Systems and methods are disclosed for monitoring anatomic position of a human subject for a radiotherapy treatment session, based on use of a regression model trained to estimate movement of a region of interest based on 2D image data input. Example operations for movement estimation include: obtaining 3D image data for a subject, which provides a reference volume and at least one defined region of interest; obtaining 2D image data corresponding to the subject, captured in real time (during the radiotherapy treatment session); extracting features from the 2D image data; analyzing the extracted features with a machine learning regression model, trained to estimate a spatial transformation in the three dimensions of the reference volume; and outputting and using a relative motion estimation of the at least one region of interest, produced from the machine learning regression model, the relative motion estimation being estimated from the extracted features.