Objective.This work provides proof-of-concept for the use of real-time ion imaging and treatment gating for lung cancer radiotherapy using 3D range modulators (3DRM).Approach.The accuracy of a fully real-time, plastic scintillator-based portal ion radiography detector was determined by tracking a 3 cm spherical plastic tumour undergoing breathing-style motion in a mock lung geometry. The ability to gate the delivered treatment using a trigger from the ion radiography detector at the desired tumour position was investigated. Finally, an offline simulated study was performed to compare the dosimetric benefits of the advanced image guidance against the standard clinical motion mitigation practice of rescanning.Main Results.The ion radiography detector was shown to track tumour motion in a mock lung phantom setup to 0.1 mm accuracy. The imaging dose was found to be approximately 1/3 of comparable x-ray fluoroscopy methods. While dynamically driving in the 3DRM is not currently possible, preliminary measurements showed modulator positioning to be reproducible to 0.3%. A technical demonstration was provided showing a real-time switch from imaging to treatment using a trigger from the ion-imaging detector, with the mock tumour found in the expected position. The simulated dosimetric study showed that the tracking accuracy in an idealised scenario allows the tumour to be treated quasi-statically, with aD95%of 98% and 99.2% using passive and active treatment beam energy switching respectively.Significance.Lung Ion-fluoroscopy Guided Hadron Therapy (LIGHT) provides a promising approach for (a) mitigating tumour motion using a real-time, in-plane ion imaging device and (b) avoiding interplay effects with scanned beams by using a patient-specific 3D-range modulator to passively scatter a mono-energetic treatment beam. This technique also shows promise for future FLASH treatment delivery methods. Future work will fully determine the tracking performance and dosimetric benefits of LIGHT in more realistic clinical scenarios.

Intrafractional motion in the thoracic and abdominal regions remains a major challenge in particle therapy representing one of the key anatomical changes during radiotherapy. Interfractional changes further contribute to cumulative uncertainties and may require adaptive strategies over the course of treatment. The high dose conformality and steep dose fall-off of particle beams, combined with motion-induced range variations, make dose delivery highly sensitive to temporal and anatomical changes. This systematic review provides an overview of clinically implemented 4D treatment approaches addressing intrafractional motion for thoracic and abdominal indications, aiming to support harmonisation of clinical practices across centres and vendors. Systematic searches in PubMed and Web of Science identified relevant publications from January 2020 to December 2025 covering the full 4D workflow in particle therapy. The focus was on clinical implementation for lung, pancreas, liver, lymphoma, oesophagus, and breast, complemented by phantom studies and ongoing research activities. Publications were screened by eight experts using predefined inclusion and exclusion criteria. Writing and synthesis were conducted by a multidisciplinary panel of eighteen experts. A total of 751 publications were identified, of which 231 were included and categorised into six key subtopics: motion management, imaging, treatment planning optimisation and evaluation, clinical indications, phantom studies, and future perspectives. The results confirm that intrafractional motion remains a major source of uncertainty across the workflow. Despite numerous proposed 4D techniques, clinical implementation varies widely. A key limitation is the lack of standardised methods for 4D dose evaluation and interplay assessment, particularly relevant for hypofractionated treatments and advanced delivery techniques. Increasing clinical experience demonstrates that motion-related challenges can be effectively managed using appropriate 4D-aware workflows. This review represents an important step towards establishing consensus and developing guidelines for treating moving targets in particle therapy.

