Search

Introduction In ARIEL3 (NCT01968213), the poly(adenosine diphosphate-ribose) polymerase inhibitor rucaparib significantly improved progression-free survival versus placebo regardless of biomarker status when used as maintenance treatment for recurrent ovarian cancer. The aim of the current analyses was to evaluate the efficacy and safety of rucaparib in subgroups based on progression-free interval following penultimate platinum, number of prior chemotherapies, and prior use of bevacizumab. Methods Patients were randomized 2:1 to rucaparib 600 mg twice daily or placebo. Within subgroups, progressionfree survival was assessed in prespecified, nested cohorts: BRCA-mutant, homologous recombination deficient (BRCA-mutant or wild-type BRCA/high genomic loss of heterozygosity), and the intent-to-treat population. Results In the intent-to-treat population, median investigator-assessed progression-free survival was 8.2 months with rucaparib versus 4.1 months with placebo (n=151 vs n=76; HR 0.33, 95% CI 0.24 to 0.46, p<0.0001) for patients with progression-free interval 6 to ≤12 months, and 13.6 versus 5.6 months (n=224 vs n=113; HR 0.39, 95% CI 0.30 to 0.52, p<0.0001) for those with progression-free interval >12 months. Median progression-free survival was 10.4 versus 5.4 months (n=231 vs n=124; HR 0.42, 95% CI 0.32 to 0.54, p<0.0001) for patients who had received two prior chemotherapies, and 11.1 versus 5.3 months (n=144 vs n=65; HR 0.28, 95% CI 0.19 to 0.41, p<0.0001) for those who had received ≥3 prior chemotherapies. Median progression-free survival was 10.3 versus 5.4 months (n=83 vs n=43; HR 0.42, 95% CI 0.26 to 0.68, p=0.0004) for patients who had received prior bevacizumab, and 10.9 versus 5.4 months (n=292 vs n=146; HR 0.35, 95% CI 0.28 to 0.45, p<0.0001) for those who had not. Across subgroups, median progression-free survival was also significantly longer with rucaparib versus placebo in the BRCA-mutant and homologous recombination deficient cohorts. Safety was consistent across subgroups. Conclusions Rucaparib maintenance treatment significantly improved progression-free survival versus placebo irrespective of progression-free interval following penultimate platinum, number of lines of prior chemotherapy, and previous use of bevacizumab. [ABSTRACT FROM AUTHOR]

Introduction The role of cytoreductive surgery in the poly-ADP ribose polymerase inhibitors era is not fully investigated. We evaluated the impact of surgery performed prior to platinum-based chemotherapy followed by olaparib maintenance in platinum-sensitive BRCAmutated recurrent ovarian cancer. Methods This retrospective study included platinumsensitive recurrent ovarian cancer BRCA-mutated patients from 13 Multicenter Italian Trials in Ovarian cancer and gynecological malignancies centers treated between September 2015 and May 2019. The primary outcomes were progression-free survival and overall survival. Data on post-progression treatment was also assessed. Results Among 209 patients, 72 patients (34.5%) underwent cytoreductive surgery followed by platinumbased chemotherapy and olaparib maintenance, while 137 patients (65.5%) underwent chemotherapy treatment alone. After a median follow-up of 37.3 months (95% CI: 33.4 to 40.8), median progression-free survival in the surgery group was not reached, compared with 11 months in patients receiving chemotherapy alone (P<0.001). Median overall survival was nearly double in patients undergoing surgery before chemotherapy (55 vs 28 months, P<0.001). Post-progression therapy was assessed in 127 patients: response rate to chemotherapy was 29.2%, 8.8%, and 9.0% in patients with platinum-free interval >12 months, between 6 and 12 months, and <6 months, respectively. Conclusion Cytoreductive surgery performed before platinum therapy and olaparib maintenance was associated with longer progression-free survival and overall survival in BRCA-mutated platinum-sensitive relapsed ovarian cancer patients. In accordance with our preliminary results, the response rate to chemotherapy given after progression during olaparib was associated with platinum-free interval. [ABSTRACT FROM AUTHOR]

Objective To explore the clinical and biological prognostic factors for advanced ovarian cancer patients receiving first-line treatment with carboplatin, paclitaxel, and bevacizumab. Methods A multicenter, phase IV, single arm trial was performed. Patients with advanced (FIGO (International Federation of Gynecology and Obstetrics) stage IIIB-IV) or recurrent, previously untreated, ovarian cancer received carboplatin (AUC (area under the curve) 5), paclitaxel (175 mg/m2) plus bevacizumab (15 mg/kg) on day 1 for six 3-weekly cycles followed by bevacizumab single agent (15 mg/kg) until progression or unacceptable toxicity up to a maximum of 22 total cycles. Here we report the final analysis on the role of clinical prognostic factors. The study had 80% power with a two-tailed 0.01 a error to detect a 0.60 hazard ratio with a factor expressed in at least 20% of the population. Both progression-free and overall survival were used as endpoints. Results From October 2012 to November 2014, 398 eligible patients were treated. After a median follow-up of 32.3 months (IQR 24.1-40.4), median progression-free survival was 20.8 months (95% CI 19.1 to 22.0) and median overall survival was 41.1 months (95% CI 39.1 to 43.5). Clinical factors significantly predicting progression-free and overall survival were performance status, stage, and residual disease after primary surgery. Neither baseline blood pressure/antihypertensive treatment nor the development of hypertension during bevacizumab were prognostic. There were two deaths possibly related to treatment, but no unexpected safety signal was reported. Conclusions Efficacy and safety of bevacizumab in combination with carboplatin and paclitaxel and as maintenance were comparable to previous data. Hypertension, either at baseline or developed during treatment, was not prognostic. Performance status, stage, and residual disease after primary surgery remain the most important clinical prognostic factors. Trial registration number EudraCT 2012-003043-29; NCT01706120. [ABSTRACT FROM AUTHOR]

