Impact of BRCA Mutation Status on Tumor Dissemination Pattern, Surgical Outcome and Patient Survival in Primary and Recurrent High-Grade Serous Ovarian Cancer: A Multicenter Retrospective Study by the Ovarian Cancer Therapy-Innovative Models Prolong Survival (OCTIPS) Consortium.

BACKGROUND: This study seeks to evaluate the impact of breast cancer (BRCA) gene status on tumor dissemination pattern, surgical outcome and survival in a multicenter cohort of paired primary ovarian cancer (pOC) and recurrent ovarian cancer (rOC). PATIENTS AND METHODS: Medical records and follow-up data from 190 patients were gathered retrospectively. All patients had surgery at pOC and at least one further rOC surgery at four European high-volume centers. Patients were divided into one cohort with confirmed mutation for BRCA1 and/or BRCA2 (BRCAmut) and a second cohort with BRCA wild type or unknown (BRCAwt). Patterns of tumor presentation, surgical outcome and survival data were analyzed between the two groups. RESULTS: Patients with BRCAmut disease were on average 4 years younger and had significantly more tumor involvement upon diagnosis. Patients with BRCAmut disease showed higher debulking rates at all stages. Multivariate analysis showed that only patient age had significant predictive value for complete tumor resection in pOC. At rOC, however, only BRCAmut status significantly correlated with optimal debulking. Patients with BRCAmut disease showed significantly prolonged overall survival (OS) by 24.3 months. Progression-free survival (PFS) was prolonged in the BRCAmut group at all stages as well, reaching statistical significance during recurrence. CONCLUSIONS: Patients with BRCAmut disease showed a more aggressive course of disease with earlier onset and more extensive tumor dissemination at pOC. However, surgical outcome and OS were significantly better in patients with BRCAmut disease compared with patients with BRCAwt disease. We therefore propose to consider BRCAmut status in regard to patient selection for cytoreductive surgery, especially in rOC.

Impact of clinical factors and surgical outcome on long-term survival in high-grade serous ovarian cancer: a multicenter analysis.

INTRODUCTION: Long-term survivors of ovarian cancer are a unique group of patients in whom prognostic factors for long-term survival have been poorly described. Such factors may provide information for a more personalized therapeutic approach. The objective of this study is to determine further characteristics of long-term survivors with high-grade serous ovarian cancer. METHODS: Long-term survivors were defined as patients living longer than 8 years after first diagnosis and were recruited within seven high volume centers across Europe from November 1988 to November 2008. The control group included patients with high-grade serous ovarian cancer with less than 5 years' survival identified from the systematic 'Tumorbank ovarian cancer' database. A subanalysis of Charité patients only was performed separately for in-depth analysis of tumor dissemination. Propensity score matching with nearest-neighbor caliper width was used to match long-term survivors and the control group regarding age, FIGO stage, and residual tumor. RESULTS: A total of 276 patients with high-grade serous ovarian cancer were included, divided into 131 long-term survivors and 145 control group patients. After propensity score matching and multivariable adjustment, platinum sensitivity (p=0.002) was an independent favorable prognostic factor whereas recurrence (p<0.001) and ascites (p=0.021) were independent detrimental predictors for long-term survival. Significantly more long-term survivors tested positive for mutation in the BRCA1 gene than the BRCA2 gene (p=0.016). Intraoperatively, these patients had less tumor involvement of the upper abdomen at initial surgery (p=0.024). Complexity of surgery and surgical techniques were similar in both cohorts. CONCLUSION: Platinum sensitivity constitutes a favorable factor for long-term survival whereas tumor involvement of the upper abdomen, ascites, and recurrence have a negative impact. Based on clinical estimation, long-term survival is associated with combinations of clinical, surgical, and molecular factors.

Low endometrial beta-catenin and cadherins expression patterns are predictive for primary infertility and recurrent pregnancy loss.

