Yondelis (Trabectedin) is a novel antitumor agent of marine origin extracted from the tunicate Ecteinascidia turbinata. This original compound is active against several human tumors including sarcoma and ovarian and breast adenocarcinoma, as evidenced in phase II clinical trials in advanced multitreated patients. Yondelis is a DNA minor groove binder that blocks cell cycle and interferes with inducible gene transcription in a selective manner. In this study, we investigated the immunomodulatory properties of Yondelis on leukocytes. Human blood monocytes were highly susceptible in vitro to its cytotoxic effect and underwent apoptosis at pharmacologically relevant concentrations (5 nmol/L), whereas lymphocytes were up to 5-fold less sensitive. Macrophages differentiated in vitro with macrophage colony-stimulating factor and tumor-associated macrophages (TAM), isolated from patients with ovarian cancer, were also susceptible. At subcytotoxic concentrations, Yondelis inhibited the in vitro differentiation of monocytes to macrophages. In tumortreated patients, drug infusion caused a selective decrease of monocyte counts and of ex vivo macrophage differentiation. The in vitro production of two proinflammatory mediators, CCL2 and IL-6, was markedly reduced by Yondelis in monocytes, macrophages, TAM, and freshly isolated ovarian tumor cells. The chemokine CCL2 is the major determinant of monocyte recruitment at tumor sites, whereas IL-6 is a growth factor for ovarian tumors. In view of the protumor activity of TAM and of the strong association between chronic inflammation and cancer progression, the inhibitory effect of Yondelis on macrophage viability, differentiation, and cytokine production is likely to contribute to the antitumor activity of this agent in inflammation-associated human tumors. (Cancer Res 2005; 65(7): 2964-71)

Conservative treatment can be proposed to all young patients when tumor is limited to the ovaries, as ovarian recurrences can always be managed successfully. Patients with G3 tumors are more likely to have distant recurrences and should be closely monitored.

No abstract

Background:The objective of this study is to evaluate the safety of fertility-sparing surgery (FSS) for early-stage epithelial ovarian cancer (EOC).Methods:A retrospective analysis was performed to identify patients treated for early-stage EOC and to compare the clinical outcomes of patients treated with FSS and radical surgery (RS).Results:A total of 1031 patients were treated at two Institutions, 242 with FSS (group A) and 789 with RS (group B). Median duration of follow-up was 11.9 years. At univariate analyses, FSS was associated with decreased risk of relapse (P=0.002) and of tumour-related death (P=0.001). Multivariate analysis did not confirm the independent positive role of FSS neither on relapse-free interval (RFI) nor on cancer-specific survival (CSS). Tumour grade was associated with shorter RFI (P<0.001) and shorter CSS (P=0.001). The type of treatment did not influence CSS or RFI in any grade group. We also found a significant association between low-grade tumours and younger age.Conclusions:Fertility-sparing surgery is an adequate treatment for patients with stage I EOC. The clinical outcome of patients with G3 tumours, which is confirmed to be the most important prognostic factor, is not determined by the type of treatment received.

ObjectiveCOVID-19 has affected gynecologic cancer management. The goal of this survey was to evaluate changes that occurred in gynecologic oncology practice during the COVID-19 pandemic.MethodsA anonymous survey consisting of 33 questions (https://sites.google.com/view/gyncacovidfmartinelli) regarding interaction between gynecologic cancers and COVID-19 was distributed online via social media from April 9 to April 30, 2020. Basic descriptive statistics were applied. Analytics of survey-diffusion and generated-interest (visualizations, engagement rates, response rate) were analyzed.ResultsThe survey received 20 836 visualizations, generating an average engagement rates by reach of 4.7%. The response rate was 30%. A total of 86% of respondents completed the survey, for a total of 187 physicians surveyed across 49 countries. The majority (143/187; 76%) were gynecologic oncologists, and most were ≤50 years old (146/187; 78%). A total of 49.7% (93/187) were facing the early phase of the COVID-19 pandemic, while 26.7% (50/187) and 23.5% (44/187) were in the peak and plateau phases, respectively. For 97.3% (182/187) of respondents COVID-19 affected or changed their respective clinical practice. Between 16% (27/165) (before surgery) and 25% (26/102) (before medical treatment) did not perform any tests to rule out COVID-19 infection among patients. The majority of respondents did not alter indications of treatment if patients were COVID-19-negative, while treatments were generally postponed in COVID-19-positive patients. Treatments were considered priority for: early stage high-risk uterine cancers (85/187; 45%), newly diagnosed epithelial ovarian cancer (76/187; 41%), and locally advanced cervical cancer (76/187; 41%). Treatment of early stage low-grade endometrioid endometrial cancer was deferred according to 49% (91/187) of respondents, with hormonal treatment as the option of therapy (31%; 56/178). A total of 77% (136/177) of respondents reported no changes in (surgical) treatment for early stage cervical cancer in COVID-19-negative patients, while treatment was postponed by 54% (96/177) of respondent, if the patient tested COVID-19-positive. Neoadjuvant chemotherapy for advanced ovarian cancers was considered by over one-third of respondents as well as hypofractionation of radiation treatment for locally advanced cervical cancers.ConclusionCOVID-19 affected the treatment of gynecologic cancers patients, both in terms of prioritization and identification of strategies to reduce hospital access and length of stay. Social media is a reliable tool to perform fast-tracking, worldwide surveys.

Purpose: Gene expression profile was analyzed in 68 stage I and 15 borderline ovarian cancers to determine if different clinical features of stage I ovarian cancer such as histotype, grade, and survival are related to differential gene expression. Experimental Design:Tumors were obtained directly at surgery and immediately frozen in liquid nitrogen until analysis. Glass arrays containing 16,000 genes were used in a dual-color assay labeling protocol. Results: Unsupervised analysis identified eight major patient partitions, one of which was statistically associated to overall survival, grading, and histotype and another with grading and histotype. Supervised analysis allowed detection of gene profiles clearly associated to histotype or to degree of differentiation. No difference was found between borderline and grade 1tumors. As to recurrence, a subset of genes able to differentiate relapsers from nonrelapsers was identified. Among these, cyclin E and minichromosome maintenance protein 5 were found particularly relevant, as their expression was inversely correlated to progression-free survival (P = 0.00033 and 0.017, respectively). Conclusions: Specific molecular signatures define different histotypes and prognosis of stage I ovarian cancer. Mucinous and clear cells histotypes can be distinguished from the others regardless of tumor grade. Cyclin E and minichromosome maintenance protein 5, whose expression was found previously to be related to a bad prognosis of advanced ovarian cancer, appear to be potential prognostic markers in stage I ovarian cancer too, independent of other pathologic and clinical variables.

Total laparoscopic radical hysterectomy (with pelvic lymphadenectomy) is a safe option in patients with endometrial cancer. Obesity is not a contraindication to perform a TRLH with no differences in surgical parameters between obese and nonobese population. TLRH show a significant decrease of complications compared to laparotomic radical surgery in obese women.

Endometrial cancer is the most common gynaecologic malignancy in developed countries and its incidence is increasing. First-level treatment, if no contraindicated, is based on surgery. Pre-operative imaging is needed for evaluation of local extent and detection of distant metastases in order to guide treatment planning. Radiological evaluation, based on transvaginal ultrasound, MR and CT, can make the difference in disease management, paying special attention to assessment of entity of myometrial invasion, cervical stromal extension, and assessment of lymph nodal involvement and distant metastases.