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Veronica Agostinelli,1 Lucia Musacchio,2 Floriana Camarda,2 Vanda Salutari,2 Maria Vittoria Carbone,2 Viola Ghizzoni,2 Camilla Nero,2 Caterina Ricci,2 Maria Teresa Perri,2 Elena Giudice,3 Sara Lardino,3 Rossana Berardi,1 Giovanni Scambia,2,3 Domenica Lorusso2,3 1Oncologic Clinic, Università Politecnica delle Marche, Ancona, Italy; 2Department of Woman, Child and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy; 3Institute of Obstetrics and Gynecology, Università Cattolica del Sacro Cuore, Rome, ItalyCorrespondence: Vanda Salutari, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo Agostino Gemelli, 8, Roma, 00168, Italy, Tel +39-06-3015-3234, Email vanda.salutari@policlinicogemelli.itAbstract: Cervical cancer is the fourth most common type of cancer in women worldwide. It is associated with a high death rate, despite the fact that it is a nearly 100% preventable disease because of very effective primary and secondary preventive strategies. Advanced and recurrent disease is uncurable with a high relapse risk and the second-line therapies are limited with modest response rates and short durability. Investigating alternative mechanisms of action is crucial because of the high request for effective new therapies. Tisotumab vedotin (TV) is the first antibody-drug conjugated to target a cell surface-expressed tissue factor, and preliminary data in patients with metastatic and recurrent cervical cancer have been promising. In addition, the trials showed a favorable tolerability profile, with limited incidence of grade 3 or worse adverse events. According to the data of ENGOT-cx6/GOG-3023/innovaTV 204, the US Food and Drug Administration granted expedited approval of TV on September 20, 2021, for women with recurrent or metastatic cervical cancer. Actually, two other trials testing TV alone or in combination with other agents are ongoing. ENGOT-cx8/GOG-3024/innovaTV 205 is a Phase Ib/II trial of TV in combination with platinum or bevacizumab or pembrolizumab, in patients with recurrent or metastatic cervical cancer who have not received prior systemic therapy or who have progressed after no more than two prior systemic therapies. ENGOT-cx12/GOG-3057/InnovaTV 301 is a Phase 3 trial of TV vs investigator’s choice chemotherapy in patients with advanced or recurrent cervical cancer who had received no more than 2 prior chemotherapy lines. The outcomes of these two trials will potentially confirm and reinforce the use of TV as a new standard of care in advanced or recurrent cervical cancer.Keywords: cervical cancer, gynecological cancer, antibody–drug conjugate, tissue factor

Introduction: Relacorilant (CORT125134, Corcept Therapeutics) is a selective glucocorticoid receptor modulator, which reverses the glucocorticoid-mediated anti-apoptotic effects and restores the taxane chemosensitivity in epithelial ovarian cancer cells. Given those preclinical findings, relacorilant is currently under investigation in clinical trials in combination with nab-paclitaxel for the platinum-resistant ovarian cancer setting., Areas Covered: Already published preclinical and clinical evidence of relacorilant antitumor activity was analyzed and discussed. Ongoing clinical trials registered on clincaltrials.gov were also reported. The review aimed to summarize the status of relacorilant, the mechanism of action, the published and ongoing trials, and its safety and efficacy., Expert Opinion: Relacorilant combined with nab-paclitaxel, may represent a promising strategy for the treatment of platinum-resistant ovarian cancer patients. After preliminary positive results in terms of clinical efficacy, a randomized phase III trial is ongoing to confirm the findings from the published phase II study.

