Laura M Divine1, Nora T Kizer2, Andrea R Hagemann1, Meredith E Pittman3, Ling Chen4, Matthew A Powell1, David G Mutch1, Janet S Rader5, Premal H Thaker6. 1. Washington University School of Medicine & Alvin J. Siteman Cancer Center, St. Louis, MO, United States. 2. Department of Obstetrics and Gynecology, Springfield Clinic, Springfield, IL, Division of Gynecologic Oncology, United States. 3. Department of Pathology, The Johns Hopkins Hospital, Baltimore, MD, United States. 4. Division of Biostatistics, Washington University School of Medicine, Alvin J. Siteman Cancer Center, Saint Louis, MO, United States. 5. Division of Gynecologic Oncology, Medical College of Wisconsin, Milwaukee, WI, United States. 6. Washington University School of Medicine & Alvin J. Siteman Cancer Center, St. Louis, MO, United States. Electronic address: thakerp@wudosis.wustl.edu.
Abstract
OBJECTIVE: No standardized treatment strategies exist for patients with gynecologic malignancies complicated by brain metastases. Identification of poor outcome characteristics, long-term survival indicators, and molecular markers could help individualize and optimize treatment. METHODS: This retrospective cohort study included 100 gynecologic cancer patients with brain metastases treated at our institution between January 1990 and June 2009. Primary outcome was overall survival (OS) from time of diagnosis of brain metastases. We used univariate and multivariate analyses to evaluate associations between OS and clinical factors. We used immunohistochemistry to examine expression of five molecular markers in primary tumors and brain metastases in a subset of patients and matched controls. Statistical tests included the Student's paired t-test (for marker expression) and Kaplan-Meier test (for correlations). RESULTS: On univariate analysis, primary ovarian disease, CA-125<81units/mL at brain metastases diagnosis, and isolated versus multi-focal metastases were all associated with longer survival. Isolated brain metastasis remained the only significant predictor on multivariate analysis (HR 2.66; CI 1.19-5.93; p=0.017). Expression of vascular endothelial growth factor A (VEGF-A) was higher in metastatic brain samples than in primary tumors of controls (p<0.0001). None of the molecular markers were significantly associated with survival. CONCLUSIONS: Multi-modality therapy may lead to improved clinical outcomes, and VEGF therapy should be investigated in treatment of brain metastases.
OBJECTIVE: No standardized treatment strategies exist for patients with gynecologic malignancies complicated by brain metastases. Identification of poor outcome characteristics, long-term survival indicators, and molecular markers could help individualize and optimize treatment. METHODS: This retrospective cohort study included 100 gynecologic cancerpatients with brain metastases treated at our institution between January 1990 and June 2009. Primary outcome was overall survival (OS) from time of diagnosis of brain metastases. We used univariate and multivariate analyses to evaluate associations between OS and clinical factors. We used immunohistochemistry to examine expression of five molecular markers in primary tumors and brain metastases in a subset of patients and matched controls. Statistical tests included the Student's paired t-test (for marker expression) and Kaplan-Meier test (for correlations). RESULTS: On univariate analysis, primary ovarian disease, CA-125<81units/mL at brain metastases diagnosis, and isolated versus multi-focal metastases were all associated with longer survival. Isolated brain metastasis remained the only significant predictor on multivariate analysis (HR 2.66; CI 1.19-5.93; p=0.017). Expression of vascular endothelial growth factor A (VEGF-A) was higher in metastatic brain samples than in primary tumors of controls (p<0.0001). None of the molecular markers were significantly associated with survival. CONCLUSIONS: Multi-modality therapy may lead to improved clinical outcomes, and VEGF therapy should be investigated in treatment of brain metastases.
Authors: Koji Matsuo; Michele L Eno; Edward H Ahn; Mian M K Shahzad; Dwight D Im; Neil B Rosenshein; Anil K Sood Journal: Am J Clin Oncol Date: 2011-10 Impact factor: 2.339
Authors: Koji Matsuo; Todd B Sheridan; Seiji Mabuchi; Kiyoshi Yoshino; Kosei Hasegawa; Kimberley D Studeman; Dwight D Im; Neil B Rosenshein; Lynda D Roman; Anil K Sood Journal: Gynecol Oncol Date: 2014-03-25 Impact factor: 5.482
Authors: Aparna A Kamat; Donna Coffey; William M Merritt; Elizabeth Nugent; Diana Urbauer; Yvonne G Lin; Creighton Edwards; Russell Broaddus; Robert L Coleman; Anil K Sood Journal: Cancer Date: 2009-06-15 Impact factor: 6.860
Authors: Ariel Takayanagi; T J Florence; Omid R Hariri; Abigail Armstrong; Pouria Yazdian; Andrew Sumida; Syed A Quadri; Joshua Cohen; Omid S Tehrani Journal: Surg Neurol Int Date: 2019-09-13
Authors: Kyo Chul Koo; Jong Soo Lee; Jong Won Kim; Kyung Suk Han; Kwang Suk Lee; Do Kyung Kim; Yoon Soo Ha; Koon Ho Rha; Sung Joon Hong; Byung Ha Chung Journal: BMC Cancer Date: 2018-04-26 Impact factor: 4.430