TY - JOUR
T1 - Radiomic MRI signature reveals three distinct subtypes of glioblastoma with different clinical and molecular characteristics, offering prognostic value beyond IDH1
AU - Rathore, Saima
AU - Akbari, Hamed
AU - Rozycki, Martin
AU - Abdullah, Kalil G.
AU - Nasrallah, Maclean P.
AU - Binder, Zev A.
AU - Davuluri, Ramana V.
AU - Lustig, Robert A.
AU - Dahmane, Nadia
AU - Bilello, Michel
AU - O'Rourke, Donald M.
AU - Davatzikos, Christos
N1 - Publisher Copyright:
© 2018 The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - The remarkable heterogeneity of glioblastoma, across patients and over time, is one of the main challenges in precision diagnostics and treatment planning. Non-invasive in vivo characterization of this heterogeneity using imaging could assist in understanding disease subtypes, as well as in risk-stratification and treatment planning of glioblastoma. The current study leveraged advanced imaging analytics and radiomic approaches applied to multi-parametric MRI of de novo glioblastoma patients (n = 208 discovery, n = 53 replication), and discovered three distinct and reproducible imaging subtypes of glioblastoma, with differential clinical outcome and underlying molecular characteristics, including isocitrate dehydrogenase-1 (IDH1), O6-methylguanine-DNA methyltransferase, epidermal growth factor receptor variant III (EGFRvIII), and transcriptomic subtype composition. The subtypes provided risk-stratification substantially beyond that provided by WHO classifications. Within IDH1-wildtype tumors, our subtypes revealed different survival (p < 0.001), thereby highlighting the synergistic consideration of molecular and imaging measures for prognostication. Moreover, the imaging characteristics suggest that subtype-specific treatment of peritumoral infiltrated brain tissue might be more effective than current uniform standard-of-care. Finally, our analysis found subtype-specific radiogenomic signatures of EGFRvIII-mutated tumors. The identified subtypes and their clinical and molecular correlates provide an in vivo portrait of phenotypic heterogeneity in glioblastoma, which points to the need for precision diagnostics and personalized treatment.
AB - The remarkable heterogeneity of glioblastoma, across patients and over time, is one of the main challenges in precision diagnostics and treatment planning. Non-invasive in vivo characterization of this heterogeneity using imaging could assist in understanding disease subtypes, as well as in risk-stratification and treatment planning of glioblastoma. The current study leveraged advanced imaging analytics and radiomic approaches applied to multi-parametric MRI of de novo glioblastoma patients (n = 208 discovery, n = 53 replication), and discovered three distinct and reproducible imaging subtypes of glioblastoma, with differential clinical outcome and underlying molecular characteristics, including isocitrate dehydrogenase-1 (IDH1), O6-methylguanine-DNA methyltransferase, epidermal growth factor receptor variant III (EGFRvIII), and transcriptomic subtype composition. The subtypes provided risk-stratification substantially beyond that provided by WHO classifications. Within IDH1-wildtype tumors, our subtypes revealed different survival (p < 0.001), thereby highlighting the synergistic consideration of molecular and imaging measures for prognostication. Moreover, the imaging characteristics suggest that subtype-specific treatment of peritumoral infiltrated brain tissue might be more effective than current uniform standard-of-care. Finally, our analysis found subtype-specific radiogenomic signatures of EGFRvIII-mutated tumors. The identified subtypes and their clinical and molecular correlates provide an in vivo portrait of phenotypic heterogeneity in glioblastoma, which points to the need for precision diagnostics and personalized treatment.
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U2 - 10.1038/s41598-018-22739-2
DO - 10.1038/s41598-018-22739-2
M3 - Article
C2 - 29572492
AN - SCOPUS:85044342729
SN - 2045-2322
VL - 8
JO - Scientific reports
JF - Scientific reports
IS - 1
M1 - 5087
ER -