Objective: Correlation between BRCA1/ 2 ( BRCA ) pathogenic variants and the response to poly (ADP-ribose) polymerase inhibitors (PARPi) has been recognized in patients with ovarian cancer. Moreover, data on the clinical implications of variants of unknown significance are lacking. The aim of this study was to evaluate differences in survival outcomes in patients with BRCA variants of unknown significance, mutated, and wild type relapsed ovarian cancer treated with PARPi., Methods: Patients with ovarian cancer whose somatic BRCA testing was available and who were receiving PARPi as maintenance treatment at the first recurrence between January 2014 and January 2021 were included in the present study and analyzed. Patients were divided into three groups according to BRCA mutational status (variant of unknown significance, mutated, and wild type). Progression-free survival was assessed in each study group., Results: Of 67 patients identified, 20 (29.9%), 24 (35.8%), and 23 (34.3%) had BRCA variant of unknown significance, mutated, and wild type, respectively. Patients received PARPi as maintenance treatment at the time of the first relapse after a complete response or partial response to platinum-based chemotherapy without differences in the previous platinum-free interval among the analyzed groups. The median progression-free survival of patients with BRCA mutation was significantly longer than for those with BRCA wild type or variant of unknown significance (not reached vs 4 months vs 7 months, respectively; p<0.001). Additionally, no significant difference was found between patients with BRCA wild type and BRCA variant of unknown significance (p=0.50)., Conclusion: Our study suggests that carriers of BRCA variant of unknown significance have survival outcomes comparable to patients with BRCA wild type and shorter progression-free survival than women harboring BRCA pathogenic variants., Competing Interests: Competing interests: CM reports consultant/advisory board for Clovis, Pharmamar, GSK, AstraZeneca, Arquer Diagnostic and travel accommodation from PharmaMar and Roche. VS reports honoraria from GSK, PharmaMar, Roche, MSD, EISAI, Clovis, Oncology, AstraZeneca. SP reports honoraria from AstraZeneca, MSD, Roche, Pfizer, Clovis, GSK, PharmaMar and research funding from MSD, Roche, AstraZeneca and Pfizer. GS reports research support from MSD and honoraria from Clovis Oncology. Consultant for Tesaro and Johnson & Johnson. DL reports research funding from Clovis, GSK and MSD, personal interests with AstraZeneca, Clovis Oncology, GSK, PharmaMar, MSD and financial interests with Clovis, Genmab, GSK, MSD. Board of Directors, GCIG (Gynecologic Cancer Inter Group)., (© IGCS and ESGO 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Next-generation sequencing (NGS) analysis has become an essential tool for endometrial carcinoma management. Moreover, molecular-driven therapies play an increasingly remarkable role in the era of precision oncology. This study aims to determine the clinical relevance of NGS testing in endometrial carcinoma management by analyzing the clinical benefit of NGS-driven targeted therapies., Methods: A single-center retrospective study was conducted on 25 endometrial carcinoma patients who underwent Foundation Medicine CDx assay at Fondazione Policlinico Universitario Agostino Gemelli, IRCCS (Rome, Italy). Tumor samples were analyzed by Foundation One CDx. A descriptive analysis of tumor genome profiles was performed. Assessment of clinical benefit according to RECIST 1.1 criteria was analyzed for patients who received a tailored treatment according to actionable targets identified by NGS testing., Results: Out of 25 endometrial carcinoma patients, 11 received targeted therapy. One patient was excluded from the clinical benefit assessment because of COVID-19-related death 1 month after starting the treatment. Eight of the remaining 10 patients benefited from targeted therapies, with an overall clinical benefit rate of 80%. A targeted agent belonging to the PI3K pathway was given to seven patients, with evidence of three partial responses (42.9%), three stable diseases (42.9%), and one progressive disease (14.2%) according to RECIST 1.1 criteria. One complete response (33.3%), one stable disease (33.3%), and one progressive disease (33.3%) were observed in the three patients treated with poly(ADP-ribose) polymerase (PARP) inhibitors according to their homologous recombination deficiency (HRD) status., Conclusion: This study highlights the importance of characterizing the mutation profile of patient tumors through NGS. Our findings suggest a clinical benefit of using NGS-driven targeted therapies