Lucia Musacchio1, Daniela Califano2, Michele Bartoletti3,4, Laura Arenare5, Domenica Lorusso1,6, Nunzia Simona Losito7, Gennaro Cormio8,9, Stefano Greggi10, Francesco Raspagliesi11, Giorgio Valabrega12, Vanda Salutari1, Carmela Pisano13, Anna Spina2, Daniela Russo2, Michele Del Sesto7, Vincenzo Canzonieri14,15, Francesco Ferraù16, Gian Franco Zannoni17,18, Vera Loizzi9, Viola Ghizzoni1, Claudia Casanova19, Valentina Tuninetti12, Monika Ducceschi11, Vittoria Del Vecchio9, Simona Scalone4, Domenico Priolo16, Francesco Perrone5, Giovanni Scambia1,6, Sandro Pignata20. 1. Department of Women and Child Health, Division of Gynecologic Oncology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy. 2. Microenvironment Molecular Targets Unit, Istituto Nazionale Tumori, IRCCS - Fondazione G. Pascale, Naples, Italy. 3. Department of Medicine (DAME), University of Udine, Udine, Italy. 4. Unit of Medical Oncology and Cancer Prevention, Department of Medical Oncology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano, Italy. 5. Clinical Trial Unit, Istituto Nazionale Tumori, IRCCS - Fondazione G.Pascale, Naples, Italy. 6. Department of Life Science and Public Health, Catholic University of Sacred Heart, Largo Agostino Gemelli, Rome, Italy. 7. Surgical Pathology Unit, Istituto Nazionale Tumori, IRCCS - Fondazione G. Pascale, Naples, Italy. 8. Gynecologic Oncology Istituto Tumori Giovanni Paolo II - IRCCS, Bari, Italy. 9. Interdisciplinary Department of Medicine, University of Bari, Bari, Italy. 10. Gynecologic Oncology Unit, Istituto Nazionale Tumori, IRCCS - Fondazione G. Pascale, Naples, Italy. 11. Gynecologic Oncology Unit, Istituto Nazionale Tumori, IRCCS, Milan, Italy. 12. Department of Oncology, University of Torino at Ordine Mauriziano Hospital, Turin, Italy. 13. Department of Urology and Gynecology, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, Napoli, Italy. 14. Pathology Unit, Centro di Riferimento Oncologico di Aviano (CRO Aviano), IRCCS, National Cancer Institute, Aviano, Italy. 15. Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy. 16. Medical Oncology Department, San Vincenzo Hospital, Taormina, Messina, Italy. 17. Department of Woman, Child and Public Health Sciences, Gynecopathology and Breast Pathology Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy. 18. Pathological Anatomy Institute, Catholic University of Sacred Hearth, Rome, Italy. 19. Oncology Department, Santa Maria delle Croci Hospital, Ravenna, Italy. 20. Department of Urology and Gynecology, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, Napoli, Italy. s.pignata@istitutotumori.na.it.
Abstract
BACKGROUND: Low-grade serous ovarian and peritoneal cancer (LGSC) is a rare disease and few data on the clinical and genomic landscape have been published. METHODS: A retrospective analysis of patients diagnosed with LGSC between 1996 and 2019 was conducted in MITO centers. Objective Response Rate (ORR) to treatments, progression-free survival (PFS) and overall survival (OS) were assessed. Additionally, the tumor molecular profile of 56 patients was evaluated using the Next Generation Sequencing (NGS) FoundationOne CDX (Foundation Medicine®). RESULTS: A total of 128 patients with complete clinical data and pathologically confirmed diagnosis of LGSC were identified. ORR to first and subsequent therapies were 23.7% and 33.7%, respectively. PFS was 43.9 months (95% CI:32.4-53.1) and OS was 105.4 months (95% CI: 82.7-not reached). The most common gene alterations were: KRAS (n = 12, 21%), CDKN2A/B (n = 11, 20%), NRAS (n = 8, 14%), FANCA (n = 8, 14%), NF1 (n = 7, 13%) and BRAF (n = 6, 11%). Unexpectedly, pathogenetic BRCA1 (n = 2, 4%), BRCA2 (n = 1, 2%) and PALB2 (n = 1, 2%) mutations were found. CONCLUSIONS: MITO 22 suggests that LGSC is an heterogenous disease for both its clinical behavior in response to standard therapies and its molecular alterations. Future prospective studies should test treatments according to biological and molecular tumor's characteristics. CLINICAL TRIAL REGISTRATION: This study is registered under NCT02408536 on ClinicalTrials.gov .
