Design of a new solid state flat panel detector for particle therapy

BackgroundTo ensure accurate, safe, and reproducible patient treatments, it is essential to have precise knowledge and a solid understanding of patient‐specific quality assurance (PSQA). For many years, the delivery of doses to all patients has been verified using dosimetric measurements. However, these measurements require substantial work, and the reasons for the occasional deviations are unclear. For these reasons, alternative methods such as independent dose calculations (IDCs) and analysis of beam‐monitor log files are increasingly discussed in the particle therapy community. Nevertheless, before replacing dose‐verification measurements with other methods, existing measurement data should be thoroughly analyzed to determine what can be learned from them and how they compare with potential alternatives. These alternative methods are mentioned in this work only to provide context and to outline possible directions for future studies.PurposeTo evaluate the dosimetric accuracy and efficiency of PSQA using a water phantom (WP) over a 10‐year period at the Heidelberg Ion Beam Therapy Center (HIT).MethodsBetween 2016 and 2025, 23014 treatment fields with protons, carbon, or helium ions were verified using a WP equipped with 24 pinpoint ionization chambers. The patient treatment plans were recalculated in the water phantom geometry and compared to measured absolute doses. The data were categorized by treatment room, ion species, treatment planning systems (TPS), range shifter (RaShi) use, indication, depth, and target volume, excluding measurements with human errors. Statistical analysis compared measured and calculated doses, focusing on mean, maximum, and minimum dose deviations. Furthermore, the workflow efficiency was assessed based on the beam time required for dosimetric verification, as well as the total time needed for preparation and analysis.ResultsMean dose deviations were in general slightly negative (t‐test, p < 0.01), within ±1 % across all categories (total mean ± SD = –0.50 ± 0.90 %), with 91 % of fields passing institutional ±5 % tolerances. Further, significant differences (p < 0.01) were also observed between treatment rooms, ion species, TPS platforms, and RaShi settings. Additionally, the RayStation TPS showed lower deviations than the Syngo TPS, and helium ions had the smallest deviations. Moreover, repeated verifications reduced variability but without significant improvement. Correlations with target depth or volume were statistically significant but clinically negligible. Less than 1 % of maximum and minimum dose measurements exceeded ±7 % annually. Finally, over 4308 h of beam time, preparation, and analysis were spent on PSQA during the 10‐year period.ConclusionsPSQA at HIT demonstrated high dosimetric accuracy and delivery stability. Integration of IDCs and log file analysis may improve efficiency and allow to omit verification measurements in well‐established cases without compromising patient safety and treatment quality, if the extensive machine QA program is maintained.

Abstract Glioblastoma (GBM) is the most aggressive primary brain tumor, characterized by rapid progression, extensive inter- and intra-tumoral heterogeneity, and resistance to standard-of-care, including radiotherapy. Radiotherapy remains a cornerstone of GBM management, but its efficacy is limited by complex tumor biology and mechanisms of radioresistance. This review explores the advances in radiotherapy for GBM, focusing on the interplay between tumor biology and emerging treatment strategies. Hallmarks of GBM biology, including hypoxia, the robust DNA repair mechanisms, the immunosuppressive tumor microenvironment, and the extensive plasticity contribute to therapeutic resistance. Innovative approaches in radiotherapy may allow to address these challenges. Charged particle therapies, including proton and carbon ion therapy, offer superior precision and enhanced biological effectiveness by delivering lethal doses to tumor cells while sparing surrounding healthy tissue. FLASH therapy, using ultra-high dose rates, could reduce normal tissue toxicity without compromising tumor control. Furthermore, targeted radionuclide therapy harnesses tumor-specific targets to systemically deliver radiopharmaceuticals carrying therapeutic radionuclides directly to cancer cells, improving specificity and reducing off-target effects. This review highlights the promise of these novel radiotherapy modalities to address GBM’s inherent heterogeneity and treatment resistance. By integrating advancements in technology with novel insights into GBM biology, these approaches may significantly improve patient outcomes.