in endometrial carcinoma patients. However, this personalized approach could benefit the health system in terms of cost-effectiveness by reducing the costs of inappropriate, ineffective, and often expensive treatments., Competing Interests: Competing interests: VS was on the advisory board for AstraZeneca, Clovis, Tesaro, GSK, MSD, EISAI, Roche, and PharmaMar. GS was a consultant and received consulting fees from Johnson & Johnson, AstraZeneca–MSD, and Covidien AG – a Medtronic company; he was on the speakers bureau and received honoraria from Olympus Europa SE & CO. KG, Baxter Healthcare SA, Intuitive Surgical Inc, and GlaxoSmithKline S.p.A. DL had a consulting or advisory role for PharmaMar, AstraZeneca, Clovis Oncology, GlaxoSmithKline, MSD, Genmab, Amgen, Seattle Genetics, Immunogen, Merck Serono, Oncoinvest, Corcept Therapeutics, and Sutro Biopharma. She was on the speakers’ bureau for AstraZeneca, Clovis Oncology, GlaxoSmithKline, MSD, and PharmaMar. Institutional Research Funding: PharmaMar, Clovis Oncology, GlaxoSmithKline, MSD, AstraZeneca, Genmab, Seagen, Immunogen, Incyte, Novartis, and Roche. She had travel expenses paid for by Roche, PharmaMar, AstraZeneca, Clovis Oncology, and GlaxoSmithKline., (© IGCS and ESGO 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Endometrial cancer (EC) is the most common gynecological cancer in developed countries. The ESGO/ESTRO/ESP updated evidence-based guidelines in 2020, introducing molecular classification to guide EC treatment. The genomic-based approach has identified four prognostic subgroups of EC. Each of these may benefit from a tailored treatment depending on the molecular profile, the histotype, and stage of disease for the adjuvant and the metastatic/recurrent setting. Several clinical trials are now ongoing to identify the best treatment according to the molecular profile of EC., Areas Covered: This review analyzes tailored treatment for EC according to the molecular profile, both in the adjuvant and in the metastatic/recurrent setting. The authors review the results of clinical studies and highlight ongoing trials., Expert Opinion: Several new agents are under evaluation in order to personalize EC treatment according to specific molecular profiles in the adjuvant, advanced, and recurrent settings. Clinical trials investigating the impact of molecular classification have yielded encouraging results. EC can no longer be considered a single tumor entity susceptible to a single treatment modality but rather be split into four distinct types, requiring tailored treatments.

Patients with primary metastatic/recurrent endometrial cancer have poor prognosis and available therapeutic options are limited. Current treatment is mainly based on platinum-based chemotherapy. Recently, the Food and Drug Administration (FDA) granted approval for the combination of pembrolizumab and lenvatinib for endometrial cancer patients without microsatellite instability (MSS) progressing on a previous line of therapy while European Medicines Agency (EMA) approved the combination for all comers patients failing previous platinum treatment. Anti programmed cell death protein-1 (PD-1) dostarlimab (TSR-042) was approved as monotherapy in patients with advanced, microsatellite instable (MSI) endometrial cancer progressing to platinum treatment. Phase II-III clinical trials in metastatic endometrial cancer are mainly focused on target therapies and immunotherapy as single agents or in combination. Unfortunately, most of these trials are lacking of predictive biomarkers of response to select patients most or at least likely to benefit from those treatments., Competing Interests: Declaration of Competing Interest VS reports grants from Clovis Oncology, grants from TESARO, grants from GSK, grants from Astra Zeneca, grants from MSD, grants from PHARMAMAR, grants from EISAI, grants from ROCHE, outside the submitted work; RB reports personal fees from Astra Zeneca, Boehringer Ingelheim, Novartis, MSD, Otsuka, Eli‐Lilly, Roche outside the submitted work; GS reports personal fees from ROCHE, personal fees from Clovis Oncology, personal fees from Astra Zeneca, personal fees from PharmaMar, personal fees from Tesaro, outside the submitted work; DL reports grants from ROCHE, grants and personal fees from GSK, grants and personal fees from Clovis Oncology, grants and personal fees from MSD, grants from Incyte, grants and personal fees from PHARMAMAR, grants from IMMUNOGEN, grants and personal fees from GENMAB, personal fees from AMGEN, grants and personal fees from ASTRA ZENECA, outside the submitted work; FT, CN, EG, LM, CR, MVC, VG, MTP, FC, MG have nothing to