Publications by authors named "Anna Fagotti"

304 Publications

Isolated tumour cells in a sentinel lymph node of apparent early-stage ovarian cancer: Ultrastaging of all other 27 lymph nodes.

Gynecol Oncol Rep 2022 Aug 20;42:101047. Epub 2022 Jul 20.

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

Sentinel lymph node (SLN) biopsy in apparent early-stage ovarian cancer may spare the surgical staging with extensive retroperitoneal dissection and its associated morbidity. However, SLN biopsy in ovarian cancer is still experimental and under investigation. A 46-year-old post-menopausal woman with bilateral apparent stage IC1 endometrioid ovarian cancer underwent surgical staging by SLN biopsy and subsequent comprehensive laparoscopic pelvic and -aortic lymphadenectomy. Out of 4 SLNs submitted to ultrastaging, one was positive for isolated tumour cells (ITCs). We submitted to ultra-staging all the other 24 pelvic and -aortic non-SLNs, which were reported negative for disease. This is the first reported case of comprehensive lymphadenectomy after SLN biopsy with universal ultrastaging of all non-SLNs in ovarian cancer. The presence of ITCs in only one SLN, with all other 27 lymph nodes negative at ultrastaging, is consistent with the SLN concept and the assumption of a reliable lymphatic pathway in ovarian cancer.
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http://dx.doi.org/10.1016/j.gore.2022.101047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9309418PMC
August 2022

Risk reducing surgery with peritoneal staging in BRCA1-2 mutation carriers. A prospective study.

Eur J Surg Oncol 2022 Jul 19. Epub 2022 Jul 19.

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

Introduction: International guidelines recommend risk-reducing salpingo-oophorectomy (RRSO) in BRCA1-2 mutations carriers to decrease ovarian cancer occurrence. In this prospective study, we describe the incidence of occult malignancies and the surgical outcomes in asymptomatic BRCA mutation carriers submitted to RRSO.

Methods: Data on BRCA1-2 carriers undergoing RRSO with peritoneal washing and peritoneal/omental biopsies (PeS), between January 2019 until March 2021, were prospectively collected.

Results: A total of 132 patients were enrolled: 74 BRCA1 and 58 BRCA2 mutation carriers. 31.1% women underwent RRSO and PeS (16.2% of BRCA1 and 50% of BRCA2 carriers), while 68.9% patients were submitted also to concomitant hysterectomy. Almost all the procedures (99.2%) were performed by minimally invasive surgery. Postoperative complications occurred in twelve patients (9.1%): 10 in the concomitant hysterectomy group and two complications in the RRSO group. At the final pathological examination, 6 (4.5%) occult carcinomas were diagnosed: 3 fallopian tube carcinomas, one ovarian carcinoma and two serous tubal intraepithelial carcinomas (STICs), with negative PeS. Median age of occult carcinomas patients at RRSO was 54 (range: 48-79) years. The mean follow up was 20 (range: 7-34) months. During the follow up, no primary peritoneal cancer has been diagnosed.

Conclusions: Occult pathologic findings in RRSO occurred in 4.5% (3% invasive carcinomas, STIC 1.5%) among our patients. The routine use of peritoneal biopsies does not improve the detection of occult malignancies. Our data confirm the importance of timely performing RRSO in BRCA1-2 carriers.
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http://dx.doi.org/10.1016/j.ejso.2022.07.007DOI Listing
July 2022

Retrospective study of histopathological and prognostic characteristics of primary fallopian tube carcinomas: twenty-year experience (SOCRATE).

Int J Gynecol Cancer 2022 Jul 22. Epub 2022 Jul 22.

Dipartimento Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Unità di Gineco-patologia e Patologia Mammaria, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

Objective: Primary fallopian tube carcinoma represents a rare entity, accounting for about 0.75%-1.2% of all gynecological malignancies. The rationale of our study is to describe the prognosis of primary fallopian tube carcinoma.

Methods: We retrospectively identified patients with FIGO stage I-IV, all histology types and grading primary fallopian tube carcinoma treated in three major oncological centers between January 2000 and March 2020. Exclusion criteria were bulky tubo-ovarian carcinomas, isolated serous tubal intraepithelial carcinoma or neoadjuvant chemotherapy.

Results: A total of 61 patients were included. The vast majority of primary fallopian tube carcinomas were serous (96.7%) and poorly differentiated (96.7%) and arose from the fimbriated end of the tube (88.5%). Larger tumor size correlated with higher probability of correct preoperative differential diagnosis of primary fallopian tube carcinoma (p=0.003). Up to 82.4% of patients with small tumors (≤15 mm) presented with high FIGO stage (≥IIA). The most common site of metastasis was pelvic peritoneum (18.8%) and among 59% of patients who underwent lymphadenectomy smaller tumors had higher rate of nodal metastasis (42.9%≤10 mm vs 27.3%>50 mm). After 46.0 months of mean follow-up there were 27 recurrences (48.2%). The most common site of relapse was diffuse peritoneal spread (18.5%). The 5-year disease-free survival was 45.2% and 5-year overall survival was 75.5%. Of note, 42.9% of patients with stage IVB survived >36 months.

Conclusion: Primary fallopian tube carcinoma is a biologically distinct tumor from primary epithelial ovarian carcinoma and it is mostly located in the fimbriated end of the tube. In addition, it is characterized by a high rate of retroperitoneal dissemination even at apparently an early stage and its size does not correlate with FIGO stage at presentation.
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http://dx.doi.org/10.1136/ijgc-2022-003468DOI Listing
July 2022

Management of oligometastatic ovarian cancer recurrence during PARP inhibitor maintenance.

Int J Gynecol Cancer 2022 Jul 22. Epub 2022 Jul 22.

Dipartimento per la Salute della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario Agostino Gemelli-IRCCS, Rome, Italy

Objective: The benefit of surgery and maintenance treatment with PARP inhibitors (PARPi) has been clearly demonstrated in ovarian cancer. Also, the efficacy and safety of stereotactic body radiotherapy has been shown in patients with metastatic, persistent, and recurrent disease. The aim of this study is to evaluate the management of oligometastatic progression during PARPi maintenance treatment.

