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784 results on '"PIGNATA S."'

1. Unraveling the complexity of HRD assessment in ovarian cancer by combining genomic and functional approaches: translational analyses of MITO16-MaNGO-OV-2 trial

Author: Pellegrino, B., Capoluongo, E.D., Bagnoli, M., Arenare, L., Califano, D., Scambia, G., Cecere, S.C., Silini, E.M., Scaglione, G.L., Spina, A., Tognon, G., Campanini, N., Pisano, C., Russo, D., Pettinato, A., Scollo, P., Iemmolo, R., De Cecco, L., Musolino, A., Marchini, S., Beltrame, L., Paracchini, L., Perrone, F., Mezzanzanica, D., and Pignata, S.
Published: 2025
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2. Under-reporting of subjective symptoms and its prognostic value: a pooled analysis of 12 cancer clinical trials

Author: Arenare, L., Di Liello, R., De Placido, P., Gridelli, C., Morabito, A., Pignata, S., Nuzzo, F., Avallone, A., Maiello, E., Gargiulo, P., Schettino, C., Gravina, A., Gallo, C., Chiodini, P., Di Maio, M., Perrone, F., and Piccirillo, M.C.
Published: 2024
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3. Olaparib plus bevacizumab first-line maintenance in ovarian cancer: final overall survival results from the PAOLA-1/ENGOT-ov25 trial

Author: Ray-Coquard, I., Leary, A., Pignata, S., Cropet, C., González-Martín, A., Marth, C., Nagao, S., Vergote, I., Colombo, N., Mäenpää, J., Selle, F., Sehouli, J., Lorusso, D., Guerra Alia, E.M., Bogner, G., Yoshida, H., Lefeuvre-Plesse, C., Buderath, P., Mosconi, A.M., Lortholary, A., Burges, A., Medioni, J., El-Balat, A., Rodrigues, M., Park-Simon, T.-W., Dubot, C., Denschlag, D., You, B., Pujade-Lauraine, E., and Harter, P.
Published: 2023
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4. Alternative academic approaches for testing homologous recombination deficiency in ovarian cancer in the MITO16A/MaNGO-OV2 trial

Author: Capoluongo, E.D., Pellegrino, B., Arenare, L., Califano, D., Scambia, G., Beltrame, L., Serra, V., Scaglione, G.L., Spina, A., Cecere, S.C., De Cecio, R., Normanno, N., Colombo, N., Lorusso, D., Russo, D., Nardelli, C., D’Incalci, M., Llop-Guevara, A., Pisano, C., Baldassarre, G., Mezzanzanica, D., Artioli, G., Setaro, M., Tasca, G., Roma, C., Campanini, N., Cinieri, S., Sergi, A., Musolino, A., Perrone, F., Chiodini, P., Marchini, S., and Pignata, S.
Published: 2022
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5. Efficacy of subsequent chemotherapy for patients with BRCA1/2-mutated recurrent epithelial ovarian cancer progressing on olaparib versus placebo maintenance: post-hoc analyses of the SOLO2/ENGOT Ov-21 trial

Author: Frenel, J.S., Kim, J.W., Aryal, N., Asher, R., Berton, D., Vidal, L., Pautier, P., Ledermann, J.A., Penson, R.T., Oza, A.M., Korach, J., Huzarski, T., Pignata, S., Colombo, N., Park-Simon, T.W., Tamura, K., Sonke, G.S., Freimund, A.E., Lee, C.K., and Pujade-Lauraine, E.
Published: 2022
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6. Pembrolizumab or placebo with chemoradiotherapy followed by pembrolizumab or placebo for newly diagnosed, high-risk, locally advanced cervical cancer (ENGOT-cx11/GOG-3047/KEYNOTE-A18): overall survival results from a randomised, double-blind, placebo-controlled, phase 3 trial

Author: Lorusso, D, Xiang, Y, Hasegawa, K, Scambia, G, Leiva, M, Ramos-Elias, P, Acevedo, A, Cvek, J, Randall, L, Pereira de Santana Gomes, A, Contreras Mejia, F, Helpman, L, Akilli, H, Lee, J, Saevets, V, Zagouri, F, Gilbert, L, Sehouli, J, Tharavichitkul, E, Lindemann, K, Colombo, N, Chang, C, Bednarikova, M, Zhu, H, Oaknin, A, Christiaens, M, Petru, E, Usami, T, Liu, P, Yamada, K, Toker, S, Keefe, S, Pignata, S, Duska, L, Lorusso D., Xiang Y., Hasegawa K., Scambia G., Leiva M., Ramos-Elias P., Acevedo A., Cvek J., Randall L., Pereira de Santana Gomes A. J., Contreras Mejia F., Helpman L., Akilli H., Lee J. -Y., Saevets V., Zagouri F., Gilbert L., Sehouli J., Tharavichitkul E., Lindemann K., Colombo N., Chang C. -L., Bednarikova M., Zhu H., Oaknin A., Christiaens M., Petru E., Usami T., Liu P., Yamada K., Toker S., Keefe S. M., Pignata S., Duska L. R., Lorusso, D, Xiang, Y, Hasegawa, K, Scambia, G, Leiva, M, Ramos-Elias, P, Acevedo, A, Cvek, J, Randall, L, Pereira de Santana Gomes, A, Contreras Mejia, F, Helpman, L, Akilli, H, Lee, J, Saevets, V, Zagouri, F, Gilbert, L, Sehouli, J, Tharavichitkul, E, Lindemann, K, Colombo, N, Chang, C, Bednarikova, M, Zhu, H, Oaknin, A, Christiaens, M, Petru, E, Usami, T, Liu, P, Yamada, K, Toker, S, Keefe, S, Pignata, S, Duska, L, Lorusso D., Xiang Y., Hasegawa K., Scambia G., Leiva M., Ramos-Elias P., Acevedo A., Cvek J., Randall L., Pereira de Santana Gomes A. J., Contreras Mejia F., Helpman L., Akilli H., Lee J. -Y., Saevets V., Zagouri F., Gilbert L., Sehouli J., Tharavichitkul E., Lindemann K., Colombo N., Chang C. -L., Bednarikova M., Zhu H., Oaknin A., Christiaens M., Petru E., Usami T., Liu P., Yamada K., Toker S., Keefe S. M., Pignata S., and Duska L. R.
Abstract: Background: At the first interim analysis of the phase 3 ENGOT-cx11/GOG-3047/KEYNOTE-A18 study, the addition of pembrolizumab to chemoradiotherapy provided a statistically significant and clinically meaningful improvement in progression-free survival in patients with locally advanced cervical cancer. We report the overall survival results from the second interim analysis of this study. Methods: Eligible patients with newly diagnosed, high-risk (FIGO 2014 stage IB2–IIB with node-positive disease or stage III–IVA regardless of nodal status), locally advanced, histologically confirmed, squamous cell carcinoma, adenocarcinoma, or adenosquamous cervical cancer were randomly assigned 1:1 to receive five cycles of pembrolizumab (200 mg) or placebo every 3 weeks with concurrent chemoradiotherapy, followed by 15 cycles of pembrolizumab (400 mg) or placebo every 6 weeks. Pembrolizumab or placebo and cisplatin were administered intravenously. Patients were stratified at randomisation by planned external beam radiotherapy type (intensity-modulated radiotherapy [IMRT] or volumetric-modulated arc therapy [VMAT] vs non-IMRT or non-VMAT), cervical cancer stage at screening (FIGO 2014 stage IB2–IIB node positive vs III–IVA), and planned total radiotherapy (external beam radiotherapy plus brachytherapy) dose (<70 Gy vs ≥70 Gy [equivalent dose of 2 Gy]). Primary endpoints were progression-free survival per RECIST 1.1 by investigator or by histopathological confirmation of suspected disease progression and overall survival defined as the time from randomisation to death due to any cause. Safety was a secondary endpoint. Findings: Between June 9, 2020, and Dec 15, 2022, 1060 patients at 176 sites in 30 countries across Asia, Australia, Europe, North America, and South America were randomly assigned to treatment, with 529 patients in the pembrolizumab–chemoradiotherapy group and 531 patients in the placebo–chemoradiotherapy group. At the protocol-specified second interim analysis (dat
Published: 2024

7. Venous Thromboembolism Prophylaxis in Gynecologic Oncology: A MITO-MaNGO Survey

Author: Mongelli, M, Lorusso, D, Zanagnolo, V, Pignata, S, Colombo, N, Cormio, G, Mongelli M., Lorusso D., Zanagnolo V., Pignata S., Colombo N., Cormio G., Mongelli, M, Lorusso, D, Zanagnolo, V, Pignata, S, Colombo, N, Cormio, G, Mongelli M., Lorusso D., Zanagnolo V., Pignata S., Colombo N., and Cormio G.
Abstract: Cancer-associated thrombosis is the second leading cause of death in cancer patients, and its incidence has been increasing in recent years. This survey was aimed at gathering information regarding the management of thromboembolic prophylaxis within the MITO (Multicenter Italian Trials in Ovarian Cancer)-MaNGO (Mario Negri Gynecologic Oncology) groups. We designed a self-administered, multiple-choice online questionnaire available only for MITO-MaNGO members for one month, starting in May 2022 and ending in June 2022. We processed one response form per center, and 50 responses were analyzed, with most of the respondents (78%) over 40 years old. We found that 82% of them consider thromboembolic prophylaxis in gynecologic oncology to be relevant. In 82% of the centers, a standardized protocol on venous thromboembolism (VTE) prophylaxis is used, which is applied to both patients undergoing surgery and those undergoing chemotherapy. In the remaining 18% of centers, prophylaxis is used exclusively for patients undergoing chemotherapy treatment. Prophylaxis of patients undergoing surgery and chemotherapy treatment is managed in most cases by the surgeon (72%) and oncologist (76%), respectively. Only 26% of respondents use a thromboembolic risk assessment scale, and of these, those used are the Caprini Score (6%), Khorana Score (6%), and Wells Score (2%). The respondents have good knowledge of low-molecular-weight heparin (90%) and average knowledge of dicumarolics (40%), direct oral anticoagulants (DOACs) (68%), and antiplatelet agents (40%). The results of our survey indicate that there is a good awareness of thromboembolic prophylaxis in gynecologic oncology. Nevertheless, it is used less in outpatients than in patients undergoing surgery. Moreover, the thromboembolic risk assessment scores are barely used.
Published: 2024

8. ESGO–ESMO–ESP consensus conference recommendations on ovarian cancer: pathology and molecular biology and early, advanced and recurrent disease

Author: Ledermann, J, Matias-Guiu, X, Amant, F, Concin, N, Davidson, B, Fotopoulou, C, González-Martin, A, Gourley, C, Leary, A, Lorusso, D, Banerjee, S, Chiva, L, Cibula, D, Colombo, N, Croce, S, Eriksson, A, Falandry, C, Fischerova, D, Harter, P, Joly, F, Lazaro, C, Lok, C, Mahner, S, Marmé, F, Marth, C, Mccluggage, W, Mcneish, I, Morice, P, Nicum, S, Oaknin, A, Pérez-Fidalgo, J, Pignata, S, Ramirez, P, Ray-Coquard, I, Romero, I, Scambia, G, Sehouli, J, Shapira-Frommer, R, Sundar, S, Tan, D, Taskiran, C, van Driel, W, Vergote, I, Planchamp, F, Sessa, C, Fagotti, A, Ledermann J. A., Matias-Guiu X., Amant F., Concin N., Davidson B., Fotopoulou C., González-Martin A., Gourley C., Leary A., Lorusso D., Banerjee S., Chiva L., Cibula D., Colombo N., Croce S., Eriksson A. G., Falandry C., Fischerova D., Harter P., Joly F., Lazaro C., Lok C., Mahner S., Marmé F., Marth C., McCluggage W. G., McNeish I. A., Morice P., Nicum S., Oaknin A., Pérez-Fidalgo J. A., Pignata S., Ramirez P. T., Ray-Coquard I., Romero I., Scambia G., Sehouli J., Shapira-Frommer R., Sundar S., Tan D. S. P., Taskiran C., van Driel W. J., Vergote I., Planchamp F., Sessa C., Fagotti A., Ledermann, J, Matias-Guiu, X, Amant, F, Concin, N, Davidson, B, Fotopoulou, C, González-Martin, A, Gourley, C, Leary, A, Lorusso, D, Banerjee, S, Chiva, L, Cibula, D, Colombo, N, Croce, S, Eriksson, A, Falandry, C, Fischerova, D, Harter, P, Joly, F, Lazaro, C, Lok, C, Mahner, S, Marmé, F, Marth, C, Mccluggage, W, Mcneish, I, Morice, P, Nicum, S, Oaknin, A, Pérez-Fidalgo, J, Pignata, S, Ramirez, P, Ray-Coquard, I, Romero, I, Scambia, G, Sehouli, J, Shapira-Frommer, R, Sundar, S, Tan, D, Taskiran, C, van Driel, W, Vergote, I, Planchamp, F, Sessa, C, Fagotti, A, Ledermann J. A., Matias-Guiu X., Amant F., Concin N., Davidson B., Fotopoulou C., González-Martin A., Gourley C., Leary A., Lorusso D., Banerjee S., Chiva L., Cibula D., Colombo N., Croce S., Eriksson A. G., Falandry C., Fischerova D., Harter P., Joly F., Lazaro C., Lok C., Mahner S., Marmé F., Marth C., McCluggage W. G., McNeish I. A., Morice P., Nicum S., Oaknin A., Pérez-Fidalgo J. A., Pignata S., Ramirez P. T., Ray-Coquard I., Romero I., Scambia G., Sehouli J., Shapira-Frommer R., Sundar S., Tan D. S. P., Taskiran C., van Driel W. J., Vergote I., Planchamp F., Sessa C., and Fagotti A.
Abstract: The European Society of Gynaecological Oncology, the European Society for Medical Oncology (ESMO) and the European Society of Pathology held a consensus conference (CC) on ovarian cancer on 15-16 June 2022 in Valencia, Spain. The CC panel included 44 experts in the management of ovarian cancer and pathology, an ESMO scientific advisor and a methodologist. The aim was to discuss new or contentious topics and develop recommendations to improve and harmonise the management of patients with ovarian cancer. Eighteen questions were identified for discussion under four main topics: (i) pathology and molecular biology, (ii) early-stage disease and pelvic mass in pregnancy, (iii) advanced stage (including older/frail patients) and (iv) recurrent disease. The panel was divided into four working groups (WGs) to each address questions relating to one of the four topics outlined above, based on their expertise. Relevant scientific literature was reviewed in advance. Recommendations were developed by the WGs and then presented to the entire panel for further discussion and amendment before voting. This manuscript focuses on the recommendation statements that reached a consensus, their voting results and a summary of evidence supporting each recommendation.
Published: 2024

9. Clinical evaluation of a low-coverage whole-genome test for detecting homologous recombination deficiency in ovarian cancer