disclose., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Low-grade serous ovarian and peritoneal cancer (LGSC) is a rare disease and few data on the clinical and genomic landscape have been published., Methods: A retrospective analysis of patients diagnosed with LGSC between 1996 and 2019 was conducted in MITO centers. Objective Response Rate (ORR) to treatments, progression-free survival (PFS) and overall survival (OS) were assessed. Additionally, the tumor molecular profile of 56 patients was evaluated using the Next Generation Sequencing (NGS) FoundationOne CDX (Foundation Medicine®)., Results: A total of 128 patients with complete clinical data and pathologically confirmed diagnosis of LGSC were identified. ORR to first and subsequent therapies were 23.7% and 33.7%, respectively. PFS was 43.9 months (95% CI:32.4-53.1) and OS was 105.4 months (95% CI: 82.7-not reached). The most common gene alterations were: KRAS (n = 12, 21%), CDKN2A/B (n = 11, 20%), NRAS (n = 8, 14%), FANCA (n = 8, 14%), NF1 (n = 7, 13%) and BRAF (n = 6, 11%). Unexpectedly, pathogenetic BRCA1 (n = 2, 4%), BRCA2 (n = 1, 2%) and PALB2 (n = 1, 2%) mutations were found., Conclusions: MITO 22 suggests that LGSC is an heterogenous disease for both its clinical behavior in response to standard therapies and its molecular alterations. Future prospective studies should test treatments according to biological and molecular tumor's characteristics., Clinical Trial Registration: This study is registered under NCT02408536 on ClinicalTrials.gov ., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

PolyADP-ribose polymerase (PARP) inhibitors (PARPis) represent the first clinically approved drugs able to provoke "synthetic lethality" in patients with homologous recombination-deficient (HRD) tumors. Four PARPis have just received approval for the treatment of several types of cancer. Besides, another three additional PARPis underlying the same mechanism of action are currently under investigation. Despite the success of these targeted agents, the increasing use of PARPis in clinical practice for the treatment of different tumors raised the issue of PARPis resistance, and the consequent disease relapse and dismal prognosis for patients. Several mechanisms of resistance have been investigated, and ongoing studies are currently focusing on strategies to address this challenge and overcome PARPis resistance. This review aims to analyze the mechanisms underlying PARPis resistance known today and discuss potential therapeutic strategies to overcome these processes of resistance in the future.

Lurbinectedin is an antitumor agent belonging to the natural marine-based tetrahydroisoquinoline family which has shown very promising clinical activity with a favorable safety profile in many types of cancer. Preclinical evidence showed that lurbinectedin inhibits active transcription and binds to GC-rich sequences, leading to irreversible degradation of RNA polymerase II and generation of single- and double-strand DNA breaks and, as a consequence, apoptosis of tumor cells. In addition, lurbinectedin has demonstrated modulation of the tumor microenvironment and activity against cancer cells harboring homologous recombination DNA repair deficiency. Although considerable improvements have been made in the treatment of epithelial ovarian cancer, most patients with advanced disease experience recurrence with a dismal prognosis due to chemotherapy (mainly platinum) resistance. Platinum-resistant/refractory ovarian cancer remains a difficult-to-treat setting of disease, and currently, the exploration of new therapeutic approaches represents a main field of interest. Although the CORAIL phase III study did not meet its primary endpoint, the results suggest that lurbinectedin might be a valid alternative for patients that have exhausted therapeutic options. This article will focus on the clinical evidence, the most recent investigations, and the future perspective regarding the use of lurbinectedin in ovarian cancer., Competing Interests: DL reports research funding from Clovis, GSK, and MSD; personal interests with AstraZeneca, Clovis Oncology, GSK, PharmaMar, and MSD; and financial interests with Clovis, Genmab, GSK, and MSD; and is part of the Board of Directors, GCIG (Gynecologic Cancer Inter Group). VS reports honoraria from GSK, PharmaMar, Roche, MSD, EISAI, Clovis, Oncology, and AstraZeneca. GS reports research support from MSD and honoraria from Clovis Oncology and is a consultant for Tesaro and Johnson & Johnson. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Musacchio, Cicala, Salutari, Camarda, Carbone, Ghizzoni, Giudice, Nero, Perri, Ricci, Tronconi, Scambia and Lorusso.)

