Scanned Carbon Ion Beam Research Articles

Dosimetric impact of stopping power for human bone porosity with dual-energy computed tomography in scanned carbon-ion therapy treatment planning

Few reports have documented how the accuracy of stopping power ratio (SPR) prediction for porous bone tissue affects the dose distribution of scanned carbon-ion beam therapy. The estimated SPR based on single-energy computed tomography (SECT) and dual-energy CT (DECT) were compared for the femur of a Rando phantom which simulates the porosity of human bone, NEOBONE which is the hydroxyapatite synthetic bone substitute, and soft tissue samples. Dose differences between SECT and DECT were evaluated for a scanned carbon-ion therapy treatment plan for the Rando phantom. The difference in the water equivalent length was measured to extract the SPR of the examined samples. The differences for SPR estimated from the DECT-SPR conversion were small with − 1.8% and − 3.3% for the Rando phantom femur and NEOBONE, respectively, whereas the differences for SECT-SPR were between 7.6 and 70.7%, illustrating a 1.5-mm shift of the range and a dose difference of 13.3% at maximum point in the evaluation of the dose distribution. This study demonstrated that the DECT-SPR conversion method better estimated the SPR of the porosity of bone tissues than SECT-SPR followed by the accurate range of the carbon-ion beams on carbon-ion dose calculations.

Development and characterization of a dedicated dose monitor for ultrahigh-dose-rate scanned carbon-ion beams

The current monochromatic beam mode (i.e., uHDR irradiation mode) of the scanned carbon-ion beam lacks a dedicated dose monitor, making the beam control challenging. We developed and characterized a dedicated dose monitor for uHDR-scanned carbon-ion beams. Furthermore, a simple measurable dose rate (dose rate per spot (DRspot)) was suggested by using the developed dose monitor and experimentally validating quantities relevant to the uHDR scanned carbon-ion beam. A large plane-parallel ionization chamber (IC) with a smaller electrode spacing was used to reduce uHDR recombination effects, and a dedicated operational amplifier was manufactured for the uHDR-scanned carbon-ion beam. The dose linearity of the IC was within ± 1% in the range of 1.8–12.3 Gy. The spatial inhomogeneity of the dose response of the IC was ± 0.38% inside the ± 40-mm detector area, and a systematic deviation of approximately 2% was measured at the edge of the detector. uHDR irradiation with beam scanning was tested and verified for different doses at the corresponding dose rates (in terms of both the average dose rate and DRspot). We confirmed that the dose monitor can highlight the characteristics (i.e., dose, dose rate, and dose profile) of uHDR-scanned carbon-ion beams at several dose levels in the monochromatic beam mode.

Investigation of Ionization Chamber Characteristics for Ultrahigh-dose-rate Scanned Carbon-ion Beams.

There are only a few studies on dosimetry with ultrahigh-dose-rate (uHDR) scanned carbon-ion beams. This study investigated the characteristics of four types of ionization chambers for the uHDR beam. We employed a newly developed large-plane parallel chamber to monitor a 208.3-MeV/u uHDR scanned carbon-ion beam with a 110-Gy/s average dose rate. The ionization chambers used were the Advanced Markus chamber (AMC), PinPoint 3D chamber (PPC), Farmer chamber (FC), and large-plane parallel chamber (StingRay). The AMC and StingRay surfaces and the PPC and FC geometric centers were aligned to the radiation isocenter using treatment room lasers. Using the voltage range stated in the instruction manuals, we obtained the saturation curves of the chambers. From these curves, we obtained the ion recombination correction factors using the two-voltage and three-voltage linear methods. The dose linearity was evaluated using five measurement points, and the chamber repeatability was verified by conducting repeated measurements for different dose values. Although all chambers, except for AMC, reached saturation when specified voltages were applied, they exhibited excellent linearity for different dose values. The ion recombination correction factors of the AMC obtained using the aforementioned linear methods were nearly 1. Additionally, all chambers exhibited excellent repeatability. Although the standard deviation of the PPC for the lowest dose was ~1.5%, those of all the other chambers were <1.0%. All ionization chambers can be used for measuring the relative dose, and absolute dose can be conveniently measured using the AMC with an uHDR carbon-ion scanned beam.

