Ovarian and uterine carcinosarcomas: a comparative analysis of prognostic variables and survival outcomes.
ABSTRACT Carcinosarcomas (malignant mixed Mullerian tumor) of the female genital tract are rare tumors associated with poor outcome. The objective of this study was to identify site-specific differences by comparing carcinosarcomas originating in the uterus and the ovaries.
Data on patients with uterine and ovarian carcinosarcomas were extracted from the Surveillance, Epidemiology, and End Results database between 1988 and 2005. Kaplan-Meier log rank and Cox proportional hazards models were used for survival analysis and for identification of possible predictors for survival.
The identified cohort included 3683 women of whom 2759 (75%) have uterine carcinosarcoma and 924 (25%) have ovarian carcinosarcomas. The patients with uterine carcinosarcoma were older than the patients with ovarian carcinosarcoma (median age, 67 vs 65 years; P < 0.001). The women with uterine carcinosarcoma compared with those with ovarian carcinosarcoma were more often African American (17.3% vs 6%; P < 0.001) and presented more often with localized disease (47% vs 10.8%; P < 0.001). Uterine carcinosarcoma compared with ovarian carcinosarcoma differed significantly with regard to the performance of lymphadenectomy (62.6% vs 41.2%; P < 0.001) and the administration of radiotherapy (38.2% vs 4.8%; P < 0.001). When controlled for the extent of disease spread, uterine carcinosarcoma had a more aggressive clinical course and shorter survival compared with ovarian carcinosarcoma. Although age (P < 0.001), race (P = 0.01), stage (P < 0.001), lymphadenectomy (P < 0.001), and radiation (P < 0.001) were all significant prognostic factors in uterine carcinosarcoma, only age (P < 0.001), stage (P < 0.001), and lymphadenectomy (P < 0.001) were significant predictors in ovarian carcinosarcoma.
Although uterine carcinosarcoma presents at an earlier stage than ovarian carcinosarcoma, it has a worse prognosis compared with ovarian carcinosarcoma, with a similar extent of disease spread. Improved survival observed in lymphadenectomy group lends support to its routine performance in patients with uterine and ovarian carcinosarcomas.
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ABSTRACT: Ovarian and uterine carcinosarcoma (CS) are characterized by their aggressive clinical behavior and poor prognosis. We evaluated the efficacy of trastuzumab-emtansine (T-DM1), against primary HER2 positive and HER2 negative CS cell lines in vitro and in vivo. Eight primary CS cell lines were evaluated for HER2 amplification and protein expression by fluorescence in situ hybridization, immunohistochemistry, flow cytometry and qRT-PCR. Sensitivity to T-DM1-induced antibody-dependent-cell-mediated-cytotoxicity (ADCC) was evaluated in 4-h-chromium-release-assays. T-DM1 cytostatic and apoptotic activities were evaluated using flow cytometry based proliferation assays. In vivo activity of T-DM1 was also evaluated. HER2 protein overexpression and gene amplification were detected in 25 % (2/8) of the primary CS cell lines. T-DM1 and T were similarly effective in inducing strong ADCC against CS overexpressing HER2 at 3+ levels. In contrast, T-DM1 was dramatically more effective than T in inhibiting cell proliferation (P < 0.0001) and in inducing G2/M phase cell cycle arrest in the HER2 expressing cell lines (shift of G2/M: mean ± SEM from 14.87 ± 1.23 to 66.57 ± 4.56 %, P < 0.0001). Importantly, T-DM1 was highly active at reducing tumor formation in vivo in CS xenografts overexpressing HER2 (P = 0.0001 and P < 0.0001 compared to T and vehicle respectively) with a significantly longer survival when compared to T and vehicle mice (P = 0.008 and P = 0.0001 respectively). T-DM1 may represent a novel treatment option for the subset of HER2 positive CS patients with disease refractory to chemotherapy.Clinical and Experimental Metastasis 11/2014; · 3.73 Impact Factor
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ABSTRACT: We report a case of 66-year-old female with previous history of histopathologically proven. Malignant mixed mullerain tumor of the uterus in whom positron emission tomography/computed tomography (CT) done for characterization of soft tissue lesion in pelvis noticed on CT, showed extensive recurrent disease in the pelvis with pulmonary metastases.World journal of nuclear medicine. 01/2014; 13(1):64-6.
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ABSTRACT: Carcinosarcomas (also known as malignant mixed müllerian tumors) are rare and highly aggressive epithelial malignancies that contain both malignant sarcomatous and carcinomatous elements. Uterine carcinosarcomas (UCs) are uncommon with approximately more than 35% presenting with extra uterine disease at diagnosis. Up to 90% ovarian carcinosarcomas (OCs) will have disease that has spread beyond the ovary. Prognosis for localized stage disease is poor with a high risk of recurrences, both local and distant, occurring within 1 year. The survival of women with advanced UC or OC is worse than survival of endometrioid or high-grade serous histologies. No improvement in survival rates has been observed in the past few decades with an overall median survival of less than 2 years. Currently, there is no clear evidence to establish consensus guidelines for therapeutic management of carcinosarcomas. Until recently, gynecological carcinosarcomas were considered as a subtype of sarcoma and treated as such. However, carcinosarcomas are now known to be metaplastic carcinomas and so should be treated as endometrial or ovarian high-risk carcinomas, despite the lack of specific data. For UCs, a comprehensive approach to management is recommended with complete surgical staging followed by systemic chemotherapy in patients with both early and advanced stage disease. Active agents include paraplatin, cisplatin, ifosfamide, and paclitaxel. The combination of carboplatin-paclitaxel is the most commonly used regimen in the adjuvant and advanced setting. Adjuvant radiotherapy (external beam irradiation and/or vaginal brachytherapy) has not shown any overall survival benefit but has been reported to decrease local recurrences. For OCs and for other ovarian epithelial cancer, the mainstay of treatment remains cytoreductive surgical effort followed, even in early stage, by platinum-based chemotherapy, usually carboplatin-paclitaxel.International Journal of Gynecological Cancer 11/2014; 24(9 Suppl 3):S55-60. · 1.95 Impact Factor