@article{davis_papp_2024, title={Rational dual certificates for weighted sums-of-squares polynomials with boundable bit size}, volume={121}, ISSN={["1095-855X"]}, url={https://doi.org/10.1016/j.jsc.2023.102254}, DOI={10.1016/j.jsc.2023.102254}, abstractNote={In Davis and Papp (2022), the authors introduced the concept of dual certificates of (weighted) sum-of-squares polynomials, which are vectors from the dual cone of weighted sums of squares (WSOS) polynomials that can be interpreted as nonnegativity certificates. This initial theoretical work showed that for every polynomial in the interior of a WSOS cone, there exists a rational dual certificate proving that the polynomial is WSOS. In this article, we analyze the complexity of rational dual certificates of WSOS polynomials by bounding the bit sizes of integer dual certificates as a function of parameters such as the degree and the number of variables of the polynomials, or their distance from the boundary of the cone. After providing a general bound, we explore several special cases, such as univariate polynomials nonnegative over the real line or a bounded interval, represented in different commonly used bases. We also provide an algorithm which runs in rational arithmetic and computes a rational certificate with boundable bit size for a WSOS lower bound of the input polynomial.}, journal={JOURNAL OF SYMBOLIC COMPUTATION}, author={Davis, Maria M. and Papp, David}, year={2024} } @article{torelli_papp_unkelbach_2023, title={Spatiotemporal fractionation schemes for stereotactic radiosurgery of multiple brain metastases}, volume={6}, ISSN={["2473-4209"]}, DOI={10.1002/mp.16457}, abstractNote={AbstractBackgroundStereotactic radiosurgery (SRS) is an established treatment for patients with brain metastases (BMs). However, damage to the healthy brain may limit the tumor dose for patients with multiple lesions.PurposeIn this study, we investigate the potential of spatiotemporal fractionation schemes to reduce the biological dose received by the healthy brain in SRS of multiple BMs, and also demonstrate a novel concept of spatiotemporal fractionation for polymetastatic cancer patients that faces less hurdles for clinical implementation.MethodsSpatiotemporal fractionation (STF) schemes aim at partial hypofractionation in the metastases along with more uniform fractionation in the healthy brain. This is achieved by delivering distinct dose distributions in different fractions, which are designed based on their cumulative biologically effective dose () such that each fraction contributes with high doses to complementary parts of the target volume, while similar dose baths are delivered to the normal tissue. For patients with multiple brain metastases, a novel constrained approach to spatiotemporal fractionation (cSTF) is proposed, which is more robust against setup and biological uncertainties. The approach aims at irradiating entire metastases with possibly different doses, but spatially similar dose distributions in every fraction, where the optimal dose contribution of every fraction to each metastasis is determined using a new planning objective to be added to the BED‐based treatment plan optimization problem. The benefits of spatiotemporal fractionation schemes are evaluated for three patients, each with >25 BMs.ResultsFor the same tumor BED10 and the same brain volume exposed to high doses in all plans, the mean brain BED2 can be reduced compared to uniformly fractionated plans by 9%–12% with the cSTF plans and by 13%–19% with the STF plans. In contrast to the STF plans, the cSTF plans avoid partial irradiation of the individual metastases and are less sensitive to misalignments of the fractional dose distributions when setup errors occur.ConclusionSpatiotemporal fractionation schemes represent an approach to lower the biological dose to the healthy brain in SRS‐based treatments of multiple BMs. Although cSTF cannot achieve the full BED reduction of STF, it improves on uniform fractionation and is more robust against both setup errors and biological uncertainties related to partial tumor irradiation.