Inadequate uterine receptivity is responsible for two-third of implanting failures. Aim of the study was to investigate the role of epithelial adherence and tight-junction molecules expressed by human endometrium in predicting womens' fertility outcome. A total of 76 consecutive women, including 24 fertile (G1), 40 primary infertile (G2), and 12 recurrent pregnancy loss (RPL, G3) women, who underwent diagnostic hysteroscopy plus endometrial biopsy between 2005 and 2016 at the Gynecology Division of Sant'Andrea Hospital, Sapienza University of Rome, in Italy, were retrospectively identified and included into the study. Endometrial biopsies were assessed for the immunohistochemical expression of beta-catenin (ß-catenin), E-cadherin and K-cadherin biomarkers. Expression profiles were compared between the three groups of patients and were correlated with patients' fertility outcome. In infertile patients there was a significant lower endometrial expression of ß-catenin (p = .001), E-cadherin (p = .001) and K-cadherin (p = .002), compared to the fertile ones. Furthermore, ß-catenin and E-cadherin intensity gradients of expression at glandular level were found totally reversed in infertile patients. Significant lower expression levels of K-catenin (p = .016) and E-cadherin (p < .0001) at glandular level were found in RPL patients. Results showed that the low endometrial expression of ß-catenin, E-cadherin and K-cadherin were associated to fertility-related problems, such as primary intertility and RPL.

Characterisation of tumour microvessel density during progression of high-grade serous ovarian cancer: clinico-pathological impact (an OCTIPS Consortium study).

BACKGROUND: High-grade serous ovarian cancer (HGSOC) intratumoural vasculature evolution remains unknown. The study investigated changes in tumour microvessel density (MVD) in a large cohort of paired primary and recurrent HGSOC tissue samples and its impact on patients' clinico-pathological outcome. METHODS: A total of 222 primary (pOC) and recurrent (rOC) intra-patient paired HGSOC were assessed for immunohistochemical expression of angiogenesis-associated biomarkers (CD31, to evaluate MVD, and VEGF-A). Expression profiles were compared between pOCs and rOCs and correlated with patients' data. RESULTS: High intratumoural MVD and VEGF-A expression were observed in 75.7% (84/111) and 20.7% (23/111) pOCs, respectively. MVDhigh and VEGF(+) samples were detected in 51.4% (57/111) and 20.7% (23/111) rOCs, respectively. MVDhigh/VEGF(+) co-expression was found in 19.8% (22/111) and 8.1% (9/111) of pOCs and rOCs, respectively (p = 0.02). Pairwise analysis showed no significant change in MVD (p = 0.935) and VEGF-A (p = 0.121) levels from pOCs to rOCs. MVDhigh pOCs were associated with higher CD3(+) (p = 0.029) and CD8(+) (p = 0.013) intratumoural effector TILs, while VEGF(+) samples were most frequently encountered among BRCA-mutated tumours (p = 0.019). Multivariate analysis showed VEGF and MVD were not independent prognostic factors for OS. CONCLUSIONS: HGSOC intratumoural vasculature did not undergo significant changes during disease progression. High concentration of CD31(+) vessels seems to promote recruitment of effector TILs. The study also provides preliminary evidence of the correlation between VEGF-positivity and BRCA status.

The prognostic impact of cancer stem-like cell biomarker aldehyde dehydrogenase-1 (ALDH1) in ovarian cancer: A meta-analysis.

