Abstract
O6-methylguanine-DNA methyl transferase (MGMT) methylation prediction models were developed using only small datasets without proper external validation and achieved good diagnostic performance, which seems to indicate a promising future for radiogenomics. However, the diagnostic performance was not reproducible for numerous research teams when using a larger dataset in the RSNA-MICCAI Brain Tumor Radiogenomic Classification 2021 challenge. To our knowledge, there has been no study regarding the external validation of MGMT prediction models using large-scale multicenter datasets. We tested recent CNN architectures via extensive experiments to investigate whether MGMT methylation in gliomas can be predicted using MR images. Specifically, prediction models were developed and validated with different training datasets: (1) the merged (SNUH + BraTS) (n = 985); (2) SNUH (n = 400); and (3) BraTS datasets (n = 585). A total of 420 training and validation experiments were performed on combinations of datasets, convolutional neural network (CNN) architectures, MRI sequences, and random seed numbers. The first-place solution of the RSNA-MICCAI radiogenomic challenge was also validated using the external test set (SNUH). For model evaluation, the area under the receiver operating characteristic curve (AUROC), accuracy, precision, and recall were obtained. With unexpected negative results, 80.2% (337/420) and 60.0% (252/420) of the 420 developed models showed no significant difference with a chance level of 50% in terms of test accuracy and test AUROC, respectively. The test AUROC and accuracy of the first-place solution of the BraTS 2021 challenge were 56.2% and 54.8%, respectively, as validated on the SNUH dataset. In conclusion, MGMT methylation status of gliomas may not be predictable with preoperative MR images even using deep learning.