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Including Linear Energy Transfer in the Objective Function for IMPT Optimization

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W Cao

W Cao1*, A Khabazian2 , G Lim3 , P Yepes4 , F Poenisch5 , D Grosshans6 , R Mohan7 , (1) UT MD Anderson Cancer Center, Manvel, TX, (2) University of Houston, Houston, TX, (3) University of Houston, Houston, TX, (4) Rice University/The University of Texas M. D. Anderson Cancer, Houston, TX, (5) MD Anderson Cancer Center, Houston, TX, (6) MD Anderson Cancer Center, Houston, TX, (7) UT MD Anderson Cancer Center, Houston, TX


TH-AB-605-6 (Thursday, August 3, 2017) 7:30 AM - 9:30 AM Room: 605

Purpose: To investigate the impact of including an additive linear energy transfer (LET)-dependent term in the objective function in intensity-modulated proton therapy (IMPT) optimization. We hypothesize that the modified objective function will produce IMPT plans that not only satisfy clinical dose criteria but also achieve reduced LET distributions (thus lower biologically effective dose distributions) in critical structures and increased LET in target volumes compared to plans created based on conventional objectives.

Methods: LET-based objectives for minimizing LET in critical structures and normal tissues and maximizing LET in target volumes were added to the conventional dose (i.e., RBE 1.1*physical dose)-based objective function. A new dose and LET optimization model is formulated using a fractional linear program (FLP) in that the intrinsic term of dose-averaged LET contains the decision variable, i.e., beamlet intensity, in both numerator and denominator. We used a variable reformulation approach to solve the FLP. Four glioblastoma patients were selected in our preliminary study. Two plans were created for each patient based on conventional dose-based optimization (Dose_Opt) and dose plus LET-based optimization (Dose&LET_Opt). The resulting plans were compared in terms of dose, LET and the product of dose and LET distributions.

Results: Both strategies, Dose_Opt and Dose&LET_Opt, were able to generate comparable dose distributions. The LET-incorporated optimization achieved pronounced reduction of LET values in critical organs such as brainstem and optic chiasm compared to dose only optimization. In the evaluation in terms of the product of LET and dose, as a surrogate of biologically effective dose, the benefit of LET inclusion was sustained.

Conclusion: Inclusion of an additive LET-dependent term in the dose-based IMPT optimization objective function leads to similar dose distributions as the conventional dose-based optimization but considerable reduction in LET distributions in normal tissues. This may have substantial advantage in reducing normal tissue toxicities.

Funding Support, Disclosures, and Conflict of Interest: NCI U19 CA021239-35

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