Deep Learning of Imaging Phenotype and Genotype for Predicting Overall Survival Time of Glioblastoma Patients

Glioblastoma (GBM) is the most common and deadly malignant brain tumor. For personalized treatment, an accurate pre-operative prognosis for GBM patients is highly desired. Recently, many machine learning-based methods have been adopted to predict overall survival (OS) time based on the pre-operative mono- or multi-modal imaging phenotype. The genotypic information of GBM has been proven to be strongly indicative of the prognosis; however, this has not been considered in the existing imaging-based OS prediction methods. The main reason is that the tumor genotype is unavailable pre-operatively unless deriving from craniotomy. In this paper, we propose a new deep learning-based OS prediction method for GBM patients, which can derive tumor genotype-related features from pre-operative multimodal magnetic resonance imaging (MRI) brain data and feed them to OS prediction. Specifically, we propose a multi-task convolutional neural network (CNN) to accomplish both tumor genotype and OS prediction tasks jointly. As the network can benefit from learning tumor genotype-related features for genotype prediction, the accuracy of predicting OS time can be prominently improved. In the experiments, multimodal MRI brain dataset of 120 GBM patients, with as many as four different genotypic/molecular biomarkers, are used to evaluate our method. Our method achieves the highest OS prediction accuracy compared to other state-of-the-art methods.

[1]  T. Makabe,et al.  Assessment of the pathological grade of astrocytic gliomas using an MRI score , 1994, Neuroradiology.

[2]  Candace Chisolm,et al.  Glioblastoma with Oligodendroglioma Component (GBM‐O): Molecular Genetic and Clinical Characteristics , 2013, Brain pathology.

[3]  Jagadeesan Jayender,et al.  Multimodal imaging for improved diagnosis and treatment of cancers , 2015, Cancer.

[4]  Geoffrey E. Hinton,et al.  ImageNet classification with deep convolutional neural networks , 2012, Commun. ACM.

[5]  Ron Kohavi,et al.  A Study of Cross-Validation and Bootstrap for Accuracy Estimation and Model Selection , 1995, IJCAI.

[6]  Jill S Barnholtz-Sloan,et al.  CBTRUS Statistical Report: Primary brain and other central nervous system tumors diagnosed in the United States in 2010–2014 , 2017, Neuro-oncology.

[7]  Michael Kistler,et al.  The Virtual Skeleton Database: An Open Access Repository for Biomedical Research and Collaboration , 2013, Journal of medical Internet research.

[8]  E. Miyaoka,et al.  A combination of TERT promoter mutation and MGMT methylation status predicts clinically relevant subgroups of newly diagnosed glioblastomas , 2016, Acta neuropathologica communications.

[9]  Pieter Wesseling,et al.  The combination of IDH1 mutations and MGMT methylation status predicts survival in glioblastoma better than either IDH1 or MGMT alone. , 2014, Neuro-oncology.

[10]  Christopher Nimsky,et al.  Gliomas: histopathologic evaluation of changes in directionality and magnitude of water diffusion at diffusion-tensor MR imaging. , 2006, Radiology.

[11]  G. Johnson,et al.  Peritumoral diffusion tensor imaging of high-grade gliomas and metastatic brain tumors. , 2003, AJNR. American journal of neuroradiology.

[12]  Andriy Fedorov,et al.  Computational Radiomics System to Decode the Radiographic Phenotype. , 2017, Cancer research.

[13]  Peter Chang,et al.  Imaging Genetic Heterogeneity in Glioblastoma and Other Glial Tumors: Review of Current Methods and Future Directions. , 2018, AJR. American journal of roentgenology.

[14]  Darell D. Bigner,et al.  Mutations in IDH1, IDH2, and in the TERT promoter define clinically distinct subgroups of adult malignant gliomas , 2014, Oncotarget.

[15]  Shahram Latifi,et al.  Machine Learning and Deep Learning Techniques to Predict Overall Survival of Brain Tumor Patients using MRI Images , 2017, 2017 IEEE 17th International Conference on Bioinformatics and Bioengineering (BIBE).

