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The aim of this study was to assess the clinical outcome, including QoL, of patients with intracranial meningiomas WHO grade 1-3 who were treated with Pencil Beam Scanning Proton Therapy (PBS PT) between 1997 and 2022. Two hundred patients (median age 50.4 years, 70% WHO grade 1) were analyzed. Acute and late side effects were classified according to CTCAE version 5.0. Time to event data were calculated. QoL was assessed descriptively by the EORTC-QLQ-C30 and BN20 questionnaires. With a median follow-up of 65 months (range: 3.8-260.8 months) the 5 year OS was 95.7% and 81.8% for WHO grade 1 and grade 2/3, respectively (p < 0.001). Twenty (10%) local failures were observed. Failures occurred significantly (p < 0.001) more frequent in WHO grade 2 or 3 meningioma (WHO grade 1: n = 7, WHO grade 2/3: n = 13), in patients with multiple meningiomas (p = 0.005), in male patients (p = 0.005), and when PT was initiated not as upfront therapy (p = 0.011). There were no high-grade toxicities in the majority (n = 176; 88%) of patients. QoL was assessed for 83 (41.5%) patients and for those patients PT did not impacted QoL negatively during the follow-up. In summary, we observed very few local recurrences of meningiomas after PBS PT, a stable QoL, and a low rate of high-grade toxicity.

BACKGROUND Experiments with ultra-high dose rates in proton therapy are of increasing interest for potential treatment benefits. The Faraday Cup (FC) is an important detector for the dosimetry of such ultra-high dose rate beams. So far, there is no consensus on the optimal design of a FC, or on the influence of beam properties and magnetic fields on shielding of the FC from secondary charged particles. PURPOSE To perform detailed Monte Carlo simulations of a Faraday cup to identify and quantify all the charge contributions from primary protons and secondary particles that modify the efficiency of the FC response as a function of a magnetic field employed to improve the detector's reading. METHODS In this paper, a Monte Carlo (MC) approach was used to investigate the Paul Scherrer Institute (PSI) FC and quantify contributions of charged particles to its signal for beam energies of 70, 150, and 228 MeV and magnetic fields between 0 and 25 mT. Finally, we compared our MC simulations to measurements of the response of the PSI FC. RESULTS For maximum magnetic fields, the efficiency (signal of the FC normalized to charged delivered by protons) of the PSI FC varied between 99.97% and 100.22% for the lowest and highest beam energy. We have shown that this beam energy-dependence is mainly caused by contributions of secondary charged particles, which cannot be fully suppressed by the magnetic field. Additionally, it has been demonstrated that these contributions persist, making the FC efficiency beam energy dependent for fields up to 250 mT, posing inevitable limits on the accuracy of FC measurements if not corrected. In particular, we have identified a so far unreported loss of electrons via the outer surfaces of the absorber block and show the energy distributions of secondary electrons ejected from the vacuum window (VW) (up to several hundred keV), together with electrons ejected from the absorber block (up to several MeV). Even though, in general, simulations and measurements were well in agreement, the limitation of the current MC calculations to produce secondary electrons below 990 eV posed a limit in the efficiency simulations in the absence of a magnetic field as compared to the experimental data. CONCLUSION TOPAS-based MC simulations allowed to identify various and previously unreported contributions to the FC signal, which are likely to be present in other FC designs. Estimating the beam energy dependence of the PSI FC for additional beam energies could allow for the implementation of an energy-dependent correction factor to the signal. Dose estimates, based on accurate measurements of the number of delivered protons, provided a valid instrument to challenge the dose determined by reference ionization chambers, not only at ultra-high dose rates but also at conventional dose rates.

anatomical and daily set-up uncertainties impede high precision delivery of proton therapy. With online adaptation, the daily plan is reoptimized on an image taken shortly before the treatment, reducing these uncertainties and, hence, allowing a more accurate delivery. This reoptimization requires target and organs-at-risk (OAR) contours on the daily image, which need to be delineated automatically since manual contouring is too slow. Whereas multiple methods for autocontouring exist, none of them are fully accurate, which affects the daily dose. This work aims to quantify the magnitude of this dosimetric effect for four contouring techniques. Approach: plans reoptimized on automatic contours are compared with plans reoptimized on manual contours. The methods include rigid and deformable registration (DIR), deep-learning based segmentation and patient-specific segmentation. Results: it was found that independently of the contouring method, the dosimetric influence of using automatic OAR contours is small (< 5% prescribed dose in most cases), with DIR yielding the best results. Contrarily, the dosimetric effect of using the automatic target contour was larger (> 5% prescribed dose in most cases), indicating that manual verification of that contour remains necessary. However, when compared to non-adaptive therapy, the dose differences caused by automatically contouring the target were small and target coverage was improved, especially for DIR. Significance: the results show that manual adjustment of OARs is rarely necessary and that several autocontouring techniques are directly usable. Contrarily, manual adjustment of the target is important. This allows prioritizing tasks during time-critical online adaptive proton therapy and therefore supports its further clinical implementation.

