The aim in radiotherapy treatment planning is to have sufficient target coverage and as low a dose to the Organs at Risk (OARs) as possible, adhering to the relevant guidelines. A high and consistent radiotherapy plan quality is vital when treatment plans are used as the foundation for patient selection in clinical trials. Proton therapy, being a substantially newer treatment modality than conventional photon therapy, is at risk of having a steeper learning curve in treatment planning. This inequality is important to investigate in a clinical study comparing the two, as this could influence the trial results. This study aims to evaluate the development of radiotherapy treatment plan quality for head and neck cancer patients receiving photon and proton therapy over time in the context of the DAHANCA 35 trial. From May 2019 to June 2023,189 patients were included in the ongoing DAHANCA 35 trial, with 63 patients in the pilot phase and 126 in the subsequent randomisation phase. In the pilot phase, all included patients were offered proton treatment, and in the randomisation phase, patients were randomised 1:2 (photon:proton). Patients were first seen at a local treatment centre, where a photon and comparative proton plan were prepared. If patients were offered proton treatment, a new clinical proton plan was made at the proton treatment centre and subsequently used for treatment. This study analysed 189 photon plans, 189 comparative proton plans, and 140 clinical proton plans. The treatment plans were prepared conforming to the DAHANCA guidelines 1 to ensure the clinical relevance of all treatment plans The plan quality was assessed separately for photon plans, comparative proton plans, and clinical proton plans in three time intervals. The mean dose was investigated individually for 13 OARs relevant for head and neck cancer: oesophagus, glottic larynx, supraglottic larynx, mandible, extended oral cavity, left and right parotid glands, upper-, middle-, and lower pharyngeal constrictor muscles, left and right submandibular glands, and thyroid gland. Furthermore, treatment plan quality was analysed using a new metric called Normalised Toxicity Index (NTI), calculated as a normalised average of the mean dose to the OARs compared to the threshold mean dose recommended by the DAHANCA guidelines. An NTI > 1 indicated that the OARs, on average, received a dose higher than the recommended thresholds, and an NTI < 1 indicated that the OARs received a dose below the thresholds. Hence, a lower NTI indicated better plan quality concerning OAR doses. The Kruskal-Wallis test was used to investigate a potential difference in the intervals for mean dose and NTI for each treatment type. The significance level was Bonferroni adjusted to account for multiple testing. The three time intervals were defined with 63 patients in the pilot phase constituting one interval (Pilot phase), the subsequent 64 patients from the randomisation phase in the next interval (Randomisation 1), and the remaining 62 patients from the randomisation phase in the third interval (Randomisation 2). The periods were 22 months for the Pilot phase, 19 months for Randomisation 1, and 14 months for Randomisation 2. Across the 13 OARs, the mean dose to individual OARs did not show a general time-dependent change, except for the right parotid gland in the clinical proton plans. Figure 1 shows a box plot with samples overlaid for the mean dose to the extended oral cavity as an example of the OARs. Display omitted The NTI was not significantly different for the photon plans, comparative proton plans, and clinical proton plans in the three consecutive intervals, as shown in Figure 2. The median NTI for the clinical proton plans was 0.88 (interquartile range 0.70,1.00) for the Pilot phase, 0.83 0.75,0.89 for Randomization 1, and 0.79 0.67,0.98 for Randomization 2. The plan quality of the clinical proton plans appears stable from this new NTI metric. Display omitted The analyses conducted in this study did not show a general time-dependent change in plan quality in any of the three types of plans. This could be caused by the nationally developed proton treatment planning template. A stable treatment plan quality can help ensure a consistent selection for clinical trials, thus providing transparency for analysis of the outcome of the trials. The plan quality will continuously be followed to ensure consistency.