Ion Beam Therapy Research Articles

Experimental helium-beam radiography with a high-energy beam: Water-equivalent thickness calibration and first image-quality results.

A clinical implementation of ion-beam radiography (iRad) is envisaged to provide a method for on-couch verification of ion-beam treatment plans. The aim of this work is to introduce and evaluate a method for quantitative water-equivalent thickness (WET) measurements for a specific helium-ion imaging system for WETs that are relevant for imaging thicker body parts in the future. Helium-beam radiographs (αRads) are measured at the Heidelberg Ion-beam Therapy Center with an initial beam energy of 239.5 MeV/u. An imaging system based on three pairs of thin silicon pixel detectors is used for ion path reconstruction and measuring the energy deposition (dE) of each particle behind the object to be imaged. The dE behind homogeneous plastic blocks is related to their well-known WETs between 280.6 and 312.6 mm with a calibration curve that is created by a fit to measured data points. The quality of the quantitative WET measurements is determined by the uncertainty of the measured WET of a single ion (single-ion WET precision) and the deviation of a measured WET value to the well-known WET (WET accuracy). Subsequently, the fitted calibration curve is applied to an energy deposition radiograph of a phantom with a complex geometry. The spatial resolution (modulation transfer function at 10 % -MTF10% ) and WET accuracy (mean absolute percentage difference-MAPD) of the WET map are determined. In the optimal imaging WET-range from ∼280 to 300 mm, the fitted calibration curve reached a mean single-ion WET precision of 1.55 0.00%. Applying the calibration to an ion radiograph (iRad) of a more complex WET distribution, the spatial resolution was determined to be MTF10% = 0.49 0.03 lp/mm and the WET accuracy was assessed as MAPD to 0.21 %. Using a beam energy of 239.5 MeV/u and the proposed calibration procedure, quantitative αRads of WETs between ∼280 and 300 mm can be measured and show high potential for clinical use. The proposed approach with the resulting image qualities encourages further investigation toward the clinical application of helium-beamradiography.

EPEN-15. Radiotherapy with helium ions has the potential to improve both endocrine and neurocognitive outcome in pediatric patients with ependymoma

BACKGROUND: Ependymoma are the third most frequent pediatric brain tumors. To prevent local recurrence, the resection site should be irradiated. Especially the treatment of pediatric patients requires precise dose application and optimal protection of organs at risk. Compared to photon radiation treatment, proton therapy often achieves better results regarding target coverage and organ-sparing. Due to their physical properties, helium ions can further reduce side effects, providing better protection of healthy tissue despite similar target coverage. PATIENTS AND METHODS: In our in-silico study, 15 pediatric patients (median age six years) with ependymoma located in the posterior cranial fossa were considered. All patients underwent adjuvant radiotherapeutic treatment with active scanned protons at Heidelberg Ion-Beam Therapy Center (HIT). Both helium ion and highly conformal IMRT plans were calculated to evaluate the potential dosimetric (and clinical) benefit of ion beam therapy compared to the current state of the art photon-based treatments. RESULTS: Target coverage was comparable in all three modalities (He, H+, Ph): homogeneity indices (HI) and inhomogeneity coefficients (IC) of HIHe=5.8±3.8, HIH+=7.5±4.0, HIPh=6.4±4.3, ICHe=0.2±0.1, ICH+=0.2±0.1, ICPh=0.2±0.1. As expected, the integral dose absorbed by the healthy brain tissue could be reduced significantly using helium ions versus IMRT (-45.3%±15.1%). Based on our preliminary results, even compared to active scanned protons – currently the most precise radiation technique worldwide – the relative dose reduction for critical neuronal structures using helium ions on average amounts to -27.2%±14.4%. CONCLUSION: Previous studies could clearly demonstrate that the dosimetric advantage of protons translates into a measurable clinical benefit for pediatric patients with brain tumors. Given the dose response relationship of critical organs at risk, the results of our in-silico study provide a strong rationale that the use of helium ions has the potential to even further reduce the risk for treatment related sequelae.

Impact of DNA Repair Kinetics and Dose Rate on RBE Predictions in the UNIVERSE.

