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. 2020 Dec 4;22(Suppl 3):iii327–iii328. doi: 10.1093/neuonc/noaa222.225

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

Sara Khan 1,2, Palma Solano-Paez 3,4, Tannu Suwal 3,5, Salma Al-Karmi 3, Mei Lu 1, Ben Ho 1, Maryam Fouladi 6, Sarah Leary 7, Jean M Mulcahy Levy 8, Alvaro Lassaletta 9, Eloy Rivas 10, Alyssa Reddy 11, G Yancey Gillespie 12, Nalin Gupta 13, Michal Yalon-Oren 14, Laura Amariglio 14, Hideo Nakamura 15, Kuo-Sheng Wu 16, Tai-Tong Wong 16, Young-Shin Ra 17, Milena La Spina 18, Policlinico Vittorio Emanuele 18, Luca Massimi 19, Anna Maria Buccoliero 20, Jordan R Hansford 21, Richard G Grundy 22, Dariusz Adamek 23, Jason Fangusaro 24, David Scharnhorst 25, Donna Johnston 26, Lucie Lafay-Cousin 27, Sandra Camelo-Piragua 28, Nabil Kabbara 29, Amar Gajjar 30, Mahjouba Boutarbouch 31, Maria Joao Gil da Costa 32, Derek Hanson 33,34, Paul Wood 35, Maysa Al-Hussaini 36, Nisreen Amayiri 36, Yin Wang 37, Daniel Catchpoole 38, Jean Michaud 39, Anne E Bendel 40, Benjamin Ellezam 41, Nicholas Gerber 42, Ashley Plant 43, Rubens Jeffery 44, Christopher Dunham 45, Christopher Moertel 46, Andrew Walter 47, David Ziegler 48, Andrew Dodgshun 49, Nicholas Gottardo 50, Ahmet Demir 51, Ramya Ramanujachar 52, Eric Raabe 53, Shago Mary 54, Peter Dirks 54, Michael Taylor 54, Hwang Eugene 55, Holly Lindsey 56, Tarik Tihan 57, Jorgensen Mette 58, Christine Dahl 58, Sharon Low 59, Amy Smith 60, Lili-Naz Hazrati 54, Jesse Kresak 60, Somers Gino 54, Enrica Tan 61, Andres Morales 62, Vicente Santa-Maria 62, Cynthia Hawkins 54, Ute Bartels 54, Derek Stephens 54, Sumihito Nobusawa 64, Christelle Dufour 65, Franck Bourdeaut 66, Nicolas Andre 67, Eric Bouffet 54, Annie Huang 1,54
PMCID: PMC7715263

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.


Articles from Neuro-Oncology are provided here courtesy of Society for Neuro-Oncology and Oxford University Press

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