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  • Oxford University Press (OUP)  (22)
  • 1
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    NIMG-22. INTEGRATION OF A RADIOMIC SIGNATURE, CLINICAL VARIABLES AND PLASMA CELL-FREE DNA IN ADULT PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA PREDICTS PATIENT SURVIVAL AND IMPROVES DISEASE STRATIFICATION
    Oxford University Press (OUP) ; 2020
    In:  Neuro-Oncology Vol. 22, No. Supplement_2 ( 2020-11-09), p. ii151-ii152
    Details
    In: Neuro-Oncology, Oxford University Press (OUP), Vol. 22, No. Supplement_2 ( 2020-11-09), p. ii151-ii152
    Abstract: We have previously demonstrated the potential role of liquid biopsy, specifically plasma cell-free DNA (cfDNA), as a non-invasive biomarker for prognostication in patients with glioblastoma. In separate prior studies, we have also developed MRI-based radiomic signatures to predict survival outcomes in glioblastoma. In this study, for the first time, we evaluated the potential of combining radiomic signatures, epidemiological and clinical variables, and plasma cfDNA quantification for upfront prediction of overall survival (OS) in patients with newly diagnosed glioblastoma. METHODS Quantitative radiomic features were extracted from multiparametric MRI (T1, T1Gd, T2, T2-FLAIR) scans of a discovery cohort of 505 and an independent replication cohort of 50 IDH-wildtype glioblastoma patients. For the independent replication cohort, pre-surgical plasma cfDNA was extracted and quantified. In the first stage, a radiomic signature was created for stratification of patients into categories of short (OS ≤ 6 months) and long (OS ≥ 18 months) survivors using a cross-validated XGBoost method based on the discovery cohort, which was tested independently on the replication cohort. In the second stage, the radiomic signature and clinical variables were integrated to build a second-stage signature using a cross-validated support vector machine (SVM) classifier to stratify the patients into short and long survivor categories. In the third stage, the value of the second-stage signature integrated with cfDNA concentration was assessed through a cross-validated SVM regression method. RESULTS The combination of radiomic, clinical, and cfDNA variables resulted in the best overall predictive accuracy, with Pearson’s correlation coefficient of 0.59 (p & lt; 0.0001) between actual and predicted OS. CONCLUSION In this study, we evaluated the value of combining plasma cfDNA, radiomic, and clinical variables for predicting OS, and showed that it could act as an effective non-invasive prognostic and patient stratification tool in patients with newly diagnosed glioblastoma.
    Type of Medium: Online Resource
    ISSN: 1522-8517 , 1523-5866
    URL: Article
    DOI: 10.1093/neuonc/noaa215.635
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
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  • 2
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    NIMG-22. AN AI-BASED COORDINATE SYSTEM ELUCIDATES RADIOGENOMIC HETEROGENEITY OF GLIOBLASTOMA VIA DEEP LEARNING AND MANIFOLD EMBEDDINGS
    Oxford University Press (OUP) ; 2022
    In:  Neuro-Oncology Vol. 24, No. Supplement_7 ( 2022-11-14), p. vii166-vii166
    Details
    In: Neuro-Oncology, Oxford University Press (OUP), Vol. 24, No. Supplement_7 ( 2022-11-14), p. vii166-vii166
    Abstract: There is evidence that molecular heterogeneity of glioblastoma is associated with heterogeneity of MR imaging signatures. Modern machine learning models, such as deep neural networks, provide a tool for capturing such complex relationships in high-dimensional datasets. This study leverages recent advances in visualizing neural networks to construct a radiogenomics coordinate system whose axes reflect the expression of imaging signatures of genetic mutations commonly found in glioblastoma. METHODS Multi-parametric MRI (mpMRI) scans (T1, T1-Gd, T2, T2-FLAIR, DSC, DTI) of 254 subjects with glioblastoma were retrospectively collected. Radiomics features, including histograms, morphologic and textural descriptors, were derived. Genetic markers were obtained through next generation sequencing (NGS) panel. A multi-label classification deep neural network was trained for predicting mutation status in key driver genes, EGFR, PTEN, NF1, TP53 and RB1. We utilized a nonlinear manifold learning method called Intensive Principal Component Analysis (InPCA), to visualize the output probability distributions from the trained model. The first three principal components (PCs) were selected for constructing the coordinate system. RESULTS The axes derived from InPCA analysis were associated with molecular pathways known to be implicated in glioblastoma: (1) Increasing values of PC1 were associated with primary involvement of P53 then RB1 then MAPK then RTK/PI3K; (2) Increasing values of PC2 were associated with primary involvement of RTK then RB1/P53/MAPK then PI3K; (3) Increasing values of PC3 were associated with primary involvement of MAPK then RB1/P53/RTK/PI3K. Imaging features significantly associated with each of three PCs (p & lt; 0.05) were identified by Pearson correlation analysis. CONCLUSION Deep learning followed by nonlinear manifold embedding identifies a radiogenomics coordinate system spanned by three components which were associated with different molecular pathways of glioblastoma. The heterogeneity of radiogenomic signatures captured by this coordinate system offers in vivo biomarkers of the molecular heterogeneity of glioblastoma.
