Particle Therapy Research Articles

Evaluation of pelvic MRI-to-CT deformable registration for adaptive MR-guided particle therapy

PurposeWe aim to assess the MRI-to-CT deformable image registration (DIR) quality of our treatment planning system in the pelvic region, as the first step of an online MRI-guided particle therapy clinical workflow. Materials and MethodsUsing two different DIR algorithms, ANACONDA, the DIR algorithm incorporated in RayStation, and Elastix, an open source registration software, we retrospectively assessed the quality of the deformed CT (dCT) generation in the pelvic region for five patients. T1- and T2-weighted daily control MRI acquired prior to treatment delivery were used for the DIR. We compared the contours automatically mapped on the dCT against the manual contours on the MRI (ground-truth), by calculating the Dice similarity coefficients (DSC) and mean distances to agreement (MDA) for OAR, targets and outer contour. We assessed the dosimetric impact of the DIR on the clinical treatment plans, comparing the dose volume histograms (DVHs) and the value of the clinical goals achieved for each dCT. The water equivalent path lengths (WEPL) and dose range 80% (R80%) maps were compared by casting on the beams' eye view. ResultsThe T1 sequences performed better for the DIR with ANACONDA compared against the T2. ANACONDA's performance agreed with Elastix. The bladder and rectum led to the worst agreement. For the remaining structures analysed, DSC above 0.80 were obtained. Maximum median deviations of 7.1 mm and 2.1 mm were observed for WEPL and R80%, respectively, on the PTV. ConclusionThis works shows a good agreement on the DIR quality achieved with ANACONDA for the structures in the beams' path. By comparing the R80% generated with ANACONDA and Elastix, we give a first quantification of the uncertainties to be considered in an online MRI-guided particle therapy workflow for pelvic treatment.

Advances in external beam radiation for hepatocellular carcinoma, stereotactic body radiation therapy (SBRT) and particle therapy

Advances in external beam radiation for hepatocellular carcinoma, stereotactic body radiation therapy (SBRT) and particle therapy

Validation of Light–Ion Quantum Molecular Dynamics (LIQMD) model for hadron therapy

Purpose:This study aims to validate the Light-Ion Quantum Molecular Dynamics (LIQMD) model, an advanced version of the QMD model for more accurate simulations in hadron therapy, incorporated into Geant4 (release 11.2). Methods:Two sets of experiments are employed. The first includes positron-emitter distributions along the beam path for 350 MeV/u 12C ions incident on a PMMA target, obtained from in–vivo Positron Emission Tomography (PET) experiments at QST (Chiba, Japan). The second comprises cross-sections for 95 MeV/u 12C ions incident on thin targets (H, C, O, Al, and Ti), obtained from experiments at GANIL (Caen, France). The LIQMD model’s performance is compared with the experimental data and the default QMD model results. Results:The LIQMD model can predict the profile shape of positron-emitting radionuclide yields with better accuracy than the default QMD model, although some discrepancies remains. The consistency observed in the production of positron-emitting radionuclides aligns with the thin target cross-section analysis. The LIQMD model significantly improves the differential and double-differential cross-sections of fragments produced in thin targets, especially in the forward direction. The overestimation of 10C production in the in–vivo PET benchmark is consistent with the 95 MeV/u 12C cross-section test. Overall, the LIQMD model demonstrates better agreement with experimental measurements for nearly all fragment species compared to the QMD model. Conclusions:The LIQMD model offers an improved description of the fragmentation process in hadron therapy. Future work should involve further validation against additional experimental measurements to confirm these findings.

Australian Particle Therapy Clinical Quality Registry (ASPIRE) protocol (TROG 21.12): a multicentre prospective study on patients with rare tumours, treated with radiation therapy

IntroductionIn 2020, the Australian Medical Services Advisory Committee (MSAC) recommended new proton beam therapy (PBT) item numbers be added to the Medicare Benefits Schedule. During the MSAC 1638 application process,...

On the microdosimetric characterisation of the radiation quality of a carbon-ion beam and the effect of the target volume thickness.

