The aim of this study was to verify the temporal accuracy of the estimated dose distribution by a 4D dose calculation (4DDC) in comparison to measurements. A single-field plan (0.6 Gy), optimised for a liver patient case (CTV volume: 403cc), was delivered to a homogeneous PMMA phantom and measured by a high resolution scintillating-CCD system at two water equivalent depths. Various motion scenarios (no motion and motions with amplitude of 10 mm and two periods: 3.7 s and 4.4 s) were simulated using a 4D Quasar phantom and logged by an optical tracking system in real-time. Three motion mitigation approaches (single delivery, 6[Formula: see text] layered and volumetric rescanning) were applied, resulting in 10 individual measurements. 4D dose distributions were retrospectively calculated in water by taking into account the delivery log files (retrospective) containing information on the actually delivered spot positions, fluences, and time stamps. Moreover, in order to evaluate the sensitivity of the 4DDC inputs, the corresponding prospective 4DDCs were performed as a comparison, using the estimated time stamps of the spot delivery and repeated periodical motion patterns. 2D gamma analyses and dose-difference-histograms were used to quantify the agreement between measurements and calculations for all pixels with [Formula: see text]5% of the maximum calculated dose. The results show that a mean gamma score of 99.2% with standard deviation 1.0% can be achieved for 3%/3 mm criteria and all scenarios can reach a score of more than 95%. The average area with more than 5% dose difference was 6.2%. Deviations due to input uncertainties were obvious for single scan deliveries but could be smeared out once rescanning was applied. Thus, the deforming grid 4DDC has been demonstrated to be able to predict the complex patterns of 4D dose distributions for PBS proton therapy with high dosimetric and geometric accuracy, and it can be used as a valid clinical tool for 4D treatment planning, motion mitigation selection, and eventually 4D optimisation applications if the correct temporal information is available.

Purpose In ultrahigh dose rate radiotherapy, the FLASH effect can lead to substantially reduced healthy tissue damage without affecting tumor control. Although many studies show promising results, the underlying biological mechanisms and the relevant delivery parameters are still largely unknown. It is unclear, particularly for scanned proton therapy, how treatment plans could be optimized to maximally exploit this protective FLASH effect. Materials and Methods To investigate the potential of pencil beam scanned proton therapy for FLASH treatments, we present a phenomenological model, which is purely based on experimentally observed phenomena such as potential dose rate and dose thresholds, and which estimates the biologically effective dose during FLASH radiotherapy based on several parameters. We applied this model to a wide variety of patient geometries and proton treatment planning scenarios, including transmission and Bragg peak plans as well as single‐ and multifield plans. Moreover, we performed a sensitivity analysis to estimate the importance of each model parameter. Results Our results showed an increased plan‐specific FLASH effect for transmission compared with Bragg peak plans (19.7% vs. 4.0%) and for single‐field compared with multifield plans (14.7% vs. 3.7%), typically at the cost of increased integral dose compared to the clinical reference plan. Similar FLASH magnitudes were found across the different treatment sites, whereas the clinical benefits with respect to the clinical reference plan varied strongly. The sensitivity analysis revealed that the threshold dose as well as the dose per fraction strongly impacted the FLASH effect, whereas the persistence time only marginally affected FLASH. An intermediate dependence of the FLASH effect on the dose rate threshold was found. Conclusions Our model provided a quantitative measure of the FLASH effect for various delivery and patient scenarios, supporting previous assumptions about potentially promising planning approaches for FLASH proton therapy. Positive clinical benefits compared to clinical plans were achieved using hypofractionated, single‐field transmission plans. The dose threshold was found to be an important factor, which may require more investigation.

In this study, a functioning and ventilated anthropomorphic phantom was further enhanced for the purpose of CT and MR imaging of the lung and liver. A deformable lung, including respiratory tract was 3D printed. Within the lung's inner structures is a solid region shaped from a patient's lung tumour and six nitro-glycerine capsules as reference landmarks. The full internal mesh was coated, and the tumour filled, with polyorganosiloxane based gel. A moulded liver was created with an external casing of silicon filled with polyorganosiloxane gel and flexible plastic internal structures. The liver, fitted to the inferior portion of the right lung, moves along with the lung's ventilation. In the contralateral side, a cavity is designed to host a dosimeter, whose motion is correlated to the lung pressure. A 4DCT of the phantom was performed along with static and 4D T1 weighted MR images. The CT Hounsfield units (HU) for the flexible 3D printed material were -600 -100HU (lung and liver structures), for the polyorganosiloxane gel 50 -120HU (lung coating and liver filling) and for the silicon 650 -800HU (liver casing). The MR image intensity units were 0 -150, 0 -100 and 80 -110 respectively. The maximum range of motion in the 4D imaging for the superior lung was 1 -3.5mm and 3.5 -8mm in the inferior portion. The liver motion was 5.5 -8.0mm at the tip and 5.7 -10.0mm at the dome. No measurable drift in motion was observed over a two hour session and motion was reproducible over three different sessions for sin 2 (t), sin 4 (t) and a patient-like breathing curve with the interquartile range of amplitudes for all breathing cycles within 0.5mm. The addition of features within the lung and of a deformable liver will allow the phantom to be used for imaging studies such as validation of 4DMRI and pseudo CT methods.