Methods: This is an observational, retrospective, single-arm study conducted from June 2017 to December 2020 in patients with recurrent ovarian cancer with oligometastatic progression under PARPi maintenance treatment and receiving surgery or stereotactic body radiotherapy for such recurrence. PARPi treatment was continued until further progression of the disease. The primary objective of the study was the median prolongation of the treatment-free interval-p (without platinum) after local treatment.

Results: A total of 186 patients with ovarian cancer were treated with PARPi at recurrence. Of these, 30 (16%) developed oligometastatic progression. The median age was 49.5 years (range 35-73). Olaparib, niraparib and rucaparib were administered to 33%, 60%, and 7% of patients, respectively. The median prolongation of the treatment-free interval-p of patients treated with surgery or stereotactic body radiotherapy was 6 and 10 months, respectively (p=0.53). The median treatment-free interval-p of patients treated with surgery or stereotactic body radiotherapy at the time of oligometastatic progression was 32 and 29 months, respectively (p=0.44). At the time of this publication, 50% of patients are still on treatment with PARPi following progression.

Conclusions: Patients with recurrent ovarian cancer who have oligometastic progression during PARPi maintenance may continue to benefit from PARPi if combined with local treatment.
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http://dx.doi.org/10.1136/ijgc-2022-003543DOI Listing
July 2022

Use of Laparoscopic and Laparotomic J-Plasma Handpiece in Gynecological Malignancies: Results From A Pilot Study in A Tertiary Care Center.

Front Oncol 2022 28;12:868930. Epub 2022 Jun 28.

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

Introduction: The J-Plasma has recently been introduced into the surgical community with different intrinsic characteristics aimed to further reduce the thermal effect and enhance precision when compared to standard radiofrequency. This study aimed to investigate the role of this new technology in different conditions of gynecological carcinomatosis characterized by the indication for regional peritonectomy and/or ablation, either in laparotomy (LPT) or in laparoscopy (LPS), in the context of a modern personalized approach to the surgical management of gynecological malignancies.

Material And Methods: From January 2019 to April 2019, 12 patients were selected for this prospective pilot study at the Division of Gynecologic Oncology, Fondazione Policlinico Universitario A. Gemelli IRCCS in Rome. In this single surgeon experience, the inclusion criteria were: histologically proven advanced ovarian/endometrial cancer, primary or interval debulking surgery, and intraoperative indication for regional peritonectomy. Six patients were treated by LPS (Group 1) and 6 by LPT (Group 2).

Results: In Group 1 the indication for debulking surgery was in 4 cases an interval debulking surgery and 2 advanced endometrial cancer. All patients in Group 2 underwent primary debulking surgery for advanced ovarian cancer. The whole cohort achieved a complete tumor excision after surgery. The median OT and median EBL were 195 min and 100 ml in Group 1, and 420 min and 500 ml in Group 2. The median hospital stay was 4 days in Group 1 and 13 days in Group 2, respectively. No intra and postoperative complications were registered within 60 days after surgery.

Conclusions: J-Plasma allows to approach delicate maneuvers on viscera, mesentery, and blood vessels with a high degree of safety and precision thanks to its limited vertical and lateral thermal spread, favoring the surgeon to push ever higher the cytoreduction/morbidity tradeoff. The use of J-Plasma in cytoreductive surgery could also increase the range of possible minimally invasive procedures, narrowing the technical distance with the open technique and thus contributing to designing a personalized surgical strategy for each patient in different scenarios of peritoneal carcinomatosis.
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http://dx.doi.org/10.3389/fonc.2022.868930DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9274254PMC
June 2022

Simplified anatomical nomenclature of lateral female pelvic spaces.

Int J Gynecol Cancer 2022 Jul 5. Epub 2022 Jul 5.

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

Objectives: The surgical management of gynecological malignancies involves the development of spaces and division of structures attaching the genital tract to other pelvic organs and to the pelvic sidewall. Definition, description, and denomination of these components are heterogeneous and may not be consistent with the anatomical nomenclature. The purpose of this article is to propose a simplified nomenclature of surgical anatomy of the female pelvis.

Methods: We performed dissection of fresh cadavers at the anatomy laboratory of the University of the Sacred Heart, Rome, Italy. Dissections were designed to illustrate surgical concepts developed by the first author. All authors agreed a consensus on the description and denomination of the nomenclature.

Results: The nomenclature system results in a simplified nomenclature, purely descriptive, avoiding eponyms, designed to be used by surgeons, teachers, staff members, and trainees.

Conclusions: Simplification of the anatomical description of the female pelvis is crucial to standardize operative reports in clinical practice.
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http://dx.doi.org/10.1136/ijgc-2022-003531DOI Listing
July 2022

Outcomes of gynecologic cancer surgery during the COVID-19 pandemic: an international, multicenter, prospective CovidSurg-Gynecologic Oncology Cancer study.

Am J Obstet Gynecol 2022 Jun 30. Epub 2022 Jun 30.

Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, United Kingdom. Electronic address:

Background: The CovidSurg-Cancer Consortium aimed to explore the impact of COVID-19 in surgical patients and services for solid cancers at the start of the pandemic. The CovidSurg-Gynecologic Oncology Cancer subgroup was particularly concerned about the magnitude of adverse outcomes caused by the disrupted surgical gynecologic cancer care during the COVID-19 pandemic, which are currently unclear.

Objective: This study aimed to evaluate the changes in care and short-term outcomes of surgical patients with gynecologic cancers during the COVID-19 pandemic. We hypothesized that the COVID-19 pandemic had led to a delay in surgical cancer care, especially in patients who required more extensive surgery, and such delay had an impact on cancer outcomes.

Study Design: This was a multicenter, international, prospective cohort study. Consecutive patients with gynecologic cancers who were initially planned for nonpalliative surgery, were recruited from the date of first COVID-19-related admission in each participating center for 3 months. The follow-up period was 3 months from the time of the multidisciplinary tumor board decision to operate. The primary outcome of this analysis is the incidence of pandemic-related changes in care. The secondary outcomes included 30-day perioperative mortality and morbidity and a composite outcome of unresectable disease or disease progression, emergency surgery, and death.