Author: Boidot, R, Blum, M, Wissler, M, Gottin, C, Ruzicka, J, Chevrier, S, Delhomme, T, Audoux, J, Jeanniard, A, Just, P, Harter, P, Pignata, S, Gonzalez-Martin, A, Marth, C, Maenpaa, J, Colombo, N, Vergote, I, Fujiwara, K, Duforet-Frebourg, N, Bertrand, D, Philippe, N, Ray-Coquard, I, Pujade-Lauraine, E, Boidot R., Blum M. G. B., Wissler M. -P., Gottin C., Ruzicka J., Chevrier S., Delhomme T. M., Audoux J., Jeanniard A., Just P. -A., Harter P., Pignata S., Gonzalez-Martin A., Marth C., Maenpaa J., Colombo N., Vergote I., Fujiwara K., Duforet-Frebourg N., Bertrand D., Philippe N., Ray-Coquard I., Pujade-Lauraine E., Boidot, R, Blum, M, Wissler, M, Gottin, C, Ruzicka, J, Chevrier, S, Delhomme, T, Audoux, J, Jeanniard, A, Just, P, Harter, P, Pignata, S, Gonzalez-Martin, A, Marth, C, Maenpaa, J, Colombo, N, Vergote, I, Fujiwara, K, Duforet-Frebourg, N, Bertrand, D, Philippe, N, Ray-Coquard, I, Pujade-Lauraine, E, Boidot R., Blum M. G. B., Wissler M. -P., Gottin C., Ruzicka J., Chevrier S., Delhomme T. M., Audoux J., Jeanniard A., Just P. -A., Harter P., Pignata S., Gonzalez-Martin A., Marth C., Maenpaa J., Colombo N., Vergote I., Fujiwara K., Duforet-Frebourg N., Bertrand D., Philippe N., Ray-Coquard I., and Pujade-Lauraine E.
Abstract: Background: The PAOLA-1/ENGOT-ov25 trial showed that maintenance olaparib plus bevacizumab increases survival of advanced ovarian cancer patients with homologous recombination deficiency (HRD). However, decentralized solutions to test for HRD in clinical routine are scarce. The goal of this study was to retrospectively validate on tumor samples from the PAOLA-1 trial, the decentralized SeqOne assay, which relies on shallow Whole Genome Sequencing (sWGS) to capture genomic instability and targeted sequencing to determine BRCA status. Methods: The study comprised 368 patients from the PAOLA-1 trial. The SeqOne assay was compared to the Myriad MyChoice HRD test (Myriad Genetics), and results were analyzed with respect to Progression-Free Survival (PFS). Results: We found a 95% concordance between the HRD status of the two tests (95% Confidence Interval (CI); 92%−97%). The Positive Percentage Agreement (PPA) of the sWGS test was 95% (95% CI; 91%−97%) like its Negative Percentage Agreement (NPA) (95% CI; 89%−98%). In patients with HRD-positive tumors treated with olaparib plus bevacizumab, the PFS Hazard Ratio (HR) was 0.38 (95% CI; 0.26–0.54) with SeqOne assay and 0.32 (95% CI; 0.22–0.45) with the Myriad assay. In patients with HRD-negative tumors, HR was 0.99 (95% CI; 0.68–1.42) and 1.05 (95% CI; 0.70–1.57) with SeqOne and Myriad assays. Among patients with BRCA-wildtype tumors, those with HRD-positive tumors, benefited from olaparib plus bevacizumab maintenance, with HR of 0.48 (95% CI: 0.29–0.79) and of 0.38 (95% CI: 0.23 to 0.63) with the SeqOne and Myriad assay. Conclusion: The SeqOne assay offers a clinically validated approach to detect HRD.
Published: 2024

10. European experts consensus: BRCA/homologous recombination deficiency testing in first-line ovarian cancer

Author: Vergote, I., Ausems, M., Brasiuniene, B., Brenton, J., Büttner, R., Colombo, N., González-Martín, A., Harter, P., Lambrechts, D., Lorusso, D., Madry, R., Mirza, M.R., Pujol, P., Ray-Coquard, I., Abreu, M., Balboni, S., Banerjee, S., Barberis, M., Barretina Ginesta, M.P., Baurain, J.-F., Bignami, M., Bjorge, L., Blecharz, P., Bruchim, I., Capilna, M., Cerana, N., Cicchetti, A., Collins, D., Concin, N., D’Incalci, M., Davidson, B., de la Motte Rouge, T., De Iaco, P., Demirkiran, F., Denys, H., Doerk, T., Dorum, A., Ferrero, A., Fidalgo, A.P., Genuardi, M., Gladieff, L., Glasspool, R., Grimm, C., Gultekin, M., Hahnen, E., Hasenburg, A., Hegmane, A., Heinzelmann, V., Hogdall, E., Janavicius, R., Jarmalaite, S., Kalachand, R., Kaneva, R., Kilickap, S., Kocian, R., Kolencik, D., Kristeleit, R., Kryzhanivska, A., Leary, A., Lemley, B., Ligtenberg, M., López-Guerrero, J.A., Lord, C.J., Avall-Lundqvist, E., Maenpaa, J., Mahner, S., Marmé, F., Marth, C., McNeish, I., Merkelbach-Bruse, S., Mourits, M., Normanno, N., Oaknin, A., Ojamaa, K., Papdimitriou, C., Penault-Llorca, F., Perrone, A.M., Pignata, S., Pikarsky, E., Rouleau, E., Rubio, M., Sapino, A., Schmalfeldt, B., Sehouli, J., Shapira, R., Steffensen, K.D., Sukhin, V., Syrios, J., Szallasi, Z., Taskiran, C., Terzic, M., Tischkowitz, M., Toth, I., Van de Vijver, K., Vardar, M.A., Wasag, B., Wimberger, P., Witteveen, E., Brenton, J.D., and Ausems, M.G.E.M.
Published: 2022
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11. Management of Metastatic Disease in Campania (MAMETIC): An Observational Multicenter Retrospective and Prospective Trial on Palliative Radiotherapy in an Italian Region. Study Protocol

Author: Di Franco R, Cascella M, Fusco M, Borzillo V, Scipilliti E, Ferraioli P, Iannacone E, De Palma G, Silvestro G, Gherardi F, Buonopane S, Alberti D, Totaro G, Manzo R, Guida G, Cuomo A, Pignata S, Di Napoli M, Rossetti S, Celentano E, Crispo A, Grimaldi M, Ravo V, and Muto P
Subjects: palliative care, metastatic disease, radiotherapy, cancer pain, breakthrough cancer pain, quality of life, Medicine (General), R5-920
Abstract: Rossella Di Franco,1 Marco Cascella,2 Mario Fusco,3 Valentina Borzillo,1 Esmeralda Scipilliti,1 Piera Ferraioli,1 Eva Iannacone,1 Giampaolo De Palma,1 Giustino Silvestro,1 Federica Gherardi,1 Sergio Buonopane,1 Domingo Alberti,1 Giuseppe Totaro,1 Roberto Manzo,1 Giovanna Guida,1 Arturo Cuomo,2 Sandro Pignata,4 Marilena Di Napoli,4 Sabrina Rossetti,4 Egidio Celentano,5 Anna Crispo,5 Maria Grimaldi,5 Vincenzo Ravo,1 Paolo Muto1 1Department of Radiation Oncology, Istituto Nazionale Tumori - IRCCS - Fondazione G. Pascale, Napoli, Italia; 2Division of Anesthesia and Pain Medicine, Istituto Nazionale Tumori, IRCCS Fondazione G. Pascale, Napoli, Italia; 3Cancer Registry Unit, ASL Napoli 3 SUD, Napoli, Italia; 4Department of Uro-Gynecological, Istituto Nazionale Tumori - IRCCS - Fondazione G. Pascale, Napoli, Italia; 5Epidemiology and Biostatistics Unit, Istituto Nazionale Tumori - IRCCS - Fondazione G. Pascale, Napoli, ItaliaCorrespondence: Rossella Di Franco, Department of Radiation Oncology, Istituto Nazionale Tumori - IRCCS - Fondazione G. Pascale, Napoli, Italia, Email r.difranco@istitutotumori.na.itBackground: In the Italian Campania Region, 30.517 new cases of solid cancer have been diagnosed, in 2019. Of those, patients with metastatic disease are up to 20%. This class of patients is extremely diversified and copious, and the offer of radiotherapy may vary in different geographical areas within the same region. The aim of this observational multicenter retrospective and prospective trial is to evaluate the occurrence of metastatic metastatic cancer patients candidates for palliative radiotherapy in several areas of a great Italian region, the management of the disease through RT approaches, and its impact on cancer-related pain and overall HRQoL.Methods: This is a multicenter, retrospective and prospective observational investigation. The retrospective part of the study concerns all patients enrolled with a diagnosis of metastatic disease and treated in RT centers within the Campania Region between January 2019 and July 2020. The prospective phase is going to involve all the metastatic patients with an indication of palliative RT. Considering regional epidemiological data, we expect an enrollment of 12.500– 21.000 patients in 5 years.Conclusion: The MAMETIC Trial in an observational study designed for investigating on the use of radiotherapy in patients with advanced disease within a regional area, and for evaluating the local response to the patient’s request. It can be a unique opportunity, not only to highlight possible geographic differences but also to regularly collect and share data to standardize the therapeutic offer within the regional area. ClinicalTrials.gov ID NCT04595032, retrospectively registered.Keywords: palliative care, metastatic disease, radiotherapy, cancer pain, breakthrough cancer pain, quality of life
Published: 2022

12. Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial

Author: Coleman, Robert L, Oza, Amit M, Lorusso, Domenica, Aghajanian, Carol, Oaknin, Ana, Dean, Andrew, Colombo, Nicoletta, Weberpals, Johanne I, Clamp, Andrew, Scambia, Giovanni, Leary, Alexandra, Holloway, Robert W, Gancedo, Margarita Amenedo, Fong, Peter C, Goh, Jeffrey C, O'Malley, David M, Armstrong, Deborah K, Garcia-Donas, Jesus, Swisher, Elizabeth M, Floquet, Anne, Konecny, Gottfried E, McNeish, Iain A, Scott, Clare L, Cameron, Terri, Maloney, Lara, Isaacson, Jeff, Goble, Sandra, Grace, Caroline, Harding, Thomas C, Raponi, Mitch, Sun, James, Lin, Kevin K, Giordano, Heidi, Ledermann, Jonathan A, investigators, ARIEL3, Buck, M, Dean, A, Friedlander, ML, Goh, JC, Harnett, P, Kichenadasse, G, Scott, CL, Denys, H, Dirix, L, Vergote, I, Elit, L, Ghatage, P, Oza, AM, Plante, M, Provencher, D, Weberpals, JI, Welch, S, Floquet, A, Gladieff, L, Joly, F, Leary, A, Lortholary, A, Lotz, J, Medioni, J, Tredan, O, You, B, El-Balat, A, Hänle, C, Krabisch, P, Neunhöffer, T, Pölcher, M, Wimberger, P, Amit, A, Kovel, S, Leviov, M, Safra, T, Shapira-Frommer, R, Stemmer, S, Bologna, A, Colombo, N, Lorusso, D, Pignata, S, Sabbatini, RF, Scambia, G, Tamberi, S, Zamagni, C, Fong, PC, O'Donnell, A, Gancedo, M Amenedo, Herraez, A Casado, Garcia-Donas, J, Guerra, EM, Oaknin, A, Palacio, I, Romero, I, Sanchez, A, Banerjee, SN, Clamp, A, Drew, Y, Gabra, HG, Jackson, D, Ledermann, JA, McNeish, IA, Parkinson, C, and Powell, M
Subjects: Reproductive Medicine, Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Orphan Drug, Clinical Research, Cancer, Genetics, Clinical Trials and Supportive Activities, Ovarian Cancer, Rare Diseases, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, 6.2 Cellular and gene therapies, Aged, Disease-Free Survival, Double-Blind Method, Female, Follow-Up Studies, Humans, Indoles, Internationality, Maintenance Chemotherapy, Middle Aged, Molecular Targeted Therapy, Neoplasm Recurrence, Local, Ovarian Neoplasms, Poly(ADP-ribose) Polymerase Inhibitors, Risk Assessment, Survival Rate, Treatment Outcome, ARIEL3 investigators, Medical and Health Sciences, General & Internal Medicine, Biomedical and clinical sciences, Health sciences
Abstract: BackgroundRucaparib, a poly(ADP-ribose) polymerase inhibitor, has anticancer activity in recurrent ovarian carcinoma harbouring a BRCA mutation or high percentage of genome-wide loss of heterozygosity. In this trial we assessed rucaparib versus placebo after response to second-line or later platinum-based chemotherapy in patients with high-grade, recurrent, platinum-sensitive ovarian carcinoma.MethodsIn this randomised, double-blind, placebo-controlled, phase 3 trial, we recruited patients from 87 hospitals and cancer centres across 11 countries. Eligible patients were aged 18 years or older, had a platinum-sensitive, high-grade serous or endometrioid ovarian, primary peritoneal, or fallopian tube carcinoma, had received at least two previous platinum-based chemotherapy regimens, had achieved complete or partial response to their last platinum-based regimen, had a cancer antigen 125 concentration of less than the upper limit of normal, had a performance status of 0-1, and had adequate organ function. Patients were ineligible if they had symptomatic or untreated central nervous system metastases, had received anticancer therapy 14 days or fewer before starting the study, or had received previous treatment with a poly(ADP-ribose) polymerase inhibitor. We randomly allocated patients 2:1 to receive oral rucaparib 600 mg twice daily or placebo in 28 day cycles using a computer-generated sequence (block size of six, stratified by homologous recombination repair gene mutation status, progression-free interval after the penultimate platinum-based regimen, and best response to the most recent platinum-based regimen). Patients, investigators, site staff, assessors, and the funder were masked to assignments. The primary outcome was investigator-assessed progression-free survival evaluated with use of an ordered step-down procedure for three nested cohorts: patients with BRCA mutations (carcinoma associated with deleterious germline or somatic BRCA mutations), patients with homologous recombination deficiencies (BRCA mutant or BRCA wild-type and high loss of heterozygosity), and the intention-to-treat population, assessed at screening and every 12 weeks thereafter. This trial is registered with ClinicalTrials.gov, number NCT01968213; enrolment is complete.FindingsBetween April 7, 2014, and July 19, 2016, we randomly allocated 564 patients: 375 (66%) to rucaparib and 189 (34%) to placebo. Median progression-free survival in patients with a BRCA-mutant carcinoma was 16·6 months (95% CI 13·4-22·9; 130 [35%] patients) in the rucaparib group versus 5·4 months (3·4-6·7; 66 [35%] patients) in the placebo group (hazard ratio 0·23 [95% CI 0·16-0·34]; p
Published: 2017

13. The forefront of ovarian cancer therapy: update on PARP inhibitors

Author: Mirza, M.R., Coleman, R.L., González-Martín, A., Moore, K.N., Colombo, N., Ray-Coquard, I., and Pignata, S.
Published: 2020
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14. PARP Inhibitors in Endometrial Cancer: Current Status and Perspectives

Author: Musacchio L, Caruso G, Pisano C, Cecere SC, Di Napoli M, Attademo L, Tambaro R, Russo D, Califano D, Palaia I, Muzii L, Benedetti Panici P, and Pignata S
Subjects: endometrial cancer, parp inhibitors, pten mutation, p53 mutation, homologous recombination deficiency, immune checkpoint inhibitors, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Lucia Musacchio,1 Giuseppe Caruso,1 Carmela Pisano,2 Sabrina Chiara Cecere,2 Marilena Di Napoli,2 Laura Attademo,2 Rosa Tambaro,2 Daniela Russo,3 Daniela Califano,3 Innocenza Palaia,1 Ludovico Muzii,1 Pierluigi Benedetti Panici,1 Sandro Pignata2 1Department of Maternal and Child Health and Urological Sciences, University “Sapienza”, Policlinico Umberto I, Rome, Italy; 2Department of Urology and Gynecology, Istituto Nazionale Tumori IRCCS “Fondazione G. Pascale”, Naples, Italy; 3Functional Genomic Unit, Istituto Nazionale Tumori IRCCS “Fondazione G. Pascale”, Naples, ItalyCorrespondence: Sandro PignataDepartment of Urology and Gynecology, Istituto Nazionale Tumori IRCCS “Fondazione G. Pascale”, Via Semmola, Naples 80131, ItalyTel +39 0815903409Fax +39 0815903861Email s.pignata@istitutotumori.na.itAbstract: Advanced, recurrent and metastatic endometrial cancer (EC) has a dismal prognosis due to poor response rates to conventional treatments. In the era of precision medicine, the improved understanding of cancer genetics and molecular biology has led to the development of targeted therapies, such as poly (ADP-ribose) polymerase (PARP) inhibitors. This class of drugs that inhibit PARP enzymes has been investigated in many different types of tumors and its use in the treatment of gynecological malignancies has rapidly increased over the past few years. Data from several clinical trials showed that PARP inhibitors have a beneficial role in cancers with a defect in the homologous DNA recombination system, regardless of the BRCA mutational status. Since EC frequently shows mutations in PTEN and TP53 genes, indirectly involved in the homologous DNA recombination pathway, several in vivo and in vitro studies investigated the efficacy of PARP inhibitors in EC, showing promising results. This review will discuss the use of PARP inhibitors in endometrial cancer, summarizing data from preclinical studies and providing an overview of the ongoing trials, with a special focus on the development of combined treatment strategies with PARP inhibitors and immune checkpoint inhibitors.Keywords: endometrial cancer, PARP inhibitors, PTEN mutation, P53 mutation, homologous recombination deficiency, immune checkpoint inhibitors
Published: 2020