    Type of Medium: Online Resource
    ISSN: 1522-8517 , 1523-5866
    URL: Article
    DOI: 10.1093/neuonc/noac209.640
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
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  • 3
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    TMOD-34. A RADIOMIC SIGNATURE OF INFILTRATION IN PERITUMORAL EDEMA PREDICTS SUBSEQUENT RECURRENCE IN GLIOBLASTOMA
    Oxford University Press (OUP) ; 2019
    In:  Neuro-Oncology Vol. 21, No. Supplement_6 ( 2019-11-11), p. vi270-vi270
    Details
    In: Neuro-Oncology, Oxford University Press (OUP), Vol. 21, No. Supplement_6 ( 2019-11-11), p. vi270-vi270
    Abstract: The malignant parenchyma in glioblastoma extends beyond the enhancing borders of tumor on postcontrast T1-weighted magnetic resonance imaging (MRI), which is the primary target of treatment. Such non-enhancing tumor invasion into the peri-tumoral edema (PED) is, however, not usually distinguishable on conventional MRI. The aim of this study was to evaluate pre-operative MRI in the PED to assess whether areas of tumor infiltration and early recurrence can be detected. METHODS A cohort of 90 de novo glioblastoma patients from a single institution (Penn) was selected. All included patients had preoperative multi-parametric MRI (mpMRI;T1,T1Gd,T2,T2-FLAIR,ADC), underwent initial gross-total-resection followed by standard chemoradiation, and had pathologically-confirmed recurrence. An extensive panel of handcrafted features, including shape, volume, intensity distributions, texture, was extracted from mpMRI scans. Predictive modeling for estimation of PED infiltration was performed using sequential feature selection approach designed with a support vector machine classifier and through a Leave-one-out cross-validation approach in the Penn cohort. Generalizability of the model was evaluated by applying it on a cohort of 20 patients from a second institution (Case), and predicted probability distributions in PED were compared in both the cohorts. RESULTS Spatial probability maps, representing the likelihood of tumor infiltration and eventual recurrence, were binarized at 50% cutoff, and compared with actual recurrence on post-recurrence scans. The cross-validated accuracy of our model within Penn cohort was 81.35% (odds-ratio=3.62, sensitivity/specificity=78.26/81.35). The model trained on the Penn cohort, when applied on the Case cohort, produced almost similar intensity distribution in the PED, suggesting that the method has potential for robust performance across institutions. The comparison of intensity distributions revealed higher ADC and T2-FLAIR in non-recurrent regions compared to recurrent ones. CONCLUSION Multi-parametric pattern analysis of mpMRI across multiple institutions generates similar, accurate estimates of spatial extent and patterns of recurrence in PED, which may guide strategies for treatment intensification in glioblastoma.
