Heidelberg Ion Beam Therapy Center Research Articles

Evaluation of Helium Ion Radiotherapy in Combination with Gemcitabine in Pancreatic Cancer In Vitro.

Pancreatic cancer is one of the most aggressive and lethal cancers. New treatment strategies are highly warranted. Particle radiotherapy could offer a way to overcome the radioresistant nature of pancreatic cancer because of its biological and physical characteristics. Within particles, helium ions represent an attractive therapy option to achieve the highest possible conformity while at the same time protecting the surrounding normal tissue. The aim of this study was to evaluate the cytotoxic efficacy of helium ion irradiation in pancreatic cancer in vitro. Human pancreatic cancer cell lines AsPC-1, BxPC-3 and Panc-1 were irradiated with photons and helium ions at various doses and treated with gemcitabine. Photon irradiation was performed with a biological cabin X-ray irradiator, and helium ion irradiation was performed with a spread-out Bragg peak using the raster scanning technique at the Heidelberg Ion Beam Therapy Center (HIT). The cytotoxic effect on pancreatic cancer cells was measured with clonogenic survival. The survival curves were compared to the predicted curves that were calculated via the modified microdosimetric kinetic model (mMKM). The experimental relative biological effectiveness (RBE) of helium ion irradiation ranged from 1.0 to 1.7. The predicted survival curves obtained via mMKM calculations matched the experimental survival curves. Mainly additive cytotoxic effects were observed for the cell lines AsPC-1, BxPC-3 and Panc-1. Our results demonstrate the cytotoxic efficacy of helium ion radiotherapy in pancreatic cancer in vitro as well as the capability of mMKM calculation and its value for biological plan optimization in helium ion therapy for pancreatic cancer. A combined treatment of helium irradiation and chemotherapy with gemcitabine leads to mainly additive cytotoxic effects in pancreatic cancer cell lines. The data generated in this study may serve as the radiobiological basis for future experimental and clinical works using helium ion radiotherapy in pancreatic cancer treatment.

Energy painting: helium-beam radiography with thin detectors and multiple beam energies

Objective. Compact ion imaging systems based on thin detectors are a promising prospect for the clinical environment since they are easily integrated into the clinical workflow. Their measurement principle is based on energy deposition instead of the conventionally measured residual energy or range. Therefore, thin detectors are limited in the water-equivalent thickness range they can image with high precision. This article presents our energy painting method, which has been developed to render high precision imaging with thin detectors feasible even for objects with larger, clinically relevant water-equivalent thickness (WET) ranges. Approach. A detection system exclusively based on pixelated silicon Timepix detectors was used at the Heidelberg ion-beam therapy center to track single helium ions and measure their energy deposition behind the imaged object. Calibration curves were established for five initial beam energies to relate the measured energy deposition to WET. They were evaluated regarding their accuracy, precision and temporal stability. Furthermore, a 60 mm × 12 mm region of a wedge phantom was imaged quantitatively exploiting the calibrated energies and five different mono-energetic images. These mono-energetic images were combined in a pixel-by-pixel manner by averaging the WET-data weighted according to their single-ion WET precision (SIWP) and the number of contributing ions. Main result. A quantitative helium-beam radiograph of the wedge phantom with an average SIWP of 1.82(5) % over the entire WET interval from 150 mm to 220 mm was obtained. Compared to the previously used methodology, the SIWP improved by a factor of 2.49 ± 0.16. The relative stopping power value of the wedge derived from the energy-painted image matches the result from range pullback measurements with a relative deviation of only 0.4 %. Significance. The proposed method overcomes the insufficient precision for wide WET ranges when employing detection systems with thin detectors. Applying this method is an important prerequisite for imaging of patients. Hence, it advances detection systems based on energy deposition measurements towards clinical implementation.

Patterns of Temporal Lobe Reaction and Radiation Necrosis after Particle Radiotherapy in Patients with Skull Base Chordoma and Chondrosarcoma-A Single-Center Experience.

The current study aims to evaluate the occurrence of temporal lobe reactions and identify possible risk factors for patients who underwent particle therapy of the skull base. 244 patients treated for skull base chordoma (n = 144) or chondrosarcoma (n = 100) at the Heidelberg Ion Beam Therapy Center (HIT) using a raster scan technique, were analyzed. Follow-up MRI-scans were matched with the initial planning images. Radiogenic reactions were contoured and analyzed based on volume and dose of treatment. 51 patients with chordoma (35.4%) and 30 patients (30%) with chondrosarcoma experienced at least one temporal lobe reaction within the follow-up period (median 49 months for chondrosarcoma, 62 months for chordoma). Age, irradiated volume, and dose values were significant risk factors for the development of temporal lobe reactions with the highest significance for the value of DMax-7 being defined as the dose maximum in the temporal lobe minus the 7cc with the highest dose (p = 0.000000000019; OR 1.087). Temporal lobe reactions are a common side effect after particle therapy of the skull base. We were able to develop a multivariate model, which predicted radiation reactions with a specificity of 99% and a sensitivity of 52.2%.