BACKGROUND:A renewed interest in upright particle therapy is currently driven by the availability of upright positioning and imaging systems. The upright positioning system could enhance fixed beamlines for effective carbon ion treatments in central body regions, with a substantial cost and space advantage. In addition, few studies have suggested advantages in patient breathing and lung volume in an upright posture. Comparative dosimetric analyses are needed to determine the clinical viability of upright patient positioning for carbon ion therapy of thoracic cancers but are challenged by various sources of bias. PURPOSE:To provide a comprehensive analysis of all parameters influencing the comparison between upright and supine carbon therapy of thoracic patients through 4D dosimetric studies. METHODS:Paired upright and supine 4DCTs were available for six patients treated at the Northwestern Medicine Proton Centre (NMPC), under the Proton Collaborative Group (PCG) registry. Deformable image registration (DIR) between upright and supine CTs was performed on a region of interest (ROI) including the rib cage for target propagation, to avoid failure in DIR caused by thorax anatomical differences. DIR quality was evaluated on lung structures through Dice similarity coefficient (DSC) and average Hausdorff distance (AHD) metrics. Paired 3D plans were optimized on the originally contoured and propagated target volumes, to investigate the effect of segmentation differences. The impact of beam geometry choice was investigated by optimizing plans with a variety of treatment angles. Single-fraction and accumulated 4D doses were calculated with the research treatment planning system TRiP4D to analyze the impact of differences in breathing-induced tumor motion in the two postures. Plan quality between upright and supine plans were assessed through D95%, HI, and V95% for the internal target volume (ITV) and V16Gy(lung) and V20Gy(heart) for lung and heart, respectively. RESULTS:Restraining DIR on the ribcage ROI enabled successful DIR. Within the ribcage ROI an average AHD of 1.5 mm and DSC of 0.95 was achieved on the propagated lung structure. Position specific angle selection showed vertical posterior/anterior beams might not be optimal for upright treatments. Comparable 3D treatment quality was achieved for five patients, while an increase of 5 pp occurred in V20Gy(heart) and V16Gy(lung) of patient P6 in upright. The 4D study showed the different positions have clinically relevant impact, increasing D95% of 3 pp for one patient with halved motion amplitude in upright posture. In addition, robustness was similar between postures, even with a more conservative 5%/5 mm uncertainty setting for upright. When assuming only a fixed beam line is available, as is the case for most carbon ion centers, a comparable plan quality with 360° beam angle flexibility in upright position was observed. CONCLUSIONS:The presented work comprehensively evaluates the influence of various parameters on the comparison of upright and supine therapy of thoracic patients. A solid understanding of these parameters is paramount to reduce bias in future larger patient cohort studies on the viability of upright positioning. The final dosimetric comparison between postures highly depends on patient characteristic and the investigated parameter. More data are needed to provide a resilient comparison between postures.

Carbon-ion radiotherapy provides high dose conformity for lung cancer, but its benefit is limited by two sources of uncertainties: interplay between scanned beam delivery and tumor motion, and dose modulation from heterogeneous lung tissue. This study quantifies the separate and combined dosimetric impact of these effects using the GSI TRiP4D treatment planning system. Eighteen lung cancer 4DCT datasets from TCIA were analyzed. A modulation power (P_mod) was assigned to lung voxels. Three values were sampled from a Gaussian distribution (200μm± 67μm), and an extreme value of 750μm was tested. Interplay doses were computed by combining scanned-beam delivery with patient-specific respiratory motion. Four scenarios were studied: static, static with modulation, interplay, and interplay with modulation. Metrics included D95%, V95%, homogeneity index (HI), lung V16Gy, and heart V20Gy. Interplay reduced target coverage by 5.2 ± 1.5 pp (D95%), 12.1 ± 5.9 pp (V95%), and 8.3 ± 2.4 pp (HI). Extreme P_mod alone caused small degradations. When combined with interplay, it partially compensated the loss. This effect decreased with 4D optimization. Fractionation mitigated interplay, leaving lung modulation as the main residual effect.

During the course of cancer treatment, radiotherapy plans often require adaptation to account for changes in tumor position and patient anatomy. This adaptive approach is especially critical in particle therapy, where organ changes and motion can cause severe dose deviations. In-beam positron emission tomography offers a potential solution for real-time dose verification and treatment adaptation in particle therapy. However, its clinical applicability is currently limited by the low signal-to-noise ratio and the spatial mismatch between activity and dose peaks. These limitations hinder accurate verification of treatment and timely intervention. Here, we demonstrate for the first time that in-beam imaging of radioactive ion beams can enable real-time adaptive treatment of a tumor in a mouse model. We show that dynamic repositioning of a b + -emitting 11 C-beam along the mouse body results in spatially resolved imaging signals that correlate with distinct treatment outcomes. These findings represent the first evidence of real-time adaptive radiotherapy using radioactive ion beams in a living organism, opening new avenues for precision image-guided particle therapy.