Accurate knowledge of the relative biological effectiveness (RBE) and its dependencies is crucial to support modern ion beam therapy and its further development. However, the influence of different dose rates of the reference radiation and ion beam are rarely considered. The ion beam RBE-model within our “UNIfied and VERSatile bio response Engine” (UNIVERSE) is extended by including DNA damage repair kinetics to investigate the impact of dose-rate effects on the predicted RBE. It was found that dose-rate effects increase with dose and biological effects saturate at high dose-rates, which is consistent with data- and model-based studies in the literature. In a comparison with RBE measurements from a high dose in-vivo study, the predictions of the presented modification were found to be improved in comparison to the previous version of UNIVERSE and existing clinical approaches that disregard dose-rate effects. Consequently, DNA repair kinetics and the different dose rates applied by the reference and ion beams might need to be considered in biophysical models to accurately predict the RBE. Additionally, this study marks an important step in the further development of UNIVERSE, extending its capabilities in giving theoretical guidance to support progress in ion beam therapy.

High-Voltage CMOS Active Pixel Sensor Chip With Counting Electronics for Beam Monitoring

This article presents the monolithic active high-voltage CMOS (HV-CMOS) pixel sensor HitPix with counting electronics and frame-based readout. It has been developed for high rate ion-beam monitoring, as used, e.g., in medical facilities for radiation therapy. The sensor elements are lowly doped n-well in p-substrate diodes. Pixel electronics is implemented within the sensor cathode (n-well). The substrate can be biased to −120 V. In this way, a large depletion zone is induced and radiation tolerance is improved. We could show the overall functionality of the sensor by laboratory measurements of the signal response characteristics and threshold distribution. Furthermore, testing the sensor in the medical ion beam of Heidelberg Ion-Beam Therapy Center (HIT) has proven the suitability of this beam monitor approach.

First application of the BIANCA biophysical model to carbon-ion patient cases

Objective. The main objective of this work consists of applying, for the first time, the BIANCA (BIophysical ANalysis of Cell death and chromosome Aberrations) biophysical model to the RBE calculation for C-ion cancer patients, and comparing the outcomes with those obtained by the LEM I model, which is applied in clinics. Indeed, the continuous development of heavy-ion cancer therapy requires modelling of biological effects of ion beams on tumours and normal tissues. The relative biological effectiveness (RBE) of heavy ions is higher than that of protons, with a significant variation along the beam path. Therefore, it requires a precise modelling, especially for the pencil-beam scanning technique. Currently, two radiobiological models, LEM I and MKM, are in use for heavy ions in scanned pencil-beam facilities. Approach. Utilizing an interface with the FLUKA Particle Therapy Tool, BIANCA was applied to re-calculate the RBE-weighted dose distribution for carbon-ion treatment of three patients (chordoma, head-and-neck and prostate) previously irradiated at CNAO, where radiobiological optimization was based on LEM I. The predictions obtained by BIANCA were based either on chordoma cell survival (RBE surv ), or on dicentric aberrations in peripheral blood lymphocytes (RBE ab ), which are indicators of late normal tissue damage, including secondary tumours. The simulation outcomes were then compared with those provided by LEM I. Main results. While in the target and in the entrance channel BIANCA predictions were lower than those obtained by LEM I, the two models provided very similar results in the considered OAR. The observed differences between RBE surv and RBE ab (which were also dependent on fractional dose and LET) suggest that in normal tissues the information on cell survival should be integrated by information more closely related to the induction of late damage, such as chromosome aberrations. Significance. This work showed that BIANCA is suitable for treatment plan optimization in ion-beam therapy, especially considering that it can predict both cell survival and chromosome aberrations and has previously shown good agreement with carbon-ion experimental data.

Energy-Loss Straggling and Delta-Ray Escape in Solid-State Microdosimeters Used in Ion-Beam Therapy

Microdosimetry is increasingly adopted in the characterization of proton and carbon ion beams used in cancer therapy. Spectra and mean values of lineal energy calculated in frequency and dose are seen by many as the tools which, by complementing dosimetric measurements, allow for the most complete characterization of the therapeutic radiation fields. The urgency is now to consolidate the experience and converge to commonly accepted methodologies. In this context, the purpose of this work is to study the effects of the energy-loss straggling and the delta-ray escape, considering slab-sensitive volumes; these are, in fact, the typical shapes of solid-state microdosimeters, which are widely used in investigating light ion therapy beams. The method considers the energy distribution of delta rays resulting from the collision of the impinging ion and, taking into account the escape, convolutes it with itself as many times as the expected number of collisions in the sensitive volume thickness. The resulting distribution is compared to the experimental microdosimetric spectrum showing a substantially good agreement. The extension of the methodology to a wider range of ion energy and detector characteristics is instrumental for a detector-independent microdosimetric assessment of the radiation fields.

