Publications by authors named "Giovanni Scambia"

952 Publications

GLUCOSE/INSULIN METABOLISM AND VITAMIN D IN WOMEN WITH RECURRENT PREGNANCY LOSS.

Am J Reprod Immunol 2021 Oct 23. Epub 2021 Oct 23.

Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, Milan, 20072, Italy.

Objective: Glucose/insulin metabolism has been related to recurrent pregnancy loss (RPL) through mechanisms not really clarified. Also, vitamin D deficiency seems to be associated to RPL. The purpose of our study was to evaluate the correlation between glucose/insulin metabolism parameters and vitamin D levels in women with history of RPL.

Study Design: Observational retrospective study on RPL women. The correlation between vitamin D levels and fasting glucose (FG), fasting insulin (FI), Homeostatic model assessment of insulin resistance (HOMA-IR) index, area under glucose curve (AUC-Glyc) and area under insulin curve (AUC-Ins), was evaluated.

Results: 127 RPL women were classified into three subgroups (0-1-2) according to the levels of FI. We found a statistically significant linear Pearson correlation between FI and HOMA-IR (r = 0.840; p = 0.001). An, inverse, but non-significant correlation both between vitamin D and FI (R = -0.202, ns) and vitamin D levels and AUC-Ins (R = -0.288, ns) was observed. The variables vitamin D, HOMA-IR and AUC-Ins were statistically significant in the considered subgroups (Vitamin D: ANOVA + Bonferroni test: 0 vs 1; P = 0.001; 0 vs 2; p = 0.010; 1 vs 2; p = 0.657; HOMA-IR: ANOVA + Bonferroni test: 0 vs 1; p = 0.014; 0 vs 2; p = 0.001; 1 vs 2; p = 0.001; AUC-Ins: ANOVA + Bonferroni test: 0 vs 1; p = 0.010; 0 vs 2; p = 0.206; 1 vs 2; p = 0.980).

Conclusions: Vitamin D might play additional roles in the pathogenesis of RPL, beyond its well known immunomodulatory role. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1111/aji.13505DOI Listing
October 2021

Breast Cancer Drug Approvals Issued by EMA: A Review of Clinical Trials.

Cancers (Basel) 2021 Oct 16;13(20). Epub 2021 Oct 16.

Scientific Directorate, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy.

Breast cancer represents the first cause of cancer worldwide and the leading cause of cancer mortality for women. Therefore, new therapies are needed to improve the prognosis of women diagnosed with this disease. In this review, we summarize the new drug indications for the treatment of breast cancer approved by European Medicines Agency between January 2015 and June 2021. In particular, we analyzed the clinical trials results leading to approvals and their update (when available), according to setting (localized and locally advanced or metastatic) and clinical features (hormone receptor positive, HER2 positive, triple negative, BRCA 1/2 mutation). The aim of this paper is to describe the clinical benefit obtained with the new indications.
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http://dx.doi.org/10.3390/cancers13205198DOI Listing
October 2021

PD-L1 Expression on Circulating Tumour-Derived Microvesicles as a Complementary Tool for Stratification of High-Grade Serous Ovarian Cancer Patients.

Cancers (Basel) 2021 Oct 16;13(20). Epub 2021 Oct 16.

Department of Women, Children and Public Health Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy.

Background: Ovarian cancer (OC) has recently attracted attention for the use of PD-1/PD-L1 axis blocking agents, with durable activity reported only in a subset of patients. The most used biomarker for sensitivity to the PD-1/PD-L1 axis blockade is tumour PD-L1 status by immunohistochemistry. However, patient stratification using this method suffers from intrinsic heterogeneity of OC, likely contributing to the unsatisfactory results obtained so far. Cells communicate with each other by releasing microvesicles (MVs) that carry parental cell surface features. Thus, we hypothesised that PD-L1 tumour cells (TC) and infiltrating PD-L1 leukocytes should shed MVs carrying surface PD-L1 that may serve as a proxy for the whole tumour PD-L1 status.

Results: We showed for the first time the presence of measurable amounts of TC- and leukocyte-derived PD-L1 MVs (range: 1.4-178.8 MVs/μL and 6.2-504.8 MVs/μL, respectively) in the plasma of high-grade serous OC (HGSOC) patients ( = 63), using a sensitive flow cytometry platform. The concentration of PD-L1 MVs of either origin did not associate with the PD-L1 status of TCs and leukocytes in the tumour biopsies, suggesting that the circulating PD-L1 MVs also included ones from locations not selected for immunohistochemistry analysis and represented the PD-L1 status of the whole tumour mass. In this study, we also describe the serendipitous discovery of circulating PD-L1 MVs of platelet origin (10.3-2409.6 MVs/μL).

Conclusions: The enumeration of circulating PD-L1 MVs in HGSOC patients may provide a novel direction for assessing the tumour PD-L1 status and contribute to HGSOC patient stratification for immunotherapy interventions. The presence of circulating PD-L1 MVs of platelet origin, a finding not yet reported in HGSOC patients, warrants further studies.
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http://dx.doi.org/10.3390/cancers13205200DOI Listing
October 2021

Evaluation of Angiogenesis-Related Genes as Prognostic Biomarkers of Bevacizumab Treated Ovarian Cancer Patients: Results from the Phase IV MITO16A/ManGO OV-2 Translational Study.

Cancers (Basel) 2021 Oct 14;13(20). Epub 2021 Oct 14.

Molecular Oncology Unit, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, National Cancer Institute, 33081 Aviano, Italy.

Background: Epithelial ovarian cancer (EOC) is a rare, highly lethal disease. In a subset of high grade EOC patients, maintenance therapy with the antiangiogenic drug Bevacizumab (BEV) is a valuable option. To date, no validated predictive or prognostic biomarkers exist for selecting EOC patients that might benefit from BEV treatment.

Methods: Immunohistochemistry and RT-qPCR evaluated the expression of seven angiogenesis-related proteins and of a twelve microRNAs angio-signature in EOC patients, treated in first line with chemotherapy plus BEV (MITO16A/ManGO OV-2 phase IV trial). Centralized statistical analyses assessed the associations between each biomarker, clinical prognostic factors and survival outcomes.