OBJECTIVE: To investigate the association of cancer stem cell biomarker aldehyde dehydrogenase-1 (ALDH1) with ovarian cancer patients' prognosis and clinico-pathological characteristics. METHODS: The electronic searches were performed in January 2018 through the databases PubMed, MEDLINE and Scopus by searching the terms: "ovarian cancer" AND "immunohistochemistry" AND ["aldehyde dehydrogenase-1" OR "ALDH1" OR "cancer stem cell"]. Studies evaluating the impact of ALDH1 expression on ovarian cancer survival and clinico-pathological variables were selected. RESULTS: 233 studies were retrieved. Thirteen studies including 1885 patients met all selection criteria. ALDH1-high expression was found to be significantly associated with poor 5-year OS (OR = 3.46; 95% CI: 1.61-7.42; P = 0.001, random effects model) and 5-year PFS (OR = 2.14; 95% CI: 1.11-4.13; P = 0.02, random effects model) in ovarian cancer patients. No correlation between ALDH1 expression and tumor histology (OR = 0.60; 95% CI: 0.36-1.02; P = 0.06, random effects model), FIGO Stage (OR = 0.65; 95% CI: 0.33-1.30; P = 0.22, random effects model), tumor grading (OR = 0.76; 95% CI: 0.40-1.45; P = 0.41, random effects model) lymph nodal status (OR = 2.05; 95% CI: 0.81-5.18; P = 0.13, random effects model) or patients' age at diagnosis (OR = 0.83; 95% CI: 0.54-1.29; P = 0.41, fixed effects model) was identified. CONCLUSIONS: Basing on the available evidence, this meta-analysis showed that high levels of ALDH1 expression correlate with worse OS and PFS in ovarian cancer patients.

Beyond circulating microRNA biomarkers: Urinary microRNAs in ovarian and breast cancer.

Breast cancer is the most common malignancy in women worldwide, and ovarian cancer is the most lethal gynecological malignancy. Women carrying a BRCA1/2 mutation have a very high lifetime risk of developing breast and ovarian cancer. The only effective risk-reducing strategy in BRCA-mutated women is a prophylactic surgery with bilateral mastectomy and bilateral salpingo-oophorectomy. However, many women are reluctant to undergo these prophylactic surgeries due to a consequent mutilated body perception, unfulfilled family planning, and precocious menopause. In these patients, an effective screening strategy is available only for breast cancer, but it only consists in close radiological exams with a significant burden for the health system and a significant distress to the patients. No biomarkers have been shown to effectively detect breast and ovarian cancer at an early stage. MicroRNAs (miRNAs) are key regulatory molecules operating in a post-transcriptional regulation of gene expression. Aberrant expression of miRNAs has been documented in several pathological conditions, including solid tumors, suggesting their involvement in tumorigenesis. miRNAs can be detected in blood and urine and could be used as biomarkers in solid tumors. Encouraging results are emerging in gynecological malignancy as well, and suggest a different pattern of expression of miRNAs in biological fluids of breast and ovarian cancer patients as compared to healthy control. Aim of this study is to highlight the role of the urinary miRNAs which are specifically associated with cancer and to investigate their role in early diagnosis and in determining the prognosis in breast and ovarian cancer.

The Efficacy of Fibrin Sealant Patches in Reducing the Incidence of Lymphatic Morbidity After Radical Lymphadenectomy: A Meta-Analysis.

BACKGROUND: Although pivotal in the oncological management of most tumors, radical lymphadenectomy is associated with a significant number of lymphatic complications. The aim of this meta-analysis is to evaluate the efficacy of fibrinogen sealant patches in reducing lymphadenectomy-related postoperative complications. METHODS/MATERIALS: The electronic databases PubMed, Medline, and Scopus were searched using the terms "lymphadenectomy" or "lymph node dissection" and "TachoSil," "TachoComb," or "fibrin sealant patch." Series evaluating the efficacy of fibrin-thrombin collagen sealant patches were included in the meta-analysis. RESULTS: Overall, 26 studies were retrieved through the literature search. Ten studies including 720 patients met selection criteria. The use of fibrin-thrombin sealant patches to the sole scope of reducing lymphadenectomy-related complications significantly reduced the incidence of lymphocele, symptomatic lymphocele, the need of percutaneous drainage procedures, the volume of lymph drained, and the duration of the drainage. No effect on wound and/or lymphocele infection was noted. CONCLUSIONS: This meta-analysis demonstrates that the use of fibrin-thrombin sealant patches significantly reduces the total volume of lymph drained, the duration of the drainage, the incidence of lymphocele and symptomatic lymphocele, and the need for postoperative percutaneous drainage procedures. Its use does not affect the incidence of wound or lymphocele infections.