}, journal={MEDICAL PHYSICS}, author={Torelli, Nathan and Papp, David and Unkelbach, Jan}, year={2023}, month={Jun} } @article{papp_regos_domokos_bozoki_2023, title={The smallest mono-unstable convex polyhedron with point masses has 8 faces and 11 vertices}, volume={310}, ISSN={["1872-6860"]}, url={https://doi.org/10.1016/j.ejor.2023.04.028}, DOI={10.1016/j.ejor.2023.04.028}, abstractNote={In the study of monostatic polyhedra, initiated by John H. Conway in 1966, the main question is to construct such an object with the minimal number of faces and vertices. By distinguishing between various material distributions and stability types, this expands into a small family of related questions. While many upper and lower bounds on the necessary numbers of faces and vertices have been established, none of these questions has been so far resolved. Adapting an algorithm presented in Bozóki et al. (2022), here we offer the first complete answer to a question from this family: by using the toolbox of semidefinite optimization to efficiently generate the hundreds of thousands of infeasibility certificates, we provide the first-ever proof for the existence of a monostatic polyhedron with point masses, having minimal number (V=11) of vertices (Theorem 3) and a minimal number (F=8) of faces. We also show that V=11 is the smallest number of vertices that a mono-unstable polyhedron can have in all dimensions greater than 1 (Corollary 6).}, number={2}, journal={EUROPEAN JOURNAL OF OPERATIONAL RESEARCH}, author={Papp, David and Regos, Krisztina and Domokos, Gabor and Bozoki, Sandor}, year={2023}, month={Oct}, pages={511–517} } @article{fabiano_torelli_papp_unkelbach_2022, title={A novel stochastic optimization method for handling misalignments of proton and photon doses in combined treatments}, volume={67}, ISSN={["1361-6560"]}, DOI={10.1088/1361-6560/ac858f}, abstractNote={Abstract 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 b and standard deviation σ b of the cumulative BED b in every voxel of a structure. For the target, a piecewise quadratic penalty function of the form b min − E b − 2 σ b + 2 is minimized, aiming for plans in which the expected BED minus two times the standard deviation exceeds the prescribed BED b min . Analogously, E b + 2 σ b − b max + 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.}, number={18}, journal={PHYSICS IN MEDICINE AND BIOLOGY}, author={Fabiano, Silvia and Torelli, Nathan and Papp, David and Unkelbach, Jan}, year={2022}, month={Sep} } @article{papp_yildiz_2021, title={Alfonso: Matlab Package for Nonsymmetric Conic Optimization}, volume={34}, ISSN={["1526-5528"]}, url={https://doi.org/10.1287/ijoc.2021.1058}, DOI={10.1287/ijoc.2021.1058}, abstractNote={ 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. }, number={1}, journal={INFORMS JOURNAL ON COMPUTING}, publisher={Institute for Operations Research and the Management Sciences (INFORMS)}, author={Papp, David and Yildiz, Sercan}, year={2021}, month={Sep} } @article{davis_papp_2022, title={DUAL CERTIFICATES AND EFFICIENT RATIONAL SUM-OF-SQUARES DECOMPOSITIONS FOR POLYNOMIAL OPTIMIZATION OVER COMPACT SETS}, volume={32}, ISSN={["1095-7189"]}, url={https://doi.org/10.1137/21M1422574}, DOI={10.1137/21M1422574}, abstractNote={We study the problem of computing weighted sum-of-squares (WSOS) certificates for positive polynomials over a compact semialgebraic set. Building on the theory of interior-point methods for convex optimization, we introduce the concept of dual cone certificates, which allows us to interpret vectors from the dual of the sum-of-squares cone as rigorous nonnegativity certificates of a WSOS polynomial. Whereas conventional WSOS certificates are alternative representations of the polynomials they certify, dual certificates are distinct from the certified polynomials; moreover, each dual certificate certifies a full-dimensional convex cone of WSOS polynomials. As a result, rational WSOS certificates can be constructed from numerically computed dual certificates at little additional cost, without any rounding or projection steps applied to the numerical certificates. As an additional algorithmic application, we present an almost entirely numerical hybrid algorithm for computing the optimal WSOS lower bound of a given polynomial along with a rational dual certificate, with a polynomial-time computational cost per iteration and linear rate of convergence.}, number={4}, journal={SIAM JOURNAL ON OPTIMIZATION}, author={Davis, Maria M. and Papp, David}, year={2022}, pages={2461–2492} } @article{papp_2023, title={Duality of sum of nonnegative circuit polynomials and optimal SONC bounds}, volume={114}, ISSN={["1095-855X"]}, DOI={10.1016/j.jsc.2022.04.015}, abstractNote={Circuit polynomials are polynomials with properties that make it easy to compute sharp and certifiable global lower bounds for them. Consequently, one may use them to find certifiable lower bounds for any polynomial by writing it as a sum of circuit polynomials with known lower bounds. Recent work has shown that sums of nonnegative circuit polynomials (or SONC polynomials for short) can be used to compute global lower bounds (called SONC bounds) for polynomials in this manner very efficiently both in theory and in practice, if the polynomial is bounded from below and its support satisfies a certain nondegeneracy assumption. The quality of the SONC bound depends on the circuits used in the computation but finding the set of circuits that yield the best attainable SONC bound among the