Background Improvement in clinical outcomes of patients with platinum-resistant disease is an unmet medical need and trials in this population are urgently needed. Checkpoint-inhibitors have already shown activity in multiple other tumor entities and ovarian cancer, especially in the combination with anti-angiogenic treatment. Primary objective To test if the activity of nonplatinum-based chemotherapy and bevacizumab could be improved by the addition of atezolizumab. study hypothesis The addition of atezolizumab to standard non-platinum combination of chemotherapy and bevacizumab improves median overall survival from 15 to 20 months. Trial design Patients are randomized to chemotherapy (paclitaxel weekly or pegylated liposomal doxorubicin) + bevacizumab + placebo vs chemotherapy + bevacizumab + atezolizumab. Stratification factors are: number of prior lines, planned type of chemotherapy, prior use of bevacizumab, and tumor programmed death-ligand 1 (PDL1) status. Major inclusion/exclusion criteria Recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer with up to three prior therapies and a treatmentfree interval after platinum of less than 6 months. Patients with three prior lines of chemotherapy are eligible irrespective of the platinum free-interval. A de novo tumor tissue sample biopsy for determination of PD-L1 status prior to randomization for stratification is mandatory. Major exclusion criteria consider bevacizumab-specific and immunotherapy-specific criteria. Primary endpoint Overall survival and progression-free survival are co-primary endpoints. sample size It is planned to randomize 664 patients. Trial registration NCT03353831. [ABSTRACT FROM AUTHOR]

Background Maintenance therapy induces remission and prolongs disease free interval in primary and recurrent ovarian disease. For the treatment decision making process, aspects of quality of life and patients' preferences are crucial, despite the fact that scientific data are lacking. Therefore, we conducted this European-wide study in patients with ovarian cancer. Methods A 25 item questionnaire was provided to ovarian cancer patients via the internet or as a paper version in 10 European countries (Austria, Belgium, France, Germany, Italy, Romania, Slovenia, Finland, Turkey, and Spain). Data recorded were demographics, tumor stage, therapy after firstline and recurrent disease, preferences for administration, and expectations concerning maintenance therapy. Results Overall, 1954 patients participated from September 2013 to March 2016; 42% had recurrent disease. Most patients (98%) with primary epithelial ovarian cancer underwent surgery followed by chemotherapy (91%). Almost one-third of participants (29%) were receiving maintenance therapy whereas 45% had only heard of it. For 70% of patients with primary epithelial ovarian cancer, they heard about maintenance therapy from their doctor, 10% heard about maintenance therapy from other patients, and 8% from the internet. The main source of information about maintenance therapy in patients with epithelial ovarian cancer relapse was from the treating physician (72%), from other patients (8%), and from the internet (7%). For patients undergoing maintenance therapy, the four most disturbing adverse effects were polyneuropathy (37%), nausea (36%), hair loss (34%), and vomiting (34%). The main objective of maintenance treatment, as perceived by patients, was to increase the chances of cure (73%), improvement in quality of life (47%), and delay in tumor growth (37%). Many patients were willing to undergo maintenance therapy until tumor progression (38%) and 39% would prefer oral administration. No significant differences were detected in the cross country subanalysis regarding expectations of maintenance therapy and patients with primary or relapsed ovarian cancer. Conclusion Patients with ovarian cancer were willing to accept maintenance therapy of prolonged duration and preferred oral administration. There is still a gap between the efficacy of maintenance therapy and patient expectations. Patients need more information on the adverse effects and treatment goals of maintenance therapy to avoid misunderstandings. [ABSTRACT FROM AUTHOR]

Objective To report results from an integrated efficacy and safety analysis supporting the European Commission's approval of the poly(ADP-ribose) polymerase inhibitor rucaparib as monotherapy treatment for relapsed, platinum-sensitive, BRCA-mutated ovarian cancer. Methods Efficacy was analyzed in platinum-sensitive patients from Study 10 (NCT01482715) and ARIEL2 (NCT01891344) who had high-grade serous or endometrioid epithelial ovarian, fallopian tube, or primary peritoneal cancer and a deleterious BRCA1 or BRCA2 mutation and received two or more prior chemotherapies (including two or more platinum-based therapies). The primary end point was investigator-assessed, confirmed objective response rate (visit cut-off: April 10, 2017). Safety was analyzed in patients with ovarian cancer, regardless of BRCA mutation status or lines of prior chemotherapies, who received at least one dose of rucaparib 600mg in either study (visit cut-off: December 31, 2017). Results In the integrated platinum-sensitive efficacy population (n=79), objective response rate was 64.6% (95% CI, 53.0 to 75.0); 10.1% (8/79) of patients had a complete response and 54.4% (43/79) had a partial response. Median duration of response was 294 days (95% CI, 224 to 393). In the integrated safety population (n=565), the most common any-grade treatment-emergent adverse events were nausea (77.7%, 439/565), asthenia/fatigue (74.7%, 422/565), vomiting (45.8%, 259/565), and hemoglobin decreased (44.2%, 250/565). Treatment-emergent adverse events led to treatment interruption, dose reduction, or discontinuation in 60.2% (340/565), 46.0% (260/565), and 16.8% (95/565) of patients. Conclusions In patients with platinum-sensitive, BRCA-mutated ovarian cancer, rucaparib demonstrated antitumor activity and is the first and currently the only poly(ADP-ribose) polymerase inhibitor approved by the European Commission as treatment for this population. The safety analysis used a more recent visit cut-off date and larger population than previously published, was consistent with prior reports, and was the basis for the treatment-indication safety population in rucaparib's recently updated European Union label. [ABSTRACT FROM AUTHOR]