    Type of Medium: Online Resource
    ISSN: 1522-8517 , 1523-5866
    URL: Article
    DOI: 10.1093/neuonc/noz175.1133
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2019
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  • 4
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    NIMG-39. RADIOMIC ANALYSIS FOR NON-INVASIVE IN VIVO PROGNOSTIC STRATIFICATION OF DE NOVO GLIOBLASTOMA PATIENTS: A MULTI-INSTITUTIONAL EVALUATION FOR GENERALIZABILITY IN THE RESPOND CONSORTIUM
    Oxford University Press (OUP) ; 2021
    In:  Neuro-Oncology Vol. 23, No. Supplement_6 ( 2021-11-12), p. vi137-vi137
    Details
    In: Neuro-Oncology, Oxford University Press (OUP), Vol. 23, No. Supplement_6 ( 2021-11-12), p. vi137-vi137
    Abstract: Multi-parametric MRI based radiomic signatures have highlighted the promise of artificial intelligence (AI) in neuro-oncology. However, inter-institution heterogeneity hinders generalization to data from unseen clinical institutions. To this end, we formulated the ReSPOND (Radiomics Signatures for PrecisiON Diagnostics) consortium for glioblastoma. Here, we seek non-invasive generalizable radiomic signatures from routine clinically-acquired MRI for prognostic stratification of glioblastoma patients. METHODS We identified a retrospective cohort of 606 patients with near/gross total tumor resection ( & gt;90%), from 13 geographically-diverse institutions. All pre-operative structural MRI scans (T1,T1-Gd,T2,T2-FLAIR) were aligned to a common anatomical atlas. An automatic algorithm segmented the whole tumors (WTs) into 3 sub-compartments, i.e., enhancing (ET), necrotic core (NC), and peritumoral T2-FLAIR signal abnormality (ED). The combination of ET+NC defines the tumor core (TC). Quantitative radiomic features were extracted to generate our AI model to stratify patients into short- ( & lt; 14mts) and long-survivors ( & gt;14mts). The model trained on 276 patients from a single institution was independently validated on 330 unseen patients from 12 left-out institutions, using the area-under-the-receiver-operating-characteristic-curve (AUC). RESULTS Each feature individually offered certain (limited but reproducible) value for identifying short-survivors: 1) TC closer to lateral ventricles (AUC=0.62); 2) larger ET/brain (AUC=0.61); 3) larger TC/brain (AUC=0.59); 4) larger WT/brain (AUC=0.55); 5) larger ET/WT (AUC=0.59); 6) smaller ED/WT (AUC=0.57); 7) larger ventricle deformations (AUC=0.6). Integrating all features and age, through a multivariate AI model, resulted in higher accuracy (AUC=0.7; 95% C.I.,0.64-0.77). CONCLUSION Prognostic stratification using basic radiomic features is highly reproducible across diverse institutions and patient populations. Multivariate integration yields relatively more accurate and generalizable radiomic signatures, across institutions. Our results offer promise for generalizable non-invasive in vivo signatures of survival prediction in patients with glioblastoma. Extracted features from clinically-acquired imaging, renders these signatures easier for clinical translation. Large-scale evaluation could contribute to improving patient management and treatment planning. *Indicates equal authorship.
