Beam Position Projection Algorithms in Proton Pencil Beam Scanning.

Beam position uncertainties along the beam trajectory arise from the accelerator, beamline, and scanning magnets (SMs). They can be monitored in real time, e.g., through strip ionization chambers (ICs), and treatments can be paused if needed. Delivery is more reliable and accurate if the beam position is projected from monitored nozzle parameters to the isocenter, allowing for accurate online corrections to be performed. Beam position projection algorithms are also used in post-delivery log file analyses. In this paper, we investigate the four potential algorithms that can be applied to all pencil beam scanning (PBS) nozzles. For some combinations of nozzle configurations and algorithms, however, the projection uses beam properties determined offline (e.g., through beam tuning or technical commissioning). The best algorithm minimizes either the total uncertainty (i.e., offline and online) or the total offline uncertainty in the projection. Four beam position algorithms are analyzed (A1-A4). Two nozzle lengths are used as examples: a large nozzle (1.5 m length) and a small nozzle (0.4 m length). Three nozzle configurations are considered: IC after SM, IC before SM, and ICs on both sides. Default uncertainties are selected for ion chamber measurements, nozzle entrance beam position and angle, and scanning magnet angle. The results for other uncertainties can be determined by scaling these results or repeating the error propagation. We show the propagation of errors from two locations and the SM angle to the isocenter for all the algorithms. The best choice of algorithm depends on the nozzle length and is A1 and A3 for the large and small nozzles, respectively. If the total offline uncertainty is to be minimized (a better choice if the offline uncertainty is not stable), the best choice of algorithm changes to A1 for the small nozzle for some hardware configurations. Reducing the nozzle length can help to reduce the gantry size and make proton therapy more accessible. This work is important for designing smaller nozzles and, consequently, smaller gantries. This work is also important for log file analyses.

Large anatomical changes in head-and-neck cancers - A dosimetric comparison of online and offline adaptive proton therapy.

Purpose: This work evaluates an online adaptive (OA) workflow for head-and-neck (H&N) intensity-modulated proton therapy (IMPT) and compares it with full offline replanning (FOR) in patients with large anatomical changes. Methods: IMPT treatment plans are created retrospectively for a cohort of eight H&N cancer patients that previously required replanning during the course of treatment due to large anatomical changes. Daily cone-beam CTs (CBCT) are acquired and corrected for scatter, resulting in 253 analyzed fractions. To simulate the FOR workflow, nominal plans are created on the planning-CT and delivered until a repeated-CT is acquired; at this point, a new plan is created on the repeated-CT. To simulate the OA workflow, nominal plans are created on the planning-CT and adapted at each fraction using a simple beamlet weight-tuning technique. Dose distributions are calculated on the CBCTs with Monte Carlo for both delivery methods. The total treatment dose is accumulated on the planning-CT. Results: Daily OA improved target coverage compared to FOR despite using smaller target margins. In the high-risk CTV, the median D98 degradation was 1.1 % and 2.1 % for OA and FOR, respectively. In the low-risk CTV, the same metrics yield 1.3 % and 5.2 % for OA and FOR, respectively. Smaller setup margins of OA reduced the dose to all OARs, which was most relevant for the parotid glands. Conclusion: Daily OA can maintain prescription doses and constraints over the course of fractionated treatment, even in cases of large anatomical changes, reducing the necessity for manual replanning in H&N IMPT.

Optically stimulated luminescence dosimeters for simultaneous measurement of point dose and dose-weighted LET in an adaptive proton therapy workflow.

