Genomic profiling of primary and recurrent ovarian cancers: A retrospective single-center experience

Background: The oncology landscape is rapidly evolving towards more personalized treatment with the use of molecular-driven therapies. Thus, genomic information has become an integral component of clinical decision-making. This study aims to analyze tumor tissue samples of high-grade serous ovarian cancer (HGSOC) to understand if genomic changes in gene mutation frequencies between primary and relapsing tumors occur and can influence the detection of actionable gene alterations. Method(s): A retrospective study approved by local Ethics Committee was conducted on OC patients treated at Fondazione Policlinico Universitario A. Gemelli, IRCCS. All subjects provided informed written consent for genetic analysis and study participation. FFPE specimens were analyzed by Foundation One CDx, which applies NGS across 324 genes known to be drivers of solid tumors, by sequencing the coding regions of 309 cancer-related genes plus introns from 36 genes. Z-test was used to analyze the mutation frequencies between primary and relapsing tumors. Result(s): 261 patients underwent Foundation Medicine testing. Out of 216 HGSOC, 151 tests were performed on primary lesion, 43 at 1st/2nd recurrence, and 22 at >3 recurrences. Statistically significant changes in BRCA1-2 frequencies were found between primitive lesions and recurrence (p=0.0013). A lower frequency in TP53 (p=0.0013) and a higher frequency of NF1 (p=0.028) and TERC (p=0.027) mutations were shown in tissue collected at recurrence compared to primary lesion. Selective chemotherapy pressure and natural enrichment of better prognosis patients at recurrence may explain the discrepancies between primary and secondary tumors. Conclusion(s): These data suggest the opportunity to re-characterize the molecular profiling of the tumors at the time of recurrence to identify potentially actionable alterations to guide treatment. Legal entity responsible for the study: The authors. Funding(s): Has not received any funding. Disclosure: V. Salutari: Financial Interests, Personal and Institutional, Advisory Board: AstraZeneca, Clovis, GSK, Tesaro, MSD, Roche, PharmaMar, Eisai. G. Scambia: Financial Interests, Personal, Invited Speaker: Johnson & Johnson, AstraZeneca & MSD, Olympus Europa, Baxter Healthcare, Intuitive Surgical Inc., GlaxoSmithKline;Financial Interests, Personal, Expert Testimony, Trainer: Covidien AG (Medtronic company);Financial Interests, Institutional, Invited Speaker, 'IsoMSLN' in Ovarian Cancer and Malignant Pleural Mesothelioma: Kiromic;Financial Interests, Institutional, Invited Speaker, Roll-over study for patients who have completed a previous cancer study with olaparib and who the investigator believes can benefit from continued treatment - ROSY-O: AstraZeneca;Financial Interests, Institutional, Invited Speaker, CATCH-R: Roll-over study to provide continuous access to clinical therapy with rucaparib: Clovis Oncology;Financial Interests, Institutional, Invited Speaker, Phase III, multicenter, placebo-controlled clinical study comparing chemo-immunotherapy (paclitaxel-carboplatin-oregovomab) versus chemotherapy (paclitaxel-carboplatin-placebo) in patients with advanced epithelial ovarian, tubal cancer of fallopian or peritoneal (FLORA-5): Oncoquest Pharmaceuticals Inc.;Financial Interests, Institutional, Invited Speaker, Phase IIb randomized, open-label, active comparator, parallel-group, multicenter study designed to evaluate the efficacy and safety of three different doses of the P2X3 receptor antagonist (BAY 1817080) versus placebo and Elagolix 150 mg in women with symptomatic endometriosis: Bayer AG;Financial Interests, Institutional, Invited Speaker, Usability of ITE transducers for sending electric fields for tumor treatment (TTFields): Novocure Ltd.;Financial Interests, Institutional, Invited Speaker, Phase III, multicentre, open-label extension trial to evaluate long-term safety and efficacy in patients with advanced cancers currently undergoing treatment or in follow-up in a pembrolizumab trial: Merck. D. Lorusso: Financial Interests, Persona , Advisory Board, Participation in Advisory Boards and Invited Speaker: GSK, Clovis Oncology, PharmaMar;Financial Interests, Personal, Advisory Board, Participation in Advisory Boards and Invited Speakers: AstraZeneca, MSD;Financial Interests, Personal, Other, Consultancy: PharmaMar, Amgen, AstraZeneca, Clovis Oncology, GSK, MSD, Immunogen, Genmab, Seagen;Financial Interests, Personal, Advisory Board, Participation in Advisory Boards: Merck Serono;Financial Interests, Personal, Advisory Board, Invited member of advisory board: Seagen, Immunogen, Genmab, Oncoinvest, Corcept, Sutro;Financial Interests, Institutional, Funding, Grant for founding academic trial: MSD, Clovis Oncology, PharmaMar;Financial Interests, Institutional, Funding, Grant for founding academic trial: GSK;Financial Interests, Institutional, Invited Speaker, ENGOT trial with institutional support for coordination: Clovis Oncology;Financial Interests, Institutional, Invited Speaker, ENGOT trial with institutional support for coordination: Genmab, MSD;Financial Interests, Institutional, Funding, Clinical trial/contracted research: AstraZeneca, Clovis Oncology, GSK, MSD, Seagen;Financial Interests, Institutional, Funding, Clinical trials/contracted research: Genmab, Immunogen, Incyte, Novartis, Roche;Non-Financial Interests, Personal, Principal Investigator, PI of several trials, no compensation received: GSK;Non-Financial Interests, Personal, Principal Investigator, PI of several trials. No personal compensation received: AstraZeneca, GenMab;Non-Financial Interests, Personal, Principal Investigator, PI in several trials. No personal compensation received: MSD;Non-Financial Interests, Personal, Principal Investigator, PI of clinical trial. No personal compensation received: immunogen, clovis, Incyte;Non-Financial Interests, Personal, Principal Investigator, PI of clinical trial. No personal compensation receive: Roche;Non-Financial Interests, P rsonal, Member, Board of Directors: GCIG. All other authors have declared no conflicts of interest. Copyright © 2022 European Society for Medical Oncology