15. Standardized and simplified reporting of next-generation sequencing results in advanced non-small-cell lung cancer: practical indications from an Italian multidisciplinary group

Author: Malapelle, U, Donne, A, Pagni, F, Fraggetta, F, Rocco, E, Pasello, G, Perrone, G, Pepe, F, Vatrano, S, Pignata, S, Pinto, C, Pruneri, G, Russo, A, Soto Parra, H, Vallone, S, Marchetti, A, Troncone, G, Novello, S, Malapelle, Umberto, Donne, Alessandro Delle, Pagni, Fabio, Fraggetta, Filippo, Rocco, Elena Guerini, Pasello, Giulia, Perrone, Giuseppe, Pepe, Francesco, Vatrano, Simona, Pignata, Sandro, Pinto, Carmine, Pruneri, Giancarlo, Russo, Antonio, Soto Parra, Hector J, Vallone, Stefania, Marchetti, Antonio, Troncone, Giancarlo, Novello, Silvia, Malapelle, U, Donne, A, Pagni, F, Fraggetta, F, Rocco, E, Pasello, G, Perrone, G, Pepe, F, Vatrano, S, Pignata, S, Pinto, C, Pruneri, G, Russo, A, Soto Parra, H, Vallone, S, Marchetti, A, Troncone, G, Novello, S, Malapelle, Umberto, Donne, Alessandro Delle, Pagni, Fabio, Fraggetta, Filippo, Rocco, Elena Guerini, Pasello, Giulia, Perrone, Giuseppe, Pepe, Francesco, Vatrano, Simona, Pignata, Sandro, Pinto, Carmine, Pruneri, Giancarlo, Russo, Antonio, Soto Parra, Hector J, Vallone, Stefania, Marchetti, Antonio, Troncone, Giancarlo, and Novello, Silvia
Abstract: Molecular biomarker testing is increasingly becoming standard of care for advanced non-small cell lung cancer (NSCLC). Tissue and liquid biopsy-based next-generation sequencing (NGS) is now highly recommended and has become an integral part of the routine management of advanced NSCLC patients. This highly sensitive approach can simultaneously and efficiently detect multiple biomarkers even in scant samples. However full optimization of NGS in clinical practice requires accurate reporting and interpretation of NGS findings. Indeed, as the number of NSCLC biomarkers continues to grow, clinical reporting of NGS data is becoming increasingly complex. In this scenario, achieving standardization, simplification, and improved readability of NGS reports is key to ensuring timely and appropriate treatment decisions. In an effort to address the complexity and lengthy reporting of NGS mutation results, an Italian group of 14 healthcare professionals involved in NSCLC management convened in 2023 to address the content, structure, and ease-of-use of NGS reporting practices and proposed a standard report template for clinical use This article presents the key discussion points addressed by the Italian working group and describes the essential elements of the report template.
Published: 2024

16. Primary neuroendocrine neoplasms of the vulva: A review of the MITO rare cancer group

Author: Barcellini, A, Golia D'Augè, T, Mandato, V, Cuccu, I, Musella, A, Fruscio, R, Vitale, M, Martinello, R, Mangili, G, Pignata, S, Palaia, I, Barcellini, Amelia, Golia D'Augè, Tullio, Mandato, Vincenzo Dario, Cuccu, Ilaria, Musella, Angela, Fruscio, Robert, Vitale, Maria Giuseppa, Martinello, Ruby, Mangili, Giorgia, Pignata, Sandro, Palaia, Innocenza, Barcellini, A, Golia D'Augè, T, Mandato, V, Cuccu, I, Musella, A, Fruscio, R, Vitale, M, Martinello, R, Mangili, G, Pignata, S, Palaia, I, Barcellini, Amelia, Golia D'Augè, Tullio, Mandato, Vincenzo Dario, Cuccu, Ilaria, Musella, Angela, Fruscio, Robert, Vitale, Maria Giuseppa, Martinello, Ruby, Mangili, Giorgia, Pignata, Sandro, and Palaia, Innocenza
Abstract: Gynecological neuroendocrine neoplasms are rare entities and can be divided into two groups: carcinoids and neuroendocrine carcinomas. Due to their rarity their management is not standardized. The aim of this work is to summarize and discuss the current literature evidence on this pathology. A scoping literature review was performed in multiple databases. Thirty-one studies were included: 30 case reports and one case series. Patients’ age ranged between 28 and 92 years. Surgery was the most used treatment and the surgical approach included local excision (N = 16/31; 51.6%) with (N = 5/16; 31.25%) or without (N = 11/16; 68.75%) inguinal lymphadenectomy. Adjuvant radiotherapy was delivered in 12 (38.7%) cases; instead, platinum-based therapies were frequently used when chemotherapy was chosen for adjuvant treatment. The overall survival ranged between 20 days to 4 years. However, further research is needed; currently, multimodal approach including surgery, chemotherapy and radiotherapy appeared safe and feasible for the treatment of these rare and aggressive diseases.
Published: 2024

17. ESGO–ESMO–ESP consensus conference recommendations on ovarian cancer: pathology and molecular biology and early, advanced and recurrent disease

Author: Ledermann, J. A., Matias-Guiu, X., Amant, F., Concin, N., Davidson, B., Fotopoulou, C., González-Martin, A., Gourley, C., Leary, A., Lorusso, Domenica, Banerjee, S., Chiva, L., Cibula, D., Colombo, N., Croce, S., Eriksson, A. G., Falandry, C., Fischerova, D., Harter, P., Joly, F., Lazaro, C., Lok, C., Mahner, S., Marmé, F., Marth, C., Mccluggage, W. G., Mcneish, I. A., Morice, P., Nicum, S., Oaknin, A., Pérez-Fidalgo, J. A., Pignata, S., Ramirez, P. T., Ray-Coquard, I., Romero, I., Scambia, Giovanni, Sehouli, J., Shapira-Frommer, R., Sundar, S., Tan, D. S. P., Taskiran, C., van Driel, W. J., Vergote, I., Planchamp, F., Sessa, C., Fagotti, Anna, Lorusso, D., Scambia, G. (ORCID:0000-0003-2758-1063), Fagotti, A. (ORCID:0000-0001-5579-335X), Ledermann, J. A., Matias-Guiu, X., Amant, F., Concin, N., Davidson, B., Fotopoulou, C., González-Martin, A., Gourley, C., Leary, A., Lorusso, Domenica, Banerjee, S., Chiva, L., Cibula, D., Colombo, N., Croce, S., Eriksson, A. G., Falandry, C., Fischerova, D., Harter, P., Joly, F., Lazaro, C., Lok, C., Mahner, S., Marmé, F., Marth, C., Mccluggage, W. G., Mcneish, I. A., Morice, P., Nicum, S., Oaknin, A., Pérez-Fidalgo, J. A., Pignata, S., Ramirez, P. T., Ray-Coquard, I., Romero, I., Scambia, Giovanni, Sehouli, J., Shapira-Frommer, R., Sundar, S., Tan, D. S. P., Taskiran, C., van Driel, W. J., Vergote, I., Planchamp, F., Sessa, C., Fagotti, Anna, Lorusso, D., Scambia, G. (ORCID:0000-0003-2758-1063), and Fagotti, A. (ORCID:0000-0001-5579-335X)
Abstract: The European Society of Gynaecological Oncology, the European Society for Medical Oncology (ESMO) and the European Society of Pathology held a consensus conference (CC) on ovarian cancer on 15-16 June 2022 in Valencia, Spain. The CC panel included 44 experts in the management of ovarian cancer and pathology, an ESMO scientific advisor and a methodologist. The aim was to discuss new or contentious topics and develop recommendations to improve and harmonise the management of patients with ovarian cancer. Eighteen questions were identified for discussion under four main topics: (i) pathology and molecular biology, (ii) early-stage disease and pelvic mass in pregnancy, (iii) advanced stage (including older/frail patients) and (iv) recurrent disease. The panel was divided into four working groups (WGs) to each address questions relating to one of the four topics outlined above, based on their expertise. Relevant scientific literature was reviewed in advance. Recommendations were developed by the WGs and then presented to the entire panel for further discussion and amendment before voting. This manuscript focuses on the recommendation statements that reached a consensus, their voting results and a summary of evidence supporting each recommendation.
Published: 2024

18. Antitumor activity and safety of pembrolizumab in patients with advanced recurrent ovarian cancer: results from the phase II KEYNOTE-100 study

Author: Matulonis, U.A., Shapira-Frommer, R., Santin, A.D., Lisyanskaya, A.S., Pignata, S., Vergote, I., Raspagliesi, F., Sonke, G.S., Birrer, M., Provencher, D.M., Sehouli, J., Colombo, N., González-Martín, A., Oaknin, A., Ottevanger, P.B., Rudaitis, V., Katchar, K., Wu, H., Keefe, S., Ruman, J., and Ledermann, J.A.
Published: 2019
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19. ESMO–ESGO consensus conference recommendations on ovarian cancer: pathology and molecular biology, early and advanced stages, borderline tumours and recurrent disease

Author: Baert, T., Banerjee, S., Belaroussi, I., Blecharz, P., Bruchim, I., Cibula, D., Colombo, N., Concin, N., Davidson, B., Dashora, A., Devouassoux-Shisheboran, M., du Bois, A., Ferrero, A., Glasspool, R., González-Martin, A., Heinzelmann-Schwarz, V., Joly, F., Kim, J.W., Kridelka, F., Ledermann, J., Lorusso, D., Mahner, S., McCluggage, W.G., McNeish, I., Mikami, M., Mirza, M.R., Morice, P., Nicum, S., Olbrecht, S., O’Donnell, D.M., Pautier, P., Planchamp, F., Pignata, S., Querleu, D., Ray-Coquard, I., Rodolakis, A., Sehouli, J., Selcukbiricik, F., Sessa, C., Singh, N., Tan, D.S.P., Timmerman, D., Tognon, G., van der Velden, J., Vergote, I., Witteveen, P.O., and Zeimet, A.G.
Published: 2019
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20. Carboplatin and paclitaxel plus avelumab compared with carboplatin and paclitaxel in advanced or recurrent endometrial cancer (MITO END-3): a multicentre, open-label, randomised, controlled, phase 2 trial

Author: Pignata, S, Scambia, G, Schettino, C, Arenare, L, Pisano, C, Lombardi, D, De Giorgi, U, Andreetta, C, Cinieri, S, De Angelis, C, Priolo, D, Casanova, C, Rosati, M, Greco, F, Zafarana, E, Schiavetto, I, Mammoliti, S, Cecere, S, Salutari, V, Scalone, S, Farolfi, A, Di Napoli, M, Lorusso, D, Gargiulo, P, Califano, D, Russo, D, Spina, A, De Cecio, R, Chiodini, P, Perrone, F, Accinno, V, Altavilla, C, Antonelli, G, Artioli, G, Avola, F, Barbara, B, Barbato, V, Bartoletti, M, Bevilacqua, S, Bordonaro, R, Borghese, O, Buonfanti, G, Camarda, F, Canzanella, G, Carbone, V, Carbone, M, Carlo Stella, G, Cassani, C, Castagna, F, Cattaneo, M, Cinefra, M, Colombo, N, Corsetti, S, Dall'Agata, M, D'Amico, M, Daniele, G, De Marino, E, De Matteis, G, De Placido, S, Del Bene, G, Del Giudice, A, Del Monte, F, Del Sesto, M, Donini, M, Drudi, G, Falcone, G, Favaretto, A, Ferrera, G, Florio, M, Forestieri, V, Gallo, M, Gallo, C, Garibaldi, F, Gerevini, F, Ghizzoni, V, Giganti, M, Gimigliano, A, Giudice, E, Gnocchi, N, Gravina, A, Greggi, S, Iaia, M, Ilardi, A, Iovine, G, Ippoliti, G, Irollo, G, Isidori, I, Lapresa, M, Lavenia, G, Longhitano, L, Lucia, B, Luzi, G, Mariano, S, Marino, V, Marrapese, G, Martino, M, Matocci, R, Mazzoni, E, Mercuri, D, Mirto, M, Pignata S., Scambia G., Schettino C., Arenare L., Pisano C., Lombardi D., De Giorgi U., Andreetta C., Cinieri S., De Angelis C., Priolo D., Casanova C., Rosati M., Greco F., Zafarana E., Schiavetto I., Mammoliti S., Cecere S. C., Salutari V., Scalone S., Farolfi A., Di Napoli M., Lorusso D., Gargiulo P., Califano D., Russo D., Spina A., De Cecio R., Chiodini P., Perrone F., Accinno V., Altavilla C., Antonelli G., Artioli G., Avola F., Barbara B., Barbato V., Bartoletti M., Bevilacqua S., Bordonaro R., Borghese O., Buonfanti G., Camarda F., Canzanella G., Carbone V., Carbone M. R., Carlo Stella G., Cassani C., Castagna F., Cattaneo M., Cinefra M., Colombo N., Corsetti S., Dall'Agata M., D'Amico M., Daniele G., De Marino E., De Matteis G., De Placido S., Del Bene G., Del Giudice A., Del Monte F., Del Sesto M., Donini M., Drudi G., Falcone G., Favaretto A., Ferrera G., Florio M., Forestieri V., Gallo M. S., Gallo C., Garibaldi F., Gerevini F., Ghizzoni V., Giganti M. O., Gimigliano A., Giudice E., Gnocchi N., Gravina A., Greggi S., Iaia M. L., Ilardi A., Iovine G., Ippoliti G., Irollo G., Isidori I., Lapresa M., Lavenia G., Longhitano L., Lucia B., Luzi G., Mariano S., Marino V., Marrapese G., Martino M., Matocci R., Mazzoni E., Mercuri D., Mirto M., Pignata, S, Scambia, G, Schettino, C, Arenare, L, Pisano, C, Lombardi, D, De Giorgi, U, Andreetta, C, Cinieri, S, De Angelis, C, Priolo, D, Casanova, C, Rosati, M, Greco, F, Zafarana, E, Schiavetto, I, Mammoliti, S, Cecere, S, Salutari, V, Scalone, S, Farolfi, A, Di Napoli, M, Lorusso, D, Gargiulo, P, Califano, D, Russo, D, Spina, A, De Cecio, R, Chiodini, P, Perrone, F, Accinno, V, Altavilla, C, Antonelli, G, Artioli, G, Avola, F, Barbara, B, Barbato, V, Bartoletti, M, Bevilacqua, S, Bordonaro, R, Borghese, O, Buonfanti, G, Camarda, F, Canzanella, G, Carbone, V, Carbone, M, Carlo Stella, G, Cassani, C, Castagna, F, Cattaneo, M, Cinefra, M, Colombo, N, Corsetti, S, Dall'Agata, M, D'Amico, M, Daniele, G, De Marino, E, De Matteis, G, De Placido, S, Del Bene, G, Del Giudice, A, Del Monte, F, Del Sesto, M, Donini, M, Drudi, G, Falcone, G, Favaretto, A, Ferrera, G, Florio, M, Forestieri, V, Gallo, M, Gallo, C, Garibaldi, F, Gerevini, F, Ghizzoni, V, Giganti, M, Gimigliano, A, Giudice, E, Gnocchi, N, Gravina, A, Greggi, S, Iaia, M, Ilardi, A, Iovine, G, Ippoliti, G, Irollo, G, Isidori, I, Lapresa, M, Lavenia, G, Longhitano, L, Lucia, B, Luzi, G, Mariano, S, Marino, V, Marrapese, G, Martino, M, Matocci, R, Mazzoni, E, Mercuri, D, Mirto, M, Pignata S., Scambia G., Schettino C., Arenare L., Pisano C., Lombardi D., De Giorgi U., Andreetta C., Cinieri S., De Angelis C., Priolo D., Casanova C., Rosati M., Greco F., Zafarana E., Schiavetto I., Mammoliti S., Cecere S. C., Salutari V., Scalone S., Farolfi A., Di Napoli M., Lorusso D., Gargiulo P., Califano D., Russo D., Spina A., De Cecio R., Chiodini P., Perrone F., Accinno V., Altavilla C., Antonelli G., Artioli G., Avola F., Barbara B., Barbato V., Bartoletti M., Bevilacqua S., Bordonaro R., Borghese O., Buonfanti G., Camarda F., Canzanella G., Carbone V., Carbone M. R., Carlo Stella G., Cassani C., Castagna F., Cattaneo M., Cinefra M., Colombo N., Corsetti S., Dall'Agata M., D'Amico M., Daniele G., De Marino E., De Matteis G., De Placido S., Del Bene G., Del Giudice A., Del Monte F., Del Sesto M., Donini M., Drudi G., Falcone G., Favaretto A., Ferrera G., Florio M., Forestieri V., Gallo M. S., Gallo C., Garibaldi F., Gerevini F., Ghizzoni V., Giganti M. O., Gimigliano A., Giudice E., Gnocchi N., Gravina A., Greggi S., Iaia M. L., Ilardi A., Iovine G., Ippoliti G., Irollo G., Isidori I., Lapresa M., Lavenia G., Longhitano L., Lucia B., Luzi G., Mariano S., Marino V., Marrapese G., Martino M., Matocci R., Mazzoni E., Mercuri D., and Mirto M.
Published: 2023

