Interpretation of the dosimetric results of three uniformity regularization methods in terms of expected treatment outcome

In IMRT treatment plan optimization there are various methods that try to regularize the variation of dose nonuniformity using purely dosimetric measures. However, although these methods can help in finding a good dose distribution, they do not provide any information regarding the expected treatment outcome. When a treatment plan optimization is performed using biological measures, the final goal should be some indication about the expected tumor control or normal tissue complications, which is the primary goal of treatment planning (the association of treatment configurations and dose prescription with the treatment outcome). In this study, this issue is analyzed distinguishing the dose-oriented treatment plan optimization from the response-oriented optimization. Three different dose distributions were obtained by using a dose-based optimization technique, an EUD-based optimization without applying any technique for regularizing the nonuniformity of the dose distribution, and an EUD-based optimization using a variational regularization technique, which controls dose nonuniformity. The clinical effectiveness of the three dose distributions was investigated by calculating the response probabilities of the tumors and organs-at-risk (OARs) involved in two head and neck and prostate cancer cases. The radiobiological models used are the linear-quadratic-Poisson and the Relative Seriality models. Furthermore, the complication-free tumor control probability and the biologically effective uniform dose (D) were used for treatment plan evaluation and comparison. The radiobiological comparison shows that the EUD-based optimization using L-curve regularization gives better results than the EUD-based optimization without regularization and dose-based optimization in both clinical cases. Concluding, it appears that the applied dose nonuniformity regularization technique is expected to improve the effectiveness of the optimized IMRT dose distributions. However, more patient cases are needed to validate the statistical significance of the results and conclusions presented in this paper.