Investigation of micro spill in RF KO extraction using tailored excitation signals

Radio Frequency Knock Out (RF KO) extraction is used to extract stored particle beams from synchrotrons through transverse excitation, delivering spills of particles for experiments and medical therapy. Minimizing the fluctuations of spill intensity is vital to prevent detector pile-up and interlocks while making most efficient use of the extracted beam. To improve the spill quality, different excitation signals with characteristic frequency spectra are explored. Results of experimental studies at the Heidelberg Ion Beam Therapy Center (HIT) are presented. These demonstrate the possible improvements by tuning multi-band spectra at different harmonics. Particle tracking simulations of the slow extraction process at HIT are used to understand how different excitation signals influence the spill quality.

Development and benchmarking of a dose rate engine for raster-scanned FLASH helium ions.

Radiotherapy with charged particles at high dose and ultra-high dose rate (uHDR) is a promising technique to further increase the therapeutic index of patient treatments. Dose rate is a key quantity to predict the so-called FLASH effect at uHDR settings. However, recent works introduced varying calculation models to report dose rate, which is susceptible to the delivery method, scanning path (in active beam delivery) and beam intensity. This work introduces an analytical dose rate calculation engine for raster scanned charged particle beams that is able to predict dose rate from the irradiation plan and recorded beam intensity. The importance of standardized dose rate calculation methods is explored here. Dose is obtained with an analytical pencil beam algorithm, using pre-calculated databases for integrated depth dose distributions and lateral penumbra. Dose rate is then calculated by combining dose information with the respective particle fluence (i.e., time information) using three dose-rate-calculation models (mean, instantaneous, and threshold-based). Dose rate predictions for all three models are compared to uHDR helium ion beam (145.7 MeV/u, range in water of approximatively 14.6cm) measurements performed at the Heidelberg Ion Beam Therapy Center (HIT) with a diamond-detector prototype. Three scanning patterns (scanned or snake-like) and four field sizes are used to investigate the dose rate differences. Dose rate measurements were in good agreement with in-silico generated distributions using the here introduced engine. Relative differences in dose rate were below 10% for varying depths in water, from 2.3 to 14.8cm, as well as laterally in a near Bragg peak area. In the entrance channel of the helium ion beam, dose rates were predicted within 7% on average for varying irradiated field sizes and scanning patterns. Large differences in absolute dose rate values were observed for varying calculation methods. For raster-scanned irradiations, the deviation between mean and threshold-based dose rate at the investigated point was found to increase with the field size up to 63% for a 10mm × 10mm field, while no significant differences were observed for snake-like scanning paths. This work introduces the first dose rate calculation engine benchmarked to instantaneous dose rate, enabling dose rate predictions for physical and biophysical experiments. Dose rate is greatly affected by varying particle fluence, scanning path, and calculation method, highlighting the need for a consensus among the FLASH community on how to calculate and report dose rate in the future. The here introduced engine could help provide the necessary details for the analysis of the sparing effect and uHDR conditions.

Proton Therapy for Advanced Juvenile Nasopharyngeal Angiofibroma.

To provide the first report on proton radiotherapy (PRT) in the management of advanced nasopharyngeal angiofibroma (JNA) and evaluate potential benefits compared to conformal photon therapy (XRT). We retrospectively reviewed 10 consecutive patients undergoing PRT for advanced JNA in a definitive or postoperative setting with a relative biological effectiveness weighted dose of 45 Gy in 25 fractions between 2012 and 2022 at the Heidelberg Ion Beam Therapy Center. Furthermore, dosimetric comparisons and risk estimations for short- and long-term radiation-induced complications between PRT plans and helical XRT plans were conducted. PRT was well tolerated, with only low-grade acute toxicities (CTCAE I-II) being reported. The local control rate was 100% after a median follow-up of 27.0 (interquartile range 13.3-58.0) months. PRT resulted in considerable tumor shrinkage, leading to complete remission in five patients and bearing the potential to provide partial or complete symptom relief. Favorable dosimetric outcomes in critical brain substructures by the use of PRT translated into reduced estimated risks for neurocognitive impairment and radiation-induced CNS malignancies compared to XRT. PRT is an effective treatment option for advanced JNA with minimal acute morbidity and the potential for reduced radiation-induced long-term complications.