21. Health-Related Quality of Life in Patients With Advanced Endometrial Cancer Treated With Lenvatinib Plus Pembrolizumab or Treatment of Physician's Choice

Author: Lorusso, D, Colombo, N, Herraez, A, Santin, A, Colomba, E, Miller, D, Fujiwara, K, Pignata, S, Baron-Hay, S, Ray-Coquard, I, Shapira-Frommer, R, Kim, Y, Mccormack, M, Massaad, R, Nguyen, A, Zhao, Q, Mckenzie, J, Prabhu, V, Makker, V, Lorusso D., Colombo N., Herraez A. C., Santin A. D., Colomba E., Miller D. S., Fujiwara K., Pignata S., Baron-Hay S. E., Ray-Coquard I. L., Shapira-Frommer R., Kim Y. M., McCormack M., Massaad R., Nguyen A. M., Zhao Q., McKenzie J., Prabhu V. S., Makker V., Lorusso, D, Colombo, N, Herraez, A, Santin, A, Colomba, E, Miller, D, Fujiwara, K, Pignata, S, Baron-Hay, S, Ray-Coquard, I, Shapira-Frommer, R, Kim, Y, Mccormack, M, Massaad, R, Nguyen, A, Zhao, Q, Mckenzie, J, Prabhu, V, Makker, V, Lorusso D., Colombo N., Herraez A. C., Santin A. D., Colomba E., Miller D. S., Fujiwara K., Pignata S., Baron-Hay S. E., Ray-Coquard I. L., Shapira-Frommer R., Kim Y. M., McCormack M., Massaad R., Nguyen A. M., Zhao Q., McKenzie J., Prabhu V. S., and Makker V.
Abstract: Purpose: Lenvatinib and pembrolizumab (LEN+PEMBRO) demonstrated clinically meaningful and statistically significant improvements in efficacy versus treatment of physician's choice (TPC) in patients with advanced endometrial cancer (aEC) in the phase 3 Study 309/KEYNOTE-775. Health-related quality-of-life (HRQoL) is reported. Patients and Methods: Patients were randomly assigned to receive LEN+PEMBRO (n = 411; LEN 20 mg/day; PEMBRO 200 mg Q3W) or TPC (n = 416; doxorubicin 60 mg/m2 Q3W or paclitaxel 80 mg/m2 [weekly, 3 weeks on/1 week off]). Impact of treatment on HRQoL assessed by the global health status/quality of life (GHS/QoL) score of the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire (EORTC QLQ-C30) was a secondary objective; other scales of the Quality-of-Life Questionnaire (QLQ-C30), EORTC QLQ-Endometrial, 24 questions (EORTC QLQ-EN24), and EuroQoL 5 dimensions, 5 levels (EQ-5D-5L) were exploratory objectives. HRQoL was assessed on day 1 of each cycle. Completion/compliance, change from baseline, time to first and definitive deterioration were assessed. No multiplicity adjustments were applied for HRQoL endpoints. Results: The latest timepoint at which the predefined rates of completion (≥60%) and compliance (≥80%) were met was week 12. HRQoL at week 12 between treatment groups was generally similar. Time to first deterioration symptom scales favoured LEN+PEMBRO for QLQ-C30 dyspnoea, and QLQ-EN24 for poor body image, tingling/numbness, and hair loss; and TPC was favoured for QLQ-C30 pain, appetite loss, and diarrhoea, and QLQ-EN24 muscular pain. While the QLQ-C30 physical functional scale favoured TPC, other functional scales were generally similar between arms. Time to definitive deterioration favoured LEN+PEMBRO on most scales. Conclusion: HRQoL data from Study 309/KEYNOTE-775, with previously published efficacy and safety results, indicate that LEN+PEMBRO has an overall favourable benefit/risk profile versus TPC fo
Published: 2023

22. Management of primary and recurrent Bartholin’s gland carcinoma: A systematic review on behalf of MITO Rare Cancer Group

Author: Turetta, C, Mazzeo, R, Capalbo, G, Miano, S, Fruscio, R, Di Donato, V, Falcone, F, Mangili, G, Pignata, S, Palaia, I, Turetta C., Mazzeo R., Capalbo G., Miano S., Fruscio R., Di Donato V., Falcone F., Mangili G., Pignata S., Palaia I., Turetta, C, Mazzeo, R, Capalbo, G, Miano, S, Fruscio, R, Di Donato, V, Falcone, F, Mangili, G, Pignata, S, Palaia, I, Turetta C., Mazzeo R., Capalbo G., Miano S., Fruscio R., Di Donato V., Falcone F., Mangili G., Pignata S., and Palaia I.
Abstract: Bartholin gland carcinoma is an extremely rare disease. Information regarding treatment is scarce and there is no strict consensus on best practice. All studies reporting cases of Bartholin’s gland cancer were screened and evaluated for inclusion. Baseline characteristics of studies were extracted. A total number of 290 manuscripts collected were available for the review process. Studies included in a previous systematic review were not duplicated. In total, details of 367 patients were collected, as follows: histological features, clinical presentation, treatment, recurrent rate, treatment of recurrence and outcome. About 35% of Bartholin gland carcinoma were squamous cell carcinoma. Almost 50% of patients presented with advanced stage. The therapeutic approach was mainly surgery, and in 61% of those women lymph node assessment was performed. Recurrence occurred in 21% of cases. Bartholin gland cancer remains a challenge for gynecologic oncologists. Guidelines, centralization to referral centers and standardized therapy are needed.
Published: 2023

23. PARP inhibitor predictive value of the Leuven HRD test compared with Myriad MyChoice CDx PLUS HRD on 468 ovarian cancer patients from the PAOLA-1/ENGOT-ov25 trial

Author: Loverix, L, Vergote, I, Busschaert, P, Vanderstichele, A, Venken, T, Boeckx, B, Harter, P, Brems, H, Van Nieuwenhuysen, E, Pignata, S, Baert, T, Gonzalez-Martin, A, Han, S, Marth, C, Neven, P, Colombo, N, Berteloot, P, Mäenpää, J, Olbrecht, S, Laga, T, Sablon, E, Ray-Coquard, I, Pujade-Lauraine, E, Lambrechts, D, Van Gorp, T, Loverix L., Vergote I., Busschaert P., Vanderstichele A., Venken T., Boeckx B., Harter P., Brems H., Van Nieuwenhuysen E., Pignata S., Baert T., Gonzalez-Martin A., Han S., Marth C., Neven P., Colombo N., Berteloot P., Mäenpää J., Olbrecht S., Laga T., Sablon E., Ray-Coquard I., Pujade-Lauraine E., Lambrechts D., Van Gorp T., Loverix, L, Vergote, I, Busschaert, P, Vanderstichele, A, Venken, T, Boeckx, B, Harter, P, Brems, H, Van Nieuwenhuysen, E, Pignata, S, Baert, T, Gonzalez-Martin, A, Han, S, Marth, C, Neven, P, Colombo, N, Berteloot, P, Mäenpää, J, Olbrecht, S, Laga, T, Sablon, E, Ray-Coquard, I, Pujade-Lauraine, E, Lambrechts, D, Van Gorp, T, Loverix L., Vergote I., Busschaert P., Vanderstichele A., Venken T., Boeckx B., Harter P., Brems H., Van Nieuwenhuysen E., Pignata S., Baert T., Gonzalez-Martin A., Han S., Marth C., Neven P., Colombo N., Berteloot P., Mäenpää J., Olbrecht S., Laga T., Sablon E., Ray-Coquard I., Pujade-Lauraine E., Lambrechts D., and Van Gorp T.
Abstract: Background: The PAOLA-1/ENGOT-ov25 trial showed improved progression-free (PFS) and overall survival (OS) in homologous recombination deficient (HRD) positive patients treated with olaparib, but not when HRD negative (HRD tested with MyChoice CDx PLUS [Myriad test]). Patients and methods: The academic Leuven HRD test consists of capture-based targeted sequencing of genome-wide single-nucleotide polymorphisms and coding exons of eight HR genes including BRCA1, BRCA2, and TP53. We compared the predictive value of the Leuven HRD versus Myriad HRD test for PFS and OS in the randomised PAOLA-1 trial. Results: 468 patients had left-over DNA after Myriad testing for Leuven HRD testing. Positive/negative/overall percent agreement for the Leuven versus Myriad HRD status was 95%/86%/91%, respectively. Tumours were HRD+ in 55% and 52%, respectively. In Leuven HRD+ patients, 5 years PFS (5yPFS) was 48.6% versus 20.3% (HR 0.431; 95% confidence intervals (CI) 0.312–0.595) for olaparib versus placebo, respectively (Myriad test 0.409; 95% CI 0.292–0.572). In Leuven HRD+/BRCAwt patients 5yPFS was 41.3% versus 12.6% (HR 0.497; 95% CI 0.316–0.783), and 43.6% versus 13.3% (HR 0.435; 95% CI 0.261–0.727) for the Myriad test. 5yOS was prolonged in the HRD+ subgroup with both tests 67.2% versus 54.4% (HR 0.663; 95% CI 0.442–0.995) for the Leuven test, and 68.0% versus 51.8% (HR 0.596 95% CI 0.393–0.904) for the Myriad test. HRD status was undetermined in 10.7% and 9.4% of the samples, respectively. Conclusions: A robust correlation between the Leuven HRD and Myriad test was observed. For HRD+ tumours, the academic Leuven HRD showed a similar difference in PFS and OS as the Myriad test.
Published: 2023

24. ESGO–ESMO–ESP consensus conference recommendations on ovarian cancer: pathology and molecular biology and early, advanced and recurrent disease

Author: Ledermann, J.A., primary, Matias-Guiu, X., additional, Amant, F., additional, Concin, N., additional, Davidson, B., additional, Fotopoulou, C., additional, González-Martin, A., additional, Gourley, C., additional, Leary, A., additional, Lorusso, D., additional, Banerjee, S., additional, Chiva, L., additional, Cibula, D., additional, Colombo, N., additional, Croce, S., additional, Eriksson, A.G., additional, Falandry, C., additional, Fischerova, D., additional, Harter, P., additional, Joly, F., additional, Lazaro, C., additional, Lok, C., additional, Mahner, S., additional, Marmé, F., additional, Marth, C., additional, McCluggage, W.G., additional, McNeish, I.A., additional, Morice, P., additional, Nicum, S., additional, Oaknin, A., additional, Pérez-Fidalgo, J.A., additional, Pignata, S., additional, Ramirez, P.T., additional, Ray-Coquard, I., additional, Romero, I., additional, Scambia, G., additional, Sehouli, J., additional, Shapira-Frommer, R., additional, Sundar, S., additional, Tan, D.S.P., additional, Taskiran, C., additional, van Driel, W.J., additional, Vergote, I., additional, Planchamp, F., additional, Sessa, C., additional, and Fagotti, A., additional
Published: 2024
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25. Corrigendum to “Under-reporting of subjective symptoms and its prognostic value: a pooled analysis of 12 cancer clinical trials”: [ESMO Open 9 (2024) 102941]

Author: Arenare, L., Di Liello, R., De Placido, P., Gridelli, C., Morabito, A., Pignata, S., Nuzzo, F., Avallone, A., Maiello, E., Gargiulo, P., Schettino, C., Gravina, A., Gallo, C., Chiodini, P., Di Maio, M., Perrone, F., and Piccirillo, M.C.
Published: 2024
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26. Latest clinical evidence and further development of PARP inhibitors in ovarian cancer

Author: Mirza, M.R., Pignata, S., and Ledermann, J.A.
Published: 2018
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27. Quality-of-life analysis of the MITO-8, MaNGO, BGOG-Ov1, AGO-Ovar2.16, ENGOT-Ov1, GCIG study comparing platinum-based versus non-platinum-based chemotherapy in patients with partially platinum-sensitive recurrent ovarian cancer

Author: Piccirillo, M.C., Scambia, G., Bologna, A., Signoriello, S., Vergote, I., Baumann, K., Lorusso, D., Murgia, V., Sorio, R., Ferrandina, G., Sacco, C., Cormio, G., Breda, E., Cinieri, S., Natale, D., Mangili, G., Pisano, C., Cecere, S.C., Di Napoli, M., Salutari, V., Raspagliesi, F., Arenare, L., Bergamini, A., Bryce, J., Daniele, G., Gallo, C., Pignata, S., and Perrone, F.
Published: 2018
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28. P080 Using your Mobile/Tablet Device at Bedtime for Work: Implications for Adult Sleep and Job Performance

Author: Lushington, K, primary, Markobotsaris, M, additional, Dollard, M, additional, Parkin, A, additional, Potter, R, additional, Zadow, A, additional, Pignata, S, additional, Afsharian, A, additional, Owen, M, additional, and Bakker, A, additional
Published: 2023
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29. The role of staging and adjuvant chemotherapy in stage I malignant ovarian germ cell tumors (MOGTs): the MITO-9 study

Author: Mangili, G., Sigismondi, C., Lorusso, D., Cormio, G., Candiani, M., Scarfone, G., Mascilini, F., Gadducci, A., Mosconi, A.M., Scollo, P., Cassani, C., Pignata, S., and Ferrandina, G.
Published: 2017
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30. The association of financial difficulties with clinical outcomes in cancer patients: secondary analysis of 16 academic prospective clinical trials conducted in Italy

Author: Perrone, F., Jommi, C., Di Maio, M., Gimigliano, A., Gridelli, C., Pignata, S., Ciardiello, F., Nuzzo, F., de Matteis, A., Del Mastro, L., Bryce, J., Daniele, G., Morabito, A., Piccirillo, M.C., Rocco, G., Guizzaro, L., and Gallo, C.
Published: 2016
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31. Prospective phase II trial of trabectedin in BRCA-mutated and/or BRCAness phenotype recurrent ovarian cancer patients: the MITO 15 trial