PD-0815 Microdosimetry with tissue-equivalent proportional counters at an ion beam therapy facility

PD-0815 Microdosimetry with tissue-equivalent proportional counters at an ion beam therapy facility

Biological Dose Optimization for Particle Arc Therapy Using Helium and Carbon Ions

To present biological dose optimization for particle arc therapy using helium and carbon ions. Treatment planning and optimization procedures were developed for spot-scanning hadron arc (SHArc) delivery using the RayStation treatment planning system and FRoG dose engine. The SHArc optimization algorithm is applicable for charged particle beams and determines angle dependencies for spot and energy selection with three main initiatives: (i) achieve standard clinical optimization goals and constraints for target and organs at risk (OARs), (ii) target dose robustness, and (iii) increase linear energy transfer (LET) in the target volume. Three patient cases previously treated at the Heidelberg Ion-beam Therapy Center (HIT) were selected for evaluation of conventional versus arc delivery for the two clinical particle beams (helium [4He] and carbon [12C] ions): glioblastoma, prostate adenocarcinoma, and skull-base chordoma. Biological dose and dose-averaged LET (LETd) distributions for SHArc were evaluated against conventional planning techniques (volumetric modulated arc therapy [VMAT] and 2-field intensity modulated particle therapy) applying the modified microdosimetric kinetic model with (α/β)x = 2 Gy. Clinical viability and deliverability were assessed via evaluation of plan quality, robustness, and irradiation time. For all investigated patient cases, SHArc treatment optimizations met planning goals and constraints for target coverage and OARs, exhibiting acceptable target coverage and reduced normal tissue volumes, with effective dose >10-GyRBE compared with conventional 2F planning. For carbon ions, LETd was increased in the target volume from ∼40-60 to ∼80-140 keV/µm for SHArc compared with conventional treatments. Favorable LETd distributions were possible with the SHArc approach, with maximum LETd in clinical target volume/gross tumor volume and potential reductions of high-LET regions in normal tissues and OARs. Compared with VMAT, SHArc affords substantial reductions in normal tissue dose (40%-70%). SHArc therapy offers potential treatment benefits such as increased normal tissue sparing from higher doses >10-GyRBE, enhanced target LETd, and potential reduction in high-LET components in OARs. Findings justify further development of robust SHArc treatment planning toward potential clinical translation.

Technical note: Impact of beamline-specific particle energy spectra on clinical plans in carbon ion beam therapy.

PurposeThe Local Effect Model version one (LEM I) is applied clinically across Europe to quantify the relative biological effectiveness (RBE) of carbon ion beams. It requires the full particle fluence spectrum differential in energy in each voxel as input parameter. Treatment planning systems (TPSs) use beamline‐specific look‐up tables generated with Monte Carlo (MC) codes. In this study, the changes in RBE weighted dose were quantified using different levels of details in the simulation or different MC codes.MethodsThe particle fluence differential in energy was simulated with FLUKA and Geant4 at 500 depths in water in 1‐mm steps for 58 initial carbon ion energies (between 120.0 and 402.8 MeV/u). A dedicated beam model was applied, including the full description of the Nozzle using GATE‐RTionV1.0 (Geant4.10.03p03). In addition, two tables generated with FLUKA were compared. The starting points of the FLUKA simulations were phase space (PhS) files from, firstly, the Geant4 nozzle simulations, and secondly, a clinical beam model where an analytic approach was used to mimic the beamline. Treatment plans (TPs) were generated with RayStation 8B (RaySearch Laboratories AB, Sweden) for cubic targets in water and 10 clinical patient cases using the clinical beam model. Subsequently, the RBE weighted dose was re‐computed using the two other fluence tables (FLUKA PhS or Geant4).ResultsThe fluence spectra of the primary and secondary particles simulated with Geant4 and FLUKA generally agreed well for the primary particles. Differences were mainly observed for the secondary particles. Interchanging the two energy spectra (FLUKA vs. GEANT4) to calculate the RBE weighted dose distributions resulted in average deviations of less than 1% in the entrance up to the end of the target region, with a maximum local deviation at the distal edge of the target. In the fragment tail, larger discrepancies of up to 5% on average were found for deep‐seated targets. The patient and water phantom cases demonstrated similar results.ConclusionRBE weighted doses agreed well within all tested setups, confirming the clinical beam model provided by the TPS vendor. Furthermore, the results showed that the open source and generally available MC code Geant4 (in particular using GATE or GATE‐RTion) can also be used to generate basic beam data required for RBE calculation in carbon ion therapy.