    Type of Medium: Online Resource
    ISSN: 1522-8517 , 1523-5866
    URL: Article
    DOI: 10.1093/neuonc/noab196.538
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
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  • 5
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    NIMG-28. PROSPECTIVE HISTOPATHOLOGY-VALIDATED MACHINE LEARNING FOR DISTINGUISHING TRUE PROGRESSION FROM TREATMENT-RELATED CHANGES IN GLIOBLASTOMA PATIENTS
    Oxford University Press (OUP) ; 2021
    In:  Neuro-Oncology Vol. 23, No. Supplement_6 ( 2021-11-12), p. vi134-vi135
    Details
    In: Neuro-Oncology, Oxford University Press (OUP), Vol. 23, No. Supplement_6 ( 2021-11-12), p. vi134-vi135
    Abstract: Decision making about the best course of treatment for glioblastoma patients becomes challenging when a new enhancing lesion appears in the vicinity of the surgical bed on follow-up MRI (after maximal safe tumor resection and chemoradiation), raising concerns for tumor progression (TP). Literature indicates 30-50% of these new lesions describe primarily treatment-related changes (TRC). We hypothesize that quantitative analysis of specific and sensitive features extracted from multi-parametric MRI (mpMRI) via machine learning (ML) techniques may yield non-invasive imaging signatures that distinguish TP from TRC and facilitate better treatment personalization. METHODS We have generated an ML model on a retrospective cohort of 58 subjects, and prospectively evaluated on an independent cohort of 58 previously unseen patients who underwent second resection for suspicious recurrence and had availability of advanced mpMRI (T1, T1-Gd, T2, T2-FLAIR, DTI, DSC). The features selected by our retrospective model, representing principal components analysis of intensity distributions, morphological, statistical, and texture descriptors, were extracted from the mpMRI of the prospective cohort. Integration of these features revealed signatures distinguishing between TP, mixed response, and TRC. Independently, a board-certified neuropathologist evaluated the resected tissue by blindly classifying it in the above three categories, based on mitotic figures, pseudopalisading necrosis, geographic necrosis, dystrophic calcification, vascular changes, and Ki67. RESULTS Tissues classified as TRC by the neuropathologist were associated with imaging phenotypes of lower angiogenesis (DSC-derived features), lower cellularity (DTI-derived features), and higher water concentration (T2, T2-FLAIR features). Our ML model characterized TP with 78% accuracy (sensitivity:86%, specificity:70%, AUC:0.80 (95%CI, 0.68-0.92)) and TRC with 81% accuracy (sensitivity:80%, specificity:81%, AUC:0.87 (95%CI, 0.72-1.00)). CONCLUSION Our proposed ML model reveals distinct non-invasive markers of TP and TRC, directly associated with histopathological changes in prospective glioblastoma patients. Reliable stratification of TP and TRC entities may help to noninvasively determine whether the course of treatment should change.
    Type of Medium: Online Resource
    ISSN: 1522-8517 , 1523-5866
    URL: Article
    DOI: 10.1093/neuonc/noab196.528
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
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  • 6
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    NIMG-33. PROGNOSTIC STRATIFICATION OF DE NOVO GLIOBLASTOMA PATIENTS ACROSS 22 GEOGRAPHICALLY DISTINCT INSTITUTIONS: UPDATES FROM THE RESPOND CONSORTIUM
    Oxford University Press (OUP) ; 2022
    In:  Neuro-Oncology Vol. 24, No. Supplement_7 ( 2022-11-14), p. vii170-vii170
    Details
    In: Neuro-Oncology, Oxford University Press (OUP), Vol. 24, No. Supplement_7 ( 2022-11-14), p. vii170-vii170
    Abstract: Glioblastoma, IDH-wildtype, is the most common primary malignant adult brain tumor with median overall survival (OS) of ~14 months, with little improvement over the last 20 years. We hypothesize that AI-based integration of quantitative tumor characteristics, independent of acquisition protocol and equipment, can reveal accurate generalizable prognostic stratification. We seek an AI-based OS predictor using routine clinically acquired MRI sequences, quantitatively evaluated across institutions of the ReSPOND (Radiomics Signatures for PrecisiON Diagnostics) consortium. METHODS We identified a retrospective cohort of 2,293 diffuse glioma (IDH-wildtype/-NOS/-NEC) patients from 22 geographically distinct institutions across 3 continents, with preoperative structural MRI scans. The entire tumor burden was automatically segmented into 3 sub-compartments, i.e., enhancing, necrotic, peritumoral T2-FLAIR abnormality. We developed our AI predictor by multivariate integration of i)patient age, ii)tumor sub-compartment volume normalized to brain volume, iii)spatial distribution characteristics (tumor location, distance to the ventricles, and laterality), and iv)morphologic descriptors (major axes’ length, axes’ ratio, extent, and number of tumors). The AI predictor returns a continuous value between 0-1, defining short-, intermediate-, and long-survivors based on thresholds on the 25th and 75th percentiles. Leave-One-Site-Out-Cross-Validation was used to assess the generalizability of our stratification. Kaplan-Meier survival curves were computed for OS analysis and evaluated by a Cox proportional hazards model for statistical significance and hazard ratios. RESULTS Survival analysis yielded a hazard ratio of 2.07 (95%CI, 2.06-2.08, p-value= 4.8e-102) for patient stratification into short-, intermediate-, and long-survivors. Pearson correlation between the predicted and actual OS yielded an R= 0.49. CONCLUSION Multivariate integration of visually quantified tumor characteristics, agnostic to acquisition protocol/equipment, yields an accurate OS surrogate index. Validation of our AI model in the largest centralized glioblastoma imaging dataset, from the ReSPOND consortium, supports its generalizability across diverse patient populations and acquisition settings, potentially contributing to equitable improvements of personalized patient care.
