Comparison of volumetric and 2D-based response methods in the PNOC-001 pediatric low-grade glioma clinical trial.

Background: Although response in pediatric low-grade glioma (pLGG) includes volumetric assessment, more simplified 2D-based methods are often used in clinical trials. The study's purpose was to compare volumetric to 2D methods. Methods: An expert neuroradiologist performed solid and whole tumor (including cyst and edema) volumetric measurements on MR images using a PACS-based manual segmentation tool in 43 pLGG participants (213 total follow-up images) from the Pacific Pediatric Neuro-Oncology Consortium (PNOC-001) trial. Classification based on changes in volumetric and 2D measurements of solid tumor were compared to neuroradiologist visual response assessment using the Brain Tumor Reporting and Data System (BT-RADS) criteria for a subset of 65 images using receiver operating characteristic (ROC) analysis. Longitudinal modeling of solid tumor volume was used to predict BT-RADS classification in 54 of the 65 images. Results: There was a significant difference in ROC area under the curve between 3D solid tumor volume and 2D area (0.96 vs 0.78, P = .005) and between 3D solid and 3D whole volume (0.96 vs 0.84, P = .006) when classifying BT-RADS progressive disease (PD). Thresholds of 15-25% increase in 3D solid tumor volume had an 80% sensitivity in classifying BT-RADS PD included in their 95% confidence intervals. The longitudinal model of solid volume response had a sensitivity of 82% and a positive predictive value of 67% for detecting BT-RADS PD. Conclusions: Volumetric analysis of solid tumor was significantly better than 2D measurements in classifying tumor progression as determined by BT-RADS criteria and will enable more comprehensive clinical management.

Systematic Literature Review of Machine Learning Algorithms Using Pretherapy Radiologic Imaging for Glioma Molecular Subtype Prediction.

BACKGROUND: The molecular profile of gliomas is a prognostic indicator for survival, driving clinical decision-making for treatment. Pathology-based molecular diagnosis is challenging because of the invasiveness of the procedure, exclusion from neoadjuvant therapy options, and the heterogeneous nature of the tumor. PURPOSE: We performed a systematic review of algorithms that predict molecular subtypes of gliomas from MR Imaging. DATA SOURCES: Data sources were Ovid Embase, Ovid MEDLINE, Cochrane Central Register of Controlled Trials, Web of Science. STUDY SELECTION: Per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, 12,318 abstracts were screened and 1323 underwent full-text review, with 85 articles meeting the inclusion criteria. DATA ANALYSIS: We compared prediction results from different machine learning approaches for predicting molecular subtypes of gliomas. Bias analysis was conducted for each study, following the Prediction model Risk Of Bias Assessment Tool (PROBAST) guidelines. DATA SYNTHESIS: Isocitrate dehydrogenase mutation status was reported with an area under the curve and accuracy of 0.88 and 85% in internal validation and 0.86 and 87% in limited external validation data sets, respectively. For the prediction of O6-methylguanine-DNA methyltransferase promoter methylation, the area under the curve and accuracy in internal validation data sets were 0.79 and 77%, and in limited external validation, 0.89 and 83%, respectively. PROBAST scoring demonstrated high bias in all articles. LIMITATIONS: The low number of external validation and studies with incomplete data resulted in unequal data analysis. Comparing the best prediction pipelines of each study may introduce bias. CONCLUSIONS: While the high area under the curve and accuracy for the prediction of molecular subtypes of gliomas are reported in internal and external validation data sets, limited use of external validation and the increased risk of bias in all articles may present obstacles for clinical translation of these techniques.

Application of novel PACS-based informatics platform to identify imaging based predictors of CDKN2A allelic status in glioblastomas.

Gliomas with CDKN2A mutations are known to have worse prognosis but imaging features of these gliomas are unknown. Our goal is to identify CDKN2A specific qualitative imaging biomarkers in glioblastomas using a new informatics workflow that enables rapid analysis of qualitative imaging features with Visually AcceSAble Rembrandtr Images (VASARI) for large datasets in PACS. Sixty nine patients undergoing GBM resection with CDKN2A status determined by whole-exome sequencing were included. GBMs on magnetic resonance images were automatically 3D segmented using deep learning algorithms incorporated within PACS. VASARI features were assessed using FHIR forms integrated within PACS. GBMs without CDKN2A alterations were significantly larger (64 vs. 30%, p = 0.007) compared to tumors with homozygous deletion (HOMDEL) and heterozygous loss (HETLOSS). Lesions larger than 8 cm were four times more likely to have no CDKN2A alteration (OR: 4.3; 95% CI 1.5-12.1; p < 0.001). We developed a novel integrated PACS informatics platform for the assessment of GBM molecular subtypes and show that tumors with HOMDEL are more likely to have radiographic evidence of pial invasion and less likely to have deep white matter invasion or subependymal invasion. These imaging features may allow noninvasive identification of CDKN2A allele status.