Introduction: The PENELOPE trial evaluated pertuzumab added to chemotherapy for biomarker-selected platinum-resistant ovarian cancer. As previously reported, pertuzumab did not statistically significantly improve progression-free survival (primary end point: HR 0.74, 95% CI 0.50 to 1.11), although results in the paclitaxel and gemcitabine cohorts suggested activity. Here, we report final overall survival and patient-reported outcomes. Patients and methods: Eligible patients had ovarian carcinoma that progressed during/within 6 months of completing ≥4 platinum cycles, low tumor human epidermal growth factor receptor 3 (HER3) mRNA expression, and ≤2 prior chemotherapy lines. Investigators selected single-agent topotecan, gemcitabine or weekly paclitaxel before patients were randomized to either placebo or pertuzumab (840→420 mg every 3 weeks), stratified by selected chemotherapy, prior anti-angiogenic therapy, and platinum-free interval. Final overall survival analysis (key secondary end point) was pre-specified after 129 deaths. Patient-reported outcomes (secondary end point) were assessed at baseline and every 9 weeks until disease progression. Results: At database lock (June 9, 2016), 130 (83%) of 156 randomized patients had died. Median follow-up was 27 months in the pertuzumab arm versus 26 months in the control arm. In the intent-to-treat population there was no overall survival difference between treatment arms (stratified HR 0.90, 95% CI 0.61 to 1.32; p=0.60). Results in subgroups defined by stratification factors indicated heterogeneity similar to previous progression-free survival results. Updated safety was similar to previously published results. Compliance with patient-reported outcomes questionnaire completion was >75% for all validated patient-reported outcomes measures. Pertuzumab demonstrated neither beneficial nor detrimental effects on patient-reported outcomes compared with placebo, except for increased diarrhea symptoms. Discussion: Consistent with the primary results, adding pertuzumab to chemotherapy for low tumor HER3 mRNA-expressing platinum-resistant ovarian cancer did not improve overall survival, but showed trends in some cohorts. Except for increased diarrhea symptoms, pertuzumab had no impact on patient-reported outcomes. ClinicalTrials.gov:: ClinicalTrials.gov: NCT01684878. [ABSTRACT FROM AUTHOR]

Background: Cervical cancer is a common malignancy among women and, when recurring, presents a dismal prognosis. After platinum failure, second-line treatments report response rates ranging from 3–15%, a median progression-free survival of about 3 months and a median overall survival of about 5.5 months. To retrospectively evaluate the activity and safety of capecitabine in patients with advanced/recurrent cervical carcinoma. Methods A retrospective review of medical records of recurrent cervical cancer patients, who had failed a previous platinum–paclitaxel treatment and received oral capecitabine 1250 mg/m2 twice daily continuously from day 1 to day 14 every 21 days, was performed from December 2013 to March 2018 at the Gynecologic Oncology Unit of the Fondazione IRCCS National Cancer Institute of Milan, Italy. The response rate was evaluated every three cycles according to Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 criteria. Common Terminology Criteria for Adverse Events version 4.0 were used to evaluate adverse events. Results: We retrospectively analyzed 35 patients with recurrent cervical carcinoma, treated with oral capecitabine. All patients had previously received and failed a combination of carboplatin plus paclitaxel as first-line therapy for advanced/recurrent disease. Median age at the first capecitabine administration was 53 years (range 27–82). All patients were evaluable for response: the overall response rate was 34.2% (2.8% complete responses and 31.4% partial responses) with a clinical benefit rate of 57% (overall response rate plus 22.8% stabilizations of disease). The most common grade 1–2 adverse events per patient were fatigue (71.3%), hand-foot syndrome (57.0%), diarrhea (31.3%), constipation (17.0%), and nausea (10.4%). Only three patients (8.5%) reported grade 3 adverse events. Conclusions: Our data suggest that oral capecitabine should be considered an active and safe treatment in patients with recurrent cervical carcinoma after platinum failure. Based on these results, we consider capecitabine as warranting further clinical evaluation. [ABSTRACT FROM AUTHOR]

Background: Pegylated liposomal doxorubicin (PLD) is an active and well-tolerable treatment in ovarian cancer relapse, either alone or in combination with other drugs. No data are available on the possibility to rechallenge PLD treatment in long survivor patients with recurrent ovarian cancer, as evaluated for platinum agent, paclitaxel and gemcitabine. The aim of the present study was to evaluate the anti-tumor activity and the toxicity profile of re-challenge of PLD in recurrent ovarian cancer patients. Methods: Data on 27 patients with epithelial ovarian cancer treated in the last ten years (2007-2017) with palliative PLD rechallenge were included in this multicenter retrospective Italian study. Results: The objective response rate to PLD re-treatment were complete response in 19%, partial response in 30% and stable disease in 37%. Only 1 case of G4 hematological toxicity was reported. No patient experienced severe cardiac impairment (G2-4). Conclusion: PLD rechallenge represents an active and safe possibility of treatment for long survivor ovarian cancer patients. [ABSTRACT FROM AUTHOR]

Objective: The aim of the study was to evaluate outcomes of patients with unresectable advanced ovarian cancer experiencing complete response (CR) to neoadjuvant chemotherapy. Methods: Data of consecutive patients undergoing neoadjuvant chemotherapy plus interval debulking surgery (IDS) were retrospectively reviewed in 4 Italian centers. Using a propensity-matching algorithm, we compared data of patients achieving CR with neoadjuvant chemotherapy (no macroscopic either microscopic residual disease (RD) at the time of IDS) with patients achieving partial response (PR). This latter group was stratified by the presence of RD (RD = 0 vs RD > 0). Results: Overall, 193 had IDS after neoadjuvant chemotherapy: 25 (13%), 81 (41.9%), and 74 (38.3%) patients had CR, PR with RD of 0, and PR with RD of more than 0, respectively. In addition, 13 (6.7%) patients had no macroscopic disease detected at DS but just microscopic disease at pathological examination. For the study purpose, 25 patients achieving CR were matched (1:2) with 50 patients having PR and RD of 0 and 50 patients having PR and RD of more than 0. As the result of propensity matching, baseline characteristics were similar between groups. Comparing survival outcomes of patients having CR and PR with RD of 0, we observed that type of response to chemotherapy did not influence disease-free (hazard ratio = 1.53 [95% confidence interval = 0.88–2.66], P = 0.127) and overall (hazard ratio = 1.74 [95% confidence interval = 0.76–4.01], P = 0.189) survivals. Patients achieving CR experienced significantly better disease-free survival (P = 0.004) and a trend toward better overall survival (P = 0.06) than patients achieving PR with RD of more than 0 at IDS. Conclusions: Complete cytoreduction might mitigate the difference in response to neoadjuvant chemotherapy. The presence of RD at IDS is associated with worse survival outcomes. [ABSTRACT FROM AUTHOR]