Author: Lorusso, D., Scambia, G., Pignata, S., Sorio, R., Amadio, G., Lepori, S., Mosconi, A., Pisano, C., Mangili, G., Maltese, G., Sabbatini, R., Artioli, G., Gamucci, T., Di Napoli, M., Capoluongo, E., Ludovini, V., Raspagliesi, F., and Ferrandina, G.
Published: 2016
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32. Alternative academic approaches for testing homologous recombination deficiency in ovarian cancer in the MITO16A/MaNGO-OV2 trial

Author: Capoluongo, E, Pellegrino, B, Arenare, L, Califano, D, Scambia, G, Beltrame, L, Serra, V, Scaglione, G, Spina, A, Cecere, S, De Cecio, R, Normanno, N, Colombo, N, Lorusso, D, Russo, D, Nardelli, C, D'Incalci, M, Llop-Guevara, A, Pisano, C, Baldassarre, G, Mezzanzanica, D, Artioli, G, Setaro, M, Tasca, G, Roma, C, Campanini, N, Cinieri, S, Sergi, A, Musolino, A, Perrone, F, Chiodini, P, Marchini, S, Pignata, S, Capoluongo E. D., Pellegrino B., Arenare L., Califano D., Scambia G., Beltrame L., Serra V., Scaglione G. L., Spina A., Cecere S. C., De Cecio R., Normanno N., Colombo N., Lorusso D., Russo D., Nardelli C., D'Incalci M., Llop-Guevara A., Pisano C., Baldassarre G., Mezzanzanica D., Artioli G., Setaro M., Tasca G., Roma C., Campanini N., Cinieri S., Sergi A., Musolino A., Perrone F., Chiodini P., Marchini S., Pignata S., Capoluongo, E, Pellegrino, B, Arenare, L, Califano, D, Scambia, G, Beltrame, L, Serra, V, Scaglione, G, Spina, A, Cecere, S, De Cecio, R, Normanno, N, Colombo, N, Lorusso, D, Russo, D, Nardelli, C, D'Incalci, M, Llop-Guevara, A, Pisano, C, Baldassarre, G, Mezzanzanica, D, Artioli, G, Setaro, M, Tasca, G, Roma, C, Campanini, N, Cinieri, S, Sergi, A, Musolino, A, Perrone, F, Chiodini, P, Marchini, S, Pignata, S, Capoluongo E. D., Pellegrino B., Arenare L., Califano D., Scambia G., Beltrame L., Serra V., Scaglione G. L., Spina A., Cecere S. C., De Cecio R., Normanno N., Colombo N., Lorusso D., Russo D., Nardelli C., D'Incalci M., Llop-Guevara A., Pisano C., Baldassarre G., Mezzanzanica D., Artioli G., Setaro M., Tasca G., Roma C., Campanini N., Cinieri S., Sergi A., Musolino A., Perrone F., Chiodini P., Marchini S., and Pignata S.
Published: 2022

33. Clear cell carcinoma of the endometrium

Author: Bogani, G, Ray-Coquard, I, Concin, N, Ngoi, N, Morice, P, Enomoto, T, Takehara, K, Denys, H, Lorusso, D, Coleman, R, Vaughan, M, Takano, M, Provencher, D, Sagae, S, Wimberger, P, Poka, R, Segev, Y, Kim, S, Kim, J, Candido dos Reis, F, Mariani, A, Leitao, M, Makker, V, Rustum, N, Vergote, I, Zannoni, G, Tan, D, Mccormack, M, Bini, M, Lopez, S, Raspagliesi, F, Panici, P, di Donato, V, Muzii, L, Colombo, N, Scambia, G, Pignata, S, Monk, B, Bogani G., Ray-Coquard I., Concin N., Ngoi N. Y. L., Morice P., Enomoto T., Takehara K., Denys H., Lorusso D., Coleman R., Vaughan M. M., Takano M., Provencher D., Sagae S., Wimberger P., Poka R., Segev Y., Kim S. I., Kim J. -W., Candido dos Reis F. J., Mariani A., Leitao M. M., Makker V., Rustum N. A., Vergote I., Zannoni G. F., Tan D. S. P., McCormack M., Bini M., Lopez S., Raspagliesi F., Panici P. B., di Donato V., Muzii L., Colombo N., Scambia G., Pignata S., Monk B. J., Bogani, G, Ray-Coquard, I, Concin, N, Ngoi, N, Morice, P, Enomoto, T, Takehara, K, Denys, H, Lorusso, D, Coleman, R, Vaughan, M, Takano, M, Provencher, D, Sagae, S, Wimberger, P, Poka, R, Segev, Y, Kim, S, Kim, J, Candido dos Reis, F, Mariani, A, Leitao, M, Makker, V, Rustum, N, Vergote, I, Zannoni, G, Tan, D, Mccormack, M, Bini, M, Lopez, S, Raspagliesi, F, Panici, P, di Donato, V, Muzii, L, Colombo, N, Scambia, G, Pignata, S, Monk, B, Bogani G., Ray-Coquard I., Concin N., Ngoi N. Y. L., Morice P., Enomoto T., Takehara K., Denys H., Lorusso D., Coleman R., Vaughan M. M., Takano M., Provencher D., Sagae S., Wimberger P., Poka R., Segev Y., Kim S. I., Kim J. -W., Candido dos Reis F. J., Mariani A., Leitao M. M., Makker V., Rustum N. A., Vergote I., Zannoni G. F., Tan D. S. P., McCormack M., Bini M., Lopez S., Raspagliesi F., Panici P. B., di Donato V., Muzii L., Colombo N., Scambia G., Pignata S., and Monk B. J.
Abstract: Clear cell endometrial carcinoma represents an uncommon and poorly understood entity. Data from molecular/genomic profiling highlighted the importance of various signatures in assessing the prognosis of endometrial cancer according to four classes of risk (POLE mutated, MMRd, NSMP, and p53 abnormal). Unfortunately, data specific to clear cell histological subtype endometrial cancer are lacking. More recently, data has emerged to suggest that most of the patients (more than 80%) with clear cell endometrial carcinoma are characterized by p53 abnormality or NSMP type. This classification has important therapeutic implications. Although it is an uncommon entity, clear cell endometrial cancer patients with POLE mutation seem characterized by a good prognosis. Chemotherapy is effective in patients with NSMP (especially in stage III and IV) and patients with p53 abnormal disease (all stages). While, preliminary data suggested that patients with MMRd are less likely to benefit from chemotherapy. The latter group appears to benefit much more from immune checkpoint inhibitors: recent data from clinical trials on pembrolizumab plus lenvatinib and nivolumab plus cabozantinib supported that immunotherapy plus tyrosine kinase inhibitors (TKI) would be the most appropriate treatment for recurrent non-endometrioid endometrial cancer (including clear cell carcinoma) after the failure of platinum-based chemotherapy. Moreover, ongoing clinical trials testing the anti-tumor activity of innovative products will clarify the better strategies for advanced/recurrent clear cell endometrial carcinoma. Further prospective evidence is urgently needed to better characterize clear cell endometrial carcinoma.
Published: 2022

34. Efficacy of subsequent chemotherapy for patients with BRCA1/2-mutated recurrent epithelial ovarian cancer progressing on olaparib versus placebo maintenance: post-hoc analyses of the SOLO2/ENGOT Ov-21 trial

Author: Frenel, J, Kim, J, Aryal, N, Asher, R, Berton, D, Vidal, L, Pautier, P, Ledermann, J, Penson, R, Oza, A, Korach, J, Huzarski, T, Pignata, S, Colombo, N, Park-Simon, T, Tamura, K, Sonke, G, Freimund, A, Lee, C, Pujade-Lauraine, E, Frenel J. S., Kim J. W., Aryal N., Asher R., Berton D., Vidal L., Pautier P., Ledermann J. A., Penson R. T., Oza A. M., Korach J., Huzarski T., Pignata S., Colombo N., Park-Simon T. W., Tamura K., Sonke G. S., Freimund A. E., Lee C. K., Pujade-Lauraine E., Frenel, J, Kim, J, Aryal, N, Asher, R, Berton, D, Vidal, L, Pautier, P, Ledermann, J, Penson, R, Oza, A, Korach, J, Huzarski, T, Pignata, S, Colombo, N, Park-Simon, T, Tamura, K, Sonke, G, Freimund, A, Lee, C, Pujade-Lauraine, E, Frenel J. S., Kim J. W., Aryal N., Asher R., Berton D., Vidal L., Pautier P., Ledermann J. A., Penson R. T., Oza A. M., Korach J., Huzarski T., Pignata S., Colombo N., Park-Simon T. W., Tamura K., Sonke G. S., Freimund A. E., Lee C. K., and Pujade-Lauraine E.
Abstract: Background: In the SOLO2 trial (ENGOT Ov-21; NCT01874353), maintenance olaparib in patients with platinum-sensitive relapsed ovarian cancer (PSROC) and BRCA mutation significantly improved progression-free survival (PFS) and prolonged overall survival (OS). Following disease progression on olaparib, efficacy of subsequent chemotherapy remains unknown. Patients and methods: We conducted a post-hoc hypothesis-generating analysis of SOLO2 data to determine the efficacy of different chemotherapy regimens following RECIST disease progression in patients who received olaparib or placebo. We evaluated time to second progression (TTSP) calculated from the date of RECIST progression to the next progression/death. Results: The study population comprised 147 patients who received chemotherapy as their first subsequent treatment after RECIST progression. Of these, 69 (47%) and 78 (53%) were originally randomized to placebo and olaparib arms, respectively. In the placebo-treated cohort, 27/69 and 42/69 received non-platinum and platinum-based chemotherapy, respectively, compared with 24/78 and 54/78, respectively, in the olaparib-treated cohort. Among patients treated with chemotherapy (N = 147), TTSP was significantly longer in the placebo than in the olaparib arm: 12.1 versus 6.9 months [hazard ratio (HR) 2.17, 95% confidence interval (CI) 1.47-3.19]. Similar result was obtained on multivariable analysis adjusting for prognostic factors at RECIST progression (HR 2.13, 95% CI 1.41-3.22). Among patients treated with platinum-based chemotherapy (n = 96), TTSP was significantly longer in the placebo arm: 14.3 versus 7.0 months (HR 2.89, 95% CI 1.73-4.82). Conversely, among patients treated with non-platinum-based chemotherapy (n = 51), the TTSP was comparable in the placebo and olaparib arms: 8.3 versus 6.0 months (HR 1.58, 95% CI 0.86-2.90). Conclusions: Following progression from maintenance olaparib in the recurrent setting, the efficacy of platinum-based subsequent chemotherap
Published: 2022

35. Biological Role of Tumor/Stromal CXCR4-CXCL12-CXCR7 in MITO16A/MaNGO-OV2 Advanced Ovarian Cancer Patients

Author: D'Alterio, C, Spina, A, Arenare, L, Chiodini, P, Napolitano, M, Galdiero, F, Portella, L, Simeon, V, Signoriello, S, Raspagliesi, F, Lorusso, D, Pisano, C, Colombo, N, Zannoni, G, Losito, N, De Cecio, R, Scognamiglio, G, Califano, D, Russo, D, Tuninetti, V, Piccirillo, M, Gargiulo, P, Perrone, F, Pignata, S, Scala, S, D'alterio C., Spina A., Arenare L., Chiodini P., Napolitano M., Galdiero F., Portella L., Simeon V., Signoriello S., Raspagliesi F., Lorusso D., Pisano C., Colombo N., Zannoni G. F., Losito N. S., De Cecio R., Scognamiglio G., Califano D., Russo D., Tuninetti V., Piccirillo M. C., Gargiulo P., Perrone F., Pignata S., Scala S., D'Alterio, C, Spina, A, Arenare, L, Chiodini, P, Napolitano, M, Galdiero, F, Portella, L, Simeon, V, Signoriello, S, Raspagliesi, F, Lorusso, D, Pisano, C, Colombo, N, Zannoni, G, Losito, N, De Cecio, R, Scognamiglio, G, Califano, D, Russo, D, Tuninetti, V, Piccirillo, M, Gargiulo, P, Perrone, F, Pignata, S, Scala, S, D'alterio C., Spina A., Arenare L., Chiodini P., Napolitano M., Galdiero F., Portella L., Simeon V., Signoriello S., Raspagliesi F., Lorusso D., Pisano C., Colombo N., Zannoni G. F., Losito N. S., De Cecio R., Scognamiglio G., Califano D., Russo D., Tuninetti V., Piccirillo M. C., Gargiulo P., Perrone F., Pignata S., and Scala S.
Abstract: This study investigated the prognostic role of the CXCR4-CXCL12-CXCR7 axis in advanced epithelial ovarian cancer (EOC) patients receiving first-line treatment within the MITO16A/MaNGO-OV2 phase-IV trial. CXCR4-CXCL12-CXCR7 expression was evaluated in the epithelial and stromal component of 308 EOC IHC-stained tumor samples. The statistical analysis focused on biomarkers’ expression, their association with other variables and prognostic value. Zero-inflated tests, shrinkage, bootstrap procedures, and multivariable models were applied. The majority of EOC (75.0%) expressed CXCR4 and CXCR7, 56.5% expressed the entire CXCR4-CXCL12-CXCR7 axis, while only 4.6% were negative for CXCL12 and its cognate receptors, in regard to the epithelial component. Stromal CXCL12 and CXCR7, expressed in 11.2% and 65.5%, respectively, were associated with the FIGO stage. High CXCL12 in epithelial cancer cells was associated with shorter progression-free and overall survival. However, after adjusting for overfitting due to best cut-off multiplicity testing, the significance was lost. This is a wide-ranging, prospective study in which CXCR4-CXCL12-CXCR7 were systematically evaluated in epithelial and stromal components, in selected stage III-IV EOC. Although CXCL12 was not prognostic, epithelial expression identified high-risk FIGO stage III patients for PFS. These data suggest that it might be worth studying the CXCL12 axis as a therapeutic target to improve treatment efficacy in EOC patients.
Published: 2022

36. Optimizing the use of lenvatinib in combination with pembrolizumab in patients with advanced endometrial carcinoma

Author: Lorusso, D, Danesi, R, Locati, L, Masi, G, De Giorgi, U, Gadducci, A, Pignata, S, Roberto, S, Savarese, A, Valabrega, G, Zamagni, C, Colombo, N, Lorusso D., Danesi R., Locati L. D., Masi G., De Giorgi U., Gadducci A., Pignata S., Roberto S., Savarese A., Valabrega G., Zamagni C., Colombo N., Lorusso, D, Danesi, R, Locati, L, Masi, G, De Giorgi, U, Gadducci, A, Pignata, S, Roberto, S, Savarese, A, Valabrega, G, Zamagni, C, Colombo, N, Lorusso D., Danesi R., Locati L. D., Masi G., De Giorgi U., Gadducci A., Pignata S., Roberto S., Savarese A., Valabrega G., Zamagni C., and Colombo N.
Abstract: Introduction: The combination of lenvatinib plus pembrolizumab demonstrated a relevant clinical benefit in patients with endometrial carcinoma. The safety profile was consistent with the established profiles of each drug in monotherapy, with the most frequent adverse events being hypertension, an on-target effect, hypothyroidism, diarrhea, nausea, vomiting, loss of appetite, fatigue, and weight loss. Areas covered: We first review the rationale based on the combination of a VEGFR inhibitor and an immune checkpoint inhibitor, highlighting the main pharmacokinetic and pharmacodynamic features of lenvatinib. Next, we focus on the common adverse events associated with lenvatinib and guide how to optimally prevent, detect, and manage them, while minimizing interruptions during lenvatinib treatment. Discussion: The side effects profile of lenvatinib is very well known, being similar across different tumor types. Most toxicities can be preventable. An appropriate, proactive, and thorough management of lenvatinib toxicities during treatment is required to maximize potential lenvatinib efficacy. Adverse events should be detected as early as possible, by both carefully monitoring the patient from lenvatinib initiation and preventing their occurrence. Patients should be followed also during treatment as some adverse events, e.g., cardiac dysfunction might appear later. Increased awareness on risk to benefit ratio among clinicians would be helpful to avoid dose interruptions or discontinuation of lenvatinib, with preferring other medical interventions and supportive care.
Published: 2022