[16]  Joseph O. Deasy,et al.  A Validated Prediction Model for Overall Survival From Stage III Non-Small Cell Lung Cancer: Toward Survival Prediction for Individual Patients , 2015, International journal of radiation oncology, biology, physics.

[17]  W. Cavenee,et al.  Heterogeneity maintenance in glioblastoma: a social network. , 2011, Cancer research.

[18]  Annette M. Molinaro,et al.  Characterization of Metabolic, Diffusion, and Perfusion Properties in GBM: Contrast-Enhancing versus Non-Enhancing Tumor12 , 2017, Translational oncology.

[19]  Ken-ichi Funahashi,et al.  On the approximate realization of continuous mappings by neural networks , 1989, Neural Networks.

[20]  Lloyd D. Fisher,et al.  Fixed Effects Analysis of Variance , 2014 .

[21]  Dinggang Shen,et al.  3D Deep Learning for Multi-modal Imaging-Guided Survival Time Prediction of Brain Tumor Patients , 2016, MICCAI.

[22]  J. Barnholtz-Sloan,et al.  CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2007-2011. , 2012, Neuro-oncology.

[23]  Glyn Johnson,et al.  Diffusion-tensor MR imaging of intracranial neoplasia and associated peritumoral edema: introduction of the tumor infiltration index. , 2004, Radiology.

[24]  Markus Neuhäuser,et al.  Wilcoxon Signed Rank Test , 2006 .

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

[26]  Dinggang Shen,et al.  Outcome Prediction for Patient with High-Grade Gliomas from Brain Functional and Structural Networks , 2016, MICCAI.

[27]  F. Cartes-Zumelzu,et al.  MRI for brain tumours: a multimodality approach , 2009 .

[28]  Isabelle Camby,et al.  Present and potential future issues in glioblastoma treatment , 2006, Expert review of anticancer therapy.

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

[30]  Anne Clavreul,et al.  Toward an effective strategy in glioblastoma treatment. Part I: resistance mechanisms and strategies to overcome resistance of glioblastoma to temozolomide. , 2015, Drug discovery today.

[31]  Víctor M. Pérez-García,et al.  Towards Uncertainty-Assisted Brain Tumor Segmentation and Survival Prediction , 2017, BrainLes@MICCAI.

[32]  Margaret Wrensch,et al.  Epidemiology and molecular pathology of glioma , 2006, Nature Clinical Practice Neurology.

[33]  G. Reifenberger,et al.  MGMT promoter methylation in malignant gliomas: ready for personalized medicine? , 2010, Nature Reviews Neurology.

[34]  E. Kaplan,et al.  Nonparametric Estimation from Incomplete Observations , 1958 .

[35]  Jürgen Scheins,et al.  Multimodal imaging utilising integrated MR-PET for human brain tumour assessment , 2012, European Radiology.

[36]  R. Jain,et al.  Deep learning for prediction of survival in idh wild-type gliomas , 2017, Journal of the Neurological Sciences.

[37]  Ying Mao,et al.  “Awake” intraoperative functional MRI (ai-fMRI) for mapping the eloquent cortex: Is it possible in awake craniotomy?☆ , 2012, NeuroImage: Clinical.

[38]  Alexander F. I. Osman,et al.  A Multi-parametric MRI-Based Radiomics Signature and a Practical ML Model for Stratifying Glioblastoma Patients Based on Survival Toward Precision Oncology , 2019, Front. Comput. Neurosci..

[39]  Otmar Schober,et al.  Multimodal Imaging of Patients With Gliomas Confirms 11C-MET PET as a Complementary Marker to MRI for Noninvasive Tumor Grading and Intraindividual Follow-Up After Therapy , 2017, Molecular imaging.

[40]  Dinggang Shen,et al.  Multi-Label Nonlinear Matrix Completion With Transductive Multi-Task Feature Selection for Joint MGMT and IDH1 Status Prediction of Patient With High-Grade Gliomas , 2018, IEEE Transactions on Medical Imaging.