Objective - Microdosimetry is gaining increasing interest in particle therapy. Thanks to the advancements in microdosimeter technologies and the increasing number of experimental studies carried out in hadron therapy frameworks, it is proving to be a reliable experimental technique for radiation quality characterisation, quality assurance, and radiobiology studies. However, considering the variety of detectors used for microdosimetry, it is important to ensure the consistency of microdosimetric results measured with different types of microdosimeters.
Approach - This work presents a novel multi-thickness microdosimeter and a methodology to characterise the radiation quality of a clinical carbon-ion beam. The novel device is a diamond detector made of three sensitive volumes (SV) of different thicknesses: 2, 6 and 12 μm. The SVs, which operate simultaneously, were accurately aligned and laterally positioned within 3mm. This allignement allowed for a comparison of the results with a negligible impact of the SVs alignment and their lateral positioning, ensuring the homogeneity of the measured radiation quality. An experimental campaign was carried out at MedAustron using a carbon-ion beam of typical clinical energy (284.7MeV/u).
Main results - The measurement results allowed for a meticulous interpretation of its radiation quality, highlighting the effect of the SV thickness. The consistency of the microdosimetric spectra measured by detectors of different thicknesses is discussed by critically analysing the spectra and the differences observed.
Significance - The methodology presented will be highly valuable for future experiments investigating the effects of the target volume size in radiobiology and could be easily adapted to the other particles employed in hadron therapy for clinical (i.e. protons) and for research purposes (e.g. helium, lithium and oxygen ions).

Dual virtual non-contrast imaging: a Bayesian quantitative approach to determine radiotherapy quantities from contrast-enhanced DECT images.

Contrast agents in CT scans can compromise the accuracy of dose calculations in radiation therapy planning, especially for particle therapy. This often requires an additional non-contrast CT scan, increasing radiation exposure and introducing potential registration errors. Our goal is to resolve these issues by accurately estimating radiotherapy parameters from dual virtual non-contrast (dual-VNC) images generated by contrast-enhanced dual-energy CT (DECT) scans, while accounting for noise and variability in tissue composition.
Approach: A new Bayesian model is introduced to estimate dual-VNC Hounsfield units from contrast-enhanced DECT data. The model defines a prior distribution that describes tissue variations in terms of elemental compositions and mass densities. Multiple reference tissues are used to estimate variations across human tissues. A likelihood distribution is also defined to model the noise contained in CT data. The model is thoroughly validated in a simulated environment including 12 virtual patients under low and high iodine uptake scenarios, while incorporating noise and beam hardening effects. The eigentissue decomposition (ETD) technique is used to derive elemental compositions and parameters critical for radiotherapy from the dual-VNC images, such as electron density (ρe), particle stopping power (SPR), and photon energy absorption coefficient (EAC)
Main results: The proposed method yields accurate voxelwise estimations for ρe, SPR, and EAC, with root mean square errors of 3.09%, 3.14%, and 1.34% for highly-enhanced tissues, compared to 5.93%, 6.39%, and 17.11% when the presence of contrast agent is ignored. It also demonstrates robustness to systematic shifts in tissue composition and bandwidth variations in the prior distribution, resulting in overall uncertainties down to 1.13%, 1.33%, and 0.86% for ρe, SPR, and EAC in soft tissues; 1.17%, 1.32%, and 1.34% in enhanced soft tissues; and 4.34%, 4.00%, and 2.50% in bone.
Significance: The proposed method accurately derives radiotherapy parameters from contrast-enhanced DECT data and demonstrates robustness against systematic errors in reference data, highlighting its potential for clinical use.

Fast and precise dose estimation for very high energy electron radiotherapy with graph neural networks

IntroductionExternal beam radiotherapy (RT) is one of the most common treatments against cancer, with photon-based RT and particle therapy being commonly employed modalities. Very high energy electrons (VHEE) have emerged as promising candidates for novel treatments, particularly in exploiting the FLASH effect, offering potential advantages over traditional modalities.MethodsThis paper introduces a Deep Learning model based on graph convolutional networks to determine dose distributions of therapeutic VHEE beams in patient tissues. The model emulates Monte Carlo (MC) simulated doses within a cylindrical volume around the beam, enabling high spatial resolution dose calculation along the beamline while managing memory constraints.ResultsTrained on diverse beam orientations and energies, the model exhibits strong generalization to unseen configurations, achieving high accuracy metrics, including a δ-index 3% passing rate of 99.8% and average relative error <1% in integrated dose profiles compared to MC simulations.DiscussionNotably, the model offers three to six orders of magnitude increased speed over full MC simulations and fast MC codes, generating dose distributions in milliseconds on a single GPU. This speed could enable direct integration into treatment planning optimization algorithms and leverage the model’s differentiability for exact gradient computation.