37. Implementation of preventive and predictive BRCA testing in patients with breast, ovarian, pancreatic, and prostate cancer: a position paper of Italian Scientific Societies

Author: Russo, A, Incorvaia, L, Capoluongo, E, Tagliaferri, P, Gori, S, Cortesi, L, Genuardi, M, Turchetti, D, De Giorgi, U, Di Maio, M, Barberis, M, Dessena, M, Del Re, M, Lapini, A, Luchini, C, Jereczek-Fossa, B, Sapino, A, Cinieri, S, Beretta, G, Bella, M, Bracarda, S, Colombo, N, Conteduca, V, Del Mastro, L, Galvano, A, Gristina, V, Guarneri, V, La Verde, N, Lorusso, D, Marchetti, P, Normanno, N, Ottini, L, Pensabene, M, Pignata, S, Procopio, G, Ricevuto, E, Silvestris, N, Tassone, P, Tucci, M, Donato, V, Carrara, S, Paiella, S, Gentilini, O, Gunelli, R, Nicolis, F, Buttitta, F, Colecchia, M, Fassan, M, Malapelle, U, Marchetti, A, Marchio, C, Scarpa, A, Truini, M, Zamboni, G, Gion, M, Trevisiol, C, Gronchi, A, Danesi, R, Di Marco, V, Carrera, P, Ghiorzo, P, Pasini, B, Varesco, L, Artibani, W, Ludovico, G, Campanella, O, Vatrano, S, Tagliafico, E, Russo A., Incorvaia L., Capoluongo E., Tagliaferri P., Gori S., Cortesi L., Genuardi M., Turchetti D., De Giorgi U., Di Maio M., Barberis M., Dessena M., Del Re M., Lapini A., Luchini C., Jereczek-Fossa B. A., Sapino A., Cinieri S., Beretta G., Bella M. A., Bracarda S., Colombo N., Conteduca V., Del Mastro L., Galvano A., Gristina V., Guarneri V., La Verde N., Lorusso D., Marchetti P., Normanno N., Ottini L., Pensabene M., Pignata S., Procopio G., Ricevuto E., Silvestris N., Tassone P., Tucci M., Donato V., Carrara S., Paiella S., Gentilini O., Gunelli R., Nicolis F., Buttitta F., Colecchia M., Fassan M., Malapelle U., Marchetti A., Marchio C., Scarpa A., Truini M., Zamboni G., Gion M., Trevisiol C., Gronchi A., Danesi R., Di Marco V., Carrera P., Ghiorzo P., Pasini B., Varesco L., Artibani W., Ludovico G., Campanella O., Vatrano S., Tagliafico E., Russo, A, Incorvaia, L, Capoluongo, E, Tagliaferri, P, Gori, S, Cortesi, L, Genuardi, M, Turchetti, D, De Giorgi, U, Di Maio, M, Barberis, M, Dessena, M, Del Re, M, Lapini, A, Luchini, C, Jereczek-Fossa, B, Sapino, A, Cinieri, S, Beretta, G, Bella, M, Bracarda, S, Colombo, N, Conteduca, V, Del Mastro, L, Galvano, A, Gristina, V, Guarneri, V, La Verde, N, Lorusso, D, Marchetti, P, Normanno, N, Ottini, L, Pensabene, M, Pignata, S, Procopio, G, Ricevuto, E, Silvestris, N, Tassone, P, Tucci, M, Donato, V, Carrara, S, Paiella, S, Gentilini, O, Gunelli, R, Nicolis, F, Buttitta, F, Colecchia, M, Fassan, M, Malapelle, U, Marchetti, A, Marchio, C, Scarpa, A, Truini, M, Zamboni, G, Gion, M, Trevisiol, C, Gronchi, A, Danesi, R, Di Marco, V, Carrera, P, Ghiorzo, P, Pasini, B, Varesco, L, Artibani, W, Ludovico, G, Campanella, O, Vatrano, S, Tagliafico, E, Russo A., Incorvaia L., Capoluongo E., Tagliaferri P., Gori S., Cortesi L., Genuardi M., Turchetti D., De Giorgi U., Di Maio M., Barberis M., Dessena M., Del Re M., Lapini A., Luchini C., Jereczek-Fossa B. A., Sapino A., Cinieri S., Beretta G., Bella M. A., Bracarda S., Colombo N., Conteduca V., Del Mastro L., Galvano A., Gristina V., Guarneri V., La Verde N., Lorusso D., Marchetti P., Normanno N., Ottini L., Pensabene M., Pignata S., Procopio G., Ricevuto E., Silvestris N., Tassone P., Tucci M., Donato V., Carrara S., Paiella S., Gentilini O., Gunelli R., Nicolis F., Buttitta F., Colecchia M., Fassan M., Malapelle U., Marchetti A., Marchio C., Scarpa A., Truini M., Zamboni G., Gion M., Trevisiol C., Gronchi A., Danesi R., Di Marco V., Carrera P., Ghiorzo P., Pasini B., Varesco L., Artibani W., Ludovico G., Campanella O., Vatrano S., and Tagliafico E.
Abstract: Constitutional BRCA1/BRCA2 pathogenic or likely pathogenic variants (PVs) are associated with an increased risk for developing breast and ovarian cancers. Current evidence indicates that BRCA1/2 PVs are also associated with pancreatic cancer, and that BRCA2 PVs are associated with prostate cancer risk. The identification of carriers of constitutional PVs in the BRCA1/2 genes allows the implementation of individual and family prevention pathways, through validated screening programs and risk-reducing strategies. According to the relevant and increasing therapeutic predictive implications, the inclusion of BRCA testing in the routine management of patients with breast, ovarian, pancreatic and prostate cancers represent a key requirement to optimize medical or surgical therapeutic and prevention decision-making, and access to specific anticancer therapies. Therefore, accurate patient selection, the use of standardized and harmonized procedures, and adherence to homogeneous testing criteria, are essential elements to implement BRCA testing in clinical practice. This consensus position paper has been developed and approved by a multidisciplinary Expert Panel of 64 professionals on behalf of the AIOM–AIRO–AISP–ANISC–AURO–Fondazione AIOM–SIAPEC/IAP–SIBioC–SICO–SIF–SIGE–SIGU–SIU–SIURO–UROP Italian Scientific Societies, and a patient association (aBRCAdaBRA Onlus). The working group included medical, surgical and radiation oncologists, medical and molecular geneticists, clinical molecular biologists, surgical and molecular pathologists, organ specialists such as gynecologists, gastroenterologists and urologists, and pharmacologists. The manuscript is based on the expert consensus and reports the best available evidence, according to the current eligibility criteria for BRCA testing and counseling, it also harmonizes with current Italian National Guidelines and Clinical Recommendations.
Published: 2022

38. Analysis of A Disintegrin and Metalloprotease 17 (ADAM17) Expression as a Prognostic Marker in Ovarian Cancer Patients Undergoing First-Line Treatment Plus Bevacizumab

Author: Fabbi, M, Costa, D, Russo, D, Arenare, L, Gaggero, G, Signoriello, S, Scambia, G, Pisano, C, Colombo, N, Losito, N, Filaci, G, Spina, A, Califano, D, Scognamiglio, G, Gadducci, A, Mezzanzanica, D, Bagnoli, M, Ferrini, S, Canzonieri, V, Chiodini, P, Perrone, F, Pignata, S, Fabbi M., Costa D., Russo D., Arenare L., Gaggero G., Signoriello S., Scambia G., Pisano C., Colombo N., Losito N. S., Filaci G., Spina A., Califano D., Scognamiglio G., Gadducci A., Mezzanzanica D., Bagnoli M., Ferrini S., Canzonieri V., Chiodini P., Perrone F., Pignata S., Fabbi, M, Costa, D, Russo, D, Arenare, L, Gaggero, G, Signoriello, S, Scambia, G, Pisano, C, Colombo, N, Losito, N, Filaci, G, Spina, A, Califano, D, Scognamiglio, G, Gadducci, A, Mezzanzanica, D, Bagnoli, M, Ferrini, S, Canzonieri, V, Chiodini, P, Perrone, F, Pignata, S, Fabbi M., Costa D., Russo D., Arenare L., Gaggero G., Signoriello S., Scambia G., Pisano C., Colombo N., Losito N. S., Filaci G., Spina A., Califano D., Scognamiglio G., Gadducci A., Mezzanzanica D., Bagnoli M., Ferrini S., Canzonieri V., Chiodini P., Perrone F., and Pignata S.
Abstract: To find prognostic factors for advanced ovarian cancer patients undergoing first-line therapy with carboplatin, paclitaxel and bevacizumab, we investigated the expression of a disintegrin and metalloprotease 17 (ADAM17) in cancer tissues. ADAM17 has been involved in ovarian cancer development, progression and cell resistance to cisplatin. Tissue microarrays from 309 ovarian cancer patients enrolled in the MITO16A/MANGO-OV2 clinical trial were analyzed by immunohistochemistry for ADAM17 protein expression. Intensity and extent of staining were combined into a semi-quantitative visual grading system (H score) which was related to clinicopathological characteristics of cases and the clinical outcome of patients by univariate and multivariate Cox regression models. ADAM17 immunostaining was detected in most samples, mainly localized in the tumor cells, with variable intensity across the cohort. Kaplan–Meier survival curves, generated according to the best cut-off value for the ADAM17 H score, showed that high ADAM17 expression was associated with worse prognosis for PFS and OS. However, after the application of a shrinkage procedure to adjust for overfitting hazard ratio estimates, the ADAM17 value as prognostic factor was lost. As subgroup analysis suggested that ADAM17 expression could be prognostically relevant in cases with no residual disease at baseline, further studies in this patient category may be worth planning.
Published: 2022

39. A New Academic Quality at Work Tool (AQ@workT) to Assess the Quality of Life at Work in the Italian Academic Context

Author: Brondino, M, Signore, F, Zambelli, A, Ingusci, E, Pignata, S, Manuti, A, Giancaspro, M, Falco, A, Girardi, D, Guglielmi, D, Depolo, M, Loera, B, Converso, D, Viotti, S, Bruno, A, Gilardi, S, Cortini, M, Pace, F, Capone, V, Platania, S, Zito, M, Pasini, M, Miglioretti, M, Dell'Aversana, G, Carrus, G, Spagnoli, P, Brondino M., Signore F., Zambelli A., Ingusci E., Pignata S., Manuti A., Giancaspro M. L., Falco A., Girardi D., Guglielmi D., Depolo M., Loera B., Converso D., Viotti S., Bruno A., Gilardi S., Cortini M., Pace F., Capone V., Platania S., Zito M., Pasini M., Miglioretti M., Dell'aversana G., Carrus G., Spagnoli P., Brondino, M, Signore, F, Zambelli, A, Ingusci, E, Pignata, S, Manuti, A, Giancaspro, M, Falco, A, Girardi, D, Guglielmi, D, Depolo, M, Loera, B, Converso, D, Viotti, S, Bruno, A, Gilardi, S, Cortini, M, Pace, F, Capone, V, Platania, S, Zito, M, Pasini, M, Miglioretti, M, Dell'Aversana, G, Carrus, G, Spagnoli, P, Brondino M., Signore F., Zambelli A., Ingusci E., Pignata S., Manuti A., Giancaspro M. L., Falco A., Girardi D., Guglielmi D., Depolo M., Loera B., Converso D., Viotti S., Bruno A., Gilardi S., Cortini M., Pace F., Capone V., Platania S., Zito M., Pasini M., Miglioretti M., Dell'aversana G., Carrus G., and Spagnoli P.
Abstract: The present study provides evidence for a valid and reliable tool, the Academic Quality at Work Tool (AQ@workT), to investigate the quality of life at work in academics within the Italian university sector. The AQ@workT was developed by the QoL@Work research team, namely a group of expert academics in the field of work and organizational psychology affiliated with the Italian Association of Psychologists. The tool is grounded in the job demands-resources model and its psychometric properties were assessed in three studies comprising a wide sample of lecturers, researchers, and professors: a pilot study (N = 120), a calibration study (N = 1084), and a validation study (N = 1481). Reliability and content, construct, and nomological validity were supported, as well as measurement invariance across work role (researchers, associate professors, and full professors) and gender. Evidence from the present study shows that the AQ@workT represents a useful and reliable tool to assist university management to enhance quality of life, to manage work-related stress, and to mitigate the potential for harm to academics, particularly during a pandemic. Future studies, such as longitudinal tests of the AQ@workT, should test predictive validity among the variables in the tool.
Published: 2022