Feasibility study of a proton CT system based on 4D-tracking and residual energy determination via time-of-flight

Objective. For dose calculations in ion beam therapy, it is vital to accurately determine the relative stopping power (RSP) distribution within the treatment volume. A suitable imaging modality to achieve the required RSP accuracy is proton computed tomography (pCT), which usually uses a tracking system and a separate residual energy (or range) detector to directly measure the RSP distribution. This work investigates the potential of a novel pCT system based on a single detector technology, namely low gain avalanche detectors (LGADs). LGADs are fast 4D-tracking detectors, which can be used to simultaneously measure the particle position and time with precise timing and spatial resolution. In contrast to standard pCT systems, the residual energy is determined via a time-of-flight (TOF) measurement between different 4D-tracking stations. Approach. To show the potential of using 4D-tracking for proton imaging, we studied and optimized the design parameters for a realistic TOF-pCT system using Monte Carlo simulations. We calculated the RSP accuracy and RSP resolution inside the inserts of the CTP404 phantom and compared the results to a simulation of an ideal pCT system. Main results. After introducing a dedicated calibration procedure for the TOF calorimeter, RSP accuracies less than 0.6% could be achieved. We also identified the design parameters with the strongest impact on the RSP resolution and proposed a strategy to further improve the image quality. Significance. This comprehensive study of the most important design aspects for a novel TOF-pCT system could help guide future hardware developments and, once implemented, improve the quality of treatment planning in ion beam therapy.

Experimental Comparison of Fiducial Markers Used in Proton Therapy: Study of Different Imaging Modalities and Proton Fluence Perturbations Measured With CMOS Pixel Sensors.

Fiducial markers are used for image guidance to verify the correct positioning of the target for the case of tumors that can suffer interfractional motion during proton therapy. The markers should be visible on daily imaging, but at the same time, they should produce minimal streak artifacts in the CT scans for treatment planning and induce only slight dose perturbations during particle therapy. In this work, these three criteria were experimentally investigated at the Heidelberg Ion Beam Therapy Center. Several small fiducial markers with different geometries and materials (gold, platinum, and carbon-coated ZrO2) were evaluated. The streak artifacts on treatment planning CT were measured with and without iMAR correction, showing significantly smaller artifacts from markers lighter than 6 mg and a clear improvement with iMAR correction. Daily imaging as X-ray projections and in-room mobile CT were also performed. Markers heavier than 6 mg showed a better contrast in the X-ray projections, whereas on the images from the in-room mobile CT, all markers were clearly visible. In the other part of this work, fluence perturbations of proton beams were measured for the same markers by using a tracker system of several high spatial resolution CMOS pixel sensors. The measurements were performed for single-energy beams, as well as for a spread-out Bragg peak. Three-dimensional fluence distributions were computed after reconstructing all particle trajectories. These measurements clearly showed that the ZrO2 markers and the low-mass gold/platinum markers (0.35mm diameter) induce perturbations being 2–3 times lower than the heavier gold or platinum markers of 0.5mm diameter. Monte Carlo simulations, using the FLUKA code, were used to compute dose distributions and showed good agreement with the experimental data after adjusting the phase space of the simulated proton beam compared to the experimental beam.

Management of elderly patients with bone and soft tissue sarcomas: JCOG Bone and Soft Tissue Tumor Study Group.

