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Dunn E.F.,University of Wisconsin - Madison | Kozak K.R.,University of Wisconsin - Madison | Moody J.S.,Moses Cone Regional Cancer Center
International Journal of Radiation Oncology Biology Physics | Year: 2010

Purpose: Despite its common and well characterized use in other gastrointestinal malignancies, little is known about radiotherapy (RT) use in nonmetastatic colon cancer in the United States. To address the paucity of data regarding RT use in colon cancer management, we examined the RT patterns of care in this patient population. Methods and Materials: Patients with nonmetastatic colon cancer, diagnosed between 1988 and 2005, were identified in the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate methods were used to identify factors associated with RT use. Results: On univariate analysis, tumor location, age, sex, race, T stage, N stage, and geographic location were each associated with differences in RT use (all p < 0.01). In general, younger patients, male patients, and patients with more advanced disease were more likely to receive RT. On multivariate analysis, tumor location, age, gender, T and N stage, time of diagnosis and geographic location were significantly associated with RT use (all p < 0.001). Race, however, was not associated with RT use. On multivariate analysis, patients diagnosed in 1988 were 2.5 times more likely to receive RT than those diagnosed in 2005 (p = 0.001). Temporal changes in RT use reflect a responsiveness to evolving evidence related to the therapeutic benefits of adjuvant RT. Conclusions: External beam RT is infrequently used for colon cancer, and its use varies according to patient and tumor characteristics. RT use has declined markedly since the late 1980s; however, it continues to be used for nonmetastatic disease in a highly individualized manner. © 2010 Elsevier Inc. All rights reserved. Source


Hasenstein J.R.,University of Wisconsin - Madison | Kasmerchak K.,University of Wisconsin - Madison | Buehler D.,University of Wisconsin - Madison | Hafez G.R.,University of Wisconsin - Madison | And 3 more authors.
Neoplasia | Year: 2012

Angiosarcomas are malignant endothelial cell tumors with few effective systemic treatments. Despite a unique endothelial origin, molecular candidates for targeted therapeutic intervention have been elusive. In this study, we explored the tunica internal endothelial cell kinase 2 (Tie2) receptor as a potential therapeutic target in angiosarcoma. Human angiosarcomas from diverse sites were shown to be universally immunoreactive for Tie2. Tie2 and vascular endothelial growth factor receptor (VEGFR) antagonists inhibited SVR and MS1-VEGF angiosarcoma cell survival in vitro. In the high-grade SVR cell line, Tie2 and VEGF antagonists inhibited cell survival synergistically, whereas effects were largely additive in the low-grade MS1-VEGF cell line. Xenograft modeling using these cell lines closely recapitulated the human disease. In vivo, Tie2 and VEGFR inhibition resulted in significant angiosarcoma growth delay. The combination proved more effective than either agent alone. Tie2 inhibition seemed to elicit tumor growth delay through increased tumor cell apoptosis, whereas VEGFR inhibition reduced tumor growth by lowering tumor cell proliferation. These data identify Tie2 antagonism as a potential novel, targeted therapy for angiosarcomas and provide a foundation for further investigation of Tie2 inhibition, alone and in combinations, in the management of this disease. © 2012 Neoplasia Press, Inc. All rights reserved. Source


Buehler D.,University of Wisconsin - Madison | Rice S.R.,University of Wisconsin - Madison | Moody J.S.,Moses Cone Regional Cancer Center | Rush P.,University of Wisconsin - Madison | And 4 more authors.
American Journal of Clinical Oncology: Cancer Clinical Trials | Year: 2013