Diamond based integrated detection system for dosimetric and microdosimetric characterization of radiotherapy ion beams.

Ion beam therapy allows for a substantial sparing of normal tissues and higher biological efficacy. Synthetic single crystal diamond is a very good material to produce high-spatial-resolution and highly radiation hard detectors for both dosimetry and microdosimetry in ion beam therapy. The aim of this work is the design, fabrication and test of an integrated waterproof detector based on synthetic single crystal diamond able to simultaneously perform dosimetric and microdosimetric characterization of clinical ion beams. The active elements of the integrated diamond device, that is, dosimeter and microdosimeter, were both realized in a Schottky diode configuration featured by different area, thickness, and shape by means of photolithography technologies for the selective growth of intrinsic and boron-doped CVD diamond. The cross-section of the sensitive volume of the dosimetric element is 4mm2 and 1μm-thick, while the microdosimetric one has an active cross-sectional area of 100×100μm2 and a thickness of about 6.2μm. The dosimetric and microdosimetric performance of the developed device was assessed at different depths in a water phantom at the MedAustron ion beam therapy facility using a monoenergetic uniformly scanned carbon ion beam of 284.7MeV/u and proton beam of 148.7MeV. The particle flux in the region of the microdosimeter was 6·107 cm2 /s for both irradiation fields. At each depth, dose and dose distributions in lineal energy were measured simultaneously and the dose mean lineal energy values were then calculated. Monte Carlo simulations were also carried out by using the GATE-Geant4 code to evaluate the relative dose, dose averaged linear energy transfer (LETd ), and microdosimetric spectra at various depths in water for the radiation fields used, by considering the contribution from the secondary particles generated in the ion interaction processes as well. Dosimetric and microdosimetric quantities were measured by the developed prototype with relatively low noise (∼2keV/μm). A good agreement between the measured and simulated dose profiles was found, with discrepancies in the peak to plateau ratio of about 3% and 4% for proton and carbon ion beams respectively, showing a negligible LET dependence of the dosimetric element of the device. The microdosimetric spectra were validated with Monte Carlo simulations and a good agreement between the spectra shapes and positions was found. Dose mean lineal energy values were found to be in close agreement with those reported in the literature for clinical ion beams, showing a sharp increase along the Bragg curve, being also consistent with the calculated LETd for all depths within the experimental error of 10%. The experimental indicate that the proposed device can allow enhanced dosimetry in particle therapy centers, where the absorbed dose measurement is implemented by the microdosimetric characterization of the radiation field, thus providing complementary results. In addition, the proposed device allows for the reduction of the experimental uncertainties associated with detector positioning and could facilitate the partial overcoming of some drawbacks related to the low sensitivity of diamond microdosimeters to low LET radiation.

Validation of robust radiobiological optimization algorithms based on the mixed beam model for intensity-modulated carbon-ion therapy.

