Publications by authors named "Claudia Marchetti"

113 Publications

Update on the secondary cytoreduction in platinum-sensitive recurrent ovarian cancer: a narrative review.

Ann Transl Med 2021 Mar;9(6):510

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

The ovarian cancer recurrence occurs in 75% of patients with advanced FIGO stage, and its treatment is a challenge for the oncologist in gynecology. The standard treatment of recurrent ovarian cancer (ROC) usually includes intravenous chemotherapy according to platinum sensitivity. Furthermore, maintenance treatment with target therapies [e.g., anti-angiogenic drug or PARP inhibitors (PARPi)], should be provided if not precedently administrated. In this scenario, secondary cytoreductive surgery (SCS) remains a practical but controversial option for platinum-sensitive ROC (PSROC). So far, several retrospective series and a Cochrane meta-analysis had concluded that SCS could determine better survival outcomes in ROC with favorable prognostic characteristics, such as the presence of a single anatomical site of recurrence, or when patients are accurately selected for surgery based on complete resection's predictive models. Recently, three randomized clinical trials (RCTs) investigated the role of SCS in PSROC patients selected with different criteria. All the three RCTs showed a significant statistical advantage in progression-free survival (PFS) in the SCS group, with an even more significant difference in patients with complete cytoreduction (about 7-month PFS increased). Data on overall survival (OS) are different in the two completed trials. The GOG213 study has documented a longer OS of PSROC patients who received chemotherapy alone compared to surgery plus chemotherapy. Contrarily, the DESKTOP III trial showed 7.7 months of increased OS in the surgery group chemotherapy alone, with a more difference in the complete tumor cytoreduction (CTC) group (12 months). These RCTs thereby suggest that undergoing complete cytoreduction may not be the only key and that the disease biology may also matter. Few recent retrospective series investigated the role of SCS according to BRCA mutation status and the effect of SCS in patients receiving emerging PARPi. A consequence of the developments in SCS and knowledge of different molecular pathways influencing the recurrent disease is that the future research objective should be to individualize and personalize the surgical approach.
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http://dx.doi.org/10.21037/atm-20-4690DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039681PMC
March 2021

Fertility preservation in patients with BRCA mutations or Lynch syndrome.

Int J Gynecol Cancer 2021 Mar;31(3):332-338

Istituto di Ostetricia e Ginecologia, Fondazione Policlinico Universitario A Gemelli IRCCS, Rome, Italy.

Guidelines and expert consensus are lacking on fertility preservation in BRCA mutation carriers and in patients with Lynch syndrome. The safety of fertility preservation in this setting is still a topic of debate and multiple factors need to be carefully considered. The aim of this review was to analyze the reproductive potential of women harboring a genetic mutation affecting the DNA repair system and explore the efficacy and safety of existing fertility preservation strategies in these patients.
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http://dx.doi.org/10.1136/ijgc-2020-002071DOI Listing
March 2021

Diet and Chemotherapy: The Effects of Fasting and Ketogenic Diet on Cancer Treatment.

Chemotherapy 2020 16;65(3-4):77-84. Epub 2020 Nov 16.

Department of Obstetrics and Gynaecology, Campus Bio-Medico, University of Rome, Rome, Italy.

Introduction: Diet may influence various aspects of human health. In fact, it is well known that diet can favour or not the development of various human pathologies, like diabetes, hypertension, and hypercholesterolaemia. Interestingly, diet has an influence in cancer development too (e.g., this relation has been studied for pancreatic, colonic, gastric, and breast cancers). Between the mechanisms that could explain this relation, there is epigenetic. In fact, thanks to epigenetic reprogramming, certain substances introduced with diet could affect gene expression, especially of those genes involved in cells' proliferation and growth. In recent years, some studies have been published about the role that diet could have on chemotherapy outcome. Especially, various studies have analysed the effects of fasting and ketogenic diet (KD) during chemotherapy. The aim of this study is to summarize scientific evidences about diet and its effects on chemotherapy on humans and to better understand if these approaches deserve to be further investigated and might be suitable and beneficial during cancer treatment.

