A method of intensity modulated radiation therapy (IMRT) treatment planning comprising: accessing, by one or more processors, patient specific data of a patient, the patient specific data including one or more parameters of an anatomical region of the patient, the anatomical region including a planning target volume for which radiation to be applied and one or more anatomical sub-regions corresponding to normal tissues; determining, by the one or more processors using the patient specific data, a first radiation beam profile by maximizing radiation to the PTV subject to a first set of constraints; determining, by the one or more processors using the first radiation beam profile, a second radiation beam profile by minimizing one or more radiation dose based functions within the one or more anatomical sub-regions corresponding to the normal tissues subject to a second set of constraints; determining, by the one or more processors, a third radiation beam profile by smoothing the second radiation beam profile subject to a third set of constraints, smoothing the second radiation beam profile including reducing differences between radiation intensities of adjacent radiation beamlets of the second radiation beam profile; determining, by the one or more processors, a radiation dose discrepancy between a first radiation dose vector being an optimization radiation dose vector determined by multiplying the third radiation beam profile with an influence matrix and a second radiation dose vector being a simulated radiation dose vector determined by simulating the third radiation beam profile the influence matrix being indicative of radiation dose delivered to each voxel of the anatomical region, each row of the influence matix corresponding to a respective voxel of the anatomical region and each column of the influence matrix corresponding to a respective beamlet of a plurality of beamlets forming a beam; and determining, by the one or more processors using the third radiation beam profile, a fourth radiation beam profile by reducing the determined radiation dose discrepancy. accessing, by one or more processors, patient specific data of a patient, the patient specific data including one or more parameters of an anatomical region of the patient, the anatomical region including a planning target volume for which radiation to be applied and one or more anatomical sub-regions corresponding to normal tissues; determining, by the one or more processors using the patient specific data, a first radiation beam profile by maximizing radiation to the PTV subject to a first set of constraints; determining, by the one or more processors using the first radiation beam profile, a second radiation beam profile by minimizing one or more radiation dose based functions within the one or more anatomical sub-regions corresponding to the normal tissues subject to a second set of constraints; determining, by the one or more processors, a third radiation beam profile by smoothing the second radiation beam profile subject to a third set of constraints, smoothing the second radiation beam profile including reducing differences between radiation intensities of adjacent radiation beamlets of the second radiation beam profile; determining, by the one or more processors, a radiation dose discrepancy between a first radiation dose vector being an optimization radiation dose vector determined by multiplying the third radiation beam profile with an influence matrix and a second radiation dose vector being a simulated radiation dose vector determined by simulating the third radiation beam profile the influence matrix being indicative of radiation dose delivered to each voxel of the anatomical region, each row of the influence matix corresponding to a respective voxel of the anatomical region and each column of the influence matrix corresponding to a respective beamlet of a plurality of beamlets forming a beam; and determining, by the one or more processors using the third radiation beam profile, a fourth radiation beam profile by reducing the determined radiation dose discrepancy.