Pulsed RF knock-out extraction: a potential enabler for FLASH hadrontherapy in the Bragg peak.

One challenge on the path to delivering FLASH-compatible beams with a synchrotron is facilitating an accurate dose control for the required ultra-high dose rates. We propose the use of pulsed RFKO extraction instead of continuous beam delivery as a way to control the dose delivered per Voxel. In a first feasibility test, dose rates in pulses of up to 600 Gy/s were observed, while the granularity at which the dose was delivered is expected to be well below 0.5 Gy.

The rationale for a carbon ion radiation therapy facility in Australia.

Australia has taken a collaborative nationally networked approach to achieve particle therapy capability. This supports the under-construction proton therapy facility in Adelaide, other potential proton centres and an under-evaluation proposal for a hybrid carbon ion and proton centre in western Sydney. A wide-ranging overview is presented of the rationale for carbon ion radiation therapy, applying observations to the case for an Australian facility and to the clinical and research potential from such a national centre.

An international approach to estimating the indications and number of eligible patients for carbon ion radiation therapy (CIRT) in Australia.

BACKGROUND AND PURPOSE: To establish the treatment indications and potential patient numbers for carbon ion radiation therapy (CIRT) at the proposed national carbon ion (and proton) therapy facility in the Westmead precinct, New South Wales (NSW), Australia. METHODS: An expert panel was convened, including representatives of four operational and two proposed international carbon ion facilities, as well as NSW-based CIRT stakeholders. They met virtually to consider CIRT available evidence and experience. Information regarding Japanese CIRT was provided pre- and post- the virtual meeting. Published information for South Korea was included in discussions. RESULTS: There was jurisdictional variation in the tumours treated by CIRT due to differing incidences of some tumours, referral patterns, differences in decisions regarding which tumours to prioritise, CIRT resources available and funding arrangements. The greatest level of consensus was reached that CIRT in Australia can be justified currently for patients with adenoid cystic carcinomas and mucosal melanomas of the head and neck, hepatocellular cancer and liver metastases, base of skull meningiomas, chordomas and chondrosarcomas. Almost 1400 Australian patients annually meet the consensus-derived indications now. CONCLUSION: A conservative estimate is that 1% of cancer patients in Australia (or 2% of patients recommended for radiation therapy) may preferentially benefit from CIRT for initial therapy of radiation resistant tumours, or to boost persistently active disease after other therapies, or for re-irradiation of recurrent disease. On this basis, one national carbon ion facility with up to four treatment rooms is justified for Australian patients.

In-field and out-of-field microdosimetric characterisation of a 62 MeV proton beam at CATANA.

PURPOSE: A 5 and 10 µm thin silicon on insulator (SOI) 3D mushroom microdosimeter was used to characterize both the in-field and out-of-field of a 62 MeV proton beam. METHODS: The SOI mushroom microdosimeter consisted of an array of cylindrical sensitive volumes (SVs), developed by the Centre for Medical Radiation Physics, University of Wollongong, was irradiated with 62 MeV protons at the CATANA (Centro di AdroTerapia Applicazioni Nucleari Avanzate) facility in Catania, Italy, a facility dedicated to the radiation treatment of ocular melanomas. Dose mean lineal energy, ( y D ¯ ), values were obtained at various depths in PMMA along a pristine and spread out Bragg peak (SOBP). The measured microdosimetric spectra at each position were then used as inputs into the modified Microdosimetric Kinetic Model (MKM) to derive the RBE for absorbed dose in a middle of the SOBP 2Gy (RBED ). Microdosimetric spectra were obtained with both the 5 and 10 µm 3D SOI microdosimeters, with a focus on the distal part of the BP. The in-field and out-of-field measurement configurations along the Bragg curve were modeled in Geant4 for comparison with experimental results. Lateral out-of-field measurements were performed to study secondary particles' contribution to normal tissue's dose, up to 12 mm from the edge of the beam field, and quality factor and dose equivalent results were obtained. RESULTS: Comparison between experimental and simulation results showed good agreement between one another for both the pristine and SOBP beams in terms of y D ¯ and RBED. Though a small discrepancy between experiment and simulation was seen at the entrance of the Bragg curve, where experimental results were slightly lower than Geant4. The dose equivalent value measured 12 mm from the edge of the target volume was 1.27 ± 0.15 mSv/Gy with a Q ¯ value of 2.52 ± 0.30, both of which agree within uncertainty with Geant4 simulation. CONCLUSIONS: These results demonstrate that SOI microdosimeters are an effective tool to predict RBED in-field as well as dose equivalent monitoring out-of-field to provide insight to probability of second cancer generation.

