A Multi-parametric MRI-Based Radiomics Signature and a Practical ML Model for Stratifying Glioblastoma Patients Based on Survival Toward Precision Oncology

Purpose: Predicting patients' survival outcomes is recognized of key importance to clinicians in oncology toward determining an ideal course of treatment and patient management. This study applies radiomics analysis on pre-operative multi-parametric MRI of patients with glioblastoma from multiple institutions to identify a signature and a practical machine learning model for stratifying patients into groups based on overall survival. Methods: This study included 163 patients' data with glioblastoma, collected by BRATS 2018 Challenge from multiple institutions. In this proposed method, a set of 147 radiomics image features were extracted locally from three tumor sub-regions on standardized pre-operative multi-parametric MR images. LASSO regression was applied for identifying an informative subset of chosen features whereas a Cox model used to obtain the coefficients of those selected features. Then, a radiomics signature model of 9 features was constructed on the discovery set and it performance was evaluated for patients stratification into short- (<10 months), medium- (10–15 months), and long-survivors (>15 months) groups. Eight ML classification models, trained and then cross-validated, were tested to assess a range of survival prediction performance as a function of the choice of features. Results: The proposed mpMRI radiomics signature model had a statistically significant association with survival (P < 0.001) in the training set, but was not confirmed (P = 0.110) in the validation cohort. Its performance in the validation set had a sensitivity of 0.476 (short-), 0.231 (medium-), and 0.600 (long-survivors), and specificity of 0.667 (short-), 0.732 (medium-), and 0.794 (long-survivors). Among the tested ML classifiers, the ensemble learning model's results showed superior performance in predicting the survival classes, with an overall accuracy of 57.8% and AUC of 0.81 for short-, 0.47 for medium-, and 0.72 for long-survivors using the LASSO selected features combined with clinical factors. Conclusion: A derived GLCM feature, representing intra-tumoral inhomogeneity, was found to have a high association with survival. Clinical factors, when added to the radiomics image features, boosted the performance of the ML classification model in predicting individual glioblastoma patient's survival prognosis, which can improve prognostic quality a further step toward precision oncology.

[1]  Paul Kinahan,et al.  Radiomics: Images Are More than Pictures, They Are Data , 2015, Radiology.

[2]  Matthew Toews,et al.  Radiomic analysis of multi-contrast brain MRI for the prediction of survival in patients with glioblastoma multiforme , 2016, 2016 38th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC).

[3]  Camel Tanougast,et al.  A quantitative study of shape descriptors from glioblastoma multiforme phenotypes for predicting survival outcome. , 2016, The British journal of radiology.

[4]  R. Barnard The classification of tumours of the central nervous system. , 1982, Neuropathology and applied neurobiology.

[5]  Luke Macyszyn,et al.  Imaging patterns predict patient survival and molecular subtype in glioblastoma via machine learning techniques. , 2016, Neuro-oncology.

[6]  Matthew Toews,et al.  Novel Radiomic Features Based on Joint Intensity Matrices for Predicting Glioblastoma Patient Survival Time , 2019, IEEE Journal of Biomedical and Health Informatics.

[7]  Alexander F. I. Osman,et al.  Automated Brain Tumor Segmentation on Magnetic Resonance Images and Patient's Overall Survival Prediction Using Support Vector Machines , 2017, BrainLes@MICCAI.

[8]  Ahmad Chaddad,et al.  Prediction of survival with multi-scale radiomic analysis in glioblastoma patients , 2018, Medical & Biological Engineering & Computing.

[9]  A. Madabhushi,et al.  Radiomic features from the peritumoral brain parenchyma on treatment-naïve multi-parametric MR imaging predict long versus short-term survival in glioblastoma multiforme: Preliminary findings , 2017, European Radiology.

[10]  Erwin G. Van Meir,et al.  Exciting New Advances in Neuro‐Oncology: The Avenue to a Cure for Malignant Glioma , 2010, CA: a cancer journal for clinicians.

[11]  Emanuele Trucco,et al.  Computer and Robot Vision , 1995 .

[12]  G. Collewet,et al.  Influence of MRI acquisition protocols and image intensity normalization methods on texture classification. , 2004, Magnetic resonance imaging.

[13]  Juan J. Martinez,et al.  Evaluation of tumor-derived MRI-texture features for discrimination of molecular subtypes and prediction of 12-month survival status in glioblastoma. , 2015, Medical physics.

[14]  Christos Davatzikos,et al.  Advancing The Cancer Genome Atlas glioma MRI collections with expert segmentation labels and radiomic features , 2017, Scientific Data.

[15]  E. Holland Progenitor cells and glioma formation , 2001, Current opinion in neurology.

[16]  Brian B. Avants,et al.  The Multimodal Brain Tumor Image Segmentation Benchmark (BRATS) , 2015, IEEE Transactions on Medical Imaging.

[17]  Yang Jie,et al.  The multimodal brain tumor image segmentation based on convolutional neural networks , 2017, 2017 2nd IEEE International Conference on Computational Intelligence and Applications (ICCIA).

