Rasmus Bokrantz

A critical evaluation of worst case optimization methods for robust intensity-modulated proton therapy planning

PURPOSE To critically evaluate and compare three worst case optimization methods that have been previously employed to generate intensity-modulated proton therapy treatment plans that are robust against systematic errors. The goal of the evaluation is to identify circumstances when the methods behave differently and to describe the mechanism behind the differences when they occur. METHODS The worst case methods optimize plans to perform as well as possible under the worst case scenario that can physically occur (composite worst case), the combination of the worst case scenarios for each objective constituent considered independently (objectivewise worst case), and the combination of the worst case scenarios for each voxel considered independently (voxelwise worst case). These three methods were assessed with respect to treatment planning for prostate under systematic setup uncertainty. An equivalence with probabilistic optimization was used to identify the scenarios that determine the outcome of the optimization. RESULTS If the conflict between target coverage and normal tissue sparing is small and no dose-volume histogram (DVH) constraints are present, then all three methods yield robust plans. Otherwise, they all have their shortcomings: Composite worst case led to unnecessarily low plan quality in boundary scenarios that were less difficult than the worst case ones. Objectivewise worst case generally led to nonrobust plans. Voxelwise worst case led to overly conservative plans with respect to DVH constraints, which resulted in excessive dose to normal tissue, and less sharp dose fall-off than the other two methods. CONCLUSIONS The three worst case methods have clearly different behaviors. These behaviors can be understood from which scenarios that are active in the optimization. No particular method is superior to the others under all circumstances: composite worst case is suitable if the conflicts are not very severe or there are DVH constraints whereas voxelwise worst case is advantageous if there are severe conflicts but no DVH constraints. The advantages of composite and voxelwise worst case outweigh those of objectivewise worst case.

An Algorithm for Approximating Convex Pareto Surfaces Based on Dual Techniques

We consider the problem of approximating Pareto surfaces of convex multicriteria optimization problems by a discrete set of points and their convex combinations. Finding the scalarization parameters that optimally limit the approximation error when generating a single Pareto optimal solution is a nonconvex optimization problem. This problem can be solved by enumerative techniques but at a cost that increases exponentially with the number of objectives. We present an algorithm for solving the Pareto surface approximation problem that is practical with 10 or less conflicting objectives, motivated by an application to radiation therapy optimization. Our enumerative scheme is, in a sense, dual to a family of previous algorithms. The proposed technique retains the quality of the best previous algorithm in this class while solving fewer subproblems. A further improvement is provided by a procedure for discarding subproblems based on reusing information from previous solves. The combined effect of the enhancements is empirically demonstrated to reduce the computational expense of solving the Pareto surface approximation problem by orders of magnitude. For problems where the objectives have positive curvature, an improved bound on the approximation error is demonstrated using transformations of the initial objectives with strictly increasing and concave functions.

Multicriteria optimization for volumetric‐modulated arc therapy by decomposition into a fluence‐based relaxation and a segment weight‐based restriction

PURPOSE To develop a method for inverse volumetric-modulated arc therapy (VMAT) planning that combines multicriteria optimization (MCO) with direct machine parameter optimization. The ultimate goal is to provide an efficient and intuitive method for generating high quality VMAT plans. METHODS Multicriteria radiation therapy treatment planning amounts to approximating the relevant treatment options by a discrete set of plans, and selecting the combination thereof that strikes the best possible balance between conflicting objectives. This approach is applied to two decompositions of the inverse VMAT planning problem: a fluence-based relaxation considered at a coarsened gantry angle spacing and under a regularizing penalty on fluence modulation, and a segment weight-based restriction in a neighborhood of the solution to the relaxed problem. The two considered variable domains are interconnected by direct machine parameter optimization toward reproducing the dose-volume histogram of the fluence-based solution. RESULTS The dose distribution quality of plans generated by the proposed MCO method was assessed by direct comparison with benchmark plans generated by a conventional VMAT planning method. The results for four patient cases (prostate, pancreas, lung, and head and neck) are highly comparable between the MCO plans and the benchmark plans: Discrepancies between studied dose-volume statistics for organs at risk were-with the exception of the kidneys of the pancreas case-within 1 Gy or 1 percentage point. Target coverage of the MCO plans was comparable with that of the benchmark plans, but with a small tendency toward a shift from conformity to homogeneity. CONCLUSIONS MCO allows tradeoffs between conflicting objectives encountered in VMAT planning to be explored in an interactive manner through search over a continuous representation of the relevant treatment options. Treatment plans selected from such a representation are of comparable dose distribution quality to conventionally optimized VMAT plans.