astronomical number of candidate circuits is a non-trivial task that has not been addressed so far. We propose an efficient method to compute the optimal SONC lower bound by iteratively identifying the optimal circuits to use in the SONC bounding process. The method is derived from a new proof of the result that every SONC polynomial decomposes into SONC polynomials on the same support. This proof is based on convex programming duality and motivates a column generation approach that is particularly attractive for sparse polynomials of high degree and with many unknowns. The method is implemented and tested on a large set of sparse polynomial optimization problems with up to 40 unknowns, of degree up to 60, and up to 3000 monomials in the support. The results indicate that the method is efficient in practice and requires only a small number of iterations to identify the optimal circuits.}, journal={JOURNAL OF SYMBOLIC COMPUTATION}, author={Papp, David}, year={2023}, pages={246–266} } @article{papp_unkelbach_2022, title={Technical note: Optimal allocation of limited proton therapy resources using model-based patient selection}, volume={6}, ISSN={["2473-4209"]}, DOI={10.1002/mp.15812}, abstractNote={AbstractPurposeWe 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.MethodsTo 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.ResultsThe 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.ConclusionsMDP 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.}, journal={MEDICAL PHYSICS}, author={Papp, David and Unkelbach, Jan}, year={2022}, month={Jun} } @article{papp_yıldız_2021, title={Code and Data Repository for alfonso: Matlab Package for Nonsymmetric Conic Optimization}, url={https://doi.org/10.1287/ijoc.2021.1058.cd}, DOI={10.1287/ijoc.2021.1058.cd}, abstractNote={The software in this repository is a snapshot (last revised on 2020/07/20) of the software that was used in the research reported in the paper alfonso: Matlab package for nonsymmetric conic optimization by Dávid Papp and Sercan Yıldız.}, journal={INFORMS Journal on Computing}, author={Papp, Dávid and Yıldız, Sercan}, year={2021}, month={Sep} } @article{loizeau_fabiano_papp_stuetzer_jakobi_bandurska-luque_troost_richter_unkelbach_2021, title={Optimal Allocation of Proton Therapy Slots in Combined Proton-Photon Radiation Therapy}, volume={111}, ISSN={["1879-355X"]}, DOI={10.1016/j.ijrobp.2021.03.054}, abstractNote={Purpose Proton therapy is a limited resource that is not available to all patients who may benefit from it. We investigated combined proton-photon treatments, in which some fractions are delivered with protons and the remaining fractions with photons, as an approach to maximize the benefit of limited proton therapy resources at a population level. Methods and Materials To quantify differences in normal-tissue complication probability (NTCP) between protons and photons, we considered a cohort of 45 patients with head and neck cancer for whom intensity modulated radiation therapy and intensity modulated proton therapy plans were previously created, in combination with NTCP models for xerostomia and dysphagia considered in the Netherlands for proton patient selection. Assuming limited availability of proton slots, we developed methods to optimally assign proton fractions in combined proton-photon treatments to minimize the average NTCP on a population level. The combined treatments were compared with patient selection strategies in which patients are assigned to single-modality proton or photon treatments. Results There is a benefit of combined proton-photon treatments compared with patient selection, owing to the nonlinearity of NTCP functions; that is, the initial proton fractions are the most beneficial, whereas additional proton fractions have a decreasing benefit when a flatter part of the NTCP curve is reached. This effect was small for the patient cohort and NTCP models considered, but it may be larger if dose-response relationships are better known. In addition, when proton slots are limited, patient selection methods face a trade-off between leaving slots unused and blocking slots for future patients who may have a larger benefit. Combined proton-photon treatments with flexible proton slot assignment provide a method to make optimal use of all available resources. Conclusions Combined proton-photon treatments allow for better use of limited proton therapy resources. The benefit over patient selection schemes depends on the NTCP models and the dose differences between protons and photons. Proton therapy is a limited resource that is not available to all patients who may benefit from it. We investigated combined proton-photon treatments, in which some fractions are delivered with protons and the remaining fractions with photons, as an approach to maximize the