Characterization of prompt gamma ray emission for in vivo range verification in particle therapy: A simulation study.

In this paper we investigate the emission and detection characteristics of prompt gamma (PG) rays for in vivo range verification during hadron therapy, using Geant4 simulations. Proton, 4He and 12C beams of varying energy are incident on water phantoms. The PG production yield, energy spectral characteristics and spatial correlation with the Bragg Peak (BP) have been quantified. Further, the angular distributions for PG detection with respect to a point-of-reference on the phantom surface have been explored. The temporal properties of PG emission and time-of-flight (TOF) of PG detection have also been investigated in correlation with the changing particle beam range. Our results show that the primary PG rays from nuclear interactions of the primary beam exhibit the closest correlation to the beam range but its signal is significantly masked by the concurrent secondary PG rays, particularly for heavier ions such as carbon ion beams. The PG TOF spectroscopy encodes the essential information of the beam range but requires high time resolution measurements to retrieve it. A hybrid PG detection system to utilize the energy, timing and spatial characteristics of PG rays is desirable for BP tracking in real-time.

INVESTIGATING VARIABLE RBE IN A 12C MINIBEAM FIELD WITH MICRODOSIMETRY AND GEANT4.

An experimental and simulation-based study was performed on a 12C ion minibeam radiation therapy (MBRT) field produced with a clinical broad beam and a brass multi-slit collimator (MSC). Silicon-on-insulator (SOI) microdosimeters developed at the Centre for Medical Radiation Physics (CMRP) with micron sized sensitive volumes were used to measure the microdosimetric spectra at varying positions throughout the MBRT field and the corresponding dose-mean lineal energies and RBE for 10% cell survival (RBE10) were calculated using the modified Microdosimetric Kinetic Model (MKM). An increase in the average RBE10 of ∼30% and 10% was observed in the plateau region compared to broad beam for experimental and simulation values, respectively. The experimental collimator misalignment was determined to be 0.7° by comparison between measured and simulated microdosimetric spectra at varying collimator angles. The simulated dose-mean lineal energies in the valley region between minibeams were found to be higher on average than in the minibeams due to higher LET particles being produced in these regions from the MSC. This work presents the first experimental microdosimetry measurements and characterisation of the local biological effectiveness in a MBRT field.

The relative biological effectiveness for carbon, nitrogen, and oxygen ion beams using passive and scanning techniques evaluated with fully 3D silicon microdosimeters.

