1. Clinical phenotypes and prognostic features of embryonal tumours with multi-layered rosettes: a Rare Brain Tumor Registry study
- Author
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Milena La Spina, Roona Sinha, Jason E. Cain, Abhaya V. Kulkarni, Nicolas Gottardo, Young-Shin Ra, Jennifer A. Chan, Bryan K. Li, Naureen Mushtaq, Lindsey Hoffman, Maria Joao Gil da Costa, Nada Jabado, Rajeev Vibhakar, Jordan R. Hansford, Palma Solano-Paez, Andrew W. Walter, Anne Bendel, Lili-Naz Hazrati, Michael A. Grotzer, Scott L. Pomeroy, Cynthia Hawkins, Maryam Fouladi, Nicholas Gerber, Ho Keung Ng, Donna L. Johnston, David S. Ziegler, Helen M. Branson, Alexander G. Weil, Tannu Suwal, Jian Qiang Lu, Gino R. Somers, Anna Maria Buccoliero, Ramya Ramanujachar, Ashley Plant, Eloy Rivas, Vanan Magimairajan, Rong Li, Ben Ho, Sandra Camelo-Piragua, Christelle Dufour, Paula Marrano, Uri Tabori, Alyssa Reddy, Sumihito Nobusawa, Jason Fangusaro, James Loukides, Haci Ahmet Demir, Cinzia Lavarino, Angelica Oviedo, Daniel Catchpoole, Yin Wang, Derek Hanson, Joseph Torkildson, Karen Wright, Mette Jorgensen, Nongnuch Sirachainan, Hideo Nakamura, Laetitia Padovani, Luca Massimi, Annie Huang, Rina Dvir, Nalin Gupta, Amy Smith, Sara Khan, Eric Bouffet, Chien-Jui Cheng, Iqra Mumal, Mariko Sato, Jeffery Rubens, Mei Lu, Peter B. Dirks, Jesse Kresak, David Samuel, James T. Rutka, G. Yancey Gillespie, Suzanne Laughlin, Samina Afzal, Salma Al-Karmi, Kuo-Sheng Wu, Claire M. Mazewski, Eugene Hwang, Roger J. Packer, Jean Michaud, Andrew Dodgshun, James M. Drake, Vicente Santa-Maria, Christine Dahl, Sebastian Perreault, Lucie Lafay-Cousin, Frank van Landeghem, Nirav Thacker, Mary Shago, Michael D. Taylor, Derek S. Tsang, Timothy E. Van Meter, Derek Stephens, Adriana Fonseca, Birgit Ertl-Wagner, Mahjouba Boutarbouch, Vijay Ramaswamy, Joanna J. Phillips, Almeida Gonzalez Cv, Jean M. Mulcahy Levy, Benjamin Ellezam, George M. Ibrahim, Nabil Kabbara, Franck Bourdeaut, Violet Shen, Tarik Tihan, Sridharan Gururangan, Tai-Tong Wong, Michal Zapotocky, Michal Yalon-Oren, Helen Toledano, Amar Gajjar, Ute Bartels, Holly Lindsay, Christopher Dunham, Nicolas André, Laura Amariglio, David Scharnhorst, Reuben Antony, Suradej Hongeng, Andres Morales La Madrid, Sharon Low, Paul Wood, Beverly Wilson, Enrica Tan, Peter A. Downie, Dariusz Adamek, Christopher L. Moertel, Alvaro Lassaletta, Chad Jacobsen, Eric H. Raabe, Sarah Leary, Richard Grundy, University of Zurich, Canadian Institutes of Health Research, Canada Research Chairs, Australian Lions Childhood Cancer Research Foundation, Junta de Andalucía, and Asociación Española de Pediatría
- Subjects
Oncology ,Male ,medicine.medical_specialty ,medicine.medical_treatment ,Brain tumor ,610 Medicine & health ,Disease ,Neurosurgical Procedures ,Internal medicine ,Developmental and Educational Psychology ,medicine ,Humans ,RNA, Messenger ,Child ,Proportional Hazards Models ,Chemotherapy ,Univariate analysis ,business.industry ,Brain Neoplasms ,Not Otherwise Specified ,Hazard ratio ,Infant, Newborn ,Infant ,Neoplasms, Germ Cell and Embryonal ,medicine.disease ,Prognosis ,Phenotype ,Combined Modality Therapy ,Progression-Free Survival ,Radiation therapy ,Gene Expression Regulation, Neoplastic ,10036 Medical Clinic ,Chemotherapy, Adjuvant ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Female ,Radiotherapy, Adjuvant ,business - Abstract
Rare Brain Tumor Registry., [Background] Embryonal tumours with multi-layered rosettes (ETMRs) are a newly recognised, rare paediatric brain tumour with alterations of the C19MC microRNA locus. Due to varied diagnostic practices and scarce clinical data, disease features and determinants of outcomes for these tumours are poorly defined. We did an integrated clinicopathological and molecular analysis of primary ETMRs to define clinical phenotypes, and to identify prognostic factors of survival and key treatment modalities for this orphan disease., [Methods] Paediatric patients with primary ETMRs and tissue available for analyses were identified from the Rare Brain Tumor Consortium global registry. The institutional histopathological diagnoses were centrally re-reviewed as per the current WHO CNS tumour guidelines, using histopathological and molecular assays. Only patients with complete clinical, treatment, and survival data on Nov 30, 2019, were included in clinicopathological analyses. Among patients who received primary multi-modal curative regimens, event-free survival and overall survival were determined using Cox proportional hazard and log-rank analyses. Univariate and multivariable Cox proportional hazard regression was used to estimate hazard ratios (HRs) with 95% CIs for clinical, molecular, or treatment-related prognostic factors., [Findings] 159 patients had a confirmed molecular diagnosis of primary ETMRs (median age at diagnosis 26 months, IQR 18–36) and were included in our clinicopathological analysis. ETMRs were predominantly non-metastatic (94 [73%] of 128 patients), arising from multiple sites; 84 (55%) of 154 were cerebral tumours and 70 (45%) of 154 arose at sites characteristic of other brain tumours. Hallmark C19MC alterations were seen in 144 (91%) of 159 patients; 15 (9%) were ETMR not otherwise specified. In patients treated with curative intent, event-free survival was 57% (95% CI 47–68) at 6 months and 31% (21–42) at 2 years; overall survival was 29% (20–38) at 2 years and 27% (18–37) at 4 years. Overall survival was associated with non-metastatic disease (HR 0·48, 95% CI 0·28–0·80; p=0·0057) and non-brainstem location (0·42 [0·22–0·81]; p=0·013) on univariate analysis, as well as with gross total resection (0·30, 0·16–0·58; p=0·0014), high-dose chemotherapy (0·35, 0·19–0·67; p=0·0020), and radiotherapy (0·21, 0·10–0·41; p, [Interpretation] Prompt molecular diagnosis and post-surgical treatment with intensive multi-modal therapy tailored to patient-specific risk features could improve ETMR survival., Canadian Institute of Health Research, Canada Research Chair Awards, Australian Lions Childhood Cancer Research Foundation, Spanish Society of Pediatrics, Consejería de Salud y Familias de la Junta de Andalucía, Miracle Marnie, Phoebe Rose Rocks, Tali's Funds, Garron Cancer Centre, Grace's Walk, Meagan's Hug, Brainchild, Nelina's Hope, and Jean Martel Foundation.
- Published
- 2021