Sunitinib malate in the treatment of recurrent or persistent uterine leiomyosarcoma: A Gynecologic Oncology Group phase II study

New agents are needed for patients with metastatic uterine leiomyosarcoma who progress after treatment with doxorubicin or gemcitabine-docetaxel. Agents targeting tumor vasculature have potential for activity in leiomyosarcoma. We aimed to assess the activity of sunitinib in patients with recurrent uterine leiomyosarcoma who had received one or two prior therapies by determining the frequency of patients who survived progression-free for at least six months or who achieved objective tumor response. We also aimed to characterize the toxicity of sunitinib and to estimate time-to-progression

WT1 gene expression as a prognostic marker in advanced serous epithelial ovarian carcinoma: an immunohistochemical study

BACKGROUND: WT1 is a tumor suppressor gene responsible for Wilms' tumor. WT1 reactivity is limited to ovarian serous carcinomas. Recent studies have shown that WT1 plays an important role in the progression of disease and indicates a poorer prognosis of human malignancies such as acute myeloid leukemia and breast cancer. The aims of this study were to determine the survival and recurrence-free survival of women with advanced serous epithelial ovarian carcinoma in relation to WT1 gene expression. METHODS: The study accrued women over an 18-year period, from 1987–2004. During the study period, 163 patients were diagnosed with advanced serous epithelial ovarian carcinoma and had undergone complete post-operative chemotherapy, but the final study group comprised 99 patients. The records of these women were reviewed and the paraffin-embedded tissue of these women stained with WT1 immunostaining. Survival analysis was performed using Kaplan-Meier and Cox regression methods. RESULTS: Fifty patients showed WT1 staining and forty-nine did not. Five-year survival of non-staining and staining groups were 39.4% and 10.7% (p < 0.00005); five-year recurrence-free survival of these groups were 29.8% and ≤ 7.5% (p < 0.00005), respectively. For survival the HR of WT1 staining, adjusted for residual tumor and chemotherapy response, was 1.98 (95% CI 1.28–3.79), and for recurrence-free survival the HR was 3.36 (95% CI 1.60–7.03). The HR for recurrence-free survival was not confounded by any other variables. CONCLUSION: This study suggests that expression of WT1 gene may be indicative of an unfavorable prognosis in patients with advanced serous epithelial ovarian carcinoma

Significance of vascular endothelial growth factor in growth and peritoneal dissemination of ovarian cancer

Vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis which drives endothelial cell survival, proliferation, and migration while increasing vascular permeability. Playing an important role in the physiology of normal ovaries, VEGF has also been implicated in the pathogenesis of ovarian cancer. Essentially by promoting tumor angiogenesis and enhancing vascular permeability, VEGF contributes to the development of peritoneal carcinomatosis associated with malignant ascites formation, the characteristic feature of advanced ovarian cancer at diagnosis. In both experimental and clinical studies, VEGF levels have been inversely correlated with survival. Moreover, VEGF inhibition has been shown to inhibit tumor growth and ascites production and to suppress tumor invasion and metastasis. These findings have laid the basis for the clinical evaluation of agents targeting VEGF signaling pathway in patients with ovarian cancer. In this review, we will focus on VEGF involvement in the pathophysiology of ovarian cancer and its contribution to the disease progression and dissemination

Combined [18F]-Fluoroethylcholine PET/CT and 99mTc-Macroaggregated Albumin SPECT/CT Predict Survival in Patients With Intermediate-Stage Hepatocellular Carcinoma

Aim The aim of this study was to retrospectively analyze the prognostic value of combined Tc-99m-macroaggregated albumin (MAA) SPECT/CT and [F-18]-fluoroethylcholine (FEC) PET/CT before radioembolization for survival of patients with intermediate-stage hepatocellular carcinoma. Methods Twenty-four patients with known hepatocellular carcinoma Barcelona Clinic Liver Cancer stage B were eligible for this analysis. All patients were scheduled for radioembolization and received a pretherapeutic [F-18]FEC PET/CT scan as well as Tc-99m-MAA SPECT/CT for hepatopulmonary shunting. Laboratory and semiquantitative PET parameters and morphologic and metabolic (intersection) volumes of MAA and FEC were evaluated. Spearman correlation with overall survival, receiver operating curve analyses, univariate and multivariate Cox regression, and Kaplan-Meier-analysis was applied. Results All patients (5 female/19 male) are deceased within the observational period. Median survival was 395 days (51 days;range, 23-1122 days). The percentage of hypervascularized metabolically active tumor volume (vascularized tumor ratio;defined as high MAA and FEC uptake) correlated significantly with survival. Vascularized tumor ratio was a significant predictor in univariate and multivariate analyses (P = 0.026;hazard ratio, 11.65;95% confidence interval, 1.62-83.73;P = 0.015). Statistical significance was not reached by all other variables in multivariate analysis. Receiver operating curve analysis for 1-year survival revealed an area under the curve of 0.77 (P = 0.024) for vascularized tumor ratio. At a cutoff value of 9%, sensitivity, specificity, and positive and negative prediction were 83%, 67%, and 71% and 80% (P = 0.036). Patients with a higher tumor vascularization had a median survival of 274 +/- 80 versus 585 +/- 284 days (P = 0.015). Conclusion: s Hepatocellular carcinoma with high vascularization in metabolic active areas as assessed by combined FEC PET/CT and Tc-MAA SPECT/CT represents an unfavorable subgroup with reduced overall survival after radioembolization