Objective: Pelvic exenteration for recurrent gynecological malignancies is characterized by a high rate of severe complications. Factors predictive of morbidity, readmission, and cost were analyzed. Methods: Data of consecutive patients undergoing pelvic exenteration between January 2007 and December 2016 were prospectively evaluated. Results: Fifty-eight patients were included in the analysis. Anterior, posterior, and total exenterations were executed in 39 (67%), 9 (16%), and 10 (17%) patients, respectively. Ten (15.5%) severe complications occurred: 8 (20.5%), 0 (0%), and 1 (10%) after anterior, posterior, and total exenterations, respectively. Radiotherapy dosage, time between radiotherapy and surgery, and previous administration of chemotherapy did not influence 90-day complications and readmission. At multivariable analysis, albumin levels less than 3.5 g/dL (odds ratio, 16.2 [95% confidence interval, 2.85–92.8]; P = 0.002) and history of deep vein thrombosis (odds ratio, 9.6 [95% confidence interval, 0.93–98.2]; P = 0.057) were associated with 90-day morbidity. Low albumin levels independently correlated with readmission (P = 0.011). The occurrence of 90-day postoperative complications and readmission increased costs of a median of +12,500 and +6000 euros, respectively (P < 0.05). Conclusions: Preoperative patient selection is a key point for the reduction of postoperative complications after pelvic exenteration. Further prospective studies are warranted to improve patient selection. [ABSTRACT FROM AUTHOR]

Objective: Extramammary Paget disease of the vulva (EPDV) is a rare occurrence with an indolent and relapsing course. Progression to invasion occurs in 4% to 19% of cases. The aim of this study is to report clinical-pathological features and outcomes of patients treated for invasive EPDV. Methods: Data of consecutive patients treated between 2000 and 2017 for invasive EPDV were reviewed. Results: Among 79 patients with EPDV, 10 (12.7%) presented a microinvasive or invasive form at first diagnosis or during follow-up. All of them underwent upfront radical surgery; 7 (70%) received subsequent radiotherapy, chemotherapy, or both. The mortality rate was 40%. The recurrence rate after treatment for invasive forms was 60%, with a mean time to first recurrence of 20 (range, 5-36) months. Conclusions: Our study confirms that invasive EPDV remains a rare gynecological neoplasm with a poor prognosis. Multicentre trials or well-organized prospective data collection could improve the knowledge about the management of invasive EPDV. [ABSTRACT FROM AUTHOR]

Objectives: Neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) may be a valuable treatment option in advanced ovarian cancer when primary cytoreduction is not feasible. However, a consensus on the ideal number of NACT cycles is still lacking. In the present investigation, we aimed to evaluate how number of cycles of NACT influenced patients' outcomes. Methods: Data of consecutive patients undergoing NACT and IDS were retrospectively reviewed in 4 Italian centers, and survival outcomes were evaluated. Results: Overall, 193 patients were included. Cycles of NACT were 3, 4, and at least 5 in 77 (40%), 74 (38%), and 43 (22%) patients, respectively. Patients undergoing 3 cycles experienced a similar disease-free survival (hazard ratio [HR], 1.12; 95% confidence interval [CI], 0.89-1.65; P = 0.20) but an improved overall survival (HR, 1.64; 95% CI, 1.05-2.4; P = 0.02) in comparison to patients receiving at least 4 cycles. Five-year overall survival was 46% and 31% for patients having 3 and at least 4 cycles. Ten-year overall survival was 26%and 18% for patients having 3 and at least 4 cycles (HR, 1.70; 95% CI, 1.13-2.55; P = 0.009). Using multivariate analysis, we observed that only Eastern Cooperative Oncology Group performance status correlated with overall survival (HR, 1.76; 95% CI, 1.2-2.49; P = 0.001). In addition, a trend toward worse overall survival was observed for patients with residual disease at IDS (HR, 1.29; 95% CI, 0.98-1.70; P = 0.06) and patients receiving at least 4 cycles (HR, 1.76; 95% CI, 0.95-3.22; P = 0.06). Conclusion: Our data underline the potential implication of number of cycles of NACT before IDS. Further prospective studies are warranted to assess this correlation. [ABSTRACT FROM AUTHOR]

Objective: Ovarian cancer recurs in most patients, with a 5-year survival rate less than 30%. Quality of life is an increasingly important issue in patients with cancer, but there are limited data in women with recurrent ovarian cancer in this regard. Materials and Methods: We used an ad hoc questionnaire to compare changes in health perceptions, burden of disease, and expectations for the future quality of life in women with and without recurrence of ovarian cancer. A total of 173 women were included, 116 with relapse and 57 without, undergoing follow-up in a routine clinical setting. Results: Substantial differences were seen in self-assessed health status between women with and without recurrence; 33.6% and 82.4% of women with and without recurrence rated their health as good to excellent, respectively. More patients with recurrence of disease reported limitations in moderate activity than those without. Furthermore, 79.0% of women without recurrence reported that pain did not affect or only slightly affected daily activities, compared with 28.2% with recurrence. Most women with recurrence (59.5%) reported that they were able to do less than they wanted to because of their emotional status compared with only 15.8% of women without recurrence. In addition, 66.4% of women with recurrence referred that they had problems concentrating at work and home versus 26.3% of women without recurrence. Conclusions: From this survey, it is clear that relapse of disease has a negative psychological and physical impact, highlighting the importance of time without recurrence and the need for effective treatment in the long term. [ABSTRACT FROM AUTHOR]