40. European experts consensus: BRCA/homologous recombination deficiency testing in first-line ovarian cancer

Author: Vergote, I, Gonzalez-Martin, A, Ray-Coquard, I, Harter, P, Colombo, N, Pujol, P, Lorusso, D, Mirza, M, Brasiuniene, B, Madry, R, Brenton, J, Ausems, M, Buttner, R, Lambrechts, D, Abreu, M, Balboni, S, Banerjee, S, Barberis, M, Barretina Ginesta, M, Baurain, J, Bignami, M, Bjorge, L, Blecharz, P, Bruchim, I, Capilna, M, Cerana, N, Cicchetti, A, Collins, D, Concin, N, D'Incalci, M, Davidson, B, de la Motte Rouge, T, De Iaco, P, Demirkiran, F, Denys, H, Doerk, T, Dorum, A, Ferrero, A, Fidalgo, A, Genuardi, M, Gladieff, L, Glasspool, R, Grimm, C, Gultekin, M, Hahnen, E, Hasenburg, A, Hegmane, A, Heinzelmann, V, Hogdall, E, Janavicius, R, Jarmalaite, S, Kalachand, R, Kaneva, R, Kilickap, S, Kocian, R, Kolencik, D, Kristeleit, R, Kryzhanivska, A, Leary, A, Lemley, B, Ligtenberg, M, Lopez-Guerrero, J, Lord, C, Avall-Lundqvist, E, Maenpaa, J, Mahner, S, Marme, F, Marth, C, Mcneish, I, Merkelbach-Bruse, S, Mourits, M, Normanno, N, Oaknin, A, Ojamaa, K, Papdimitriou, C, Penault-Llorca, F, Perrone, A, Pignata, S, Pikarsky, E, Rouleau, E, Rubio, M, Sapino, A, Schmalfeldt, B, Sehouli, J, Shapira, R, Steffensen, K, Sukhin, V, Syrios, J, Szallasi, Z, Taskiran, C, Terzic, M, Tischkowitz, M, Toth, I, Van de Vijver, K, Vardar, M, Wasag, B, Wimberger, P, Witteveen, E, Vergote I., Gonzalez-Martin A., Ray-Coquard I., Harter P., Colombo N., Pujol P., Lorusso D., Mirza M. R., Brasiuniene B., Madry R., Brenton J. D., Ausems M. G. E. M., Buttner R., Lambrechts D., Ausems M., Brenton J., Abreu M., Balboni S., Banerjee S., Barberis M., Barretina Ginesta M. P., Baurain J. -F., Bignami M., Bjorge L., Blecharz P., Bruchim I., Capilna M., Cerana N., Cicchetti A., Collins D., Concin N., D'Incalci M., Davidson B., de la Motte Rouge T., De Iaco P., Demirkiran F., Denys H., Doerk T., Dorum A., Ferrero A., Fidalgo A. P., Genuardi M., Gladieff L., Glasspool R., Grimm C., Gultekin M., Hahnen E., Hasenburg A., Hegmane A., Heinzelmann V., Hogdall E., Janavicius R., Jarmalaite S., Kalachand R., Kaneva R., Kilickap S., Kocian R., Kolencik D., Kristeleit R., Kryzhanivska A., Leary A., Lemley B., Ligtenberg M., Lopez-Guerrero J. A., Lord C. J., Avall-Lundqvist E., Maenpaa J., Mahner S., Marme F., Marth C., McNeish I., Merkelbach-Bruse S., Mourits M., Normanno N., Oaknin A., Ojamaa K., Papdimitriou C., Penault-Llorca F., Perrone A. M., Pignata S., Pikarsky E., Rouleau E., Rubio M., Sapino A., Schmalfeldt B., Sehouli J., Shapira R., Steffensen K. D., Sukhin V., Syrios J., Szallasi Z., Taskiran C., Terzic M., Tischkowitz M., Toth I., Van de Vijver K., Vardar M. A., Wasag B., Wimberger P., Witteveen E., Vergote, I, Gonzalez-Martin, A, Ray-Coquard, I, Harter, P, Colombo, N, Pujol, P, Lorusso, D, Mirza, M, Brasiuniene, B, Madry, R, Brenton, J, Ausems, M, Buttner, R, Lambrechts, D, Abreu, M, Balboni, S, Banerjee, S, Barberis, M, Barretina Ginesta, M, Baurain, J, Bignami, M, Bjorge, L, Blecharz, P, Bruchim, I, Capilna, M, Cerana, N, Cicchetti, A, Collins, D, Concin, N, D'Incalci, M, Davidson, B, de la Motte Rouge, T, De Iaco, P, Demirkiran, F, Denys, H, Doerk, T, Dorum, A, Ferrero, A, Fidalgo, A, Genuardi, M, Gladieff, L, Glasspool, R, Grimm, C, Gultekin, M, Hahnen, E, Hasenburg, A, Hegmane, A, Heinzelmann, V, Hogdall, E, Janavicius, R, Jarmalaite, S, Kalachand, R, Kaneva, R, Kilickap, S, Kocian, R, Kolencik, D, Kristeleit, R, Kryzhanivska, A, Leary, A, Lemley, B, Ligtenberg, M, Lopez-Guerrero, J, Lord, C, Avall-Lundqvist, E, Maenpaa, J, Mahner, S, Marme, F, Marth, C, Mcneish, I, Merkelbach-Bruse, S, Mourits, M, Normanno, N, Oaknin, A, Ojamaa, K, Papdimitriou, C, Penault-Llorca, F, Perrone, A, Pignata, S, Pikarsky, E, Rouleau, E, Rubio, M, Sapino, A, Schmalfeldt, B, Sehouli, J, Shapira, R, Steffensen, K, Sukhin, V, Syrios, J, Szallasi, Z, Taskiran, C, Terzic, M, Tischkowitz, M, Toth, I, Van de Vijver, K, Vardar, M, Wasag, B, Wimberger, P, Witteveen, E, Vergote I., Gonzalez-Martin A., Ray-Coquard I., Harter P., Colombo N., Pujol P., Lorusso D., Mirza M. R., Brasiuniene B., Madry R., Brenton J. D., Ausems M. G. E. M., Buttner R., Lambrechts D., Ausems M., Brenton J., Abreu M., Balboni S., Banerjee S., Barberis M., Barretina Ginesta M. P., Baurain J. -F., Bignami M., Bjorge L., Blecharz P., Bruchim I., Capilna M., Cerana N., Cicchetti A., Collins D., Concin N., D'Incalci M., Davidson B., de la Motte Rouge T., De Iaco P., Demirkiran F., Denys H., Doerk T., Dorum A., Ferrero A., Fidalgo A. P., Genuardi M., Gladieff L., Glasspool R., Grimm C., Gultekin M., Hahnen E., Hasenburg A., Hegmane A., Heinzelmann V., Hogdall E., Janavicius R., Jarmalaite S., Kalachand R., Kaneva R., Kilickap S., Kocian R., Kolencik D., Kristeleit R., Kryzhanivska A., Leary A., Lemley B., Ligtenberg M., Lopez-Guerrero J. A., Lord C. J., Avall-Lundqvist E., Maenpaa J., Mahner S., Marme F., Marth C., McNeish I., Merkelbach-Bruse S., Mourits M., Normanno N., Oaknin A., Ojamaa K., Papdimitriou C., Penault-Llorca F., Perrone A. M., Pignata S., Pikarsky E., Rouleau E., Rubio M., Sapino A., Schmalfeldt B., Sehouli J., Shapira R., Steffensen K. D., Sukhin V., Syrios J., Szallasi Z., Taskiran C., Terzic M., Tischkowitz M., Toth I., Van de Vijver K., Vardar M. A., Wasag B., Wimberger P., and Witteveen E.
Abstract: Background: Homologous recombination repair (HRR) enables fault-free repair of double-stranded DNA breaks. HRR deficiency is predicted to occur in around half of high-grade serous ovarian carcinomas. Ovarian cancers harbouring HRR deficiency typically exhibit sensitivity to poly-ADP ribose polymerase inhibitors (PARPi). Current guidelines recommend a range of approaches for genetic testing to identify predictors of sensitivity to PARPi in ovarian cancer and to identify genetic predisposition. Design: To establish a European-wide consensus for genetic testing (including the genetic care pathway), decision making and clinical management of patients with recently diagnosed advanced ovarian cancer, and the validity of biomarkers to predict the effectiveness of PARPi in the first-line setting. The collaborative European experts’ consensus group consisted of a steering committee (n = 14) and contributors (n = 84). A (modified) Delphi process was used to establish consensus statements based on a systematic literature search, conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Results: A consensus was reached on 34 statements amongst 98 caregivers (including oncologists, pathologists, clinical geneticists, genetic researchers, and patient advocates). The statements concentrated on (i) the value of testing for BRCA1/2 mutations and HRR deficiency testing, including when and whom to test; (ii) the importance of developing new and better HRR deficiency tests; (iii) the importance of germline non-BRCA HRR and mismatch repair gene mutations for predicting familial risk, but not for predicting sensitivity to PARPi, in the first-line setting; (iv) who should be able to inform patients about genetic testing, and what training and education should these caregivers receive. Conclusion: These consensus recommendations, from a multidisciplinary panel of experts from across Europe, provide clear guidance on the use of BRCA and HRR de
Published: 2022

41. A randomized trial of intensive versus minimal surveillance of patients with resected Dukes B2-C colorectal carcinoma

Author: Rosati, G., Ambrosini, G., Barni, S., Andreoni, B., Corradini, G., Luchena, G., Daniele, B., Gaion, F., Oliverio, G., Duro, M., Martignoni, G., Pinna, N., Sozzi, P., Pancera, G., Solina, G., Pavia, G., Pignata, S., Johnson, F., Labianca, R., Apolone, G., Zaniboni, A., Monteforte, M., Negri, E., Torri, V., Mosconi, P., and Fossati, R.
Published: 2016
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42. 19 A large, multicenter, retrospective study on efficacy and safety of stereotactic body radiotherapy (SBRT) in oligometastatic ovarian cancer (MITO RT1 study)

Author: Macchia, G, Lazzari, R, Colombo, N, Laliscia, C, Capelli, G, D’Agostino, GR, Deodato, F, Trippa, F, Ippolito, E, Ronchi, S, Pajar, F, Scorsetti, M, Cilla, S, Ingargiola, R, Huscher, A, Cerrotta, AM, Andrei, F, Vicenzi, L, Russo, D, Borghesi, S, Perrucci, E, Pignata, S, Aristei, C, Morganti, AG, Scambia, G, Valentini, V, Jereczek-Fossa, BA, and Ferrandina, G
Published: 2019
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43. Efficacy and Safety of Mirvetuximab Soravtansine in Patients With Platinum-Resistant Ovarian Cancer With High Folate Receptor Alpha Expression: Results From the SORAYA Study

Author: Matulonis, U, Lorusso, D, Oaknin, A, Pignata, S, Dean, A, Denys, H, Colombo, N, Van Gorp, T, Konner, J, Marin, M, Harter, P, Murphy, C, Wang, J, Noble, E, Esteves, B, Method, M, Coleman, R, Matulonis, Ursula A, Lorusso, Domenica, Oaknin, Ana, Pignata, Sandro, Dean, Andrew, Denys, Hannelore, Colombo, Nicoletta, Van Gorp, Toon, Konner, Jason A, Marin, Margarita Romeo, Harter, Philipp, Murphy, Conleth G, Wang, Jiuzhou, Noble, Elizabeth, Esteves, Brooke, Method, Michael, Coleman, Robert L, Matulonis, U, Lorusso, D, Oaknin, A, Pignata, S, Dean, A, Denys, H, Colombo, N, Van Gorp, T, Konner, J, Marin, M, Harter, P, Murphy, C, Wang, J, Noble, E, Esteves, B, Method, M, Coleman, R, Matulonis, Ursula A, Lorusso, Domenica, Oaknin, Ana, Pignata, Sandro, Dean, Andrew, Denys, Hannelore, Colombo, Nicoletta, Van Gorp, Toon, Konner, Jason A, Marin, Margarita Romeo, Harter, Philipp, Murphy, Conleth G, Wang, Jiuzhou, Noble, Elizabeth, Esteves, Brooke, Method, Michael, and Coleman, Robert L
Published: 2023

44. Reply to Z.R. McCaw et al

Author: Matulonis, U, Lorusso, D, Oaknin, A, Pignata, S, Dean, A, Denys, H, Colombo, N, Van Gorp, T, Konner, J, Marin, M, Harter, P, Murphy, C, Wang, J, Noble, E, Esteves, B, Method, M, Coleman, R, Matulonis, Ursula A, Lorusso, Domenica, Oaknin, Ana, Pignata, Sandro, Dean, Andrew, Denys, Hannelore, Colombo, Nicoletta, Van Gorp, Toon, Konner, Jason A, Marin, Margarita Romeo, Harter, Philipp, Murphy, Conleth G, Wang, Jiuzhou, Noble, Elizabeth, Esteves, Brooke, Method, Michael, Coleman, Robert L, Matulonis, U, Lorusso, D, Oaknin, A, Pignata, S, Dean, A, Denys, H, Colombo, N, Van Gorp, T, Konner, J, Marin, M, Harter, P, Murphy, C, Wang, J, Noble, E, Esteves, B, Method, M, Coleman, R, Matulonis, Ursula A, Lorusso, Domenica, Oaknin, Ana, Pignata, Sandro, Dean, Andrew, Denys, Hannelore, Colombo, Nicoletta, Van Gorp, Toon, Konner, Jason A, Marin, Margarita Romeo, Harter, Philipp, Murphy, Conleth G, Wang, Jiuzhou, Noble, Elizabeth, Esteves, Brooke, Method, Michael, and Coleman, Robert L
Published: 2023

45. Consensus statements and treatment algorithm to guide clinicians in the selection of maintenance therapy for patients with newly diagnosed, advanced ovarian carcinoma: Results of a Delphi study

Author: Colombo, N, Gadducci, A, Landoni, F, Lorusso, D, Sabbatini, R, Artioli, G, Berardi, R, Ceccherini, R, Cecere, S, Cormio, G, De Angelis, C, Legge, F, Lissoni, A, Mammoliti, S, Mangili, G, Naglieri, E, Petrella, M, Ricciardi, G, Ronzino, G, Salutari, V, Sambataro, D, Savarese, A, Scandurra, G, Tasca, G, Tomao, F, Valabrega, G, Zavallone, L, Pignata, S, Colombo, Nicoletta, Gadducci, Angiolo, Landoni, Fabio, Lorusso, Domenica, Sabbatini, Roberto, Artioli, Grazia, Berardi, Rossana, Ceccherini, Rita, Cecere, Sabrina Chiara, Cormio, Gennaro, De Angelis, Carmine, Legge, Francesco, Lissoni, Andrea, Mammoliti, Serafina, Mangili, Giorgia, Naglieri, Emanuele, Petrella, Maria Cristina, Ricciardi, Giuseppina Rosaria Rita, Ronzino, Graziana, Salutari, Vanda, Sambataro, Daniela, Savarese, Antonella, Scandurra, Giuseppa, Tasca, Giulia, Tomao, Federica, Valabrega, Giorgio, Zavallone, Laura, Pignata, Sandro, Colombo, N, Gadducci, A, Landoni, F, Lorusso, D, Sabbatini, R, Artioli, G, Berardi, R, Ceccherini, R, Cecere, S, Cormio, G, De Angelis, C, Legge, F, Lissoni, A, Mammoliti, S, Mangili, G, Naglieri, E, Petrella, M, Ricciardi, G, Ronzino, G, Salutari, V, Sambataro, D, Savarese, A, Scandurra, G, Tasca, G, Tomao, F, Valabrega, G, Zavallone, L, Pignata, S, Colombo, Nicoletta, Gadducci, Angiolo, Landoni, Fabio, Lorusso, Domenica, Sabbatini, Roberto, Artioli, Grazia, Berardi, Rossana, Ceccherini, Rita, Cecere, Sabrina Chiara, Cormio, Gennaro, De Angelis, Carmine, Legge, Francesco, Lissoni, Andrea, Mammoliti, Serafina, Mangili, Giorgia, Naglieri, Emanuele, Petrella, Maria Cristina, Ricciardi, Giuseppina Rosaria Rita, Ronzino, Graziana, Salutari, Vanda, Sambataro, Daniela, Savarese, Antonella, Scandurra, Giuseppa, Tasca, Giulia, Tomao, Federica, Valabrega, Giorgio, Zavallone, Laura, and Pignata, Sandro
Abstract: Introduction: Standard treatment of newly diagnosed, advanced ovarian carcinoma (OC) consists of cytoreductive surgery followed by platinum-based chemotherapy with or without bevacizumab. Maintenance therapy with PARP inhibitors and olaparib-bevacizumab has recently shown to significantly improve progression-free survival in the first-line setting. Some practical aspects of maintenance therapy, however, are still poorly defined. Aim of the study: To provide guidance to clinicians in the selection of maintenance therapy for newly diagnosed, advanced ovarian carcinoma. Methods: A board of six gynecologic oncologists with expertise in the treatment of OC in Italy convened to address issues related to the new options for maintenance treatment. Based on scientific evidences, the board produced practice-oriented statements. Consensus was reached via a modified Delphi study that involved a panel of 22 experts from across Italy. Results: Twenty-seven evidence- and consensus-based statements are presented, covering the following areas of interest: use of biomarkers (BRCA mutations and presence of homologous recombination deficiency); timing and outcomes of surgery; selection of patients eligible for bevacizumab; definition of response to treatment; toxicity and contraindications; evidence of synergy of bevacizumab plus PARP inhibitor. Two treatment algorithms are also included, for selecting maintenance therapy based on timing and outcomes of surgery, response to platinum-based chemotherapy and biomarker status. A score for the assessment of response to chemotherapy is proposed, but its validation is ongoing. Conclusions: We provide here consensus statements and treatment algorithms to guide clinicians in the selection of appropriate and personalized maintenance therapy in the first-line setting of advanced OC management.
Published: 2023

46. Olaparib plus bevacizumab first-line maintenance in ovarian cancer: final overall survival results from the PAOLA-1/ENGOT-ov25 trial

