nalugoda, Fred; Casper, Corey; Phipps, Warren T.; Ocama, Ponsiano; Thomas, David L.; Reynolds, Steven J.
    Co-infection with HepatitisB(HBV) and HIV iscommonin sub-Saharan Africa (SSA) and accelerates progression of liver disease to cirrhosis, hepatocellular carcinoma (HCC) andother complications. About 60% of HCC in Africa is attributed to HBV. In Uganda, 80% of HCC patients have HBVand20%have HIV/HBV coinfection.HCCis the 4th commonest cancer among Ugandan males and the 6th commonest in females. It is almost always a fatal malignancy in SSA. Prevention of HBV is best achieved through vaccination. Vaccination of HIV-infected adults for HBV is standard of care in developed countries but not in SSA where HBV is believed to be acquired in childhood and where there is lack of HBV incidence data. We investigated the incidence and risk factors associated with HBV among HIV-infected adults in Rakai, Uganda.
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    Association Between HIV Infection and Cancer Stage at Presentation at the Uganda Cancer Institute
    (J Glob Oncol, 2018-10-16) Menon, Manoj P.; Mutyaba, Innocent O.; Okuku, Fred M.; Orem, Jackson; Casper, Corey
    The HIV epidemic has contributed to the increasing incidence of cancer in sub-Saharan Africa, where most patients with cancer present at an advanced stage. However, improved access to HIV care and treatment centers in sub-Saharan Africa may facilitate earlier diagnosis of cancer among patients who are HIV positive. To test this hypothesis, we characterized the stage of cancer and evaluated the factors associated with advanced stage at presentation among patients in Uganda. We conducted a retrospective analysis of adult patients with any of four specific cancers who presented for care in Kampala, Uganda, between 2003 and 2010. Demographic, clinical, and laboratory data were abstracted from the medical record, together with the outcome measure of advanced stage of disease (clinical stage III or IV). We identified measures for inclusion in a multivariate logistic regression model We analyzed 731 patients with both AIDS-defining cancers (cervical [43.1%], and non-Hodgkin lymphoma [18.3%]), and non–AIDS-defining cancers (breast [30.0%] and Hodgkin lymphoma [8.6%]). Nearly 80% of all patients presented at an advanced stage and 37% had HIV infection. More than 90% of patients were symptomatic and the median duration of symptoms before presentation was 5 months. In the multivariate model, HIV-positive patients were less likely to present at an advanced stage as were patients with higher hemoglobin and fewer symptoms. Patients with limited access to primary care may present with advanced cancer because of a delay in diagnosis. However, patients with HIV now have better access to clinical care. Use of this growing infrastructure to increase cancer screening and referral is promising and deserves continued support, because the prognosis of HIV-positive patients with advanced cancer is characterized by poor survival globally.
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    Clinical Presentation and Outcome of Epidemic Kaposi Sarcoma in Ugandan Children
    (Pediatric blood & cancer, 2010) Gantt, Soren; Kakuru, Abel; Wald, Anna; Walusansa, Victoria; Corey, Lawrence; Casper, Corey; Orem, Jackson
    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/ml and 7.4%, respectively. Those children with lymphadenopathic KS were younger (mean difference 3.7 years; P¼0.01) and had higher CD4 T-cell counts (mean difference 242 cells/ml; P¼0.03) 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. Pediatr Blood Cancer
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    Impact of a Quality Improvement Project on Pediatric Endemic Burkitt Lymphoma Outcomes in Uganda
    (Blood, 2016-12-02) McGoldrick, Suzanne M.; Omoding, Abrahams; Mutyaba, Innocent; Krantz, Elizabeth; Orem, Jackson; Casper, Corey
    Endemic Burkitt Lymphoma (eBL) is the most common childhood cancer in many countries of sub-Saharan Africa (SSA). Reported overall survival (OS) rates in SSA are low at 30-50%, especially compared to survival of children with sporadic Burkitt Lymphoma treated in high-resource settings (OS 85-95%)(Patte, Auperin et al. 2007, Buckle, Maranda et al. 2016, Stanley, Westmoreland et al. 2016). The Burkitt Lymphoma (BL) project in Uganda was initiated as a collaboration between the Fred Hutchinson Cancer Research Center and Uganda Cancer Institute (UCI) in July 2012. The project provided resources for timely pathologic diagnosis, chemotherapy during stock-outs, case management to improve adherence, transportation, and standardized recording of care and clinical outcomes. We sought to determine OS and response to treatment in this patient population with eBL who received enhanced care through this demonstration project. Every child presenting to the UCI with suspected BL and enrolled in the BL project between July 2012 and December 2014 underwent diagnostic evaluation with a core needle biopsy of the tumor, abdominal ultrasound, and chest radiography. Patients with confirmed BL at enrollment, as