Optimization approaches to volumetric modulated arc therapy planning

Volumetric modulated arc therapy (VMAT) has found widespread clinical application in recent years. A large number of treatment planning studies have evaluated the potential for VMAT for different disease sites based on the currently available commercial implementations of VMAT planning. In contrast, literature on the underlying mathematical optimization methods used in treatment planning is scarce. VMAT planning represents a challenging large scale optimization problem. In contrast to fluence map optimization in intensity-modulated radiotherapy planning for static beams, VMAT planning represents a nonconvex optimization problem. In this paper, the authors review the state-of-the-art in VMAT planning from an algorithmic perspective. Different approaches to VMAT optimization, including arc sequencing methods, extensions of direct aperture optimization, and direct optimization of leaf trajectories are reviewed. Their advantages and limitations are outlined and recommendations for improvements are discussed.

Advantages and limitations of navigation-based multicriteria optimization (MCO) for localized prostate cancer IMRT planning

Efficacy of inverse planning is becoming increasingly important for advanced radiotherapy techniques. This studys aims were to validate multicriteria optimization (MCO) in RayStation (v2.4, RaySearch Laboratories, Sweden) against standard intensity-modulated radiation therapy (IMRT) optimization in Oncentra (v4.1, Nucletron BV, the Netherlands) and characterize dose differences due to conversion of navigated MCO plans into deliverable multileaf collimator apertures. Step-and-shoot IMRT plans were created for 10 patients with localized prostate cancer using both standard optimization and MCO. Acceptable standard IMRT plans with minimal average rectal dose were chosen for comparison with deliverable MCO plans. The trade-off was, for the MCO plans, managed through a user interface that permits continuous navigation between fluence-based plans. Navigated MCO plans were made deliverable at incremental steps along a trajectory between maximal target homogeneity and maximal rectal sparing. Dosimetric differences between navigated and deliverable MCO plans were also quantified. MCO plans, chosen as acceptable under navigated and deliverable conditions resulted in similar rectal sparing compared with standard optimization (33.7 ± 1.8 Gy vs 35.5 ± 4.2 Gy, p = 0.117). The dose differences between navigated and deliverable MCO plans increased as higher priority was placed on rectal avoidance. If the best possible deliverable MCO was chosen, a significant reduction in rectal dose was observed in comparison with standard optimization (30.6 ± 1.4 Gy vs 35.5 ± 4.2 Gy, p = 0.047). Improvements were, however, to some extent, at the expense of less conformal dose distributions, which resulted in significantly higher doses to the bladder for 2 of the 3 tolerance levels. In conclusion, similar IMRT plans can be created for patients with prostate cancer using MCO compared with standard optimization. Limitations exist within MCO regarding conversion of navigated plans to deliverable apertures, particularly for plans that emphasize avoidance of critical structures. Minimizing these differences would result in better quality treatments for patients with prostate cancer who were treated with radiotherapy using MCO plans.

Necessary and sufficient conditions for Pareto efficiency in robust multiobjective optimization

We provide necessary and sufficient conditions for robust efficiency (in the sense of Ehrgott et al., 2014) to multiobjective optimization problems that depend on uncertain parameters. These conditions state that a solution is robust efficient (under minimization) if it is optimal to a strongly increasing scalarizing function, and only if it is optimal to a strictly increasing scalarizing function. By counterexample, we show that the necessary condition cannot be strengthened to convex scalarizing functions, even for convex problems. We therefore define and characterize a subset of the robust efficient solutions for which an analogous necessary condition holds with respect to convex scalarizing functions. This result parallels the deterministic case where optimality to a convex and strictly increasing scalarizing function constitutes a necessary condition for efficiency. By a numerical example from the field of radiation therapy treatment plan optimization, we illustrate that the curvature of the scalarizing function influences the conservatism of an optimized solution in the uncertain case.