Author: Ray-Coquard, I, Leary, A, Pignata, S, Cropet, C, González-Martin, A, Marth, C, Nagao, S, Vergote, I, Colombo, N, Mäenpää, J, Selle, F, Sehouli, J, Lorusso, D, Alia, E, Bogner, G, Yoshida, H, Lefeuvre-Plesse, C, Buderath, P, Mosconi, A, Lortholary, A, Burges, A, Medioni, J, El-Balat, A, Rodrigues, M, Park-Simon, T, Dubot, C, Denschlag, D, You, B, Pujade-Lauraine, E, Harter, P, Alia, E M Guerra, Mosconi, A M, Park-Simon, T-W, Ray-Coquard, I, Leary, A, Pignata, S, Cropet, C, González-Martin, A, Marth, C, Nagao, S, Vergote, I, Colombo, N, Mäenpää, J, Selle, F, Sehouli, J, Lorusso, D, Alia, E, Bogner, G, Yoshida, H, Lefeuvre-Plesse, C, Buderath, P, Mosconi, A, Lortholary, A, Burges, A, Medioni, J, El-Balat, A, Rodrigues, M, Park-Simon, T, Dubot, C, Denschlag, D, You, B, Pujade-Lauraine, E, Harter, P, Alia, E M Guerra, Mosconi, A M, and Park-Simon, T-W
Abstract: Background: In the PAOLA-1/ENGOT-ov25 primary analysis, maintenance olaparib plus bevacizumab demonstrated a significant progression-free survival (PFS) benefit in newly diagnosed advanced ovarian cancer patients in clinical response after first-line platinum-based chemotherapy plus bevacizumab, irrespective of surgical status. Prespecified, exploratory analyses by molecular biomarker status showed substantial benefit in patients with a BRCA1/BRCA2 mutation (BRCAm) or homologous recombination deficiency (HRD; BRCAm and/or genomic instability). We report the prespecified final overall survival (OS) analysis, including analyses by HRD status. Patients and methods: Patients were randomized 2 : 1 to olaparib (300 mg twice daily; up to 24 months) plus bevacizumab (15 mg/kg every 3 weeks; 15 months total) or placebo plus bevacizumab. Analysis of OS, a key secondary endpoint in hierarchical testing, was planned for ∼60% maturity or 3 years after the primary analysis. Results: After median follow-up of 61.7 and 61.9 months in the olaparib and placebo arms, respectively, median OS was 56.5 versus 51.6 months in the intention-to-treat population [hazard ratio (HR) 0.92, 95% confidence interval (CI) 0.76-1.12; P = 0.4118]. Subsequent poly(ADP-ribose) polymerase inhibitor therapy was received by 105 (19.6%) olaparib patients versus 123 (45.7%) placebo patients. In the HRD-positive population, OS was longer with olaparib plus bevacizumab (HR 0.62, 95% CI 0.45-0.85; 5-year OS rate, 65.5% versus 48.4%); at 5 years, updated PFS also showed a higher proportion of olaparib plus bevacizumab patients without relapse (HR 0.41, 95% CI 0.32-0.54; 5-year PFS rate, 46.1% versus 19.2%). Myelodysplastic syndrome, acute myeloid leukemia, aplastic anemia, and new primary malignancy incidence remained low and balanced between arms. Conclusions: Olaparib plus bevacizumab provided clinically meaningful OS improvement for first-line patients with HRD-positive ovarian cancer. These prespecified expl
Published: 2023

47. Maintenance olaparib in patients with platinum-sensitive relapsed ovarian cancer: Outcomes by somatic and germline BRCA and other homologous recombination repair gene mutation status in the ORZORA trial

Author: Pignata, S, Oza, A, Hall, G, Pardo, B, Madry, R, Cibula, D, Klat, J, Montes, A, Glasspool, R, Colombo, N, Pete, I, Herrero Ibáñez, A, Marín, M, Ilieva, R, Timcheva, C, Di Maio, M, Blakeley, C, Taylor, R, Barnicle, A, Clamp, A, Pignata, S, Oza, A, Hall, G, Pardo, B, Madry, R, Cibula, D, Klat, J, Montes, A, Glasspool, R, Colombo, N, Pete, I, Herrero Ibáñez, A, Marín, M, Ilieva, R, Timcheva, C, Di Maio, M, Blakeley, C, Taylor, R, Barnicle, A, and Clamp, A
Abstract: Background: The open-label, single-arm, multicenter ORZORA trial (NCT02476968) evaluated the efficacy and safety of maintenance olaparib in patients with platinum-sensitive relapsed ovarian cancer (PSR OC) who had tumor BRCA mutations (BRCAm) of germline (g) or somatic (s) origin or non-BRCA homologous recombination repair mutations (HRRm) and were in response to their most recent platinum-based chemotherapy after ≥2 lines of treatment. Methods: Patients received maintenance olaparib capsules (400 mg twice daily) until disease progression. Prospective central testing at screening determined tumor BRCAm status and subsequent testing determined gBRCAm or sBRCAm status. Patients with predefined non-BRCA HRRm were assigned to an exploratory cohort. The co-primary endpoints were investigator-assessed progression-free survival (PFS; modified Response Evaluation Criteria in Solid Tumors v1.1) in BRCAm and sBRCAm cohorts. Secondary endpoints included health-related quality of life (HRQoL) and tolerability. Results: 177 patients received olaparib. At the primary data cut-off (17 April 2020), the median follow-up for PFS in the BRCAm cohort was 22.3 months. The median PFS (95% CI) in BRCAm, sBRCAm, gBRCAm and non-BRCA HRRm cohorts was 18.0 (14.3-22.1), 16.6 (12.4-22.2), 19.3 (14.3-27.6) and 16.4 (10.9-19.3) months, respectively. Most patients with BRCAm reported improvements (21.8%) or no change (68.7%) in HRQoL and the safety profile was as expected. Conclusions: Maintenance olaparib had similar clinical activity in PSR OC patients with sBRCAm and those with any BRCAm. Activity was also observed in patients with a non-BRCA HRRm. ORZORA further supports use of maintenance olaparib in all patients with BRCA-mutated, including sBRCA-mutated, PSR OC.
Published: 2023

48. Endometrial carcinosarcoma

Author: Bogani, G, Ray-Coquard, I, Concin, N, Ngoi, N, Morice, P, Caruso, G, Enomoto, T, Takehara, K, Denys, H, Lorusso, D, Coleman, R, Vaughan, M, Takano, M, Provencher, D, Sagae, S, Wimberger, P, Póka, R, Segev, Y, Kim, S, Kim, J, Candido Dos Reis, F, Ramirez, P, Mariani, A, Leitao, M, Makker, V, Abu-Rustum, N, Vergote, I, Zannoni, G, Tan, D, Mccormack, M, Paolini, B, Bini, M, Raspagliesi, F, Benedetti Panici, P, Di Donato, V, Muzii, L, Colombo, N, Pignata, S, Scambia, G, Monk, B, Bogani, Giorgio, Ray-Coquard, Isabelle, Concin, Nicole, Ngoi, Natalie Yan Li, Morice, Philippe, Caruso, Giuseppe, Enomoto, Takayuki, Takehara, Kazuhiro, Denys, Hannelore, Lorusso, Domenica, Coleman, Robert, Vaughan, Michelle M, Takano, Masashi, Provencher, Diane Michele, Sagae, Satoru, Wimberger, Pauline, Póka, Robert, Segev, Yakir, Kim, Se Ik, Kim, Jae-Weon, Candido Dos Reis, Francisco Jose, Ramirez, Pedro T, Mariani, Andrea, Leitao, Mario, Makker, Vicky, Abu-Rustum, Nadeem R, Vergote, Ignace, Zannoni, Gianfranco, Tan, David, McCormack, Mary, Paolini, Biagio, Bini, Marta, Raspagliesi, Francesco, Benedetti Panici, Pierluigi, Di Donato, Violante, Muzii, Ludovico, Colombo, Nicoletta, Pignata, Sandro, Scambia, Giovanni, Monk, Bradley J, Bogani, G, Ray-Coquard, I, Concin, N, Ngoi, N, Morice, P, Caruso, G, Enomoto, T, Takehara, K, Denys, H, Lorusso, D, Coleman, R, Vaughan, M, Takano, M, Provencher, D, Sagae, S, Wimberger, P, Póka, R, Segev, Y, Kim, S, Kim, J, Candido Dos Reis, F, Ramirez, P, Mariani, A, Leitao, M, Makker, V, Abu-Rustum, N, Vergote, I, Zannoni, G, Tan, D, Mccormack, M, Paolini, B, Bini, M, Raspagliesi, F, Benedetti Panici, P, Di Donato, V, Muzii, L, Colombo, N, Pignata, S, Scambia, G, Monk, B, Bogani, Giorgio, Ray-Coquard, Isabelle, Concin, Nicole, Ngoi, Natalie Yan Li, Morice, Philippe, Caruso, Giuseppe, Enomoto, Takayuki, Takehara, Kazuhiro, Denys, Hannelore, Lorusso, Domenica, Coleman, Robert, Vaughan, Michelle M, Takano, Masashi, Provencher, Diane Michele, Sagae, Satoru, Wimberger, Pauline, Póka, Robert, Segev, Yakir, Kim, Se Ik, Kim, Jae-Weon, Candido Dos Reis, Francisco Jose, Ramirez, Pedro T, Mariani, Andrea, Leitao, Mario, Makker, Vicky, Abu-Rustum, Nadeem R, Vergote, Ignace, Zannoni, Gianfranco, Tan, David, McCormack, Mary, Paolini, Biagio, Bini, Marta, Raspagliesi, Francesco, Benedetti Panici, Pierluigi, Di Donato, Violante, Muzii, Ludovico, Colombo, Nicoletta, Pignata, Sandro, Scambia, Giovanni, and Monk, Bradley J
Abstract: Endometrial carcinosarcoma is a rare and aggressive high-grade endometrial carcinoma with secondary sarcomatous trans-differentiation (conversion theory). The clinical presentation and diagnostic work-up roughly align with those of the more common endometrioid counterpart, although endometrial carcinosarcoma is more frequently diagnosed at an advanced stage. Endometrial carcinosarcoma is not a single entity but encompasses different histological subtypes, depending on the type of carcinomatous and sarcomatous elements. The majority of endometrial carcinosarcomas are characterized by p53 abnormalities. The proportion of POLE and microsatellite instablity-high (MSI-H) is directly related to the epithelial component, being approximately 25% and 3% in endometrioid and non-endometrioid components.The management of non-metastatic disease is based on a multimodal approach with optimal surgery followed by (concomitant or sequential) chemotherapy and radiotherapy, even for early stages. Palliative chemotherapy is recommended in the metastatic or recurrent setting, with carboplatin/paclitaxel doublet being the first-line regimen. Although the introduction of immunotherapy plus/minus a tyrosine kinase inhibitor shifted the paradigm of treatment of patients with recurrent endometrial cancer, patients with endometrial carcinosarcoma were excluded from most studies evaluating single-agent immunotherapy or the combination. However, the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) approved the use of pembrolizumab and lenvatinib in endometrial cancer (all histotypes) after progression on chemotherapy and single-agent immunotherapy in MSI-H cancers. In the era of precision medicine, emerging knowledge on molecular endometrial carcinosarcoma is opening new promising therapeutic options for more personalized treatment. The present review outlines state-of-the-art knowledge and future directions for patients with endometrial carcinosarcoma.
Published: 2023

49. Homologous Recombination Repair Gene Mutations to Predict Olaparib Plus Bevacizumab Efficacy in the First-Line Ovarian Cancer PAOLA-1/ENGOT-ov25 Trial

Author: Pujade-Lauraine, E, Brown, J, Barnicle, A, Wessen, J, Lao-Sirieix, P, Criscione, S, du Bois, A, Lorusso, D, Romero, I, Petru, E, Yoshida, H, Vergote, I, Colombo, N, Hietanen, S, Provansal, M, Schmalfeldt, B, Pignata, S, Martín Lorente, C, Berton, D, Runnebaum, I, Ray-Coquard, I, Pujade-Lauraine, Eric, Brown, Jessica, Barnicle, Alan, Wessen, Jonathan, Lao-Sirieix, Pierre, Criscione, Steven W, du Bois, Andreas, Lorusso, Domenica, Romero, Ignacio, Petru, Edgar, Yoshida, Hiroyuki, Vergote, Ignace, Colombo, Nicoletta, Hietanen, Sakari, Provansal, Magali, Schmalfeldt, Barbara, Pignata, Sandro, Martín Lorente, Cristina, Berton, Dominique, Runnebaum, Ingo B, Ray-Coquard, Isabelle, Pujade-Lauraine, E, Brown, J, Barnicle, A, Wessen, J, Lao-Sirieix, P, Criscione, S, du Bois, A, Lorusso, D, Romero, I, Petru, E, Yoshida, H, Vergote, I, Colombo, N, Hietanen, S, Provansal, M, Schmalfeldt, B, Pignata, S, Martín Lorente, C, Berton, D, Runnebaum, I, Ray-Coquard, I, Pujade-Lauraine, Eric, Brown, Jessica, Barnicle, Alan, Wessen, Jonathan, Lao-Sirieix, Pierre, Criscione, Steven W, du Bois, Andreas, Lorusso, Domenica, Romero, Ignacio, Petru, Edgar, Yoshida, Hiroyuki, Vergote, Ignace, Colombo, Nicoletta, Hietanen, Sakari, Provansal, Magali, Schmalfeldt, Barbara, Pignata, Sandro, Martín Lorente, Cristina, Berton, Dominique, Runnebaum, Ingo B, and Ray-Coquard, Isabelle
Abstract: Purpose: The PAOLA-1/ENGOT-ov25 trial of maintenance olaparib plus bevacizumab for newly diagnosed advanced high-grade ovarian cancer demonstrated a significant progression-free survival (PFS) benefit over placebo plus bevacizumab, particularly in patients with homologous recombination deficiency (HRD)-positive tumors. We explored whether mutations in non-BRCA1 or BRCA2 homologous recombination repair (non-BRCA HRRm) genes predicted benefit from olaparib plus bevacizumab in PAOLA-1. Methods: Eight hundred and six patients were randomly assigned (2:1). Tumors were analyzed using the Myriad MyChoice HRD Plus assay to assess non-BRCA HRRm and HRD status; HRD was based on a genomic instability score (GIS) of ≥ 42. In this exploratory analysis, PFS was assessed in patients harboring deleterious mutations using six non-BRCA HRR gene panels, three devised for this analysis and three previously published. Results: The non-BRCA HRRm prevalence ranged from 30 of 806 (3.7%) to 79 of 806 (9.8%) depending on the gene panel used, whereas 152 of 806 (18.9%) had non-BRCA1 or BRCA2 mutation HRD-positive tumors. The majority of tumors harboring non-BRCA HRRm had a low median GIS; however, a GIS of > 42 was observed for tumors with mutations in five HRR genes (BLM, BRIP1, RAD51C, PALB2, and RAD51D). Rates of gene-specific biallelic loss were variable (0% to 100%) in non-BRCA HRRm tumors relative to BRCA1-mutated (99%) or BRCA2-mutated (86%) tumors. Across all gene panels tested, hazard ratios for PFS (95% CI) ranged from 0.92 (0.51 to 1.73) to 1.83 (0.76 to 5.43). Conclusion: Acknowledging limitations of small subgroup sizes, non-BRCA HRRm gene panels were not predictive of PFS benefit with maintenance olaparib plus bevacizumab versus placebo plus bevacizumab in PAOLA-1, irrespective of the gene panel tested. Current gene panels exploring HRRm should not be considered a substitute for HRD determined by BRCA mutation status and genomic instability testing in first-line high-grade ov
Published: 2023

50. The role of psychosocial safety climate on flexible work from home digital job demands and work-life conflict

Author: Parkin, A.K., Zadow, A.J., Potter, R.E., Afsharian, A., Dollard, M.F., Pignata, S., Bakker, Arnold, Lushington, K., Parkin, A.K., Zadow, A.J., Potter, R.E., Afsharian, A., Dollard, M.F., Pignata, S., Bakker, Arnold, and Lushington, K.
Abstract: Due to the COVID-19 pandemic, the number of employees in flexible work from home has increased markedly along with a reliance on information communication technologies. This study investigated the role of an organisational factor, psychosocial safety climate (PSC; the climate for worker psychological health and safety), as an antecedent of these new kinds of demands (specifically work from home digital job demands) and their effect on work-life conflict. Data were gathered via an online survey of 2,177 employees from 37 Australian universities. Multilevel modelling showed that university level PSC to demands, y=-0.09, SE=0.03, p<0.01, and demands to work-life conflict, y=0.51, SE=0.19, p<0.05, relationships were significant. Supporting the antecedent theory, university level PSC was significantly indirectly related to work-life conflict via demands (LL -0.10 UL -0.01). Against expectations PSC did not moderate the demand to work-life conflict relationship. The results imply that targeting PSC could help prevent work from home digital job demands, and therefore, work-life conflict. Further research is needed on the role of digital job resources as flexible and hybrid work takes hold post COVID.
Published: 2023

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