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We consider the following scenario: A radiotherapy clinic has a limited number of proton therapy slots available each day to treat cancer patients of a given tumor site. The clinic's goal is to minimize the expected number of complications in the cohort of all patients of that tumor site treated at the clinic, and thereby maximize the benefit of its limited proton resources.

To address this problem, we extend the normal tissue complication probability (NTCP) model–based approach to proton therapy patient selection to the situation of limited resources at a given institution. We assume that, on each day, a newly diagnosed patient is scheduled for treatment at the clinic with some probability and with some benefit from protons over photons, which is drawn from a probability distribution. When a new patient is scheduled for treatment, a decision for protons or photons must be made, and a patient may wait only for a limited amount of time for a proton slot becoming available. The goal is to determine the thresholds for selecting a patient for proton therapy, which optimally balance the competing goals of making use of all available slots while not blocking slots with patients with low benefit. This problem can be formulated as a Markov decision process (MDP) and the optimal thresholds can be determined via a value‐policy iteration method.

The optimal thresholds depend on the number of available proton slots, the average number of patients under treatment, and the distribution of values. In addition, the optimal thresholds depend on the current utilization of the facility. For example, if one proton slot is available and a second frees up shortly, the optimal threshold is lower compared to a situation where all but one slot remain blocked for longer.

MDP methodology can be used to augment current NTCP model–based patient selection methods to the situation that, on any given day, the number of proton slots is limited. The optimal threshold then depends on the current utilization of the proton facility. Although, the optimal policy yields only a small nominal benefit over a constant threshold, it is more robust against variations in patient load.

 

Objective.Combined proton–photon treatments, where most fractions are delivered with photons and only a few are delivered with protons, may represent a practical approach to optimally use limited proton resources. It has been shown that, when organs at risk (OARs) are located within or near the tumor, the optimal multi-modality treatment uses protons to hypofractionate parts of the target volume and photons to achieve near-uniform fractionation in dose-limiting healthy tissues, thus exploiting the fractionation effect. These plans may be sensitive to range and setup errors, especially misalignments between proton and photon doses. Thus, we developed a novel stochastic optimization method to directly incorporate these uncertainties into the biologically effective dose (BED)-based simultaneous optimization of proton and photon plans.Approach.The method considers the expected value$E\left(b\right)$and standard deviation$\sigma \left(b\right)$of the cumulative BED$b$in every voxel of a structure. For the target, a piecewise quadratic penalty function of the form${\left[b^{\min }-\left(E\left(b\right)-2\sigma \left(b\right)\right)\right]}_{+}^2$is minimized, aiming for plans in which the expected BED minus two times the standard deviation exceeds the prescribed BED$b^{\min }.$Analogously,${\left[\left(E\left(b\right)+2\sigma \left(b\right)\right)-b^{\max }\right]}_{+}^2$is considered for OARs.Main results.Using a spinal metastasis case and a liver cancer patient, it is demonstrated that the novel stochastic optimization method yields robust combined treatment plans. Tumor coverage and a good sparing of the main OARs are maintained despite range and setup errors, and especially misalignments between proton and photon doses. This is achieved without explicitly considering all combinations of proton and photon error scenarios.Significance.Concerns about range and setup errors for safe clinical implementation of optimized proton–photon radiotherapy can be addressed through an appropriate stochastic planning method.

 

We present alfonso, an open-source Matlab package for solving conic optimization problems over nonsymmetric convex cones. The implementation is based on the authors’ corrected analysis of a method of Skajaa and Ye. It enables optimization over any convex cone as long as a logarithmically homogeneous self-concordant barrier is available for the cone or its dual. This includes many nonsymmetric cones, for example, hyperbolicity cones and their duals (such as sum-of-squares cones), semidefinite and second-order cone representable cones, power cones, and the exponential cone. Besides enabling the solution of problems that cannot be cast as optimization problems over a symmetric cone, algorithms for nonsymmetric conic optimization also offer performance advantages for problems whose symmetric cone programming representation requires a large number of auxiliary variables or has a special structure that can be exploited in the barrier computation. The worst-case iteration complexity of alfonso is the best known for nonsymmetric cone optimization: [Formula: see text] iterations to reach an ε-optimal solution, where ν is the barrier parameter of the barrier function used in the optimization. Alfonso can be interfaced with a Matlab function (supplied by the user) that computes the Hessian of a barrier function for the cone. A simplified interface is also available to optimize over the direct product of cones for which a barrier function has already been built into the software. This interface can be easily extended to include new cones. Both interfaces are illustrated by solving linear programs. The oracle interface and the efficiency of alfonso are also demonstrated using an optimal design of experiments problem in which the tailored barrier computation greatly decreases the solution time compared with using state-of-the-art, off-the-shelf conic optimization software. Summary of Contribution: The paper describes an open-source Matlab package for optimization over nonsymmetric cones. A particularly important feature of this software is that, unlike other conic optimization software, it enables optimization over any convex cone as long as a suitable barrier function is available for the cone or its dual, not limiting the user to a small number of specific cones. Nonsymmetric cones for which such barriers are already known include, for example, hyperbolicity cones and their duals (such as sum-of-squares cones), semidefinite and second-order cone representable cones, power cones, and the exponential cone. Thus, the scope of this software is far larger than most current conic optimization software. This does not come at the price of efficiency, as the worst-case iteration complexity of our algorithm matches the iteration complexity of the most successful interior-point methods for symmetric cones. Besides enabling the solution of problems that cannot be cast as optimization problems over a symmetric cone, our software can also offer performance advantages for problems whose symmetric cone programming representation requires a large number of auxiliary variables or has a special structure that can be exploited in the barrier computation. This is also demonstrated in this paper via an example in which our code significantly outperforms Mosek 9 and SCS 2.