This study investigates a novel optimization framework that integrates the newly developed MCF MKM relative biological effectiveness (RBE) model into intensity modulated particle therapy (IMPT) planning for carbon ion therapy. Unlike conventional RBE models such as MKM or LEM, the MCF MKM provides detailed microdosimetric information, which improves predictive accuracy of cell survival but elevates both memory and time requirement in the optimization process. Furthermore, to the implicit nature of the MCF MKM, the gradient information, which is essential in inverse planning, is hardly accessible. In response, a randomized gradient-free optimization method (RGFM) was developed to mitigate the computational challenge and achieve improved RBE dose distributions. An RBE dose optimization problem was formulated based on the discretized MCF MKM, known as the Abridged Microdosimetry Distribution Model (AMDM). The RGFM was derived to find feasible and high-quality settings of monitor unit for IMPT plans without the need for explicit gradient calculations. To verify the clinical plausibility of the proposed method, it was tested on two clinical scenarios-prostate and brain cases in comparison with benchmark plans derived solely from physical dose optimization. Computational times and dose-volume histograms (DVHs) for both physical and RBE doses were evaluated. The RGFM algorithm successfully optimized the MCF MKM-based IMPT plans. Compared to the benchmark, the RBE dose distributions showed improved coverage of the target and reduced hot spots. Such improvements were observed to coincide with trade-offs in physical dose distributions. The complexity of the MCF MKM extended the computational time, yet high-quality solutions were attainable in a clinically reasonable timeframe. Multi-field optimization (MFO) further enhanced target coverage and critical organ sparing over single-field optimization (SFO). This proof-of-principle study confirmed the feasibility of using a randomized gradient-free method to optimize RBE dose based on the MCF MKM in IMPT planning for carbon ion therapy. The approach provides a pathway for clinical adoption of advanced RBE models, potentially leading to more biologically informed and effective carbon ion therapy treatments. Future work involves refining algorithms, incorporating parallel computing, and performing additional case studies to improve computational efficiency and generalizability.

Accurate dosimetry is crucial in radiotherapy and particle therapy to ensure that prescribed doses are delivered to tumors while minimizing damage to healthy tissue. Advanced dosimetry systems are needed to meet the challenges of modern techniques (small fields, high dose gradients, ultra-high dose rates). Silicon carbide (SiC), a wide bandgap semiconductor, has emerged as a promising material for next-generation radiation detectors. This review highlights the role of SiC in dosimetry for photon, electron, proton, and carbon ion beams, including the new FLASH ultra-high dose rate radiotherapy. We summarize SiC’s advantageous physical properties and survey its use in various detector architectures. In conclusion, SiC shows excellent linearity, radiation tolerance, and the potential to complement or outperform conventional dosimeters. Ongoing developments and multidisciplinary research are expected to address remaining challenges and pave the way for SiC’s integration into clinical dosimetry and future high-performance applications.

Objective.Range and dose monitoring with secondary radiation can help minimizing the issues of range uncertainties in proton cancer therapy. Prompt gammas (PGs) have been widely investigated as a promising secondary radiation forin vivoverification. Since it can be argued that for a proper delivery of the intended treatment the most desirable quantity to assess is the dose distributionin vivo, this work aims at the reconstruction of the delivered proton dose from distributions of PG radiation.Approach.Some techniques have already been proposed in the literature to reconstruct the dose from a distribution of detected secondary radiation, mostly positron emitters. Among them, very promising methods are the analytical deconvolution approach, the evolutionary algorithm and the maximum-likelihood expectation-maximization (MLEM) algorithm. Herein, the feasibility of the application of these approaches to PG distributions at emission stage is assessed with simulated mono- and polyenergetic proton beams, irradiating homogeneous and inhomogeneous phantoms, and a realistic case of a head and neck (H&N) tumor patient.Main results.The accuracy of the reconstructed dose is evaluated via comparison with the corresponding simulated ground truth dose distributions using different metrics. For the case of 1D reconstruction on phantoms, theΔR80,ΔR50andΔR10, withΔR%being the difference of the positions at the % of the dose maximum in the distal fall-off region between the simulated and reconstructed curves, are always less or of the order of 1 mm in absolute value. For 3D reconstruction on phantoms and on the H&N case, theγ(1%/1 mm) passing rate is always above or equal to 97%.Significance.This study demonstrates the applicability of the analytical deconvolution, the evolutionary and the MLEM algorithms to dose reconstruction from PG emissions, providing a step forward toward the final goal of real-time verification of the dose delivery for real-time adaptive particle therapy.