Carbon ion therapy is one of the most advanced forms of radiotherapy, promising improved efficacy against resistant cancers. However, the high precision offered by the carbon ion Bragg peak requires precise knowledge of the beam range inside the patient. We report the first experimental realization of range monitoring and portal imaging with a mixed ion beam, where carbon ions are treating the tumor while helium ions simultaneously accelerated to the same velocity fully traverse the patient and provide treatment feedback. Using the GSI synchrotron, a beam of 12C3+ and 4He1+ ions is accelerated, exploiting their nearly identical charge-to-mass ratios. Stable extraction with controlled helium fractions down to 7

BACKGROUND:Treatment adaptation is particularly critical in particle therapy, where even small range deviations can compromise target coverage or lead to unintended dose delivered to surrounding healthy tissues. In-beam positron emission tomography (PET) has emerged as a promising approach for range verification during irradiation with protons or stable carbon ion beams. However, its clinical use is limited by low signal-to-noise ratio and by the spatial mismatch between activity and dose distributions, reducing verification accuracy and limiting timely intervention. METHODS:We used radioactive ion beams for real-time range adaptation in 10 weeks old C3H/ HeNRj female mice bearing LM8-osteosarcoma tumors. Three 11C beam range settings were planned: short (S), right (R), and long (L). The range of a collimated monoenergetic probing beam was monitored in real-time with the SIRMIO in-beam PET scanner by tracking the activity peak along the beam path, while range adaptation was achieved with a remotely controlled range shifter. Each plan (S, R and L) was also delivered, and tumor growth, toxicity assays, and histological analyses were performed to evaluate each treatment outcomes. RESULTS:Dynamic repositioning of the 11C beam produced spatially resolved PET signals that correlated with distinct biological outcomes. Toxicity was observed only in the L group, while adequate tumor coverage was achieved in both R and L groups. In contrast, the S group showed continued tumor growth. CONCLUSIONS:We provide the first demonstration that in-beam imaging of radioactive ion beams can enable real-time range-guided radiotherapy in a living organism. These findings establish radioactive ion beams as a promising platform for precision range-guided particle therapy.

Objective. To identify suitable combination strategies for treatment planning and beam delivery in scanned carbon ion therapy of moving tumors. Approach. Carbon ion treatment plans for five abdominal tumors were optimized on four-dimensional (4D) computed tomography (CT) data using the following approaches. 4DITV across all phases and within a gating window, single phase uniform dose, and an innovative 4D tracking internal target volume (ITV) strategy. Delivered single-fraction doses were calculated on time-resolved virtual CT images reconstructed from 2D cine-magnetic resonance imaging series, using a deformable image registration pipeline. Treatment plans were combined with various beam delivery techniques: three-dimensional (no motion mitigation), rescanning, gating, beam tracking, and multi-phase 4D delivery with and without residual tracking (MP4D and MP4DRT) to form in total 11 treatment modalities. Single fraction doses were accumulated to simulate a fractionated treatment. Main results. Breath-sampled treatments using the MP4D and MP4DRT delivery techniques were the only to achieve D95 > 95% for hypofractionated treatments, with little dependence on the number of fractions. A combination of MP4DRT with the new 4D tracking ITV approach resulting in conformal dose distributions and demonstrated the greatest robustness against irregular motion and anatomical changes. Significance. This study demonstrates, that real-time adaptive beam delivery strategies can deliver conformal doses within single fractions, thereby enabling hypofractionated treatment schemes that are not feasible with conventional strategies.

Tumor motion is a major challenge for scanned ion-beam therapy. In the case of lung tumors, strong under- and overdosage can be induced due to the high density gradients between the tumor- and bone tissues compared to lung tissues. This work proposes a non-invasive concept for 4D monitoring of high density gradients in carbon ion beam therapy, by detecting charged fragments. The method implements CMOS particle trackers that are used to reconstruct the fragment vertices, which define the emission points of nuclear interactions between the primary carbon ions and the patient tissues. A 3D treatment plan was optimized to deliver 2 Gy to a static spherical target volume. The goodness of the method was assessed by comparing reconstructed vertices measured in two static cases to the ones in a non-compensated moving case with an amplitude of 20 mm. The measurements, performed at the Marburg Ion-Beam Therapy Center (MIT), showed promising results to assess the conformity of the delivered dose. In particular to measure overshoots induced by high density gradients due to motion with 83.0 ± 1.5% and 92.0 ± 1.5% reliability based on the ground truth provided by the time-resolved motor position and depending on the considered volume and the iso-energy layers.