Ovarian cancer (OC) is the most lethal gynecological malignancy and very little is known about the underlying tumorigenesis mechanisms. For other tumors, like colorectal cancer, a relationship between several opportunistic pathogens and cancer development and progression has been proven. Recent researches also underline a possible correlation between gut microbiota dysbiosis and cancer treatment efficacy and adverse effects. Several studies have also demonstrated a link between abdominal surgery and gut microbiota modifications. In this paper, we aim to review the available evidences of this issue in OC to understand if there is a relationship between gut microbiota modifications and efficacy and adverse effects of cancer therapies, either surgical and medical treatments. Well-designed clinical studies, with a robust translational component, are required to better understand the modulation of gut microbiota during OC treatment. The microbiota/microbiome composition analysis, in the near future, could represent a novel instrument to personalize anticancer therapies., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Platinum-resistant ovarian cancer patients have a poor prognosis and few treatment options are available. Preclinical and clinical data demonstrated that the combination of poly-ADP ribose polymerase inhibitors with immune checkpoint inhibitors could have a synergistic antitumor activity in this setting of patients., Primary Objective: The primary objective is to assess the efficacy of niraparib plus dostarlimab compared with chemotherapy in recurrent ovarian cancer patients not suitable for platinum treatment., Study Hypothesis: This trial will assess the hypothesis that niraparib plus dostarlimab therapy is effective to increase overall survival, progression-free survival, and time to first subsequent therapy respect to chemotherapy alone, with an acceptable toxicity profile., Trial Design: This is a phase III, multicenter trial, where recurrent ovarian cancer patients not eligible for platinum re-treatment will be randomized 1:1 to receive niraparib plus dostarlimab vs physician's choice chemotherapy until disease progression, intolerable toxicity, or withdrawal of patient consent. The study will be performed according to European Network for Gynaecological Oncological Trial groups (ENGOT) model B and patients will be recruited from 40 sites across MITO, CEEGOG, GINECO, HeCOG, MANGO, and NOGGO groups., Major Inclusion/exclusion Criteria: Eligible patients must have recurrent epithelial ovarian cancer not eligible for platinum retreatment. Patients who received previous treatment with poly-ADP ribose polymerase inhibitors and/or immune checkpoint inhibitors will be eligible. No more than two prior lines of treatment are allowed., Primary Endpoint: The primary endpoint is overall survival defined as the time from the randomization to the date of death by any cause., Sample Size: 427 patients will be randomized., Estimated Dates for Completing Accrual and Presenting Results: June 2024 TRIAL REGISTRATION NUMBER: NCT04679064., Competing Interests: Competing interests: VS reports personal financial interest with Roche, Pharmamar, Astrazeneca, MSD, Clovis, Tesaro, GSK, and EISAI. SP reports honoraria from GSK, Roche, AstraZeneca, MSD, Clovis, and Pharmamar. EB reports funded research from EU, BMBF, AstraZeneca, Roche Diagnostics, Bayer, and MSD, honoraria/travels from Roche, Amgen, MSD, Clovis, AstraZeneca, Tesaro, GSK, and Roche Diagnostics, consulting/advisory board for Amgen, AstraZeneca, Clovis, Eisai, GSK, MSD, Tesaro, Roche, and Seattle Genetics. DC has been part of the advisory board of Roche, AstraZeneca, Merck, GSK, and Sotio. NC reports personal financial interest with Pharmamar, AstraZeneca, Roche, MSD/Merck, Clovis