[41]  Yanqi Huang,et al.  Radiomics Signature: A Potential Biomarker for the Prediction of Disease-Free Survival in Early-Stage (I or II) Non-Small Cell Lung Cancer. , 2016, Radiology.

[42]  Daniel J Brat,et al.  Genetic Markers in Glioblastoma: Prognostic Significance and Future Therapeutic Implications: On: Impact of Genotype Morphology on the Prognosis of Glioblastoma. Schmidt MC Antweiler S, Urban N, et al. J Neuropathol Exp Neurol 2002;61:321–328. , 2003, Advances in anatomic pathology.

[43]  B. Scheithauer,et al.  The New WHO Classification of Brain Tumours , 1993, Brain pathology.

[44]  Dinggang Shen,et al.  Overall survival time prediction for high-grade glioma patients based on large-scale brain functional networks , 2018, Brain Imaging and Behavior.

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

[46]  Dinggang Shen,et al.  Robust Deformable-Surface-Based Skull-Stripping for Large-Scale Studies , 2011, MICCAI.

[47]  Pieter Wesseling,et al.  Oligodendroglioma: pathology, molecular mechanisms and markers , 2015, Acta Neuropathologica.

[48]  Andreas Christmann,et al.  Support vector machines , 2008, Data Mining and Knowledge Discovery Handbook.

[49]  Liang Ruofei,et al.  TERT mutation in glioma: Frequency, prognosis and risk , 2016, Journal of Clinical Neuroscience.

[50]  Jieping Ye,et al.  Large-scale sparse logistic regression , 2009, KDD.

[51]  N. Mantel Evaluation of survival data and two new rank order statistics arising in its consideration. , 1966, Cancer chemotherapy reports.

[52]  Pengfei Xu,et al.  PANDA: a pipeline toolbox for analyzing brain diffusion images , 2013, Front. Hum. Neurosci..

[53]  Andy Liaw,et al.  Classification and Regression by randomForest , 2007 .

[54]  Dinggang Shen,et al.  Multi-Channel 3D Deep Feature Learning for Survival Time Prediction of Brain Tumor Patients Using Multi-Modal Neuroimages , 2019, Scientific Reports.

[55]  Paul S Mischel,et al.  MR imaging correlates of survival in patients with high-grade gliomas. , 2005, AJNR. American journal of neuroradiology.

[56]  Bozena Kaminska,et al.  Clinical and immunological correlates of long term survival in glioblastoma , 2018, Contemporary oncology.

[57]  Andre Dekker,et al.  Radiomics: the process and the challenges. , 2012, Magnetic resonance imaging.

[58]  Chul-Kee Park,et al.  The frequency and prognostic effect of TERT promoter mutation in diffuse gliomas , 2017, Acta Neuropathologica Communications.

[59]  M. Götz,et al.  Radiomic Profiling of Glioblastoma: Identifying an Imaging Predictor of Patient Survival with Improved Performance over Established Clinical and Radiologic Risk Models. , 2016, Radiology.

[60]  V. P. Collins,et al.  Intratumor heterogeneity in human glioblastoma reflects cancer evolutionary dynamics , 2013, Proceedings of the National Academy of Sciences.

[61]  Raymond Y Huang,et al.  Multimodal imaging patterns predict survival in recurrent glioblastoma patients treated with bevacizumab. , 2016, Neuro-oncology.

[62]  Daoqiang Zhang,et al.  Integration of Network Topological and Connectivity Properties for Neuroimaging Classification , 2014, IEEE Transactions on Biomedical Engineering.

[63]  Leo Breiman,et al.  Random Forests , 2001, Machine Learning.

[64]  Khan M. Iftekharuddin,et al.  Glioblastoma and Survival Prediction , 2017, BrainLes@MICCAI.

[65]  Rasheed Zakaria,et al.  The impact of MGMT methylation and IDH-1 mutation on long-term outcome for glioblastoma treated with chemoradiotherapy , 2016, Acta Neurochirurgica.