Background Hypoxia is known to be prevalent in solid tumors such as non-small cell lung cancer (NSCLC) and reportedly correlates with poor prognostic clinical outcome. PET imaging can provide in-vivo hypoxia measurements to support targeted radiotherapy treatment planning. We explore the potential of proton therapy in performing patient-specific dose escalation and compare it with photon volumetric modulated arc therapy (VMAT). Methods Dose escalation has been calibrated to the patient specific tumor response of ten stage IIb-IIIb NSCLC patients by combining HX4-PET imaging and radiobiological modelling of oxygen enhancement ratio (OER) to target variable tumor hypoxia. In a dose-escalation-by-contour approach, escalated dose levels were simulated to the most hypoxic region of the primary target and its effectiveness in improving loco-regional tumor control was assessed. Furthermore, the impact on normal tissue of proton treatments including dose escalation was evaluated in comparison to the normal tissue complication probability (NTCP) of conventional VMAT plans. Results Ignoring regions of tumor hypoxia can cause overestimation of TCP values by up to 10%, which can effectively be recovered on average to within 0.9% of the nominal TCP, using patient-specific dose escalations of up to 22% of the prescribed dose to PET defined hypoxic regions. Despite such dose escalations, the use of protons could also simultaneously reduce mean doses to the heart (− 14.3 GyRBE), lung (− 8.3 GyRBE), esophagus (− 6.9 GyRBE) and spinal cord (− 3.8 Gy) compared to non-escalated VMAT plans. These reductions are predicted to lead to clinically relevant decreases in NTCP for radiation-induced pneumonitis (− 11.3%), high grade heart toxicity (− 7.4%) and esophagitis (− 7.5%). Conclusions This study suggests that the administration of proton therapy for dose escalation to patient specific regions of tumor hypoxia in the treatment of NSCLC can mitigate TCP reduction due to hypoxia-induced radio resistance, while simultaneously reducing NTCP levels even when compared to non-escalated treatments delivered with state-of-the-art photon techniques., Radiation Oncology, 16 (1)

Purpose The use of motion mitigation techniques such as breath-hold can reduce the dosimetric uncertainty of lung cancer proton therapy. We studied the feasibility of hypofractionated pencil beam scanning (PBS) proton therapy field delivery within a single breath-hold at PSI’s Gantry 2. Treatment delivery time in PBS proton therapy depends on beam-on time and the dead time between proton spots (time required to change the energy and/or lateral spot position). We studied ways to reduce beam-on and lateral scanning time, without sacrificing dosimetric plan quality, aiming at a single field delivery time of 15 seconds at maximum. We tested this approach on ten lung cancer cases with varying target volumes (PTV volume range 137-379 cm3). Methods To reduce the beam-on time, we increased the beam current at the isocenter by developing new beam optics for PSI’s PROSCAN beamline and Gantry 2. Experimentally we obtained up to factor 5 higher transmission for all proton energies. To reduce the dead time between the spots, we used spot-reduced plan optimization. First, a 3-field SFUD treatment plan was generated for all 10 cases using the in-house clinical planning system ‘PSIplan’. Spot-reduced plans were subsequently generated while mimicking relevant dosimetric plan parameters of the clinical plans to ensure comparable plan quality. The spot reduction technique reduced the number of spots by 95% compared with the clinical planning system for the lung cases considered. For the clinical and spot-reduced plans, 6-Gy(RBE) fractions were delivered with PSI’s Gantry 2 using the clinical and transmission-efficient beam optics, respectively. We extracted delivery times, including both beam-on time and dead time, from the log files. Results We found that it is possible to achieve hypofractionated (6 Gy(RBE)/fraction) field delivery times within a single breath-hold (6 Gy(RBE)/fraction) field delivery times within a single breath-hold (, 55th SSRMP Annual Meeting. Booklet