Results: We included 3973 patients (3784 operated and 189 nonoperated) from 227 centers in 52 countries and 7 world regions who were initially planned to have cancer surgery. In 20.7% (823/3973) of the patients, the standard of care was adjusted. A significant delay (>8 weeks) was observed in 11.2% (424/3784) of patients, particularly in those with ovarian cancer (213/1355; 15.7%; P<.0001). This delay was associated with a composite of adverse outcomes, including disease progression and death (95/424; 22.4% vs 601/3360; 17.9%; P=.024) compared with those who had operations within 8 weeks of tumor board decisions. One in 13 (189/2430; 7.9%) did not receive their planned operations, in whom 1 in 20 (5/189; 2.7%) died and 1 in 5 (34/189; 18%) experienced disease progression or death within 3 months of multidisciplinary team board decision for surgery. Only 22 of the 3778 surgical patients (0.6%) acquired perioperative SARS-CoV-2 infections; they had a longer postoperative stay (median 8.5 vs 4 days; P<.0001), higher predefined surgical morbidity (14/22; 63.6% vs 717/3762; 19.1%; P<.0001) and mortality (4/22; 18.2% vs 26/3762; 0.7%; P<.0001) rates than the uninfected cohort.

Conclusion: One in 5 surgical patients with gynecologic cancer worldwide experienced management modifications during the COVID-19 pandemic. Significant adverse outcomes were observed in those with delayed or cancelled operations, and coordinated mitigating strategies are urgently needed.
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http://dx.doi.org/10.1016/j.ajog.2022.06.052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9242690PMC
June 2022

Introducing the New Surgical Robot HUGO™ RAS: System Description and Docking Settings for Gynecological Surgery.

Front Oncol 2022 9;12:898060. Epub 2022 Jun 9.

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

This study provides a detailed description of the new HUGO™ RAS System and suggests docking settings for gynecological surgery. The system is composed of an "open" surgical console with an HD-3D passive display, a system tower, and four arm carts. Each arm has an extremely wide range of adaptability resulting from the numerous joints. The human cadaver labs were performed at the ORSI Academy between August and December 2021. All procedures were performed by two surgical teams, each composed of a high-volume surgeon experienced in robotic surgery, gynecologic oncology, and pelvic sidewall surgery, and one bedside assistant. Three main gynecological surgical scenarios were identified: standard pelvic surgery, pelvic sidewall surgery, and para-aortic/upper abdominal surgery. Concerning the port placement, the chosen options were called "straight" and "bridge"; instead, the so-called "compact" and "butterfly" configurations were identified for the arm cart positioning. Four cadavers were used to perform total hysterectomy, radical hysterectomy, pelvic exenteration, pelvic and para-aortic lymphadenectomy, and omentectomy. We performed several tests, identifying the best system configurations to draw the proper efficiency from the flexibility of the system in all gynecological surgical scenarios. The straight port placement seems to be adequate for standard pelvic surgery. The bridge trocar position is best to reach the deeper and lateral anatomical regions of the female pelvis. The compact and butterfly arm cart allocations are adequate for both straight and bridge port placement. When deep pelvic surgery was performed, the bedside assistant became more proficient by working with a standard laparoscopic instrument from an ancillary port placed in the left iliac fossa. The arm carts needed to be moved in an open manner, like for the proposed butterfly configuration. On the contrary, the compact disposition left enough space to assist from Palmer's point port. Several basic and advanced gynecological surgical procedures were performed and completed successfully without encountering any technical or surgical issue, the results obtained were judged sufficient to proceed with the clinical experience in daily practice. The HUGO™ RAS system is flexible and highly performative in various surgical scenarios.
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http://dx.doi.org/10.3389/fonc.2022.898060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9218341PMC
June 2022

Diagnostic performance of ultrasound in assessing the extension of disease in advanced ovarian cancer.

Am J Obstet Gynecol 2022 Jun 23. Epub 2022 Jun 23.

Dipartimento Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario Agostino Gemelli, Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy. Electronic address:

Background: Surgical exploration remains the gold standard for evaluating the extension of disease and predicting resectability. A laparoscopy-based scoring model was developed by Fagotti and colleagues in 2006 and updated in 2015, based on the intraoperative presence or absence of some specific cancer features. The model proved an overall accuracy rate of 77% to 100% and is considered the reference test for assessing resectability in our institution.

Objective: The primary aim of the study was to analyze the agreement between preoperative ultrasound examination and laparoscopic findings in assessing the extension of intraabdominal disease using 6 parameters described by Fagotti's score.

Study Design: This was a prospective single-center observational study. Between January 2019 and June 2020, consecutive patients with clinical or radiological suspicion of ovarian or peritoneal cancer were assessed with preoperative ultrasound examination and assigned a score based on the 6 Fagotti score parameters (great omentum, liver surface, lesser omentum/stomach/spleen, parietal peritoneum, diaphragms, bowel disease). Presence of mesenteral retraction of the small bowel and miliary carcinomatosis on the serosa were also evaluated. Each parameter was correlated with laparoscopic findings. Concordance was calculated between ultrasound and laparoscopic parameters using Cohen's kappa.

Results: Cohen's kappa ranged from 0.70 to 0.90 for carcinomatosis on the small or large bowel, supracolic omentum, liver surface, and diaphragms. Cohen's kappa test was lower for carcinomatosis on the parietal peritoneum (k=0.63) and on the lesser omentum or lesser curvature of the stomach or spleen (k=0.54). The agreement between ultrasound and surgical predictive index value (score) was k=0.74. For the evaluation of mesenteral retraction and miliary carcinomatosis, the agreement was low (k=0.57 and k=0.36, respectively).

Conclusion: The results of ultrasound and laparoscopy in the assessment of intraabdominal tumor spread were in substantial agreement for almost all the parameters. Ultrasound examination can play a useful role in the preoperative management of patients with ovarian cancer when used in dedicated referral centers.
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http://dx.doi.org/10.1016/j.ajog.2022.05.029DOI Listing
June 2022

Preclinical models of epithelial ovarian cancer: practical considerations and challenges for a meaningful application.

Cell Mol Life Sci 2022 Jun 16;79(7):364. Epub 2022 Jun 16.

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, Largo A. Gemelli 8, 00168, Rome, Italy.

