Invasion and proliferation kinetics in enhancing gliomas predict IDH1 mutation status.
BACKGROUND
Glioblastomas with a specific mutation in the isocitrate dehydrogenase 1 (IDH1) gene have a better prognosis than gliomas with wild-type IDH1.


METHODS
Here we compare the IDH1 mutational status in 172 contrast-enhancing glioma patients with the invasion profile generated by a patient-specific mathematical model we developed based on MR imaging.


RESULTS
We show that IDH1-mutated contrast-enhancing gliomas were relatively more invasive than wild-type IDH1 for all 172 contrast-enhancing gliomas as well as the subset of 158 histologically confirmed glioblastomas. The appearance of this relatively increased, model-predicted invasive profile appears to be determined more by a lower model-predicted net proliferation rate rather than an increased model-predicted dispersal rate of the glioma cells. Receiver operator curve analysis of the model-predicted MRI-based invasion profile revealed an area under the curve of 0.91, indicative of a predictive relationship. The robustness of this relationship was tested by cross-validation analysis of the invasion profile as a predictive metric for IDH1 status.


CONCLUSIONS
The strong correlation between IDH1 mutation status and the MRI-based invasion profile suggests that use of our tumor growth model may lead to noninvasive clinical detection of IDH1 mutation status and thus lead to better treatment planning, particularly prior to surgical resection, for contrast-enhancing gliomas.
Department of Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois (A.L.B., C.B., R.C.R., K.R.S.); Northwestern Brain Tumor Institute, Robert H. Lurie Comprehensive Cancer Center, Chicago, Ilinois (A.L.B., C.B., R.C.R., K.R.S.); Department of Pathology/Neuropathology, University of Washington School of Medicine, Seattle, Washington (K.Y., S.A., M.N., S.K.J.); Department of Pathology/Neuropathology, Stanford University, Stanford, California (D.E.B.); Department of Radiation Oncology, University of Washington School of Medicine, Seattle Washington (A.D.T., J.K.R.); Department of Integrated Mathematical Oncology, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida (D.B., J.S.); Department of Neurological Surgery, Columbia University, New York, New York (H.M., A.M.S.); Department of Pathology and Cell Biology, Columbia University, New York, New York (P.C.); Department of Neurology, University of Washington School of Medicine, Seattle, Washington (M.M.M.); Department of Applied Mathematics, University of Washington, Seattle, Washington (R.C.R., K.R.S.); Department of Engineering Sciences and Applied Mathematics, Northwestern University, Evanston, Illinois (K.R.S.).
Anne L
AL
Baldock
Department of Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois (A.L.B., C.B., R.C.R., K.R.S.); Northwestern Brain Tumor Institute, Robert H. Lurie Comprehensive Cancer Center, Chicago, Ilinois (A.L.B., C.B., R.C.R., K.R.S.); Department of Pathology/Neuropathology, University of Washington School of Medicine, Seattle, Washington (K.Y., S.A., M.N., S.K.J.); Department of Pathology/Neuropathology, Stanford University, Stanford, California (D.E.B.); Department of Radiation Oncology, University of Washington School of Medicine, Seattle Washington (A.D.T., J.K.R.); Department of Integrated Mathematical Oncology, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida (D.B., J.S.); Department of Neurological Surgery, Columbia University, New York, New York (H.M., A.M.S.); Department of Pathology and Cell Biology, Columbia University, New York, New York (P.C.); Department of Neurology, University of Washington School of Medicine, Seattle, Washington (M.M.M.); Department of Applied Mathematics, University of Washington, Seattle, Washington (R.C.R., K.R.S.); Department of Engineering Sciences and Applied Mathematics, Northwestern University, Evanston, Illinois (K.R.S.).
Kevin
K
Yagle
Department of Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois (A.L.B., C.B., R.C.R., K.R.S.); Northwestern Brain Tumor Institute, Robert H. Lurie Comprehensive Cancer Center, Chicago, Ilinois (A.L.B., C.B., R.C.R., K.R.S.); Department of Pathology/Neuropathology, University of Washington School of Medicine, Seattle, Washington (K.Y., S.A., M.N., S.K.J.); Department of Pathology/Neuropathology, Stanford University, Stanford, California (D.E.B.); Department of Radiation Oncology, University of Washington School of Medicine, Seattle Washington (A.D.T., J.K.R.); Department of Integrated Mathematical Oncology, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida (D.B., J.S.); Department of Neurological Surgery, Columbia University, New York, New York (H.M., A.M.S.); Department of Pathology and Cell Biology, Columbia University, New York, New York (P.C.); Department of Neurology, University of Washington School of Medicine, Seattle, Washington (M.M.M.); Department of Applied Mathematics, University of Washington, Seattle, Washington (R.C.R., K.R.S.); Department of Engineering Sciences and Applied Mathematics, Northwestern University, Evanston, Illinois (K.R.S.).
