Linear Energy Transfer (LET) - Guided Optimization Incorporating Biological Effectiveness for Intensity-Modulated Proton Therapy



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Relative biological effectiveness (RBE) is used to measure the biological effect of treatment plans in Intensity modulated proton therapy (IMPT). However, this approach is challenging because of considerable model uncertainties for clinical tissues. Therefore, the primary goal of this dissertation research is to develop biological effectiveness incorporated optimization approaches to enhance understanding of the biological impact of IMPT in radiation therapy research. First, our work considers LET as a physical surrogate of biological effect in treatment planning. By maximizing dose-averaged LET in the target and minimizing it on OARs, the method not only can produce satisfactory dose distributions but also achieve reduced LET distributions in critical structures as well as an increased LET in the target volume. Then, we develop a new mathematical model to increase the biological effect in radioresistant tumors in such a way that a robust biological effect distribution can be achieved. To accomplish this purpose, the sum of the differences between the highest and the lowest biological effect in each voxel, approximated by the product of dose and LET, is penalized. After that, we noticed that using LET as a surrogate will increase the model complexity and ignore the difference between dose and LET distribution, which is a more fundamental property. A study focuses on the potential benefits of LET keeps going up after the physical dose Bragg Peak is come up with to improve the biological effect performance. avoid high values of LET in critical structures located within or near the target and increase LET in the tumor area, without compromising the target coverage. In the final work, the impact of BAOpt on the biological effect in IMPT is investigated.



IMPT, Optimization, Biological


Portions of this document appear in: Bai, Xuemin, Gino Lim, Hans-Peter Wieser, Mark Bangert, David Grosshans, Radhe Mohan, and Wenhua Cao. "Robust optimization to reduce the impact of biological effect variation from physical uncertainties in intensity-modulated proton therapy." Physics in Medicine & Biology 64, no. 2 (2019): 025004.