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Comparison of olaparib (OLA) monotherapy versus chemotherapy in patients with platinum-sensitive (PSOC) or platinum-resistant ovarian cancer (PROC).Patients with measurable disease and ≥ 1 prior line of chemotherapy (CT) were randomized 2:1 to OLA (300 mg tablets, BID) or physician's choice CT.: for PSOC: Carboplatin-Pegylated-Liposomal-Doxorubicin (PLD) or Carboplatin-Gemcitabine; for PROC: PLD, Topotecan, Paclitaxel or Gemcitabine.160 patients (60 with PSOC and 100 with PROC) were randomized 2:1 to OLA (n = 107) or CT (n = 53). Baseline characteristics were similar between both arms. Overall objective response rate (ORR) for OLA and CT were similar (24.3% (26/107) and 28.3% (15/53), respectively). Clinical benefit rate (≥ 12 weeks) was similar with 54.2% (58/107) and 56.6% (30/53), respectively. In PSOC, ORR was 35.0% (14/40) and 65.0% (13/20) for OLA and CT (p = 0.053); in PROC, ORR was 17.9% (12/67) and 6.1% (2/33) for OLA and CT (p = 0.134). ORR in heavily pretreated PROC (4 prior lines) was 22.9% (8/35) with OLA versus 0% (0/14) for CT. ORR of 35.7% (5/14) and 13.2% (7/53) was observed in BRCA-mutated and -wildtype PROC cases, respectively. Median PFS in PROC was not significantly different with 2.9 months (95% CI 2.8-5.1 in the OLA group versus 3.8 months (95% CI 3.0-6.4) in the CT group (hazard ratio [HR] 1.11 [95% CI 0.72-1.78]; log-rank p = 0.600).OLA monotherapy showed overall an equal response rate in relapsed ovarian cancer compared with CT. In PROC, ORR and TFST tended to be higher with OLA than with CT. In heavily pretreated patients (four lines or more) with PROC disease, OLA treatment seemed to be more effective than CT.

Objective. Based on its expression profile, folate receptor alpha (FRA) is an attractive candidate for targeted diagnostics and therapeutics. However, applicability of these agents in residual or recurrent disease could be influenced by chemotherapy. We evaluated whether chemotherapy modified FRA expression in non-mucinous epithelial ovarian (EOC) and endometrial carcinoma (EC). Methods. FRA staining was evaluated by immunohistochemistry, using MAb 26B3, in 81 patients (41 EOCs and 40 ECs) and 17 control tissues (5 benign ovarian cysts, 5 normal ovarian, and 7 normal endometrial tissues). Chemotherapy effect was evaluated in 42 patients (30 paired samples at primary and interval debulking surgery and 12 from primary and recurrent disease). FRA expression was assessed using a semi-quantitative staining algorithm, the M-score (range 0-50). Results. Median difference in M-score between tumor and control samples was 27.5 for EOC (95% CI 10.0 to 45.0) and 6.7 for EC (95% CI 6.7 to 21.7). Paired samples from both primary and interval debulking surgery did not differ in ERA expression in EOC (median difference of M-score between paired samples of 0.0 [95% CI - 2.6 to 2.6]). Recurrent EOC tumors reflected ERA status at diagnosis (median difference of M-score between paired samples of 33 [95% CI - 7.0 to 13.6]). Conclusions. This study shows no significant difference in FRA expression after chemotherapy, strengthening the rationale for FRA targeted diagnostics and therapeutics in FRA expressing tumors, whether newly diagnosed or at recurrence. (C) 2013 Elsevier Inc. All rights reserved

Objective. To evaluate the "Leuven" weekly paclitaxel/carboplatinum (TC) regimen in recurrent ovarian cancer in a retrospective study. Methods. Eighteen courses of paclitaxel (60 mg/m(2)) and carboplatinum (AUC 2.7) were administered weekly. Platinum-resistance was defined as progression during or within 6 months after platinum-based chemotherapy. Results. Sixty-three patients were included with a median number of prior treatment regimens of 4 (range 0-10). Forty-three patients were platinum resistant and 20 were platinum sensitive (14 intermediate sensitive and 5 sensitive). One patient in the platinum resistant group and 2 patients in the platinum sensitive group achieved complete remission, 15 patients in the platinum resistant and 5 patients in the platinum sensitive group achieved partial remission according to RECIST. In the entire patient population evaluable for response (n=62), the median progression free survival (PFS) was 6.7 months; the median overall survival (OS) was 9.7 months. Median PFS was 6 months for the platinum resistant and 8 months for the platinum sensitive group. The median OS was 9 months in the platinum resistant and 11 months in the platinum sensitive group. Toxicity was mostly bone marrow related with neutropenia grade 3/4 in 67% and neutropenic fever in 6% of patients. Dose reduction was necessary in 24% of patients. Nausea, vomiting and fatigue were the most frequent non-hematological side effects. Conclusion. Weekly paclitaxel and carboplatin is an effective regimen for patients with recurrence of ovarian cancer with a response rate of 37% in platinum resistant disease and a manageable toxicity profile. (C) 2012 Elsevier Inc. All rights reserved

