Maximizing the benefit of limited proton therapy resources through combined proton-photon treatments

Objective: Although rapidly growing, proton therapy (PT) is a limited resource, which is not available to all patients who may benefit from it. Here, we investigate combined proton-photon treatments as an approach to optimally use the limited PT resources and maximize the benefit of PT at a population level. As an example, we consider a clinic offering both photons and protons and a scenario, in which only limited PT slots are available per day for treating head and neck cancer (HNC) patients.
Materials and methods: We assume a fixed number of available proton slots per day and, on average, 2 new HNC patients per week, each receiving 30 fractions over 6 weeks. We designed a slot allocation model that selects, on a daily basis, those patients currently under treatment who benefit the most from a proton treatment on the respective day. The remaining patients on that day receive a photon fraction. The model is based on modern normal tissue complication probability (NTCP) models (e.g. for xerostomia [2]). This daily slot allocation strategy is compared (in terms of average NTCP values) to a threshold-based PT patient selection in which patients are selected for whole PT treatment if a slot is available at start of fractionated treatment and their ΔNTCP exceeds a threshold (5%, 10%, 15%). To simulate many patients, the doses in relevant OARs (e.g. contralateral parotid gland) are sampled from a 2D gaussian distribution (Figure 1) derived from the OAR doses of 45 HNC patients for which IMRT and IMPT plans were previously created [1] and rescaled to a standard of care prescription (1.8 Gy to PTV, 2.3 Gy to GTV).
Results: The daily slot allocation strategy leads to a higher reduction of the average NTCP values for xerostomia than the threshold-based PT patient selection as shown in Figure 2 for any number of available proton slot per day. If all patients receive only photons or only protons, the average NTCP values for xerostomia are 16.9% and 6.3%, respectively. If 3 proton slots are available per day for HNC patients, the average NTCP value for xerostomia is 12.5% for the daily slot allocation strategy and 14.0% for the threshold-based PT patient selection which would select patients with 10% ΔNTCP threshold. The NTCP benefit of 1.5% can be explained by two considerations: 1) combined proton-photon treatments make optimal use of all proton slots whereas patient selection strategies face a trade-off between leaving slots unused or blocking slots for future patients with higher benefit; 2) on the convex part of the NTCP curve, the first proton fractions delivered are the most beneficial.
Conclusion: Limited proton therapy resources can be more efficiently utilized, from a global health system perspective, with combined proton-photon treatments with daily allocation of proton slots compared to single-modality treatments with optimal patient selection.
[1] Jakobi A. et al., IJROBP, 92.5 (2015): 1165-1174 [2] Houweling A.C. et al., IJROBP, 76.4 (2010): 1259-1265