Despite many improvements in ovarian cancer diagnosis and treatment, until now, conventional chemotherapy and new biological drugs have not been shown to cure the disease, and the overall prognosis remains poor. Over 90% of ovarian malignancies are categorized as epithelial ovarian cancers (EOC), a collection of different types of neoplasms with distinctive disease biology, response to chemotherapy, and outcome. Advances in our understanding of the histopathology and molecular features of EOC subtypes, as well as the cellular origins of these cancers, have given a boost to the development of clinically relevant experimental models. The overall goal of this review is to provide a comprehensive description of the available preclinical investigational approaches aimed at better characterizing disease development and progression and at identifying new therapeutic strategies. Systems discussed comprise monolayer (2D) and three-dimensional (3D) cultures of established and primary cancer cell lines, organoids and patient-derived explants, animal models, including carcinogen-induced, syngeneic, genetically engineered mouse, xenografts, patient-derived xenografts (PDX), humanized PDX, and the zebrafish and the laying hen models. Recent advances in tumour-on-a-chip platforms are also detailed. The critical analysis of strengths and weaknesses of each experimental model will aid in identifying opportunities to optimize their translational value.
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http://dx.doi.org/10.1007/s00018-022-04395-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9200670PMC
June 2022

CT-Based Radiomics and Deep Learning for BRCA Mutation and Progression-Free Survival Prediction in Ovarian Cancer Using a Multicentric Dataset.

Cancers (Basel) 2022 May 31;14(11). Epub 2022 May 31.

Department of Bioimaging, Radiation Oncology and Hematology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo A. Gemelli 8, 00168 Rome, Italy.

Purpose: Build predictive radiomic models for early relapse and BRCA mutation based on a multicentric database of high-grade serous ovarian cancer (HGSOC) and validate them in a test set coming from different institutions.

Methods: Preoperative CTs of patients with HGSOC treated at four referral centers were retrospectively acquired and manually segmented. Hand-crafted features and deep radiomics features were extracted respectively by dedicated software (MODDICOM) and a dedicated convolutional neural network (CNN). Features were selected with and without prior harmonization (ComBat harmonization), and models were built using different machine learning algorithms, including clinical variables.

Results: We included 218 patients. Radiomic models showed low performance in predicting both BRCA mutation (AUC in test set between 0.46 and 0.59) and 1-year relapse (AUC in test set between 0.46 and 0.56); deep learning models demonstrated similar results (AUC in the test of 0.48 for BRCA and 0.50 for relapse). The inclusion of clinical variables improved the performance of the radiomic models to predict BRCA mutation (AUC in the test set of 0.74).

Conclusions: In our multicentric dataset, representative of a real-life clinical scenario, we could not find a good radiomic predicting model for PFS and BRCA mutational status, with both traditional radiomics and deep learning, but the combination of clinical and radiomic models improved model performance for the prediction of BRCA mutation. These findings highlight the need for standardization through the whole radiomic pipelines and robust multicentric external validations of results.
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http://dx.doi.org/10.3390/cancers14112739DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9179845PMC
May 2022

ASO Author Reflections: Laparoscopic Ovarian Transposition for Locally Advanced Cervical Cancer-Tailoring the Treatment with the Standardization of a Surgical Procedure.

Ann Surg Oncol 2022 Sep 7;29(9):5908-5909. Epub 2022 Jun 7.

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

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http://dx.doi.org/10.1245/s10434-022-11969-4DOI Listing
September 2022

Low-grade serous ovarian cancer in pregnancy.

Int J Gynecol Cancer 2022 06 6;32(6):804-808. Epub 2022 Jun 6.

Department of Woman's and Child Health and Public Health Sciences, Gynecologic Oncology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy

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http://dx.doi.org/10.1136/ijgc-2022-003577DOI Listing
June 2022

Laparoscopic Ovarian Transposition with Extraperitonealization of the Infundibulopelvic Ligament for Cervical Cancer in Ten Steps.

Ann Surg Oncol 2022 Sep 24;29(9):5906-5907. Epub 2022 May 24.

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

Preservation of ovarian function is important for the physical and psychosexual well-being of young patients with cancer. Patients with pelvic malignancies such as cervical or rectal cancer planned for radiotherapy may benefit from ovarian transposition with the aim of moving the ovaries outside the radiation field. Different surgical techniques have been reported previously. With the present video, we aim to standardize the surgical technique of laparoscopic ovarian transposition in ten steps. We present the case of a 30-year-old nulliparous woman diagnosed with grade 3 squamous cell cervical carcinoma having a largest tumor diameter of 41 mm on magnetic resonance imaging (MRI) scan. The tumor was staged as FIGO 2018 stage IIIC1r with a common iliac lymphadenopathy reported on both MRI and positron emission tomography (PET)/computed tomography (CT) scan. The multidisciplinary team recommended exclusive chemoradiation extended to paraaortic area. The patient underwent laparoscopic bilateral salpingectomy and bilateral ovarian transposition with extraperitonealization of the infundibulopelvic ligament. The procedure was divided into the following ten steps: division of uteroovarian ligament, incision of lateral pelvic peritoneum, identification of ureter, incision of medial pelvic peritoneum, skeletonization of the infundibulopelvic ligament, retroperitoneal tunnel in paracolic gutter, creating the window (as high as possible), mobilization of the ovary without torsion, intraperitonealization of the ovary, and fix ovary with clips (Fig. 1). Surgical time was 30 min, with minimal estimated blood loss. No intra- or postoperative complication was recorded. The patient started radiotherapy 14 days after the procedure. In conclusion, we showed that laparoscopic ovarian transposition in cervical cancer before radiotherapy can be standardized in ten steps with encouraging perioperative results, making it an easily reproducible procedure. Ovarian function is reported to be preserved in 62-65% of cases undergoing ovarian transposition and radiation therapy. Fig. 1 Laparoscopic view of right ovary transposed below the liver edge after extraperitonealization of the infudibulopelvic ligament.
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http://dx.doi.org/10.1245/s10434-022-11870-0DOI Listing
September 2022

Role of tertiary cytoreductive surgery in recurrent epithelial ovarian cancer: Systematic review and meta-analysis.

Gynecol Oncol 2022 Jul 9;166(1):181-187. Epub 2022 May 9.

City of Hope, California, USA.

Objective: To evaluate the clinical utility of tertiary cytoreductive surgery (TCS) in recurrent ovarian cancer.