Results: High miR-484 expression was associated with longer progression-free and overall survival. Notably, the combined expression of miR-484 and its target VEGFB identified a subset of patients that might mostly benefit from BEV treatment. No other significant correlations were found between the other analyzed biomarkers and patients' survival. The application of a shrinkage procedure to adjust for over-fitting hazard ratio estimates reduced the association significance.

Conclusions: The analysis of angiogenesis related biomarkers in EOC patients homogenously treated with BEV in first line provides novel insight in their prognostic value and suggests that some of them might merit to be tested as predictive markers of drug activity in dedicated randomized trials.
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http://dx.doi.org/10.3390/cancers13205152DOI Listing
October 2021

CD93 a potential player in cytotrophoblast and endothelial cell migration.

Cell Tissue Res 2021 Oct 21. Epub 2021 Oct 21.

Department of Experimental and Clinical Medicine, Università Politecnica Delle Marche, 60126, Ancona, Italy.

CD93, also known as complement component C1q receptor, is expressed on the surface of different cellular types such as monocytes, neutrophils, platelets, microglia, and endothelial cells, and it plays a pivotal role in cell proliferation, cell migration, and formation of capillary-like structures. These processes are strictly regulated, and many fetal and maternal players are involved during placental development. At present, there are no studies in literature regarding CD93 in placental development, so we investigated CD93 expression in first and third trimester and PE placentas by immunohistochemistry and western blotting analysis. In addition, we performed in vitro experiments under oxidative stress conditions to demonstrate how oxidative stress acts on CD93 protein expression. Our data showed that CD93 was expressed in villous cytotrophoblast cells, in some fetal vessels of first and third trimester and PE placentas and in the extravillous cytotrophoblast of cell columns in the first trimester placentas. Moreover, we detected a significant decrease of CD93 expression in third trimester and PE placentas compared to first trimester placentas, while no differences were detected between third and PE placentas. No differences of CD93 expression were detected in oxidative stress conditions. We suggest that CD93 can guide extravillous cytotrophoblast migration through β1-integrin in uterine spiral arteries during placentation in the first trimester of pregnancy and that the decrease of CD93 expression in third trimester and PE placentas could be linked to the poor extravillous cytotrophoblast cells migration. So, it might be interesting to understand the role of CD93 in the first phases of PE onset.
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http://dx.doi.org/10.1007/s00441-021-03543-3DOI Listing
October 2021

Pearls and Potential Pitfalls for Correct Diagnosis of Ovarian Cystadenofibroma in MRI: A Pictorial Essay.

Korean J Radiol 2021 Sep 24. Epub 2021 Sep 24.

Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A Gemelli IRCCS, Rome, Italy.

Ovarian cystadenofibroma is a benign ovarian tumor that is characterized by a consistent percentage of masses, which remain indeterminate in ultrasonography and require magnetic resonance (MR) investigation; they may mimic borderline or malignant lesions. Three main morphologic patterns, resembling different ovarian neoplasms, can be identified in cystadenofibromas: multilocular solid lesions, unilocular cystic lesions with parietal thickening, and purely cystic masses. However, a cystoadenofibroma has typical features, such as T2-weighted hypointensity associated with no restrictions in diffusion-weighted imaging (the so-called "dark-dark appearance") and progressive post-contrast enhancement (type I perfusion curve). The purpose of this study was to review the features of ovarian cystadenofibromas in MR imaging and to suggest pearls and pitfalls regarding their correct diagnosis.
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http://dx.doi.org/10.3348/kjr.2020.1312DOI Listing
September 2021

Evolution of Clinical Trials in Ovarian Cancer Management over the Past 20 Years: Never Settle Down, Always Go Beyond.

J Oncol 2021 7;2021:1682532. Epub 2021 Oct 7.

Department of Woman, Child and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

Purpose: A practice synthesis of available evidence-based medicine data in ovarian cancer (OC), aiming to provide directions for future research.

Materials And Methods: We performed a systematic review. PubMed was searched for relevant OC trials between January 2000 and December 2019.

Results: Out of 865 references screened, 199 trials were found eligible for inclusion. Most trials were multicenter (83.9%). There was a trend reduction in the number of patients enrolled/per study over the years. Studies testing targeted/biological therapies dominated the second decade (60 trials in 2010-2019 versus 2 trials in 2000-2009). The proportion of trials with positive survival and clinical outcomes significantly increased from 23.8% in early 2000s to 54.1% in the last 5 years. Trials with histology/molecular biomarker criteria were more likely to meet progression-free survival endpoint than those without these selection criteria (69.2% versus 32.6%).

Conclusion: This systematic review suggests a trend of increased positive studies, mainly linked to precision medicine.
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http://dx.doi.org/10.1155/2021/1682532DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8516526PMC
October 2021

Infiltrating T lymphocytes and programmed cell death protein-1/programmed death-ligand 1 expression in endometriosis-associated ovarian cancer.

Fertil Steril 2021 Oct 13. Epub 2021 Oct 13.

Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Dipartimento per le Scienze della salute della donna, del bambino e di Sanità Pubblica, Roma, Italia; Università Cattolica del Sacro Cuore, Roma, Italia.

Objective: To characterize T lymphocyte infiltration and programmed cell death protein-1 (PD-1)/programmed death-ligand 1 (PD-L1) expression in early-stage endometriosis-associated ovarian cancer (EAOC), ovarian endometriosis (OE), atypical endometriosis (AE), and deep endometriosis (DE).

Design: Case-control, retrospective study.

Setting: Research University Hospital.

Patient(s): A total of 362 patients with a histologic diagnosis of EAOC, OE, AE, or DE were identified between 2000 and 2019 from Fondazione Policlinico Universitario Agostino Gemelli IRCCS and Gemelli Molise SpA tissue data banks. A 1:1 propensity score-matched method yielded matched pairs of 55 subjects with EAOC, 55 patients with OE, 12 patients with AE, and 42 patients with DE, resulting in no differences in family history of cancer, parity, and use of oral contraceptives.

Intervention(s): Immunohistochemistry assays using the following primary antibodies: CD3+; CD4+; CD8+; PD-1; and PD-L1.

Main Outcome Measure(s): To characterize T lymphocyte infiltration and PD-1/PD-L1 expression in 4 different endometriosis-related diseases.