Objective: Transfusions represent one of the main progresses of modern medicine. However, accumulating evidence supports that transfusions correlate with worse survival outcomes in patients affected by solid cancers. In the present study, we aimed to investigate the effects of perioperative blood transfusion in locally advanced cervical cancer. Methods: Data of consecutive patients affected by locally advanced cervical cancer scheduled to undergo neoadjuvant chemotherapy plus radical surgery were retrospectively searched to test the impact of perioperative transfusions on survival outcomes. Five-year survival outcomes were evaluated using Kaplan-Meier and Cox models. Results: The study included 275 patients. Overall, 170 (62%) patients had blood transfusion. Via univariate analysis,we observed that transfusion correlated with an increased risk of developing recurrence (hazard ratio [HR], 2.2; 95% confidence interval [CI], 1.09-4.40; P = 0.02). Other factors associated with 5-year disease-free survival were noncomplete clinical response after neoadjuvant chemotherapy (HR, 2.99; 95%CI, 0.92-9.63;P= 0.06) and pathological (P= 0.03) response at neoadjuvant chemotherapy as well as parametrial (P= 0.004), vaginal (P G 0.001), and lymph node (P = 0.002) involvements. However, via multivariate analysis, only vaginal (HR, 3.07; 95%CI, 1.20-7.85; P = 0.01) and lymph node involvements (HR, 2.4; 95% CI, 1.00-6.06; P = 0.05) correlate with worse disease-free survival. No association with worse outcomes was observed for patients undergoing blood transfusion (HR, 2.71; 95% CI, 0.91-8.03; P = 0.07). Looking at factors influencing overall survival, we observed that lymph node status (P = 0.01) and vaginal involvement (P = 0.06) were independently associated with survival. Conclusions: The role of blood transfusions in increasing the risk of developing recurrence in LAAC patients treated by neoadjuvant chemotherapy plus radical surgery remains unclear; further prospective studies are warranted. [ABSTRACT FROM AUTHOR]

Objective: Optimal cytoreduction is one the main factors improving survival outcomes in patients affected by ovarian cancer (OC). It is estimated that approximately 40%ofOCpatients have gross disease located on the diaphragm. However, no mature data evaluating outcomes of surgical techniques for the management of diaphragmatic carcinosis exist. In the present study, we aimed to estimate surgery-related morbidity of different surgical techniques for diaphragmatic cytoreduction in advanced or recurrent OC. Methods: PubMed(MEDLINE),Web of Science, andClincaltrials.gov databaseswere searched for records estimating outcomes of diaphragmatic peritoneal stripping (DPS) or diaphragmatic full-thickness resection (DFTR) for OC. The meta-analysiswas performed using the Cochrane Review software. Results: For the final analysis, 5 articles were available, including 272 patients. Diaphragmatic peritoneal stripping and DFTR were performed in 197 patients (72%) and 75 patients (28%), respectively. Pooled analysis suggested that the estimated pleural effusion ratewas 43% and 51% after DPS and DFTR, respectively. The need for pleural punctures or chest tube placement was 4% and 9% after DPS and DFTR, respectively. The rate of postoperative pneumothorax (4% vs 9%; odds ratio, 0.31; 95% confidence interval, 0.05Y2.08) and subdiaphragmatic abscess (3% vs 3%; odds ratio, 0.45; 95% confidence interval, 0.09Y2.31) were similar after the execution of DPS and DFTR. Conclusions: Diaphragmatic surgery is a crucial step during cytoreduction for advanced or recurrent OC. Obviously, the choice to perform DPS or DFTR depends on the infiltration of the diaphragmatic muscle or not. Both the procedures are associated with a low pulmonary complication and chest tube placement rates. [ABSTRACT FROM AUTHOR]

Clear cell carcinomas of the uterine corpus and cervix are rare gynecological cancers with limited information regarding the pathogenesis and biology. At present, the approach to management is the same as for patients with the more common histological subtypes of endometrioid endometrial cancer and adenocarcinoma of the cervix. Surgical resection is the standard treatment for patients with early-stage disease, but there is no evidence-based approach to direct the management of patients with more advanced-stage disease at presentation or with recurrent disease. We review the epidemiology, pathology, and what is known about both uterine corpus and cervical clear cell cancers and make management recommendations. [ABSTRACT FROM AUTHOR]

Most women diagnosed with malignant ovarian germ cell tumors have curable disease and experience excellent survival with manageable treatment-associated morbidity, related both to tumor biology and improvements in treatment over the last 4 decades. Malignant ovarian germ cell tumors occur predominantly in girls, adolescents, and young women and are often unilateral tumors of early stage, although advanced-stage disease occurs in approximately 30% of patients. Tumors are usually chemosensitive, thereby allowing fertility-sparing surgery in most women with high chance of cure. Differences in practice do exist among providers in various subspecialties and geographic areas. In most settings, collaborative efforts among specialties allow the optimal treatment of women with these rare tumors, and implementation of standard guidelines at an international level should translate to effective clinical trial design, rapid accrual to clinical trials, and universally improved patient outcomes.This consensus guideline represents a summary of recommendations for diagnosis and management that has been agreed upon by cooperative groups worldwide. It builds upon individual publications including previously published summary documents and provides the most current practice standards validated worldwide. [ABSTRACT FROM AUTHOR]

The objective of this study was to provide a consensus review on gestational trophoblastic disease diagnosis and management from the combined International Society for the Study of Trophoblastic Disease, European Organisation for the Treatment of Trophoblastic Disease, and the Gynecologic Cancer InterGroup.A joint committee representing various groups reviewed the literature obtained from PubMed searches.Guidelines were constructed on the basis of literature review. After initial diagnosis in local centers, centralization of pathology review and ongoing care is recommended to achieve the best outcomes. [ABSTRACT FROM AUTHOR]

