A Trasolini1,2, C Erker1,3, S Cheng4, C Crowell1,5, K McFadden1,6, R Moineddin7, M A Sargent8, D Mata-Mbemba9,10,11. 1. From the IWK Health Centre (A.T., C.E., C.C., K.M., D.M.-M.), Halifax, Nova Scotia, Canada. 2. Dalhousie University Medical School (A.T.), Halifax, Nova Scotia, Canada. 3. Departments of Pediatrics (C.E.). 4. Division of Hematology, Oncology, and Bone Marrow Transplant (S.C.), Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada. 5. Faculty of Science (C.C.), Dalhousie University, Halifax, Nova Scotia, Canada. 6. Pathology (K.M.). 7. University of Toronto Dalla Lana School of Public Health (R.M.), Toronto, Ontario, Canada. 8. Department of Radiology (M.A.S.), British Columbia Children's Hospital and University of British Columbia, Vancouver, British Columbia, Canada. 9. From the IWK Health Centre (A.T., C.E., C.C., K.M., D.M.-M.), Halifax, Nova Scotia, Canada Daddy.Mata-Mbemba@iwk.nshealth.ca. 10. Diagnostic Radiology (D.M.-M.). 11. Department of Diagnostic Imaging (D.M.-M.), IWK Health Centre, Halifax, Nova Scotia, Canada.
Abstract
BACKGROUND AND PURPOSE: The prognosis and treatment of pediatric low-grade gliomas is influenced by their molecular subtype. MR imaging remains the mainstay for initial work-up and surgical planning. We aimed to determine the relationship between imaging patterns and molecular subtypes of pediatric low-grade gliomas. MATERIALS AND METHODS: This was a retrospective bi-institutional study for patients diagnosed from 2004 to 2021 with pathologically confirmed pediatric low-grade gliomas molecularly defined as BRAF fusion, BRAF V600E mutant, or wild-type (which is neither BRAF V600E mutant nor BRAF fusion). Two neuroradiologists, blinded, independently reviewed imaging parameters from diagnostic MRIs, and discrepancies were resolved by consensus. Bivariate analysis was used followed by pair-wise comparison of the Dwass-Steel-Critchlow-Fligner method to compare the 3 molecular subtypes. Interreader agreement was assessed using κ. RESULTS: We included 70 patients: 30 BRAF fusion, 19 BRAF V600E mutant, and 21 wild-type. There was substantial agreement between the readers for overall imaging variables (κ = 0.75). BRAF fusion tumors compared with BRAF V600E and wild-type tumors were larger (P = .0022), and had a greater mass effect (P = .0053), increased frequency of hydrocephalus (P = .0002), and diffuse enhancement (p <.0001). BRAF V600E mutant tumors were more often hemispheric (P < .0001), appeared more infiltrative (P = .0002), and, though infrequent, were the only group demonstrating diffusion restriction (qualitatively; P = .0042) with a lower ADC ratio (quantitatively) (P = .003). CONCLUSIONS: BRAF fusion and BRAF V600E mutant pediatric low-grade gliomas have unique imaging features that can be used to differentiate them from each other and wild-type pediatric low-grade glioma using a standard radiology review with high interreader agreement. In the era of targeted therapy, these features can be useful for therapeutic planning before surgery.
BACKGROUND AND PURPOSE: The prognosis and treatment of pediatric low-grade gliomas is influenced by their molecular subtype. MR imaging remains the mainstay for initial work-up and surgical planning. We aimed to determine the relationship between imaging patterns and molecular subtypes of pediatric low-grade gliomas. MATERIALS AND METHODS: This was a retrospective bi-institutional study for patients diagnosed from 2004 to 2021 with pathologically confirmed pediatric low-grade gliomas molecularly defined as BRAF fusion, BRAF V600E mutant, or wild-type (which is neither BRAF V600E mutant nor BRAF fusion). Two neuroradiologists, blinded, independently reviewed imaging parameters from diagnostic MRIs, and discrepancies were resolved by consensus. Bivariate analysis was used followed by pair-wise comparison of the Dwass-Steel-Critchlow-Fligner method to compare the 3 molecular subtypes. Interreader agreement was assessed using κ. RESULTS: We included 70 patients: 30 BRAF fusion, 19 BRAF V600E mutant, and 21 wild-type. There was substantial agreement between the readers for overall imaging variables (κ = 0.75). BRAF fusion tumors compared with BRAF V600E and wild-type tumors were larger (P = .0022), and had a greater mass effect (P = .0053), increased frequency of hydrocephalus (P = .0002), and diffuse enhancement (p <.0001). BRAF V600E mutant tumors were more often hemispheric (P < .0001), appeared more infiltrative (P = .0002), and, though infrequent, were the only group demonstrating diffusion restriction (qualitatively; P = .0042) with a lower ADC ratio (quantitatively) (P = .003). CONCLUSIONS: BRAF fusion and BRAF V600E mutant pediatric low-grade gliomas have unique imaging features that can be used to differentiate them from each other and wild-type pediatric low-grade glioma using a standard radiology review with high interreader agreement. In the era of targeted therapy, these features can be useful for therapeutic planning before surgery.
