A probabilistic evaluation of the Dutch robustness and model-based selection protocols for Head-and-Neck IMPT: A multi-institutional study

Background and purpose: In the Netherlands, 2 protocols have been standardized for PT among the 3 proton centers: a robustness evaluation (RE) to ensure adequate CTV dose and a model-based selection (MBS) approach for IMPT patient-selection. This multi-institutional study investigates (i) inter-patient and inter-center variation of target dose from the RE protocol and (ii) the robustness of the MBS protocol against treatment errors for a cohort of head-and-neck cancer (HNC) patients treated in the 3 Dutch proton centers. 

Materials and methods: Clinical treatment plans of 100 HNC patients were evaluated. Polynomial Chaos Expansion (PCE) was used to perform a comprehensive robustness evaluation per plan, enabling the probabilistic evaluation of 100,000 complete fractionated treatments. PCE allowed to derive scenario distributions of clinically relevant dosimetric parameters to assess CTV dose (D_99.8%/D_0.2%, based on a prior photon plan calibration) and tumour control probabilities (TCP) as well as the evaluation of the dose to OARs and normal tissue complication probabilities (NTCP) per center. 

Results: For the CTV_70.00, doses from the RE protocol were consistent with the clinical plan evaluation metrics used in the 3 centers. For the CTV_54.25, D_99.8% were consistent with the clinical plan evaluation metrics at center 1 and 2 while, for center 3, a reduction of 1 GyRBE was found on average. This difference did not impact modelled TCP at center 3. Differences between expected and nominal NTCP were below 0.3 percentage point for most patients. 

Conclusion: The standardization of the RE and MBS protocol lead to comparable results in terms of TCP and the NTCPs. Still, significant inter-patient and inter-center variation in dosimetric parameters remained due to clinical practice differences at each institution. The MBS approach is a robust protocol to qualify patients for PT.