Purpose Advanced non-small cell lung cancer (NSCLC) is still a challenging indication for conventional photon radiotherapy. Proton therapy has the potential to improve outcomes, but proton treatment slots remain a limited resource despite an increasing number of proton therapy facilities. This work investigates the potential benefits of optimally combined proton–photon therapy delivered using a fixed horizontal proton beam line in combination with a photon Linac, which could increase accessibility to proton therapy for such a patient cohort. Materials and methods A treatment planning study has been conducted on a patient cohort of seven advanced NSCLC patients. Each patient had a planning computed tomography scan (CT) and multiple repeated CTs from three different days and for different breath-holds on each day. Treatment plans for combined proton–photon therapy (CPPT) were calculated for individual patients by optimizing the combined cumulative dose on the initial planning CT only (non-adapted) as well as on each daily CT respectively (adapted). The impact of inter-fractional changes and/or breath-hold variability was then assessed on the repeat breath-hold CTs. Results were compared to plans for IMRT or IMPT alone, as well as against combined treatments assuming a proton gantry. Plan quality was assessed in terms of dosimetric, robustness and NTCP metrics. Results Combined treatment plans improved plan quality compared to IMRT treatments, especially in regard to reductions of low and medium doses to organs at risk (OARs), which translated into lower NTCP estimates for three side effects. For most patients, combined treatments achieved results close to IMPT-only plans. Inter-fractional changes impact mainly the target coverage of combined and IMPT treatments, while OARs doses were less affected by these changes. With plan adaptation however, target coverage of combined treatments remained high even when taking variability between breath-holds into account. Conclusions Optimally combined proton-photon plans improve treatment plan quality compared to IMRT only, potentially reducing the risk of toxicity while also allowing to potentially increase accessibility to proton therapy for NSCLC patients., Medical Physics, 49 (8), ISSN:0094-2405, ISSN:2473-4209, ISSN:1522-8541

To treat moving tumors effectively with PBS proton therapy, it is required to use motion mitigation techniques such as breath-hold, rescanning, and gating. However, these techniques are not efficient in terms of delivery time. Treatment delivery time in PBS proton therapy depends on beam-on time and the dead time (time required to change energy-layers and/or lateral position). To shorten the beam-on time, we increased the beam current reaching the patient by developing new beam optics for PSI’s PROSCAN beamline and Gantry 2. Experimentally, we obtained factor 5 high beam current while achieving clinical beam size at the isocenter. To reduce the dead time, we developed a novel energy modulation unit that comprises two identical ridge filters placed just before the isocenter. Both ridge-filters are movable relative to each other to change the Bragg peak’s characteristics dynamically. By using a dynamic ridge-filter we could reduce the number of energy layers and spots required to generate dose distribution while being independent of energy. For the feasibility study, we evaluated the effect of the ridge filter on three different geometrical shaped homogeneous water phantoms assuming single-beam plans with 1Gy/fraction. We calculated the dose delivery time using high beam currents and ridge-filter and compared it with the clinical setting. For all shapes, we managed to reduce the delivery time at least by 60% compared to clinically used settings. These methods to reduce delivery time are easily adaptable for other proton therapy facilities to treat moving targets.

In Proton therapy, the potential of using high dose rates in cancer treatment is being explored. High dose rates could improve efficiency and throughput in standard clinical practice, allow efficient utilization of motion mitigation techniques for moving targets, and potentially enhance normal tissue sparing due to the FLASH effect. However, high dose rates are difficult to reach when lower energy beams are applied in cyclotron-based proton therapy facilities, because they result in large beam sizes and divergences downstream of the degrader, incurring large losses from the cyclotron to the patient. In current facilities the emittance after the degrader is reduced using circular collimators (emittance selection collimators after the energy degrader); this however does not provide an optimal matching to the acceptance of the following beamline, causing a low transmission for these energies. We, therefore, propose to use a collimation system asymmetric in both beam size and divergence, which allows to maximize the transmission of low energy beams, while resulting in symmetric emittance in both planes as required for a gantry system. Using a specifically designed asymmetric collimation system, we found in simulations that low energy (70 MeV) beam transmission increases almost 6 times compared to the currently used circular collimator system [1]. Such a system could easily be implemented in facilities interested in increasing dose rates for efficient motion mitigation and FLASH experiments alike. [1] Maradia et. al., “A new emittance selection system to maximize beam transmission for low-energy beams in cyclotron-based proton therapy facilities with gantry,” doi: https://doi.org/10.1002/mp.15278.

In cyclotron-based proton therapy facilities, an energy selection system is typically used to lower beam energy from the fixed value provided by the accelerator (250/230MeV) to the one needed for the treatment (230-70MeV). Such a system has drawback of introducing an energy-dependent beam current at the patient location, resulting in energy-dependent beam intensity ratios of about 10³ between high and low energies. This complicates treatment delivery and challenges patient safety systems. As such, we propose the use of a dual-energy degrader method that can reduce beam intensity for high-energy beams. The first degrader is made of high Z material and the second is made of low Z material and are placed next to each other. For high energies (230-180MeV), we use only first degrader to increase beam emittance after degrader and thus lose intensity in emittance selection collimators. For intermediate energy beams (180-100MeV) we use the combination of both degraders, whereas for low energy beams (100-70MeV), only the second degrader limits the increase in emittance. With this approach, energy-independent beam intensities can be achieved, whilst localizing beam losses around the degrader., Proceedings of the 13th International Particle Accelerator Conference, IPAC2022, Bangkok, Thailand