Donald E
DE
Born
Department of Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois (A.L.B., C.B., R.C.R., K.R.S.); Northwestern Brain Tumor Institute, Robert H. Lurie Comprehensive Cancer Center, Chicago, Ilinois (A.L.B., C.B., R.C.R., K.R.S.); Department of Pathology/Neuropathology, University of Washington School of Medicine, Seattle, Washington (K.Y., S.A., M.N., S.K.J.); Department of Pathology/Neuropathology, Stanford University, Stanford, California (D.E.B.); Department of Radiation Oncology, University of Washington School of Medicine, Seattle Washington (A.D.T., J.K.R.); Department of Integrated Mathematical Oncology, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida (D.B., J.S.); Department of Neurological Surgery, Columbia University, New York, New York (H.M., A.M.S.); Department of Pathology and Cell Biology, Columbia University, New York, New York (P.C.); Department of Neurology, University of Washington School of Medicine, Seattle, Washington (M.M.M.); Department of Applied Mathematics, University of Washington, Seattle, Washington (R.C.R., K.R.S.); Department of Engineering Sciences and Applied Mathematics, Northwestern University, Evanston, Illinois (K.R.S.).
Sunyoung
S
Ahn
Department of Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois (A.L.B., C.B., R.C.R., K.R.S.); Northwestern Brain Tumor Institute, Robert H. Lurie Comprehensive Cancer Center, Chicago, Ilinois (A.L.B., C.B., R.C.R., K.R.S.); Department of Pathology/Neuropathology, University of Washington School of Medicine, Seattle, Washington (K.Y., S.A., M.N., S.K.J.); Department of Pathology/Neuropathology, Stanford University, Stanford, California (D.E.B.); Department of Radiation Oncology, University of Washington School of Medicine, Seattle Washington (A.D.T., J.K.R.); Department of Integrated Mathematical Oncology, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida (D.B., J.S.); Department of Neurological Surgery, Columbia University, New York, New York (H.M., A.M.S.); Department of Pathology and Cell Biology, Columbia University, New York, New York (P.C.); Department of Neurology, University of Washington School of Medicine, Seattle, Washington (M.M.M.); Department of Applied Mathematics, University of Washington, Seattle, Washington (R.C.R., K.R.S.); Department of Engineering Sciences and Applied Mathematics, Northwestern University, Evanston, Illinois (K.R.S.).
Andrew D
AD
Trister
Department of Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois (A.L.B., C.B., R.C.R., K.R.S.); Northwestern Brain Tumor Institute, Robert H. Lurie Comprehensive Cancer Center, Chicago, Ilinois (A.L.B., C.B., R.C.R., K.R.S.); Department of Pathology/Neuropathology, University of Washington School of Medicine, Seattle, Washington (K.Y., S.A., M.N., S.K.J.); Department of Pathology/Neuropathology, Stanford University, Stanford, California (D.E.B.); Department of Radiation Oncology, University of Washington School of Medicine, Seattle Washington (A.D.T., J.K.R.); Department of Integrated Mathematical Oncology, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida (D.B., J.S.); Department of Neurological Surgery, Columbia University, New York, New York (H.M., A.M.S.); Department of Pathology and Cell Biology, Columbia University, New York, New York (P.C.); Department of Neurology, University of Washington School of Medicine, Seattle, Washington (M.M.M.); Department of Applied Mathematics, University of Washington, Seattle, Washington (R.C.R., K.R.S.); Department of Engineering Sciences and Applied Mathematics, Northwestern University, Evanston, Illinois (K.R.S.).