We conducted a survey on various parameters and methods of treatment planning for particle therapy. A questionnaire was distributed among particle therapy facilities in Japan. The data collection period was from October 2024 to December 2024. Responses were collected from 21 facilities. For prostate, the largest number of facilities used a posterior PTV margin of 5mm. The majority of facilities used 3mm, 5mm and 5mm PTV margins for the treatment of head and neck cancer, liver cancer, and lung cancer, respectively. The majority of facilities used 2-4 fields for each site. For robustness considerations, 48% of the facilities used robust optimization, with the largest number of 10 facilities using a range uncertainty of 3-4%. Set-up uncertainties of 3-5mm were most frequently used for each site. Regarding optimization methods, single field uniform dose (SFUD) was most commonly used for the prostate, liver, and lung treatments, and intensity modulated particle therapy (IMPT) for the head and neck treatment. While the majority of facilities created treatment plans with the stopping power ratio (SPR) for intestinal gas as is, 28.6% of the facilities replaced it with a water SPR. The majority of facilities did not replace the lipiodol and metal marker SPRs with tissue SPRs and no replacement, respectively. The trend of setting parameters regarding particle therapy planning was identified. These data could contribute to the launch of new treatments and facilities. They could provide important data for assuring treatment quality in future clinical trials.

Neon ion (20Ne) beam radiotherapy was one of the primary particle therapy candidates investigated during the clinical trials beginning in the 1970s at the Lawrence Berkely National Laboratory (LBNL), which shutdown in the early 1990's. Currently, therapeutic neon ion beams are available at only one clinical facility worldwide, the National Institutes for Quantum Science and Technology (QST) in Chiba, Japan. Recently, neon ion beams were commissioned at QST Hospital as part of the first clinical multi-ion therapy (MIT) program, which aims to improve clinical outcome by escalating higher linear energy transfer (LET) radiation in the tumor for treating therapy-resistant disease. With the advancement of high-precision scanning delivery techniques, neon ion treatments in the present day could be more targeted and safely delivered compared to the first and only clinical application decades prior at LBNL using passive scattering technology. Despite their promising results, pre-clinical investigations of neon ions are scarce outside of Japan and more independent studies are needed. Clinically, neon ion therapy may offer significant benefits for certain malignancies through LET escalation in the tumor, but its limited availability and high costs restrict its current use and adoption. Studies have shown that 20Ne or multi-ion mixtures (4He, 12C, 16O and/or 20Ne) can provide larger degrees of freedom in optimization of dose, LET and RBE, otherwise unattainable with other single ion techniques. Neon ion beams are under investigation in the on-going MIT clinical trials which will establish their broader applicability. Here, a comprehensive review of the technology, physics, radiobiology, and potential clinical applications of neon ion beams is outlined. The status of therapeutic neon ion beams is provided while discussing future research and clinical directions, including technological development of novel particle therapy delivery techniques, such as multi-ion, mini-beam, arc and ultra-high dose rate.