BACKGROUND:Integrated mode proton imaging is a clinically accessible method for proton radiographs (pRads), but its spatial resolution is limited by multiple Coulomb scattering (MCS). As the amplitude of MCS decreases with increasing particle charge, heavier ions such as carbon ions produce radiographs with better resolution (cRads). Improving image resolution of pRads may thus be achieved by transferring individual proton pencil beam images to the equivalent carbon ion data using a trained image translation network. The approach can be interpreted as applying a data-driven deconvolution operation with a spatially variant point spread function. PURPOSE:Propose a deep learning framework based on paired proton-carbon data to increase the resolution of integrated mode pRads. METHODS:A conditional generative adversarial network, Proton2Carbon, was developed to translate proton pencil beam images into synthetic carbon ion beam images. The model was trained on 547 224 paired proton-carbon images acquired with a scintillation detector at the Marburg Ion Therapy Centre. Image reconstruction was performed using a 2D lateral method, and the model was evaluated on internal and external datasets for spatial resolution, using custom 3D-printed line pair modules. RESULTS:The Proton2Carbon model improved the spatial resolution of pRads from 1.7 to 2.7 lp/cm on internal data and to 2.3 lp/cm on external data, demonstrating generalizability. Water equivalent thickness accuracy remained consistent with pRads and cRads. Evaluation on an anthropomorphic head phantom showed enhanced structural clarity, though some increased noise was observed. CONCLUSIONS:This study demonstrates that deep learning can enhance pRad image quality by leveraging paired proton-carbon data. Proton2Carbon can be integrated into existing imaging workflows to improve clinical and research applications of proton radiography. To facilitate further research, the full dataset used to train Proton2Carbon is publicly released and available at https://zenodo.org/records/14945165.

Despite remarkable advances, radiation therapy (RT) remains inefficient for some bulky tumors, radioresistant tumors, and certain pediatric tumors. Minibeam radiation therapy (MBRT) has emerged as a promising approach, reducing normal tissue toxicity while enhancing immune responses. Preclinical studies using X-rays and proton MBRT have demonstrated enhanced therapeutic index for aggressive tumor models. Combining MBRT’s advantages of spatial dose fractionation with the physical and biological benefits of carbon ions could be a step further toward unleashing the full potential of MBRT. This study aims to perform the first in vivo study of local and systemic responses of a subcutaneous mouse osteosarcoma (metastatic) model to carbon MBRT (C-MBRT) versus conventional carbon ion therapy (CT). Irradiations were conducted at the GSI Helmholtz Centre in Germany using 180 MeV/u 12C ions beam. All irradiated animals received an average dose (20 Gy) and displayed a significant and similar tumor growth delay in addition to a decreased metastasis score compared to the non-irradiated group. In the C-MBRT group, 70% of the tumor volume received the valley dose, which is a very low dose of 1.5 Gy. The remaining 30% of the tumor received the peak dose of 105 Gy, resulting in an average dose of 20 Gy. These results suggest that C-MBRT triggered distinct mechanisms from CT and encourage further investigations to confirm the potential of C-MBRT for efficient treatment of radioresistant tumors.