Materials And Methods: We performed an electronic literature search of the PubMed database, using the combination of following terms: "fasting" or "ketogenic" with "chemotherapy," "cancer treatment." We included studies on humans about fasting and KD during chemotherapy, excluding reviews, case series including <10 patients, studies conducted on animals or limited to radiotherapy treatment, and studies that were mostly about molecular mechanisms. Results/Discussion In our analysis we included 4 studies (1 randomized controlled trial, 1 retrospective study, and 2 prospective pilot studies) about KD and 4 studies (1 prospective cohort study, 1 case series report, and 2 randomized trials) about fasting during oncological treatments. Authors suggested an improvement of quality of life (QoL) and fatigue in patients under chemotherapy, especially in the 8 days after chemotherapy treatment. We found that both fasting and KD demonstrated to be tolerable and feasible during oncological treatments. Conversely, data about survival outcomes are still controversial, but it should be underlined that it was not the outcome of these preliminary studies.

Conclusions: All comparatives studies have demonstrated that even fasting then KD results in a reduction of collateral effects of adjuvant chemotherapy (due to reduction of drugs toxicity) and a better QoL than in patients that follow no diet. Unfortunately, despite the fact that various laboratory and animal studies confirm advantages from KD and fasting, few data are today disposable on humans: further studies are needed to confirm data exposed in this review.
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http://dx.doi.org/10.1159/000510839DOI Listing
November 2020

Pembrolizumab for advanced cervical cancer: safety and efficacy.

Expert Rev Anticancer Ther 2021 Feb 26;21(2):221-228. Epub 2020 Nov 26.

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

: Pembrolizumab is an immune checkpoint inhibitor with high specificity for binding to the programmed cell death 1 (PD-1) receptor. It has been approved by the FDA in patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express the programmed cell death ligand 1 (PD-L1).: Clinical studies of pembrolizumab in cervical cancer were analyzed and discussed. Data were obtained by searching for English peer-reviewed articles on PubMed, clinical trials registered on clincaltrials.gov and related abstracts on the ASCO meeting library. The aim was to review the status of pembrolizumab, the published and ongoing trials, and its safety and efficacy.: Pembrolizumab may ultimately represent a treatment of choice for advanced cervical cancer with PD-L1 expression, both in metastatic and recurrent setting. However, it is essential to better identify and characterize patients that will benefit the most.
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http://dx.doi.org/10.1080/14737140.2021.1850279DOI Listing
February 2021

ASO Author Reflections: Secondary Cytoreductive Surgery in Recurrent Ovarian Cancer.

Ann Surg Oncol 2020 Oct 29. Epub 2020 Oct 29.

Department of Radiotherapy, Policlinico Umberto I, "Sapienza" University of Rome, Rome, Italy.

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http://dx.doi.org/10.1245/s10434-020-09260-5DOI Listing
October 2020

The Role of Secondary Cytoreductive Surgery in Recurrent Ovarian Cancer: A Systematic Review and Meta-Analysis.

Ann Surg Oncol 2020 Oct 16. Epub 2020 Oct 16.

Department of Radiotherapy, Policlinico Umberto I, "Sapienza" University of Rome, Rome, Italy.

Background: Phase 3 randomized clinical trials have been designed to compare secondary cytoreductive surgery followed by systemic therapy with systemic therapy alone for management of patients with recurrent ovarian cancer. This study aimed to compare differences in clinical outcomes between these two treatment approaches.

Methods: The PRISMA statement was applied. Only phase 3 randomized clinical trials were included in the final analysis.

Results: Three randomized clinical trials (n = 1250 patients) were identified. Secondary cytoreductive surgery was associated with significantly better progression-free survival (PFS) improvement than systemic therapy alone (hazard ratio [HR], 95% CI, 0.61-0.78; p < 0.001). The PFS benefit was greater for the complete resection subpopulation (HR, 0.56; 95% CI, 0.48-0.66; p < 0.001). The HR of overall survival (OS) was similar between the groups (HR, 0.93; 95% CI, 0.78-1.10; p = 0.37), but it was 0.73 (95% CI, 0.59-0.91) in favor of the complete resection subpopulation.

Conclusion: This meta-analysis showed secondary cytoreductive surgery as superior to systemic therapy alone in terms of PFS. The PFS and OS benefits were particularly observed for complete surgical resection. The impact on OS in the general population remains to be proven.
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http://dx.doi.org/10.1245/s10434-020-09226-7DOI Listing
October 2020

Ovarian cancer predisposition beyond BRCA1 and BRCA2 genes.

Int J Gynecol Cancer 2020 11 6;30(11):1803-1810. Epub 2020 Sep 6.