Genetic Versus Epigenetic BRCA1 Silencing Pathways: Clinical Effects in Primary Ovarian Cancer Patients: A Study of the Tumor Bank Ovarian Cancer Consortium.

OBJECTIVES: The aim of the present study was to assess in a large cohort of primary epithelial ovarian cancer patients the incidence and the clinical effect of BRCA1 genetic and epigenetic silencing mechanisms. METHODS: A total of 188 primary epithelial ovarian cancer patients, treated between 2000 and 2011 at the Charité University Hospital of Berlin, were included. The patients' tumor and blood samples were obtained from the Tumor Bank Ovarian Cancer Network (www.toc-network.de). Direct sequencing of BRCA1 exon 11 was performed to detect germline mutations, whereas tumor samples were assessed for BRCA1 promoter hypermethylation by bisulphite-converted methylation-specific polymerase chain reaction. Basing on their BRCA1 status, patients were compared regarding clinicopathological variables and survival. RESULTS: Twenty-one patients (11.2%) showed hypermethylation in BRCA1 promoter (HMB), and 18 patients (9.6%) presented germline mutations in BRCA1 exon 11 (GMB). Patients with HMB showed a significantly younger age at diagnosis compared with BRCA1 wild type (BWT) patients (54 vs 61 years, P = 0.045), and both GMB and HMB patients were more likely to have high-grade serous ovarian cancer (76.2% and 77.8% vs 52.7%, P = 0.043 and P = 0.043). Positive family history of breast or ovarian cancer (OC) was more frequently reported among GMB patients with respect to BWT patients (44.4% vs 13.5%, P = 0.003); GMB, HMB, and BWT patients did not show significant differences in terms of tumor dissemination pattern, surgical outcomes, platinum response or survival; neither mutational nor hypermethylation BRCA1 status was found to be an independent prognostic factor for OC patients. CONCLUSIONS: Hypermethylation in BRCA1 is associated with earlier occurrence of OC. In addition, the coexistence of both GBM and HMB is an infrequent event, occurring in 0.5% of OC cases. Silencing of BRCA1 through mutation and hypermethylation confers to distinct clinical characteristics of OC patients but similar clinical outcome with respect to BWT patients.

Sentinel Node Mapping in Cervical and Endometrial Cancer: Indocyanine Green Versus Other Conventional Dyes-A Meta-Analysis.

BACKGROUND: Historically, blue dyes, (99)Tc or a combination of the two tracers have been used for sentinel lymph node (SLN) mapping in cervical and endometrial cancer patients. Indocyanine green (ICG), as a tracer, has been recently introduced in this setting. Our goal was to assess the differences in overall and bilateral detection rates as well as in false-negative rates among the different tracers. METHODS: The electronic databases PubMed, MEDLINE, and Scopus were searched in January 2016 by searching the terms "sentinel lymph node" and "dye" and "indocyanine green," and "cervical cancer" or "endometrial cancer." Series comparing different tracers injected intracervically and reporting the detection rate and/or SLN false-negative rate were selected. RESULTS: Forty-five studies were retrieved. Six studies including 538 patients met selection criteria. Compared with blue dyes, ICG SLN mapping had higher overall (odds ratio [OR] 0.27; 95 % confidence interval [CI] 0.15-0.50; p < 0.0001) and bilateral detection rates (OR 0.27; 95 % CI 0.19-0.40; p < 0.00001). No differences were found between ICG and (99)TC, although these results are based on data of a single series. No differences in overall and bilateral detection rates were found between ICG and the combination of blue dyes and (99)TC. The pooled analysis of false-negative rates data showed no difference in false-negative rates between tracers. CONCLUSIONS: In cervical and endometrial cancer, ICG SLN mapping seems to be equivalent to the combination of blue dyes and (99)TC in terms of overall and bilateral detection rates. Its safety profile and ease of use may favor its employment respect to conventional tracers.

Effects of Neoadjuvant Chemotherapy Plus Radical Surgery as Front Line Treatment Strategy in Patients Affected by FIGO Stage III Cervical Cancer.