Methods: MEDLINE via PubMed, Embase (Elsevier), ClinicalTrials.gov, Scopus (Elsevier) and Web of Science for studies from inception to 4/09/2021. Studies reporting disease specific survival (DSS) and overall survival (OS) among women who underwent optimal cytoreductive surgery as compared to those who had a suboptimal cytoreductive surgery at time of TCS were abstracted. Study quality was assessed with the Quality In Prognosis Studies (QUIPS) tool. The data were extracted independently by multiple observers. Random-effects models were used to pool associations and to analyze the association between survival and surgical outcomes.

Results: 10 studies met all the criteria for inclusion in the systematic review. Patients with optimal tertiary cytoreductive surgery had better DSS (HR = 0.35; 95% CI, 0.19-0.64, P < 0.001), with low heterogeneity (I = 0%, P = 0.41) when compared to those with suboptimal tertiary cytoreductive surgery. Pooled results from these studies also demonstrated a better OS (HR = 0.34; 95% CI, 0.15-0.74, P < 0.007) with moderate heterogeneity (I = 59%, P = 0.09) when compared to patients with a suboptimal tertiary cytoreductive surgery. This remained significant in a series of sensitivity analyses. Due to the limited number of studies, we were unable to do further subgroup analyses looking at outcomes comparing tertiary cytoreductive surgery to chemotherapy.

Conclusion: In this systematic review and meta-analysis of observational studies examining tertiary cytoreductive surgery for recurrent ovarian cancer, optimal tertiary cytoreductive surgery was associated with improved OS and DSS survival compared to suboptimal tertiary cytoreductive surgery.
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http://dx.doi.org/10.1016/j.ygyno.2022.04.005DOI Listing
July 2022

Different Surgical Approaches for Early-Stage Ovarian Cancer Staging. A Large Monocentric Experience.

Front Med (Lausanne) 2022 25;9:880681. Epub 2022 Apr 25.

Department of Medicine and Health Science, "V.Tiberio" Università Degli Studi del Molise, Campobasso, Italy.

Introduction: Ovarian cancer is the third most frequent gynecological cancer. In early stage ovarian cancer (ESOC) comprehensive surgical staging is recommended. Surgical staging is traditionally approached by laparotomy, although minimally invasive surgery can be a valid alternative in selected patients. This study aims to analyze the surgical and oncological outcomes of three different surgical approaches in a large series of patients.

Methods: We retrospectively included all histologically proven ESOC cases treated between January 2014 and December 2017. ESOC was defined as stage IA to IIB according to the 2018 FIGO staging system. Subjects were divided into groups 1, 2, and 3, based on the surgical approach (open abdominal, laparoscopic, or robotic, respectively).

Results: Within patients enrolled during the study period, 455 met the inclusion criteria. No difference in intraoperative complications was recorded in the three groups ( = 0.709). Conversely, a significant difference occurred in postoperative complications (16.2 vs. 3.8 vs. 11.1%, in groups 1, 2, and 3 respectively, = 0.004). No difference was found in overall survival (OS) (32 vs. 31 vs. 25 months, = 0.481) and disease-free survival (DFS) (26 vs. 29 vs. 24 months, = 0.178) in groups 1, 2, and 3, respectively. At univariate analysis FIGO stage I ( = 0.004) showed a lower recurrence rate compared to FIGO stage II.

Conclusion: No significant difference was found in OS and DFS among the three groups (open, laparoscopic, and robotic). The minimally invasive approach showed lower rate of complications than the laparotomic approach.
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http://dx.doi.org/10.3389/fmed.2022.880681DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9081786PMC
April 2022

A Laparoscopic Adjusted Model Able to Predict the Risk of Intraoperative Capsule Rupture in Early-stage Ovarian Cancer: Laparoscopic Ovarian Cancer Spillage Score (LOChneSS Study).

J Minim Invasive Gynecol 2022 Apr 29. Epub 2022 Apr 29.

Department of Obstetrics and Gynecology (Drs. Ghirardi, Rosati, Ergasti, Gueli Alletti, Mascilini, Scambia, Fagotti), Università Cattolica del Sacro Cuore, Rome, Italy.; Division of Gynecologic Oncology (Drs. Ghirardi, Rosati, Ergasti, Alletti, Mascilini, Scambia, Fagotti), Fondazione Policlinico Universitario A. Gemelli - IRCCS, Rome, Italy.. Electronic address:

Study Objective: To identify preoperative/intraoperative patient and tumor characteristics associated with an increased risk of tumor spillage during minimally invasive surgery (MIS) for early-stage ovarian cancer (OC). The secondary end point was to develop a score system able to estimate the risk of tumor rupture during MIS.

Design: Retrospective observational study.

Setting: Patients with International Federation of Gynecology and Obstetrics stage I OC.

Patients: Patients aged ≥18 years old, with International Federation of Gynecology and Obstetrics stage IA to IC1 OC of any histology.

Interventions: Preoperative and intraoperative characteristics of patients treated with MIS for early-stage OC at Policlinico Universitario Agostino Gemelli, IRCCS in Rome, Italy, from January 1, 2001, to December 31, 2017, were collected.

Measurements And Main Results: A total of 151 patients were included. Previous pelvic surgery was more represented in patients with nonruptured tumors (46.0% vs 63.4%; p = .042). In addition, a larger tumor diameter (p <.001), a higher body mass index (p = .032), ultrasound characteristics (p = .029), and adhesions to large bowel (14% vs 2.0%; p = .003), uterus (44% vs 6.9%; p <.001), contralateral ovary (8.0% vs 0%; p = .004), ovarian fossa (64% vs 14.9%; p <.001), and pouch of Douglas peritoneum (32% vs 4.0%; p <.001) increased rupture rate. At multivariate analysis, a larger tumor diameter (p <.001) and adhesions to ovarian fossa peritoneum (p = .007) were independently associated with intraoperative cancer spillage and included in the score calculation. A disease-free survival (DFS) difference between the rupture group and the no-rupture group was detected (5-year DFS, 74.9% vs 94.4%; p = .011), with superimposable overall survival (5-year overall survival, 91.2% vs 97.9%; p = .089).

Conclusion: Some preoperative/intraoperative characteristics increase the risk of tumor rupture during MIS for early-stage OC. A laparoscopic predictive model of capsule disruption could be considered to intraoperatively tailor surgical approach to prevent tumor spillage and avoid affecting patient's DFS.
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http://dx.doi.org/10.1016/j.jmig.2022.04.014DOI Listing
April 2022

Implementing a Personalized Antimicrobial Stewardship Program for Women with Gynecological Cancers and Healthcare-Associated Infections.