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

Several genes associated with hereditary ovarian cancer have been discovered as a result of the work done with next generation sequencing. It is estimated that approximately 23% of ovarian carcinomas have a hereditary predisposition. The most common hereditary condition is represented by germline mutations in BRCA1 or BRCA2 genes that account for 20-25% of high grade serous ovarian cancer. A number of other hereditary ovarian cancers are associated with different genes, with a crucial role in the DNA damage response pathway, such as the mismatch repair genes in Lynch syndrome, TP53 in Li-Fraumeni syndrome, STK11 in Peutz-Jeghers syndrome, CHEK2, RAD51, BRIP1, and PALB2. The goal of this manuscript is to summarize the published data regarding the molecular pathways involved in the pathogenesis of non-BRCA related hereditary ovarian cancer and to provide a tool that might be useful in discussing risk assessment, genetic testing, prevention strategies, as well as clinical and therapeutic implications for patients with ovarian cancer.
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http://dx.doi.org/10.1136/ijgc-2020-001556DOI Listing
November 2020

status assessment in epithelial ovarian cancer and the challenge of tumor testing.

Int J Gynecol Cancer 2020 09 4;30(9):1465-1466. Epub 2020 Aug 4.

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

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http://dx.doi.org/10.1136/ijgc-2020-001670DOI Listing
September 2020

Immunotherapy in cervical cancer: the advent of precision medicine.

Ann Transl Med 2020 Jun;8(12):773

Department of Woman and Child Sciences, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Rome, Italy.

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http://dx.doi.org/10.21037/atm.2020.02.153DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7333096PMC
June 2020

Feasibility of tumor testing for BRCA status in high-grade serous ovarian cancer using fresh-frozen tissue based approach.

Gynecol Oncol 2020 09 15;158(3):740-746. Epub 2020 Jun 15.

Department of Woman, Child and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy; Catholic University of the Sacred Heart, Rome, Italy.

Objective: For many years, BRCA mutational status has only been considered as a predictor of ovarian cancer susceptibility and as a prognostic factor. Nonetheless, in the era of precision medicine, it has also become a predictive biomarker of response to platinum-based-chemotherapy and, more recently, to PARP-inhibitors, also in the frontline setting. We assessed the feasibility of a fresh frozen tissue-based-BRCA-screening workflow in a tertiary referral center.

Methods: We consecutively enrolled a series of 456 newly diagnosed FIGO-Stage IIIC-IV, high grade serous-ovarian cancer patients. All patients receiving tumor-biopsy underwent tBRCA-testing.

Results: Clinically relevant tissue-BRCA (tBRCA) variants were observed in 145 women (31.8%), particularly we recognized 89 (61.4%) patients with BRCA1-pathogenetic variants (PVs) and 56 women (38.6%) with BRCA2-PVs. Among 292 tBRCA wild-type (wt) patients, 88 cases were germline BRCA tested (gBRCA) and 86 (97.8%) were confirmed as gBRCAwt, while 1 (1.1%) had gBRCA variant of uncertain significance and 1 had gBRCA mutation (1.1%). The concordance of tumor test versus germline BRCA test was 86.3% (209/242). Large genomic rearrangements (LGRs) were suspected in 13/292 tBRCAwt patients (4.5%) by using bioinformatic algorithm and multiplex ligation-dependent probe amplification (MLPA) was performed, with evidence of PVs in only 1 case.

Conclusions: Fresh-frozen tissue-based BRCA screening workflow is feasible and reliable. It allows to enlarge the BRCA mutated population that might receive PARPi with the greatest benefit, without missing cascade testing for family members and therefore, maintaining its preventive role.
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http://dx.doi.org/10.1016/j.ygyno.2020.06.479DOI Listing
September 2020

High resolution melting profiles (HRMPs) obtained by magnetic induction cycler (MIC) have been used to monitor the BRCA2 status highlighted by next generation tumor sequencing (NGTS): a combined approach in a diagnostic environment.

Mol Biol Rep 2020 Jun 28;47(6):4897-4903. Epub 2020 May 28.

Molecular and Genomic Diagnostics Unit, Fondazione Policlinico Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.