Oncology, Tesaro/GSK, Novartis, Pfizer, Takeda, Biocad, Immonogen, Mersana, and EISAI, and institutional financial interests (Research Grants) with AstraZeneca, Pharmamar, and Roche. JSF has been part of the advisory board of Novartis, Pfizer, AstraZeneca, Lilly, Roche, Biocad, Daiichi, Tesaro, GSK, and Pierre Fabre. FZ reports honoraria for lectures and advisory role for AstraZeneca, Daiichi, Eli-Lilly, Merck, Novartis, and Pfizer. GS reports Grant/Research Support by MSD and consultant for Tesaro, Johnson & Johnson, and AstraZeneca. DL reports personal financial interests (advisory roles) with AstraZeneca, Clovis Oncology, Merck, Roche, Tesaro-GSK, Amgen, and Pharmamar, and institutional financial interests (Study Grants) with Tesaro/GSK, Merck, Roche, Pharmamar, and Clovis. Board of Directors, and GCIG (Gynecologic Cancer Inter Group)., (© IGCS and ESGO 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Olaparib is approved as maintenance therapy in patients with BRCA mutated platinum sensitive (PS) recurrent ovarian cancer (OC) after response to last platinum based therapy. Few data are available regarding the use out of the registration trials and on response to further treatments after progression., Materials Ad Methods: In this non interventional, retrospective study, patients treated with olaparib in 13 centers, according to the label, have been collected and analyzed. Primary objectives of the study are to describe effectiveness and safety of olaparib in a real world setting with a focus on post progression treatments and response., Results: 234 patients were analyzed. All patients were BRCA mutated and most of them had germline mutations. Around 50% of the patients received olaparib after 3 or more lines of platinum based chemotherapy achieving a radiologic complete (CR) or partial response. 12.4% patients with stable disease were also included. Median PFS was 14.7 months (95% CI:12.6-18), with statistically longer PFS in patients with normal serum Ca125 at baseline, a CR after last platinum based therapy and that received olaparib after second platinum based therapy. Median OS was not reached. Most frequent G3-G4 toxicity was anaemia (6%) with dose discontinuation and dose reduction in 11 (4.7%) and 49 (20.9%) of cases, respectively. Among 66 patients receiving further treatment after olaparib progression and evaluable for response, ORR was 22.2, 11.1% and 9.5% in patients with Platinum Free interval (PFI) of more than 12 months, between 6 and 12 months and less than 6 months, respectively., Conclusions: Olaparib is effective and safe in real world setting. Data on post-progression treatments seem to suggest cross resistance with chemotherapy and need to be confirmed in larger studies because of the potential importance in clinical practice decisions., (Copyright © 2019. Published by Elsevier Inc.)

Ovarian cancer is the fifth leading cause of cancer death among women and the most lethal gynecologic malignancy. Most women with advanced epithelial ovarian cancer will experience many episodes of recurrent disease with progressively shorter disease-free intervals. For women whose disease continues to respond to platinum-based drugs, the disease can often be controlled for 5 years or more. Enormous progress has been made in the management of this disease, and new targeted treatments such as antiangiogenic drugs, poly(adenosine diphosphate-ribose) polymerase inhibitors, and immune checkpoint inhibitors offer potential for improved survival. A variety of combination strategies are being evaluated to leverage these agents. The objective of this review is to summarize results from clinical trials that tested cytotoxic drugs and target strategies for the treatment of ovarian cancer with particular attention to Phase III and ongoing trials.