Clinical relevance of NGS analysis in endometrial cancer (EC) management

Background: After the introduction of the molecular classification in EC guidelines, Next Generation Sequencing (NGS) analysis has become an essential tool for EC management. Molecular-driven therapies have also been recently tested, and some have obtained FDA approval. This retrospective cohort study aims to determine the clinical benefit rate (CBR) with the use of targeted therapies based on NGS in ECs patients. Method(s): After approval of the local Ethics Committee, a retrospective study was conducted on EC patients undergoing Foundation Medicine testing at Fondazione Policlinico Universitario Agostino Gemelli IRCCS. All patients provided written informed consent. Formalin-fixed, paraffin-embedded (FFPE) tumor tissue specimens were analyzed by Foundation One CDx, which detects 324 genes known to be drivers of solid tumors based on NGS assay. Efficacy outcomes were estimated by the Kaplan-Meier method and expressed as median with its 95% confidence interval. IBM-SPSS v.27.0 software was used for statistical analyses. Result(s): Out of 35 tests performed, 11 patients received a targeted therapy based on actionable mutations detected with the NGS assays. All the 11 patients had been heavily pretreated (>=3 prior lines). One patient died because of COVID-19 and thus was excluded from the analysis. Out of the 10 patients included, targeted therapies showed an overall CBR of 80% in 8 patients (10% CR, 33.3% PR, 40% SD, and 20% PD). 7 patients were treated with a targeted agent belonging to the PI3K pathway, with 3 PR (42.9%), 3 SD (42.9%), and 1 PD (14.2%). 3 patients received PARP inhibitor treatment according to their HRD status, with 1 CR (33.3%), 1 SD (33.3%), and 1 PD (33.3%). Conclusion(s): In our series, an outstanding CBR of 80% was achieved with the use of targeted therapy according to NGS assays in heavily pretreated patients (>=3 prior lines). Our finding underlines the importance of molecular-driven treatments and requires further investigation to confirm these results in terms of clinical benefit in a broader population. Besides, the use of molecular-driven treatments may avoid unnecessary exposure to potentially more toxic therapies and reduce the costs associated with inappropriate treatments. Legal entity responsible for the study: The authors. Funding(s): Has not received any funding. Disclosure: V. Salutari: Financial Interests, Personal and Institutional, Advisory Board: AstraZeneca, Clovis, GSK, Tesaro, MSD, Roche, PharmaMar, Eisai. G. Scambia: Financial Interests, Personal, Invited Speaker, Speaker: Johnson & Johnson, AstraZeneca & MSD, Olympus Europa, Baxter Healthcare, Intuitive Surgical Inc., GlaxoSmithKline;Financial Interests, Personal, Expert Testimony, Trainer: Covidien AG (Medtronic company);Financial Interests, Institutional, Invited Speaker, 'IsoMSLN' in Ovarian Cancer and Malignant Pleural Mesothelioma: Kiromic;Financial Interests, Institutional, Invited Speaker, Roll-over study for patients who have completed a previous cancer study with olaparib and who the investigator believes can benefit from continued treatment - ROSY-O: AstraZeneca;Financial Interests, Institutional, Invited Speaker, CATCH-R: Roll-over study to provide continuous access to clinical therapy with rucaparib: Clovis Oncology;Financial Interests, Institutional, Invited Speaker, Phase III, multicenter, placebo-controlled clinical study comparing chemo-immunotherapy (paclitaxel-carboplatin-oregovomab) versus chemotherapy (paclitaxel-carboplatin-placebo) in patients with advanced epithelial ovarian, tubal cancer of fallopian or peritoneal (FLORA-5): Oncoquest Pharmaceuticals Inc.;Financial Interests, Institutional, Invited Speaker, Phase IIb randomized, open-label, active comparator, parallel-group, multicenter study designed to evaluate the efficacy and safety of three different doses of the P2X3 receptor antagonist (BAY 1817080) versus placebo and Elagolix 150 mg in women with symptomatic endometriosis: Bayer AG;Financial Interests, Institutional, Invited Speaker, Usability of ITE transducers for sending electr c fields for tumor treatment (TTFields): Novocure Ltd.;Financial Interests, Institutional, Invited Speaker, Phase III, multicentre, open-label extension trial to evaluate long-term safety and efficacy in patients with advanced cancers currently undergoing treatment or in follow-up in a pembrolizumab trial: Merck. D. Lorusso: Financial Interests, Personal, Advisory Board, Participation in Advisory Boards and Invited Speaker: GSK, Clovis Oncology, PharmaMar;Financial Interests, Personal, Advisory Board, Participation in Advisory Boards and Invited Speakers: AstraZeneca, MSD;Financial Interests, Personal, Other, Consultancy: PharmaMar, Amgen, AstraZeneca, Clovis Oncology, GSK, MSD, Immunogen, Genmab, Seagen;Financial Interests, Personal, Advisory Board, Participation in Advisory Boards: Merck Serono;Financial Interests, Personal, Advisory Board, Invited member of advisory board: Seagen, Immunogen, Genmab, Oncoinvest, Corcept, Sutro;Financial Interests, Institutional, Funding, Grant for founding academic trial: MSD, Clovis Oncology, PharmaMar;Financial Interests, Institutional, Funding, Grant for founding academic trial: GSK;Financial Interests, Institutional, Invited Speaker, ENGOT trial with institutional support for coordination: Clovis Oncology;Financial Interests, Institutional, Invited Speaker, ENGOT trial with institutional support for coordination: Genmab, MSD;Financial Interests, Institutional, Funding, Clinical trial/contracted research: AstraZeneca, Clovis Oncology, GSK, MSD, Seagen;Financial Interests, Institutional, Funding, Clinical trials/contracted research: Genmab, Immunogen, Incyte, Novartis, Roche;Non-Financial Interests, Personal, Principal Investigator, PI of several trials, no compensation received: GSK;Non-Financial Interests, Personal, Principal Investigator, PI of several trials. No personal compensation received: AstraZeneca, Genmab;Non-Financial Interests, Personal, Principal Investigator, PI in several trials. No personal compensation received: MSD;Non-Financial Interests, Personal, Principal Investigator, PI of clinical trial. No personal compensation received: Immunogen, Clovis, Incyte;Non-Financial Interests, Personal, Principal Investigator, PI of clinical trial. No personal compensation receive: Roche;Non-Financial Int rests, Personal, Member, Board of Directors: GCIG. All other authors have declared no conflicts of interest. Copyright © 2022 European Society for Medical Oncology