BACKGROUND: To assess the clinical efficacy and prognostic outcome of neoadjuvant chemotherapy (NACT) plus radical surgery (RS) as front line treatment in patients with FIGO stage III cervical cancer (CC). METHODS: In this retrospective study, 52 FIGO stage III CC patients treated from 2005 to 2015 were included. All patients received platinum-based chemotherapy. Patients reporting clinical response or stable disease after NACT underwent to RS and bilateral systematic pelvic lymphadenectomy with or without aortic lymphadenectomy or anterior exenteration. Patients with progressive disease underwent palliative management. RESULTS: After NACT, clinical response was observed in 23 patients (44 %): 4 (7.7 %) complete and 19 (36.5 %) partial responses, respectively. Also, 15 patients (28.8 %) had stable disease and 14 (26.9 %) showed disease progression. RS was performed in 40 cases (76.9 %): respectively, 28 (70 %) and 7 (17.5 %) underwent type C2 and D radical hysterectomy, while 5 patients (12.5 %) underwent anterior exenteration. At pathological evaluation, 23 patients (57.5 %) had positive pelvic nodes and 4 (10 %) also had positive aortic nodes. In 6 patients (15 %), moderate-severe (G3-G5) complications occurred. A total of 27 patients (67.5 %) received adjuvant therapy: 16 patients (40 %) received chemotherapy, 10 (25 %) received chemoradiation and 1 (2.5 %) received radiotherapy. Disease relapse occurred in 24 cases (60 %). After follow-up period of 60 months, the median OS of the whole population included was 37 months. Among the 40 surgically treated patients, median OS and DFS were 48 and 23 months, respectively. CONCLUSIONS: NACT plus RS represent a valid alternative with acceptable morbidity for patients with stage III CC.

Cediranib in ovarian cancer: state of the art and future perspectives.

Despite the dramatic improvements achieved in cancer treatment through a better understanding of the tumor biology, ovarian cancer is still characterized by a poor prognosis: most patients diagnosed with this disease will ultimately die from it. In various clinical trials conducted over a time span of two decades, new combinations of conventional chemotherapy regimens have failed to achieve significant improvements in oncologic outcome in ovarian cancer patients. We have now entered an era of "personalized medicine" in which new medications are designed to specifically target molecular pathways involved in carcinogenesis and cancer progression. Encouraging results in different tumor types have been reported, applying an increasing number of target therapies that are still under evaluation. In this setting, one of the most successfully targeted molecular pathways is tumor angiogenesis. Bevacizumab, a monoclonal antibody binding vascular endothelial growth factor (VEGF), has been recently incorporated in the treatment of primary and recurrent ovarian cancer patients after multiple phase III randomized controlled trials have proven its clinical benefit. Based on these positive results, more anti-angiogenic molecules using different mechanisms of action have been developed and are currently under investigation. Among these molecules, the tyrosine kinases inhibitors are probably the most promising ones. Cediranib is a tyrosine kinase inhibitor targeting VEGF receptors that has been tested in various trials with promising results. The aim of this manuscript is to review the current role of cediranib in the treatment of ovarian cancer and to present an overview of the ongoing clinical trials in this setting.

Circulating tumor cells as trigger to hematogenous spreads and potential biomarkers to predict the prognosis in ovarian cancer.

Despite several improvements in the surgical field and in the systemic treatment, ovarian cancer (OC) is still characterized by high recurrence rates and consequently poor survival. In OC, there is still a great lack of knowledge with regard to cancer behavior and mechanisms of recurrence, progression, and drug resistance. The OC metastatization process mostly occurs via intracoelomatic spread. Recent evidences show that tumor cells generate a favorable microenvironment consisting in T regulatory cells, T infiltrating lymphocytes, and cytokines which are able to establish an "immuno-tolerance mileau" in which a tumor cell can become a resistant clone. When the disease responds to treatment, immunoediting processes and cancer progression have been stopped. A similar inhibition of the immunosuppressive microenvironment has been observed after optimal cytoreductive surgery as well. In this scenario, the early identification of circulating tumor cells could represent a precocious signal of loss of the immune balance that precedes cancer immunoediting and relapse. Supporting this hypothesis, circulating tumor cells have been demonstrated to be a prognostic factor in several solid tumors such as colorectal, pancreatic, gastric, breast, and genitourinary cancer. In OC, the role of circulating tumor cells is still to be defined. However, as opposed to healthy women, circulating tumor cells have been demonstrated in peripheral blood of OC patients, opening a new research field in OC diagnosis, treatment monitoring, and follow-up.