BACKGROUND Uterine arteriovenous malformation (AVM) is an uncommon lesion characterized by an abnormal connection between arterial and venous circulation that can be congenital or acquired. Acquired uterine AVMs are generally traumatic and follow delivery, abortion, curettage, or uterine surgery. CASE REPORT A 45-year-old female who was gravida 1 para 0 presented to our hospital with severe vaginal bleeding. Two weeks before, the patient underwent therapeutic abortion. At admission, a transvaginal ultrasound showed an unclear intrauterine lesion that spread out to the myometrium. Color Doppler evaluation demonstrated an elevated color score. Beta human chorionic gonadotropin (beta-hCG) levels were measured at admission and daily repeated, with a progressive decrease of values up to a negative level. A pelvic magnetic resonance imaging described an area of tubular and tortuous structures involving the myometrium. A computed tomography angiography confirmed the presence of a lesion infiltrating the endometrium and myometrium containing arteriovenous structures with a highly enhanced effect. Despite these findings, the patient was clinically stable. A diagnosis of uterine AVM was made and, after accurate counselling with the patient, she was discharged and underwent "watch and wait" management. After 35 days, the patient had a follow-up ultrasound that showed a complete resolution of the uterine lesion. CONCLUSIONS AVM should be considered in the presence of heavy and sudden vaginal bleeding in a patient with risk factors for acquired AVM. A color Doppler ultrasound scan should be performed as the first approach and an expectant management should be taken into account especially with a patient of childbearing age and hemodynamic instability.

Objective: The identification of patients with endometrial cancer (EC) at higher risk for relapse is critical to individualize and better tailor postoperative treatment. No evidence is available regarding the possible association between tumor size (TS) and the risk of local recurrence. The purpose of this study was to analyze the correlation between TS and risk/type of recurrence in EC patients, stratified according to the new European Society of Medical Oncology-European Society of Gynecological Oncology-European Society for Radiotherapy and Oncology classification., Methods: Data of patients with histologically proven EC who received primary surgical treatment between November 1999 and June 2015 were retrospectively retrieved from 5 institutions. Optimal TS cutoff was calculated using a receiver operating characteristic curve. Site of recurrence as a function of TS and groups of risk were analyzed. Local recurrence-free survival, recurrence-free survival, and overall survival were calculated using the Kaplan-Meier method., Results: Data of 1166 patients were analyzed. Among them, 514 (44.1%) had low-risk EC, 174 (14.9%) had intermediate risk EC, 173 (14.8%) had high-intermediate risk EC, and 305 (26.2%) had high-risk EC. A total of 134 (11.5%) women had recurrence: 47 (4%) of them had local relapse, 30 (2.6%) had locoregional relapse, and 57 (4.9%) had distant relapse. Tumor size 25 mm or greater emerged as the threshold for the prediction of a higher rate of local recurrence (P < 0.0001, hazard ratio = 18.2, P = 0.005) and a lower local recurrence-free survival and recurrence-free survival (P < 0.0001) only in patients with low-risk EC. There was no statistically significant correlation between TS and recurrence in the other risk groups., Conclusions: In this very large series, tumor size emerges as an independent prognostic factor of local recurrence in women with low-risk EC and could be a valuable additional criterion to personalize the treatment approach to these patients.

Introduction: The aim of the current study is to evaluate the detection rate of micro- and macro-metastases of the One-Step Nucleic Acid Amplification (OSNA) compared to frozen section examination and subsequent ultra-staging examination in early stage endometrial cancer (EC)., Material and Methods: From March 2016 to June 2016, data of 40 consecutive FIGO stage I EC patients were prospectively collected in an electronic database. The sentinel lymph node mapping was performed in all patients. All mapped nodes were removed and processed. Sentinel lymph nodes were sectioned and alternate sections were respectively examined by OSNA and by frozen section analysis. After frozen section, the residual tissue from each block was processed with step-level sections (each step at 200 micron) including H&E and IHC slides., Results: Sentinel lymph nodes mapping was successful in 29 patients (72.5%). In the remaining 11 patients (27.5%), a systematic pelvic lymphadenectomy was performed. OSNA assay sensitivity and specificity were 87.5% and 100% respectively. Positive and negative predictive values were 100% and 99% respectively, with a diagnostic accuracy of 99%. As far as frozen section examination and subsequent ultra-staging analysis was concerned, we reported sensitivity and specificity of 50% and 94.4% respectively; positive and negative predictive values were 14.3% and 99%, respectively, with an accuracy of 93.6%. In one patient, despite negative OSNA and frozen section analysis of the sentinel node, a macro-metastasis in 1 non-sentinel node was found., Conclusions: The combination of OSNA procedure with the sentinel lymph node mapping could represent an efficient intra-operative tool for the selection of early-stage EC patients to be submitted to systematic lymphadenectomy.