Maxwell
M
Neal
Department of Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois (A.L.B., C.B., R.C.R., K.R.S.); Northwestern Brain Tumor Institute, Robert H. Lurie Comprehensive Cancer Center, Chicago, Ilinois (A.L.B., C.B., R.C.R., K.R.S.); Department of Pathology/Neuropathology, University of Washington School of Medicine, Seattle, Washington (K.Y., S.A., M.N., S.K.J.); Department of Pathology/Neuropathology, Stanford University, Stanford, California (D.E.B.); Department of Radiation Oncology, University of Washington School of Medicine, Seattle Washington (A.D.T., J.K.R.); Department of Integrated Mathematical Oncology, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida (D.B., J.S.); Department of Neurological Surgery, Columbia University, New York, New York (H.M., A.M.S.); Department of Pathology and Cell Biology, Columbia University, New York, New York (P.C.); Department of Neurology, University of Washington School of Medicine, Seattle, Washington (M.M.M.); Department of Applied Mathematics, University of Washington, Seattle, Washington (R.C.R., K.R.S.); Department of Engineering Sciences and Applied Mathematics, Northwestern University, Evanston, Illinois (K.R.S.).
Sandra K
SK
Johnston
Department of Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois (A.L.B., C.B., R.C.R., K.R.S.); Northwestern Brain Tumor Institute, Robert H. Lurie Comprehensive Cancer Center, Chicago, Ilinois (A.L.B., C.B., R.C.R., K.R.S.); Department of Pathology/Neuropathology, University of Washington School of Medicine, Seattle, Washington (K.Y., S.A., M.N., S.K.J.); Department of Pathology/Neuropathology, Stanford University, Stanford, California (D.E.B.); Department of Radiation Oncology, University of Washington School of Medicine, Seattle Washington (A.D.T., J.K.R.); Department of Integrated Mathematical Oncology, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida (D.B., J.S.); Department of Neurological Surgery, Columbia University, New York, New York (H.M., A.M.S.); Department of Pathology and Cell Biology, Columbia University, New York, New York (P.C.); Department of Neurology, University of Washington School of Medicine, Seattle, Washington (M.M.M.); Department of Applied Mathematics, University of Washington, Seattle, Washington (R.C.R., K.R.S.); Department of Engineering Sciences and Applied Mathematics, Northwestern University, Evanston, Illinois (K.R.S.).
Carly A
CA
Bridge
Department of Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois (A.L.B., C.B., R.C.R., K.R.S.); Northwestern Brain Tumor Institute, Robert H. Lurie Comprehensive Cancer Center, Chicago, Ilinois (A.L.B., C.B., R.C.R., K.R.S.); Department of Pathology/Neuropathology, University of Washington School of Medicine, Seattle, Washington (K.Y., S.A., M.N., S.K.J.); Department of Pathology/Neuropathology, Stanford University, Stanford, California (D.E.B.); Department of Radiation Oncology, University of Washington School of Medicine, Seattle Washington (A.D.T., J.K.R.); Department of Integrated Mathematical Oncology, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida (D.B., J.S.); Department of Neurological Surgery, Columbia University, New York, New York (H.M., A.M.S.); Department of Pathology and Cell Biology, Columbia University, New York, New York (P.C.); Department of Neurology, University of Washington School of Medicine, Seattle, Washington (M.M.M.); Department of Applied Mathematics, University of Washington, Seattle, Washington (R.C.R., K.R.S.); Department of Engineering Sciences and Applied Mathematics, Northwestern University, Evanston, Illinois (K.R.S.).
David
D
Basanta
Department of Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois (A.L.B., C.B., R.C.R., K.R.S.); Northwestern Brain Tumor Institute, Robert H. Lurie Comprehensive Cancer Center, Chicago, Ilinois (A.L.B., C.B., R.C.R., K.R.S.); Department of Pathology/Neuropathology, University of Washington School of Medicine, Seattle, Washington (K.Y., S.A., M.N., S.K.J.); Department of Pathology/Neuropathology, Stanford University, Stanford, California (D.E.B.); Department of Radiation Oncology, University of Washington School of Medicine, Seattle Washington (A.D.T., J.K.R.); Department of Integrated Mathematical Oncology, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida (D.B., J.S.); Department of Neurological Surgery, Columbia University, New York, New York (H.M., A.M.S.); Department of Pathology and Cell Biology, Columbia University, New York, New York (P.C.); Department of Neurology, University of Washington School of Medicine, Seattle, Washington (M.M.M.); Department of Applied Mathematics, University of Washington, Seattle, Washington (R.C.R., K.R.S.); Department of Engineering Sciences and Applied Mathematics, Northwestern University, Evanston, Illinois (K.R.S.).