OBJECTIVE: The endometrial origin of uterine carcinosarcoma has recently been well established. The current study investigates whether uterine carcinosarcomas can be included in protocols on high-risk endometrial cancer, given the similarities in biologic behavior of both entities. METHODS: Pathological and surgical notes of patients diagnosed with grade 3 endometrioid, carcinosarcoma, serous and clear cell endometrial cancer subtypes were retrospectively analyzed with special attention to the spread pattern of the different subtypes. Information on site of relapse and time to recurrence was obtained. RESULTS: We traced 146 patients of which 9 patients were ineligible. Histological subtypes of the remaining 137 patients were as follows: 50 (37%) grade 3 endometrioid carcinoma, 54 (39%) serous or clear cell carcinoma (non-endometrioid carcinoma), and 33 (24%) carcinosarcomas. Distribution of early stage disease (I and II) was 67, 46, and 78% for grade 3 endometrioid, non-endometrioid, and carcinosarcoma, respectively. Although we could not trace differences in hematogenic and transperitoneal spread among the three subtypes, non-endometrioid and carcinosarcomas were more likely to spread to pelvic and paraaortic lymph nodes (P

Objective The objective was to look for the incidence and clinicopathologic findings of women in whom the diagnosis of endometrial stromal sarcoma was initially missed. Methods We carried out a retrospective analysis of cases treated at our institution from 1990 to 2002. Results In 6/15 (40%) women suffering from endometrial stromal sarcoma, the diagnosis initially was missed. The first diagnosis was uterine leiomyoma ( n = 2), myxoid leiomyoma ( n = 2), cellular leiomyoma ( n = 1), or lymphatic disorder ( n = 1). The final diagnosis was only made after consultation of a pathologist with a special interest in gynecological oncology. The mean age of this group was only 34 years (range, 18–53). A mean delay in diagnosis of 143 months (range, 24–408) resulted in stage 4 disease in 5/6 women. After a mean follow-up of 16 years (range, 5–43), 4/6 are without macroscopic evidence of disease, 1/6 with evidence of disease, and 1/6 died of disease. Conclusion Especially in younger women, the diagnosis of endometrial stromal sarcoma can be problematic.

Objective. To prospectively assess the value of PET/CT for staging, diagnosis and operability of ovarian cancer, with special attention to the peritoneal spread. Methods. From June 2009 to March 2011,69 patients with suspicion of having an ovarian cancer underwent an (18) F-FDG PET/CT. To identify the diagnostic value of PET/CT, the results were compared with the findings at diagnostic laparoscopy and/or debulking surgery. Results. There were 56 patients with malignant tumors and 13 with benign tumors. We observed a sensitivity and specificity of 93% and 77%, respectively for malignant tumors with PET/CT. CT alone had a sensitivity and specificity of 96% and 38%, respectively. The overall FIGO classification evaluation for PET/CT and CT were the same. For the evaluation of metastases, the sensitivity of PET/CT was worse, while the specificity was better than CT. Retroperitoneal lymph node metastases were diagnosed better with PET/CT, while there was no difference for peritoneal spread and for the intestines. PET/CT detected another unknown primary tumor in 3 (4.3%) cases. Conclusion. PET/CT is better than CT in detecting retroperitoneal lymph node metastases, but not for peritoneal metastases. (C) 2013 Elsevier Inc. All rights reserved

Gynecologic-oncologic patients are at increased risk for complications with closed laparoscopy. Open laparoscopy eliminates the steps of blind insufflation and trocar insertion. This study is the first large series of open laparoscopies to assess the feasibility and safety of the open laparoscopy technique in patients with gynecologic malignancies. We performed 90 open laparoscopies in 89 oncologic patients with previous major surgery (65%) and/or radiotherapy (17%) or a large omental cake (18%). Complications due to the laparoscopic access technique occurred in one patient (1%) for whom a laparotomy was performed for a small bowel perforation. The incidence of complications of the open laparoscopy technique (1%) is favorable compared to the complication rate of closed laparoscopy in gynecologic-oncologic patients. It is concluded that open laparoscopy is a safe and feasible technique in gynecologic-oncologic patients.

