Reconstruction of projection images of a CBCT scan is performed by generating simulated projection data, comparing the simulated projection data to the projection images of the CBCT scan, determining a residual volume based on the comparison, and using the residual volume to determine an accurate reconstructed volume. The reconstructed volume can be used to segment a tumor (and potentially one or more organs) and align the tumor to a planning volume (e.g., from a CT scan) to identify changes, such as shape of the tumor and proximity of the tumor to an organ. These changes can be used to update a radiation therapy procedure, such as by altering a radiation treatment plan and fine-tuning a patient position.