Germline mutations of BRCA1 gene exon 11 are not associated with platinum response neither with survival advantage in patients with primary ovarian cancer: understanding the clinical importance of one of the biggest human exons. A study of the Tumor Bank Ovarian Cancer (TOC) Consortium.

Germline mutations in BRCA1 gene have been reported in up to 20 % of epithelial ovarian cancer (EOC) patients. Distinct clinical characteristics have been attributed to this special EOC population. We hypothesized that mutations in different BRCA1 gene exons may differently affect the clinical course of the disease. The aim of this study was to analyze, in a large cohort of primary EOCs, the clinical impact of mutations in BRCA1 gene exon 11, the largest exon of the gene sequence encoding the 60 % of BRCA1 protein. Two hundred sixty-three primary EOC patients, treated between 2000 and 2008 at Charité University Hospital of Berlin, were included. Patients' blood samples were obtained from the Tumor Ovarian Cancer (TOC) Network ( www.toc-network.de ). Direct sequencing of BRCA1 gene exon 11 was performed for each patient to detect mutations. Based on their BRCA1 exon 11 mutational status, patients were compared regarding clinico-pathological variables and survival. Mutations in BRCA1 exon 11 were found in 18 out of 263 patients (6.8 %). Further 10/263 (3.8 %) cases showed variants of uncertain significance (VUS). All exon 11 BRCA1-positive tumors (100 %) were Type 2 ovarian carcinomas (p = 0.05). Age at diagnosis was significantly younger in Type 2 exon 11 mutated patients (p = 0.01). On multivariate analysis, BRCA1 exon 11 mutational status was not found to be an independent predictive factor for optimal cytoreduction, platinum response, or survival. Mutations in BRCA1 gene exon 11 seem to predispose women to exclusively develop a Type 2 ovarian cancer at younger age. Exon 11 BRCA1-mutated EOC patients showed distinct clinico-pathological features but similar clinical outcome with respect to sporadic EOC patients.

Dose-Dense Neoadjuvant Chemotherapy plus Radical Surgery in Locally Advanced Cervical Cancer: A Phase II Study.

OBJECTIVE: To assess the efficacy and toxicity profile of dose-dense cisplatin-based neoadjuvant chemotherapy (NACT) followed by radical surgery in patients affected by locally advanced cervical cancer. METHODS: Patients affected by carcinoma of the uterine cervix FIGO (International Federation of Obstetrics and Gynecology) stage IB2-IIIB were enrolled into the study. The treatment schedule consisted of 5 cycles of intravenous paclitaxel 60 mg/m(2) plus cisplatin 60 mg/m(2) every 10 days; patients were then submitted to radical hysterectomy and pelvic lymphadenectomy. RESULTS: From January 2011 to March 2013, 22 patients were enrolled. Median age was 47 (26-83) years. FIGO stages included 1 IIA, 15 IIB, 1 IIIA, and 5 IIIB. Ninety-one percent of patients completed all the 5 planned cycles of NACT. Three patients experienced allergic reactions to paclitaxel. Grade 3-4 hematological toxicity was observed in 18% of cases. In 3 cases, grade 3-4 extra-hematological adverse and life-threatening events were reported (1 ototoxicity, 1 transient ischemic attack, and 1 myocardial infarction). No treatment-related death occurred. The operability rate was 86.4%. The overall response rate was 52.6%: 5 patients (26.3%) experienced clinical complete response, and 5 (26.3%) showed a clinical partial response. Stable disease was observed in 47.4% of patients, with no progressive disease recorded. Pathological response was observed in 57.9% of cases. Six out of 19 (31.6%) patients were submitted to adjuvant treatment. CONCLUSION: Dose-dense cisplatin-based NACT showed a response rate in approximately half of patients. However, in consideration of the reported extra-hematological toxicity, further studies on and new strategies with dose-dense platinum-based NACT are required to improve outcome in cervical cancer patients.