[18]  R. Tibshirani The lasso method for variable selection in the Cox model. , 1997, Statistics in medicine.

[19]  D. Dong,et al.  Development and Validation of a MRI-Based Radiomics Prognostic Classifier in Patients with Primary Glioblastoma Multiforme. , 2019, Academic radiology.

[20]  Bill Triggs,et al.  Histograms of oriented gradients for human detection , 2005, 2005 IEEE Computer Society Conference on Computer Vision and Pattern Recognition (CVPR'05).

[21]  Eric C Leuthardt,et al.  Molecular and cellular heterogeneity: the hallmark of glioblastoma. , 2014, Neurosurgical focus.

[22]  V. Vapnik Estimation of Dependences Based on Empirical Data , 2006 .

[23]  Georg Heinze,et al.  Variable selection – A review and recommendations for the practicing statistician , 2018, Biometrical journal. Biometrische Zeitschrift.

[24]  R. Tibshirani Regression Shrinkage and Selection via the Lasso , 1996 .

[25]  D. Dong,et al.  Radiomics Features of Multiparametric MRI as Novel Prognostic Factors in Advanced Nasopharyngeal Carcinoma , 2017, Clinical Cancer Research.

[26]  Matti Pietikäinen,et al.  Multiresolution Gray-Scale and Rotation Invariant Texture Classification with Local Binary Patterns , 2002, IEEE Trans. Pattern Anal. Mach. Intell..

[27]  Robert M. Haralick,et al.  Textural Features for Image Classification , 1973, IEEE Trans. Syst. Man Cybern..

[28]  B. Ang,et al.  Overall survival prediction in glioblastoma multiforme patients from volumetric, shape and texture features using machine learning. , 2018, Surgical oncology.

[29]  Zev A. Binder,et al.  Radiomic MRI signature reveals three distinct subtypes of glioblastoma with different clinical and molecular characteristics, offering prognostic value beyond IDH1 , 2018, Scientific Reports.

[30]  R. Kay The Analysis of Survival Data , 2012 .

[31]  G. McLachlan Discriminant Analysis and Statistical Pattern Recognition , 1992 .

[32]  Edward A. Patrick,et al.  A Generalized k-Nearest Neighbor Rule , 1970, Inf. Control..

[33]  Guangtao Zhai,et al.  A Deep Learning-Based Radiomics Model for Prediction of Survival in Glioblastoma Multiforme , 2017, Scientific Reports.

[34]  Tamim Niazi,et al.  Radiomics in Glioblastoma: Current Status and Challenges Facing Clinical Implementation , 2019, Front. Oncol..

[35]  R. Subramaniam Precision Medicine and PET/Computed Tomography: Challenges and Implementation. , 2017, PET clinics.

[36]  N. Meinshausen,et al.  High-dimensional graphs and variable selection with the Lasso , 2006, math/0608017.

[37]  Hongbing Lu,et al.  The effect of glioblastoma heterogeneity on survival stratification: a multimodal MR imaging texture analysis , 2018, Acta radiologica.

[38]  P. Kleihues,et al.  Population-based studies on incidence, survival rates, and genetic alterations in astrocytic and oligodendroglial gliomas. , 2005, Journal of neuropathology and experimental neurology.

[39]  Maximilian Reiser,et al.  Radiomic Analysis Reveals Prognostic Information in T1-Weighted Baseline Magnetic Resonance Imaging in Patients With Glioblastoma , 2017, Investigative radiology.

[40]  David T. W. Jones,et al.  Radiomic subtyping improves disease stratification beyond key molecular, clinical, and standard imaging characteristics in patients with glioblastoma , 2018, Neuro-oncology.

[41]  Sean D. McGarry,et al.  Magnetic Resonance Imaging-Based Radiomic Profiles Predict Patient Prognosis in Newly Diagnosed Glioblastoma Before Therapy , 2016, Tomography.

[42]  Ahmad Chaddad,et al.  Radiomics texture feature extraction for characterizing GBM phenotypes using GLCM , 2015, 2015 IEEE 12th International Symposium on Biomedical Imaging (ISBI).

[43]  T. Jiang,et al.  A radiomic signature as a non-invasive predictor of progression-free survival in patients with lower-grade gliomas , 2018, NeuroImage: Clinical.

[44]  et al.,et al.  Identifying the Best Machine Learning Algorithms for Brain Tumor Segmentation, Progression Assessment, and Overall Survival Prediction in the BRATS Challenge , 2018, ArXiv.

[45]  Tin Kam Ho,et al.  The Random Subspace Method for Constructing Decision Forests , 1998, IEEE Trans. Pattern Anal. Mach. Intell..

[46]  Weiwei Zong,et al.  Abstract 3351: Overall survival prediction of glioblastoma patients combining clinical factors with texture features extracted from 3-D convolutional neural networks , 2019, Science and Health Policy.

[47]  Guigang Zhang,et al.  Deep Learning , 2016, Int. J. Semantic Comput..