Glioma Survival Prediction with Combined Analysis of In Vivo C-MET PET Features, Ex Vivo Features, and Patient Features by Supervised Machine Learning

Gliomas are the most common type of tumor in the brain. Although the definite diagnosis is routinely made ex vivo by histopathologic and molecular examination, diagnostic work-up of patients with suspected glioma is mainly done using MRI. Nevertheless, l--methyl-C-methionine (C-MET) PET holds great potential in the characterization of gliomas. The aim of this study was to establish machine-learning-driven survival models for glioma built on in vivo C-MET PET characteristics, ex vivo characteristics, and patient characteristics. The study included 70 patients with a treatment-naïve glioma that was C-MET-positive and had histopathology-derived ex vivo feature extraction, such as World Health Organization 2007 tumor grade, histology, and isocitrate dehydrogenase 1 R132H mutational status. The C-MET-positive primary tumors were delineated semiautomatically on PET images, followed by the extraction of tumor-to-background-based general and higher-order textural features by applying 5 different binning approaches. In vivo and ex vivo features, as well as patient characteristics (age, weight, height, body mass index, Karnofsky score), were merged to characterize the tumors. Machine-learning approaches were used to identify relevant in vivo, ex vivo, and patient features and their relative weights for predicting 36-mo survival. The resulting feature weights were used to establish 3 predictive models per binning configuration: one model based on a combination of in vivo, ex vivo, and clinical patient information (M36); another based on in vivo and patient information only (M36); and a third based on in vivo information only (M36). In addition, a binning-independent model based on ex vivo and patient information only (M36) was created. The established models were validated in a Monte Carlo cross-validation scheme. The most prominent machine-learning-selected and -weighted features were patient-based and ex vivo-based, followed by in vivo-based. The highest areas under the curve for our models as revealed by the Monte Carlo cross-validation were 0.9 for M36, 0.87 for M36, 0.77 for M36, and 0.72 for M36 Prediction of survival in amino acid PET-positive glioma patients was highly accurate using computer-supported predictive models based on in vivo, ex vivo, and patient features.