Objective To determine the activity and tolerability of gemcitabine in the palliative treatment of ovarian cancer. Methods Patients affected by ovarian cancer, and with progressive disease after treatment with platinum/paclitaxel-based chemotherapy, were enrolled into this phase II study. Gemcitabine, 1000 mg/m 2 , was administered on days 1, 8, and 15, by 30-min intravenous infusion. Cycles were repeated every 28 days. Results Fifty patients were enrolled. All the patients were platinum and/or paclitaxel resistant (median number of previous regimens, 2; range, 1–5). Median platinum-free interval was 3 (range, 1–11) months and median paclitaxel-free interval was 6 (range, 1–36) months. A total of 210 courses were evaluable for toxicity, with a median number of four cycles administered per patient (range, 1–10). A grade 3 or 4 hematological toxicity was observed in 27 patients (54%) (anemia grade 3, 16%; grade 4, 2%; neutropenia grade 3, 24%; grade 4, 18%; thrombocytopenia grade 3, 8%; grade 4, 0%). A 20–50% dose reduction was required for 36 patients (72%, 55% of cycles). Blood transfusions were necessary for 15 patients (30%), while 2 (4%) were treated with erythropoetin. Granulocyte colony-stimulating factor was necessary in 4 patients (8%). Nonhematological toxicity was mild and manageable. Only 4 patients (8%) experienced a grade 3 hepatic toxicity (elevated liver enzymes). Forty-one patients (82%) are, so far, evaluable for response. Among them, 7 partial responses (17%; 95% confidence interval [CI], 6–29), 15 disease stabilizations (>16 weeks) (36.6%; 95% CI, 21.9–51.3), and 19 progressions (46.3%; 95% CI, 31.0–61.6) have been registered. An overall clinical benefit was observed in 53.7% of patients. Thirteen patients (31.7%) had a time-to-progression exceeding 24 weeks. Conclusions This study confirms the activity and safety of gemcitabine in heavily pretreated patients with recurrent ovarian cancer.

Objective. The aim of this study was to evaluate the use of a gastrostomy instead of a nasogastric tube following surgery for advanced ovarian cancer. Design. This was a retrospective observational study. Setting. The study was performed in a university teaching hospital. Participants. Thirty-four women undergoing debulking surgery for ovarian carcinoma participated. Methods. In order to increase patients' comfort during the first postoperative days we inserted for gastric decompression a transcutaneous instead of a transnasal tube following debulking surgery. Only patients with bowel involvement and/or extensive tumor load in the upper abdomen were included in the study. In this study we report on the use of a gastrostomy using a Cystofix drainage catheter, resulting in what we call a "Gastrofix." The Gastrofix was placed in 34 patients with ovarian cancer. In 32 (94%) patients an extraperitoneal hysterectomy and bilateral salpingo-oophorectomy was performed, in 16 (47%) a resection of the diaphragmatic peritoneum, in 14 (41%) patients a paraaortic lymphadenectomy, and in 12 (35%) patients part of the bowel was resected. Results. Free oral liquid intake and poor fiber diet were started after 5.5 days (median, range from 3–8 days) and 8 days (median, range from 4–12 days), respectively. The catheter was clamped off after 5 days (median, range from 2–8 days) and removed after 7 days (median, range from 3–11 days). Of the 34 patients only 12 (35%) received antiemetics (median of 4 days, range from 1–7 days). In 1 patient (3%) pain at the insertion site was observed on the third and fourth postoperative days. In 3 patients (9%) some fluid leakage at the insertion site was noted. In 4 patients (12%) the catheter fell out prematurely on days 0, 4, 6, and 9, respectively. In none of the patients were infection or fistulas at the insertion site noted. In all patients there was a satisfactory drainage of gastric content. Conclusion. After debulking surgery, the use of a Gastrofix resulted in an adequate gastrointestinal decompression without major complications. This technique may increase the comfort of the patient during the postoperative phase considerably.