Neuroendocrine tumors (NETs) are a heterogeneous group of neoplasms most commonly occurring in the gastrointestinal tract or the lungs. More frequent are gastrointestinal tumors, but over the past 30 years, there have been a number of small series or anecdotal case reports on ovarian NETs. Neuroendocrine tumors in the gynecologic tract are uncommon and account for about 2% of all gynecologic malignancies but may also be metastatic from other sites. They require a multimodality therapeutic approach determined by the extent of disease and the primary organ of involvement. Pathological diagnosis is critical to guide therapy. Surgery is the cornerstone of treatment for localized disease. There have been many new developments for treatment of advanced NETs including somatostatin analogs, hepatic artery embolization, chemotherapy, interferons, mammalian target of rapamycin inhibitors and radiolabeled somatostatin analogs. Given the rarity and lack of level I evidence, this is by nature more of a guidance and recommendation for management of these rare tumors until we can mount international studies. [ABSTRACT FROM AUTHOR]

Squamous cell carcinoma of the ovary is a rare complication of mature cystic teratoma. The epidemiology, pathology, diagnosis, and management of this rare tumor are reviewed. Clinical characteristics, preoperative imaging, and tumor markers may help to predict malignancy preoperatively. Complete cytoreduction should be the aim of surgery. The prognosis for stage 1A disease is good, but for women with advanced or recurrent disease, it is very poor and has not improved in recent years. At present, there are insufficient data to provide clear guidance on the optimal management strategy for advanced disease, and there is a need to gain an understanding of the biology and to develop novel effective therapies. This will require coordinated international collaboration. [ABSTRACT FROM AUTHOR]

Uterine carcinosarcoma (CS) is a rare neoplasm whose adjuvant treatment has not been yet defined. We report on the activity and toxicity of cisplatin-ifosfamide and carboplatin-paclitaxel as adjuvant treatments for patients with uterine CS.Data of International Federation of Gynecology and Obstetrics (FIGO) stage I to IV uterine CS patients treated between 2006 and 2012 with adjuvant chemotherapy (cisplatin 20 mg/mq and ifosfamide 1500 mg/mq day 1 to 4 every 3 weeks plus prophylactic Granulocyte colony-stimulating factor (G-CSF) support [group A] or carboplatin area under the curve -5 (AUC-5) and paclitaxel 175 mg/mq d1q21 [group B]) were retrospectively reviewed. Progression-free survival, overall survival, and chemotherapy-related toxicities were compared between the 2 groups. A subanalysis of oncologic outcomes according to the sarcomatous component (homologous vs heterologous) was performed.Forty-six women were evaluated—21 in group A and 25 in group B. At a median follow-up of 30 months, the median progression-free survival was 11.6 months (95% confidence interval [CI], 6.3-16.9) and 16.6 months (95% CI, 14.7-18.5) for group A and B, respectively (P = 0.20). The median overall survival was 17.1 months (95% CI, 12.6-21.5) and 35.1 months (95% CI, 26.3-43.7) for group A and B, respectively (P = 0.14). No differences were identified among heterologous or homologous components according to chemotherapy treatment. Toxicity profiles widely differ between treatment arms.Because of the super imposable activity and the better toxicity profile, carboplatin-paclitaxel may be a suitable alternative to cisplatin-ifosfamide in the treatment of uterine CS. [ABSTRACT FROM AUTHOR]

Neoadjuvant chemotherapy (NACT) followed by surgery is a different therapeutic approach to locally advanced cervical adenocarcinoma (LACA) and seems to offer specific advantages over chemoradiation. This phase II trial was designed to evaluate the toxicity and activity of NACT with cisplatin-adriamycin-paclitaxel (TAP) in patients with LACA.Patients with International Federation of Gynecology and Obstetrics stage IB2-IIB uterine adenocarcinoma were treated with NACT TAP for 3 cycles. After the last cycle, patients underwent radical surgery with lymph node dissection. Pathological response was classified as no residual tumor (pCR), residual disease with less than 3-mm stromal invasion (pR1), or residual disease with more than 3-mm stromal invasion (pR2).Between 2003 and 2010, 30 women were enrolled. Fourteen complete clinical responses, 10 partial responses, and 6 stabilizations of disease were registered. Three patients achieved a pCR, 6 a pR1 response, and 21 a pR2 response. At a median follow-up of 45 months, progression-free survival and overall survival were 37 and 48 months, respectively. Hematologic toxicity was the most relevant adverse effect.The TAP combination seems to be feasible with an acceptable toxicity profile and a promising response rate for the treatment of LACA. [ABSTRACT FROM AUTHOR]

