Application of Tumor Control (TCP) and Normal Tissue-Complication Probabilities (NTCP) to Determine the Best Robust Optimization (RO) Approaches for Proton Head and Neck Radiotherapy

Abstract

Implementation of RO for intensity modulated proton therapy (IMPT) can be performed with coupled or uncoupled geometric and stopping power (range) uncertainties. Currently, there is no clinical consensus regarding the optimal approach. TCP and NTCP models can be used as a relative metric to help determine the approach that may lead to better clinical outcomes. IMPT plans were created for ten anonymized head and neck (HN) patients previously treated with volumetric modulated arc therapy (VMAT). Comparison plans were created utilizing RO with both coupled and uncoupled geometric and stopping power uncertainties using equivalent optimization parameters. Equivalent-uniform dose (EUD), logistic-response modeling of multi-volume TCPs and NTCPs of the parotids (≥ Grade 2 xerostomia), constrictors (≥ Grade 2 dysphagia), and larynx (≥ Grade 2 edema) were used to compare plans under 20 separate uncertainty, coupled and uncoupled, evaluation scenarios (geometric uncertainties of ±3mm and stopping power uncertainties of ±3%). Although there are patient-by-patient variations, mean total NTCP, for the three OARs analyzed, were comparable under both coupled and uncoupled RO scenarios. Compared to nominal uncoupled plans, the total mean NTCP increased by a maximum of 10.7±4.8% (uncoupled RO) and 9.9±6.3% (coupled RO). Both maximums occurred for an evaluation with 3mm superior shifts coupled with underestimation (-3%) of stopping powers. Compared to the same nominal plans, multiplicative TCP rates varied precipitously under various evaluation scenarios, ranging from a loss of TCP of 72.7±26.6% to a TCP gain of 10.2±9.8%. Regardless of the magnitude of the TCP change, the coupled and uncoupled plans for each scenario were within ±16.1% of each other with a mean difference of 0.2±3.2%. Plans with uncoupled RO had 5.2% greater relative TCP than coupled RO plans when stopping powers were underestimated. Conversely, plans with coupled RO had 4.5% greater relative TCP than uncoupled RO plans when stopping powers were overestimated. The ideal RO implementation for head and neck IMPT is primarily dependent on the accuracy of the planned stopping power ratio to the true stopping power ratio of each beam. When planned stopping power is overestimated, RO with uncoupled uncertainty parameters outperform coupled uncertainties in terms of overall TCP and NTCP. The opposite is observed when planned stopping power is underestimated. High HU streaking from metal implants is the most common artifact that affects head and neck proton planning, likely leading to an overestimation of stopping powers, making uncoupled RO preferred for head and neck treatment planning.