Objective: Angiosarcoma is an aggressive malignancy with endothelial differentiation and notoriously poor prognosis despite aggressive therapy. Limited data are available to guide management decisions. To address this limitation, we present a large retrospective analysis of angiosarcoma patients treated at a single institution over a 25-year period.Methods: To identify factors that impact angiosarcoma outcomes, we reviewed demographic, tumor, and treatment characteristics of angiosarcoma patients evaluated at the University of Wisconsin Hospital between 1987 and 2012.Results: The cohort included 81 patients diagnosed at ages 19 to 90 years (median, 67y). Fifty-five (68%) patients presented with localized disease, whereas 26 (32%) presented with metastases. The primary sites were visceral/deep soft tissue (42%), head and neck/cutaneous (37%), breast (16%), and limbs in the setting of Stewart-Treves (5%). The 5-year overall survival was 40% with a median of 16 months. By univariate analysis, significant adverse predictors of survival included metastases at presentation, visceral/deep soft tissue tumor location, tumor size>5cm, tumor necrosis, and the absence of surgical excision. A trend toward prolonged survival was observed with radiation therapy and for chemotherapy in patients with metastases. Age, sex, and prior radiation showed no correlation with survival.Conclusions: Our large single institution series confirms the poor prognosis of angiosarcoma, supports a central role for surgical excision in management, and highlights the need for novel therapies particularly in patients who present with metastatic disease. Copyright © 2013 by Lippincott Williams & Wilkins. Source


Hamidi M.,University of Wisconsin - Madison | Moody J.S.,Moses Cone Regional Cancer Center | Kozak K.R.,University of Wisconsin - Madison
American Journal of Clinical Oncology: Cancer Clinical Trials | Year: 2010

Objectives: Despite evidence that radiation therapy (RT) improves outcome in multiple malignancies, some patients with strong clinical indications still refuse RT. Data on factors associated with RT refusal are limited. Furthermore, the effect of RT refusal on outcome has not been clearly defined. Methods: Patients with nonmetastatic cancer, diagnosed between 1988 and 2005, were identified in the Surveillance, Epidemiology, and End Results database. Univariate and multivariate methods were used to identify factors associated with RT refusal and the impact of refusal on outcomes. Results: On univariate analysis, age, sex, marital status, tumor site, and tumor stage were associated with RT refusal (P < 0.001). On multivariate analysis, sex and tumor stage were not found to be associated with RT refusal. In contrast, age, race, marital status, and tumor location were significantly associated with RT refusal. The median survival of compliant patients was 171 months compared with just 96 months among patients who refused RT. Conclusions: A significant percentage of patients continue to refuse RTdespite medical advice and evidence. Subgroups at particular risk of RT refusal include elderly, black and widowed patients. RT refusal is associated with markedly worse clinical outcomes. © 2010 by Lippincott Williams & Wilkins. Source


Kozak K.R.,University of Wisconsin - Madison | Hamidi M.,University of Wisconsin - Madison | Manning M.,Moses Cone Regional Cancer Center | Moody J.S.,Moses Cone Regional Cancer Center
International Journal of Radiation Oncology Biology Physics | Year: 2012

Purpose: This study examines the management and outcomes of muscle-invasive bladder cancer in the United States. Methods and Materials: Patients with muscle-invasive bladder cancer diagnosed between 1988 and 2006 were identified in the Surveillance, Epidemiology, and End Results (SEER) database. Patients were classified according to three mutually exclusive treatment categories based on the primary initial treatment: no local management, radiotherapy, or surgery. Overall survival was assessed with Kaplan-Meier analysis and Cox models based on multiple factors including treatment utilization patterns. Results: The study population consisted of 26,851 patients. Age, sex, race, tumor grade, histology, and geographic location were associated with differences in treatment (all p < 0.01). Patients receiving definitive radiotherapy tended to be older and have less differentiated tumors than patients undergoing surgery (RT, median age 78 years old and 90.6% grade 3/4 tumors; surgery, median age 71 years old and 77.1% grade 3/4 tumors). No large shifts in treatment were seen over time, with most patients managed with surgical resection (86.3% for overall study population). Significant survival differences were observed according to initial treatment: median survival, 14 months with no definitive local treatment; 17 months with radiotherapy; and 43 months for surgery. On multivariate analysis, differences in local utilization rates of definitive radiotherapy did not demonstrate a significant effect on overall survival (hazard ratio, 1.002; 95% confidence interval, 0.999-1.005). Conclusions: Multiple factors influence the initial treatment strategy for muscle-invasive bladder cancer, but definitive radiotherapy continues to be used infrequently. Although patients who undergo surgery fare better, a multivariable model that accounted for patient and tumor characteristics found no survival detriment to the utilization of definitive radiotherapy. These results support continued research into bladder preservation strategies and suggest that definitive radiotherapy represents a viable initial treatment strategy for those who wish to attempt to preserve their native bladder. © 2012 Elsevier Inc. All rights reserved. Source

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