determined by pathology review and physician assessment, were staged based on physical exam according to Ziegler. Most received first-line therapy consisting of cyclophosphamide, vincristine and methotrexate (COM) every two weeks for six planned cycles. Treatment response was evaluated ≤ 3 months from starting the 6th cycle of COM. Following completion of therapy, patients were followed monthly for three months, then every three months for up to a year. Follow-up data through March 26, 2015 was included. Kaplan-Meier methodology was used to estimate 1-year OS. A total of 202 patients with suspected BL were followed by the BL project during this time period. Of these, 142 (70%) were confirmed to have BL. The remainder had other cancers or benign diseases (24%) or had inadequate diagnostic data (6%). The median age of patients with BL was 7 years and the majority were male (63%). Approximately half of patients had late-stage disease (49% Ziegler stages C, D or AR) and had a high LDH at presentation (54%). Of the 142 with BL, 78% initiated COM, 6% other chemotherapy, and 16% were not treated with chemotherapy (18 died in the first 40 days and 5 were exited). Among 110 patients who initiated COM, the treatment response after 6 cycles was complete response (CR) for 46%, partial response (PR) for 7%, stable (SD) or progressive disease (PD) for 2%, relapsed disease (RD) for 1%, but there was no response assessment within 3 months of the 6th cycle for 10%. The remaining patients who did not complete 6 cycles either switched to second line therapy (7%), abandoned treatment (9%), died (9%), exited the program (3%), or were censored (6%) within 6 months of starting treatment. Among the subset of 73 patients who completed six cycles of treatment, the responses after 6 cycles were as follows: CR 70%, PR 11%, SD or PD 3%, RD 1%, unknown 15%. At 1 year, OS for the entire cohort with confirmed eBL was 53% (95% CI 43%, 62%; Figure 1). Among the patients who initiated COM, survival at 1 year post treatment initiation was 60% (95% CI 49%, 70%; Figure 2). These data represent preliminary results of our ongoing analysis. An updated analysis, along with associations of baseline factors, including CNS status, anemia, thrombocytopenia, B symptoms, tumor lysis syndrome and HIV status, as well as other infections (malaria, Hepatitis B), with clinical outcomes will be presented. Survival ofpatients with eBL treated in a low-resource setting remains inferior compared to children treated for sporadic BL in higher resource settings. The BL project was able to provide pathologic diagnoses, assure access to chemotherapy, enhance supportive care, and reduce abandonment to less than 10%, but still only slightly more than half of patients with a confirmed diagnosis survived one year. Ongoing obstacles to improving outcomes are inaccurate diagnosis and lacking supportive care to allow more intensive therapies. Improved diagnostic capacity as well as the ability to provide more potent and potentially less toxic treatment modalities may help to address the poor survival of children with a disease that is so successfully treated in higher resource settings.
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    Presentation and Outcomes of Childhood Cancer Patients at Uganda Cancer Institute
    (Global Pediatric Health, 2019-05-18) Mutyaba, Innocent; Wabinga, Henry R.; Orem, Jackson; Casper, Corey; Phipps, Warren
    Limited data suggest that children with cancer in sub-Saharan Africa have poor survival. We aimed to describe the presentation, treatment outcomes, and factors associated with survival among children with cancer managed at Uganda Cancer Institute. Methods. We retrospectively evaluated patients with childhood cancer (age ≤19 years) from Kyadondo County treated at Uganda Cancer Institute from 2006 to 2009. Cox’s regression and Kaplan-Meier methods were used to study 1-year survival. Results. Among 310 patients studied, median age was 7 years (range = 0.25-19 years), 64% were boys, and 92% had histological confirmation of cancer diagnosis. The commonest diagnoses were Burkitt lymphoma (BL, N = 87), Kaposi sarcoma (KS, N = 68), non-BL non-Hodgkin lymphoma (NHL, N = 32), acute lymphoblastic leukemia (ALL, N = 28), Wilms (N = 28), and Hodgkin disease (HD, N = 20). Advanced disease at diagnosis was common for all cancers (ranging from 45% for KS to 83% for non-BL NHL). Overall, 33.2% abandoned treatment. One-year survival was 68% for HD (95% confidence interval [CI] = 11.3-40.6), 67% for KS (95% CI = 52.1-77.9), 55% for BL (95% CI = 42-66.9), 44% for Wilms (95% CI = 22.5-63), 43% for non-BL NHL (95% CI = 23.3-61.3), and 20% for ALL (95% CI = 6.4-38.7). In univariate and multivariate analysis, anemia and thrombocytopenia were associated with mortality for several cancers. Conclusion. Survival among children with cancer in Uganda is poor. Advanced stage disease and loss to follow-up likely contribute to poor outcomes. Anemia and thrombocytopenia may augment traditional staging methods to provide better prognostic factors in Uganda and warrant further evaluation.