Deliverable navigation for multicriteria IMRT treatment planning by combining shared and individual apertures

We consider the problem of deliverable Pareto surface navigation for step-and-shoot intensity-modulated radiation therapy. This problem amounts to calculation of a collection of treatment plans with the property that convex combinations of plans are directly deliverable. Previous methods for deliverable navigation impose restrictions on the number of apertures of the individual plans, or require that all treatment plans have identical apertures. We introduce simultaneous direct step-and-shoot optimization of multiple plans subject to constraints that some of the apertures must be identical across all plans. This method generalizes previous methods for deliverable navigation to allow for treatment plans with some apertures from a collective pool and some apertures that are individual. The method can also be used as a post-processing step to previous methods for deliverable navigation in order to improve upon their plans. By applying the method to subsets of plans in the collection representing the Pareto set, we show how it can enable convergence toward the unrestricted (non-navigable) Pareto set where all apertures are individual.

Projections onto the Pareto surface in multicriteria radiation therapy optimization

PURPOSE To eliminate or reduce the error to Pareto optimality that arises in Pareto surface navigation when the Pareto surface is approximated by a small number of plans. METHODS The authors propose to project the navigated plan onto the Pareto surface as a postprocessing step to the navigation. The projection attempts to find a Pareto optimal plan that is at least as good as or better than the initial navigated plan with respect to all objective functions. An augmented form of projection is also suggested where dose-volume histogram constraints are used to prevent that the projection causes a violation of some clinical goal. The projections were evaluated with respect to planning for intensity modulated radiation therapy delivered by step-and-shoot and sliding window and spot-scanned intensity modulated proton therapy. Retrospective plans were generated for a prostate and a head and neck case. RESULTS The projections led to improved dose conformity and better sparing of organs at risk (OARs) for all three delivery techniques and both patient cases. The mean dose to OARs decreased by 3.1 Gy on average for the unconstrained form of the projection and by 2.0 Gy on average when dose-volume histogram constraints were used. No consistent improvements in target homogeneity were observed. CONCLUSIONS There are situations when Pareto navigation leaves room for improvement in OAR sparing and dose conformity, for example, if the approximation of the Pareto surface is coarse or the problem formulation has too permissive constraints. A projection onto the Pareto surface can identify an inaccurate Pareto surface representation and, if necessary, improve the quality of the navigated plan.

Distributed approximation of Pareto surfaces in multicriteria radiation therapy treatment planning

We consider multicriteria radiation therapy treatment planning by navigation over the Pareto surface, implemented by interpolation between discrete treatment plans. Current state of the art for calculation of a discrete representation of the Pareto surface is to sandwich this set between inner and outer approximations that are updated one point at a time. In this paper, we generalize this sequential method to an algorithm that permits parallelization. The principle of the generalization is to apply the sequential method to an approximation of an inexpensive model of the Pareto surface. The information gathered from the model is sub-sequently used for the calculation of points from the exact Pareto surface, which are processed in parallel. The model is constructed according to the current inner and outer approximations, and given a shape that is difficult to approximate, in order to avoid that parts of the Pareto surface are incorrectly disregarded. Approximations of comparable quality to those generated by the sequential method are demonstrated when the degree of parallelization is up to twice the number of dimensions of the objective space. For practical applications, the number of dimensions is typically at least five, so that a speed-up of one order of magnitude is obtained.

Scenario-based radiation therapy margins for patient setup, organ motion, and particle range uncertainty

This work extends and validates the scenario-based generalization of margins presented in Fredriksson and Bokrantz (2016 Phys. Med. Biol. 61 2067-82). Scenario-based margins are, in their original form, a method for robust planning under setup uncertainty where the sum of a plan evaluation criterion over a set of scenarios is optimized. The voxelwise penalties in the summands are weighted by a distribution of coefficients defined such that the method is mathematically equivalent to the use of conventional geometric margins if the scenario doses are calculated using the static dose cloud approximation. The purpose of this work is to extend scenario-based margins to general types of geometric uncertainty and to validate their use on clinical cases. Specifically, we outline how to incorporate density heterogeneity in the calculation of coefficients and demonstrate the extended methods ability to safeguard against setup errors, organ motion, and range shifts (and combinations thereof). For a water phantom with a high-density slab partly covering the target, the extended form of scenario-based margins method led to improved target coverage robustness compared to the original method. At most minor differences in robustness were, however, observed between the extended and original method for a prostate and two lung patients, all treated with intensity-modulated proton therapy, yielding evidence that the calculation of weighting coefficients is generally insensitive to tissue heterogeneities. The scenario-based margins were, furthermore, verified to provide a comparable level of robustness to expected value and worst case optimization while circumventing some known shortcomings of these methods.