benefit of limited proton therapy resources at a population level. To quantify differences in normal-tissue complication probability (NTCP) between protons and photons, we considered a cohort of 45 patients with head and neck cancer for whom intensity modulated radiation therapy and intensity modulated proton therapy plans were previously created, in combination with NTCP models for xerostomia and dysphagia considered in the Netherlands for proton patient selection. Assuming limited availability of proton slots, we developed methods to optimally assign proton fractions in combined proton-photon treatments to minimize the average NTCP on a population level. The combined treatments were compared with patient selection strategies in which patients are assigned to single-modality proton or photon treatments. There is a benefit of combined proton-photon treatments compared with patient selection, owing to the nonlinearity of NTCP functions; that is, the initial proton fractions are the most beneficial, whereas additional proton fractions have a decreasing benefit when a flatter part of the NTCP curve is reached. This effect was small for the patient cohort and NTCP models considered, but it may be larger if dose-response relationships are better known. In addition, when proton slots are limited, patient selection methods face a trade-off between leaving slots unused and blocking slots for future patients who may have a larger benefit. Combined proton-photon treatments with flexible proton slot assignment provide a method to make optimal use of all available resources. Combined proton-photon treatments allow for better use of limited proton therapy resources. The benefit over patient selection schemes depends on the NTCP models and the dose differences between protons and photons.}, number={1}, journal={INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS}, author={Loizeau, Nicolas and Fabiano, Silvia and Papp, David and Stuetzer, Kristin and Jakobi, Annika and Bandurska-Luque, Anna and Troost, Esther G. C. and Richter, Christian and Unkelbach, Jan}, year={2021}, month={Sep}, pages={196–207} } @article{alfonso: matlab package for nonsymmetric conic optimization_2021, year={2021}, month={Jan} } @article{duality of sum of nonnegative circuit polynomials and optimal sonc bounds_2019, year={2019}, month={Dec} } @article{gaddy_unkelbach_papp_2019, title={Robust spatiotemporal fractionation schemes in the presence of patient setup uncertainty}, volume={46}, ISSN={["2473-4209"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85067341334&partnerID=MN8TOARS}, DOI={10.1002/mp.13593}, abstractNote={PurposeSpatiotemporal fractionation schemes for photon radiotherapy have recently arisen as a promising technique for healthy tissue sparing. Because spatiotemporally fractionated treatments have a characteristic pattern of delivering high doses to different parts of the tumor in each fraction, uncertainty in patient positioning is an even more pressing concern than in conventional uniform fractionation. Until now, such concerns in patient setup uncertainty have not been addressed in the context of spatiotemporal fractionation.MethodsA stochastic optimization model is used to incorporate patient setup uncertainty to optimize spatiotemporally fractionated plans using expected penalties for deviations from prescription values. First, a robust uniform reference plan is optimized with a stochastic optimization model. Then, a spatiotemporal plan is optimized with a constrained stochastic optimization model that minimizes a primary clinical objective and constrains the spatiotemporal plan to be at least as good as the uniform reference plan with respect to all other objectives. A discrete probability distribution is defined to characterize the random setup error occurring in each fraction. For the optimization of uniform plans, the expected penalties are computed exactly by exploiting the symmetry of the fractions, and for the spatiotemporal plans, quasi‐Monte Carlo sampling is used to approximate the expectation.ResultsUsing five clinical liver cases, it is demonstrated that spatiotemporally fractionated treatment plans maintain the same robust tumor coverage as a stochastic uniform reference plan and exhibit a reduction in the expected mean BED of the uninvolved liver. This is observed for a spectrum of probability distributions of random setup errors with shifts in the patient position of up to 5 mm from the nominal position. For probability distributions with small variance in the patient position, the spatiotemporal plans exhibit an 8–30% reduction in expected mean BED in the healthy liver tissue for shifts up to 2.5 mm and reductions of 5–25% for shifts up to 5 mm.ConclusionsIn the presence of patient setup uncertainty, spatiotemporally fractionated treatment plans exhibit the same robust tumor coverage as their uniformly fractionated counterparts and still retain the benefit in sparing healthy tissues.