Currently, treatment planning systems (TPSs) that can compute the intensities of intensity-modulated carbon-ion therapy (IMCT) using scanned carbon-ion beams are limited. In the present study, the computational efficacy of the newly designed IMCT algorithms was analyzed for the first time based on the mixed beam model with respect to the physical and biological doses; moreover, the validity and effectiveness of the robust radiobiological optimization were verified. A dose calculation engine was independently generated to validate a clinical dose determined in the TPS. A biological assay was performed using the HSGc-C5 cell line to validate the calculated surviving fraction (SF). Both spot control (SC) and voxel-wise worst-case scenario (WC) algorithms were employed for robust radiobiological optimization followed by their application in a Radiation Therapy Oncology Group benchmark phantom under homogeneous and heterogeneous conditions and a clinical case for range and position errors. Importantly, for the first time, both SC and WC algorithms were implemented in the integrated TPS platform that can compute the intensities of IMCT using scanned carbon-ion beams for robust radiobiological optimization. For assessing the robustness, the difference between the maximum and minimum values of a dose-volume histogram index in the examined error scenarios was considered as a robustness index. The relative biological effectiveness (RBE) determined by the independent dose calculation engine exhibited a -0.6% difference compared with the RBE defined by the TPS at the isocenter, whereas the measured and the calculated SF were similar. Regardless of the objects, compared with the conventional IMCT, the robust radiobiological optimization enhanced the sensitivity of the examined error scenarios by up to 19% for the robustness index. The computational efficacy of the novel IMCT algorithms was verified according to the mixed beam model with respect to the physical and biological doses. The robust radiobiological optimizations lowered the impact of range and position uncertainties considerably in the examined scenarios. The robustness of the WC algorithm was more enhanced compared with that of the SC algorithm. Nevertheless, the SC algorithm can be used as an alternative to the WC IMCT algorithm with respect to the computational cost.

Simulation study of comparative dosimetric analysis of coplanar horizontal-port scanned carbon-ion beam therapy in the head and neck.

Carbon-ion radiotherapy (CIRT) has demonstrated success in treating radioresistant disease within the head and neck, owing to its unique physical and radiobiological properties. Construction cost remains prohibitive; a center offering only a horizontal port may bridge this difficulty, but removal of the vertical port may prohibit treatment of disease near critical organs-at-risk. Building a center only containing a horizontal treatment port has been proposed as one method for cost savings. 20 complex cases of head and neck cancer previously treated with conventional CIRT were retrospectively planned using horizontal-port-only treatment incorporating non-coplanar treatment angles to achieve greater degrees of freedom. These were dosimetrically compared with the previous plans. Comparable D95 coverage of both planning target volume and gross tumor volume with ability to meet organ-at-risk constraints were feasible with horizontal-port-only treatment. Collectively differences were noted in PTV D95, brain stem Dmax, contralateral eye Dmax and V10 Gy (RBE); further qualitative differences were noted on a plan-by-plan basis dependent on disease location. Horizontal-port-only treatment employing non-coplanar angles was feasible for complicated head and neck disease typically treated with CIRT, though careful consideration is necessary on a plan-by-plan basis. It is worth noting that non-coplanar approaches are not typically used with the current treatment gantry and may extend further the difference between horizontal port planning and a gantry-based gold-standard.

Ultra-high Dose-rate Carbon-ion Scanning Beam With a Compact Medical Synchrotron Contributing to Further Development of FLASH Irradiation.

The focus of this report is establishing an irradiation arrangement to realize an ultra-high dose-rate (uHDR; FLASH) of scanned carbon-ion irradiation possible with a compact commonly available medical synchrotron. Following adjustments to the operation it became possible to extract ≥1.0×109 carbon ions at 208.3 MeV/u (86 mm in range) per 100 ms. The design takes the utmost care to prevent damage to monitors, particularly in the nozzle, achieved by the uHDR beam not passing through this part of the apparatus. Doses were adjusted by extraction times, using a function generator. After one scan by the carbon-ion beam it became possible to create a field within the extraction time. The Advanced Markus chamber (AMC) and Gafchromic film are then able to measure the absolute dose and field size at a plateau depth, with the operating voltage of the chamber at 400 V at the uHDR for the AMC. The beam scanning utilizing this uHDR irradiation could be confirmed at a dose of 6.5±0.08 Gy (±3% homogeneous) at this volume over at least 16×16 mm2 corresponding to a dose-rate of 92.3 Gy/s (±1.3%). The dose was ca. 0.7, 1.5, 2.9, and 5.4 Gy depending on dose-rate and field size, with the rate of killed cells increasing with the irradiation dose. The compact medical synchrotron achieved FLASH dose-rates of >40 Gy/s at different dose levels and in useful field sizes for research with the apparatus and arrangement developed here.

