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In the Netherlands, the Dutch Proton Therapy group has a standardized plan evaluation protocol to assess robustness of CTV dose for intensity-modulated proton therapy (IMPT). However, its performance to ensure adequate CTV dose might be impacted by (i) differences in dose prescription and treatment planning and (ii) differences between the treatment delivery machines (UMCG/IBA, HPTC/Varian, Maastro/Mevion). Our aim is to assess inter-patient and inter-institutional variation in terms of CTV dose, for a cohort of head-and-neck cancer (HNC) patients treated in the three Dutch proton centers.

Sixty clinical IMPT HNC plans were included, divided in subcohorts of 20 plans per center. Patients were treated to 70 GyRBE and 54.25 GyRBE for the primary and elective CTVs respectively, using 3mm/3% setup/range robustness (SR/RR) settings. Dose was prescribed to different prescription dose levels (L) per center, to the voxel-wise minimum dose of 28 evaluation scenarios: VWmin-D98%,CTVs ≥ L (%) Dpres (Table I). Polynomial Chaos Expansion (PCE) was applied to generate a fast patient- and plan-specific model of voxel doses, enabling a probabilistic robustness evaluation of 100,000 simulated treatment courses for each plan. Setup systematic (Σ) and random (σ) errors were sampled from Gaussian distributions with errors (1SD) of (i) Σ=0.92mm and σ=1.00mm and, consistent with a 3mm margin based on van Herk’s recipe: M=2.5Σ+0.7σ. A systematic range error of 1.5% (1SD) from literature was used, in line with the 3% RR setting. For each plan, scenario D98%, D99.8%, D2%, D0.2% and V95% CTV distributions were determined from the simulated treatment courses. Based on a prior photon plan calibration, per center population D99.8% histograms were derived from the simulated treatment courses to probabilistically assess adequate CTV dose and, subsequently, to be compared to their prescribed near minimum dose.

Figure 1 shows population D99.8%,CTVs dose histograms for each center. The other probabilistic dose metrics are summarized in Table I. For center 1 and 2, the 10th-90th percentile range of D99.8% was above their prescription dose levels, with the smallest inter-patient variation for the elective CTV in center 1. In contrast, the D99.8% values of center 3 were partly (primary CTV) or completely (elective CTV) below the 94%/93% prescription level used in that center. Compared to the prescribed VWmax-D2%, CTV dose inhomogeneity was consistent and smaller for center 1 and 2 according to their D0.2% values. For center 3, a higher D0.2% of 75.3 GyRBE was achieved on average, which exceeded the clinical prescribed VWmax-D2% value.

Despite the standardization of the Dutch robustness protocol, inconsistencies were present in the population CTV doses. VWmin-D98% dose metrics showed limitations when robustness in CTV dose was not achieved. These results can be used to further optimize and harmonize the treatment planning and evaluation protocols in Head and Neck IMPT.