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    Treatment Recommendations for Patients with NHL at the Uganda Cancer Institute
    (Blood, 2013-11-15) Menon, Manoj P.; Mutyaba, Innocent; Harlan, John M.; Okuku, Fred; Orem, Jackson; Casper, Corey
    It is estimated that nearly half a million people will die of cancer in sub-Saharan Africa (SSA) in 2020, and that the incidence of cancer will increase more than 40% between now and then. Unfortunately, treatment options in SSA are often hampered by a sub-optimal health care infrastructure resulting in advanced disease at presentation and the limited availability of effective, but cost prohibitive, chemotherapy. Consequently patient outcomes are typically poor and there is an unmet need to identify those cancer patients who would benefit most from the limited resources available. In resource-abundant areas, low hemoglobin [hgb], advanced disease stage, and poor patient performance status (PS) are associated with a poor prognosis and often serve to direct cancer care towards palliation instead of cure. Similarly, the international prognostic index (IPI) provides prognostic information among patients with non-Hodgkin lymphoma (NHL). However, the utility of such measures in therapeutic decision making in resource-poor areas is less studied. Here we describe characteristics of patients with a new diagnosis of NHL presenting for care in Uganda and identify factors associated with those patients recommended to receive cancer-directed therapy. We conducted a retrospective analysis of all patients > 18 at the time of diagnosis of NHL between 2003 and 2010 who were residents of Kyandondo County (Uganda). Cases were identified from the Kampala Cancer Registry (KCR), a national population-based cancer registry. Patient lists from the KCR were transferred to the Uganda Cancer Institute (UCI), the nation's sole cancer center and Mulago Hospital, a university teaching hospital located in Kampala. Additionally, eligible patients who had not yet been recorded in the KCR were identified from patient records at the UCI or Mulago Hospital. Medical records were reviewed for all eligible patients. Patients determined to have a prior malignancy were excluded from this analysis. Demographic, clinical, and laboratory data were abstracted from the medical record. PS data were not routinely recorded in the medical record. The outcome measure was whether chemotherapy was recommended by clinical staff. We assessed whether demographic, clinical, and laboratory measurements were associated with the recommendation for treatment with chemotherapy. Those variable which were associated with the recommendation for chemotherapy (p <0.20) were included in the multivariate analysis. A total of 134 patients met our inclusion criteria. 48% of the patients were female with a median age of all patients of 40.7 years (range 19-82 years). Over half of the patients (57.5%) were HIV positive. Nearly 90% of the patients presented with stage 3 or stage 4 disease. The vast majority of patients (97.0%) reported at least 1 symptom. Fever (55.8%), a palpable mass (79.7%), and wasting (52.3%) were the most common symptoms reported at presentation. Approximately three-fourths of the patients had at least 1 comorbidity. The median baseline hgb level was 10.8 g/dl; 10% had a hgb <7g/dl. The median LDH level was elevated at 416 IU/L, however data were only obtained for 66 (49%) patients. Chemotherapy was recommended to 91.2% of the patients. In the multivariate logistic regression model, older age (p=.02), lower stage of disease (p <.001), and fewer comorbidities (p=.01) were associated with the failure to recommend for cancer-directed therapy. Given their independent effect on response to therapy and overall survival, clinical prognostic indices are often used in resource-abundant countries to identify which patients will derive a benefit from cancer-directed therapy and which patients are better served by supportive measures. In our analysis, the recommendation for cancer-directed therapy was nearly universal. Collecting complete prospective data on IPI variables and follow-up data can validate the IPI in Uganda, allow Ugandan clinicians to determine whether such measures inform survival, and potentially optimize treatment decisions among patients with NHL. In resource-poor areas, the allocation of scarce health care resources to those patients that will be most likely to derive a meaningful benefit is imperative. Targeting therapy will not only save limited resources, it will also prevent harm in those patients unlikely to realize an effect of cancer-directed therapy.