}, number={7}, journal={MEDICAL PHYSICS}, author={Gaddy, Melissa R. and Unkelbach, Jan and Papp, David}, year={2019}, month={Jul}, pages={2988–3000} } @article{papp_yildiz_2019, title={SUM-OF-SQUARES OPTIMIZATION WITHOUT SEMIDEFINITE PROGRAMMING}, volume={29}, ISSN={["1095-7189"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85065410798&partnerID=MN8TOARS}, DOI={10.1137/17M1160124}, abstractNote={We propose a homogeneous primal-dual interior-point method to solve sum-of-squares optimization problems by combining non-symmetric conic optimization techniques and polynomial interpolation. The approach optimizes directly over the sum-of-squares cone and its dual, circumventing the semidefinite programming (SDP) reformulation which requires a large number of auxiliary variables. As a result, it has substantially lower theoretical time and space complexity than the conventional SDP-based approach. Although our approach circumvents the semidefinite programming reformulation, an optimal solution to the semidefinite program can be recovered with little additional effort. Computational results confirm that for problems involving high-degree polynomials, the proposed method is several orders of magnitude faster than semidefinite programming.}, number={1}, journal={SIAM JOURNAL ON OPTIMIZATION}, author={Papp, David and Yildiz, Sercan}, year={2019}, pages={822–851} } @article{semi-infinite programming_2019, url={http://dx.doi.org/10.1002/9781118445112.stat02391.pub2}, DOI={10.1002/9781118445112.stat02391.pub2}, abstractNote={Abstract Semi‐infinite programs are optimization problems with either infinitely many constraints or infinitely many variables (but not both). This article reviews the fundamental duality theory and optimality conditions of such optimization problems and the most popular algorithmic strategies for their numerical solution. Easily implementable general methods are presented first, which require the solution of a sequence of conventional (finite) nonlinear optimization problems. Conic optimization problems, for which more efficient specialized methods are available, are also discussed.}, journal={Wiley StatsRef: Statistics Reference Online}, year={2019}, month={Aug} } @article{gaddy_yildiz_unkelbach_papp_2018, title={Optimization of spatiotemporally fractionated radiotherapy treatments with bounds on the achievable benefit}, volume={63}, ISSN={["1361-6560"]}, url={http://dx.doi.org/10.1088/1361-6560/aa9975}, DOI={10.1088/1361-6560/aa9975}, abstractNote={Abstract Spatiotemporal fractionation schemes, that is, treatments delivering different dose distributions in different fractions, can potentially lower treatment side effects without compromising tumor control. This can be achieved by hypofractionating parts of the tumor while delivering approximately uniformly fractionated doses to the surrounding tissue. Plan optimization for such treatments is based on biologically effective dose (BED); however, this leads to computationally challenging nonconvex optimization problems. Optimization methods that are in current use yield only locally optimal solutions, and it has hitherto been unclear whether these plans are close to the global optimum. We present an optimization framework to compute rigorous bounds on the maximum achievable normal tissue BED reduction for spatiotemporal plans. The approach is demonstrated on liver tumors, where the primary goal is to reduce mean liver BED without compromising any other treatment objective. The BED-based treatment plan optimization problems are formulated as quadratically constrained quadratic programming (QCQP) problems. First, a conventional, uniformly fractionated reference plan is computed using convex optimization. Then, a second, nonconvex, QCQP model is solved to local optimality to compute a spatiotemporally fractionated plan that minimizes mean liver BED, subject to the constraints that the plan is no worse than the reference plan with respect to all other planning goals. Finally, we derive a convex relaxation of the second model in the form of a semidefinite programming problem, which provides a rigorous lower bound on the lowest achievable mean liver BED. The method is presented on five cases with distinct geometries. The computed spatiotemporal plans achieve 12–35% mean liver BED reduction over the optimal uniformly fractionated plans. This reduction corresponds to 79–97% of the gap between the mean liver BED of the uniform reference plans and our lower bounds on the lowest achievable mean liver BED. The results indicate that spatiotemporal treatments can achieve substantial reductions in normal tissue dose and BED, and that local optimization techniques provide high-quality plans that are close to realizing the maximum potential normal tissue dose reduction.