Resistance can be the result of secondary tissue variants (STVs), which restore the open reading frame of the germline BRCA allele, producing functional BRCA protein in germline BRCA1/2 (BRCA) pathogenic variant (PV) carriers, treated with platinum-based chemotherapy or poly-(ADP-ribose) polymerase inhibitors (PARP-1). We reported recently a BRCA2 mutant high grade serous ovarian cancer (HGSOC) patient with acquired resistance to the PARP-1 olaparib due to a STV detected by next generation tumor sequencing (NGTS). The aim of this study was to evaluate the versatility of the high-resolution melting analysis (HRMA) obtained by magnetic induction cycler (MIC) to monitor the BRCA2 status in formalin-fixed paraffin-embedded (FFPE) tissue samples of this patient and to compare the results obtained by NGTS. HRMA highlighted the BRCA2 STV previously detected in the IIIrd HGSOC recurrence following the tissue BRCA2 tissue status comparing the high resolution melting profiles (HRMPs). HRMPs differentiate not only BRCA2 alleles, but also their different allele abundance. We underline that (1) the MIC uses a latest generation technology guaranteeing temperature uniformity and maintenance in each well allowing high and accurate performance to obtain reported results and (2) the HRMA maintains a high sensitivity and specificity when it is performed on FFPE samples. Finally, this study represents an additional use of the HRMA, confirming its extreme versatility in the diagnostic environment.
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http://dx.doi.org/10.1007/s11033-020-05504-5DOI Listing
June 2020

Ovarian cancer treatment is evolving: more choices, more chances.

Int J Gynecol Cancer 2020 06 9;30(6):726-727. Epub 2020 Apr 9.

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

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http://dx.doi.org/10.1136/ijgc-2020-001407DOI Listing
June 2020

Letrozole in the management of advanced ovarian cancer: an old drug as a new targeted therapy.

Int J Gynecol Cancer 2020 07 26;30(7):1058-1064. Epub 2020 Mar 26.

Dipartimento Scienze della Salute della Donna e del Bambino, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy.

At present, there is no standard of care on the use of letrozole in ovarian cancer management. We performed a systematic review of the available literature addressing this issue. Data demonstrated a role for letrozole in ovarian cancer, in both the primary and recurrent setting. Letrozole, which has a favorable toxicity profile, seems to assure a prolonged recurrence-free interval, particularly when used as maintenance treatment, in low grade serous ovarian cancer; in recurrent cases it had also led to prolonged disease control. However, the optimal setting and biologically relevant patient population needs to be defined in larger trials.
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http://dx.doi.org/10.1136/ijgc-2019-001128DOI Listing
July 2020

Sharing real-world experiences to optimize the management of olaparib toxicities: a practical guidance from an Italian expert panel.

Support Care Cancer 2020 May 11;28(5):2435-2442. Epub 2020 Feb 11.

Division of Medical Oncology 2, Istituto Oncologico Veneto, Via Gattamelata, 64, 35128, Padua, Italy.

Olaparib is the first poly(ADP-ribose) polymerase inhibitor approved as maintenance therapy of recurrent ovarian cancer (OC) patients with a BRCA mutation. To achieve the maximum clinical benefit, adherence to olaparib must be persistent. However, in clinical practice, this is challenged by the frequent suboptimal management of toxicities. In view of the expanding use of olaparib also in Italy, physicians must learn how to adequately and promptly manage drug toxicities not to unnecessarily interrupt or reduce the dose. The experts agreed that nausea,vomiting, anemia, and fatigue are the most frequent events experienced by OC patients on olaparib, and that these toxicities usually develop early during treatment, are mainly of grade 1-2 and transient and can be managed with simple non-pharmacological interventions. By sharing their real-world experiences, the panel prepared, for each toxicity, an algorithm organized by grade and besides the procedures indicated in the local label, included supportive care interventions based also on nutritional and lifestyle modifications and psycho-oncology consultation. Moreover, in view of the tablet entry into the Italian market, the full and reduced dosages of capsules and tablets were compared. This practical guidance is intended to be a tool to support especially less-experienced physicians in the management of these complex patients, with the aim to help preventing the worsening of patients' conditions and the unnecessary interruption/reduction of olaparib dosage, which may jeopardize treatment efficacy.
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http://dx.doi.org/10.1007/s00520-020-05320-4DOI Listing
May 2020

Secondary cytoreduction in platinum-sensitive recurrent ovarian cancer: are we missing something?

Ann Transl Med 2019 Dec;7(Suppl 8):S372

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

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http://dx.doi.org/10.21037/atm.2019.12.94DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6976449PMC
December 2019

MiR-200c sensitizes Olaparib-resistant ovarian cancer cells by targeting Neuropilin 1.

J Exp Clin Cancer Res 2020 Jan 2;39(1). Epub 2020 Jan 2.