The aim of this study was to develop a scoring system of the immunohistochemical (IHC) expression of luteinizing hormone/human chorionic gonadotropin receptor (LHCG-R) in endometrial cancer (EC) patients. Nonconsecutive hysterectomy specimens containing EC collected from April 2013 to October 2015 were selected. Hematoxylin-eosin stained sections from each case were reviewed and representative sections from each tumor were selected. IHC staining was performed for the detection of LHCG-R. The percentage of stained cells and the staining intensity were assessed in order to develop an immunohistochemical score. Moreover, we examined the correlation of the score with grading and lymphovascular space invasion (LVSI). There was a statistically significant positive correlation between grading and IHC scoring ( p = 0.01) and a statistically significant positive correlation between LVSI and IHC score ( p < 0.01). In conclusion, we suggest that the immunohistochemical score presented here could be used as a marker of bad prognosis of EC patients. Nevertheless, further studies are needed in order to validate it. The study was registered in the Careggi Hospital public trials registry with the following number: 2013/0011391.

BACKGROUND Troponin I is the gold standard for the diagnosis of adult acute coronary syndrome. Although it is known that a hypoxic fetus may produce cTnI, fetal cTnI passage in maternal blood has never been documented. CASE REPORT We report a case where the rise of cTnI in the blood of a pregnant woman was not related to maternal heart disease. Instead, it might be suggestive of a fetal cardiac origin, as there was a severe placental insufficiency with a fetal intrauterine growth restriction. CONCLUSIONS This study suggests that the rise of cTnI in maternal blood in a cardiovascular healthy pregnant woman might have a fetal origin. After having excluded any maternal causes, cTnI elevation could be explained with the transfer of fetal cTnI through an injured placenta.

Purpose: The main aim of this study was to evaluate the incidence of endometriosis and intrahepatic cholestasis (ICP) and induction of labor in pregnant women with endometriosis compared with women without endometriosis. The secondary aim was to confirm increased incidence of already known endometriosis-related pregnancy complications in these patients., Methods: This is a retrospective cohort study performed at a tertiary hospital between January 2009 and December 2014 to compare obstetrics outcome between women with endometriosis and women without endometriosis. Pregnant patients with endometriosis were included in the study group. Patients were divided in the following subgroups: patients with deep infiltrating endometriosis (DIE subgroup) and patients without deep infiltrating endometriosis (non-DIE subgroup); patients with singleton pregnancy and spontaneous conception (subgroup A) and patients with multiple pregnancy and/or patients who underwent assisted reproductive technology (subgroup B). To form a control group, for each patient with endometriosis, two patients without endometriosis were selected as the control group by means of matched sample., Results: The study population included 262 pregnant women with endometriosis and 524 controls. Patients of the study population had significantly increased risks of placenta praevia (p < 0.05), ICP (p < 0.01), induction of labor (p < 0.01) and preterm birth (p < 0.01). DIE patients had a significantly higher percentage only of preterm birth (p < 0.01), while in non-DIE group all complications had a higher incidence except for placenta praevia, which did not differ with control. Subgroup A had a statistically higher incidence of placenta praevia (p < 0.01), ICP (p < 0.01), induction of labor (p < 0.01) and preterm birth (p < 0.01) compared to its control subgroup. There was no difference in distribution of pregnancy complications between subgroup B and control subgroup., Conclusions: Our results showed for the first time that women with endometriosis are at higher risk of developing ICP and experiencing an induced labor. Further studies are warranted to clarify whether the history of endometriosis might be taken into account in the antenatal care of these patients.