}, number={1}, journal={PHYSICS IN MEDICINE AND BIOLOGY}, author={Gaddy, Melissa R. and Yildiz, Sercan and Unkelbach, Jan and Papp, David}, year={2018}, month={Jan} } @article{unkelbach_papp_gaddy_andratschke_hong_guckenberger_2018, title={PO-0900: Spatiotemporal fractionation schemes for liver stereotactic body radiotherapy}, volume={127}, ISSN={0167-8140}, url={http://dx.doi.org/10.1016/S0167-8140(18)31210-6}, DOI={10.1016/S0167-8140(18)31210-6}, abstractNote={ESTRO 37 S479 response relations affect the potential benefit of dosepainting and how they can be accounted for using robust optimization. Material and MethodsFor this purpose, robust dose-painting was developed and implemented in our fully automated clinical TPS, such that the expected TCP is optimized for both uncertain dose-response relations and Gaussian systematic (∑=3 mm) and random (σ=5.5 mm) set-up uncertainties.The TCP of the tumor was modeled as the product of the TCPs over all voxels, which were described by sigmoid shaped dose-response relations with uncertain parameters that followed Gaussian distributions.The effect of uncertainty was modeled for different geometrical situations and for a range of TCP parameters.The geometrical situations consisted of 3 phantoms (Fig 1) and a patient case (Fig 2).The TCP parameters varied with ΔTD50 (difference in TD50 between the resistant and sensitive regions) ranging from 0 to 35 Gy.Optimizations were performed for different levels of uncertainty, expressed by the SD of the TD50 (TD50σ), that varied from 0 (no uncertainty) to 10 Gy.For a fair evaluation, dose-painting was compared to non-specific dose escalation with the same dose constraints.}, journal={Radiotherapy and Oncology}, publisher={Elsevier BV}, author={Unkelbach, J. and Papp, D. and Gaddy, M. and Andratschke, N. and Hong, T. and Guckenberger, M.}, year={2018}, month={Apr}, pages={S479–S480} } @book{tóth_nagy_papp_2018, title={Reaction kinetics: Exercises, programs and theorems: Mathematica for deterministic and stochastic kinetics}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85061518011&partnerID=MN8TOARS}, DOI={10.1007/978-1-4939-8643-9}, journal={Reaction Kinetics: Exercises, Programs and Theorems: Mathematica for Deterministic and Stochastic Kinetics}, author={Tóth, J. and Nagy, A.L. and Papp, D.}, year={2018}, pages={1–469} } @article{papp_2017, title={SEMI-INFINITE PROGRAMMING USING HIGH-DEGREE POLYNOMIAL INTERPOLANTS AND SEMIDEFINITE PROGRAMMING}, volume={27}, ISSN={["1095-7189"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85032876902&partnerID=MN8TOARS}, DOI={10.1137/15m1053578}, abstractNote={In a common formulation of semi-infinite programs, the infinite constraint set is a requirement that a function parametrized by the decision variables is nonnegative over an interval. If this function is sufficiently closely approximable by a polynomial or a rational function, then the semi-infinite program can be reformulated as an equivalent semidefinite program. Solving this semidefinite program is challenging if the polynomials involved are of high degree, due to numerical difficulties and bad scaling arising both from the polynomial approximations and from the fact that the semidefinite programming constraints coming from the sum-of-squares representation of nonnegative polynomials are badly scaled. We combine rational function approximation techniques and polynomial programming to overcome these numerical difficulties, using sum-of-squares interpolants. Specifically, it is shown that the conditioning of the reformulations using sum-of-squares interpolants does not deteriorate with increasing degrees, and problems involving sum-of-squares interpolants of hundreds of degrees can be handled without difficulty. The proposed reformulations are sufficiently well scaled that they can be solved easily with every commonly used semidefinite programming solver, such as SeDuMi, SDPT3, and CSDP. Motivating applications include convex optimization problems with semi-infinite constraints and semidefinite conic inequalities, such as those arising in the optimal design of experiments. Numerical results align with the theoretical predictions; in the problems considered, available memory was the only factor limiting the degrees of polynomials, to approximately 1000.}, number={3}, journal={SIAM JOURNAL ON OPTIMIZATION}, author={Papp, David}, year={2017}, pages={1858–1879} } @article{unkelbach_papp_gaddy_andratschke_hong_guckenberger_2017, title={Spatiotemporal fractionation schemes for liver stereotactic body radiotherapy}, volume={125}, ISSN={0167-8140}, url={http://dx.doi.org/10.1016/j.radonc.2017.09.003}, DOI={10.1016/j.radonc.2017.09.003}, abstractNote={