J Pers Med 2022 Apr 18;12(4). Epub 2022 Apr 18.

UOC Ginecologia Oncologica, Dipartimento di Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario A, Gemelli IRCCS, 00168 Roma, Italy.

Healthcare-associated infections (HCAIs) represent a major cause of morbidity and mortality in gynecologic cancer patients, requiring personalized cures. A retrospective study on gynecologic patients with HCAIs, managed through an antimicrobial stewardship program, was performed, focusing on rates of clinical cure, breakthrough/relapse of infections, death, and time of hospital stay (THS). In total, 27 patients (median 60 years, mainly suffering from ovarian, cervical, and uterine cancer) were evaluated by a specialist in infectious diseases and were mainly diagnosed with complicated urinary tract (cUTIs, 12 cases, 44.4%) and bloodstream infections (BSIs, 9 cases, 33.3%). A total of 15 cases (11 cUTIs, 73.3%) were managed with no need for hospitalization and received a median of 11 days of outpatient parenteral antimicrobial therapy (OPAT). In the remaining 12 cases (BSIs in 8 cases, 66.7%), the median THS was 11 days, with 15 days median overall duration of antimicrobial therapy (median 5-day reduction in THS). The management of patients also included source control and wound care. All patients reached clinical cure, with no case of breakthrough infection, one case of relapse, and one death within 30 days (not attributable to the infection). HCAIs in patients with gynecologic tumors can be managed through a patient-centered, multidisciplinary antimicrobial stewardship program.
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http://dx.doi.org/10.3390/jpm12040650DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9027292PMC
April 2022

Risk Factors for Anastomotic Leakage in Advanced Ovarian Cancer Surgery: A Large Single-Center Experience.

Ann Surg Oncol 2022 Aug 18;29(8):4791-4802. Epub 2022 Apr 18.

Division of Gynecologic Oncology, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy.

Background: Cytoreductive surgery is currently the main treatment for advanced epithelial ovarian cancer (OC), and several surgical maneuvers, including colorectal resection, are often needed to achieve no residual disease. High surgical complexity carries an inherent risk of postoperative complications, including anastomosis leakage (AL). Albeit rare, AL is a life-threatening condition. The aim of this single-center retrospective study is to assess the AL rate in patients undergoing colorectal resection and anastomosis during primary surgery for advanced epithelial OC through a standardized surgical technique and to evaluate possible pre/intra- and postoperative risk factors to identify the population at greatest risk.

Methods: A retrospective analysis of clinical and surgical characteristics of 515 patients undergoing colorectal resection and anastomosis during primary or interval debulking surgery between December 2011 and October 2019 was performed. Several pre/intra- and postoperative variables were evaluated by multivariate analysis as potential risk factors for AL.

Results: The overall anastomotic leakage rate was 2.9% (15/515) with a significant negative impact on postoperative course. Body mass index < 18 kg/m, preoperative albumin value lower than 30 mg/dL, section of the inferior mesenteric artery at its origin, and medium-low colorectal anastomosis (< 10 cm from the anal verge) were identified as independent risk factors for AL on multivariate analysis.

Conclusions: AL is confirmed to be an extremely rare but severe postoperative complication of OC surgery, being responsible for increased early postoperative mortality. Preoperative nutritional status and surgical characteristics, such as blood supply and anastomosis level, appear to be the most significant risk factors.
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http://dx.doi.org/10.1245/s10434-022-11686-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9246984PMC
August 2022

ASO Author Reflections: Risk Factors for Anastomotic Leakage in Advanced Ovarian Cancer Surgery-What We Know and Future Perspectives.

Ann Surg Oncol 2022 08 16;29(8):4803-4804. Epub 2022 Apr 16.

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

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http://dx.doi.org/10.1245/s10434-022-11690-2DOI Listing
August 2022

Needleoscopic-assisted risk-reducing bilateral salpingo-oophorectomy in BRCA1/2 mutation carriers: Peri-operative outcomes and psychological impact.

Eur J Obstet Gynecol Reprod Biol 2022 Jun 30;273:1-6. Epub 2022 Mar 30.

Fondazione Policlinico Universitario A. Gemelli, IRCCS, UOC Ginecologia Oncologica, Dipartimento per la salute della Donna e del Bambino e della Salute Pubblica, Rome, Italy; Università Cattolica del Sacro Cuore, Rome, Italy. Electronic address:

Objective: To investigate the role of needleoscopic-assisted laparoscopy in terms of surgical impact and psychological outcomes in RR-BSO for BRCA1/2 patients.

Study Design: Prospective monocentric trial conducted at the Division of Gynecologic Oncology, "Fondazione Policlinico Universitario A. Gemelli" IRCSS in Rome. Between March 2016 and March 2018, 26 consecutive patients were prospectively enrolled in the study and underwent RR-BSO. Peri-operative surgical variables were collected. The psychological interview was performed at the discharge and during the first post-operative follow-up visit (between 30 and 60 days after surgery).

Results: We reported a median OT of 18.5 min (range, 15-37), a median EBL of 0 mL (0-20), and no conversion to laparoscopy or laparotomy. The median VAS score was "at rest" of 2, 3, and 1; while under "Valsalva maneuver" was 4, 3, 2, respectively at 2, 4, and 24 h. 77% (20/26) of the whole population had a previous diagnosis of breast cancer. All patients expressed great cosmetic satisfaction both at discharge and after 30/60 days, with an 84.6% of score 5 and a 15.4% of score 4. The highest number of "score 5", concerning the cosmetic outcomes, were clustered in the subgroup of breast cancer survivors with a 95% of score 5 versus 50% of score 5 in patients with no previous breast cancer (p = 0.0073). Similarly, the maximal psychological advantage of the ultra-MIS approach was revealed in the breast cancer survivors (70% of score 5 versus 16% of score 5, p = 0.02).

Conclusions: The use of 2.4 mm instruments raises the possibility of decreasing post-operative incisional pain, reducing hospitalization, and ensuring better cosmetic and psychological outcomes without increasing complications. The full psychosomatic benefit of ultra-MIS within BRCA mutation carriers is revealed in breast cancer survivors, probably due to the comparison with the mutilating and invasive previous breast surgery.
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http://dx.doi.org/10.1016/j.ejogrb.2022.03.040DOI Listing
June 2022

Ovarian cancer metastases in the liver area: proposal of a standardized anatomo-surgical classification.

