Motion and uncertainty in radiotherapy is traditionally handled via margins. The clinical target volume (CTV) is expanded to a larger planning target volume (PTV), which is irradiated to the prescribed dose. However, the PTV concept has several limitations, especially in proton therapy. Therefore, robust and probabilistic optimization methods have been developed that directly incorporate motion and uncertainty into treatment plan optimization for intensity modulated radiotherapy (IMRT) and intensity modulated proton therapy (IMPT). Thereby, the explicit definition of a PTV becomes obsolete and treatment plan optimization is directly based on the CTV. Initial work focused on random and systematic setup errors in IMRT. Later, inter-fraction prostate motion and intra-fraction lung motion became a research focus. Over the past ten years, IMPT has emerged as a new application for robust planning methods. In proton therapy, range or setup errors may lead to dose degradation and misalignment of dose contributions from different beams -a problem that cannot generally be addressed by margins. Therefore, IMPT has led to the first implementations of robust planning methods in commercial planning systems, making these methods available for clinical use. This paper first summarizes the limitations of the PTV concept. Subsequently, robust optimization methods are introduced and their applications in IMRT and IMPT planning are reviewed.Abstract. Motion and uncertainty in radiotherapy is traditionally handled via 31 margins. The clinical target volume (CTV) is expanded to a larger planning target 32 volume (PTV), which is irradiated to the prescribed dose. However, the PTV 33 concept has several limitations, especially in proton therapy. Therefore, robust and 34 probabilistic optimization methods have been developed that directly incorporate 35 motion and uncertainty into treatment plan optimization for intensity modulated 36 radiotherapy (IMRT) and intensity modulated proton therapy (IMPT). Thereby, the 37 explicit definition of a PTV becomes obsolete and treatment plan optimization is 38 directly based on the CTV. Initial work focused on random and systematic setup errors 39 in IMRT. Later, inter-fraction prostate motion and intra-fraction lung motion became 40 a research focus. Over the past 10 years, IMPT has emerged as a new application for 41 robust planning methods. In proton therapy, range or setup errors may lead to dose 42 degradation and misalignment of dose contributions from different beams a problem 43 Robust radiotherapy planning 2 that cannot generally be addressed by margins. Therefore, IMPT has led to the first 44 implementations of robust planning methods in commercial planning systems, making 45 these methods available for clinical use. This paper first summarizes the limitations 46 of the PTV concept. Subsequently, robust optimization methods are introduced and 47 their applications in IMRT and IMPT planning are reviewed. 48 1. Introduction 49Radiotherapy aims at delivering curative doses of radiation ...

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. C 2015 American Association of Physicists in Medicine. [http://dx

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.

We give a scenario-based treatment plan optimization formulation that is equivalent to planning with geometric margins if the scenario doses are calculated using the static dose cloud approximation. If the scenario doses are instead calculated more accurately, then our formulation provides a novel robust planning method that overcomes many of the difficulties associated with previous scenario-based robust planning methods. In particular, our method protects only against uncertainties that can occur in practice, it gives a sharp dose falloff outside high dose regions, and it avoids underdosage of the target in "easy" scenarios. The method shares the benefits of the previous scenario-based robust planning methods over geometric margins for applications where the static dose cloud approximation is inaccurate, such as irradiation with few fields and irradiation with ion beams. These properties are demonstrated on a suite of phantom cases planned for treatment with scanned proton beams subject to systematic setup uncertainty.

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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.

W e 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.

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.