    Type of Medium: Online Resource
    ISSN: 1522-8517 , 1523-5866
    URL: Article
    DOI: 10.1093/neuonc/noac209.651
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
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  • 7
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    TMOD-40. IN VIVO EVALUATION OF O6-METHYLGUANINE-DNA-METHYLTRANSFERASE (MGMT) PROMOTER METHYLATION STATUS FOR DE NOVO GLIOBLASTOMA PATIENTS USING DEEP LEARNING FEATURES
    Oxford University Press (OUP) ; 2019
    In:  Neuro-Oncology Vol. 21, No. Supplement_6 ( 2019-11-11), p. vi271-vi272
    Details
    In: Neuro-Oncology, Oxford University Press (OUP), Vol. 21, No. Supplement_6 ( 2019-11-11), p. vi271-vi272
    Abstract: High expression of O6-methylguanine-DNA methyltransferase (MGMT) in glioblastoma is associated with resistance to temozolomide, as tumor cells lacking MGMT activity are significantly more sensitive to the cytotoxic effects of temozolomide. The MGMT promoter methylation status (MGMTpms) is typically determined as MGMT-methylated or MGMT-unmethylated. Some single-center studies have reported results ranging from 70–95% detection rates using MRI. We aim to further validate these findings using a multi-institutional data set. We hypothesize that transfer learning based features when integrated via machine learning may lead to non-invasive determination of MGMTpms. METHODS A total of 270 patients were included across the 3 institutions (Hospital of the University of Pennsylvania (HUP), Jefferson University Hospital (JUH); the TCIA). JUH and TCIA datasets comprised conventional modalities (T1,T2,T2-FLAIR,T1-Gd), whereas HUP dataset had additional modalities (DSC,DTI) as well. We used transfer learning and adapted a convolutional neural network (CNN) model pre-trained on 1.2 million 3-channel images of the ImageNet to extract deep learning features from the given images. A support vector machine multivariately integrated these features towards a non-invasive marker of MGMTpms. RESULTS The cross-validated accuracy of our MGMT marker in classifying the mutation status in individual patients was 86.95%, 81.56%, and 82.43%, respectively, in HUP, JUH, and TCIA. Our marker revealed MGMT-methylated tumors with lower neovascularization and cell density, when compared with MGMT-unmethylated tumors. MGMT-unmethylated tumors were found to be more lateralized to the right hemisphere, when compared with MGMT-methylated tumors. CONCLUSION Our findings suggest that transfer learning features when integrated via machine learning allow robust prediction of MGMTpms on mpMRI acquired within multiple institutions. The proposed non-invasive MGMT marker may contribute to (i) MGMTpms determination for patients with inadequate tissue/inoperable tumors, (ii) stratification of patients into clinical trials, (iii) patient selection for targeted therapy, and (iv) personalized treatment planning.