Final overall survival (OS) results from the phase III PAOLA-1/ENGOT-ov25 trial evaluating maintenance olaparib (ola) plus bevacizumab (bev) in patients (pts) with newly diagnosed advanced ovarian cancer (AOC)

Background: In the PAOLA-1/ENGOT-ov25 (NCT02477644) primary analysis, adding ola to maintenance bev after first-line (1L) platinum-based chemotherapy (PBC) + bev led to a significant progression-free survival (PFS) benefit in AOC (HR 0.59, 95% CI 0.49-0.72;P<0.001), particularly in pts with homologous recombination deficiency (HRD+;BRCA1/2 mutation [BRCAm] and/or genomic instability;Ray-Coquard et al NEJM 2019). Here, we report the prespecified final OS analysis. Method(s): Pts with high-grade AOC, in response after PBC + bev, were randomized 2:1 to ola tablets (300 mg bid;up to 24 months [mo]) + bev (15 mg/kg q3w;15 mo total) or placebo [pbo] + bev. OS (intent-to-treat [ITT] population) was a key secondary endpoint, with analysis planned for 3 years after the primary analysis as part of hierarchical testing. Result(s): 537 pts were randomized to ola + bev and 269 to pbo + bev (median follow-up 61.7 and 61.9 mo, respectively;OS data maturity: 55.3%). Median OS in the ITT population was 56.5 mo with ola + bev vs 51.6 mo with pbo + bev (HR 0.92, 95% CI 0.76-1.12;P=0.4118;OS at 5 y, 47.3 vs 41.5%). In HRD+ pts, OS was prolonged with ola + bev (HR 0.62, 95% CI 0.45-0.85;OS at 5 y, 65.5 vs 48.4%), with benefit in HRD+ pts with or without a tumour BRCAm (tBRCAm;Table). No benefit was seen in HRD- pts (HR 1.19, 95% CI 0.88-1.63). Subsequent PARP inhibitor therapy was received by 105 (19.6%) ola + bev pts vs 123 (45.7%) pbo + bev pts. Myelodysplastic syndrome, acute myeloid leukaemia and aplastic anaemia incidence, and new primary malignancy incidence, was respectively: ola + bev, 9 pts [1.6%] and 22 pts [4.1%];pbo + bev, 6 pts [2.2%]) and 8 pts [2.9%]). [Formula presented] Conclusion(s): Despite a high proportion of pts in the control arm receiving a PARP inhibitor post-progression, ola + bev provided a clinically meaningful improvement in OS for 1L HRD+ pts with and without a tBRCAm, confirming ola + bev as standard of care in this setting. Clinical trial identification: NCT02477644. Editorial acknowledgement: Medical writing assistance was provided by Rachel Dodd, PhD, at Cence, funded by AstraZeneca and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. Legal entity responsible for the study: AstraZeneca. Funding(s): ARCAGY Research, AstraZeneca, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, and F. Hoffmann-La Roche. Disclosure: I.L. Ray-Coquard: Financial Interests, Personal, Advisory Board: Roche, GSK, AstraZeneca, Mersana, Deciphera, Amgen, Oxnea, Merck Sereno, Agenus, Novartis, Macrogenics, Clovis, EQRX, adaptimmun, Esai, SUTRO;Financial Interests, Institutional, Other, COLIBRI translational research: BMS;Financial Interests, Institutional, Advisory Board, translational research NEOPREMBROV trial: MSD;Non-Financial Interests, Personal, Principal Investigator: PAOLA1;Non-Financial Interests, Personal, Other, President: GINECO. K. Fujiwara: Financial Interests, Personal, Other, Consulting fees and grant support: Pfizer, Eisai, Merck Sharp & Dohme, Taiho, Zeria, Chugai Pharmaceutical, Genmab, Takeda Pharmaceutical;Financial Interests, Personal, Research Grant: Immunogen, Oncotherapy, Regeneron;Financial Interests, Personal, Other, Consulting fees: Novartis, Kyowa Hakko Kirin, Daiichi Sankyo, Mochida Pharmaceutical, NanoCarrier. A. Leary: Financial Interests, Personal, Advisory Board: Zentalis;Financial Interests, Personal, Invited Speaker, Educational: GSK, Medscape, Onko+;Financial Interests, Institutional, Other, Steering committee: MSD;Financial Interests, Institutional, Advisory Board: GSK, AZ, Clovis, Ability Pharma, MSD, Tesaro, Merck Serono, Apmonia, Blueprint;Financial Interests, Institutional, Invited Speaker, Educational: Kephren publishing;Financial Interests, Institutional, Other, Consultancy: Orion;Financial Interests, Institutional, Invited Speaker: Tesaro, AZ, Clovis;Financial Interests, Personal, Other, Consultancy: GLG;Financial Interests, Institutional, Research Grant, PI translational research: ARCAGY-GINECO, Sanofi, A ;Financial Interests, Institutional, Funding, CI