S Mohammed1,2, V Ravikumar2, E Warner2, S H Patel3, S Bakas4,5, A Rao1,2,6,7,8, R Jain9,10. 1. From the Departments of Biostatistics (S.M., A.R.) ukarvind@umich.edu. 2. Computational Medicine & Bioinformatics (S.M., V.R., E.W., A.R.). 3. Department of Radiology & Medical Imaging (S.H.P.), University of Virginia School of Medicine, Charlottesville, Virginia. 4. Departments of Radiology (S.B.). 5. Pathology & Laboratory Medicine (S.B.), University of Pennsylvania, Philadelphia, Pennsylvania. 6. Radiation Oncology (A.R.). 7. Michigan Institute for Data Sciences (A.R.). 8. Department of Biomedical Engineering (A.R.), University of Michigan, Ann Arbor, Michigan. 9. Departments of Radiology (R.J.). 10. Neurosurgery (R.J.), New York University Grossman School of Medicine, New York, New York.
Abstract
BACKGROUND AND PURPOSE: The T2-FLAIR mismatch sign is a validated imaging sign of isocitrate dehydrogenase-mutant 1p/19q noncodeleted gliomas. It is identified by radiologists through visual inspection of preoperative MR imaging scans and has been shown to identify isocitrate dehydrogenase-mutant 1p/19q noncodeleted gliomas with a high positive predictive value. We have developed an approach to quantify the T2-FLAIR mismatch signature and use it to predict the molecular status of lower-grade gliomas. MATERIALS AND METHODS: We used multiparametric MR imaging scans and segmentation labels of 108 preoperative lower-grade glioma tumors from The Cancer Imaging Archive. Clinical information and T2-FLAIR mismatch sign labels were obtained from supplementary material of relevant publications. We adopted an objective analytic approach to estimate this sign through a geographically weighted regression and used the residuals for each case to construct a probability density function (serving as a residual signature). These functions were then analyzed using an appropriate statistical framework. RESULTS: We observed statistically significant (P value = .05) differences between the averages of residual signatures for an isocitrate dehydrogenase-mutant 1p/19q noncodeleted class of tumors versus other categories. Our classifier predicts these cases with area under the curve of 0.98 and high specificity and sensitivity. It also predicts the T2-FLAIR mismatch sign within these cases with an under the curve of 0.93. CONCLUSIONS: On the basis of this retrospective study, we show that geographically weighted regression-based residual signatures are highly informative of the T2-FLAIR mismatch sign and can identify isocitrate dehydrogenase-mutation and 1p/19q codeletion status with high predictive power. The utility of the proposed quantification of the T2-FLAIR mismatch sign can be potentially validated through a prospective multi-institutional study.
BACKGROUND AND PURPOSE: The T2-FLAIR mismatch sign is a validated imaging sign of isocitrate dehydrogenase-mutant 1p/19q noncodeleted gliomas. It is identified by radiologists through visual inspection of preoperative MR imaging scans and has been shown to identify isocitrate dehydrogenase-mutant 1p/19q noncodeleted gliomas with a high positive predictive value. We have developed an approach to quantify the T2-FLAIR mismatch signature and use it to predict the molecular status of lower-grade gliomas. MATERIALS AND METHODS: We used multiparametric MR imaging scans and segmentation labels of 108 preoperative lower-grade glioma tumors from The Cancer Imaging Archive. Clinical information and T2-FLAIR mismatch sign labels were obtained from supplementary material of relevant publications. We adopted an objective analytic approach to estimate this sign through a geographically weighted regression and used the residuals for each case to construct a probability density function (serving as a residual signature). These functions were then analyzed using an appropriate statistical framework. RESULTS: We observed statistically significant (P value = .05) differences between the averages of residual signatures for an isocitrate dehydrogenase-mutant 1p/19q noncodeleted class of tumors versus other categories. Our classifier predicts these cases with area under the curve of 0.98 and high specificity and sensitivity. It also predicts the T2-FLAIR mismatch sign within these cases with an under the curve of 0.93. CONCLUSIONS: On the basis of this retrospective study, we show that geographically weighted regression-based residual signatures are highly informative of the T2-FLAIR mismatch sign and can identify isocitrate dehydrogenase-mutation and 1p/19q codeletion status with high predictive power. The utility of the proposed quantification of the T2-FLAIR mismatch sign can be potentially validated through a prospective multi-institutional study.