Advanced or recurrent endometrial cancer is associated with a poor prognosis, and results obtained with systemic therapy are far from being impressive. Myocet is an interesting formulation of citrate conjugated doxorubicin encapsulated in nonpegylated liposomes. This phase 2 study was designed to evaluate the objective response rate and the toxicity profile of Myocet in women with advanced or recurrent endometrial cancer.Patients with diagnosis of advanced or recurrent endometrial cancer failing 1 previous carboplatin-paclitaxel chemotherapy were enrolled. Myocet was administered at the dose of 60 mg/m2 intravenously on day 1 every 4 weeks.Eighteen patients were enrolled in our institution from September 2007 to January 2010. No complete or partial response was observed. Stable disease was registered in 5 patients (27.5%). Median time to progression was 9 weeks. Median time to death was 24 weeks. Grade 3/4 anemia was reported in 2 patients (11%). Grade 3/4 neutropenia was observed in 16.5% and 44% of patients, respectively. The major nonhematologic toxicities (grades 3/4) were fatigue (22%), nausea, and vomiting (5.5%).Myocet presents no activity, and only few stabilizations of disease of limited duration in this recurrent endometrial carcinoma population previously treated with platinum-taxane chemotherapy are reported. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the outcome of patients with malignant ovarian germ cell tumors (MOGCTs) and to define the risk factors for recurrence.A total of 123 patients with MOGCTs were retrospectively reviewed among MITO centers. Eighty-one patients had primary treatment in a MITO center, whereas the other 42 were referred for adjuvant chemotherapy or recurrence. The clinicopathologic characteristics were evaluated for association with relapse or death.Median age was 24 years (range, 11-76 years). Forty-nine (39.8%) had dysgerminomas, 35 (28.5%) had immature teratomas, 12 (9.8%) had mixed germ cell tumors, 26 (21.1%) had yolk sac tumors, and 1 (0.8%) had embryonal carcinoma. International Federation of Gynecology and Obstetrics stage distribution was as follows: stage I, 87 (70.7%); stage II, 3 (2.4%); stage III, 29 (23.6%); and stage IV, 4 (3.3%). Fertility-sparing surgery was performed in 92 patients, whereas the remaining 31 received radical surgery; 65.8% of patients received adjuvant chemotherapy. Recurrence rate was 17.8% and the median time to recurrence was 9 months. Univariate and multivariate analyses showed that patient age (>45 years) and treatment outside a referral (MITO) center were the most important predictors of recurrence. The 5-year overall survival rate was 88.8%, with a median follow-up of 61 months. Univariate and multivariate analyses demonstrated that stage greater than I and yolk sac tumors were independent poor prognostic indicators.This study confirms that MOGCTs have excellent prognosis, with 5-year overall survival rates of 95.6% and 73.2% in stage I and advanced stages, respectively. Age older than 45 years and treatment not in a referral center are independent risk factors for recurrence, whereas stage greater than I and yolk sac histology are independent poor prognostic indicators. [ABSTRACT FROM AUTHOR]

The DESKTOP I trial proposed a score for the prediction of complete cytoreduction in recurrent ovarian cancer. Resectability was assumed if 3 factors were present: (1) complete resection at first surgery, (2) good performance status, and (3) absence of ascites. The DESKTOP II trial was planned to verify this hypothesis prospectively in a multicenter setting.Participating centers prospectively enrolled all consecutive patients with platinum-sensitive first or second relapse. The score was applied to all patients, but centers were free to decide on therapy. All further therapies were documented, and the outcome of patients was analyzed. A 75% complete resection rate in 110 prospectively classified patients had to be achieved to confirm a positive predictive value of 2 or higher of 3 with 95% probability.A total of 516 patients were screened within 19 months; of these, 261 patients (51%) were classified as score positive, and 129 patients with a positive score and first relapse were operated on. The rate of complete resection was 76%, thus confirming the validity of this score regarding positive prediction of complete resectability in 2 or more of 3 patients. Complication rates were moderate including second operations in 11% and perioperative mortality in 0.8%.This score is the first prospectively validated instrument to positively predict surgical outcome in recurrent ovarian cancer. It can aid in the selection of patients who might benefit from secondary cytoreductive surgery and will be enrolled in the recently started randomized prospective DESKTOP III trial investigating the role of surgery in recurrent platinum-sensitive ovarian cancer. [ABSTRACT FROM AUTHOR]

Introduction The majority of high-grade ovarian carcinomas have serous histology; however, a subset of patients have tumours of endometrioid or clear-cell histology at diagnosis. In a post hoc analysis, we investigated the clinical activity of rucaparib in patients with recurrent ovarian carcinoma with nonserous histology who enrolled in clinical studies in the maintenance (ARIEL3 [CO-338-014; NCT01968213]) or treatment setting (CO-338-010 [Study 10; NCT01482715] and ARIEL2 [CO-338-017; NCT01891344]). Patients and Methods ARIEL3 was a randomised, double-blind, placebo-controlled study of rucaparib (Coleman et al. Lancet. 2017;390:1949-61). A post hoc analysis evaluated investigator-assessed progression-free survival (PFS) in the subgroup of ARIEL3 patients who had high-grade ovarian carcinoma with endometrioid histology. Data for 1 additional patient in ARIEL3 with other nonserous histology are summarised descriptively. Study 10 and ARIEL2 were open-label, nonrandomised studies that investigated rucaparib (Kristeleit et al. Clin Cancer Res. 2017;23:4095-106; Swisher et al. Lancet Oncol. 2017;18:75-87). Data for patients in Study 10 and ARIEL2 with nonserous histology are summarised descriptively. For all studies, diagnoses were histologically confirmed locally and tumour responses were assessed by the investigators using RECIST v1.1. No patients with mixed histologies were included in these analyses. Results: In ARIEL3, 16 of 375 (4.3%) patients from the rucaparib arm and 7 of 189 (3.7%) patients from the placebo arm had endometrioid histology. Of the 16 patients in the rucaparib arm, 3 (18.8%) had a BRCA1 (2 somatic) or BRCA2 (1 germline) mutation. Of the 7 patients in the placebo arm, 4 (57.1%) had a BRCA1 (1 somatic, 1 unknown) or BRCA2 (2 germline) mutation. As of 15 April 2017 (visit cutoff date), median investigator-assessed PFS for the subgroup of patients with endometrioid histology was 13.7 months in the rucaparib arm vs 7.1 months in the placebo arm. In ARIEL3, 1 patient with transitional histology and a germline BRCA1 mutation who achieved a complete response to their last platinum-based regimen remained progression free for 35.7 months while receiving rucaparib. Three patients with endometrioid histology and 1 patient with clear cell histology received rucaparib in the treatment setting (Study 10 and ARIEL2). A partial response was achieved by 3 patients: 1 patient with clear cell histology and a germline BRCA1 mutation (9.7 months) and 2 patients with endometrioid histology and a germline BRCA1 mutation (13.6 months and 34+ months [response ongoing]). One patient with endometrioid histology and a germline BRCA2 mutation had stable disease for 7.3 months. In this small subset of patients from ARIEL3, Study 10, and ARIEL2, treatment-emergent adverse events were consistent with the overall safety profile reported for rucaparib in the overall populations for these studies, with no apparent difference due to histology. Conclusion Rucaparib had antitumour activity in a small subset of patients with recurrent high-grade ovarian carcinoma of grade 3 endometrioid and nonserous histology, including carcinomas associated with a BRCA1 or BRCA2 mutation. [ABSTRACT FROM AUTHOR]