Purpose: To demonstrate the suitability of optically stimulated luminescence detectors (OSLDs) for accurate simultaneous measurement of the absolute point dose and dose-weighted linear energy transfer (LETD) in an anthropomorphic phantom for experimental validation of daily adaptive proton therapy. Methods: A clinically realistic intensity-modulated proton therapy (IMPT) treatment plan was created based on a CT of an anthropomorphic head-and-neck phantom made of tissue-equivalent material. The IMPT plan was optimized with three fields to deliver a uniform dose to the target volume covering the OSLDs. Different scenarios representing inter-fractional anatomical changes were created by modifying the phantom. An online adaptive proton therapy workflow was used to recover the daily dose distribution and account for the applied geometry changes. To validate the adaptive workflow, measurements were performed by irradiating Al2O3:C OSLDs inside the phantom. In addition to the measurements, retrospective Monte Carlo simulations were performed to compare the absolute dose and dose-averaged LET (LETD) delivered to the OSLDs. Results: The online adaptive proton therapy workflow was shown to recover significant degradation in dose conformity resulting from large anatomical and positioning deviations from the reference plan. The Monte Carlo simulations were in close agreement with the OSLD measurements, with an average relative error of 1.4% for doses and 3.2% for LETD. The use of OSLDs for LET determination allowed for a correction for the ionization quenched response. Conclusion: The OSLDs appear to be an excellent detector for simultaneously assessing dose and LET distributions in proton irradiation of an anthropomorphic phantom. The OSLDs can be cut to almost any size and shape, making them ideal for in-phantom measurements to probe the radiation quality and dose in a predefined region of interest. Although we have presented the results obtained in the experimental validation of an adaptive proton therapy workflow, the same approach can be generalized and used for a variety of clinical innovations and workflow developments that require accurate assessment of point dose and/or average LET.

Low-Dose Computed Tomography Scanning Protocols for Online Adaptive Proton Therapy of Head-and-Neck Cancers.

PURPOSE: To evaluate the suitability of low-dose CT protocols for online plan adaptation of head-and-neck patients. METHODS: We acquired CT scans of a head phantom with protocols corresponding to CT dose index volume CTDIvol in the range of 4.2-165.9 mGy. The highest value corresponds to the standard protocol used for CT simulations of 10 head-and-neck patients included in the study. The minimum value corresponds to the lowest achievable tube current of the GE Discovery RT scanner used for the study. For each patient and each low-dose protocol, the noise relative to the standard protocol, derived from phantom images, was applied to a virtual CT (vCT). The vCT was obtained from a daily CBCT scan corresponding to the fraction with the largest anatomical changes. We ran an established adaptive workflow twice for each low-dose protocol using a high-quality daily vCT and the corresponding low-dose synthetic vCT. For a relative comparison of the adaptation efficacy, two adapted plans were recalculated in the high-quality vCT and evaluated with the contours obtained through deformable registration of the planning CT. We also evaluated the accuracy of dose calculation in low-dose CT volumes using the standard CT protocol as reference. RESULTS: The maximum differences in D98 between low-dose protocols and the standard protocol for the high-risk and low-risk CTV were found to be 0.6% and 0.3%, respectively. The difference in OAR sparing was up to 3%. The Dice similarity coefficient between propagated contours obtained with low-dose and standard protocols was above 0.982. The mean 2%/2 mm gamma pass rate for the lowest-dose image, using the standard protocol as reference, was found to be 99.99%. CONCLUSION: The differences between low-dose protocols and the standard scanning protocol were marginal. Thus, low-dose CT protocols are suitable for online adaptive proton therapy of head-and-neck cancers. As such, considering scanning protocols used in our clinic, the imaging dose associated with online adaption of head-and-neck cancers treated with protons can be reduced by a factor of 40.

Integrating Structure Propagation Uncertainties in the Optimization of Online Adaptive Proton Therapy Plans.

Currently, adaptive strategies require time- and resource-intensive manual structure corrections. This study compares different strategies: optimization without manual structure correction, adaptation with physician-drawn structures, and no adaptation. Strategies were compared for 16 patients with pancreas, liver, and head and neck (HN) cancer with 1-5 repeated images during treatment: 'reference adaptation', with structures drawn by a physician; 'single-DIR adaptation', using a single set of deformably propagated structures; 'multi-DIR adaptation', using robust planning with multiple deformed structure sets; 'conservative adaptation', using the intersection and union of all deformed structures; 'probabilistic adaptation', using the probability of a voxel belonging to the structure in the optimization weight; and 'no adaptation'. Plans were evaluated using reference structures and compared using a scoring system. The reference adaptation with physician-drawn structures performed best, and no adaptation performed the worst. For pancreas and liver patients, adaptation with a single DIR improved the plan quality over no adaptation. For HN patients, integrating structure uncertainties brought an additional benefit. If resources for manual structure corrections would prevent online adaptation, manual correction could be replaced by a fast 'plausibility check', and plans could be adapted with correction-free adaptation strategies. Including structure uncertainties in the optimization has the potential to make online adaptation more automatable.