Result(s): Endometriosis-associated ovarian cancer cases displayed significantly higher levels of PD-1/PD-L1 expression compared with all other endometriosis-related diseases (vs. OE vs. AE vs. DE). Moreover, a significantly lower count of infiltrating T lymphocytes was observed in EAOC cases compared with OE ones. Finally, one-third of OE cases showed a cancer-like PD-1/PD-L1 expression profile.

Conclusion(s): Endometriosis-associated ovarian cancer is characterized by higher levels of PD-1/PD-L1 expression compared with benign endometriosis-related diseases. This profile was found in one-third of clinically benign cases, suggesting that it develops early in the carcinogenesis process.
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http://dx.doi.org/10.1016/j.fertnstert.2021.08.032DOI Listing
October 2021

Anti-inflammatory therapy in ischaemic heart disease: from canakinumab to colchicine.

Eur Heart J Suppl 2021 Oct 8;23(Suppl E):E13-E18. Epub 2021 Oct 8.

Università Cattolica del Sacro Cuore, Rome, Italy.

Four large trials have recently evaluated the effects of anti-inflammatory drugs in the secondary prevention of major cardiovascular events (MACE) in over 25 000 patients followed for 1.9-3.7 years. CANTOS tested subcutaneous canakinumab [an anti-interleukin (IL) 1β antibody] 300 mg every 3 months against placebo in patients with a history of myocardial infarction (MI) and serum C-reactive protein (CRP) >2 mg/L, demonstrating efficacy in preventing MACE but increased rates of fatal infections. COLCOT (in patients with recent MI) and LoDoCo2 (in patients with chronic coronary syndromes) tested oral colchicine (an NLRP3 inflammasome inhibitor) 0.5 mg daily vs. placebo, demonstrating prevention of MACE with a slightly increased risk of pneumonia in COLCOT (0.9 vs. 0.4%) but not in LoDoCo2. CIRT tested oral methotrexate (an anti-rheumatic anti-nuclear factor-kB) 15-20 mg per week against placebo in ischaemic heart disease patients with diabetes or metabolic syndrome, without significant reduction in MACE rates or in circulating IL6 or CRP levels, and with increased risk of skin cancers. In summary, canakinumab and colchicine have shown efficacy in preventing MACE in ischaemic heart disease patients, but only colchicine has acceptable safety (and cost) for use in secondary cardiovascular prevention. Clinical results are expected with the anti-IL6 ziltivekimab.
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http://dx.doi.org/10.1093/eurheartj/suab084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8503530PMC
October 2021

Tumor BRCA testing in ovarian cancer and EQA scheme: our experience of a critical evaluation.

Mol Biol Rep 2021 Oct 13. Epub 2021 Oct 13.

Molecular and Genomic Diagnostics Unit (MGDUnit), Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

Next generation sequencing (NGS) is a widespread molecular biology method integrated into clinical practice to detect genetic variants, for diagnostic and prognostic purposes. The scheduled external quality assessments (EQA) is integral part of clinical molecular laboratory quality assurance. The EQA provides an efficient system to compare analytic test performances among different laboratories, which is essential to evaluate consistency of molecular test. EQA failures demands targeted corrective action plans. In this context, the complexity of the NGS techniques requires careful and continuous quality control procedures. We report a tumor BRCA1/2 (tBRCA) testing benchmark discrepancy provided by the European Molecular Genetics Quality Network in our laboratory during a round of EQA for somatic mutation testing of BRCA genes in relation to ovarian cancer. The critical analysis emerging from the tBRCA EQA is presented. We underline that harmonization processes are still required for the EQA in the molecular biology field, especially if applied to the evaluation of methods characterized by high complexity.
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http://dx.doi.org/10.1007/s11033-021-06812-0DOI Listing
October 2021

Stat1 confers sensitivity to radiation in cervical cancer cells by controlling Parp1 levels: a new perspective for Parp1 inhibition.

Cell Death Dis 2021 Oct 12;12(10):933. Epub 2021 Oct 12.

Unità di Medicina Traslazionale per la Salute della Donna e del Bambino, Dipartimento Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Roma, Italia.

Cervical cancer (CC) is the fourth most common cause of cancer-related death in women. According to international guidelines, a standard treatment for locally advanced cervical cancer (LACC) consists of exclusive concurrent chemoradiation treatment (CRT). However, chemoradioresistance and subsequent relapse and metastasis of cancer occur in many patients, and survival for these women has generally remained poor. Therefore, strategies to overcome resistance are urgently needed. We have recently reported a radiosensitizing effect of the signal transducer and activator of transcription 1 (STAT1) in CC, associated with the control of [Poly(ADP-ribose) polymerase -1] PARP1 levels, a key factor in cell response to DNA damage induced by radiation. Here, we sought to decipher the underlying mechanism of STAT1-mediated control of PARP1, elucidating its role as a radiosensitizer in CC. Functional and molecular biology studies demonstrated that STAT1 may act at both transcriptional and posttranscriptional levels to modulate PARP1 expression in CC cells. In light of these results, we tested the effect of Olaparib in sensitizing CC cells to radiation and investigated signaling pathways involved in the activity observed. Results showed that PARP1 inhibition, at clinically achievable doses, may indeed selectively improve the sensitivity of resistant CC cells to DNA-damaging treatment. The translational relevance of our findings was supported by preliminary results in a limited patient cohort, confirming that higher PARP1 levels are significantly associated with a radioresistant phenotype. Finally, bioinformatics analysis of GEPIA and TCGA databases, demonstrated that PARP1 mRNA is higher in CC than in normal tissues and that increased PARP1 mRNA expression levels are associated with poor prognosis of LACC patients. Overall, our data open new opportunities for the development of personalized treatments in women diagnosed with CC.
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http://dx.doi.org/10.1038/s41419-021-04229-yDOI Listing
October 2021

Comparison Between Laparoscopic and Robotic Surgery in Elderly Patients With Endometrial Cancer: A Retrospective Multicentric Study.

Front Oncol 2021 22;11:724886. Epub 2021 Sep 22.

Dipartimento Scienze della Salute della Donna, del Bambino, e di Sanità Pubblica, Ginecologia Oncologica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

Introduction: Elderly endometrial cancer (EEC) patients represent a challenging clinical situation because of the increasing number of clinical morbidities. In this setting of patients, minimally invasive surgery (MIS) has been shown to improve surgical and clinical outcomes. The aim of this study was to evaluate the peri-operative and oncological outcomes of EEC patients who had undergone laparoscopic (LS) or robotic surgery (RS).

