ETMR-22. TITLE: DEFINING THE CLINICAL AND PROGNOSTIC LANDSCAPE OF EMBRYONAL TUMORS WITH MULTI-LAYERED ROSETTES (ETMRs), A RARE BRAIN TUMOR REGISTRY (RBTC) STUDY. (4th December 2020)

• Record Type: Journal Article
• Authors: Khan, Sara; Solano-Paez, Palma; Suwal, Tannu; Al-Karmi, Salma; Lu, Mei; Ho, Ben; Fouladi, Maryam; Leary, Sarah; Levy, Jean M Mulcahy; Lassaletta, Alvaro; Rivas, Eloy; Reddy, Alyssa; Gillespie, G Yancey; Gupta, Nalin; Yalon-Oren, Michal; Amariglio, Laura; Nakamura, Hideo; Wu, Kuo-Sheng; Wong, Tai-Tong; Ra, Young-Shin; Spina, Milena La; Emanuele, Policlinico Vittorio; Massimi, Luca; Buccoliero, Anna Maria; Hansford, Jordan R; Grundy, Richard G; Adamek, Dariusz; Fangusaro, Jason; Scharnhorst, David; Johnston, Donna; Lafay-Cousin, Lucie; Camelo-Piragua, Sandra; Kabbara, Nabil; Gajjar, Amar; Boutarbouch, Mahjouba; da Costa, Maria Joao Gil; Hanson, Derek; Wood, Paul; Al-Hussaini, Maysa; Amayiri, Nisreen; Wang, Yin; Catchpoole, Daniel; Michaud, Jean; Bendel, Anne E; Ellezam, Benjamin; Gerber, Nicholas; Plant, Ashley; Jeffery, Rubens; Dunham, Christopher; Moertel, Christopher; Walter, Andrew; Ziegler, David; Dodgshun, Andrew; Gottardo, Nicholas; Demir, Ahmet; Ramanujachar, Ramya; Raabe, Eric; Mary, Shago; Dirks, Peter; Taylor, Michael; Eugene, Hwang; Lindsey, Holly; Tihan, Tarik; Mette, Jorgensen; Dahl, Christine; Low, Sharon; Smith, Amy; Hazrati, Lili-Naz; Kresak, Jesse; Gino, Somers; Tan, Enrica; Morales, Andres; Santa-Maria, Vicente; Hawkins, Cynthia; Bartels, Ute; Stephens, Derek; Nobusawa, Sumihito; Dufour, Christelle; Bourdeaut, Franck; Andre, Nicolas; Bouffet, Eric; Huang, Annie;
• Is Part Of: Neuro-oncology. Volume 22(2020)Supplement 3
• Page Start: iii327
• Page End: iii328
• Publication Date: 2020-12-04
• Subjects: Brain Neoplasms -- Periodicals; Brain -- Tumors -- Periodicals; Brain -- Cancer -- Periodicals; Nervous system -- Cancer -- Periodicals; 616.99481
• DOI: 10.1093/neuonc/noaa222.225
• Languages: English
• ISSNs: 1522-8517

Abstract

Abstract: ETMR, an aggressive disease characterised by C19MC alterations, were previously categorised as various histologic diagnoses. The clinical spectrum and impact of conventional multi-modal therapy on this new WHO diagnostic category remains poorly understood as a majority of ~200 cases reported to date lack molecular confirmation. We undertook comprehensive clinico-pathologic studies of a large molecularly confirmed cohort to improve disease recognition and treatment approaches. Amongst 623 CNS-PNETs patients enrolled in the RBTC registry, 159 primary ETMRs were confirmed based on a combination of FISH (125), methylation analysis (88), SNP and RNAseq (32) analyses; 91% had C19MC amplification/gains/fusions, 9% lacked C19MC alterations but had global methylation features of ETMR NOS. ETMRs arose in young patients (median age 26 months) predominantly as localized disease (M0-72%, M2-3 -18%) at multiple locations including cerebrum (60%) cerebellum (18%), midline structures (6%); notably 10% were brainstem primaries mimicking DIPG. Uni-and multivariate analyses of clinical and treatment details of curative regimens available for 110 patients identified metastatic disease (p=0.002), brainstem locations(p=0.005), extent of surgery, receipt of multi-modal therapy including high dose chemotherapy and radiation (P<0.001) as significant treatment prognosticators, while C19MC status, age and gender were non-significant risk factors. Analyses of events in all patients showed respective EFS at 3 and 12 months of 84%(95%CI:77–91) and 37%(95%CI:20–41) and 4yr OS of 27%(95%CI:18–37) indicating despite intensified therapies ETMR is a rapidly progressive and fatal disease. Our comprehensive data on the largest cohort of molecularly-confirmed ETMRs provides a critical framework to guide current clinical management and development of clinical trials.