Browsing by Subject "Endometrial cancer"
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Item A phase II trial of bevacizumab and rucaparib in recurrent carcinoma of the cervix or endometrium(Elsevier, 2022) Jackson, C. G.; Moore, K. N.; Cantrell, L.; Erickson, B. K.; Duska, L. R.; Richardson, D. L.; Landrum, L. M.; Holman, L. L.; Walker, J. L.; Mannel, R. S.; Moxley, K. M.; Queimado, L.; Cohoon, A.; Ding, K.; Dockery, L. E.; Obstetrics and Gynecology, School of MedicineObjective: The aim of this study was to examine the tolerability and efficacy of combination bevacizumab rucaparib therapy in patients with recurrent cervical or endometrial cancer. Patients & methods: Thirty-three patients with recurrent cervical or endometrial cancer were enrolled. Patients were required to have tumor progression after first line treatment for metastatic, or recurrent disease. Rucaparib was given at 600 mg BID twice daily for each 21-day cycle. Bevacizumab was given at 15 mg/kg on day 1 of each 21-day cycle. The primary endpoint was efficacy as determined by objective response rate or 6-month progression free survival. Results: Of the 33 patients enrolled, 28 were evaluable. Patients with endometrial cancer had a response rate of 17% while patients with cervical cancer had a response rate of 14%. Median progression free survival was 3.8 months (95% C·I 2.5 to 5.7 months), and median overall survival was 10.1 months (95% C·I 7.0 to 15.1 months). Patients with ARID1A mutations displayed a better response rate (33%) and 6-month progression free survival (PFS6) rate (67%) than the entire study population. Observed toxicity was similar to that of previous studies with bevacizumab and rucaparib. Conclusions: The combination of bevacizumab with rucaparib did not show significantly increased anti-tumor activity in all patients with recurrent cervical or endometrial cancer. However, patients with ARID1A mutations had a higher response rate and PFS6 suggesting this subgroup may benefit from the combination of bevacizumab and rucaparib. Further study is needed to confirm this observation. No new safety signals were seen.Item Changes in receipt of adjuvant brachytherapy for endometrial cancer patients before and after affordable care act: The impact of Medicaid expansion(Termedia Publishing, 2023) Le, Amy; Holmes, Jordan A.; Radiation Oncology, School of MedicinePurpose: For patients with high-intermediate risk (HIR) endometrial cancer, adjuvant radiation (RT) reduces the risk of recurrence, but many patients do not receive RT. Under the Affordable Care Act (ACA), most states expanded Medicaid coverage. Our hypothesis was patients would be more likely to receive indicated adjuvant RT in states that expanded Medicaid compared with patients in states that did not expand Medicaid. Material and methods: National Cancer Database (NCDB) was used to identify patients aged 40-64 years with HIR endometrial adenocarcinoma, stage IA and grade 3 or stage IB and grade 1 or 2, diagnosed from 2010-2018. We conducted a difference-in-differences (DID) cross-sectional retrospective analysis comparing receipt of adjuvant RT among patients residing in Medicaid expansion and non-expansion states before and after ACA implementation (January 2014). Results: Expansion states had higher rates of adjuvant RT prior to January 2014 compared with non-expansion states (49.21% vs. 36.46%), and the proportion of patients who received adjuvant RT increased over the study period across both Medicaid expansion and non-expansion states. After Medicaid expansion, the non-expansion states had a larger absolute increase in adjuvant radiation resulting in a non-significant change in the difference in adjuvant radiation rates compared with baseline (crude increase: 9.63% vs. 7.45%, adjusted DID: -2.68 [95% CI: -7.12-1.75], p = 0.236). Conclusions: Medicaid expansion is likely not the most significant factor affecting access or receipt of adjuvant RT for HIR endometrial cancer patients. Further study could help inform policy and efforts to ensure all patients have access to guideline-recommended RT.Item Clinical and Biological Activity of Chemoimmunotherapy in Advanced Endometrial Adenocarcinoma: A