Systems, methods, and related computer program products for image- guided radiation treatment (IGRT) are described. Provided according to one preferred embodiment is an IGRT apparatus including a barrel-style rotatable gantry structure that provides high mechanical stability, versatility in radiation delivery, and versatility in target tracking. Methods for treatment radiation delivery using the IGRT apparatus include conical non-coplanar rotational arc therapy and cono-helical non-coplanar rotational arc therapy. A radiation treatment head (MV source) and a treatment guidance imaging system including a kV imaging source are mounted to and rotatable with a common barrel-style rotatable gantry structure, or alternatively the MV and kV sources are mounted to separate barrel-style rotatable gantry structures independently rotatable around a common axis of rotation. Methods for intra-fraction target tracking in a gantry-style IGRT system based on comparisons between a pre- acquired planning image and intrafraction x-ray tomosynthesis images and/or intrafraction cone beam CT (CBCT) images are also described.