Machine Learning Models for Classifying High- and Low-Grade Gliomas: A Systematic Review and Quality of Reporting Analysis.

Objectives: To systematically review, assess the reporting quality of, and discuss improvement opportunities for studies describing machine learning (ML) models for glioma grade prediction. Methods: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses of Diagnostic Test Accuracy (PRISMA-DTA) statement. A systematic search was performed in September 2020, and repeated in January 2021, on four databases: Embase, Medline, CENTRAL, and Web of Science Core Collection. Publications were screened in Covidence, and reporting quality was measured against the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) Statement. Descriptive statistics were calculated using GraphPad Prism 9. Results: The search identified 11,727 candidate articles with 1,135 articles undergoing full text review and 85 included in analysis. 67 (79%) articles were published between 2018-2021. The mean prediction accuracy of the best performing model in each study was 0.89 ± 0.09. The most common algorithm for conventional machine learning studies was Support Vector Machine (mean accuracy: 0.90 ± 0.07) and for deep learning studies was Convolutional Neural Network (mean accuracy: 0.91 ± 0.10). Only one study used both a large training dataset (n>200) and external validation (accuracy: 0.72) for their model. The mean adherence rate to TRIPOD was 44.5% ± 11.1%, with poor reporting adherence for model performance (0%), abstracts (0%), and titles (0%). Conclusions: The application of ML to glioma grade prediction has grown substantially, with ML model studies reporting high predictive accuracies but lacking essential metrics and characteristics for assessing model performance. Several domains, including generalizability and reproducibility, warrant further attention to enable translation into clinical practice. Systematic Review Registration: PROSPERO, identifier CRD42020209938.

Identifying clinically applicable machine learning algorithms for glioma segmentation: recent advances and discoveries.

Background: While there are innumerable machine learning (ML) research algorithms used for segmentation of gliomas, there is yet to be a US FDA cleared product. The aim of this study is to explore the systemic limitations of research algorithms that have prevented translation from concept to product by a review of the current research literature. Methods: We performed a systematic literature review on 4 databases. Of 11 727 articles, 58 articles met the inclusion criteria and were used for data extraction and screening using TRIPOD. Results: We found that while many articles were published on ML-based glioma segmentation and report high accuracy results, there were substantial limitations in the methods and results portions of the papers that result in difficulty reproducing the methods and translation into clinical practice. Conclusions: In addition, we identified that more than a third of the articles used the same publicly available BRaTS and TCIA datasets and are responsible for the majority of patient data on which ML algorithms were trained, which leads to limited generalizability and potential for overfitting and bias.

Trends in Development of Novel Machine Learning Methods for the Identification of Gliomas in Datasets That Include Non-Glioma Images: A Systematic Review.

PURPOSE: Machine learning has been applied to the diagnostic imaging of gliomas to augment classification, prognostication, segmentation, and treatment planning. A systematic literature review was performed to identify how machine learning has been applied to identify gliomas in datasets which include non-glioma images thereby simulating normal clinical practice. MATERIALS AND METHODS: Four databases were searched by a medical librarian and confirmed by a second librarian for all articles published prior to February 1, 2021: Ovid Embase, Ovid MEDLINE, Cochrane trials (CENTRAL), and Web of Science-Core Collection. The search strategy included both keywords and controlled vocabulary combining the terms for: artificial intelligence, machine learning, deep learning, radiomics, magnetic resonance imaging, glioma, as well as related terms. The review was conducted in stepwise fashion with abstract screening, full text screening, and data extraction. Quality of reporting was assessed using TRIPOD criteria. RESULTS: A total of 11,727 candidate articles were identified, of which 12 articles were included in the final analysis. Studies investigated the differentiation of normal from abnormal images in datasets which include gliomas (7 articles) and the differentiation of glioma images from non-glioma or normal images (5 articles). Single institution datasets were most common (5 articles) followed by BRATS (3 articles). The median sample size was 280 patients. Algorithm testing strategies consisted of five-fold cross validation (5 articles), and the use of exclusive sets of images within the same dataset for training and for testing (7 articles). Neural networks were the most common type of algorithm (10 articles). The accuracy of algorithms ranged from 0.75 to 1.00 (median 0.96, 10 articles). Quality of reporting assessment utilizing TRIPOD criteria yielded a mean individual TRIPOD ratio of 0.50 (standard deviation 0.14, range 0.37 to 0.85). CONCLUSION: Systematic review investigating the identification of gliomas in datasets which include non-glioma images demonstrated multiple limitations hindering the application of these algorithms to clinical practice. These included limited datasets, a lack of generalizable algorithm training and testing strategies, and poor quality of reporting. The development of more robust and heterogeneous datasets is needed for algorithm development. Future studies would benefit from using external datasets for algorithm testing as well as placing increased attention on quality of reporting standards. SYSTEMATIC REVIEW REGISTRATION: www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020209938, International Prospective Register of Systematic Reviews (PROSPERO 2020 CRD42020209938).