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

• Published in: Radiotherapy and oncology 2024-10, Vol.199, p.110441, Article 110441
• Main Authors: Rojo-Santiago, Jesús, Habraken, Steven J.M., Unipan, Mirko, Both, Stefan, Bosmans, Geert, Perkó, Zoltán, Korevaar, Erik, Hoogeman, Mischa S.
• Format: Article
• Language: English
• Subjects: Head and Neck; Model-based selection; Polynomial Chaos Expansion; Probabilistic planning; Proton therapy; Robust planning; Robustness analysis; Robustness evaluation
• ISSN: 0167-8140; 1879-0887; 1879-0887
• DOI: 10.1016/j.radonc.2024.110441

•Despite its consistency in terms of TCP, the Dutch RE protocol lead to substantial inter-patient and inter-center variation in terms of CTV dose.•The Dutch MBS protocol for PT patient selection is robust against treatment errors.•Probabilistic evaluations could aid in the harmonization and consensus of robustness evaluation protocols.•Polynomial Chaos Expansion (PCE) allows for a better comprehension of the robustness of treatment plans and evaluation protocols. 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. 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 (D99.8%/D0.2%, 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. For the CTV70.00, doses from the RE protocol were consistent with the clinical plan evaluation metrics used in the 3 centers. For the CTV54.25, D99.8% 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. 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.