Ultra-High Dose-Rate Carbon-Ion Scanning Irradiation with a Compact Type Medical Synchrotron toward FLASH Research

<h3>Purpose/Objective(s)</h3> To establish an irradiation system to enable the ultra-high dose-rate (uHDR; FLASH) scanned carbon-ion irradiation with a compact type medical synchrotron. <h3>Materials/Methods</h3> After technical adjustments of the accelerator operation parameters, the medical synchrotron extracted ≥1.0 × 10⁹ carbon-ions (2.0 nC/spill) at 208.3 MeV/u (86 mm in range) within a maximum 100 ms. The uHDR carbon-ion beam delivery system was designed to prevent damage to monitors in the nozzle due to the uHDR beam by avoiding passage through the nozzle. The dose amount was adjusted by the extraction time of the total spill with a function generator. The carbon-ion beam was scanned once to create a field within the extraction time. Advanced Markus chamber and radiographic film were used to measure the absolute dose and the field size respectively, at a plateau depth. Operation voltage of the chamber was set to 400 V at the uHDR. <h3>Results</h3> The FLASH irradiation utilizing beam scanning was confirmed with a dose of 5.4 Gy (homogeneity of ±2%) for the beam in a volume of at least 16 mm × 16 mm in a square field and a corresponding dose-rate of 95 Gy/s (± 1%). The dose was changed to about 0.7, 1.5, 2.9 Gy for the dose-rate and the field size. Details of the results are shown in Table1. <h3>Conclusion</h3> The FLASH dose-rates >40 Gy/s at different dose levels were achieved in a useful field size for research created by the scanned carbon-ion beams with the compact type medical synchrotron. This study reported promising beam characteristics of uHDR scanned carbon-ion beams, at different dose levels, and can be used for further investigation of carbon-ion FLASH research. The dose and dose-rate established with the uHDR irradiation system can be applied in biological experiments.

Commissioning a newly developed treatment planning system, VQA Plan, for fast-raster scanning of carbon-ion beams.

In this study, we report our experience in commissioning a commercial treatment planning system (TPS) for fast-raster scanning of carbon-ion beams. This TPS uses an analytical dose calculation algorithm, a pencil-beam model with a triple Gaussian form for the lateral-dose distribution, and a beam splitting algorithm to consider lateral heterogeneity in a medium. We adopted the mixed beam model as the relative biological effectiveness (RBE) model for calculating the RBE values of the scanned carbon-ion beam. To validate the modeled physical dose, we compared the calculations with measurements of various relevant quantities as functions of the field size, range and width of the spread-out Bragg peak (SOBP), and depth-dose and lateral-dose profiles for a 6-mm SOBP in water. To model the biological dose, we compared the RBE calculated with the newly developed TPS to the RBE calculated with a previously validated TPS that is in clinical use and uses the same RBE model concept. We also performed patient-specific measurements to validate the dose model in clinical situations. The physical beam model reproduces the measured absolute dose at the center of the SOBP as a function of field size, range, and SOBP width and reproduces the dose profiles for a 6-mm SOBP in water. However, the profiles calculated for a heterogeneous phantom have some limitations in predicting the carbon-ion-beam dose, although the biological doses agreed well with the values calculated by the validated TPS. Using this dose model for fast-raster scanning, we successfully treated more than 900 patients from October 2018 to October 2020, with an acceptable agreement between the TPS-calculated and measured dose distributions. We conclude that the newly developed TPS can be used clinically with the understanding that it has limited accuracies for heterogeneous media.

Feasibility of lattice radiotherapy using proton and carbon-ion pencil beam for sinonasal malignancy.

