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Previs R.,University of Texas M. D. Anderson Cancer Center | Leath C.A.,University of Alabama at Birmingham | Coleman R.L.,University of Texas M. D. Anderson Cancer Center | Herzog T.J.,University of Cincinnati | And 4 more authors.
Gynecologic Oncology | Year: 2015

Objective Type I epithelial ovarian cancers (EOCs) are reported to be relatively chemoresistant. This study sought to compare pretreatment chemoresponse assays in Type I vs. Type II EOCs. Study design 383 women with stage III-IV EOC enrolled in an observational study, with known chemoresponse assay results for 7 common therapeutic agents, were included. Type I EOCs were defined as grade 1 serous/endometrioid cancers and all clear cell/mucinous cancers. Type II EOCs were classified as grade 2-3 serous/endometrioid cancers and undifferentiated cancers. Chemotherapy assay responses were classified as sensitive (S), intermediately sensitive (I), or resistant (R). All patients were treated with platinum/taxane therapy following cytoreductive surgery. Results Thirty (7.8%) tumors were classified as Type I EOC, and 353 (92.2%) as Type II EOC. Type I patients were younger at the time of diagnosis (median age: 57 vs. 62 years, p = 0.018) and had longer survival compared to Type II patients (mPFS: 25.8 vs. 16.4 months, HR = 1.71, p = 0.042). Eighty-six percent of Type I EOC specimens demonstrated a sensitive chemoresponse assay result to at least 1 agent; 35.7% were pan-S to all 7 agents. After adjusting for stage, debulking status, and type of EOC, multi-drug resistance was twice as likely in women with Type I EOC compared to Type II EOC (pan-R, 14.3% vs. 6.8% (p = 0.268); pan-S, 35.7% vs. 51.2% (p = 0.183)), but did not attain statistical significance. Conclusion(s) The majority of women with Type I EOC displayed assay sensitivity to at least one agent. Given the small sample size these findings need to be evaluated further. © 2015 Elsevier Inc. All rights reserved. Source

Chase D.M.,Creighton University | Sill M.W.,Gynecologic Oncology Group Statistical and Data Center | Sill M.W.,State University of New York at Buffalo | Monk B.J.,Creighton University | And 8 more authors.
Gynecologic Oncology | Year: 2012

Objective: To explore feasibility of measuring tumor blood flow as marker for antiangiogenic activity using DCE-MRI (Dynamic Contrast-Enhanced Magnetic Resonance Imaging) in women with recurrent EOC/PPC treated with bevacizumab. Methods: In a phase II study, 62 patients with recurrent/persistent EOC/PPC were treated with bevacizumab (15 mg/kg IV q21days) until disease progression. DCE-MRI was performed pre-cycle 1 and 4 of bevacizumab. Images were analyzed retrospectively by a single experienced blinded radiologist. Tumor and muscle contrast enhancement was measured by region of interest signal intensity within the same DCE-MRI images. Flow rates were obtained with concentration of dye as a function of time. Relative blood flow (RBF) was calculated as a ratio of average blood flow into tumor to muscle tissue. Associations between RBF and characteristics/outcomes were explored. Results: Sixty-two patients were eligible for study. Unfortunately, only 14 (23%) patients had imaging data available for analysis at baseline and 13 of those same patients (21%) had imaging data available for analysis pre-cycle 4. The RBF distribution was similar from pre-cycle 1 to 4. RBF remained stable for the majority of the cases (median change -0.21). Baseline RBF was not significantly associated with being progression-free at 6 months, microvessel density, 17 month overall survival, tumor response, or platinum sensitivity. However, increases in blood flow rates were associated with likelihood to be progression-free at 6 months. Conclusion: Functional imaging of tumor blood flow is a potential research endpoint that may be explored further. Consideration should be given to timing of endpoint and standardizing the technique. © 2012 Elsevier Inc. All rights reserved. Source

Hensley M.L.,Sloan Kettering Cancer Center | Hensley M.L.,New York Medical College | Wathen J.K.,Janssen Research and Development LLC | Maki R.G.,Mt Sinai Medical Center | And 6 more authors.
Cancer | Year: 2013