Proof-of-principle of 3D-printed track-end detectors for dosimetry in proton therapy.

Dosimetric equipment in particle therapy (PT) is associated with high costs. There is a lack of versatile, tissue-equivalent detectors suitable for in-vivo dosimetry. Faraday-cup (FC) type detectors are sensitive to stopped protons, that is, to track-ends (TEs). They experience a renaissance in PT as they can cope with high dose rates. Owing to their simple functional principle, production of FC could benefit from the dynamic technological developments in additive manufacturing ofsensors. To build FC-type detectors for PT by standard 3D-printing. This study seeks to build an integrating, single-channel (SC) FC for replacement of a traditional FC and a array of FC elements indicating the feasibility of a spatially resolvingdetector. Samples of FCs were produced with a dual-extruder 3D-printer with polylactic-acid filaments, which contained graphite in the conductive parts of the detector. Production was optimized in terms of materials and printing temperature. Samples were characterized by electrical tests and non-destructive 3D x-ray imaging. Beam tests were conducted at a clinical PTmachine. Operational FC-type detectors for proton fields were printed. The detected charge of the SC FC corresponded qualitatively to the one of a traditional FC. A FC array was fabricated in a single run. There was a linear relationship between the response of the individual FC elements and the machineoutput. 3D-printing is a viable method for producing low-cost, tissue-equivalent, FC-type detectors for PT. They could potentially be used as TE detectors in anthropomorphicphantoms.

ASO Visual Abstract: Comparison of Prognostic Outcomes Between Repeat Liver Resection and Particle Therapy for Patients with Recurrent Hepatocellular Carcinoma.

ASO Visual Abstract: Comparison of Prognostic Outcomes Between Repeat Liver Resection and Particle Therapy for Patients with Recurrent Hepatocellular Carcinoma.

Comparison of the dosimetry and cell survival effect of 177Lu and 161Tb somatostatin analog radiopharmaceuticals in cancer cell clusters and micrometastases

Background177Lu-based radiopharmaceuticals (RPs) are the most used for targeted radionuclide therapy (TRT) due to their good response rates. However, the worldwide availability of 177Lu is limited. 161Tb represents a potential alternative for TRT, as it emits photons for SPECT imaging, β−-particles for therapy, and also releases a significant yield of internal conversion (IE) and Auger electrons (AE). This research aimed to evaluate cell dosimetry with the MIRDcell code considering a realistic localization of three 161Tb- and 177Lu-somatostatin (SST) analogs in different subcellular regions as reported in the literature, various cell cluster sizes (25–1000 µm of radius) and percentage of labeled cells. Experimental values of the α- and β-survival coefficients determined by external beam photon irradiation were used to estimate the survival fraction (SF) of AR42J pancreatic cell clusters and micrometastases.ResultsThe different localization of RPs labeled with the same radionuclide within the cells, resulted in only slight variations in the dose absorbed by the nuclei (ADN) of the labeled cells with no differences observed in either the unlabeled cells or the SF. ADN of labeled cells (MDLC) produced by 161Tb-RPs were from 2.8–3.7 times higher than those delivered by 177Lu-RPs in cell clusters with a radius lower than 0.1 mm and 10% of labeled cells, due to the higher amount of energy emitted by 161Tb-disintegration in form of IE and AE. However, the 161Tb-RPs/177Lu-RPs MDLC ratio decreased below 1.6 in larger cell clusters (0.5–1 mm) with > 40% labeled cells, due to the significantly higher 177Lu-RPs cross-irradiation contribution. Using a fixed number of disintegrations, SFs of 161Tb-RPs in clusters with > 40% labeled cells were lower than those of 177Lu-RPs, but when the same amount of emitted energy was used no significant differences in SF were observed between 177Lu- and 161Tb-RPs, except for the smallest cluster sizes.ConclusionsDespite the emissions of IE and AE from 161Tb-RPs, their localization within different subcellular regions exerted a negligible influence on the ADN. The same cell damage produced by 177Lu-RPs could be achieved using smaller quantities of 161Tb-RPs, thus making 161Tb a suitable alternative for TRT.

