e14032 Background: Prediction of future tumor growth and recurrence are critical in the management of patients with glioblastoma multiforme (GBM). This study develops a deep learning method for estimating future areas of GBM spread across multiple timepoints using MRI in patients receiving tumor treating fields (TTFields) therapy. Methods: A single institutional database was queried to identify adult patients with histologically confirmed newly diagnosed and/or recurrent GBM undergoing TTFields therapy. For newly diagnosed GBM, patients received TTFields with temozolomide after maximal debulking surgery and chemoradiation therapy. For recurrent GBM, patients received TTFields as monotherapy. For each patient, all serial follow-up MRI exams were obtained, including T1 (pre-/post-contrast), T2, and T2/FLAIR sequences. On each exam, all regions of enhancing tumor core (excluding peritumoral edema, necrotic core, or resection cavity) were delineated and aligned across time points using nonlinear deformable registration. For any given pair of serial exams, a convolutional neural network (CNN) was designed to predict future GBM tumor on the follow-up exam given the precursor exam and time interval between the studies. The model is implemented as a 3D encoder-decoder architecture yielding a dense per-voxel prediction of future tumor probability optimized using a binary cross-entropy loss function. Class weights were used to develop high sensitivity and high positive predictive value (PPV) model variants. To generate final logit scores, time information is concatenated to the penultimate feature map as an additional feature channel, allowing the model to calibrate each estimate based on elapsed time between any pair of exams. Upon convergence, a 4D learned representation allows for prediction of spatial distribution of GBM tumor at any future time point. Results: A total of 123 patients (1112 total MR exams) were identified. For any given single patient, a median of 6 follow-up exams (IQR 2.5-12.5) at a median interval follow-up time of 46 days (IQR 15.75-63 days) between exams was observed. Upon five-fold cross-validation, the model demonstrated a 0.44 Dice score overlap between predicted and true areas of future GBM tumor growth. The high sensitivity model yielded a per-voxel sensitivity of 0.91 (IQR 0.77-0.99) and PPV of 0.26 (IQR 0.17 to 0.32), while the high PPV model yielded a per-voxel sensitivity of 0.14 (IQR 0.00 to 0.46) and PPV of 0.75 (IQR 0.56 to 0.94). Upon visual confirmation, model predictions across incremental time values for any given exam yielded expected gradual growth of tumor over time. Conclusions: A deep learning model can accurately predict future areas of GBM tumor growth in patients receiving TTFields therapy, with optimal performance that may be calibrated for high sensitivity or high PPV based on clinical use case.