Int J Gynecol Cancer 2022 07 4;32(7):955-956. Epub 2022 Jul 4.

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

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http://dx.doi.org/10.1136/ijgc-2021-003307DOI Listing
July 2022

The impact of secondary cytoreductive surgery in platinum sensitive recurrent ovarian cancer treated with upfront neoadjuvant chemotherapy and interval debulking surgery.

Gynecol Oncol 2022 06 6;165(3):453-458. Epub 2022 Apr 6.

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

Objective: The aims of the present study were to assess the oncological outcomes of platinum-sensitive recurrent ovarian cancer patients undergoing secondary cytoreduction (SCS) after treatment with neoadjuvant chemotherapy (NACT) and interval debulking surgery (IDS) at diagnosis and to compare the performance of different selection models in these patients.

Methods: Retrospective, observational, single-center cohort study including patients with platinum-sensitive recurrent epithelial ovarian cancer with abdominal/inguinal/cardiophrenic disease between November 2012 and November 2020. Patients were selected as surgical candidates with PET/CT-scan and with diagnostic laparoscopy.

Results: 272 patients were included in the study. Of these, 165 (60.7%) patients were treated with PDS at diagnosis and 107 (39.3%) with IDS. SCS was performed in 178 (65.4%) cases, with complete gross resection achieved in 155/178 (87.1%). No progression-free survival (PFS) difference was demonstrated when patients treated with PDS were compared with those treated with NACT+IDS at first diagnosis (median 21 versus 21 months; p = 0.684); no post-recurrence survival (PRS) difference was evident between the two groups (median 81 versus 77 months, respectively; p = 0.574). Current selection models to candidate patients to SCS adequately performed in patients treated with IDS at diagnosis, as well as in the PDS group, with combination of PET/CT-scan and laparoscopy being an accurate tool in prediction of no gross residual disease at SCS in this pre-selected population.

Conclusions: Patients with platinum-sensitive recurrent epithelial ovarian cancer treated with NACT/IDS as primary treatment have similar post-recurrence survival outcomes of those treated with PDS. Current models to select patients for SCS can be safely applied to IDS patients.
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http://dx.doi.org/10.1016/j.ygyno.2022.03.024DOI Listing
June 2022

How should randomized controlled trials in epithelial ovarian cancer be interpreted?

Int J Gynecol Cancer 2022 05 3;32(5):693. Epub 2022 May 3.

Department of Woman's and Child Health and Public Health Sciences, Gynecologic Oncology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy

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http://dx.doi.org/10.1136/ijgc-2022-003541DOI Listing
May 2022

A commentary on the discrepancy between blood and tumour BRCA testing: An open question.

BJOG 2022 08 5;129(9):1422-1426. Epub 2022 Apr 5.

Departmental Unit of Molecular and Genomic Diagnostics, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

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http://dx.doi.org/10.1111/1471-0528.17158DOI Listing
August 2022

status and platinum sensitivity in advanced ovarian cancer according to Chemotherapy Response Score.

Int J Gynecol Cancer 2022 05 3;32(5):639-645. Epub 2022 May 3.

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

Objective: To evaluate a relation between status and the Chemotherapy Response Score in patients with epithelial ovarian cancer undergoing neoadjuvant chemotherapy and interval debulking surgery.

Methods: Data were retrospectively collected on patients with unresectable disease undergoing three or four cycles of neoadjuvant chemotherapy and interval debulking surgery at the Gynecologic Oncology Unit of the Catholic University of the Sacred Heart from January 2016 to December 2020. All patients were assessed for somatic mutation at diagnosis. The omental specimens obtained at the interval surgery were evaluated according to Bohm's Chemotherapy Response Score System.

Results: A total of 172 patients were included in the analysis, 69 (40%) patients were mutation carriers and 103 (60%) patients were wild type. In the wild-type group (), 73 (70.9%) patients had a Chemotherapy Response Score of 1 or 2 and 30 (29.1%) patients had a score of 3. In the carriers group (), 39 (56.5%) patients had a score of 1 or 2 and 30 (43.5%) patients had a score of 3. Among the group, those with a Chemotherapy Response Score of 3 had a prolonged median progression-free survival (22 vs 15 months, p=0.003). Among the carriers group, no differences were found (30 vs 27 months, p=0.55). No difference in overall survival was observed in either the carriers population (p=0.23) or the population (60 vs 44 months, p=0.06).

Conclusions: Patients with seem to achieve a score of 1, 2 or 3 with the same frequency. In contrast, patients with seem to have a score of 1 or 2 more frequently than a score of 3. In patients with , this score may not be an indicator of chemosensitivity.
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http://dx.doi.org/10.1136/ijgc-2021-003116DOI Listing
May 2022

Identification of a novel gene signature predicting response to first-line chemotherapy in BRCA wild-type high-grade serous ovarian cancer patients.

J Exp Clin Cancer Res 2022 Feb 4;41(1):50. Epub 2022 Feb 4.

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, Largo A. Gemelli 8, 00168, Rome, Italy.

Background: High-grade serous ovarian cancer (HGSOC) has poor survival rates due to a combination of diagnosis at advanced stage and disease recurrence as a result of chemotherapy resistance. In BRCA1 (Breast Cancer gene 1) - or BRCA2-wild type (BRCAwt) HGSOC patients, resistance and progressive disease occur earlier and more often than in mutated BRCA. Identification of biomarkers helpful in predicting response to first-line chemotherapy is a challenge to improve BRCAwt HGSOC management.

Methods: To identify a gene signature that can predict response to first-line chemotherapy, pre-treatment tumor biopsies from a restricted cohort of BRCAwt HGSOC patients were profiled by RNA sequencing (RNA-Seq) technology. Patients were sub-grouped according to platinum-free interval (PFI), into sensitive (PFI > 12 months) and resistant (PFI < 6 months). The gene panel identified by RNA-seq analysis was then tested by high-throughput quantitative real-time PCR (HT RT-qPCR) in a validation cohort, and statistical/bioinformatic methods were used to identify eligible markers and to explore the relevant pathway/gene network enrichments of the identified gene set. Finally, a panel of primary HGSOC cell lines was exploited to uncover cell-autonomous mechanisms of resistance.

