Optimal allocation of proton therapy slots in combined proton-photon radiotherapy

Purpose: Proton therapy is a limited resource, which is not available to all patients who may benefit from it. We investigate 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: To quantify differences in normal tissue complication probability (NTCP) between protons and photons, we consider a cohort of 45 head-and-neck cancer patients for which IMRT and IMPT 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 develop methods to optimally assign proton fractions in combined proton-photon treatments to minimize the average NTCP on a population level. Such combined treatments are compared to 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 over patient selection due to the nonlinearity of NTCP functions, i.e. 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 may be larger if dose-response relationships are better known. In addition, when proton slots are limited, patient selection methods face a tradeoff 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 a better utilization of limited proton therapy resources. The benefit over patient selection schemes depends on the NTCP models and the dose differences between protons and photons.