Session Item

The aim of the study was to investigate an integrated strategy to quantify potential benefits in terms of toxicity reduction of intensity-modulated proton therapy (IMPT) compared to volumetric modulated arc therapy (VMAT) for nasopharyngeal carcinoma (NPC) patients.

For 50 consecutive locally advanced NPC patients already treated with definitive VMAT and chemotherapy, IMPT plans were optimized and compared evaluating target coverage, homogeneity and conformity indexes (CI), mean and near-to-maximum doses to organs at risk (OARs). Normal tissue complication probability (NTCP) differences were calculated using sixteen validated models (ΔNTCPx-p) and stratified for tumor staging. The patient eligibility for IMPT was assessed using a model-based selection (MBS) strategy following the results on ΔNTCPx-p for 7/16 models describing the most clinically relevant endpoints. A single ΔNTCPx-p threshold of 15% to 5% was set on each model, depending on the severity of the considered complication, or a composite ΔNTCPx-p threshold of 35%. Finally, we developed a comprehensive toxicity score (CTS), defined as the weighted sum of all 16 ΔNTCPx-p, where weights follow a clinical rationale.

Target dose coverage was guaranteed for all plans (PTV D_99% ≥ 67.5 Gy(RBE)), with IMPT showing comparable homogeneity and improved conformity (DCI of -10.9%) over VMAT. For OARs, mean dose deviations were in favor of IMPT (DD_mean ≥14% for cord, esophagus, brainstem and glottic larynx). The risk of toxicity significantly decreased for xerostomia (-12.5%), brain necrosis (-2.3%), mucositis (-3.2%), tinnitus (-8.6%), hypothyroidism (-9.3%) and trismus (-5.4.%). Following MBS strategy, forty per cent of the analyzed patients resulted eligible for proton therapy, with a greater advantage for T3-T4 staging (see Table 1). Significantly different CTS were observed in patients qualifying for IMPT.

Table 1: Percentage of patients eligible for PT with MBS strategy and passing rates relative to single and composite threshold. Values were shown relative to each subgroup of the cohort stratification.

The MBS strategy successfully drives the clinical identification of NPC patients, who are most likely to benefit from IMPT. CTS well summarizes the expected global gain.