The low relative charge-to-mass ratio offset of 0.065% between fully ionized helium-4 and carbon-12 ions enables simultaneous acceleration in hadron therapy synchrotrons. At the same energy per mass, helium ions exhibit a stopping range approximately 3 times greater than carbon ions. They can therefore be exploited for online range verification downstream of the patient during carbon ion beam irradiation. One possibility for creating this mixed beam is accelerating the two ion species sequentially through the LINAC and subsequently “mixing” them at injection energy in the synchrotron with a double multiturn injection scheme. This work reports the first successful generation, acceleration, and extraction of a mixed helium and carbon ion beam using this double multiturn injection scheme, which was achieved at the MedAustron therapy accelerator in Austria. A description of the double multiturn injection scheme, particle tracking simulations, and details on the implementation at the MedAustron accelerator facility are presented and discussed. Finally, measurements of the mixed beam at delivery in the irradiation room using a radiochromic film and a low-gain avalanche diode detector are presented.

To investigate the current practice patterns in image-guided proton therapy (IGPT) for brain tumours. A multi-institutional survey was distributed to European particle therapy centres to analyse the current practice of IGPT for neuro-oncology. The survey was subsequently used for driving a DELPHI consensus analysis aiming at defining the minimum requirements and the optimal workflow. Seven centres participated in the survey on proton therapy for brain tumours. All reported access to pencil beam scanning and rotating gantries; one also used passive scattering. Supine positioning with standard immobilisation tools was common, while prone and paediatric-specific methods were rare. Multimodal imaging with CT and MRI was standard; PET use was limited and SPECT absent. Rigid registration between imaging modalities was widely used, though MR imaging in treatment position was uncommon. Verification practices varied. Six centres joined the DELPHI consensus, reaching agreement on minimum requirements for immobilisation, imaging for treatment planning, image registration and pre-treatment setup. Disagreement remained on robustness criteria, imaging frequency, and dose tracking, highlighting the need for unified clinical guidelines and workflow optimisation. There is generally agreement across European proton centres, but variability remained in key components of treatment planning, verification and workflow optimisation, including the frequency and modality of control imaging, plan robustness criteria, and treatment position imaging protocols. These differences reflect both local resource availability and the absence of harmonised guidelines. The minimal requirements for image guidance in brain proton therapy achieved good consensus level and will be very useful for new centres.

Objective.At the National Institutes for Quantum Science and Technology, helium, carbon, oxygen, and neon ion beams are utilized together in multi-ion therapy to enhance the therapeutic efficacy of charged-particle therapy. When accelerated ions traverse a medium, a fraction will undergo nuclear interactions, some of which, in turn, produce positron-emitting nuclei. This study investigates the accuracy of ion beam range determination using the annihilation photons emitted from the nuclei measured with an in-house online PET system (OpenPET).Approach.A polymethyl methacrylate phantom was irradiated separately with un-scanned helium, carbon, oxygen, and neon ion beams to 1.5 Gy physical doses at the Bragg peak. Annihilation photons were measured with OpenPET. Each irradiation was simulated using the Particle and Heavy Ion Transport code System (PHITS) to obtain the predicted annihilation photon distributions. The range of beams in the phantom was determined by comparing measured and simulated planar-integrated annihilation photon distributions (PIADs). Fisher information was used to quantify the expected accuracy of range determinations.Main results.The measured PIADs showed good agreement with the simulated PIADs for carbon, oxygen, and neon ions. However, discrepancies were observed for helium ions, likely due to uncertainties in the cross section data used in PHITS. The range was determined within an accuracy of 2 mm for four ion species for the measurement times longer than 3 min. Neon ions had the most Fisher information for measurement times shorter than 135 s, whereas beyond that, oxygen ions had the most information, offering the highest range determination accuracy.Significance.The range was determined within an accuracy of 2 mm for helium, carbon, oxygen, and neon ion beams by the OpenPET measurements of 180 s. Among the four ion species, neon ions showed the highest accuracy in range determination within 135 s, while oxygen ions performed best for measurement times beyond 135 s.