clinical trial: AZ;Financial Interests, Institutional, Research Grant, Int CI clinical trial: OSE immuno;Financial Interests, Institutional, Funding, PI clinical trial: Agenus, BMS, Iovance, GSK;Financial Interests, Institutional, Funding, PI 5 clinical trials: Roche;Financial Interests, Institutional, Funding, PI 2 clinical trials: AZ;Financial Interests, Institutional, Funding, PI 3 clinical trials and steering committee: MSD;Non-Financial Interests, Institutional, Other, Academic research project: Owkin, LXRepair;Non-Financial Interests, Personal, Proprietary Information, IDMC member: Clovis;Non-Financial Interests, Personal, Proprietary Information, IDMC chair: Pfizer. S. Pignata: Financial Interests, Personal, Advisory Board: Roche, AZ, MSD, Clovis, GSK, PharmaMar;Financial Interests, Institutional, Funding: Roche, MSD, Pfizer, AZ. A.J. Gonzalez Martin: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Clovis, GSK, Genmab, Alkermes, Sutro, Roche, Sotio, PharmaMar, Oncoinvent, Novartis, Mersana, MSD, Macrogenics;Financial Interests, Personal, Invited Speaker: GSK, AstraZeneca, Clovis, Roche, Novocure, MSD;Financial Interests, Institutional, Invited Speaker, PI of ANITA trial: GSK, Roche;Financial Interests, Personal, Invited Speaker, Member of ENGOT ov43-SC: MSD;Financial Interests, Institutional, Invited Speaker, ENGOT PI of EPIK-O trial: Novartis;Financial Interests, Institutional, Invited Speaker, ENGOT PI of AVB-500 phase III trial: ARAVIVE. G. Bogner: Financial Interests, Personal, Advisory Board: AstraZeneca, Roche and GSK;Financial Interests, Personal, Other, Medical conferences: AstraZeneca, Roche and GSK. I.B. Vergote: Financial Interests, Personal, Advisory Board, Consulting: Agenus (2021), Aksebio China (2021), AstraZeneca (2021-2022), Bristol Myers Squibb (2021), Deciphera Pharmaceuticals (2021), Eisai (2021), F. Hoffmann-La Roche Ltd. (2021), Genmab (2021), GSK (2021), Immunogen Inc. (2021-2022), Jazzpharma (2021-2022), Karyopharm (2021), MSD (2021-2022), Novocure (2020-2022), Novartis (2021), Oncoinvent AS (2021-2022), Seagen (2021), Sotio a.s. (2021-2022);Financial Interests, Institutional, Advisory Board, Consulting: AstraZeneca (2019-2020), eciphera Pharmaceuticals (2020), Elevar Therapeutics (2020), F. Hoffmann-La Roche Ltd. (2019-2020), Genmab (2019-2020), GSK (2019-2020), Mersana (2020), MSD (2019-2020), Oncoinvent AS (2019-2020), Sotio a.s. (2019-2020), Verastem Oncology (2020), Zentalis (2020), Amgen (Europe) 2019, Clovis Oncology Inc (2019), Carrick Therapeutics (2019), Millennium Pharmaceuticals (2019);Financial Interests, Institutional, Research Grant, Contracted Research ( via KU Leuven): Oncoinvent AS (2019-2020);Financial Interests, Institutional, Research Grant, Contracted Research (via KU Leuven): Genmab (2019);Financial Interests, Institutional, Research Grant, Corporate sponsored research: Amgen (2019-2020), Roche (2019-2020). N. Colombo: Financial Interests, Personal, Advisory Board, Various: Roche, PharmaMar, AstraZeneca, MSD/Merck, Clovis Oncology, Tesaro, GSK, Pfizer, Takeda, BIOCAD, Immunogen, Mersana;Financial Interests, Personal, Invited Speaker, Congress, Symposia, Lectures: AstraZeneca, Tesaro;Financial Interests, Personal, Invited Speaker, Lectures: Novartis;Financial Interests, Personal, Advisory Board, Lectures: Eisai;Financial Interests, Personal, Advisory Board, Advisory role: Nuvation Bio, Pieris;Financial Interests, Personal, Advisory Board, Advisory Role: Onxerna;Financial Interests, Institutional, Research Grant: AstraZeneca, PharmaMar, Roche;Non-Financial Interests, Personal, Other, Sterring committee member Clinical Guidelines: ESMO;Non-Financial Interests, Personal, Leadership Role, Chair, Scientific Committee: ACTO( Alleanza contro il tumore ovarico). J. Maenpaa: Financial Interests, Personal, Other, Honoraria: AstraZeneca and GSK. F. Selle: Financial Interests, Personal, Other, Honoraria: AstraZeneca, GSK Tesaro, MSD, Sandoz (Novartis), and Clovis Oncology;Financial Int rests, Institutional, Funding: Roche, GSK Tesaro, AstraZeneca, Immunogen, MSD, Incyte, and Agenus. B. Schmalfeldt: Financial Interests, Personal, Other, Honoraria: Roche, AstraZeneca, Tesaro, Clovis, GSK, MSD;Financial Interests, Personal, Advisory