Introduction and Objectives High-grade vaginal intra-epithelial neoplasia (vaginal HSIL) is a rare conditions, being its incidence approximately 100-fold lower than cervical intraepithelial neoplasia. Here, we aimed to investigate outcomes of women presenting with recurrent vaginal HSIL. Methods Data of consecutive women diagnosed with recurrent vaginal HSIL after primary treatments were retrieved. Risk of developing new recurrence over the time was assessed using Kaplan-Meier and Cox models. Results Data of 117 women were available for the analysis. At primary diagnosis, 41 (35%), 4 (3.4%) and 72 (61.6%) patients had had LASER, pure surgical and medical treatments, respectively. Secondary treatments included CO2 LASER ablation and medical treatment in 95 (81.2%) and 22 (18.8%) cases, respectively. After a mean (SD) follow-up of 72.3 (39.5) months, 37 (31.6%) out of the entire cohort of 117 patients developed a third vaginal HSIL recurrence. Median time to recurrence was 20 (range, 5-42) months. Patients with recurrent vaginal HSIL undergoing medical treatments were at higher risk of developing a new vaginal HSIL recurrence in comparison to women having LASER treatment (p=0.013, log-rank test). Considering the subgroup of 41 patients having primary LASER treatment, the execution of medical treatments at the time of vaginal HSIL recurrence is associated to a slightly but not significant increased risk of recurrence (p=0.148, log-rank test). After we corrected our results for type of treatment used for recurrent vaginal HSIL, we observed that the execution of primary LASER treatment was independently associated with a slightly risk of developing new vaginal HSIL recurrence (HR: 0.46 (95%CI: 0.21, 0.99); p=0.050). The other variable that is independently associated with a new vagina HSIL recurrence is the persistent infection from HPV16 or 18 (HR: 3.87 (95%CI: 1.15, 13.0); p=0.028). Nine (7.7%) patients developed cancers arising in the lower genital tract. Conclusions: Patients with recurrent vaginal HSIL are at high risk of developing persistent vaginal dysplasia. Our data underline that the choice of primary treatment might have an impact of further outcomes, therefore patients with diagnosis of vaginal HSIL have to be centralized in centre specialized in their treatment and in LASER therapy. [ABSTRACT FROM AUTHOR]

Objective To examine outcomes related to the execution of neoadjuvant chemotherapy, surgery and adjuvant treatments in newly diagnosed advanced stage low-grade serous ovarian cancer. Methods We conducted a retrospective case series of women affected by advanced stage (stage IIIB or more) low-grade ovarian cancer undergoing surgery in a single oncologic centre between January 2000 and December 2016. Data including demographic as well as histological characteristics, various treatment modality and outcomes were recorded. Survival outcomes were assessed using Kaplan-Meier and Cox models. Results Data of 72 patients were retrieved. Mean (SD) patients age was 59.6 (18.3) years. Stage distribution included FIGO stage IIIB, IIIC, IVA and IVB in 9, 56, 1 and 7 cases, respectively. Primary cytoreductive surgery was attempted in 68 (94.4%) patients: 44 (64.7%) patients had complete resection, optimal resection was achieved in 65% and 72% patients; while 24 (35.3%) had residual disease after primary. Interval debulking surgery was attempted in 15 of these patients and the remaining four patients having not primary debulking surgery. Twelve out of 19 (63.1%) patients having interval debulking had residual disease. After a mean follow-up was 61.6 (37.2) months, 50 (69.4%) and 22 (30.5%) patients recurred and died of disease, respectively. Via univariate analysis, presence of residual disease (HR: 2.16 (95%CI: 1.23, 3.79); p=0.007), non-optimal cytoreduction (HR: 2.99 (95%CI: 1.68, 5.33); p<0.001) and FIGO stage IV (HR: 4.11 (95%CI: 1.80, 9.34); p=0.001) were associated with an increased risk of recurrence. Via multivariate analysis, non-optimal cytoreduction (HR: 2.79 (95%CI: 1.16, 6.70); p=0.021) and FIGO stage IV (HR: 3.15 (95%CI: 1.29, 7.66); p=0.011) remained associated with disease-free survival. Overall survival was influenced by patients' comorbidity (HR: 0.42 (95%CI: 0.25, 0.94); p=0.033), type of surgical approach (HR: 3.00 (95CI: 1.25, 7.20) for patients who had interval debulking instead of primary surgery; p=0.014), presence of residual disease (HR: 2.25 (95%CI: 0.95, 5.30); p=0.064) and FIGO stage IV (HR: 3.46 (95%CI: 1.23, 9.70); p=0.018). Via multivariate analysis, absence of significant comorbidities (HR: 0.56 (95%CI: 0.29, 1.10); p=0.093) and primary instead of interval debulking surgery (HR: 2.95 (95%CI: 1.12, 7.74); p=0.027) remained independently associated with an improved overall survival. Conclusion Low grade serous ovarian cancer are at high risk of early recurrence. However, owing to the indolent nature of the disease, the majority of patients are long-term survivors. Complete cytoreduction plays an important role in improving long-term outcomes of women affected by advanced stage low-grade serous ovarian cancer. Even possible primary surgery should be preferred over interval debulking since the poor response to neoadjuvant chemotherapy do not improve our ability to achieve cytoreduction. [ABSTRACT FROM AUTHOR]