Quality assurance and temporal stability of a 1.5 T MRI scanner for MR-guided Photon and Particle Therapy

PurposeTo describe performance measurements, adaptations and time stability over 20 months of a diagnostic MR scanner for integration into MR-guided photon and particle radiotherapy. Material and methodsFor realization of MR-guided photon and particle therapy (MRgRT/MRgPT), a 1.5 T MR scanner was installed at the Heidelberg Ion Beam Therapy Center. To integrate MRI into the treatment process, a flat tabletop and dedicated coil holders for flex coils were used, which prevent deformation of the patient external contour and allow for the use of immobilization tools for reproducible positioning. The signal-to-noise ratio (SNR) was compared for the diagnostic and therapy-specific setup using the flat couch top and flexible coils for the a) head & neck and b) abdominal region as well as for different bandwidths and clinical pulse sequences. Additionally, a quality assurance (QA) protocol with monthly measurements of the ACR phantom and measurement of geometric distortions for a large field-of-view (FOV) was implemented to assess the imaging quality parameters of the device over the course of 20 months. ResultsThe SNR measurements showed a decreased SNR for the RT-specific as compared to the diagnostic setup of (a) 26% to 34% and (b) 11% to 33%. No significant bandwidth dependency for this ratio was found. The longitudinal assessment of the image quality parameters with the ACR and distortion phantom confirmed the long-term stability of the MRI device. ConclusionA diagnostic MRI was commissioned for use in MR-guided particle therapy. Using a radiotherapy specific setup, a high geometric accuracy and signal homogeneity was obtained after some adaptions and the measured parameters were shown to be stable over a period of 20 months.

Neutron shielding assessment of a 16O hadron therapy room by means of Monte Carlo simulations with the PHITS code

Hadron radiation therapy is of great interest worldwide. Heavy-ion beams provide ideal therapeutic conditions for deep-seated local tumours. At the Heidelberg Ion Beam Therapy Center (HIT, Germany), protons and carbon ions are already integrated into the clinical routine, while 16O ions are still used for research only. To ensure the protection of the technical staff and members of the public, it is required to estimate the neutron dose distribution for optimal working conditions and at different locations. The Particle and Heavy Ion Transport Code System (PHITS) is used in this work to evaluate the dose rate distribution of secondary neutrons in a treatment room at HIT where 16O ions are used: an equivalent target in soft tissue is considered in the shielding assessment to simulate the interaction of the beam with patients. The angular dependence of neutron fluences and energy spectra around the considered phantom were calculated. Alongside the spatial distribution of the neutron and photon fluence, a map of the effective dose rate was estimated using the ICRP fluence-to-effective dose conversion coefficients, exploiting the PHITS code’s built-in capabilities. The capability of the actual shielding design of the studied HIT treatment room was approved.

Commissioning of Helium Ion Therapy and the First Patient Treatment With Active Beam Delivery

Helium ions offer intermediate physical and biological properties to the clinically used protons and carbon ions. This work presents the commissioning of the first clinical treatment planning system (TPS) for helium ion therapy with active beam delivery to prepare the first patients' treatment at the Heidelberg Ion-Beam Therapy Center (HIT). Through collaboration between RaySearch Laboratories and HIT, absorbed and relative biological effectiveness (RBE)-weighted calculation methods were integrated for helium ion beam therapy with raster-scanned delivery in the TPS RayStation. At HIT, a modified microdosimetric kinetic biological model was chosen as reference biological model. TPS absorbed dose predictions were compared against measurements with several devices, using phantoms of different complexities, from homogeneous to heterogeneous anthropomorphic phantoms. RBE and RBE-weighted dose predictions of the TPS were verified against calculations with an independent RBE-weighted dose engine. The patient-specific quality assurance of the first treatment at HIT using helium ion beam with raster-scanned delivery is presented considering standard patient-specific measurements in a water phantom and 2 independent dose calculations with a Monte Carlo or an analytical-based engine. TPS predictions were consistent with dosimetric measurements and independent dose engines computations for absorbed and RBE-weighted doses. The mean difference between dose measurements to the TPS calculation was 0.2% for spread-out Bragg peaks in water. Verification of the first patient treatment TPS predictions against independent engines for both absorbed and RBE-weighted doses presents differences within 2% in the target and with a maximum deviation of 3.5% in the investigated critical regions of interest. Helium ion beam therapy has been successfully commissioned and introduced into clinical use. Through comprehensive validation of the absorbed and RBE-weighted dose predictions of the RayStation TPS, the first clinical TPS for helium ion therapy using raster-scanned delivery was employed to plan the first helium patient treatment at HIT.