Role: Roche, AstraZeneca, Tesaro, Clovis, GSK, MSD;Financial Interests, Personal, Speaker's Bureau: Roche, AstraZeneca, Tesaro, Clovis, GSK, MSD;Financial Interests, Personal, Funding: Roche, AstraZeneca, Tesaro, Clovis, GSK, MSD;Financial Interests, Personal, Other, Travel or accommodation expenses: Roche, AstraZeneca, Tesaro. G. Scambia: Financial Interests, Personal, Invited Speaker, Speaker: Johnson & Johnson, AstraZeneca&MSD, Olympus Europa, Baxter Healthcare, Intuitive Surgical Inc., GlaxoSmithKline;Financial Interests, Personal, Expert Testimony, Trainer: Covidien AG (Medtronic company);Financial Interests, Institutional, Invited Speaker, 'IsoMSLN' in Ovarian Cancer and Malignant Pleural Mesothelioma: Kiromic;Financial Interests, Institutional, Invited Speaker, Roll-over study for patients who have completed a previous cancer study with olaparib and who the investigator believes can benefit from continued treatment - ROSY-O: AstraZeneca;Financial Interests, Institutional, Invited Speaker, CATCH-R: Roll-over study to provide continuous access to clinical therapy with rucaparib.: Clovis Oncology;Financial Interests, Institutional, Invited Speaker, Phase 3, multicenter, placebo-controlled clinical study comparing chemo-immunotherapy (paclitaxel-carboplatin-oregovomab) versus chemotherapy (paclitaxel-carboplatin-placebo) in patients with advanced epithelial ovarian, tubal cancer of fallopian or peritoneal (FLORA-5): Oncoquest Pharmaceuticals Inc.;Financial Interests, Institutional, Invited Speaker, Phase 2b randomized, open-label,active comparator, parallel-group, multicenter study designed to evaluate the efficacy and safety of three different doses of the P2X3 receptor antagonist (BAY 1817080) versus placebo and Elagolix 150 mg in women with symptomatic endometriosis: Bayer AG;Financial Interests, Institutional, Invited Speaker, Usability of ITE transducers for sending electric fields for tumor treatment (TTFields): Novocure Ltd.;Financial Interests, Institutional, Invited Speaker Phase III, multicentre, open-label extension trial to evaluate long-term safety and efficacy in patients with advanced cancers currently undergoing treatment or in follow-up in a pembrolizumab trial.: Merck. E.M. Guerra Alia: Financial Interests, Institutional, Invited Speaker: PharmaMar, Pfizer;Financial Interests, Personal, Invited Speaker: Pfizer. C. Lefeuvre-Plesse: Financial Interests, Personal, Advisory Role: Pfizer, AstraZeneca, Roche, and Daiichi-Sanko;Financial Interests, Personal, Other, Travel/accommodation/medical congress expenses: Roche, Novartis, Pfizer, and Pierre Fabre. A. Belau: Financial Interests, Personal, Other, Honoraria: Roche, AstraZeneca, Clovis, MSD, Daiichi Sankyo Company, Lilly, Seagen;Financial Interests, Personal, Advisory Role: Pfizer, Roche, AstraZeneca, MSD, Lilly, Daiichi Sankyo Company, Seagen;Financial Interests, Personal, Other, Travel or accommodation expenses: Roche, AstraZeneca, Daiichi Sankyo Company. A. lortholary: Financial Interests, Personal, Advisory Board: AstraZeneca, MSD and Tesaro;Financial Interests, Personal, Speaker's Bureau: Clovis Oncology, and Roche;Financial Interests, Personal, Other, Participation in a medical congress: Novartis, Pfizer, MSD, Lilly and Roche. E. Pujade-Lauraine: Financial Interests, Personal, Other, Lecture fees: AstraZeneca, Tesaro, Roche, Clovis Oncology, Incyte, Pfizer;Financial Interests, Personal, Speaker's Bureau: AstraZeneca, Tesaro, and Roche;Financial Interests, Personal, Other, Travel/accommodation: AstraZeneca, Tesaro, and Roche;Financial Interests, Personal, Full or part-time Employment: ARCAGY Research. P. Harter: Financial Interests, Personal, Advisory Board, Value includes honoraria for lectures: AstraZeneca;Financial Interests, Personal, Advisory Board, includes honoraria for lectu es: GSK, Roche, MSD;Financial Interests, Personal, Invited Speaker: Amgen, Stryker, Zailab;Financial Interests, Personal, Advisory Board: Clovis, Immunogen;Financial Interests, Personal, Other, IDMC member: Sotio;Financial Interests, Institutional, Invited Speaker: AstraZeneca, Roche, GSK, Genmab, Immunogen;Financial Interests, Institutional, Funding: Seagen, Clovis. All other authors have declared no conflicts of interest. Copyright © 2022