Phase II Trial of the Big Ten Cancer Research Consortium(American Association for Cancer Research, 2022) Barber, Emma L.; Chen, Siqi; Pineda, Mario Javier; Robertson, Sharon E.; Hill, Emily K.; Teoh, Deanna; Schilder, Jeanne; O’Shea, Kaitlyn L.; Kocherginsky, Masha; Zhang, Bin; Matei, Daniela; Obstetrics and Gynecology, School of MedicinePurpose: The objective of this study was to assess the efficacy and safety of pembrolizumab in combination with standard carboplatin/paclitaxel in patients with advanced endometrial cancer (EC). Patients and methods: This single-arm, open-label, multi-center phase II study enrolled patients with RECIST measurable advanced EC. Patients could have received < 1 prior platinum-based regimen and < one non-platinum chemotherapy. The primary endpoint was objective response rate (ORR). Planned sample size of 46 subjects provided 80% power to detect 15% ORR improvement compared to historical control rate of 50%. Results: 46 patients were enrolled, and 43 were evaluable for ORR. Median age was 66 (range: 43-86). Thirty-four (73.9%) patients had recurrent and 12 (26.1%) primary metastatic EC. Patients received carboplatin AUC 6, paclitaxel 175mg/m2 and pembrolizumab 200mg IV every 3 weeks for up to 6 cycles. ORR was 74.4% (32/43), higher than historic controls (p = 0.001). Median PFS was 10.6 months (95% CI 8.3-13.9 months). The most common grade 1-2 treatment related adverse event (TRAEs) included anemia (56.5%), alopecia (47.8%), fatigue (47.8%) and neuropathy (13%), while the most common grade 3-4 TRAEs were lymphopenia, leukopenia, and anemia (19.6% each). High-dimensional spectral flow cytometry (CyTEK) identified enrichment in peripheral CD8+ and CD4+ T cell populations at baseline in responders. The CD8+ T cell compartment in responders exhibited greater expression levels of PD-1 and PD-L1 and higher abundance of effector memory CD8+ cells compared to non-responders. Conclusions: Addition of pembrolizumab to carboplatin and paclitaxel for advanced EC was tolerated and improved ORR compared to historical outcomes.Item Proton Pump Inhibitor Use and Obesity-Associated Cancer in the Women's Health Initiative(Taylor & Francis, 2023) Ballinger, Tarah J.; Djuric, Zora; Sardesai, Sagar; Hovey, Kathleen M.; Andrews, Chris A.; Brasky, Theodore M.; Zhang, Jian Ting; Rohan, Thomas E.; Saquib, Nazmus; Shadyab, Aladdin H.; Simon, Michael; Wactawski-Wende, Jean; Wallace, Robert; Kato, Ikuko; Medicine, School of MedicineProton pump inhibitors (PPIs) have off-target activity on fatty acid synthase (FASN), a critical enzyme in energy balance and cancer growth. We evaluated risk of common obesity-related cancers: breast, colorectal (CRC), and endometrial, with use of PPI and histamine-2 receptor antagonists (H2RA) in 124,931 postmenopausal women enrolled in the Women's Health Initiative. Incident cancer cases were physician-adjudicated. Cox proportional hazards models were used to estimate multivariable hazard ratios (HR) and 95% confidence intervals (CI) for cancer incidence after year 3. There were 7956 PPI ever users and 9398 H2RA only users. Ever use of either PPI or H2RA was not associated with risk of breast cancer (n = 9186) nor risk of endometrial cancer (n = 1231). The risk of CRC (n = 2280) was significantly lower in PPI users (HR = 0.75, 95% CI = 0.61-0.92), but not in H2RA users (HR = 1.13, 95% CI = 0.97-1.31). The association of PPI use with CRC was apparent regardless of BMI or NSAID use, and was stronger with longer PPI duration (p = 0.006) and potency (p = 0.005). The findings that PPI use, but not H2RA use, demonstrate an inverse dose-response relationship with risk of CRC is consistent with preclinical data showing FASN inhibition prevents colon cancer progression and supports a role of PPI in CRC prevention.Item Rare Case of 6cm Right Atrial Myxoma in Patient with Synchronous Endometrial Adenocarcinoma(Hindawi, 2021-10-11) Altujjar, Mohammad; Zaiem, Feras; Sheehan, Erin; Gan, Willy; Mhanna, Mohammed; Khokher, Waleed; Ullah, Ikram; Mujtaba, Mohammad Tokir; Medicine, School of MedicinePrimary cardiac tumors are extremely rare. Cardiac myxomas most frequently appear in the left atrium. In this article, we present