Authors: Daniel J Brat; Roel G W Verhaak; Kenneth D Aldape; W K Alfred Yung; Sofie R Salama; Lee A D Cooper; Esther Rheinbay; C Ryan Miller; Mark Vitucci; Olena Morozova; A Gordon Robertson; Houtan Noushmehr; Peter W Laird; Andrew D Cherniack; Rehan Akbani; Jason T Huse; Giovanni Ciriello; Laila M Poisson; Jill S Barnholtz-Sloan; Mitchel S Berger; Cameron Brennan; Rivka R Colen; Howard Colman; Adam E Flanders; Caterina Giannini; Mia Grifford; Antonio Iavarone; Rajan Jain; Isaac Joseph; Jaegil Kim; Katayoon Kasaian; Tom Mikkelsen; Bradley A Murray; Brian Patrick O'Neill; Lior Pachter; Donald W Parsons; Carrie Sougnez; Erik P Sulman; Scott R Vandenberg; Erwin G Van Meir; Andreas von Deimling; Hailei Zhang; Daniel Crain; Kevin Lau; David Mallery; Scott Morris; Joseph Paulauskis; Robert Penny; Troy Shelton; Mark Sherman; Peggy Yena; Aaron Black; Jay Bowen; Katie Dicostanzo; Julie Gastier-Foster; Kristen M Leraas; Tara M Lichtenberg; Christopher R Pierson; Nilsa C Ramirez; Cynthia Taylor; Stephanie Weaver; Lisa Wise; Erik Zmuda; Tanja Davidsen; John A Demchok; Greg Eley; Martin L Ferguson; Carolyn M Hutter; Kenna R Mills Shaw; Bradley A Ozenberger; Margi Sheth; Heidi J Sofia; Roy Tarnuzzer; Zhining Wang; Liming Yang; Jean Claude Zenklusen; Brenda Ayala; Julien Baboud; Sudha Chudamani; Mark A Jensen; Jia Liu; Todd Pihl; Rohini Raman; Yunhu Wan; Ye Wu; Adrian Ally; J Todd Auman; Miruna Balasundaram; Saianand Balu; Stephen B Baylin; Rameen Beroukhim; Moiz S Bootwalla; Reanne Bowlby; Christopher A Bristow; Denise Brooks; Yaron Butterfield; Rebecca Carlsen; Scott Carter; Lynda Chin; Andy Chu; Eric Chuah; Kristian Cibulskis; Amanda Clarke; Simon G Coetzee; Noreen Dhalla; Tim Fennell; Sheila Fisher; Stacey Gabriel; Gad Getz; Richard Gibbs; Ranabir Guin; Angela Hadjipanayis; D Neil Hayes; Toshinori Hinoue; Katherine Hoadley; Robert A Holt; Alan P Hoyle; Stuart R Jefferys; Steven Jones; Corbin D Jones; Raju Kucherlapati; Phillip H Lai; Eric Lander; Semin Lee; Lee Lichtenstein; Yussanne Ma; Dennis T Maglinte; Harshad S Mahadeshwar; Marco A Marra; Michael Mayo; Shaowu Meng; Matthew L Meyerson; Piotr A Mieczkowski; Richard A Moore; Lisle E Mose; Andrew J Mungall; Angeliki Pantazi; Michael Parfenov; Peter J Park; Joel S Parker; Charles M Perou; Alexei Protopopov; Xiaojia Ren; Jeffrey Roach; Thaís S Sabedot; Jacqueline Schein; Steven E Schumacher; Jonathan G Seidman; Sahil Seth; Hui Shen; Janae V Simons; Payal Sipahimalani; Matthew G Soloway; Xingzhi Song; Huandong Sun; Barbara Tabak; Angela Tam; Donghui Tan; Jiabin Tang; Nina Thiessen; Timothy Triche; David J Van Den Berg; Umadevi Veluvolu; Scot Waring; Daniel J Weisenberger; Matthew D Wilkerson; Tina Wong; Junyuan Wu; Liu Xi; Andrew W Xu; Lixing Yang; Travis I Zack; Jianhua Zhang; B Arman Aksoy; Harindra Arachchi; Chris Benz; Brady Bernard; Daniel Carlin; Juok Cho; Daniel DiCara; Scott Frazer; Gregory N Fuller; JianJiong Gao; Nils Gehlenborg; David Haussler; David I Heiman; Lisa Iype; Anders Jacobsen; Zhenlin Ju; Sol Katzman; Hoon