The Impact of Covid-19 on Delaying Diagnostic-Therapeutic Pathways of Endometrial Cancer Patients: The Italian Real-World Scenario

Background: Coronavirus disease 2019 (COVID-19) outbreak has correlated with the disruption of screening activities and diagnostic assessments. Endometrial cancer (EC) is one of the most common gynecological malignancies and it is often detected at an early stage, because it frequently produces symptoms. Here, we aim to investigate the impact of COVID-19 outbreak on patterns of presentation and treatment of EC patients. Material(s) and Method(s): This is a retrospective study involving 54 centers in Italy. We evaluated patterns of presentation and treatment of EC patients before (period 1: March 1, 2019 to February 29, 2020) and during (period 2: April 1, 2020 to March 31, 2021) the COVID-19 outbreak. Result(s): Charts of 5,164 EC patients were retrieved. Overall, 2,718 and 2,446 women with EC received treatment in period 1 and 2, respectively. The prevalence of patients aged > 65 years was similar between the 2 study periods (1,400 [51.5%] in period 1 vs. 1,248 [51.0%];p=0.726). Considering data on the histological characterization, the prevalence of endometrioid FIGO grade 1, 2, and 3 was consistent over the study period (p=0.855). However, the prevalence of non-endometrioid EC was lower in period 1 than in period 2 (15.6% vs. 17.9%;p=0.032). Surgery was the mainstay of treatment before and during the COVID-19 pandemic. Overall, 2,539 and 2,286 women received surgery in period 1 and 2, respectively (93.4% vs. 93.5%;p=0.948). Primary conservative attempts (i.e., progesterone-based therapy) was performed in 72 (2.7%) and 56 (2.3%) patients in period 1 and 2, respectively (p=0.406). The adoption of minimally invasive surgery was consistent in the two study periods (p=0.976). Overall, 1,280 (50.4%) and 1,021 (44.7%) patients had no adjuvant therapy in period 1 and 2, respectively (p<0.001). The adoption of vaginal brachytherapy as adjuvant treatment remained stable in the study periods (11.9% vs. 11.1%;p=0.325). Adjuvant therapies indication has increased during the COVID-19 pandemic (p<0.001). In particular, the use of adjuvant radiotherapy (26.8% vs. 30.7%;p=0.001) and chemotherapy (25.1% vs. 30.1%;p<0.001) alone or in combination increased from period 1 to 2. Conclusion(s): Our data suggest that the COVID-19 pandemic had a significant impact on the characteristics and patterns of care of EC patients. These findings highlight the need to implement healthcare services during the pandemic.

Safety of Radiation exposure during pregnancy in COVID-19 affected women

Radiologic imaging in the evaluation of pregnant patients has significantly grown with the outbreak of the severe acute respiratory syndrome related to SARS-CoV-2 pandemic. Lung ultrasound is an emerging non-invasive bedside technique used to diag-nose interstitial lung syndrome through evaluation and quantitation of the number of B-lines, pleural irregularities and nodules or consolidations. In pregnant COVID-19 patients, lung ultrasound should be considered on ac-count of its various strengths, such as its being easily carried out bedside by trained sonographers for the monitoring of lung involvement in follow-ups, and its repeatability and affordability. However, pregnant patients could need chest radiography or computed tomo-graphic (CT) examinations for the diagnosis of pneumonia. Concerns and mis-conceptions about potential radiation-related risks for the embryo or fetus are still widespread among clinicians and can lead to excessive anxiety among pa-tients. Several well-recognized guidance documents were published in the last years as to the safety of a single-phase CT or an X-ray chest and related carcino-genic and teratogenic risk. This paper summarizes the safety of radiological examination for pneumonia in pregnant women affected by COVID 19, based on the estimated embryo-fetal radiation absorption per procedure (mGy).

Future medico-legal implications on obstetrics and gynaecology practice in the SARS-CoV-2 pandemic

Since February 2020, the Italian National Healthcare System had to mitigate the possibility of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) transmission to vulnerable patients. Healthcare professionals rapidly reviewed their workflow to maintain a safe and high standard treatment, but weak scientific evidences and organizational limits resulted in the adoption of heterogeneous measures. Adherence to screening protocols and follow-up programs pregnant women and oncological patients has not been always guaranteed: this scenario could evolve in an enormous number of medico-legal actions. This context, showing the weakness of the Italian law No. 24/2017, imposes an urgent reorganization of the legal framework to homogenize the judgements to “protect” healthcare professionals involved in this epochal emergency.

Access to early phase clinical trials during the Covid-19 pandemic

Background: The Covid-19 pandemic has radically changed healthcare organizations. Here, we describe the attitude among Italian physicians toward referring patients to early-phase clinical trials during the pandemic. Methods: We analyzed the responses recorded in the first 72 hours from the beginning of the survey. A 20-question web survey was sent to all the associates of the Italian Association of Medical Oncology. Results: Ninety-five physicians completed the survey;87 (96%) were medical oncologists. Table 1 summarizes participants' characteristics. Overall, 37% of the respondents work in an early clinical trial unit. The vast majority of interviewees (74%) already used to refer patients to early clinical trials in the pre- COVID era. Among these, about 30% sent fewer patients during the pandemic particularly due to logistical issues. Interestingly, 25 (26%) never referred patients because of ineffective networking among institutions. It will take more than 12 months to return to pre-pandemic attitude according to half of the physicians. Most of the respondents affirm that one possible tool to facilitate the recovery is: fostering the clinical research network, favouring alliances between referral and satellite centers, and strengthening telemedicine. More than 70% of participants believe that the COVID-19 pandemic will have an impact on the development of new molecules in the coming years both due to a decrease in the number of open studies and to a diversion of funds towards Covid-19 research. Conclusions: In this analysis, we intended to offer an early snapshot of the Covid -19 effects on early phase trials in Italy. One-third of the participants had to decrease the number of referred patients due to the difficulties of a system exposed to unprecedented stress. Furthermore, the challenges of the last year will have repercussions on drug development in the coming years for the majority of interviewees.