Jacob
J
Scott
Department of Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois (A.L.B., C.B., R.C.R., K.R.S.); Northwestern Brain Tumor Institute, Robert H. Lurie Comprehensive Cancer Center, Chicago, Ilinois (A.L.B., C.B., R.C.R., K.R.S.); Department of Pathology/Neuropathology, University of Washington School of Medicine, Seattle, Washington (K.Y., S.A., M.N., S.K.J.); Department of Pathology/Neuropathology, Stanford University, Stanford, California (D.E.B.); Department of Radiation Oncology, University of Washington School of Medicine, Seattle Washington (A.D.T., J.K.R.); Department of Integrated Mathematical Oncology, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida (D.B., J.S.); Department of Neurological Surgery, Columbia University, New York, New York (H.M., A.M.S.); Department of Pathology and Cell Biology, Columbia University, New York, New York (P.C.); Department of Neurology, University of Washington School of Medicine, Seattle, Washington (M.M.M.); Department of Applied Mathematics, University of Washington, Seattle, Washington (R.C.R., K.R.S.); Department of Engineering Sciences and Applied Mathematics, Northwestern University, Evanston, Illinois (K.R.S.).
Hani
H
Malone
Department of Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois (A.L.B., C.B., R.C.R., K.R.S.); Northwestern Brain Tumor Institute, Robert H. Lurie Comprehensive Cancer Center, Chicago, Ilinois (A.L.B., C.B., R.C.R., K.R.S.); Department of Pathology/Neuropathology, University of Washington School of Medicine, Seattle, Washington (K.Y., S.A., M.N., S.K.J.); Department of Pathology/Neuropathology, Stanford University, Stanford, California (D.E.B.); Department of Radiation Oncology, University of Washington School of Medicine, Seattle Washington (A.D.T., J.K.R.); Department of Integrated Mathematical Oncology, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida (D.B., J.S.); Department of Neurological Surgery, Columbia University, New York, New York (H.M., A.M.S.); Department of Pathology and Cell Biology, Columbia University, New York, New York (P.C.); Department of Neurology, University of Washington School of Medicine, Seattle, Washington (M.M.M.); Department of Applied Mathematics, University of Washington, Seattle, Washington (R.C.R., K.R.S.); Department of Engineering Sciences and Applied Mathematics, Northwestern University, Evanston, Illinois (K.R.S.).
Adam M
AM
Sonabend
Department of Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois (A.L.B., C.B., R.C.R., K.R.S.); Northwestern Brain Tumor Institute, Robert H. Lurie Comprehensive Cancer Center, Chicago, Ilinois (A.L.B., C.B., R.C.R., K.R.S.); Department of Pathology/Neuropathology, University of Washington School of Medicine, Seattle, Washington (K.Y., S.A., M.N., S.K.J.); Department of Pathology/Neuropathology, Stanford University, Stanford, California (D.E.B.); Department of Radiation Oncology, University of Washington School of Medicine, Seattle Washington (A.D.T., J.K.R.); Department of Integrated Mathematical Oncology, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida (D.B., J.S.); Department of Neurological Surgery, Columbia University, New York, New York (H.M., A.M.S.); Department of Pathology and Cell Biology, Columbia University, New York, New York (P.C.); Department of Neurology, University of Washington School of Medicine, Seattle, Washington (M.M.M.); Department of Applied Mathematics, University of Washington, Seattle, Washington (R.C.R., K.R.S.); Department of Engineering Sciences and Applied Mathematics, Northwestern University, Evanston, Illinois (K.R.S.).
Peter
P
Canoll
Department of Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois (A.L.B., C.B., R.C.R., K.R.S.); Northwestern Brain Tumor Institute, Robert H. Lurie Comprehensive Cancer Center, Chicago, Ilinois (A.L.B., C.B., R.C.R., K.R.S.); Department of Pathology/Neuropathology, University of Washington School of Medicine, Seattle, Washington (K.Y., S.A., M.N., S.K.J.); Department of Pathology/Neuropathology, Stanford University, Stanford, California (D.E.B.); Department of Radiation Oncology, University of Washington School of Medicine, Seattle Washington (A.D.T., J.K.R.); Department of Integrated Mathematical Oncology, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida (D.B., J.S.); Department of Neurological Surgery, Columbia University, New York, New York (H.M., A.M.S.); Department of Pathology and Cell Biology, Columbia University, New York, New York (P.C.); Department of Neurology, University of Washington School of Medicine, Seattle, Washington (M.M.M.); Department of Applied Mathematics, University of Washington, Seattle, Washington (R.C.R., K.R.S.); Department of Engineering Sciences and Applied Mathematics, Northwestern University, Evanston, Illinois (K.R.S.).