Dualistic classification of epithelial ovarian cancer: surgical and survival outcomes in a large retrospective series.

BACKGROUND: Ovarian cancers have been recently categorized into types I and II according to a dualistic model of tumorigenesis. Data on the correlation between this classification and clinical outcome are still scarce and controversial. METHODS: A retrospective analysis of patients with ovarian cancer treated from 1998 to 2013 and operated by the same surgeon was conducted. Patients were classified into two groups: type I (125 patients), including low-grade serous, mucinous, endometrioid, and clear cell tumors; and type II (286 patients), including high-grade serous tumors, unspecified adenocarcinomas, and undifferentiated carcinomas. RESULTS: Type II patients had a significantly higher incidence of advanced disease than type I (88.4 vs. 65.6 %, P = 0.0001) and required more aggressive surgical procedures. Rates of optimal tumor debulking were almost similar between groups (92.6 vs. 91.7 %, type I vs. II, P = NS). After a median follow-up of 41 months, 207 patients (50.4 %) were alive and 204 (49.6 %) were dead; 79 type I patients (63.8 %) and 237 type II patients (82.7 %) experienced relapse (P = 0.02). Progression-free survival was significantly different between groups: 25 months for type I vs. 17 months for type II (P = 0.023). Overall survival was not significantly different between groups, with a median overall survival of 75 months for type I vs. 62 months for type II (P = 0.116). CONCLUSIONS: The dualistic histotype-based classification into types I and II of ovarian cancer does not seem to correlate with prognosis. Different molecular characteristics of type I and II tumors may have therapeutic implications and should be deeply investigated.

Effects of unilateral ovariectomy on female fertility outcome.

PURPOSE: To compare the fertility outcome among women subjected to unilateral ovariectomy and other abdominal or non-gynaecologic pelvic surgery. METHODS: In this retrospective cohort study, 113 fertile women, surgically treated between 1990 and 2001 at Sapienza University of Rome with unilateral ovariectomy (UO), appendectomy (AP) or cholecystectomy (CO) for benign disease, were analysed for fertility outcome. Patients with assessed pre-surgical fertility defects, previous abdominal or pelvic surgeries and post-surgical contraception were not included. RESULTS: Thirty-five women underwent UO, 39 were subjected to AP and 39 were treated with CO. After a minimum 10-year post-surgical interval, the overall number of successful pregnancies was 75. The rate of women who experienced at least one post-operative successful pregnancy was: 48.5 % in UO, 41 % in AP and 53.8 % in CO (UO vs. AP, P = 0.55; UO vs. CO, P = 0.99; AP vs. CO, P = 0.53). One patient (2.8 %) in UO, one patient (2.6 %) in AP and two patients (5.1 %) in CO underwent Assisted Reproductive Technology to become pregnant. The rate of women who reported at least one miscarriage was: 10/35 (28.5 %) in UO, 11/39 (28.2 %) in AP, 12/39 (30.8 %) in CO (UO vs. AP, P = 0.93; UO vs. CO, P = 0.89; AP vs. CO, P = 0.81). One ectopic pregnancy was reported in CO group and one stillbirth occurred in one AP patient. CONCLUSIONS: No statistical difference in terms of post-operative fertility outcome between patients subjected to UO, AP or CO was found, thus allowing to suppose that the removal of one ovary does not significantly worsen the female fertility outcome respect to other abdominal or pelvic procedures.

Precision Oncology Targeting FGFRs: A Systematic Review on Pre-clinical Activity and Clinical Outcomes of Pemigatinib.