BackgroundSinonasal malignancies are a treatment challenge because of their complex anatomy and close proximity to organs at risk (OARs). We aimed to investigate the feasibility of lattice radiotherapy (LRT) using pencil beam scanning (PBS) proton or carbon-ion beams in the treatment of sinonasal malignancies.MethodsA total of 10 patients with nonoperative and bulky sinonasal adenoid cystic carcinomas (ACC) were enrolled. Spherical vertices with a 1 cm diameter and average center-to-center (c-t-c) distance of 3.51 cm were delineated within the gross tumor volumes (GTVs). The prescription doses were 15 Gy[relative biologic effectiveness (RBE)] to the vertices and 3 to 3.5 Gy(RBE) to the periphery, delivered as clinical target volume boosts (CTVboosts) in 1 fraction. Photon, proton, and carbon-ion LRT plans were generated. Peak-to-valley dose ratios (PVDRs) and the doses delivered to the vertices, the CTVboost, and OARs were compared among the 3 plans.ResultsThe mean PVDRmin values for the photon, proton, and carbon-ion LRT plans were 4.78 (range, 4.34 to 5.36), 4.82 (range, 4.15 to 5.37), and 4.69 (range, 4.31 to 5.28), respectively. The mean PVDRmean values for the same plans were 3.42 (range, 3.15 to 3.79), 2.93 (range, 2.19 to 3.74), and 3.58 (range, 3.09 to 4.68), respectively. There were no significant differences between the PVDRmin and PVDRmean values across the 3 LRT plans. Most critical organs were better protected in the proton and carbon-ion LRT plans than in the photon LRT plans. The photon LRT plans showed the highest maximum degree (Dmax) of vertices. Furthermore, these plans did not introduce more doses to the OARs compared to the 1-fraction clinical boost plan.ConclusionsDespite minimal differences in PVDR, proton and carbon-ion LRT plans can better protect OARs than photon LRT plans.

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).

Technical Note: A simple and fast daily quality assurance solution for modulated scanning proton and carbon ion beams.

A typical ion beam treatment facility has multiple treatment rooms and may treat with more than one ion species, thus requiring a significant quality assurance (QA) effort. The goal of this work was to perform daily QA using a single irradiation per ion species to obtain the beam dosimetry parameters of dose per monitor unit (D/MU), range, and spot position. The X-ray alignment system should also be checked and the entire procedure performed by therapists. This goal was achieved by designing a jig for the Sun Nuclear Daily QA™ 3 device and combining it with specific brass boluses, a standard QA plan, and a cuboid polyethylene phantom for positioning/repositioning tests. The design of the plan used for each ion species delivery ensured that there was no interference between the tests of the various characteristics. The 1-year monitoring results showed the proposed daily QA procedure was reliable and able to reflect each of the specified QA items of the proton and carbon ion beams. To simplify the daily analysis, the tolerances for the D/MU, beam range, and spot position (±1.5%, ±0.3mm, ±1.5mm, respectively) are checked using only the detector readings without the need for additional data processing. The proposed daily QA procedure was clinically implemented in our facility in April 2019 and has run smoothly for the first 2 years of operation. The total daily QA time for the four-room facility decreased from 1 to 1.5h to 30 to 40 min and was achieved not by reducing QA tests but rather by implementing new technology and procedures permitting acquisition of multiple beam information.

2D range modulator for high-precision water calorimetry in scanned carbon-ion beams

Ionization chamber-based dosimetry for carbon-ion beams still shows a significantly higher standard uncertainty than high-energy photon dosimetry. This is mainly caused by the high standard uncertainty of the correction factor for beam quality . Due to a lack of experimental data, the given values for are based on theoretical calculations. To reduce this standard uncertainty, factors for different irradiation conditions and ionization chambers (ICs) can be determined experimentally by means of water calorimetry. To perform such measurements in a spread-out Bragg peak (SOBP) for a scanned carbon-ion beam, we describe the process of creating an almost cubic dose distribution of about 6 × 6 × 6 cm3 using a 2D range modulator. The aim is to achieve a field homogeneity with a standard deviation of measured dose values in the middle of the SOBP (over a lateral range and a depth of about 4 cm) below 2% within a scanning time of under 100 s, applying a dose larger than 1 Gy. This paper describes the optimization and characterization of the dose distribution in detail.

