A biological effect-guided optimization approach using beam distal-edge avoidance for intensity-modulated proton therapy

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Purpose: Linear energy transfer (LET)-guided methods have been applied to intensity-modulated proton therapy (IMPT) to improve its biological effect. However, using LET as a surrogate for biological effect ignores the topological relationship of the scanning spot to different structures of interest. In this study, we developed an optimization method that takes advantage of the continuing increase in LET beyond the physical dose Bragg peak. This method avoids placing high biological effect values in critical structures and increases biological effect in the tumor area without compromising target coverage. Methods: We selected the cases of two patients with brain tumors and two patients with head and neck tumors who had been treated with proton therapy at our institution. Three plans were created for each case: a plan based on conventional dose-based optimization (DoseOpt), one based on LET-incorporating optimization (LETOpt), and one based on the proposed distal-edge avoidance-guided optimization method (DEAOpt). In DEAOpt, an L1-norm sparsity term, in which the penalty of each scanning spot was set according to the topological relationship between the organ positions and the location of the peak scaled LET-weighted dose (c LETxD) was added to a conventional dose-based optimization objective function. All plans were normalized to give the same target dose coverage. Dose (assuming a constant relative biological effectiveness value of 1.1, as in clinical practice), biological effect (c LETxD), and computing time consumption were evaluated and compared among the three optimization approaches for each patient case. Results: For all four cases, all three optimization methods generated comparable dose coverage in both target and critical structures. The LETOpt plans and DEAOpt plans reduced biological effect hot spots in critical structures and increased biological effect in the target volumes to a similar extent. For the target, the c LETxD98% and c LETxD2% in the DEAOpt plans were on average 7.2% and 11.74% higher than in the DoseOpt plans, respectively. For the brainstem, the c LETxDmean in the DEAOpt plans was on average 33.38% lower than in the DoseOpt plans. In addition, the DEAOpt method saved 30.37% of the computation cost over the LETOpt method. Conclusions: DEAOpt is an alternative IMPT optimization approach that correlates the location of scanning spots with biological effect distribution. IMPT could benefit from the use of DEAOpt because this method not only delivers comparable biological effects to LETOpt plans, but also is faster.

Original languageEnglish (US)
JournalMedical physics
StateAccepted/In press - 2020


  • biological effect
  • IMPT
  • LET
  • RBE

ASJC Scopus subject areas

  • Biophysics
  • Radiology Nuclear Medicine and imaging

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