Approximately, 40% of bone sarcomas and 60% of soft tissue sarcoma arise in patients aged ≥65years. However, because sarcoma is very rare, there is little evidence regarding the management of elderly patients with sarcoma. Age has been reported as a prognostic factor in patients with sarcomas. The standard therapy for all localized bone and soft tissue sarcomas is surgical resection, even in elderly patients. Radiation or ion-beam therapy can be considered for unresectable sarcomas. Although adjuvant chemotherapy is standard for osteosarcoma, the usefulness of adjuvant chemotherapy for elderly patients has not been verified; therefore, it may not be recommended for elderly patients with osteosarcoma. For elderly patients with advanced osteosarcoma, if general conditions permit, doxorubicin- and/or ifosfamide-based regimens as well as molecular-targeted therapies, including sorafenib, regorafenib and everolimus, may be considered, although these drugs have not been approved for sarcoma in Japan. Adjuvant chemotherapy with doxorubicin plus ifosfamide is recommended for patients with high-risk localized soft tissue sarcoma if they are aged ≤70years. For first-line treatment of advanced soft tissue sarcoma in elderly patients, doxorubicin monotherapy is considered to be the standard regimen, and pazopanib can be an alternative. For second-line treatment, gemcitabine-based regimens, pazopanib, trabectedin and eribulin may be options for elderly patients with advanced soft tissue sarcoma.

Development, Monte Carlo simulations and experimental evaluation of a 3D range-modulator for a complex target in scanned proton therapy

The purpose of this work was to develop and manufacture a 3D range-modulator (3D RM) for a complex target contour for scanned proton therapy. The 3D RM is considered to be a viable technique for the very fast dose application in patient-specific tumors with only one fixed energy. The RM was developed based on a tumor from a patient CT and manufactured with high-quality 3D printing techniques with both polymer resin and aluminum. Monte Carlo simulations were utilized to investigate its modulating properties and the resulting dose distribution. Additionally, the simulation results were validated with measurements at the Marburg Ion-Beam Therapy Centre. For this purpose, a previously developed water phantom was used to conduct fast, automated high-resolution dose measurements. The results show a very good agreement between simulations and measurements and indicate that highly homogeneous dose distributions are possible. The delivered dose is conformed to the distal as well as to the proximal edge of the target. The 3D range-modulator concept combines a high degree of dose homogeneity and conformity, comparable to standard IMPT with very short irradiation times, promising clinically applicable dose distributions for lung and/or FLASH treatment, comparable and competitive to those from conventional irradiation techniques.

Direct determination of k Q for Farmer-type ionization chambers in a clinical scanned carbon-ion beam using water calorimetry

Within two studies, k Q factors for two Farmer-type ionization chambers have been experimentally determined by means of water calorimetry in the entrance channel (EC) of a monoenergetic carbon-ion beam (Osinga-Blättermann et al 2017 Phys. Med. Biol. 62 2033–54) and for a passively modulated spread-out Bragg peak (SOBP) (Holm et al 2021 Phys. Med. Biol. 66 145012). Both studies were performed at the Heidelberg Ion Beam Therapy Center (HIT) using the PTB portable water calorimeter but applying different initial beam energies of 429 MeV u−1 for the EC and 278 MeV u−1 for the SOBP as well as different scanning patterns of the irradiated field. Comparing their results revealed differences between the experimental k Q factors of up to 1.9% between the EC and the SOBP. To further investigate this unexpected difference, we performed additional k Q determinations for the EC of an 278 MeV u−1 monoenergetic carbon-ion beam and reevaluated the original data of Osinga-Blättermann et al (2017 Phys. Med. Biol. 62 2033–54). This new experimental data indicated no difference between the k Q factors for the EC and the SOBP and the reevaluation led to a substantial reduction of the originally published k Q factors for the EC of the 429 MeV u−1 beam (Osinga-Blättermann et al 2017 Phys. Med. Biol. 62 2033–54). Finally, no significant difference between the data for the EC and the data for the SOBP can be found within the standard measurement uncertainty of experimental k Q factors of 0.8%. The results presented here are intended to correct and replace the k Q data published by Osinga-Blättermann et al (2017 Phys. Med. Biol. 62 2033–54) and in Osinga-Blättermann and Krauss (2018 Phys. Med. Biol. 64 015009).