Results: RNA-seq identified a 42-gene panel discriminating sensitive and resistant BRCAwt HGSOC patients and pathway analysis pointed to the immune system as a possible driver of chemotherapy response. From the extended cohort analysis of the 42 DEGs (differentially expressed genes), a statistical approach combined with the random forest classifier model generated a ten-gene signature predictive of response to first-line chemotherapy. The ten-gene signature included: CKB (Creatine kinase B), CTNNBL1 (Catenin, beta like 1), GNG11 (G protein subunit gamma 11), IGFBP7 (Insulin-like growth factor-binding protein 7), PLCG2 (Phospholipase C, gamma 2), RNF24 (Ring finger protein 24), SLC15A3 (Solute carrier family 15 member 3), TSPAN31 (Tetraspanin 31), TTI1 (TELO2 interacting protein 1) and UQCC1 (Ubiquinol-cytochrome c reductase complex assembly factor). Cytotoxicity assays, combined with gene-expression analysis in primary HGSOC cell lines, allowed to define CTNNBL1, RNF24, and TTI1 as cell-autonomous contributors to tumor resistance.

Conclusions: Using machine-learning techniques we have identified a gene signature that could predict response to first-line chemotherapy in BRCAwt HGSOC patients, providing a useful tool towards personalized treatment modalities.
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http://dx.doi.org/10.1186/s13046-022-02265-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8815250PMC
February 2022

Toll-like receptor 8 agonists improve NK-cell function primarily targeting CD56CD16 subset.

J Immunother Cancer 2022 01;10(1)

Department of Immunology, Bambino Gesu Pediatric Hospital, Roma, Italy

Background: Toll-like receptors (TLRs) are pattern-recognition sensors mainly expressed in innate immune cells that directly recognize conserved pathogen structures (pathogen-associated molecular patterns-PAMPs). Natural killer (NK) cells have been described to express different endosomal TLRs triggered by RNA and DNA sequences derived from both viruses and bacteria. This study was addressed to establish which endosomal TLR could directly mediate NK activation and function after proper stimuli. It was also important to establish the most suitable TLR agonist to be used as adjuvant in tumor vaccines or in combined cancer immunotherapies.

Methods: We assessed endosomal TLR expression in total NK cells by using RT-qPCR and western blotting technique. In some experiments, we purified CD56CD16 and CD56CD16 cells subsets by using NK Cell Isolation Kit Activation marker, cytokine production, CD107a expression and cytotoxicity assay were evaluated by flow cytometry. Cytokine release was quantified by ELISA. NK cells obtained from ovarian ascites underwent the same analyses.

Results: Although the four endosomal TLRs (TLR3, TLR7/8, and TLR9) were uniformly expressed on CD56CD16 and CD56CD16 cell subsets, the TLR7/8 (R848), TLR3 (polyinosinic-polycytidylic acid, Poly I:C) and TLR9 (ODN2395) ligands promoted NK-cell function only in the presence of suboptimal doses of cytokines, including interleukin (IL)-2, IL-12, IL-15, and IL-18, produced by other environmental cells. We showed that R848 rather than TLR3 and TLR9 agonists primarily activated CD56CD16 NK cells by increasing their proliferation, cytokine production and cytotoxic activity. Moreover, we demonstrated that R848, which usually triggers TLR7 and TLR8 on dendritic cells, macrophages and neutrophils cells, activated CD56CD16 NK-cell subset only via TLR8. Indeed, specific TLR8 but not TLR7 agonists increased cytokine production and cytotoxic activity of CD56CD16 NK cells. Importantly, these activities were also observed in peritoneal NK cells from patients with metastatic ovarian carcinoma, prevalently belonging to the CD56CD16 subset.

Conclusion: These data highlight the potential value of TLR8 in NK cells as a new target for immunotherapy in patients with cancer.
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http://dx.doi.org/10.1136/jitc-2021-003385DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8804697PMC
January 2022

Hyperthermic intraperitoneal chemotherapy (HIPEC) after primary debulking surgery in advanced epithelial ovarian cancer: Is BRCA mutational status making the difference?

Cancer Treat Res Commun 2022 14;31:100518. Epub 2022 Jan 14.

Fondazione Policlinico Universitario A. Gemelli, IRCCS, UOC Ginecologia Oncologica, Dipartimento per la salute della Donna e del Bambino e della Salute Pubblica, Rome, Italy; Universita' Cattolica del Sacro Cuore, Rome, Italy. Electronic address:

Introduction: The role of a molecular pattern predictive of hyperthermic intraperitoneal chemotherapy (HIPEC) efficacy in advanced ovarian cancer (AOC) patients has been poorly investigated. We aimed to assess the effect of HIPEC after primary debulking surgery (PDS) in AOC according to patient's Breast Cancer Gene (BRCA) mutational status.

Methods: This is a retrospective, single center, case-control study. Data on AOC patients receiving HIPEC at the end of PDS as previously enrolled in a phase II monocentric trial (HIPEC group), were retrieved and matched for clinical and surgical characteristics with a group of cases who underwent PDS without receiving HIPEC between 01/2010 and 01/2015 (No HIPEC group). Patients with International Federation of Gynecology and Obstetrics (FIGO) stage ≥IIIB disease, aged between 18 and 70 years, with a laparoscopic Predictive Index value (PIV) ≤8 and residual disease ≤2.5 mm were included.

Results: 70 patients were included. With the except of age (p = 0.012), the populations were balanced for the main characteristics. At a median follow-up of 48 months, no differences in Progression Free Survival (PFS) (p = 0.968) and Overall Survival (OS) (p = 0.789) were recorded. Survival analysis according to HIPEC administration and BRCA mutational status showed an improved PFS (p = 0.011) and OS (p = 0.003) in BRCA mutated compared to wild-type patients when HIPEC was not administered, whilst they were superimposable in case of HIPEC administration (p = 0.857 vs p = 0.372; respectively). No differences in terms of neither intra-operative (p = 1.0) nor early post-operative complications (p = 0.920) were detected.

Conclusions: Our results show that HIPEC in AOC may be a promising treatment in BRCA wild-type patients, as it seems to balance their decreased chemosensitivity compared to mutation carriers.
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http://dx.doi.org/10.1016/j.ctarc.2022.100518DOI Listing
May 2022
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