Department of Experimental Medicine, Sapienza University of Rome, Viale Regina Elena 324, 00161, Rome, Italy.

Background: Ovarian cancer (OC) is the most lethal gynecological malignancy and the second leading cause of cancer-related death in women. Treatment with PARP inhibitors (PARPi), such as Olaparib, has been recently introduced for OC patients, but resistance may occur and underlying mechanisms are still poorly understood. The aim of this study is to identify target genes within the tumor cells that might cause resistance to Olaparib. We focused on Neuropilin 1 (NRP1), a transmembrane receptor expressed in OC and correlated with poor survival, which has been also proposed as a key molecule in OC multidrug resistance.

Methods: Using three OC cell lines (UWB, UWB-BRCA and SKOV3) as model systems, we evaluated the biological and molecular effects of Olaparib on OC cell growth, cell cycle, DNA damage and apoptosis/autophagy induction, through MTT and colony forming assays, flow cytometry, immunofluorescence and Western blot analyses. We evaluated NRP1 expression in OC specimens and cell lines by Western blot and qRT-PCR, and used RNA interference to selectively inhibit NRP1. To identify miR-200c as a regulator of NRP1, we used miRNA target prediction algorithms and Pearsons' correlation analysis in biopsies from OC patients. Then, we used a stable transfection approach to overexpress miR-200c in Olaparib-resistant cells.

Results: We observed that NRP1 is expressed at high levels in resistant cells (SKOV3) and is upmodulated in partially sensitive cells (UWB-BRCA) upon prolonged Olaparib treatment, leading to poor drug response. Our results show that the selective inhibition of NRP1 is able to overcome Olaparib resistance in SKOV3 cells. Moreover, we demonstrated that miR-200c can target NRP1 in OC cells, causing its downmodulation, and that miR-200c overexpression is a valid approach to restore Olaparib sensitivity in OC resistant cells.

Conclusions: These data demonstrate that miR-200c significantly enhanced the anti-cancer efficacy of Olaparib in drug-resistant OC cells. Thus, the combination of Olaparib with miRNA-based therapy may represent a promising treatment for drug resistant OC, and our data may help in designing novel precision medicine trials for optimizing the clinical use of PARPi.
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http://dx.doi.org/10.1186/s13046-019-1490-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6939329PMC
January 2020

ToleRability of BevacizUmab in elderly Ovarian cancer patients (TURBO study): a case-control study of a real-life experience.

J Gynecol Oncol 2020 Jan 25;31(1):e6. Epub 2019 Jul 25.

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

Objective: Bevacizumab maintenance following platinum-based chemotherapy is an effective treatment for epithelial ovarian cancer (EOC), both in primary and recurrent disease. Our aim was to identify criteria to select elderly patients who can safely benefit from bevacizumab addition.

Methods: This is a case-control study on patients with primary or recurrent EOC who received platinum-based chemotherapy plus bevacizumab, between January 2015 and December 2016. Patient characteristics, treatment details and adverse events were reviewed and analyzed in 2 settings: younger (<65 years, group 1) and elderly (≥65 years, group 2). A binary logistic model was applied to correlate clinical variables and severe (grade ≥3) toxicity risk.

Results: Overall, 283 patients with EOC were included, with 72 (25.4%) older patients compared with 211 (74.6%) younger women. Bevacizumab had been administered to 234 patients (82.7%) as first-line treatment and in 49 (17.3%) with recurrent disease. At diagnosis, elderly patients presented with at least one comorbidity and were taking at least 1 medication in 84.7% and 80.6% of the cases respectively, compared with correspondingly 47.4% and 37.4% in group 1 (p<0.001). Nonetheless, the occurrence of serious (grade ≥3) adverse events did not increase among the older group. Creatinine serum levels >1.1 g/dL, estimated glomerular filtration rate (eGFR) ≤60 mL/min, ≥3 comorbidities were independently associated with a higher severe toxicity.

Conclusions: Elderly patients with EOC can safely be treated with bevacizumab; factors other than age, as higher creatinine serum levels, eGFR and number of comorbidities should be considered to better estimate bevacizumab-related toxicity risk.
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http://dx.doi.org/10.3802/jgo.2020.31.e6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6918885PMC
January 2020

Olaparib as maintenance therapy in patients with BRCA 1-2 mutated recurrent platinum sensitive ovarian cancer: Real world data and post progression outcome.

Gynecol Oncol 2020 01 4;156(1):38-44. Epub 2019 Nov 4.