The Evolution of Lateral Dose Distributions of Helium Ion Beams in Air: From Measurement and Modeling to Their Impact on Treatment Planning

To start clinical trials with the first clinical treatment planning system supporting raster-scanned helium ion therapy, a comprehensive database of beam characteristics and parameters was required for treatment room-specific beam physics modeling at the Heidelberg Ion-Beam Therapy Center (HIT). At six different positions in the air gap along the beam axis, lateral beam profiles were systematically measured for 14 initial beam energies covering the full range of available energies at HIT. The 2D-array of liquid-filled ionization chambers OCTAVIUS from PTW was irradiated by a pencil beam focused at the central axis. With a full geometric representation of HIT’s monitoring chambers and beamline elements in FLUKA, our Monte Carlo beam model matches the measured lateral beam profiles. A second set of measurements with the detector placed in a water tank was used to validate the adjustments of the initial beam parameters assumed in the FLUKA simulation. With a deviation between simulated and measured profiles below ±0.8 mm for all investigated beam energies, the simulated profiles build part of the database for the first clinical treatment planning system for helium ions. The evolution of beamwidth was also compared to similar simulations of the clinically available proton and carbon beam. This allows a choice of treatment modality based on quantitative estimates of the physical beam properties. Finally, we investigated the influence of beamwidth variation on patient treatment plans in order to estimate the relevance and necessary precision limits for lateral beam width models.

Investigation of Suitable Detection Angles for Carbon-Ion Radiotherapy Monitoring in Depth by Means of Secondary-Ion Tracking.

The dose conformity of carbon-ion beam radiotherapy, which allows the reduction of the dose deposition in healthy tissue and the escalation of the dose to the tumor, is associated with a high sensitivity to anatomical changes during and between treatment irradiations. Thus, the monitoring of inter-fractional anatomical changes is crucial to ensure the dose conformity, to potentially reduce the size of the safety margins around the tumor and ultimately to reduce the irradiation of healthy tissue. To do so, monitoring methods of carbon-ion radiotherapy in depth using secondary-ion tracking are being investigated. In this work, the detection and localization of a small air cavity of 2 mm thickness were investigated at different detection angles of the mini-tracker relative to the beam axis. The experiments were conducted with a PMMA head phantom at the Heidelberg Ion-Beam Therapy Center (HIT) in Germany. In a clinic-like irradiation of a single field of 3 Gy (RBE), secondary-ion emission profiles were measured by a 2 cm2 mini-tracker composed of two silicon pixel detectors. Two positions of the cavity in the head phantom were studied: in front and in the middle of the tumor volume. The significance of the cavity detection was found to be increased at smaller detection angles, while the accuracy of the cavity localization was improved at larger detection angles. Detection angles of 20° – 30° were found to be a good compromise for accessing both, the detectability and the position of the air cavity along the depth in the head of a patient.

The accuracy of helium ion CT based particle therapy range prediction: an experimental study comparing different particle and x-ray CT modalities

This work provides a quantitative assessment of helium ion CT (HeCT) for particle therapy treatment planning. For the first time, HeCT based range prediction accuracy in a heterogeneous tissue phantom is presented and compared to single-energy x-ray CT (SECT), dual-energy x-ray CT (DECT) and proton CT (pCT). HeCT and pCT scans were acquired using the US pCT collaboration prototype particle CT scanner at the Heidelberg Ion-Beam Therapy Center. SECT and DECT scans were done with a Siemens Somatom Definition Flash and converted to RSP. A Catphan CTP404 module was used to study the RSP accuracy of HeCT. A custom phantom of 20 cm diameter containing several tissue equivalent plastic cubes was used to assess the spatial resolution of HeCT and compare it to DECT. A clinically realistic heterogeneous tissue phantom was constructed using cranial slices from a pig head placed inside a cylindrical phantom (ø150 mm). A proton beam (84.67 mm range) depth-dose measurement was acquired using a stack of GafchromicTM EBT-XD films in a central dosimetry insert in the phantom. CT scans of the phantom were acquired with each modality, and proton depth-dose estimates were simulated based on the reconstructions. The RSP accuracy of HeCT for the plastic phantom was found to be 0.3 ± 0.1%. The spatial resolution for HeCT of the cube phantom was 5.9 ± 0.4 lp cm−1 for central, and 7.6 ± 0.8 lp cm−1 for peripheral cubes, comparable to DECT spatial resolution (7.7 ± 0.3 lp cm−1 and 7.4 ± 0.2 lp cm−1, respectively). For the pig head, HeCT, SECT, DECT and pCT predicted range accuracy was 0.25%, −1.40%, −0.45% and 0.39%, respectively. In this study, HeCT acquired with a prototype system showed potential for particle therapy treatment planning, offering RSP accuracy, spatial resolution, and range prediction accuracy comparable to that achieved with a commercial DECT scanner. Still, technical improvements of HeCT are needed to enable clinical implementation.