Perturbation analysis of 4D dose distribution for scanned carbon-ion beam radiotherapy

PurposeTo evaluate the patients’ set-up error-induced perturbation effects on 4D dose distributions (4DDD) of range-adapted internal target volume-based (raITV) treatment plan using lung and liver 4DCT data sets. MethodsWe enrolled 20 patients with lung and liver cancer treated with respiratory-gated carbon-ion beam scanning therapy. PTVs were generated by adding a 2 mm range-adapted set-up margin on the raITVs. Set-up errors were simulated by shifting the beam isocenter in three translational directions of ±2 mm, ±4 mm, and ±6 mm. 4DDDs were calculated for both nominal and isocenter-shifted situations. Dose metrics of CTV dose coverage (D95) and normal tissue sparing were evaluated. Statistical significance with p < 0.01 was considered by Wilcoxon signed rank test. ResultsThe CTV dose coverage was more sensitive to set-up errors for lung cases than for liver cases, and more serious in superior-inferior direction. The sufficient CTV-D95 > 98% could be achieved with set-up errors less than ±2 mm in all shift directions both for lung and liver cases. With the increase of set-up error, the CTV dose coverage decreased gradually. The clinical criterial of CTV-D95 > 95% could not be fulfilled with set-up error reached to ±4 mm for lung cases, and ±6 mm for liver cases. OAR doses did not have a significant difference with each set-up error for both lung and liver cases. ConclusionsThe range-adapted set-up margin successfully prevented dose degradation of 4DDDs in the presence of the same magnitude of set-up error for raITV-based carbon-ion beam scanning therapy.

Modeling RBE-weighted dose variations in irregularly moving abdominal targets treated with carbon ion beams.

To model four-dimensional (4D) relative biological effectiveness (RBE)-weighted dose variations in abdominal lesions treated with scanned carbon ion beam in case of irregular breathing motion. The proposed method, referred to as bioWED method, combines the simulation of tumor motion in a patient- and beam-specific water equivalent depth (WED)-space with RBE modeling, aiming at the estimation of RBE-weighted dose changes due to respiratory motion. The method was validated on a phantom, simulating gated and free breathing dose delivery, and on a patient case, for which free breathing irradiation was assumed and both amplitude and baseline breathing irregularities were simulated through a respiratory motion model. We quantified (a) the effect of motion on the equivalent uniform dose (EUD) and the RBE-weighted dose-volume histograms (DVH), by comparing the planned dose distribution with "ground truth" 4D RBE-weighted doses computed using 4D computed tomography data, and (ii) the estimation error, by comparing the doses estimated with the bioWED method to "ground truth" 4D RBE-weighted doses. In the phantom validation, the estimation error on the EUD was limited with respect to the motion effect and the median estimation error on relevant RBE-weighted DVH metrics remained within 5%. In the patient study, the estimation error as computed on the EUD was smaller than the corresponding motion effect, exhibiting the largest values in the baseline irregularity simulation. However, the median estimation error over all simulations was below 3.2% considering relevant DVH metrics. In the evaluated cases, the bioWED method showed proper accuracy when compared to deformable image registration-based 4D dose calculation. Therefore, it can be seen as a tool to test treatment plan robustness against irregular breathing motion, although its accuracy decreases as a function of increasing soft tissue deformation and should be evaluated on a larger patient dataset.

A GEMPix-based integrated system for measurements of 3D dose distributions in water for carbon ion scanning beam radiotherapy.