BACKGROUND: Low-grade serous ovarian and peritoneal cancer (LGSC) is a rare disease and few data on the clinical and genomic landscape have been published. METHODS: A retrospective analysis of patients diagnosed with LGSC between 1996 and 2019 was conducted in MITO centers. Objective Response Rate (ORR) to treatments, progression-free survival (PFS) and overall survival (OS) were assessed. Additionally, the tumor molecular profile of 56 patients was evaluated using the Next Generation Sequencing (NGS) FoundationOne CDX (Foundation Medicine®). RESULTS: A total of 128 patients with complete clinical data and pathologically confirmed diagnosis of LGSC were identified. ORR to first and subsequent therapies were 23.7% and 33.7%, respectively. PFS was 43.9 months (95% CI:32.4-53.1) and OS was 105.4 months (95% CI: 82.7-not reached). The most common gene alterations were: KRAS (n = 12, 21%), CDKN2A/B (n = 11, 20%), NRAS (n = 8, 14%), FANCA (n = 8, 14%), NF1 (n = 7, 13%) and BRAF (n = 6, 11%). Unexpectedly, pathogenetic BRCA1 (n = 2, 4%), BRCA2 (n = 1, 2%) and PALB2 (n = 1, 2%) mutations were found. CONCLUSIONS: MITO 22 suggests that LGSC is an heterogenous disease for both its clinical behavior in response to standard therapies and its molecular alterations. Future prospective studies should test treatments according to biological and molecular tumor's characteristics. CLINICAL TRIAL REGISTRATION: This study is registered under NCT02408536 on ClinicalTrials.gov .
Authors: David M Gershenson; Charlotte C Sun; Revathy B Iyer; Anais L Malpica; John J Kavanagh; Diane C Bodurka; Kathleen Schmeler; Michael Deavers Journal: Gynecol Oncol Date: 2012-03-06 Impact factor: 5.482
Authors: Anis Kaldawy; Yakir Segev; Ofer Lavie; Ron Auslender; Victoria Sopik; Steven A Narod Journal: Gynecol Oncol Date: 2016-08-28 Impact factor: 5.482
Authors: Heather J Dalton; Nicole D Fleming; Charlotte C Sun; Priya Bhosale; Kathleen M Schmeler; David M Gershenson Journal: Gynecol Oncol Date: 2017-01-27 Impact factor: 5.482
Authors: Jacek P Grabowski; Philipp Harter; Florian Heitz; Eric Pujade-Lauraine; Alexander Reuss; Gunnar Kristensen; Isabelle Ray-Coquard; Julia Heitz; Alexander Traut; Jacobus Pfisterer; Andreas du Bois Journal: Gynecol Oncol Date: 2016-01-22 Impact factor: 5.482
Authors: Peter F Rambau; Robert A Vierkant; Maria P Intermaggio; Linda E Kelemen; Marc T Goodman; Esther Herpel; Paul D Pharoah; Stefan Kommoss; Mercedes Jimenez-Linan; Beth Y Karlan; Aleksandra Gentry-Maharaj; Usha Menon; Susanna Hernando Polo; Francisco J Candido Dos Reis; Jennifer Anne Doherty; Simon A Gayther; Raghwa Sharma; Melissa C Larson; Paul R Harnett; Emma Hatfield; Jurandyr M de Andrade; Gregg S Nelson; Helen Steed; Joellen M Schildkraut; Micheal E Carney; Estrid Høgdall; Alice S Whittemore; Martin Widschwendter; Catherine J Kennedy; Frances Wang; Qin Wang; Chen Wang; Sebastian M Armasu; Frances Daley; Penny Coulson; Micheal E Jones; Micheal S Anglesio; Christine Chow; Anna de Fazio; Montserrat García-Closas; Sara Y Brucker; Cezary Cybulski; Holly R Harris; Andreas D Hartkopf; Tomasz Huzarski; Allan Jensen; Jan Lubiński; Oleg Oszurek; Javier Benitez; Fady Mina; Annette Staebler; Florin Andrei Taran; Jana Pasternak; Aline Talhouk; Mary Anne Rossing; Joy Hendley; Robert P Edwards; Sian Fereday; Francesmary Modugno; Roberta B Ness; Weiva Sieh; Mona A El-Bahrawy; Stacey J Winham; Jenny Lester; Susanne K Kjaer; Jacek Gronwald; Peter Sinn; Peter A Fasching; Jenny Chang-Claude; Kirsten B Moysich; David D Bowtell; Brenda Y Hernandez; Hugh Luk; Sabine Behrens; Mitul Shah; Audrey Jung; Prafull Ghatage; Jennifer Alsop; Kathryn Alsop; Jesús García-Donas; Pamela J Thompson; Anthony J Swerdlow; Chloe Karpinskyj; Alicia Cazorla-Jiménez; María J García; Susha Deen; Lynne R Wilkens; José Palacios; Andrew Berchuck; Jennifer M Koziak; James D Brenton; Linda S Cook; Ellen L Goode; David G Huntsman; Susan J Ramus; Martin Köbel Journal: J Pathol Clin Res Date: 2018-09-21
Authors: Sally M Hunter; Michael S Anglesio; Georgina L Ryland; Raghwa Sharma; Yoke-Eng Chiew; Simone M Rowley; Maria A Doyle; Jason Li; C Blake Gilks; Phillip Moss; Prue E Allan; Andrew N Stephens; David G Huntsman; Anna deFazio; David D Bowtell; Kylie L Gorringe; Ian G Campbell Journal: Oncotarget Date: 2015-11-10