Materials And Methods: This is a retrospective multi-institutional study in which endometrial cancer patients of 70 years or older who had undergone MIS for EC from April 2002 to October 2018 were considered. Owing to the non-randomized nature of the study design and the possible allocation biases arising from the retrospective comparison between LS and RS groups, we also performed a propensity score-matched analysis (PSMA).

Results: A total of 537 patients with EC were included in the study: 346 who underwent LS and 191 who underwent RS. No significant statistical differences were found between the two groups in terms of surgical and survival outcomes. 188 were analyzed after PSMA (94 patients in the LS group were matched with 94 patients in the RS group). The median estimated blood loss was higher in the LS group (p=0.001) and the median operative time was higher in the RS group (p=0.0003). No differences emerged between LS and RS in terms of disease free survival (DFS) (p=0.890) and overall survival (OS) (p=0.683).

Conclusions: Our study showed that when compared LS and RS, RS showed lower blood losses and higher operative times. However, none of the two approaches demonstrated to be superior in terms of survival outcomes. For this reason, each patient should be evaluated individually to determine the best surgical approach.
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http://dx.doi.org/10.3389/fonc.2021.724886DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8493293PMC
September 2021

Hypotension Prediction Index with non-invasive continuous arterial pressure waveforms (ClearSight): clinical performance in Gynaecologic Oncologic Surgery.

J Clin Monit Comput 2021 Oct 7. Epub 2021 Oct 7.

Department of Scienze dell'Emergenza, Anestesiologiche e della Rianimazione, IRCCS Fondazione Policlinico A. Gemelli, Rome, Italy.

Intraoperative hypotension (IOH) is common during major surgery and is associated with a poor postoperative outcome. Hypotension Prediction Index (HPI) is an algorithm derived from machine learning that uses the arterial waveform to predict IOH. The aim of this study was to assess the diagnostic ability of HPI working with non-invasive ClearSight system in predicting impending hypotension in patients undergoing major gynaecologic oncologic surgery (GOS). In this retrospective analysis hemodynamic data were downloaded from an Edwards Lifesciences HemoSphere platform and analysed. Receiver operating characteristic curves were constructed to evaluate the performance of HPI working on the ClearSight pressure waveform in predicting hypotensive events, defined as mean arterial pressure < 65 mmHg for > 1 min. Sensitivity, specificity, positive predictive value and negative predictive value were computed at a cutpoint (the value which minimizes the difference between sensitivity and specificity). Thirty-one patients undergoing GOS were included in the analysis, 28 of which had complete data set. The HPI predicted hypotensive events with a sensitivity of 0.85 [95% confidence interval (CI) 0.73-0.94] and specificity of 0.85 (95% CI 0.74-0.95) 15 min before the event [area under the curve (AUC) 0.95 (95% CI 0.89-0.99)]; with a sensitivity of 0.82 (95% CI 0.71-0.92) and specificity of 0.83 (95% CI 0.71-0.93) 10 min before the event [AUC 0.9 (95% CI 0.83-0.97)]; and with a sensitivity of 0.86 (95% CI 0.78-0.93) and specificity 0.86 (95% CI 0.77-0.94) 5 min before the event [AUC 0.93 (95% CI 0.89-0.97)]. HPI provides accurate and continuous prediction of impending IOH before its occurrence in patients undergoing GOS in general anesthesia.
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http://dx.doi.org/10.1007/s10877-021-00763-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8496438PMC
October 2021

Randomized phase III trial on niraparib-TSR-042 (dostarlimab) versus physician's choice chemotherapy in recurrent ovarian, fallopian tube, or primary peritoneal cancer patients not candidate for platinum retreatment: NItCHE trial (MITO 33).

Int J Gynecol Cancer 2021 Oct;31(10):1369-1373

Department of Women and Child Health, Division of Gynaecologic Oncology, Policlinico Universitario Fondazione Agostino Gemelli, IRCCS, Rome, Lazio, Italy

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.
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http://dx.doi.org/10.1136/ijgc-2021-002593DOI Listing
October 2021

Practice changes in Italian Gynaecologic Units during the COVID-19 pandemic: a survey study.

J Obstet Gynaecol 2021 Sep 28:1-8. Epub 2021 Sep 28.

Department of Obstetrics and Gynaecology, AOUI Verona, University of Verona, Verona, Italy.

The impact of Coronavirus disease 2019 pandemic on Italian Gynaecological Units practice and the compliance and satisfaction with available guidelines/recommendations is unknown. Therefore, a survey was conducted among all Italian Gynaecological Units Directors in April 2020. The response rate was 90% (135/150). 77.8% of centres performed surgery only for oncologic or not deferrable pathologies, and 9.6% was closed. 68.7% of directors were at least moderately satisfied by published guidelines/recommendations, but 94.8% of respondents identified limitations, mainly (83%) the absent definition of benign non-deferrable pathology. Responders considered as non-deferrable severe endometriosis (69.6%), endometriosis with organ failure/dysfunction (74.1%), and unresponsive symptomatic fibroids (89.6%). Despite guidelines/recommendations, respondents treated ovarian (77%) and endometrial (71.6%) cancer as usual. Only a minority of respondents reduced the laparoscopic approach (11.2%) and adopted all recommended surgical precautions (9.6%). Compliance with available guidelines/recommendations appears incomplete. Reconsidering guidelines/recommendations regarding oncological cases and specify non-deferrable benign pathologies would improve guidelines/recommendations compliance.Impact statement The SARS-CoV-2 pandemic has profoundly influenced medical routine practice worldwide. Surgery units have been forced to reduce or even completely restrict their activity to re-allocate human resources. Many major international gynaecological societies have released statements and guidelines, providing various recommendations to guide practice changes. However, the impact of the SARS-CoV-2 pandemic on Italian Gynaecological Units practice and the compliance and satisfaction with available guidelines/recommendations is unknown. Study results provide evidence showing how the SARS-CoV-2 pandemic has changed surgical activity in the Italian Gynaecological Units. Most centres reduced surgical activity, limiting surgery only for oncologic or not deferrable pathologies. Moreover, our research shows the level of compliance and satisfaction with available guidelines/recommendations and where they need to be improved. Most directors were at least moderately satisfied but identified different limitations. Guidelines/recommendations do not provide enough details, such as the absent definition of benign non-deferrable pathologies. The limited compliance with available guidelines/recommendations and identified limitations suggest reconsidering guidelines/recommendations focussing on identified gaps. Provide more details, such as specifying non-deferrable benign pathologies, would improve guidelines/recommendations compliance.
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http://dx.doi.org/10.1080/01443615.2021.1954149DOI Listing
September 2021

Refining Adjuvant Therapy for Endometrial Cancer: New Standards and Perspectives.