ObjectiveTo evaluate the clinical efficacy, safety, and changes in the immune status of advanced non-small cell lung cancer (NSCLC) patients with disease progression after chemoradiotherapy treated with CT-guided 125I radioactive seed implantation.Materials and methodsFrom January 2016 to June 2022, 34 NSCLC patients who progressed after radiotherapy and chemotherapy were studied retrospectively. There were 34 evaluable lesions, and 125I seeds were implanted into the lesions under CT guidance. The study’s endpoints were as follows: short-term clinical efficacy, quality of life score, and adverse reaction status assessment, with patients being collected for immune status assessment.ResultsThe average postoperative follow-up period was 16.58 ± 7.41 months. The 1-year postoperative survival rate was 76.47% (26/34), the 2-year postoperative survival rate was 58.82% (20/34), and the median overall survival was 16 (6–24) months (95% CI: 13.7–18.3). The 1-year progression-free survival (PFS) rate after the operation was 61.76% (21/34), the 2-year PFS rate was 41.18% (14/34), and the median PFS was 12.5 (1–24) months (95% CI: 10.8–16.2). Postoperative pneumothorax occurred in 11.76% of patients, minor bleeding in 5.88%, and pneumonia in 2.94%, all of which improved after symptomatic treatment. Compared with the preoperative results, the percentages of CD3+ and CD4+ T lymphocytes in the treatment group increased 1, 2, 3, and 6 months after surgery; the percentage of NK cells increased 3 and 6 months after surgery. The positive immune factor levels of IL-2 and TNF-α were increased at 2, 3, and 6 months after surgery; γ-IFN levels were increased at 1, 2, 3, and 6 months after surgery; IL-4 levels were decreased at 3 and 6 months after surgery; and IL-10 levels were decreased at 6 months after surgery. TH17 (IL-17) levels decreased at 1, 2, 3, and 6 months after surgery.ConclusionCT-guided 125I particle therapy may be an effective treatment for NSCLC that has progressed following radiotherapy and chemotherapy. Local treatments improve patients’ quality of life and reduce tumor burden. CT-guided 125I radioactive seed implantation may improve the immune status of patients with recurrent or progressive NSCLC after radiotherapy and chemotherapy and may enhance the antitumor immune response.

A systematic review of particle-based treatment modalities for adenoid cystic carcinomas of the head and neck.

Evaluation of Boron Neutron Capture Therapy for treating canine oral malignant melanoma.

Characterization of a 144-channel front-end board for ion beam counting in particle therapy

Improving range estimation for carbon ion radiotherapy using artificial neural networks with Si/CdTe Compton camera.

One of the main advantages of Compton Cameras (CC) with respect to mechanically collimated gamma cameras is a potentially higher efficiency, which is a key feature for imaging devices developed for applications such as emission tomography in nuclear medicine or radioactive environmental monitoring. Several Monte Carlo (MC) simulation toolkits are available to study the optimal detector configuration with good accuracy but generally low computational efficiency. Here, we propose a simplified numerical model of the classical two-tier CC for multi-parameter optimization via stochastic simulations. Designed as a user-friendly, low-cost alternative to traditional Monte Carlo tools, it helps estimate system efficiency and reduce the need for extensive simulations. The model calculates scatter and absorber efficiencies, both geometrical and intrinsic, based on inputs that include detector dimensions, distances, material density, and cross-sections, and outputs partial and total detection efficiencies. The impact of the principal geometrical and physical parameters on the total efficiency has been analyzed for a heterogeneous CC for hadron therapy featuring GAGG and LYSO scintillators as scatter and absorber detectors, respectively. The results were validated through ANTS2 simulation package (Morozov et al., 2016) and a GATE (Allison et al., 2016) simulated data of a CC available in literature (Barrientos et al., 2023), showing good agreement, confirming the model's reliability. The developed tool estimates the impact of various parameters on system efficiency in just a few minutes per CC configuration, significantly faster than conventional Monte Carlo simulations, which typically take several hours.