Authors: Jason Fangusaro; Arzu Onar-Thomas; Tina Young Poussaint; Shengjie Wu; Azra H Ligon; Neal Lindeman; Anuradha Banerjee; Roger J Packer; Lindsay B Kilburn; Stewart Goldman; Ian F Pollack; Ibrahim Qaddoumi; Regina I Jakacki; Paul G Fisher; Girish Dhall; Patricia Baxter; Susan G Kreissman; Clinton F Stewart; David T W Jones; Stefan M Pfister; Gilbert Vezina; Jessica S Stern; Ashok Panigrahy; Zoltan Patay; Benita Tamrazi; Jeremy Y Jones; Sofia S Haque; David S Enterline; Soonmee Cha; Michael J Fisher; Laurence Austin Doyle; Malcolm Smith; Ira J Dunkel; Maryam Fouladi Journal: Lancet Oncol Date: 2019-05-28 Impact factor: 41.316
Authors: Tore Stokland; Jo-Fen Liu; James W Ironside; David W Ellison; Roger Taylor; Kathryn J Robinson; Susan V Picton; David A Walker Journal: Neuro Oncol Date: 2010-09-22 Impact factor: 12.300
Authors: Craig Horbinski; Marina N Nikiforova; Jill M Hagenkord; Ronald L Hamilton; Ian F Pollack Journal: Neuro Oncol Date: 2012-04-05 Impact factor: 12.300
Authors: Guillaume Bergthold; Pratiti Bandopadhayay; Wenya Linda Bi; Lori Ramkissoon; Charles Stiles; Rosalind A Segal; Rameen Beroukhim; Keith L Ligon; Jacques Grill; Mark W Kieran Journal: Biochim Biophys Acta Date: 2014-02-28
Authors: Liana Nobre; Michal Zapotocky; Vijay Ramaswamy; Scott Ryall; Julie Bennett; Daniel Alderete; Julia Balaguer Guill; Lorena Baroni; Ute Bartels; Abhishek Bavle; Miriam Bornhorst; Daniel R Boue; Adela Canete; Murali Chintagumpala; Scott L Coven; Ofelia Cruz; Sonika Dahiya; Peter Dirks; Ira J Dunkel; David Eisenstat; Cecile Faure Conter; Elizabeth Finch; Jonathan L Finlay; Didier Frappaz; Maria Luisa Garre; Karen Gauvain; Anne Grete Bechensteen; Jordan R Hansford; Inga Harting; Peter Hauser; Lili-Naz Hazrati; Annie Huang; Sarah G Injac; Valentina Iurilli; Matthias Karajannis; Gurcharanjeet Kaur; Martin Kyncl; Lenka Krskova; Normand Laperriere; Valerie Larouche; Alvaro Lassaletta; Sarah Leary; Frank Lin; Samantha Mascelli; Tara McKeown; Till Milde; Andres Morales La Madrid; Giovanni Morana; Helena Morse; Naureen Mushtaq; Diana S Osorio; Roger Packer; Zdenek Pavelka; Eduardo Quiroga-Cantero; James Rutka; Magnus Sabel; Duarte Salgado; Palma Solano; Jaroslav Sterba; Jack Su; David Sumerauer; Michael D Taylor; Helen Toledano; Derek S Tsang; Mariana Valente Fernandes; Frank van Landeghem; Cornelis M van Tilburg; Bev Wilson; Olaf Witt; Josef Zamecnik; Eric Bouffet; Cynthia Hawkins; Uri Tabori Journal: JCO Precis Oncol Date: 2020-05-20
Authors: Cheng-Ying Ho; Bret C Mobley; Heather Gordish-Dressman; Christopher J VandenBussche; Gary E Mason; Miriam Bornhorst; Adam J Esbenshade; Mahtab Tehrani; Brent A Orr; Delecia R LaFrance; Joseph M Devaney; Beatrix W Meltzer; Sean E Hofherr; Peter C Burger; Roger J Packer; Fausto J Rodriguez Journal: Acta Neuropathol Date: 2015-08-12 Impact factor: 17.088
Authors: Zachary J Reitman; Brenton R Paolella; Guillaume Bergthold; Kristine Pelton; Sarah Becker; Robert Jones; Claire E Sinai; Hayley Malkin; Ying Huang; Leslie Grimmet; Zachary T Herbert; Yu Sun; Jessica L Weatherbee; John A Alberta; John F Daley; Orit Rozenblatt-Rosen; Alexandra L Condurat; Kenin Qian; Prasidda Khadka; Rosalind A Segal; Daphne Haas-Kogan; Mariella G Filbin; Mario L Suva; Aviv Regev; Charles D Stiles; Mark W Kieran; Liliana Goumnerova; Keith L Ligon; Alex K Shalek; Pratiti Bandopadhayay; Rameen Beroukhim Journal: Nat Commun Date: 2019-08-19 Impact factor: 14.919