Department of Urology and Gynecology, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale Napoli, Italy. Electronic address:

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.
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http://dx.doi.org/10.1016/j.ygyno.2019.10.023DOI Listing
January 2020

Can somatic BRCA2 status solve a case of olaparib monotherapy resistance?

Int J Gynecol Cancer 2019 11 19;29(9):1440-1445. Epub 2019 Sep 19.

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

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http://dx.doi.org/10.1136/ijgc-2019-000757DOI Listing
November 2019

Etirinotecan pegol in women with recurrent platinum-resistant or refractory ovarian cancer.

Expert Opin Investig Drugs 2019 Aug 30;28(8):667-673. Epub 2019 Jul 30.

a Department of Maternal and Child Health and Urological Sciences, "Sapienza" University of Rome , Policlinico Umberto I, Rome , Italy.

: A PEGylated form of irinotecan, a topoisomerase I inhibitor, is now available in commerce; its safety and efficacy have been tested in platinum resistant/refractory ovarian cancer (PROC) patients. This novel agent is known as Etirinotecan Pegol (EP). EP, like irinotecan, exerts its action through its principal metabolite SN-38. : This drug evaluation article focuses on the most recent investigations and clinical progress regarding EP, a long-acting polymer conjugate of irinotecan for the treatment of PROC. : EP provides prolonged and continuous exposure of SN-38 in tumors, when compared to its parent drug irinotecan. Results from phase II studies are comparable in terms of efficacy to other agents of proven use in PROC. A limitation of the use of EP is the schedule-dependent toxicities (mainly diarrhea and dehydration). In the future, EP could be investigated in association with other agents, even in attempts to restore sensitivity to other treatments. PROC remains a very difficult setting and EP might be a valid agent for patients with good performance status that have exhausted therapeutic options. In such a setting, participation in clinical trials is strongly encouraged.
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http://dx.doi.org/10.1080/13543784.2019.1648430DOI Listing
August 2019

Immune check-point in endometrial cancer.

Int J Clin Oncol 2019 Aug 2;24(8):910-916. Epub 2019 May 2.

Department of Gynecological, Obstetrical Sciences and Urological Sciences "Sapienza" University of Rome, Rome, Italy.

Background: Endometrial cancer (EC) is one of the most frequent tumors in women. Despite recent advances in treatment approaches, the prognosis in advanced, recurrent, or metastatic disease remains poor. The aim was to provide the clinician with an update, the current status, and the new developments in the management of EC. Based on the new EC molecular classification, we focused on the impact of immune check-point inhibitors.

Methods: Pivotal trials, published literature, and conference proceedings were reviewed. PubMed and Scopus databases were searched to select English-language articles.

Results: Immune check-point inhibitors are the subject of ongoing studies and their benefit seems to be related to microsatellite instability (MSI) status.

Conclusions: Immune check-point inhibitors should be considered a promising treatment option to better personalize therapeutic strategies in EC.
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http://dx.doi.org/10.1007/s10147-019-01437-7DOI Listing
August 2019

Fighting against the challenge of treating patients with late-line ovarian cancer: are we there yet?

Lancet Oncol 2019 05 1;20(5):603-605. Epub 2019 Apr 1.

Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Rome 00168, Italy; Catholic University of the Sacred Heart, Rome, Italy.

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http://dx.doi.org/10.1016/S1470-2045(19)30087-7DOI Listing
May 2019

Metformin reduces maternal weight gain in obese pregnant women: A systematic review and meta-analysis of two randomized controlled trials.

Diabetes Metab Res Rev 2019 09 14;35(6):e3164. Epub 2019 May 14.

Department of Gynecological, Obstetrical and Urological Sciences, "Sapienza" University of Rome, Rome, Italy.

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http://dx.doi.org/10.1002/dmrr.3164DOI Listing
September 2019

Role of intraperitoneal chemotherapy in ovarian cancer in the platinum-taxane-based era: A meta-analysis.

Crit Rev Oncol Hematol 2019 Apr 1;136:64-69. Epub 2019 Feb 1.

Department of Gynecological and Obstetrical Sciences and Urological Sciences, "Sapienza" University of Rome, Rome, Italy.

Purpose: Intravenous (IV) chemotherapy has been compared with intraperitoneal (IP) chemotherapy in randomized clinical trials in advanced ovarian cancer (OC). The aim of this meta-analysis was to evaluate efficacy and toxicity of IV and IP and identify differences in outcomes.