Horizontal beam response at extraction conditions at the Heidelberg Ion-beam Therapy Centre

The Heidelberg Ion-Beam Therapy Centre’s synchrotron makes use of the sextupole driven RF-KO method near the third-order resonance in order to slowly extract the beam that is delivered to the patients. The horizontal beam response of a coasting beam was studied experimentally and with simulations at extraction conditions in order to deduce regions of interest for an optimal excitation signal spectrum. Two narrow frequency regions were found where the beam reacts coherently. With these information an RF signal was proposed for the resonant slow extraction.

Development and benchmarking of the first fast Monte Carlo engine for helium ion beam dose calculation: MonteRay.

Monte Carlo (MC) simulations are considered the gold-standard for accuracy in radiotherapy dose calculation; however, general purpose MC engines are computationally demanding and require long runtimes. For this reason, several groups have recently developed fast MC systems dedicated mainly to photon and proton external beam therapy, affording both speed and accuracy. To support research and clinical activities at the Heidelberg Ion-beam Therapy Center (HIT) with actively scanned helium ion beams, this work presents MonteRay, the first fast MC dose calculation engine for helium ion therapy. MonteRay is a CPU MC dose calculation engine written in C++, capable of simulating therapeutic proton and helium ion beams. In this work, development steps taken to include helium ion beams in MonteRay are presented. A detailed description of the newly implemented physics models for helium ions, for example, for multiple coulomb scattering and inelastic nuclear interactions, is provided. MonteRay dose computations of helium ion beams are evaluated using a comprehensive validation dataset, including measurements of spread-out Bragg peaks (SOBPs) with varying penetration depths/field sizes, measurements with an anthropomorphic phantom and FLUKA simulations of a patient plan. Improvement in computational speed is demonstrated in comparison against reference FLUKA simulations. Dosimetric comparisons between MonteRay and measurements demonstrated good agreement. Comparing SOBPs at 5, 12.5, and 20cm depth, mean absolute percent dose differences were 0.7%, 0.7%, and 1.4%, respectively. Comparison against measurements behind an anthropomorphic head phantom revealed mean absolute dose differences of about 1.2% (FLUKA: 1.5%) with per voxel errors ranging from -4.5% to 4.1% (FLUKA: -6% to 3%). Computed global 3%/3mm 3D-gamma passing rates of ∼99% were achieved, exceeding those previously reported for an analytical dose engine. Comparisons against FLUKA simulations for a patient plan revealed local 2%/2mm 3D-gamma passing rates of 98%. Compared to FLUKA in voxelized geometries, MonteRay saw run-time reductions ranging from 20× to 60×, depending on the beam's energy. MonteRay, the first fast MC engine dedicated to helium ion therapy, has been successfully developed with a focus on both speed and accuracy. Validations against dosimetric measurements in homogeneous and heterogeneous scenarios and FLUKA MC calculations have proven the validity of the physical models implemented. Timing comparisons have shown significant speedups between 20 and 60 when compared to FLUKA, making MonteRay viable for clinical routine. MonteRay will support research and clinical practice at HIT, for example, TPS development, validation and treatment design for upcoming clinical trials for raster-scanned helium ion therapy.

Radiotherapy with Helium Ions Has the Potential to Improve Both Endocrine and Neurocognitive Outcome in Pediatric Patients with Ependymoma

Ependymomas are the third most-frequent pediatric brain tumors. To prevent local recurrence, the resection site should be irradiated. Compared to photon radiation treatment, proton therapy often achieves even better results regarding target coverage and organ-sparing. Due to their physical properties, helium ions could further reduce side effects, providing better protection of healthy tissue despite similar target coverage. In our in silico study, 15 pediatric ependymoma patients 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 advantage of ion beam therapy compared to the current state-of-the-art photon-based treatments. To estimate the potential clinical benefit of helium ions, normal tissue complication probabilities (NTCP) were calculated. Target coverage was comparable in all three modalities. As expected, the integral dose absorbed by healthy brain tissue could be significantly reduced with protons by up to -48% vs. IMRT. Even compared to actively scanned protons, relative dose reductions for critical neuronal structures of up to another -39% were achieved when using helium ions. The dose distribution of helium ions is significantly superior when compared to proton therapy and IMRT due to the improved sparing of OAR. In fact, 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 combined with NTCP calculation, the results of our study provide a strong rationale that the use of helium ions has the potential to even further reduce the risk for treatment related sequelae.