BACKGROUND:Hypoxia significantly affects radiotherapy by increasing tumor radioresistance. High linear energy transfer radiation, such as carbon ion therapy, can help mitigate this issue. Carbon ion arc therapy offers the potential to increase LET in hypoxic tumor regions, offering a promising approach to improve treatment outcomes, but lacks robustness. PURPOSE:We introduced and quantitatively evaluated a new heavy ion therapy treatment strategy named LET bOost by heavy Particle Arc RaDiation (LEOPARD), which combines intensity-modulated particle therapy (IMPT) with spot-scanning hadron arc (SHArc) strategy. LEOPARD aims to increase dose and the dose-averaged linear energy transfer ( LET d ${\rm LET}_{\mathrm{d}}$ ) within the hypoxic target volume (HTV) while maintaining plan quality and robustness. IMPT and SHArcBoost are used as reference strategies for comparison. METHODS:A proof of concept for LEOPARD was realized on 15 head & neck cancer patients with an artificially contoured HTV generated from isotropic shrinking of the clinical target volume (CTV). The LEOPARD plans integrate a full arc field (0 ∘ $^\circ$ to 358 ∘ $^\circ$ , step = 2 ∘ $^\circ$ , 180 fields) delivering a boost dose to the HTV with additional IMPT fields(10 ∘ $^\circ$ and 170 ∘ $^\circ$ ) that simultaneously provide the prescribed dose to the CTV, combining both approaches in a unified treatment plan. To evaluate the potential of LEOPARD, we compared it to intensity modulated particle therapy dose boost plans (IMPTBoost) which included 2 IMPT fields (10 ∘ $^\circ$ and 170 ∘ $^\circ$ ) for CTV, with 2 identical fields added to boost dose in HTV, and SHArc-only boost plans (SHArcBoost) which used same arc fields as LEOPARD aimed at both CTV and HTV but without IMPT fields. Plans were evaluated for dosimetric accuracy, robustness, LET d ${\rm LET}_{\mathrm{d}}$ , and cell survival fraction considering the oxygen-enhancement ratio. Treatment delivery times were calculated using an in-house dynamic carbon ion arc therapy delivery simulator. RESULTS:LEOPARD combined treatment demonstrated a capacity to balance plan quality by mitigating the robustness issues inherent in SHArc plans while improving the LET distribution compared to IMPTBoost plans. Compared with SHArcBoost, LEOPARD showed higher mean D95 in the HTV (96.1% vs. 95.4%; p < 0.001 $p < 0.001$ ), lower mean D2 (113.2% vs. 117.0%; p < 0.001 $p < 0.001$ ) and HI (18.3% vs. 22.6%; p < 0.001 $p < 0.001$ ). Compared with IMPTBoost, mean LET d ${\rm LET}_{\mathrm{d}}$ 50 in the HTV increased by 16.9% ( p < 0.001 $p < 0.001$ ), and mean SF50 in the HTV reduced by 3.8% ( p < 0.001 $p < 0.001$ ). CONCLUSION:We developed a new treatment strategy-LEOPARD, which can generate higher LET d ${\rm LET}_{\mathrm{d}}$ in the HTV than IMPTBoost, while achieving better dose distribution and plan robustness compared to SHArcBoost. This work therefore indicates promising potential of LEOPARD for the treatment of hypoxic tumors.

BACKGROUND:Incorporating image guidance into ion beam therapy is critical for minimizing beam range uncertainties and realizing the modality's potential. One promising avenue for image guidance is to capture transmission ion radiographs (iRads) before and/or during treatment. iRad image quality is typically maximized using a single-event imaging system, which involves tracking individual ions, albeit the approach is generally not suited to clinical beam settings. An alternative faster and clinically compatible method is integrated mode imaging, where individual pencil beam data is acquired, rather than single ion data. To evaluate the usefulness of transmission ion imaging for image guidance, it is crucial to evaluate the image quality of integrated mode iRad systems. PURPOSE:We report extensive image quality metrics of integrated mode carbon ion radiographs (cRads) and compare them with proton radiographs (pRads). METHODS:iRads were obtained at the Marburg Ion Beam Therapy Center using a plastic volumetric scintillator equipped with CCD cameras. The detector captures orthogonal views of the 3D energy deposition in the scintillator from individual pencil beams. Four phantoms were scanned using a 15 × 15 cm 2 $15\times 15 \ {\rm cm}^2$ field of view and a beam spacing of 1 mm. First, 9 tissue-substitute inserts were used to evaluate water equivalent thickness (WET) accuracy. Radiographs of those inserts were reconstructed for beam spacings ranging from 1 to 7 mm to evaluate the impact of spacing on quantitative accuracy. For spatial resolution, custom 3D printed line pair (lp) modules ranging from 0.5 to 10 lp/cm were scanned. To evaluate low contrast detectability, a custom 3D printed low contrast module consisting of 20 holes with depths ranging from 1 to 8 mm and diameters from 1 to 10 mm was scanned. iRads of an anthropomorphic head phantom were also obtained. RESULTS:Spatial resolution and low contrast detection are systematically improved for cRads compared to pRads. Image resolution was 3.7 lp/cm for cRads and 1.7 lp/cm for pRads in the center of the field of view. Spatial resolution was found to vary with the object's location in the field of view. While pRads could mostly resolve low contrast holes of 10 mm in diameter, cRads could resolve holes of up in 4 mm diameter. WET accuracy is similar for both ion species, with a root mean squared error of approximately 1 mm. WET accuracy was stable (maximum of 0.1 mm increase) across beam spacings, although important under-sampling artifacts were observed for iRads reconstructed using large beam spacings, especially for cRads. iRads of the anthropomorphic head phantom showed improved apparent contrast using cRads, especially to identify bony structures. CONCLUSIONS:This work is the first investigation of image quality metrics such as spatial resolution and low contrast detectability for integrated mode cRads, with a full comparison with pRads. Enhanced image quality is obtained with cRads compared to pRads, although pRads still maintain high WET accuracy and deliver image quality within acceptable bounds.