CT-on-Rails Versus In-Room CBCT for Online Daily Adaptive Proton Therapy of Head-and-Neck Cancers.

PURPOSE: To compare the efficacy of CT-on-rails versus in-room CBCT for daily adaptive proton therapy. METHODS: We analyzed a cohort of ten head-and-neck patients with daily CBCT and corresponding virtual CT images. The necessity of moving the patient after a CT scan is the most significant difference in the adaptation workflow, leading to an increased treatment execution uncertainty σ. It is a combination of the isocenter-matching σi and random patient movements induced by the couch motion σm. The former is assumed to never exceed 1 mm. For the latter, we studied three different scenarios with σm = 1, 2, and 3 mm. Accordingly, to mimic the adaptation workflow with CT-on-rails, we introduced random offsets after Monte-Carlo-based adaptation but before delivery of the adapted plan. RESULTS: There were no significant differences in accumulated dose-volume histograms and dose distributions for σm = 1 and 2 mm. Offsets with σm = 3 mm resulted in underdosage to CTV and hot spots of considerable volume. CONCLUSION: Since σm typically does not exceed 2 mm for in-room CT, there is no clinically significant dosimetric difference between the two modalities for online adaptive therapy of head-and-neck patients. Therefore, in-room CT-on-rails can be considered a good alternative to CBCT for adaptive proton therapy.

Commissioning of a clinical pencil beam scanning proton therapy unit for ultra-high dose rates (FLASH).

PURPOSE: The purpose of this work was to provide a flexible platform for FLASH research with protons by adapting a former clinical pencil beam scanning gantry to irradiations with ultra-high dose rates. METHODS: PSI Gantry 1 treated patients until December 2018. We optimized the beamline parameters to transport the 250 MeV beam extracted from the PSI COMET accelerator to the treatment room, maximizing the transmission of beam intensity to the sample. We characterized a dose monitor on the gantry to ensure good control of the dose, delivered in spot-scanning mode. We characterized the beam for different dose rates and field sizes for transmission irradiations. We explored scanning possibilities in order to enable conformal irradiations or transmission irradiations of large targets (with transverse scanning). RESULTS: We achieved a transmission of 86% from the cyclotron to the treatment room. We reached a peak dose rate of 9000 Gy/s at 3 mm water equivalent depth, along the central axis of a single pencil beam. Field sizes of up to 5 × 5 mm2 were achieved for single-spot FLASH irradiations. Fast transverse scanning allowed to cover a field of 16 × 1.2 cm2 . With the use of a nozzle-mounted range shifter, we are able to span depths in water ranging from 19.6 to 37.9 cm. Various dose levels were delivered with precision within less than 1%. CONCLUSIONS: We have realized a proton FLASH irradiation setup able to investigate continuously a wide dose rate spectrum, from 1 to 9000 Gy/s in single-spot irradiation as well as in the pencil beam scanning mode. As such, we have developed a versatile test bench for FLASH research.

Beam monitor detectors for medical applications.

Beam monitoring is fundamental for any particle accelerator. In particular, it is a crucial issue in medical applications of particle physics due to the required high precision and reliability. Radioisotope production and cancer radiotherapy require specific beam monitor detectors. In this paper, three recently designed instruments are reviewed. One of them is a newly designed beam monitor detector based on doped silica and optical fibres. It represents a promising solution. This apparatus can be used with various types of beams and for both hadrontherapy and radioisotope production. For this reason, a more detailed description of this multipurpose detector is provided.