PurposeCommercially available systems for ion beam reference dosimetry in water are mainly based on ionization chambers. In those systems, a large number of small detectors are typically arranged in a two‐dimensional (2D) array or matrix to achieve high spatial resolution (order of several millimeters) and large field coverage at the same time. The goal of this work was to investigate the reliability of a detector of superior spatial resolution to perform three‐dimensional (3D) ionization measurements in carbon ion pencil beams.MethodsThe GEMPix is a small gaseous detector with a highly pixelated readout, consisting of a drift region (with 2.8 cm3 × 2.8 cm3 × 0.3 cm3 volume), three gas electron multipliers (GEMs) for signal amplification and four Timepix ASICs with 55 µm pixel pitch and a total of 262,144 pixels. An integrated system was designed and built, which consists of a commercial water phantom with a three‐axis motorized arm, a reference large‐area ionization chamber for signal normalization to the beam output and the GEMPix itself. Measurements at different depths in water have been performed at the Italian National Centre for Oncological Hadrontherapy (CNAO) with three carbon ion beam energies. Lateral beam profiles measured with the GEMPix at the shallowest depth were compared to those measured with radiochromic EBT3 films in air in the position of the reference ionization chamber. The Timepix readout was calibrated in energy by using one independent depth scan with carbon ions of 150 mm range. Bragg peak curves were also simulated using the Monte Carlo FLUKA code as a reference.ResultsBeam profiles measured with the GEMPix were smooth and showed similar shape and full width at half maximum when compared to those measured with radiochromic EBT3 films. Smooth, reproducible Bragg curves were obtained with statistical uncertainties of about 2%, matching FLUKA simulations of the Bragg curves within 15% for most data points. This difference is partially explained for the measurement with carbon ions of 150 mm range by a saturation effect in the GEMs. The high granularity of the readout allowed to produce 2D images of the deposited dose at different depths, as well as 3D data distributions.ConclusionsThis paper demonstrates the capability of the GEMPix detector to measure the 3D dose distribution of carbon ions in water for a clinical pencil beam reliably. In the future, the detector area will be increased to cover fields of scanned beams. Measurements at higher beam intensities and with protons are planned.

Effect of general ion recombination on dose measurement for high dose rate carbon-ion scanning beam

We confirmed the effect of ion recombination using a parallel-plate ionization chamber: dose monitor for clinical use and the Advanced Markus chamber. A 290 MeV/u carbon-ion beam was irradiated using the continuous spot-scanning method in a field size of 5 cm by 5 cm with 2 mm spacing. We tested three beam intensities (1.35 × 108, 2.69 × 109, and 4.03 × 109 particle per second (pps)) at two linear energy transfers (12 keV/μm and 200 keV/μm). The charge (Q) was measured by changing the voltage of the Advanced Markus chamber and that of the dose monitor. Then, Boag’s method was used to calculate the saturated charge (Qsat). For the Advanced Markus chamber, 300 V is a sufficient potential to collect charge. For the dose monitor, Qsat/Q at 2500 V was 1.024 for 4.03 × 109 pps, indicating that the general recombination correction cannot be ignored when high dose rate treatment is performed using a carbon-ion scanning beam.

Microdosimetric characterization of clinical carbon-ion beams using synthetic diamond detectors and spectral conversion methods.