Biology (Basel) 2021 Aug 30;10(9). Epub 2021 Aug 30.

Institute of Obstetrics and Gynecology, Università Cattolica del Sacro Cuore, Largo Agostino Gemelli 8, 00168 Rome, Italy.

Endometrial carcinoma is the most frequent cancer of the reproductive female organs. Most endometrial cancers are diagnosed at early stage (75%). Treatment options depend on pathogenetic, histopathologic and clinical characteristic at the diagnosis. To improve patient management in the near future, recent research has focused on new molecular features; evidence has shown that these give a better definition of patient prognosis and can help in tailoring adjuvant treatments by identifying specific subgroups of patients whose tumors may benefit from specific therapeutic approaches. In this review, we will focus on current knowledge of adjuvant treatment of endometrial carcinoma, using a prognostic-risk group stratification based on pathogenetic, clinical and molecular features, and will take a look at the ongoing trials that will further change the therapeutic approach in coming years.
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http://dx.doi.org/10.3390/biology10090845DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8470828PMC
August 2021

A Multicentric Randomized Trial to Evaluate the ROle of Uterine MANipulator on Laparoscopic/Robotic HYsterectomy for the Treatment of Early-Stage Endometrial Cancer: The ROMANHY Trial.

Front Oncol 2021 10;11:720894. Epub 2021 Sep 10.

Division of Gynecologic Oncology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

Objective: This prospective randomized trial aimed to assess the impact of the uterine manipulator in terms of lymph vascular space invasion (LVSI) in patients undergoing minimally invasive staging for early-stage endometrial cancer.

Methods: In this multicentric randomized trial, enrolled patients were randomly allocated in two groups according to the no use (arm A) or the use (arm B) of the uterine manipulator. Inclusion criteria were G1-G2 early-stage endometrial cancer at preoperative evaluation. The variables collected included baseline demographic characteristics, perioperative data, final pathology report, adjuvant treatment, and follow-up.

Results: In the study, 154 patients (76 in arm A and 78 in arm B) were finally included. No significant differences were recorded regarding the baseline characteristics. A statistically significant difference was found in operative time for the laparoscopic staging (p=0.005), while no differences were reported for the robotic procedures (p=0.419). The estimated blood loss was significantly lower in arm A (p=0.030). No statistically significant differences were recorded between the two study groups in terms of peritoneal cytology, LVSI (p=0.501), and pattern of LVSI (p=0.790). No differences were detected in terms of overall survival and disease-free survival (p=0.996 and p=0.480, respectively). Similarly, no differences were recorded in the number of recurrences, 6 (7.9%) in arm A and 4 (5.2%) in arm B (p=0.486). The use of the uterine manipulator had no impact on DFS both at univariable and multivariable analyses.

Conclusions: The intrauterine manipulator does not affect the LVSI in early-stage endometrial cancer patients undergoing laparoscopic/robotic staging.

Clinical Trial Registration: https://clinicaltrials.gov, identifier (NCT: 02762214).
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http://dx.doi.org/10.3389/fonc.2021.720894DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8461311PMC
September 2021

Maintenance treatment with rucaparib for recurrent ovarian carcinoma in ARIEL3, a randomized phase 3 trial: The effects of best response to last platinum-based regimen and disease at baseline on efficacy and safety.

Cancer Med 2021 Oct 21;10(20):7162-7173. Epub 2021 Sep 21.

Department of Gynecologic Oncology and Reproductive Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

Background: The efficacy and safety of rucaparib maintenance treatment in ARIEL3 were evaluated in subgroups based on best response to most recent platinum-based chemotherapy and baseline disease.

Methods: Patients were randomized 2:1 to receive either oral rucaparib at a dosage of 600 mg twice daily or placebo. Investigator-assessed PFS was assessed in prespecified, nested cohorts: BRCA-mutated, homologous recombination deficient (HRD; BRCA mutated or wild-type BRCA/high loss of heterozygosity), and the intent-to-treat (ITT) population.

Results: Median PFS for patients in the ITT population with a complete response to most recent platinum-based chemotherapy was 11.1 months in the rucaparib arm (126 patients) versus 5.6 months in the placebo arm (64 patients) (HR, 0.33 [95% CI, 0.23-0.48]), and in patients with a partial response (249 vs. 125), it was 9.0 versus 5.3 months (HR, 0.38 [0.30-0.49]). In subgroups of the ITT population based on baseline disease, median PFS was 8.2 versus 5.3 months (HR, 0.40 [0.28-0.57]) in patients with measurable disease (141 rucaparib vs. 66 placebo), 10.4 versus 4.5 months (HR, 0.31 [0.20-0.48]) in those with nonmeasurable but evaluable disease (104 vs. 56), and 14.1 versus 7.3 months (HR, 0.35 [0.24-0.51]) in those with no residual disease (130 vs. 67). Across subgroups, significantly longer median PFS was observed with rucaparib versus placebo in the BRCA-mutated and HRD cohorts. Objective responses were reported in patients with measurable disease and in patients with nonmeasurable but evaluable baseline disease. Safety was consistent across subgroups.

Conclusion: Rucaparib maintenance treatment provided clinically meaningful efficacy benefits across subgroups based on response to last platinum-based chemotherapy or baseline disease.
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http://dx.doi.org/10.1002/cam4.4260DOI Listing
October 2021

Adjuvant Treatment Recommendations in Early-Stage Endometrial Cancer: What Changes With the Introduction of The Integrated Molecular-Based Risk Assessment.

Front Oncol 2021 1;11:612450. Epub 2021 Sep 1.

