Chapter 6 describes the advanced dose optimization methods that can be used to compute the optimal OER-based dose distributions using direct and in-direct optimization of the EUAD. The EUAD is needed to derive non-uniform dose distributions in the hypoxic tumors that are expected to improve the therapeutic ratio of radiation therapy. The optimized beam intensity functions which produce the optimal dose distributions are obtained using algorithms of inverse treatment planning that is an ill-posed problem. To stabilize the numerical solutions, special regularization techniques have been developed. We propose to customize these techniques for inverse treatment planning algorithms to improve quality of numerical solutions and, in turn, the modality of dose delivery to the cancer tumor. We apply to the inverse treatment planning the L-curve method which was developed to determine the regularization parameter in the discrete ill-posed problems.