Fibroblast Growth Factor Receptors (FGFRs) are emerging as key factors involved in tumorigenesis, tumor microenvironment remodeling and acquired resistance to targeted therapies. Pemigatinib is a Tyrosine-Kinase Inhibitor that selectively targets aberrant FGFR1, FGFR2 and FGFR3. Pemigatinib is now approved for advanced-stage cholangiocarcinoma (CCA) but data suggests that other tumor histotypes exhibit FGFR alterations, thus hypothesizing its potential efficacy in other cancer settings. The present systematic review, based on PRISMA guidelines, aims to synthetize and critically interpret the results of all available preclinical and clinical evidence regarding Pemigatinib use in cancer. In April 2024, an extensive search was performed in PubMed, MEDLINE, and Scopus databases using the keyword "Pemigatinib". Twenty-seven studies finally met all inclusion criteria. The promising results emerging from Pemigatinib preclinical and clinical studies pave the way for Pemigatinib extension to multiple solid cancer settings.

Quality of life and sexual functioning among endometrial cancer patients treated with one week adjuvant high-dose-rate vaginal brachytherapy schedule.

Purpose: To examine quality of life (QOL) and sexual functioning in a series of patients with intermediate- and high-intermediate risk endometrial cancer, treated with exclusive adjuvant one week high-dose-rate (HDR) vaginal brachytherapy (VBT) schedule. Material and methods: Between July 2008 and October 2013, 55 patients with diagnosis of endometrial cancer were treated with adjuvant exclusive VBT. All patients had undergone surgical treatment with a laparotomy approach before VBT. Post-operative VBT was administered 6-8 weeks after surgery. Treatment was delivered to vaginal vault using Nucletron HDR unit with iridium-192 source at a dose of 21 Gy/3 fractions of 7 Gy each, three times a week, every other day, prescribed at 0.5 cm depth of vaginal wall, and 3 cm in length from the apex. QOL was assessed using European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire Core-30 (QLQ-C30), and EORTC cancer-specific quality of life questionnaire (QLQ-CX24). Results: Median follow-up time was 92 months (range, 42-162 months). Questionnaires were carried out respectively at 1, 3, 6, 12, 24, 36, 48, and 60 months after the end of BT. Response rate to questionnaires was 100% (n = 55). Nineteen patients (35%) answered all the questions of surveys, while 36 patients (65%) completed the surveys, except for questions on sex activity, vaginal function, and sex enjoyment. Longitudinal analysis during 5-year follow-up period showed a statistically significant trend towards worsening of fatigue, constipation, and diarrhea. Overall physical functioning and role functioning was not impaired after VBT. Over the time, sex enjoyment improved, except for elderly patients. For emotional functioning, sex worry and social functioning presented no significant time-related effect. Conclusions: One week brachytherapy schedule to vaginal cuff is generally well-tolerated. QOL does not worsen after applying vaginal brachytherapy.

Monoclonal antibodies in gynecological cancer: a critical point of view.

During the last decades, several improvements in treating gynecological malignancies have been achieved. In particular, target therapies, mostly monoclonal antibodies, have emerged as an attractive option for the treatment of these malignancies. In fact, various molecular-targeted agents have been developed for a variety of malignancies with the objective to interfere with a precise tumor associated receptor, essential for cancer cell survival or proliferation, blocking its function, of the cancer cells. Alternatively, monoclonal antibodies have been developed to block immune suppression or enhance functions of immune effector cells. So far, several monoclonal antibodies have been tested for clinical efficacy for the treatment of gynecological cancers. Antibodies against Vascular Endothelial Growth Factor (VEGF) and Epidermal Growth Factor Receptor (EGFR) have been used in different neoplasms such as ovarian and cervical cancer. Catumazumab, a bivalent antibody against CD3 and EpCAM, is effective in the treatment of neoplastic ascites. Other antibodies are peculiar for specific cancer-associated antigen such as Oregovomab against CA125 or Farletuzumab against the folate receptor. Here we describe the preclinical and clinical experience gained up to now with monoclonal antibodies in tumors of the female genital tract and trace future therapeutic and research venues.