a case of an asymptomatic 6 cm right atrial mass in a patient undergoing staging for endometrial cancer. The mass was resected, and final pathology was consistent with cardiac myxoma.Item Unique Molecular Features in High-Risk Histology Endometrial Cancers(MDPI, 2019-10-27) Pandita, Pooja; Wang, Xiyin; Jones, Devin E.; Collins, Kaitlyn; Hawkins, Shannon M.; Obstetrics and Gynecology, School of MedicineEndometrial cancer is the most common gynecologic malignancy in the United States and the sixth most common cancer in women worldwide. Fortunately, most women who develop endometrial cancer have low-grade early-stage endometrioid carcinomas, and simple hysterectomy is curative. Unfortunately, 15% of women with endometrial cancer will develop high-risk histologic tumors including uterine carcinosarcoma or high-grade endometrioid, clear cell, or serous carcinomas. These high-risk histologic tumors account for more than 50% of deaths from this disease. In this review, we will highlight the biologic differences between low- and high-risk carcinomas with a focus on the cell of origin, early precursor lesions including atrophic and proliferative endometrium, and the potential role of stem cells. We will discuss treatment, including standard of care therapy, hormonal therapy, and precision medicine-based or targeted molecular therapies. We will also discuss the impact and need for model systems. The molecular underpinnings behind this high death to incidence ratio are important to understand and improve outcomes.Item Utilization Patterns of Lymph Node Dissection in Endometrial Cancer Patients Without Distant Metastasis in the United States(2021-06) Alyea, Jennifer Marie; Dixon, Brian E.; Song, Yiqing; Zhang, Jianjun; Hess, Lisa M.; Method, Michael W.Endometrial cancer is the most common gynecologic cancer in the United States, and patients with early-stage endometrioid adenocarcinoma have a favorable prognosis. Over the past decade, the gynecologic oncology community has debated whether potential harms of systematic lymph node dissection (LND) outweigh potential benefits for these patients. To minimize number of nodes removed, sentinel lymph node dissection (SLND) is under investigation as an alternative. However, ongoing uncertainty of LND/SLND best practices may result in variations in disease management and discrepant outcomes. Methods Three retrospective cohort studies examined LND/SLND use in patients with endometrioid adenocarcinoma. Two examined temporal and geographic variations, respectively, utilizing the Surveillance, Epidemiology, and End Results (SEER) 18 dataset for the years 2004 through 2015. The third used the SEER-Medicare dataset from 2003 through 2016 to quantify and compare the risk of developing 6-month post-surgical lymphedema, lymphocele, hemorrhage, ileus, infection, thrombosis, and all-cause death by number of lymph nodes removed (0, 1-4, 5-9, or 10+). Results Time trend analyses found LND increased from 2004 through 2008, followed by a significant decline through 2015. SLND was rare and did not increase significantly. Significant geographic variation existed for LND use but not SLND. Per 1,000 patients, analyses of 6-month post-surgical complications found 6.5 experienced lymphedema, 3.9 experienced lymphocele, 15.7 experienced hemorrhage, 28.7 experienced ileus, 37.1 experienced infection, 18.6 experienced thrombosis, and 19.8 died. Controlling for size of primary tumor, tumor grade, comorbidities, race/ethnicity, age at diagnosis, adjuvant chemotherapy, and radiotherapy, adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) showed greater risk for ileus (HR: 1.53; 95% CI: 1.24-1.90), infection (HR: 1.52; 95% CI: 1.25-1.83), and thrombosis (HR: 1.41; 95% CI: 1.09-1.82) when comparing removal of 10+ nodes versus 0 nodes. Conclusion Overall, these studies found significant temporal and geographic variation in LND, as well as increasing risk of post-surgical complications associated with increasing numbers of lymph nodes removed. Should continued research into SLND find strong evidence that it effectively detects cancer spread, patients may benefit through decreased risk of post-surgical ileus, infection, and thrombosis.