BACKGROUND: Between 30% and 50% of women who have high-grade uterine leiomyosarcoma (uLMS) limited to the uterus at diagnosis remain progression-free at 2 years. Adjuvant pelvic radiation does not improve outcome. The objective of the current study was to determine the 2-year and 3-year progression-free survival (PFS) among a prospective cohort of women who received adjuvant gemcitabine plus docetaxel followed by doxorubicin. METHODS: Women with uterus-limited, high-grade uLMS and adequate organ function were eligible. Within 12 weeks of complete resection and after confirmation that they had no evidence of disease on computed tomography (CT) images, the patients received 4 cycles of fixed-dose-rate gemcitabine plus docetaxel. Those who were confirmed disease-free on CT scans after cycle 4 received 4 cycles of doxorubicin. CT imaging for recurrence was performed every 3 months for 2 years, then every 6 months for 3 years. RESULTS: In total, 47 women were enrolled (46 evaluable) in 3 years. Characteristics included a median age of 53 years; 1988 International Federation of Gynecology and Obstetrics stage I disease in 81% of patients, stage II disease in 15%, and serosa-only stage IIIA disease in 4%; American Joint Committee on Cancer stage II disease in 13% of patients and stage III disease in 87%; a median tumor size of 8 cm (range, 2.5-30 cm); and a median mitotic rate of 18 mitoses per 10 high-power fields (range, 5-83 mitoses per 10 high-power fields). At a median follow-up of 39.8 months, 21 of 46 patients developed recurrent disease (45.7%). The median time to recurrence was 27.4 months (range, 3-40 months). Seventy-eight percent of patients (95% confidence interval, 67%-91%) were progression-free at 2 years, and 57% (95% confidence interval, 44%-74%) were progression-free at 3 years. The median PFS was not reached and exceeded 36 months. CONCLUSIONS: Among women with high-grade, uterus-limited uLMS who received treatment with adjuvant gemcitabine plus docetaxel followed by doxorubicin, 78% remained progression-free at 2 years, and 57% remained progression-free at 3 years. A randomized trial of adjuvant chemotherapy versus observation to determine whether adjuvant chemotherapy can improve survival in women with uterus-limited uLMS is underway. © 2013 American Cancer Society. Source

Nahas S.,Gynecologic Oncology | Yi J.,Mayo Medical School | Magrina J.,Mayo Medical School
Journal of Minimally Invasive Gynecology | Year: 2013

Objective: To evaluate the surgical outcome and the anatomic and sexual function in 10 women with Rokitansky syndrome who underwent the laparoscopic Vecchietti procedure at our center. Design: Retrospective analysis. Methods: Data were analyzed on the basis of short-term and long-term surgical outcome and sexual function. All patients underwent clinical follow-up at 1, 2, and 6 months after surgery. Measurements and Main Results: In all 10 patients, the procedure produced anatomic and functional success. Conclusion: The laparoscopic Vecchietti technique is safe, simple, and effective for treatment of vaginal agenesis. Results are comparable to those of all European studies, and the procedure should gain more popularity in North America. © 2013 AAGL. Source

Singh R.K.,Advanced Center for Treatment | Gaikwad S.M.,Advanced Center for Treatment | Jinager A.,Advanced Center for Treatment | Chaudhury S.,Advanced Center for Treatment | And 2 more authors.
Cancer Letters | Year: 2014

The kinetics and effect of hyper activated IGF-1R signaling is not well investigated during acquirement of platinum and taxol resistance in ovarian cancer cells. Herein we reported an upregulated IGF-1R expression in early stages of cisplatin paclitaxel and cisplatin-taxol resistance. Picropodophyllin, an IGF-1R inhibitor, alone and in combination with cisplatin, paclitaxel or both at lowest possible doses could reverse the resistance at early stages. Upregulated IGF-1R was also found in primary tumors of ovarian cancer patients after three to four cycles of platinum-taxol treatment. These findings indicate that a combination of cytotoxic agents and IGF-1R inhibitor is more effective at early stages of chemoresistant ovarian cancer. © 2014 Elsevier Ireland Ltd. Source

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