Kim; Theo Knijnenburg; Richard Bailey Kreisberg; Michael S Lawrence; William Lee; Kalle Leinonen; Pei Lin; Shiyun Ling; Wenbin Liu; Yingchun Liu; Yuexin Liu; Yiling Lu; Gordon Mills; Sam Ng; Michael S Noble; Evan Paull; Arvind Rao; Sheila Reynolds; Gordon Saksena; Zack Sanborn; Chris Sander; Nikolaus Schultz; Yasin Senbabaoglu; Ronglai Shen; Ilya Shmulevich; Rileen Sinha; Josh Stuart; S Onur Sumer; Yichao Sun; Natalie Tasman; Barry S Taylor; Doug Voet; Nils Weinhold; John N Weinstein; Da Yang; Kosuke Yoshihara; Siyuan Zheng; Wei Zhang; Lihua Zou; Ty Abel; Sara Sadeghi; Mark L Cohen; Jenny Eschbacher; Eyas M Hattab; Aditya Raghunathan; Matthew J Schniederjan; Dina Aziz; Gene Barnett; Wendi Barrett; Darell D Bigner; Lori Boice; Cathy Brewer; Chiara Calatozzolo; Benito Campos; Carlos Gilberto Carlotti; Timothy A Chan; Lucia Cuppini; Erin Curley; Stefania Cuzzubbo; Karen Devine; Francesco DiMeco; Rebecca Duell; J Bradley Elder; Ashley Fehrenbach; Gaetano Finocchiaro; William Friedman; Jordonna Fulop; Johanna Gardner; Beth Hermes; Christel Herold-Mende; Christine Jungk; Ady Kendler; Norman L Lehman; Eric Lipp; Ouida Liu; Randy Mandt; Mary McGraw; Roger Mclendon; Christopher McPherson; Luciano Neder; Phuong Nguyen; Ardene Noss; Raffaele Nunziata; Quinn T Ostrom; Cheryl Palmer; Alessandro Perin; Bianca Pollo; Alexander Potapov; Olga Potapova; W Kimryn Rathmell; Daniil Rotin; Lisa Scarpace; Cathy Schilero; Kelly Senecal; Kristen Shimmel; Vsevolod Shurkhay; Suzanne Sifri; Rosy Singh; Andrew E Sloan; Kathy Smolenski; Susan M Staugaitis; Ruth Steele; Leigh Thorne; Daniela P C Tirapelli; Andreas Unterberg; Mahitha Vallurupalli; Yun Wang; Ronald Warnick; Felicia Williams; Yingli Wolinsky; Sue Bell; Mara Rosenberg; Chip Stewart; Franklin Huang; Jonna L Grimsby; Amie J Radenbaugh; Jianan Zhang Journal: N Engl J Med Date: 2015-06-10 Impact factor: 91.245
Authors: David N Louis; Arie Perry; Guido Reifenberger; Andreas von Deimling; Dominique Figarella-Branger; Webster K Cavenee; Hiroko Ohgaki; Otmar D Wiestler; Paul Kleihues; David W Ellison Journal: Acta Neuropathol Date: 2016-05-09 Impact factor: 17.088
Authors: Rajan Jain; Derek R Johnson; Sohil H Patel; Mauricio Castillo; Marion Smits; Martin J van den Bent; Andrew S Chi; Daniel P Cahill Journal: Neuro Oncol Date: 2020-07-07 Impact factor: 12.300
Authors: Vincent K Y Ho; Jaap C Reijneveld; Roelien H Enting; Henri P Bienfait; Pierre Robe; Brigitta G Baumert; Otto Visser Journal: Eur J Cancer Date: 2014-06-24 Impact factor: 9.162
Authors: Martinus P G Broen; Marion Smits; Maarten M J Wijnenga; Hendrikus J Dubbink; Monique H M E Anten; Olaf E M G Schijns; Jan Beckervordersandforth; Alida A Postma; Martin J van den Bent Journal: Neuro Oncol Date: 2018-09-03 Impact factor: 13.029
Authors: Russell T Shinohara; Elizabeth M Sweeney; Jeff Goldsmith; Navid Shiee; Farrah J Mateen; Peter A Calabresi; Samson Jarso; Dzung L Pham; Daniel S Reich; Ciprian M Crainiceanu Journal: Neuroimage Clin Date: 2014-08-15 Impact factor: 4.881