Direzione Scientifica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

Adjuvant therapy recommendations for endometrial cancer were historically based on the individual patient's risk of disease recurrence using clinicopathologic factors such as age, stage, histologic subtype, tumor grade, and lymphovascular space invasion. Despite the excellent prognosis for early stages, considerable under- and overtreatment remains. Integrated genomic characterization by the Cancer Genome Atlas (TCGA) in 2013 defined four distinct endometrial cancer subgroups (POLE mutated, microsatellite instability, low copy number, and high copy number) with possible prognostic value. The validation of surrogate markers (p53, Mismatch repair deficiency, and POLE) to determine these subgroups and the addition of other molecular prognosticators (CTNNB1, L1CAM) resulted in a practical and clinically useful molecular classification tool. The incorporation of such molecular alterations into established clinicopathologic risk factors resulted in a refined, improved risk assessment. Thus, the ESGO/ESTRO/ESP consensus in 2020 defined for the first time different prognostic risk groups integrating molecular markers. Finally, the feasibility and clinical utility of molecular profiling for tailoring adjuvant therapy in the high-intermediate-risk group is currently under investigation (NCT03469674).
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http://dx.doi.org/10.3389/fonc.2021.612450DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8442623PMC
September 2021

Circulating Placental Vesicles Carry HLA-DR in Pre-Eclampsia: A New Potential Marker of the Syndrome.

Front Immunol 2021 3;12:717879. Epub 2021 Sep 3.

Department of Biomedical Sciences, Humanitas University, Milan, Italy.

Background: Pre-eclampsia (PE) is a common disorder of pregnancy that usually presents with hypertension and proteinuria. The clinical presentation arises from soluble factors released into the maternal circulation from the placenta owing to the stress of syncytiotrophoblast, consequence of defective placentation occurring in the first half of pregnancy. Reduced tolerance of the semiallogeneic fetus by the maternal immune system has been proposed as first trigger leading to poor placentation. We previously observed aberrant expression of human leukocyte antigen (HLA)-DR molecules in the syncytiotrophoblast of a subset of women with PE. Aim of this study was to investigate abnormal expression of circulating HLA-DR in syncytiotrophoblast-derived extracellular vesicles (STBEVs) in women with PE compared to normal pregnant women.

Methods: peripheral venous blood was collected from 22 women with PE and 22 normal pregnant women. Circulating STBEVs were collected by ultra-centrifugation (120000 g) and analyzed for the expression of HLA-DR and placental alkaline phosphatase (PLAP), a specific marker of the placenta, by Western blot analysis and flow cytometry.

Results: circulating STBEVs positive for HLA-DR were observed in 64% of PE women while no HLA-DR positivity was detected in any of the controls (P<0.01).

Conclusions: Aberrant expression of HLA-DR in circulating STBEVs is specifically associated to PE. Further studies are required: a) to define the role of aberrant placental expression of HLA-DR molecules in the pathogenesis of PE; b) evaluate a possible application of detecting circulating HLA-DR positive STBEVs in the diagnosis and prediction of PE in the first and second trimester of pregnancy.
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http://dx.doi.org/10.3389/fimmu.2021.717879DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8446281PMC
September 2021

Lurbinectedin versus pegylated liposomal doxorubicin or topotecan in patients with platinum-resistant ovarian cancer: A multicenter, randomized, controlled, open-label phase 3 study (CORAIL).

Gynecol Oncol 2021 Sep 11. Epub 2021 Sep 11.

Fondazione IRCCS - Istituto Nazionale dei Tumori, Milano, and Fondazione Policlinico Gemelli IRCCS, Rome, Italy.

Objective: The randomized phase 3 CORAIL trial evaluated whether lurbinectedin improved progression-free survival (PFS) compared to pegylated liposomal doxorubicin (PLD) or topotecan in patients with platinum-resistant ovarian cancer.

Methods: Patients were randomly assigned (1:1) to lurbinectedin 3.2 mg/m 1-h i.v. infusion q3wk (experimental arm), versus PLD 50 mg/m 1-h i.v. infusion q4wk or topotecan 1.50 mg/m 30-min i.v. infusion Days 1-5 q3wk (control arm). Stratification factors were PS (0 vs. ≥1), prior PFI (1-3 months vs. >3 months), and prior chemotherapy lines (1-2 vs. 3). The primary endpoint was PFS by Independent Review Committee in all randomized patients. This study was registered with ClinicalTrials.gov, NCT02421588.

Results: 442 patients were randomized: 221 in lurbinectedin arm and 221 in control arm (127 PLD and 94 topotecan). With a median follow-up of 25.6 months, median PFS was 3.5 months (95% CI, 2.1-3.7) in the lurbinectedin arm and 3.6 months (95% CI, 2.7-3.8) in the control arm (stratified log-rank p = 0.6294; HR = 1.057). Grade ≥ 3 treatment-related adverse events (AEs) were most frequent in the control arm: 64.8% vs. 47.9% (p = 0.0005), mainly due to hematological toxicities. The most common grade ≥ 3 AEs were: fatigue (7.3% of patients) and nausea (5.9%) with lurbinectedin; mucosal inflammation (8.5%) and fatigue (8.0%) in the control arm.

Conclusions: The primary endpoint of improvement in PFS was not met. Lurbinectedin showed similar antitumor efficacy and was better tolerated than current standard of care in patients with platinum-resistant ovarian cancer.
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http://dx.doi.org/10.1016/j.ygyno.2021.08.032DOI Listing
September 2021

ConCerv: a prospective trial of conservative surgery for low-risk early-stage cervical cancer.

Int J Gynecol Cancer 2021 Oct 7;31(10):1317-1325. Epub 2021 Sep 7.

Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

Objective: The objective of the ConCerv Trial was to prospectively evaluate the feasibility of conservative surgery in women with early-stage, low-risk cervical cancer.