Methods: The preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement was applied. Random-effects models were used. Primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS) and the proportion of patients with grade ≥2 acute toxicity.

Results: Four randomized clinical trials representing 2461 patients were identified. The hazard ratio (HR) of PFS was 0.88 (95% CI 0.80-0.98; p = 0.01, I = 24%) in favor of IP chemotherapy. IP chemotherapy was also associated with significant OS improvement compared with IV chemotherapy, with HR of 0.79 (95% CI 0.67-0.92; p = 0.003, I = 0%). Globally, grade ≥2 toxicities were reduced with IV chemotherapy.

Conclusion: This meta-analysis shows the superiority of IP chemotherapy over IV infusion in terms of clinical outcomes but toxicity rates. Its precise role in the management of advanced OC remains to be determined.
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http://dx.doi.org/10.1016/j.critrevonc.2019.01.002DOI Listing
April 2019

First-line treatment of women with advanced ovarian cancer: focus on bevacizumab.

Onco Targets Ther 2019 8;12:1095-1103. Epub 2019 Feb 8.

Department of Gynecological-Obstetrical and Urological Sciences, Sapienza University of Rome, Rome, Italy,

Ovarian cancer is the fifth most common cause of cancer death in women in Europe. Despite the progress, almost 70% of the patients relapse. The standard treatment is cytoreductive surgery followed by platinumtaxane chemotherapy; in patients with a disseminated disease, one option is neoadjuvant chemotherapy with delayed surgery (ie, interval debulking surgery). The most important change in the last decades involved the schedule treatment and the addition of new drugs to first-line therapy. Because of the pathogenetic role of angiogenesis in solid-tumor growth and metastasis, research has been concentrated on anti-angiogenetic drug. Bevacizumab, the most promising anti-angiogenetic drug, is a humanized monoclonal IgG antibody that targets vascular endothelial growth factor receptor. It was approved on December 23, 2011 by the European Medicines Agency and on June 13, 2018 by the Food and Drug administration as first-line treatment in epithelial ovarian, fallopian tube, or primary peritoneal cancer stage III or IV in combination with carboplatin and paclitaxel. There are still some doubts, regarding the schedule, dosage, duration of the treatment, safety, and tolerability, both in first-line and in neoadjuvant chemotherapy treatments. This review tries to answer clinical practice questions and summarizes the evidence from Phase III studies, emerging data, and ongoing trials.
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http://dx.doi.org/10.2147/OTT.S155425DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6371937PMC
February 2019

Corrigendum to "Bartholin gland cancer" [Crit. Rev. Oncol./Hematol. 117 (September) (2017) 1-11].

Crit Rev Oncol Hematol 2019 01 16;133:84. Epub 2018 Nov 16.

Department of Gynecological, Obstetrical and Urological Sciences, "Sapienza" University of Rome, Italy.

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http://dx.doi.org/10.1016/j.critrevonc.2017.11.004DOI Listing
January 2019

Management of endometriosis from diagnosis to treatment: roadmap for the future.

Minerva Ginecol 2019 Feb 11;71(1):54-61. Epub 2018 Oct 11.

Department of Obstetrics and Gynecology, Sapienza University, Rome, Italy.

Endometriosis, in spite of decades of research on the topic, remains a mysterious and elusive disease. Both in the fields of diagnosis and treatment, many issues remain unresolved, and the scientific community strives in trying to find universal criteria for diagnosis, and algorithms of treatment that may be universally applied. Recently, there has been a shift away from the view of the need of invasive diagnosis and therapy with the universal use of laparoscopy. Today the diagnosis of endometriosis may be reliably performed with noninvasive methods, and therapy can be nonsurgical in most cases. Recent guidelines state that diagnostic laparoscopy may be better seen as a second line of investigation, whereas medical therapy with either oral estroprogestins or progestogens is the first therapeutic option in case of associated pain. A thorough discussion with the patient should address all the available treatments, so as to make a shared decision on which treatment best fits the needs of that single patient.
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http://dx.doi.org/10.23736/S0026-4784.18.04320-4DOI Listing
February 2019

Midtrimester isolated short femur and perinatal outcomes: A systematic review and meta-analysis.

Acta Obstet Gynecol Scand 2019 01 31;98(1):11-17. Epub 2018 Oct 31.

Department of Gynecological, Obstetrical and Urological Sciences, Sapienza University, Policlinico Umberto I Hospital, Rome, Italy.

