Browsing by Author "McGoldrick, Suzanne M."

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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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    Survival of children with endemic Burkitt lymphoma in a prospective clinical care project in Uganda
    (Pediatric blood & cancer, 2019-06-03) McGoldrick, Suzanne M.; Mutyaba, Innocent; Namirembe, Constance; Nabakooza, Susan; Ndagire, Mariam
    “Endemic” Burkitt lymphoma (BL) is a common childhood cancer in Africa. Social and treatment factors may contribute to poor survival. With the aim of improving BL outcomes in Uganda, we undertook a comprehensive project (BL Project) that provided diagnostic support, access to standard chemotherapy, nutritional evaluations, and case management. We evaluated survival of children with BL in the context of the project. Patients followed by the BL Project who consented to research were enrolled in this study. Children with a pathology diagnosis consistent with BL were eligible. Data were collected prospectively. First-line chemotherapy generally consisted of six cycles of cyclophosphamide, vincristine, low-dose methotrexate (COM). We used Kaplan–Meier and Cox regression analyses to evaluate factors associated with overall survival (OS). Between July 2012 and June 2017, 341 patients with suspected BL presented to the BL Project. One hundred eighty patients with a pathology-based diagnosis were included in this study. The median age was seven years (interquartile range, 5–9), 74% lived ≥100 km from the Uganda Cancer Institute, 61% had late-stage disease, 84% had ECOG performance status < 3, 63% reported B-symptoms, and 22% showed neurologic symptoms. Fewer than 10% abandoned therapy. The four-year OS rate was 44% (95% CI, 36%–53%). In a multivariate model, ECOG status was significantly associated with mortality. The BL Project reduced effects of lacking supportive care and oncology resources, and allowed patients from Uganda to receive curative intent therapy with minimal loss to follow-up. Nonetheless, OS remains unacceptably low. Improved therapeutic approaches to endemic BL are urgently needed in Africa.