Proton bunch monitors for the clinical translation of prompt gamma-ray timing

Objective. Prompt gamma-ray timing is an emerging technology in the field of particle therapy treatment verification. This system measures the arrival times of gamma rays produced in the patient body and uses the cyclotron radio frequency signal as time reference for the beam micro-bunches. Its translation into clinical practice is currently hindered by observed instabilities in the phase relation between the cyclotron radio frequency and the measured arrival time of prompt gamma rays. To counteract this, two proton bunch monitors are presented, integrated into the prompt gamma-ray timing workflow and evaluated.Approach. The two monitors are (a) a diamond detector placed at the beam energy degrader, and (b) a cyclotron monitor signal measuring the phase difference between dee current and voltage. First, the two proton bunch monitors as well as their mutual correlation were characterized. Then, a prompt gamma-ray timing measurement was performed aiming to quantify the present magnitude of the phase instabilities and to evaluate the ability of the proton bunch monitors to correct for these instabilities.Main results. It was found that the two new monitors showed a very high correlation for intermediate proton energies after the first second of irradiation, and that they were able to reduce fluctuations in the detected phase of prompt gamma rays. Furthermore, the amplitude of the phase instabilities had intrinsically decreased from about 700 ps to below 100 ps due to cyclotron upgrades.Significance. The uncertainty of the prompt gamma-ray timing method for proton treatment verification was reduced. For routine clinical application, challenges remain in accounting for detector load effects, temperature drifts and throughput limitations.

GEANT4 simulation for controlling and focusing of laser-accelerated proton beam for particle therapy using pulsed power solenoids

Laser-accelerated proton beams (LAP) have inspired innovative applications that can leverage proton bunch properties distinct from those of conventionally accelerated proton beams. A new multifunctional LAP beamline has been proposed, utilizing the GEANT4 toolkit, and the solenoids have been simulated using high-precision components.We present the design of the initial segment of the transport beamline and energy selection system for the effective transport of a radiation pressure acceleration source with a high energy spread. This study examines the effects of solenoids on proton beam quality, specifically focusing on profiles, FWHM, and transmission efficiency. The results obtained using our developed GEANT4 toolkit validate the analytical formulas and findings from the DYNAMION code regarding emittance and proton profiles. Additionally, the presented GEANT4 LAP beamline is capable of calculating the flux of secondary particles, such as neutrons and photons. It was observed that careful attention to the precise structure of the solenoids is critical.

Ongoing prospective studies on reirradiation: A systematic review of a clinical trials database

IntroductionReirradiation has gained increasing interest, as advances in systemic therapy increase the survival of patients with cancer, and modern radiation techniques allow more precise treatments. However, high-quality prospective evidence on the safety and efficacy of reirradiation to guide clinical practice remains scarce. This systematic review evaluates ongoing prospective studies on reirradiation to identify research gaps and priorities. MethodsA systematic review of ClinicalTrials.gov was conducted on July 11, 2024, using search terms related to reirradiation. Inclusion criteria were prospective studies that were “recruiting,” “not yet recruiting,” or “active, not recruiting.” Studies with published results, retrospective, and in-silico studies were excluded. The review followed PRISMA 2020 guidelines and recommendations for systematic searches of clinical trial registries. ResultsAmong 1026 identified studies, 307 were screened, 99 were included. Fourty (40%) focused on central nervous system (CNS), 23 (23%) head and neck, and 17 (17%) on pelvic reirradiation. Most studies (90%) were interventional, with 32 (32%) phase II and 4 (4%) phase III trials. Sixteen trials were randomized (RCTs), including the 4 phase III trials for recurrent glioblastoma, rectal and nasopharyngeal cancer. Ten dose escalation trials focus on recurrent prostate, rectal, and non-small cell lung cancer as well as glioma. Modern high-precision radiotherapy techniques were frequently used, with 21 (21%) studies using stereotactic radiotherapy and 17 (17%) using particle therapy. Combinations with systemic therapies were investigated in 41 (41%) studies. ConclusionOngoing studies most frequently focus on CNS, head and neck, and pelvic reirradiation. There remains a critical need for RCTs, in particular for lung, breast, and gynecological cancers. Dose escalation trials, application of precision radiation techniques and combinations with modern systemic therapy may help define the optimal multimodality treatment schedules.