To investigate for the first time the potentialities of obtaining microdosimetric measurements in scanned clinical carbon-ion beams using synthetic single crystal diamond detector and to verify the spectral conversion methods. Microdosimetric measurements were performed at different depths in a water phantom at the therapeutic scanned carbon-ion beam of the National Center of Oncological Hadrontherapy (CNAO) in Pavia, using waterproof encapsulated diamond microdosimeter developed at "Tor Vergata" University. A monoenergetic carbon-ion beam of 195MeV/μ scanned over a square field of 2×2cm2 was used. Experimental microdosimetric spectra were compared with those obtained with a propane-filled Tissue Equivalent Proportional Counters (TEPCs) microdosimeter in the same facility at the same conditions. To this purpose, the spectra in diamond were converted to the spectra that would have been collected with a propane-filled cylindrical sensitive volume by means of a novel analytic methodology, recently developed at MedAustron. The microdosimetric spectra acquired by the diamond microdosimeter show different shapes in the 10keVµm-1 ÷103 keVµm-1 lineal-energy range at different water depths. In spite of the high counting rate, no spectral distortion, due to pile-up events and polarization effects, were observed. The experimental spectra have a low detection threshold of about 6keVµm-1 due to the electronic noise in the irradiation room. The comparison between the spectra converted to propane from diamond detector and the spectra collected directly with propane-filled TEPC shows a good agreement in the whole lineal-energy range. Furthermore this comparison confirms that diamond detector response is LET independent. The frequency- and dose-mean lineal energy values were also assessed for all spectra. The frequency-mean values obtained with diamond microdosimeter at different depths scales rather well with the absorbed dose values. Microdosimetric characterization of a synthetic single crystal diamond detector in high-energy scanned carbon-ion beams was performed. The results of the present study showed that this detector is suitable for microdosimetry of clinical carbon ion beams. In addition, the good agreement between the converted diamond spectra and those obtained with TEPC provides the first experimental validation of the spectra conversion methodologies as valuable tools for the comparison of spectra collected with different detectors.

Simultaneous optimization of RBE-weighted dose and nanometric ionization distributions in treatment planning with carbon ions

Inverse treatment planning in intensity modulated particle therapy (IMPT) with scanned carbon–ion beams is currently based on the optimization of RBE-weighted dose to satisfy requirements of target coverage and limited toxicity to organs-at-risk (OARs) and healthy tissues. There are many feasible IMPT plans that meet these requirements, which allows the introduction of further criteria to narrow the selection of a biologically optimal treatment plan. We propose a novel treatment planning strategy based on the simultaneous optimization of RBE-weighted dose and nanometric ionization details (ID) as a new physical characteristic of the delivered plan beyond LET. In particular, we focus on the distribution of large ionization clusters (more than 3 ionizations) to enhance the biological effect across the target volume while minimizing biological effect in normal tissues. Carbon–ion treatment plans for different patient geometries and beam configurations generated with the simultaneous optimization strategy were compared against reference plans obtained with RBE-weighted dose optimization alone. Quality indicators, inhomogeneity index and planning volume histograms of RBE-weighted dose and large ionization clusters were used to evaluate the treatment plans. We show that with simultaneous optimization, ID distributions can be optimized in carbon–ion radiotherapy without compromising the RBE-weighted dose distributions. This strategy can potentially be used to account for optimization of endpoints closely related to radiation quality to achieve better tumor control and reduce risks of complications.

Evaluation of patient positional reproducibility on the treatment couch and its impact on dose distribution using rotating gantry system in scanned carbon-ion beam therapy

PurposeThe daily variations in patient setup may cause beam range uncertainties. We evaluated the reproducibility of relative position between the patient and the treatment couch throughout the treatment course and assessed its effects on dose distributions when a beam passes through treatment couch using rotating gantry system. MethodsWe enrolled 1023 patients (=13072 fractions) treated by carbon-ion pencil beam scanning therapy. Seven treatment sites including prostate, head and neck, bone and soft tissue, rectum, liver, lung, and pancreas were investigated. Inter-fractional changes in couch position relative to the patient were defined as translational errors. Changes in couch rotation were defined as rotational errors. Treatment planning was performed for 4 patients in each of the treatment sites. Dose distributions were then re-calculated after the couch was shifted according to average, 95th percentile, and maximum values of translational error. ResultsLarge positional errors (>1.5 cm) were observed in 5% of treatment fractions. Positional errors were largest in prostate and pancreas patients, while smallest in head and neck and lung patients. There were no or only small changes in PTV-D95 and CTV-D95 values for almost all treatment sites. Clinically significant changes were observed in the duodenum (difference in D2cc values ranged from −55% to 28% with maximum couch shift) in pancreas treatment. ConclusionsAlthough underdosage to the PTV or CTV was limited, significant overdoses to organs at risk were found. The improvement of immobilization technique and appropriate selection of gantry angles could reduce the uncertainties due to changes in patient position.