Reduction of recombination effects in large plane parallel beam monitors for FLASH radiotherapy with scanned ion beams

Purpose:Radiotherapy escalating dose rates above 50Gys−1, might offer a great potential in treating tumours while further sparing healthy tissue. However, these ultra-high intensities of FLASH-RT lead to new challenges with regard to dosimetry and beam monitoring. FLASH experiments at HIT (Heidelberg Ion Beam Therapy Center) and at GSI (GSI Helmholtz Centre for Heavy Ion Research) have shown a significant loss of signal in the beam monitoring system due to recombination effects. To enable accurate beam monitoring, this work investigates the recombination loss of different fill gases in the plane parallel ionisation chambers (ICs). Methods:Therefore, saturation curves at high intensities were measured for the currently used fill gases Ar/CO2 (80/20) and pure He and also for He/CO2 mixtures as alternative fill gases. Furthermore, breakdown voltages and ion mobilities were measured in ICs filled with He/CO2 mixtures. A numerical model for volume recombination in plane parallel ionisation chambers was developed and implemented in Python. This includes a novel simulation method of the space charge effect from the charge carriers in the detector volume and predicts a significant effect on the electric field for high intensity beams. Results:Even at high intensities the He/CO2 mixtures allow operation of the ICs at an electric field strength of 2 kVcm−1 or more which reduces recombination to negligible levels at intensities larger than 3 × 101012C-ions per second. Our measurements show that added fractions of CO2 to He decrease the ion mobility in the fill gas but significantly increase the breakdown voltage in the ICs compared to pure He.

Proton and carbon ion beam treatment with active raster scanning method in 147 patients with skull base chordoma at the Heidelberg Ion Beam Therapy Center—a single-center experience

BackgroundThis study aimed to compare the results of irradiation with protons versus irradiation with carbon ions in a raster scan technique in patients with skull base chordomas and to identify risk factors that may compromise treatment results.MethodsA total of 147 patients (85 men, 62 women) were irradiated with carbon ions (111 patients) or protons (36 patients) with a median dose of 66 Gy (RBE (Relative biological effectiveness); carbon ions) in 4 weeks or 74 Gy (RBE; protons) in 7 weeks at the Heidelberg Ion Beam Therapy Center (HIT) in Heidelberg, Germany. The median follow-up time was 49.3 months. All patients had gross residual disease at the beginning of RT. Compression of the brainstem was present in 38%, contact without compression in 18%, and no contact but less than 3 mm distance in 16%. Local control and overall survival were evaluated using the Kaplan–Meier Method based on scheduled treatment (protons vs. carbon ions) and compared via the log rank test. Subgroup analyses were performed to identify possible prognostic factors.ResultsDuring the follow-up, 41 patients (27.9%) developed a local recurrence. The median follow-up time was 49.3 months (95% CI: 40.8–53.8; reverse Kaplan–Meier median follow-up time 56.3 months, 95% CI: 51.9–60.7). No significant differences between protons and carbon ions were observed regarding LC, OS, or overall toxicity. The 1‑year, 3‑year, and 5‑year LC rates were 97%, 80%, and 61% (protons) and 96%, 80%, and 65% (carbon ions), respectively. The corresponding OS rates were 100%, 92%, and 92% (protons) and 99%, 91%, and 83% (carbon ions). No significant prognostic factors for LC or OS could be determined regarding the whole cohort; however, a significantly improved LC could be observed if the tumor was > 3 mm distant from the brainstem in patients presenting in a primary situation.ConclusionOutcomes of proton and carbon ion treatment of skull base chordomas seem similar regarding tumor control, survival, and toxicity. Close proximity to the brainstem might be a negative prognostic factor, at least in patients presenting in a primary situation.

Optimization of the spill quality for the hadron therapy at the Heidelberg Ion-Beam Therapy Centre

The Heidelberg Ion-Beam Therapy Centre’s synchrotron makes use of the well established slow extraction RF KO method near the third-order resonance. The spill quality is essential for therapy, since the reproducibility and fidelity in the parameters of the extracted beam translate in a reduction of irradiation time. The horizontal beam response was studied experimentally and with simulations at extraction conditions in order to deduce regions of interest for an optimal excitation signal spectrum. Two narrow frequency regions were found near the betatron resonance. With these results a new signal was engineered for the emittance blow-up scheme. The new excitation signal improves significantly the spill quality for the extraction configurations; for instance the lower interquartile value of the spill duty factor distribution for the most rigid carbon-ion beam Ekin= 430MeV/u improves from 82.2% to 94.8%. For the proton beam the improvement is more significant, where the spill duty factor is kept over the 90% level.

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.

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.

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.

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.