    Type of Medium: Online Resource
    ISSN: 1522-8517 , 1523-5866
    URL: Article
    DOI: 10.1093/neuonc/noz175.1139
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2019
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  • 8
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    NIMG-40. RADIOGENOMIC SIGNATURES OF DRIVER GENES IN NEWLY DIAGNOSED GLIOBLASTOMA PATIENTS BASED ON PRE-OPERATIVE MULTI-PARAMETRIC MRI
    Oxford University Press (OUP) ; 2020
    In:  Neuro-Oncology Vol. 22, No. Supplement_2 ( 2020-11-09), p. ii156-ii157
    Details
    In: Neuro-Oncology, Oxford University Press (OUP), Vol. 22, No. Supplement_2 ( 2020-11-09), p. ii156-ii157
    Abstract: Non-invasive and quantitative biomarkers of somatic mutations derived from multi-parametric MRI (MP-MRI) could potentially help in predicting the response of patients to therapy, leading to development of targeted and personalized treatments. In this study, we developed radiogenomic signatures of multiple driver genes using artificial intelligence (AI) methods. METHODS In this study, 2740 radiomic features, including shape and volumetric measures computed for different tumorous regions, and characteristics derived from histograms and gray-level co-occurrence matrix (GLCM), were extracted from pre-operative MP-MRI (T1, T1Gd, T2, T2-FLAIR, DTI, and DSC-MRI) scans of 161 patients with newly diagnosed glioblastoma. The tumor samples, collected surgically from these patients, were sequenced using an in-house targeted next generation sequencing (NGS) panel of genes. We constructed quantitative imaging signatures of somatic mutations in several genes from 161 IDH-wildtype glioblastoma patients, including ATRX, FGFR2, EGFR, MET, NF1, PDGFRA, PIK3CA, PTEN, RB1, TP53, using cross-validated SVM classifiers. RESULTS The cross-validated classification performance for each signature was assessed by area under the receiver operating characteristic (ROC) curve (AUC), indicating the following results: PTEN (n = 69, AUC = 0.64), EGFR (n = 52, AUC = 0.72), TP53 (n = 51, AUC = 0.67), NF1 (n = 33, AUC = 0.74), ATRX (n = 22; AUC = 0.74), FGFR2 (n = 6, AUC = 0.82), MET (n = 26, AUC = 0.77), PDGFRA (n = 14, AUC = 0.82), PIK3CA (n = 14, AUC = 0.78), RB1 (n = 14, AUC = 0.81). CONCLUSION Using multi-parametric MRI, we developed quantitative non-invasive in vivo signatures with the potential for pre-operative assessment of a glioblastoma’s molecular characteristics. These non-invasive radiogenomic biomarkers may be useful for understanding the molecular composition of a glioblastoma prior to surgical resection, thus enabling earlier selection of patients for targeted therapy trials and possible neoadjuvant treatment.
    Type of Medium: Online Resource
    ISSN: 1522-8517 , 1523-5866
    URL: Article
    DOI: 10.1093/neuonc/noaa215.653
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
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  • 9
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    NIMG-66. AI-BASED PROGNOSTIC IMAGING BIOMARKERS FOR PRECISION NEUROONCOLOGY AND THE RESPOND CONSORTIUM
    Oxford University Press (OUP) ; 2020
    In:  Neuro-Oncology Vol. 22, No. Supplement_2 ( 2020-11-09), p. ii162-ii163
    Details
    In: Neuro-Oncology, Oxford University Press (OUP), Vol. 22, No. Supplement_2 ( 2020-11-09), p. ii162-ii163
    Abstract: AI-based methods have shown great promise in a variety of biomedical research fields, including neurooncologic imaging. For example, machine learning methods have offered informative predictions of overall survival (OS) and progression-free survival (PFS), differentiation between pseudoprogression (PsP) and progressive disease (PD), and estimation of mutational status from imaging data. Despite their promise, AI, and especially the emerging deep learning (DL) methods, are challenged by several factors, including imaging heterogeneity across scanners and lack of sufficiently large and diverse training datasets, which limits their reproducibility and general acceptance. These challenges prompted the development of the ReSPOND (Radiomics Signatures for PrecisiON Diagnostics) consortium on glioblastoma, a growing effort to bring together a community of researchers sharing imaging, demographic, clinical and (currently) limited molecular data in order to address the following aims: 1) pool and harmonize data across diverse hospitals and patient populations worldwide; 2) derive robust and generalizable AI models for prediction of (initially) OS, PFS, PsP vs. PD, and recurrence; 3) test these predictive models across multiple sites. In its first phase, ReSPOND aims to pool together approximately 3,000MRI scans (from 10institutions plus TCIA), along with demographics, KPS, and (for a subset) MGMT/IDH1 status. We present initial results testing the generalization of a previously trained model of OS on 505Penn datasets to 2independent cohorts from Case Western Reserve University and University Hospitals (N=44), and Penn (N=67). The results indicate good generalization, with correlation coefficients between OS/predicted-OS between 0.25 to 0.5, depending on variable availability, which is comparable to cross-validated accuracy previously obtained from the training set itself (N=505). Additional preliminary studies evaluating prediction of future recurrence from baseline pre-operative scans in de novo patients (Penn model applied to CWR) indicated potential for guiding targeted dose escalation and supra-total resection (excellent predictions in 6/12 patients, modest in 1/12, and poor in 5/12).