Methods: From April 2010 to March 2019, a prospective, single-arm, multicenter study evaluated conservative surgery in participants from 16 sites in nine countries. Eligibility criteria included: (1) FIGO 2009 stage IA2-IB1 cervical carcinoma; (2) squamous cell (any grade) or adenocarcinoma (grade 1 or 2 only) histology; (3) tumor size 2 cm; (4) no lymphovascular space invasion; (5) depth of invasion 10 mm; (6) negative imaging for metastatic disease; and (7) negative conization margins. Cervical conization was performed to determine eligibility, with one repeat cone permitted. Eligible women desiring fertility preservation underwent a second surgery with pelvic lymph node assessment, consisting of sentinel lymph node biopsy and/or full pelvic lymph node dissection. Those not desiring fertility preservation underwent simple hysterectomy with lymph node assessment. Women who had undergone an 'inadvertent' simple hysterectomy with an unexpected post-operative diagnosis of cancer were also eligible if they met the above inclusion criteria and underwent a second surgery with pelvic lymph node dissection only.

Results: 100 evaluable patients were enrolled. Median age at surgery was 38 years (range 23-67). Stage was IA2 (33%) and IB1 (67%). Surgery included conization followed by lymph node assessment in 44 women, conization followed by simple hysterectomy with lymph node assessment in 40 women, and inadvertent simple hysterectomy followed by lymph node dissection in 16 women. Positive lymph nodes were noted in 5 patients (5%). Residual disease in the post-conization hysterectomy specimen was noted in 1/40 patients-that is, an immediate failure rate of 2.5%. Median follow-up was 36.3 months (range 0.0-68.3). Three patients developed recurrent disease within 2 years of surgery-that is, a cumulative incidence of 3.5% (95% CI 0.9% to 9.0%).

Discussion: Our prospective data show that select patients with early-stage, low-risk cervical carcinoma may be offered conservative surgery.
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http://dx.doi.org/10.1136/ijgc-2021-002921DOI Listing
October 2021

Chemotherapy resistance in epithelial ovarian cancer: Mechanisms and emerging treatments.

Semin Cancer Biol 2021 Aug 28. Epub 2021 Aug 28.

Division of Gynecologic Oncology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy; Department Woman and Child Health Sciences, Catholic University of the Sacred Heart, Rome, Italy.

Ovarian cancer (OC) remains a fatal malignancy because most patients experience recurrent disease, which is resistant to chemotherapy. The outcomes for patients with platinum-resistant OC are poor, response rates to further chemotherapy are low and median survival is lower than 12 months. The complexity of platinum-resistant OC, which comprises a heterogeneous spectrum of diseases, is indeed far from being completely understood. Therefore, comprehending tumors' biological behaviour to identify reliable biomarkers, which may predict responses to therapies, is a demanding challenge to improve OC management. In the age of precision medicine, efforts to overcome platinum resistance in OC represent a dynamic and vast field in which innovative drugs and clinical trials rapidly develop. This review will present the exceptional biochemical environment implicated in OC and highlights mechanisms of chemoresistance. Furthermore, innovative molecules and new therapeutic opportunities are presented, along with currently available therapies and ongoing clinical trials.
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http://dx.doi.org/10.1016/j.semcancer.2021.08.011DOI Listing
August 2021

Thromboembolic events and antithrombotic prophylaxis in advanced ovarian cancer patients treated with bevacizumab: secondary analysis of the phase IV MITO-16A/MaNGO-OV2A trial.

Int J Gynecol Cancer 2021 Oct 30;31(10):1348-1355. Epub 2021 Aug 30.

Dipartimento di Salute Mentale e Fisica e Medicina Preventiva, Università degli Studi della Campania Luigi Vanvitelli, Napoli, Italy.

Introduction: The use of routine antithrombotic prophylaxis is not recommended for advanced cancer patients receiving chemotherapy. The effect of bevacizumab-containing therapy on the risk of thromboembolic events remains controversial in ovarian cancer patients. We report on the incidence of thromboembolic events and the prevalence of antithrombotic therapy in patients enrolled in the single arm, phase IV, MITO-16A/MaNGO-OV2A trial.

Methods: In this trial, potential prognostic factors for patients with previously untreated ovarian cancer receiving a combination of platinum-based chemotherapy and bevacizumab were explored and the final analysis has already been reported. In this secondary analysis, the occurrence of thromboembolic events and the use of antithrombotic therapy were described according to the clinical characteristics of the patients. The prognostic role of thromboembolic events for progression-free and overall survival were also evaluated.

Results: From October 2012 to November 2014, 398 eligible patients were enrolled. 76 patients (19.1%) were receiving some type of anticoagulant or anti-aggregant treatment at baseline. Overall, 24 thromboembolic events were reported (cumulative incidence of 6.0%). The occurrence of thromboembolic events was not associated with baseline patient characteristics and was not modified by the use of antithrombotic prophylaxis (HR 0.60, 95% CI 0.18 to 2.0). Occurrence of thromboembolic events was not associated with progression-free survival (HR 1.34, 95% CI 0.83 to 2.15) or overall survival (HR 0.78, 95% CI 0.37 to 1.61).

Conclusions: In our study, a 6.0% rate of thromboembolic events was reported during treatment with bevacizumab plus chemotherapy. Thromboembolic events were not associated with the clinical characteristics of the patients or with the use of antithrombotic prophylaxis, nor did they significantly affect the long-term prognosis.

Trial Registration Number: NCT01706120.
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http://dx.doi.org/10.1136/ijgc-2021-002786DOI Listing
October 2021

Evidence-based tailored nutrition educational intervention improves adherence to dietary guidelines, anthropometric measures and serum metabolic biomarkers in early-stage breast cancer patients: A prospective interventional study.

Breast 2021 Aug 21;60:6-14. Epub 2021 Aug 21.

University of Verona, Verona, Italy; Division of Gynecologic Oncology, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma, Italy. Electronic address:

Purpose: The impact of the adherence to dietary guidelines of early-stage breast cancer (EBC) patients on body composition changes during treatment is not entirely defined. This study aimed to evaluate the role of an evidence-based nutrition educational intervention, according to adherence to dietary guidelines, in EBC patients.

Methods: This prospective study included EBC patients, candidates for neoadjuvant/adjuvant therapy. Patients received an evidence-based tailored nutrition educational intervention. The adherence to dietary guidelines, anthropometric and dietary assessments, and blood glucose and lipid profile tests were evaluated at baseline and after a 12-months nutritional intervention.