Characteristics and Patterns of Care of Endometrial Cancer before and during COVID-19 pandemic

Background: COVID-19 outbreak has correlated with the disruption of screening activities, regular follow up visits, and diagnostic assessments. The risk of misdiagnosis and delayed diagnosis has consequently increased during the pandemic. Endometrial cancer is one of the most common gynecological malignancies and it is often detected at an early stage, because it frequently produces symptoms (e.g. abnormal vaginal bleeding). Here, we aim to investigate the impact of COVID-19 outbreak on patterns of presentation and treatment of endometrial cancer patients. Material and methods: This is a retrospective study involving 53 centers in Italy. We evaluated patterns of presentation and treatment of endometrial cancer patients before (i.e. period 1: from 03/01/2019 to 02/29/2020) and during (i.e. period 2: from 01/04/2020 to 3/31/2021) the COVID-19 outbreak. Results: Medical records of 5,117 endometrial cancer patients have been retrieved: 2,688 and 2,429 women treated in period 1 and period 2, respectively. The prevalence of endometrioid International Federation of Obstetrics and Gynecologists (FIGO) grade 1, 2, and 3 was consistent over the study period (p=0.769). However, the prevalence of non-endometrioid endometrial cancer was lower in period 1 than in period 2 (15.7% vs. 17.9%;p=0.015). The characteristics and pattern of different surgical approaches were consistent in the two study periods (p=0.664). Before COVID-19 pandemic, 1,838 (73.2%), 647 (25.7%), and 25 (0.9%) patients had minimally invasive, open and vaginal surgery, respectively. During the COVID-19 pandemic, 1,661 (73.2%), 567 (24.9%), and 41 (1.8%) patients had minimally invasive, open, and vaginal surgery, respectively. Nodal assessment was omitted in 684 (27.3%) and 478 (21%) patients treated in period 1 and 2, respectively (p<0.001). While, the prevalence of patients undergoing sentinel node mapping (with or without backup lymphadenectomy) has increased during the COVID-19 pandemic (46.8% in period 1 vs. 53.1% in period 2;p<0.001). Adjuvant therapy was omitted in 1,269 (50.5%) and 1,019 (44.9%) patients receiving treatment in period 1 and 2, respectively (p<0.001). Adjuvant therapy use has increased during the COVID-19 pandemic (p<0.001). Conclusions: Our data suggest that the COVID-19 pandemic had a significant impact on the characteristics and patterns of care of endometrial cancer patients. These findings highlight the need to implement healthcare services during the pandemic.

Impact of COVID-19 in gynecologic oncology: a nationwide Italian survey

ObjectiveSeveral attempts are done in order to control COVID-19 and promote a fair allocation of resources during the outbreak. The Italian society of obstetrics and gynecologist (SIGO), and the Multicenter Italian Trials in Ovarian cancer and gynecologic malignancies (MITO) are promoting research activities in the field of gynecologic oncology on a national basis, even in the era of COVID-19.MethodsThe SIGO and MITO group promoted a national survey aiming to evaluate the impact of COVID-19 on clinical activity of gynecologist oncologists and the implementation of containment measures of COVID-19 diffusion.ResultsOverall, 604 participants completed the questionnaire with a response rate of 70%. The results of this survey suggest that gynecologic oncology units had set a proactive approach to COVID-19 outbreak. Triage methods were adopted in order to minimize the in-hospital diffusion of COVID-19. Although 73% of the participants stated that COVID-19 has not significantly modified their everyday practice, 21% declared a decrease in the use of laparoscopy in favor of open (19%) and vaginal (2%) surgery. Interestingly, about 5% of the participants stated that the use of laparoscopic surgery has increased during the COVID-19 outbreak. However, less than 50% of surgeons adopted specific protection against COVID-19. Additionally, responders suggested to delay cancer treatment (10–15%), and to perform less radical surgical procedures (20–25%) during COVID-19 pandemic.ConclusionsInternational cooperation is of paramount importance, as heavily affected nations can serve as an example to find out ways to safely preserve clinical activity during the COVID-19 outbreak

Web-mediated counseling to counteract the emotional impact of COVID-19 for women with interstitial cystitis/bladder pain syndrome.

OBJECTIVE: Interstitial Cystitis (IC) is a chronic and rare disease, more frequent in women. Symptoms of continuous pain can produce psychological disorders, such as anxiety and depression. The spread of COVID-19 pandemic added to distress experienced by patients with IC emotions, such as fear, sadness, boredom, frustration and anger. MATERIALS AND METHODS: A research on very recent literature outlines the necessity for patients facing the complexity of IC during the COVID-19 outbreak to prevent the temporary crisis, to broaden perspectives, to deal with confusion, to support in struggling with unpleasant and unexpected events. CONCLUSIONS: People affected by IC have a psychological vulnerability that needs tailored support interventions, particularly in the COVID era. A multidisciplinary approach offers a personalized treatment through a web-mediated counseling intervention for patients and their caregivers: a space for continuous discussion and reflection can favour a relationship-based process of change aimed at an improvement in quality of life.