Ultra-High Dose Rate (FLASH) Carbon Ion Irradiation: Dosimetry and First Cell Experiments

To establish a beam monitoring and dosimetry system to enable the FLASH dose rate carbon ion irradiation and investigate, at different oxygen concentrations, the in vitro biological response in comparison to the conventional dose rate. CHO-K1 cell response to irradiation at different dose rates and at different levels of oxygenation was studied using clonogenic assay. The Heidelberg Ion-Beam Therapy Center (HIT) synchrotron, after technical improvements, was adjusted to extract ≥5×108 12C ions within approximately 150 milliseconds. The beam monitors were filled with helium. The FLASH irradiation with beam scanning yields a dose of 7.5 Gy (homogeneity of ±5%) for a 280 MeV/u beam in a volume of at least 8 mm in diameter and a corresponding dose rate of 70 Gy/s (±20%). The dose repetition accuracy is better than 2%, the systematic uncertainty is better than 2%. Clonogenic assay demonstrates a significant FLASH sparing effect which is strongly oxygenation-dependent and mostly pronounced at 0.5% O2 but absent at 0% and 21% O2. The FLASH dose rates >40 Gy/s were achieved with carbon beams. Cell survival analysis revealed FLASH dose rate sparing in hypoxia (0.5%-4% O2).

Development and Benchmarking of a Monte Carlo Dose Engine for Proton Radiation Therapy

Dose calculation algorithms based on Monte Carlo (MC) simulations play a crucial role in radiotherapy. Here, the development and benchmarking of a novel MC dose engine, MonteRay, is presented for proton therapy aiming to support clinical activity at the Heidelberg Ion Beam Therapy center (HIT) and the development of MRI (magnetic resonance imaging)-guided particle therapy. Comparisons against dosimetric data and gold standard MC FLUKA calculations at different levels of complexity, ranging from single pencil beams in water to patient plans, showed high levels of agreement, validating the physical approach implemented in the dose engine. Additionally, MonteRay has been found to match satisfactorily to FLUKA dose predictions in magnetic fields both in homogeneous and heterogeneous scenarios advocating its use for future MRI-guided proton therapy applications. Benchmarked on 150 MeV protons transported on a 2 × 2 × 2 mm3 grid, MonteRay achieved a high computational throughput and was able to simulate the histories of more than 30,000 primary protons per second on a single CPU core.

Dual-layer spectral CT for proton, helium, and carbon ion beam therapy planning of brain tumors.

Pretreatment computed tomography (CT) imaging is an essential component of the particle therapy treatment planning chain. Treatment planning and optimization with charged particles require accurate and precise estimations of ion beam range in tissues, characterized by the stopping power ratio (SPR). Reduction of range uncertainties arising from conventional CT‐number‐to‐SPR conversion based on single‐energy CT (SECT) imaging is of importance for improving clinical practice. Here, the application of a novel imaging and computational methodology using dual‐layer spectral CT (DLCT) was performed toward refining patient‐specific SPR estimates.A workflow for DLCT‐based treatment planning was devised to evaluate SPR prediction for proton, helium, and carbon ion beam therapy planning in the brain. DLCT‐ and SECT‐based SPR predictions were compared in homogeneous and heterogeneous anatomical regions. This study included eight patients scanned for diagnostic purposes with a DLCT scanner. For each patient, four different treatment plans were created, simulating tumors in different parts of the brain.For homogeneous anatomical regions, mean SPR differences of about 1% between the DLCT‐ and SECT‐based approaches were found. In plans of heterogeneous anatomies, relative (absolute) proton range shifts of 0.6% (0.4 mm) in the mean and up to 4.4% (2.1 mm) at the distal fall‐off were observed. In the investigated cohort, 12% of the evaluated organs‐at‐risk (OARs) presented differences in mean or maximum dose of more than 0.5 Gy (RBE) and up to 6.8 Gy (RBE) over the entire treatment. Range shifts and dose differences in OARs between DLCT and SECT in helium and carbon ion treatment plans were similar to protons.In the majority of investigated cases (75th percentile), SECT‐ and DLCT‐based range estimations were within 0.6 mm. Nonetheless, the magnitude of patient‐specific range deviations between SECT and DLCT was clinically relevant in heterogeneous anatomical sites, suggesting further study in larger, more diverse cohorts. Results indicate that patients with brain tumors may benefit from DLCT‐based treatment planning.