Systems and methods are provided for single isocenter radiotherapy of multiple targets. Conformal arc information may be used in a Conformal Arc Informed Volumetric Modulated Arc Therapy (CAVMAT) method that includes single isocenter radiotherapy of multiple targets where conformal multi-leaf collimator (MLC) trajectories may be used as the starting point for limited inverse optimization. Single isocenter radiotherapy of multiple targets may provide flexibility with less complex MLC trajectories, and fully block between targets with the MLC.