Objective. This work aims to evaluate the ability of novel detector components to measure with submillimeter resolution in beam positron emission tomography (PET) signals produced by 10C and 11C radioactive ion beams stopped in PMMA targets and to validate a simulation toolkit for reproducing beam physics and PET detector responses within the framework of the biomedical applications of radioactive ion beam (BARB) project. Approach. The PET system response was assessed by visualizing the radioactive distributions of the beams stopped in tissue surrogate phantoms, and the capacity of the simulation toolkit was evaluated by comparing the experimental results with simulations, both for the depth-dose distribution and PET imaging. Main results. The detector assembly accurately visualized the PET signal with submillimeter resolution, achieving the objective of measuring the difference in the positron range between 10C and 11C. The simulation toolkit effectively reproduced the beam characteristics and detector responses, showing a high degree of agreement between the simulated and experimental PET profiles under different beam delivery conditions. Significance. These findings demonstrate the precision and reliability of the novel in-beam PET detector technology and simulation toolkit for small animals, establishing a solid foundation for the second phase of the BARB project, which involves preclinical irradiation of living mice.

Monte Carlo (MC) simulations provide gold-standard accuracy for carbon ion therapy dose calculations but are computationally intensive. Analytical pencil beam algorithms offer speed but reduced accuracy in heterogeneous tissues. We developed the first AI-based dose engine capable of predicting absorbed dose, the alpha and beta parameters for relative biological effectiveness (RBE)- weighted optimisation in carbon ion therapy, delivering MC-level accuracy with drastically reduced computation time. We extended the transformer-based DoTA model to predict absorbed dose (C-DoTA-d), alpha (C-DoTA-alpha), and beta (C-DoTA-beta), introducing a cross-attention mechanism for alpha and beta to combine dose and energy inputs. The training dataset consisted of 70,000 pencil beams from 187 head-and-neck patients, with ground-truth values obtained using the GPU-accelerated MC toolkit FRED. Performance was evaluated on an independent test set using gamma pass rate (1

Purpose: This work presents a proof-of-concept study of HyperSHArc, spot-scanning hadron arc (SHArc) therapy for single-isocenter stereotactic radiosurgery of multiple brain metastases (MBMs). HyperSHArc plans using proton, helium, and carbon ions were compared with state-of-the-art volumetric modulated photon arc therapy. Methods and Materials: Treatment design and optimization procedures were devised using commercial and in-house treatment planning systems. Planning and delivery methods considered dedicated energy, spot, and multiarc selection strategies. Proton, helium, and carbon HyperSHArc plans were generated for patients with MBM exhibiting 3 to 11 intracranial lesions with gross tumor volumes (GTVs) between 0.03 and 19.8 cc, at prescribed doses between 19 and 21Gy in a single-fraction. Planning target volumes (PTVs) considered a 1-mm isotropic margin around the GTV, and robust optimization with 2.5%/1 mm criteria for range and position uncertainty was applied. Photon hyper-arc volumetric modulated arc therapy (HA-VMAT) plans were optimized for the PTVs using the HyperArc® single-isocenter stereotactic radiosurgery platform (Varian, Palo Alto, CA, USA). Results: HyperSHArc plans were comparable between particle species, achieving highly conformal target doses and satisfying clinical coverage criteria. Particle arc plans reduced V2Gy and V4Gy in the healthy brain compared with HA-VMAT, while intermediate doses (V8Gy-V16Gy) were similar or reduced depending on the number of lesions. Particularly for the case with 11 targets, a considerable reduction in V12Gy was observed that could be relevant for reducing the risk of treatment-induced radionecrosis. HyperSHArc using carbon ions boosted dose-averaged linear energy transfer inside the target relevant to overcoming radioresistance factors (>100 keV/μm). Conclusions: We present the first particle arc therapy strategies for MBM. Results demonstrate that with HyperSHArc, dose conformity comparable or superior to HA-VMAT is achievable while reducing the low-dose bath and increasing mean dose-averaged linear energy transfer in the GTV. Our findings suggest that HyperSHArc using light and heavy ions could be an effective and efficient means of treating MBM. Further development of HyperSHArc optimization and delivery is justified.