Clinicopathologic characteristics and survival of patients with gynecologic malignancies metastatic to the brain.
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.



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).



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.



Multi-modality therapy may lead to improved clinical outcomes, and VEGF therapy should be investigated in treatment of brain metastases.
Washington University School of Medicine & Alvin J. Siteman Cancer Center, St. Louis, MO, United States.
Laura M
LM
Divine
Department of Obstetrics and Gynecology, Springfield Clinic, Springfield, IL, Division of Gynecologic Oncology, United States.
Nora T
NT
Kizer
Washington University School of Medicine & Alvin J. Siteman Cancer Center, St. Louis, MO, United States.
Andrea R
AR
Hagemann
Department of Pathology, The Johns Hopkins Hospital, Baltimore, MD, United States.
Meredith E
ME
Pittman
Division of Biostatistics, Washington University School of Medicine, Alvin J. Siteman Cancer Center, Saint Louis, MO, United States.
Ling
L
Chen
Washington University School of Medicine & Alvin J. Siteman Cancer Center, St. Louis, MO, United States.
Matthew A
MA
Powell
Washington University School of Medicine & Alvin J. Siteman Cancer Center, St. Louis, MO, United States.
David G
DG
Mutch
Division of Gynecologic Oncology, Medical College of Wisconsin, Milwaukee, WI, United States.
Janet S
JS
Rader
Washington University School of Medicine & Alvin J. Siteman Cancer Center, St. Louis, MO, United States. Electronic address: thakerp@wudosis.wustl.edu.
Premal H
PH
Thaker
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis; D001932:Brain Neoplasms / Q000401:mortality / Q000473:pathology / Q000556:secondary* / Q000628:therapy; D015331:Cohort Studies; D005260:Female; D005833:Genital Neoplasms, Female / Q000378:metabolism / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009367:Neoplasm Staging; D012189:Retrospective Studies; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
D014408:Biomarkers, Tumor; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A
Brain metastases; Cervical cancer; Endometrial cancer; Gynecologic cancer; Ovarian cancer; Vascular endothelial growth factor