Maciej M
MM
Mrugala
Department of Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois (A.L.B., C.B., R.C.R., K.R.S.); Northwestern Brain Tumor Institute, Robert H. Lurie Comprehensive Cancer Center, Chicago, Ilinois (A.L.B., C.B., R.C.R., K.R.S.); Department of Pathology/Neuropathology, University of Washington School of Medicine, Seattle, Washington (K.Y., S.A., M.N., S.K.J.); Department of Pathology/Neuropathology, Stanford University, Stanford, California (D.E.B.); Department of Radiation Oncology, University of Washington School of Medicine, Seattle Washington (A.D.T., J.K.R.); Department of Integrated Mathematical Oncology, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida (D.B., J.S.); Department of Neurological Surgery, Columbia University, New York, New York (H.M., A.M.S.); Department of Pathology and Cell Biology, Columbia University, New York, New York (P.C.); Department of Neurology, University of Washington School of Medicine, Seattle, Washington (M.M.M.); Department of Applied Mathematics, University of Washington, Seattle, Washington (R.C.R., K.R.S.); Department of Engineering Sciences and Applied Mathematics, Northwestern University, Evanston, Illinois (K.R.S.).
Jason K
JK
Rockhill
Department of Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois (A.L.B., C.B., R.C.R., K.R.S.); Northwestern Brain Tumor Institute, Robert H. Lurie Comprehensive Cancer Center, Chicago, Ilinois (A.L.B., C.B., R.C.R., K.R.S.); Department of Pathology/Neuropathology, University of Washington School of Medicine, Seattle, Washington (K.Y., S.A., M.N., S.K.J.); Department of Pathology/Neuropathology, Stanford University, Stanford, California (D.E.B.); Department of Radiation Oncology, University of Washington School of Medicine, Seattle Washington (A.D.T., J.K.R.); Department of Integrated Mathematical Oncology, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida (D.B., J.S.); Department of Neurological Surgery, Columbia University, New York, New York (H.M., A.M.S.); Department of Pathology and Cell Biology, Columbia University, New York, New York (P.C.); Department of Neurology, University of Washington School of Medicine, Seattle, Washington (M.M.M.); Department of Applied Mathematics, University of Washington, Seattle, Washington (R.C.R., K.R.S.); Department of Engineering Sciences and Applied Mathematics, Northwestern University, Evanston, Illinois (K.R.S.).
Russell C
RC
Rockne
Department of Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois (A.L.B., C.B., R.C.R., K.R.S.); Northwestern Brain Tumor Institute, Robert H. Lurie Comprehensive Cancer Center, Chicago, Ilinois (A.L.B., C.B., R.C.R., K.R.S.); Department of Pathology/Neuropathology, University of Washington School of Medicine, Seattle, Washington (K.Y., S.A., M.N., S.K.J.); Department of Pathology/Neuropathology, Stanford University, Stanford, California (D.E.B.); Department of Radiation Oncology, University of Washington School of Medicine, Seattle Washington (A.D.T., J.K.R.); Department of Integrated Mathematical Oncology, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida (D.B., J.S.); Department of Neurological Surgery, Columbia University, New York, New York (H.M., A.M.S.); Department of Pathology and Cell Biology, Columbia University, New York, New York (P.C.); Department of Neurology, University of Washington School of Medicine, Seattle, Washington (M.M.M.); Department of Applied Mathematics, University of Washington, Seattle, Washington (R.C.R., K.R.S.); Department of Engineering Sciences and Applied Mathematics, Northwestern University, Evanston, Illinois (K.R.S.).
Kristin R
KR
Swanson
D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology*; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D007700:Kinetics; D009154:Mutation; D009361:Neoplasm Invasiveness
D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human
IDH1; glioma; growth kinetics; invasion; mathematical model; patient-specific; proliferation