Detection resolving power of SiC Timepix3 detector to electrons, neutrons, ions and protons

Silicon Carbide is a suitable semiconductor sensor for radiation measurement and nuclear applications. It has been recently implemented as a position-sensitive and radiation imaging device coupled to the Timepix3 ASIC chip in the form of a miniaturized radiation camera MiniPIX-Timepix3 SiC. In this work we systematically evaluate the detection resolving power to different radiation species: electrons, fast neutrons, ions and protons. Experimental calibrations were made at well-defined reference fields in terms of particle type, energy and direction. The spectral-sensitive tracking response and characteristic morphology of the particle tracks are analyzed by pattern recognition algorithms. The low thickness of the radiation sensitive volume (65 μm) of the SiC sensor limits the directional tracking response and angular resolution. Three broad classes of particle-type events are resolved. The detector together with suitable data processing can be used for radiation dosimetry and particle tracking tasks in space, particle therapy, nuclear physics and nuclear reactors and particle accelerator environments.

Review of real time 2D dosimetry in external radiotherapy: Advancements and techniques

The objective of this paper is to provide a comprehensive review of the advancements and techniques in real time two-dimensional (2D) dosimetry for external radiation therapy with emphasis in vivo dosimetry and patient specific quality assurance. External radiation therapy plays a crucial role in cancer treatment, delivering high-energy radiation beams to target tumours while minimizing damage to surrounding healthy tissues. Accurate dosimetry, as both the measurement of the dose and its delivered location, is paramount to ensure effective treatment outcomes and minimize potential side effects.The planned content of this paper encompasses a thorough examination of the advancements made in 2D dosimetry techniques, including solid state and electronic systems. The evolution from traditional passive dosimetry to modern real time detectors, such as portal imaging, has revolutionized the field, offering enhanced precision, efficiency, and convenience. This review will discuss the principles, advantages, and limitations of these systems, along with their practical implementation and calibration procedures.Furthermore, the paper will highlight novel technologies, such as luminescence coatings, for quality assurance (QA) and real-time dose verification during treatment. The use of innovative materials and designs in dosemeters, including high spatial resolution detectors and tissue-equivalent phantoms, will also be explored. Additionally, the incorporation of advanced data analysis techniques, such as machine/deep learning algorithms, for dose reconstruction and QA will be addressed.The review will also explore the application of real time 2D dosimetry in modern clinical and pre-clinical modalities, including intensity-modulated radiation therapy and volumetric modulated arc therapy, stereotactic radiosurgery, image-guided radiation therapy, particle therapy, adaptive radiotherapy, electron and proton ultra-high dose rate therapy and very high energy electrons.By providing an up-to-date overview of the state-of-the-art in real time 2D dosimetry in vivo dosimetry and patient specific quality assurance, this paper aims to inform and guide professionals in the field, facilitating the adoption of cutting-edge techniques and improving the accuracy and safety of external radiotherapy treatments.

Advancing Proton Therapy: A Review of Geant4 Simulation for Enhanced Planning and Optimization in Hadron Therapy

Abstract Proton therapy is a cancer treatment method that uses high-energy proton beams to target and destroy cancer cells. In recent years, the use of proton therapy in cancer treatment has increased due to its advantages over traditional radiation methods, such as higher accuracy and reduced damage to healthy tissues. For accurate planning and delivery of proton therapy, advanced software tools are needed to model and simulate the interaction between the proton beam and the patient’s body. One of these tools is the Monte Carlo simulation software called Geant4, which provides accurate modeling of physical processes during radiation therapy. The purpose of this study is to investigate the effectiveness of the Geant4 toolbox in proton therapy in the conducted research. This review article searched for published articles between 2002 and 2023 in reputable international databases including Scopus, PubMed, Scholar, Google Web of Science, and ScienceDirect. Geant4 simulations are reliable and accurate and can be used to optimize and evaluate the performance of proton therapy systems. Obtaining some data from experiments carried out in the real world is very effective. This makes it easy to know how close the values obtained from simulations are to the behavior of ions in reality.

Advances in Stereotactic Body Radiation Therapy for Lung Cancer.

Stereotactic body radiation therapy (SBRT) delivers curative-intent radiation to patients with early-stage non-small cell lung cancer and inoperable thoracic lesions. With improved techniques in tumor delineation, motion management, and delivery of radiation treatments, the therapeutic window within the thorax is able to be maximized. Ongoing technological advances enable highly targeted ablative radiation therapy while sparing adjacent sensitive organs at risk. Further applications of SBRT with combinatorial immunotherapy, the usage of particle therapy, and for patients with more advanced stages of lung cancer and other histologies mark exciting possibilities for the role of SBRT within the thorax.