Impact of covid-19 in gynecologic oncology: A nationwide Italian survey

Background: The spread of Coronavirus (COVID-19), after involving China, has also begun to interest Europe and the ed States. Several attempts are done in order to control the spread of the virus and promote a fair allocation of resources during COVID-19 outbreak. COVID-19 threatens to curtail patient access to evidence-based treatment. The Italian society of obstetrics and gynecologist (SIGO), and the Multicenter Italian Trials in Ovarian cancer and gynecologic malignancies (MITO) are promoting research activities in the field of gynecologic oncology on a national basis, even in the COVID-19 era. Methods: The SIGO and MITO group promoted a national survey aiming to evaluate the impact of COVID-19 on clinical activity of gynecologist oncologists and the implementation of containment measures of COVID-19 diffusion. Results: Overall, 604 participants completed the questionnaire with a response-rate of 70%. The results of this survey suggest that gynecologic oncology units had set a proactive approach to COVID-19 outbreak. Triage methods were adopted in order to minimize the in-hospital diffusion of COVID-19. Overall, only 38% of gynecologic surgeons were concerned about COVID-19 outbreak. Although 73% of the participants stated that COVID-19 has not significantly modified their everyday practice, 21% declared a decrease of the use of laparoscopy in favor of open (19%) and vaginal (2%) surgery. Interestingly, about 5% of the participants stated that the use of laparoscopic surgery has increased during the COVID-19 outbreak. However, less than 50% of surgeons adopted specific protection against COVID-19. Additionally, responders suggested to delay cancer treatment (10-15%), and to perform less radical surgical procedures (20-25%) during COVID-19 pandemic. Conclusions: National guidelines should be implemented to further promote the safety of patients and health care providers. International cooperation is of paramount importance, as heavily affected nations can serve as an example to find out ways to safely preserve clinical activity during the COVID-19 outbreak.

IPSICO survey on the psychological impact of COVID-19 on healthcare providers in obstetrics: A study design

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is giving rise to a relevant impact on the wellbeing and mental health of several Health Care Providers (HCPs). Among HCPs, those who work in the field of obstetrics repre-sent a particular group of HCPs who are susceptible to stressful events, given the stress derived from a physically, emotionally, and intellectually demanding work, the difficulty in reschedul-ing and postponing daily activities during a health emergency, and the special ability to develop personal resilience. Based on this background, the aim of the present study is to assess the acute psychological and professional impact of the SARS-CoV-2 outbreak on this group of HCPs at four University Hospitals in Italy (Verona, Roma Policlinico Gemelli, Varese, Brescia). For this purpose, a 104-items survey named Impatto PSicologico Covid in Ostetricia (IPSICO) has been developed and administered with a web-based platform. This survey, divided into four sections, will collect demographic data and information about past personal and mental health history, the impact of the epidemic on the personal and professional life, and the outcomes of this health care emergency. The results of this survey will help to plan effective strategies in order to face the psychological consequences of possible future new health care emergencies of this type.

Clinical application of Lung Ultrasound for the management of pregnant women with suspicion of COVID-19: A review of literature

COVID-19 is an infectious illness caused by a virus named SARS-CoV-2. Recent studies underlined the need for chest computed tomography (CT) in COVID-19 patients to assess lung involvement. However, CT has a series of disadvantages, such as the need to move the patient from an isolation room to a Radiology Department, the difficulty in protecting and disinfecting the machine, the high cost of the equipment. These disadvantages apply especially to pregnant women, in particular because of the exposure to a significant amount of radiation to the fetus. In order to avoid these disadvantages, a series of manuscript were published on the alternative use of Lung Ultrasound (LUS) during COVID-19 outbreak. Therefore, we carried out a review of the published studies and case reports, in order to underline the advantages, the correct technique, the typical LUS manifestations of COVID-19 and to help researchers in the diagnosis and monitoring of the disease, especially for obstetricians and gynecologists who already use ultrasound in their clinical practice.

Management of obstetrics and gynaecological patients with COVID-19

The widespread SARS-CoV-2 implies the application of procedures aimed to detect, isolate, and appropriately manage affected patients in the setting of obstetrics and gynaecologic emergency room and in inpatient setting, such as during labour, delivery, and postpartum. Here we report specific recommendations for the management of suspected and confirmed gynaecologic and obstetrics patients with COVID-19. The checklist developed by the Società Italiana di Malattie Infettive e Tropicali (SIMIT-2, available in English, Italian, Chinese) represents the first step to clas-sify patients who need to be managed following the SIMIT-1 flowchart, applying all the appropriate infection control procedures. In this scenario, the management of pregnant women needs to follow the same procedures as the general population. Nevertheless, as for other potentially severe respiratory infections, pregnant women could be more vulnerable. In this regard, the maternal and foetal interests can be conflicting, such as the choice of the time and mode of delivery or the use of steroids for foetal maturation. More-over, available evidence suggests a maternal-foetal transmission via contact with respiratory secretions and seems to exclude in utero transmission. Therefore, the appropriate management of breastfeeding is unclear, and the temporary separation of the infant from the mother could be an option. Finally, in general, delivery represents a moment of a high risk of infection for healthcare providers, and specific behaviours are mandatory.