In the field of radiation physics, understanding the impact of low-energy ions with high-linear energy transfer (LET) is crucial for assessing both radiation protection and particle therapy risks. However, predicting their biological effectiveness is challenging, because commonly assumed track-segment conditions, where ions maintain a constant LET and energy, no longer hold at low energies. Additionally, as ion track sizes shrink to the scale of chromatin structures, inhomogeneities within the cell nucleus can be resolved and the assumption of a uniformly sensitive nucleus becomes inadequate. To address these challenges, we present a low-energy adaption (LEA) of the local effect model (LEM IV), which introduces three key modifications: 1. modeling ion deceleration within the cell nucleus by dividing it into discrete slices to account for energy and LET gradients; 2. incorporating a heterogeneous target structure by distinguishing between radiation-sensitive and insensitive chromatin domains; 3. a more accurate prediction of the linear-quadratic parameter βion by introducing a saturation correction for very high LET. Our results demonstrate that the LEA LEM IV notably improves predictive accuracy at low ion energies. With these adaptions, the LEA successfully reflects the reduced inactivation cross sections observed experimentally, which remain below the geometric cross section of the nucleus. The model shows good agreement with three sets of experimental data, including inactivation cross sections for carbon, argon, and uranium ions, as well as αion values for alpha particles. While computationally more intensive, the LEA provides a crucial tool for precise modeling in low-energy scenarios.

Low gain avalanche diodes (LGADs) and thin n-on-p silicon diodes, when read out by fast and custom electronics, exhibit characteristics that make them promising candidates for the development of new detectors for clinical applications such as beam commissioning, diagnostics and monitoring, dosimetry, and online treatment delivery verification. Compared to gas ionization chambers, these detectors offer significantly higher sensitivity, enabling the detection of single particles at fluxes of up to 10 8 particles/cm 2 s—sufficient to cover the entire clinical intensity range of carbon ion therapy and approximately one order of magnitude lower for proton therapy. Various front-end electronics have been developed and characterized for readout configurations, ranging from single channels (pads or strips) to arrays of up to 144 strips. These systems have been applied to single-particle identification for beam monitors in particle therapy, as well as to two-dimensional beam monitoring and dosimetry in ultra-high dose rate and spatially fractionated radiotherapy. This review summarizes the detectors based on LGADs and thin n-on-p silicon diodes developed within the INFN-CSN5 projects MoVeIT, SIG, and FRIDA. Specifically, we present a 2.7 × 2.7 cm 2 particle counter for measuring beam fluence and position, a beam energy detector based on the primary particle’s time-of-flight, a setup for studying beam time structure at the nanosecond scale, and a system for range verification via prompt gamma timing. Current advances in various technologies are reviewed, together with challenges and future perspectives on the application of LGADs and thin silicon diodes in radiotherapy.

BackgroundThis retrospective study evaluated outcomes and toxicity in patients with WHO Grade II and III meningiomas treated with modern photon or particle radiotherapy, with emphasis on skull base versus non-skull base tumors.MethodsNinety-seven patients received photon (58.2%) or particle therapy (41.8%). Median age was 61 years (range, 15–88). Tumor location was non-skull base in 69.1% and skull base in 30.9%. All patients underwent fractionated radiotherapy with a median dose of 59.4 Gy (range, 34–68). Follow-up included MRI and assessment of local control (LC), progression-free survival (PFS), overall survival (OS), and toxicity (CTCAE v5).ResultsAt last follow-up, 94 patients (96.9%) were alive. Median OS was not reached, with survival rates of 100% at 2 and 5 years and 99% at 8 years. Median PFS was 32.0 months, with 2- and 5-year rates of 88.7% and 66.0%. Median LC was 33.0 months, with 2- and 5-year rates of 91.8% and 72.2%. Disease progression occurred in 40 patients (41.2%), including 30 in-field and 22 outside the irradiated volume. Early toxicities were mainly Grade I–II, most commonly alopecia, fatigue, and headache. Late toxicities were less frequent, including headache, seizures, vertigo, and radiation-induced cerebral contrast enhancement (RICE). Severe late toxicity (Grade III) was rare (n = 3). Particle therapy was associated with lower rates of vertigo and headache.ConclusionHigh-precision photon and particle radiotherapy achieved effective long-term control with favorable safety in high-grade meningiomas. Most adverse effects were mild and manageable, supporting the role of particle therapy in reducing selected late toxicities.