Multichannel Sensor Array Design for Minimizing Detector Complexity and Power Consumption in Ionoacoustic Proton Beam Tomography

Ionoacoustic tomography exploits the acoustic signal generated by the fast energy deposition along the path of pulsed particle beams to reconstruct with sub-mm precision the dose deposition, with promising envisioned applications in hadron therapy treatment monitoring. State-of-the-art ionoacoustic detectors mainly rely on single-channel sensors and time-of-flight measurements to provide 1D localization of the maximum dose deposition at the so-called Bragg peak. This work investigates the design challenges of multichannel sensors for ionoacoustic tomography in terms of their ability to accurately reconstruct the dose deposition of a 200 MeV clinical proton beam, highlighting the impact of the number of channels in the array and their directivity. A complete acoustic model of the sensors and environment has been developed and used to find an optimum tradeoff between accuracy, evaluated numerically through the gamma index, and hardware complexity due to higher channel numbers, thus minimizing the system-level power consumption of the detector.

Development of a Tumor Growth-responsive Robust Planning Method for Head and Neck Cancer in Carbon-ion Radiotherapy.

The current study aimed to evaluate a treatment planning method that is robust against tumor growth and to assess its effectiveness in particle therapy for head and neck cancer. The proposed method optimizes dose distribution by replacing the relative stopping power ratio (rSPR) of the clinical target volume (CTV) cavity region with a tumor-equivalent rSPR (Condition 1). The optimized initial treatment plan template was then recalculated using in-room CT images acquired in the same treatment position, and the doses to the tumor and organs at risk were compared with those in the initial treatment plan. We evaluated this method in 10 patients with head and neck cancer treated with carbon ion radiotherapy. To evaluate the effectiveness of the proposed method, we compared it to the initial treatment plan without the replacement (Condition 2). CTV V95% reduction relative to that of the initial treatment plan at the end of treatment was 1.3%±2.9% and 2.6%±3.7% for Condition 1 and Condition 2, respectively, with Condition 1 (Replacement condition) providing better CTV coverage. Subgroup analysis showed a higher change in target coverage in the mucosal melanoma than in the adenoid cystic carcinoma, suggesting that this was influenced by the rate of tumor growth. The proposed treatment planning method, which adjusts for tumor growth by modifying the rSPR in the cavity region, improved robustness in carbon ion radiotherapy for head and neck cancer. Condition 1 (with replacement) achieved better CTV coverage than Condition 2 (without replacement), particularly in fast-growing tumors like mucosal melanoma. This method ensures consistent dose delivery to tumors while maintaining safe doses to organs at risk, offering potential for improved treatment outcomes.

First experimental verification of prompt gamma imaging with carbon ion irradiation

Prompt Gamma Imaging (PGI) is a promising technique for range verification in Particle Therapy. This technique was already tested in clinical environment with a knife-edge-collimator camera for proton treatments but remains relatively unexplored for Carbon Ion Radiation Therapy (CIRT). Previous FLUKA simulations suggested that PG profile shifts could be detected in CIRT with a precision of \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\sim$$\\end{document} 4 mm (\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$2 \\sigma$$\\end{document}) for a particle statistic equal to \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$5 \\cdot 10^{7}$$\\end{document} C-ions using a 10 × 10 cm2 camera. An experimental campaign was carried out at CNAO (Pavia, Italy) to verify these results, using a knife-edge-collimator camera prototype based on a 5 × 5 cm2 pixelated LYSO crystal. PG profiles were measured irradiating a plastic phantom with a C-ion pencil beam at clinical energies and intensities, also moving the detector to extend the FOV to 13 × 5 cm2. The prototype detected Bragg-peak shifts with \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\sim$$\\end{document} 4 mm precision for a statistic of \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\sim 4 \\cdot 10^{8}$$\\end{document} C-ions (\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$3 \\cdot 10^{8}$$\\end{document} for the extended FOV), slightly larger than expected. Nevertheless, the detector demonstrated significant potential for verifying the precision in dose delivery following a treatment fraction, which remains fundamental in the clinical environment. For the first time to our knowledge, range verification based on PGI was applied to a C-ion beam at clinical energy and intensities.