Introduction: Fetal femur length below the expected value has been described as a marker of aneuploidy, skeletal dysplasia, intrauterine growth restriction and small-for-gestational-age neonate. The aim of this systematic review and meta-analysis was to evaluate the strength of association between isolated short femur length and intrauterine growth restriction or small-for-gestational-age, and perinatal adverse outcomes.

Material And Methods: PubMed, EMBASE and Medline were searched from the inception of each database to May 2018. Selection criteria included prospective and retrospective cohort studies of singleton pregnancies between 18 and 28 weeks of gestation, with sonographic finding of isolated short femur length, without any structural chromosomal abnormality. The meta-analysis was performed by computing odds ratios using both fixed and random-effects models. Quality assessment of the included studies was performed using the Newcastle-Ottawa Scale.

Results: Six studies including 3078 cases of isolated short femur length (study group) and 222 303 normal femur length (control group) were included. The prevalence of intrauterine growth restriction or small-for-gestational-age in the study group was 14.2%, compared with 5.2% in the control group (odds ratio of 4.04, 95% confidence interval 3.63-4.50). Isolated short femur length was associated with a higher incidence of low birthweight (study group: 22.10% vs control group: 8.57%, odds ratio 3.24, 95% confidence interval 2.34-4.48), Apgar <7 at 5 minutes (study group: 3.98% vs control group: 1.79%, odds ratio 3.56, 95% confidence interval 1.87-6.77), preterm birth (study group: 12.16% vs control group: 8.16%, odds ratio 3.09, 95% confidence interval 1.57-6.08), fetal death (study group: 1.83% vs control group: 0.44%, odds ratio 6.48, 95% confidence interval 3.70-11.35) and neonatal intensive care unit admission (study group: 15.34% vs control group: 14.81%, odds ratio 2.11, 95% confidence interval 0.56-7.93).

Conclusions: There is a significant association between isolated short femur length and intrauterine growth restriction or small-for-gestational-age and poor perinatal outcome.
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http://dx.doi.org/10.1111/aogs.13470DOI Listing
January 2019

Comparison of Anogenital Distance and Correlation with Vulvo-vaginal Atrophy: A Pilot Study on Premenopausal and Postmenopausal Women.

J Menopausal Med 2018 Aug 31;24(2):108-112. Epub 2018 Aug 31.

Department of Gynecological and Obstetric Sciences, and Urological Sciences, University "Sapienza" of Rome, Rome, Italy.

Objectives: Anogenital distance (AGD) represents the space between labia posterior commissure and anus. This was pilot study to investigate how menopause and so lack of oestrogens affects AGD.

Methods: A total of 109 patients were enrolled. AGD was measured in lithotomy position using sterile paper ruler. Anogenital index (AGI) was used to control 2 variables of height and weight (body mass index, kg/m). Vaginal health index (VHI) was used to evaluate vaginal wellness. Female sexual function index (FSFI) questionnaire was administered to all women to evaluate the impact of menopause on their sexual function.

Results: AGD (30.87 ± 2.98 vs. 17.57 ± 2.18; = 0.0001) and AGI (1.40 ± 0.21 vs. 0.70 ± 0.15; = 0.0001) were both significantly lower in the postmenopausal group. Postmenopausal women were affected by vulvovaginal atrophy (VVA) significantly. Thus, VHI scores were dramatically worse in postmenopausal group (23.95 ± 1.28 vs. 10.75 ± 3.41; = 0.0001) as well as FSFI results (32.68 ± 2.25 vs. 19.78 ± 5.46; = 0.0001).

Conclusions: This study confirms that AGD in post-menopausal women was significantly shorter than AGD in premenopausal women, correlating with an increase of VVA and sexual impairment. Changes of AGD and AGI demonstrated to predict hormonal changes that may occur after menopause.
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http://dx.doi.org/10.6118/jmm.2018.24.2.108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6127022PMC
August 2018

Correction to: BRCA Mutation Status to Personalize Management of Recurrent Ovarian Cancer: A Multicenter Study.

Ann Surg Oncol 2018 12;25(Suppl 3):996

Department of Woman and Child Sciences, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Università Cattolica del Sacro Cuore, Roma, Italia.

In the original version of the article, Angelo Minucci's last name was spelled incorrectly. It is correct as shown here. The original article has been corrected.
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http://dx.doi.org/10.1245/s10434-018-6726-9DOI Listing
December 2018