    Type of Medium: Online Resource
    ISSN: 1522-8517 , 1523-5866
    URL: Article
    DOI: 10.1093/neuonc/noaa215.679
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
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  • 10
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    NIMG-37. JOINT LEARNING OF IMAGING AND GENOMIC DATA REVEALS DISTINCT GLIOBLASTOMA SUBTYPES
    Oxford University Press (OUP) ; 2022
    In:  Neuro-Oncology Vol. 24, No. Supplement_7 ( 2022-11-14), p. vii171-vii171
    Details
    In: Neuro-Oncology, Oxford University Press (OUP), Vol. 24, No. Supplement_7 ( 2022-11-14), p. vii171-vii171
    Abstract: The significant heterogeneity of glioblastoma is typically displayed on both phenotypical and molecular levels. Non-invasive in vivo approaches to characterize this heterogeneity would potentially facilitate personalized therapies. Here we leverage advanced unsupervised machine learning to integrate radiomic imaging features and genomics to identify distinct subtypes of glioblastoma. METHODS A retrospective cohort of 571 IDH-wildtype glioblastoma patients were collected with pre-operative multi-parametric MRI (T1, T1CE, T2, T2-FLAIR, DSC, DTI) scans (available in 462/571 patients) and targeted next-generation sequencing (NGS) data (available in 355/571 patients). Radiomic features (n= 971) were extracted from these MRI scans and a subset of 12 features were selected by L21-norm minimization. A total of 14 key driver genes in the 5 main pathways that are most frequently altered in glioblastoma were chosen. Subtypes were identified by a joint learning approach called Anchor-based Partial Multi-modal Clustering (APMC) on both radiomic and genomic modalities. RESULTS Three distinct glioblastoma subtypes were discovered by APMC based on 14-dimension NGS data together with 12 selected radiomic features representing characteristics from histograms, shape, and volumetric measures for different tumor sub-regions. The identified subtypes were 1) high-risk; 2) medium-risk; and 3) low-risk, in terms of their overall survival outcome in Kaplan-Meier analysis (p= 5.52e-6, log-rank test; HR= 1.51, 95%CI:1.20-1.74, Cox proportional hazard model). The three subtypes also displayed different molecular characteristics: subtype 1 exhibited increased frequency of mutation in [EGFR, PIK3CA, PTEN, NF1], subtype 3 showed frequently mutated [PDGFRA, ATRX] , while subtype 2 did not show significant differences for mutations in any of these genes. CONCLUSION Our results revealed the synergistic value of integrated radiomic signatures and molecular characteristics for glioblastoma subtyping. Joint learning on both modalities could help better understand the molecular basis of phenotypical signatures of glioblastoma and further provide insights into the biologic underpinnings of tumor formation and progression.
    Type of Medium: Online Resource
    ISSN: 1522-8517 , 1523-5866
    URL: Article
    DOI: 10.1093/neuonc/noac209.655
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
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