Results: Two hundred and forty-three patients were enrolled. At baseline, 38.3% and 23.9% of patients were overweight and obese, weight gain ≥5% (compared to 6-months before enrollment) and central obesity were observed in 47.3% and 52.7% of patients, respectively. Adherence to dietary guidelines was low (median Med-Diet score: 6 [IQR 4-8]). After the nutritional intervention (median follow-up: 22 months [range 12-45]), adherence to dietary guidelines significantly increased (median Med-Diet score: 12 [IQR 8-13]), p < 0.0001). High adherence to dietary guidelines (defines as Med-Diet score ≥10) significantly correlated with: 1) overall weight loss ≥5% (21.8% vs. 2.5%, p = 0.003); 2) median BMI drop (from 25.6 kg/m to 24.4 kg/m, p = 0.003); 3) lower prevalence of central obesity (38.2% vs. 7.2%, p = 0.01); 4) improvement in blood glucose levels and lipid profile.

Conclusion: This study suggests that an evidence-based tailored nutrition educational intervention during treatment for EBC significantly increases overall adherence to dietary guidelines, and it improves both anthropometric measures and serum metabolic biomarkers in patients with high adherence.
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http://dx.doi.org/10.1016/j.breast.2021.08.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8399332PMC
August 2021

Let-7a-5p, miR-100-5p, miR-101-3p, and miR-199a-3p Hyperexpression as Potential Predictive Biomarkers in Early Breast Cancer Patients.

J Pers Med 2021 Aug 20;11(8). Epub 2021 Aug 20.

Faculty of Medicine and Surgery, Università Cattolica Del Sacro Cuore, Largo F. Vito 8, 00168 Rome, Italy.

Background: The aim of this study is to identify miRNAs able to predict the outcomes in breast cancer patients after neoadjuvant chemotherapy (NAC).

Patients And Methods: We retrospectively analyzed 24 patients receiving NAC and not reaching pathologic complete response (pCR). miRNAs were analyzed using an Illumina Next-Generation-Sequencing (NGS) system.

Results: Event-free survival (EFS) and overall survival (OS) were significantly higher in patients with up-regulation of let-7a-5p (EFS = 0.006; OS = 0.0001), mirR-100-5p (EFS s = 0.01; OS = 0.03), miR-101-3p (EFS = 0.05; OS = 0.01), and miR-199a-3p (EFS = 0.02; OS = 0.01) in post-NAC samples, independently from breast cancer subtypes. At multivariate analysis, only let-7a-5p was significantly associated with EFS ( = 0.009) and OS ( = 0.0008).

Conclusion: Up-regulation of the above miRNAs could represent biomarkers in breast cancer.
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http://dx.doi.org/10.3390/jpm11080816DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8400663PMC
August 2021

Ovarian Reserve after Chemotherapy in Breast Cancer: A Systematic Review and Meta-Analysis.

J Pers Med 2021 Jul 23;11(8). Epub 2021 Jul 23.

Gynecology and Breast Care Center, Mater Olbia Hospital, 07026 Olbia, Italy.

: Worldwide, breast cancer (BC) is the most common malignancy in the female population. In recent years, its diagnosis in young women has increased, together with a growing desire to become pregnant later in life. Although there is evidence about the detrimental effect of chemotherapy (CT) on the menses cycle, a practical tool to measure ovarian reserve is still missing. Recently, anti-Mullerian hormone (AMH) has been considered a good surrogate for ovarian reserve. The main objective of this paper is to evaluate the effect of CT on AMH value.

Methods: A systematic review and meta-analysis were conducted on the PubMed and Scopus electronic databases on articles retrieved from inception until February 2021. Trials evaluating ovarian reserves before and after CT in BC were included. We excluded case reports, case-series with fewer than ten patients, reviews (narrative or systematic), communications and perspectives. Studies in languages other than English or with polycystic ovarian syndrome (PCOS) patients were also excluded. AMH reduction was the main endpoint. Egger's and Begg's tests were used to assess the risk of publication bias.

Results: Eighteen trials were included from the 833 examined. A statistically significant decline in serum AMH concentration was found after CT, persisting even after years, with an overall reduction of -1.97 (95% CI: -3.12, -0.82). No significant differences in ovarian reserve loss were found in the BRCA1/2 mutation carriers compared to wild-type patients.

Conclusions: Although this study has some limitations, including publication bias, failure to stratify the results by some important factors and low to medium quality of the studies included, this metanalysis demonstrates that the level of AMH markedly falls after CT in BC patients, corresponding to a reduction in ovarian reserve. These findings should be routinely discussed during oncofertility counseling and used to guide fertility preservation choices in young women before starting treatment.
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http://dx.doi.org/10.3390/jpm11080704DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8400427PMC
July 2021

Towards Personalized Medicine: Non-Coding RNAs and Endometrial Cancer.

Healthcare (Basel) 2021 Jul 30;9(8). Epub 2021 Jul 30.

Obstetrics and Gynecology Department, USL Roma2, Sant'Eugenio Hospital, 00144 Rome, Italy.

Endometrial cancer (EC) is the most frequent female cancer associated with excellent prognosis if diagnosed at an early stage. The risk factors on which clinical staging is based are constantly updated and genetic and epigenetic characteristics have recently been emerging as prognostic markers. The evidence shows that non-coding RNAs (ncRNAs) play a fundamental role in various biological processes associated with the pathogenesis of EC and many of them also have a prognosis prediction function, of remarkable importance in defining the therapeutic and surveillance path of EC patients. Personalized medicine focuses on the continuous updating of risk factors that are identifiable early during the EC staging to tailor treatments to patients. This review aims to show a summary of the current classification systems and to encourage the integration of various risk factors, introducing the prognostic role of non-coding RNAs, to avoid aggressive therapies where not necessary and to treat and strictly monitor subjects at greater risk of relapse.
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http://dx.doi.org/10.3390/healthcare9080965DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8393611PMC
July 2021

ASO Author Reflections: Minimally Invasive Surgical Staging in Endometrial Cancer Diagnosed After Supracervical Hysterectomy - The Role of Cervical Injection to Detect Sentinel Lymph Node with Indocyanine Green.

Ann Surg Oncol 2021 Aug 23. Epub 2021 Aug 23.

UOC Ginecologia Oncologica, Dipartimento per la salute della Donna e del Bambino e della Salute Pubblica, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy.

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http://dx.doi.org/10.1245/s10434-021-10694-8DOI Listing
August 2021
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