BACKGROUND: The aim of this study was to measure the microdosimetric distributions of a carbon pencil beam scanning (PBS) and passive scattering system as well as to evaluate the relative biological effectiveness (RBE) of different ions, namely 12 C, 14 N, and 16 O, using a silicon-on-insulator (SOI) microdosimeter with well-defined 3D-sensitive volumes (SV). Geant4 simulations were performed with the same experimental setup and results were compared to the experimental results for benchmarking. METHOD: Two different silicon microdosimeters with rectangular parallelepiped and cylindrical shaped SVs, both 10 µm in thickness were used in this study. The microdosimeters were connected to low noise electronics which allowed for the detection of lineal energies as low as 0.15 keV/µm in tissue. The silicon microdosimeters provide extremely high spatial resolution and can be used for in-field and out-of-field measurements in both passive scattering and PBS deliveries. The response of the microdosimeters was studied in 290 MeV/u 12 C, 180 MeV/u 14 N, 400 MeV/u 16 O passive ion beams, and 290 MeV/u 12 C scanning carbon therapy beam at heavy ion medical accelerator in Chiba (HIMAC) and Gunma University Heavy Ion Medical Center (GHMC), Japan, respectively. The microdosimeters were placed at various depths in a water phantom along the central axis of the ion beam, and at the distal part of the Spread Out Bragg Peak (SOBP) in 0.5 mm increments. The RBE values of the pristine Bragg peak (BP) and SOBP were derived using the microdosimetric lineal energy spectra and the modified microdosimetric kinetic model (MKM), using MKM input parameters corresponding to human salivary gland (HSG) tumor cells. Geant4 simulations were performed in order to verify the calculated depth-dose distribution from the treatment planning system (TPS) and to compare the simulated dose-mean lineal energy to the experimental results. RESULTS: For a 180 MeV/u 14 N pristine BP, the dose-mean lineal energy yD¯ obtained with two types of silicon microdosimeters started from approximately 29 keV/µm at the entrance to 92 keV/µm at the BP, with a maximum value in the range of 412 to 438 keV/µm at the distal edge. For 400 MeV/u 16 O ions, the dose-mean lineal energy yD¯ started from about 24 keV/µm at the entrance to 106 keV/µm at the BP, with a maximum value of approximately 381 keV/µm at the distal edge. The maximum derived RBE10 values for 14 N and 16 O ions were found to be 3.10 ± 0.47 and 2.93 ± 0.45, respectively. Silicon microdosimetry measurements using pencilbeam scanning 12 C ions were also compared to the passive scattering beam. CONCLUSIONS: These SOI microdosimeters with well-defined three-dimensional (3D) SVs have applicability in characterizing heavy ion radiation fields and measuring lineal energy deposition with sub-millimeter spatial resolution. It has been shown that the dose-mean lineal energy increased significantly at the distal part of the BP and SOBP due to very high LET particles. Good agreement was observed for the experimental and simulation results obtained with silicon microdosimeters in 14 N and 16 O ion beams, confirming the potential application of SOI microdosimeter with 3D SV for quality assurance in charged particle therapy.

Microdosimetric measurements of a clinical proton beam with micrometer-sized solid-state detector.

PURPOSE: Microdosimetry is a vital tool for assessing the microscopic patterns of energy deposition by radiation, which ultimately govern biological effect. Solid-state, silicon-on-insulator microdosimeters offer an approach for making microdosimetric measurements with high spatial resolution (on the order of tens of micrometers). These high-resolution, solid-state microdosimeters may therefore play a useful role in characterizing proton radiotherapy fields, particularly for making highly resolved measurements within the Bragg peak region. In this work, we obtain microdosimetric measurements with a solid-state microdosimeter (MicroPlus probe) in a clinical, spot-scanning proton beam of small spot size. METHODS: The MicroPlus probe had a 3D single sensitive volume on top of silicon oxide. The sensitive volume had an active cross-sectional area of 250 µm × 10 µm and thickness of 10 µm. The proton facility was a synchrotron-based, spot-scanning system with small spot size (σ ≈ 2 mm). We performed measurements with the clinical beam current (≈1 nA) and had no detected pulse pile-up. Measurements were made in a water-equivalent phantom in water-equivalent depth (WED) increments of 0.25 mm or 1.0 mm along pristine Bragg peaks of energies 71.3 MeV and 159.9 MeV, respectively. For each depth, we measured lineal energy distributions and then calculated the dose-weighted mean lineal energy, y¯D. The measurements were repeated for two field sizes: 4 × 4 cm2 and 20 × 20 cm2 . RESULTS: For both 71.3 MeV and 159.9 MeV and for both field sizes, y¯D increased with depth toward the distal edge of the Bragg peak, a result consistent with Monte Carlo calculations and measurements performed elsewhere. For the 71.3 MeV, 4 × 4 cm2 beam (range at 80% distal falloff, R80  = 3.99 cm), we measured y¯D=1.96±0.08 keV/µm at WED = 2 cm, and y¯D=10.6±0.32 keV/µm at WED = 3.95 cm. For the 71.3 MeV, 20 × 20 cm2 beam, we measured y¯D=2.46±0.12 keV/µm at WED = 2.6 cm, and y¯D=11.0±0.24 keV/µm at WED = 3 cm. For the 159.9 MeV, 4 × 4 cm2 beam (R80  = 17.7 cm), y¯D=2.24±0.15 keV/µm at WED = 5 cm, and y¯D=8.99±0.71 keV/µm at WED = 17.6 cm. For the 159.9 MeV, 20 × 20 cm2 beam, y¯D=2.56±0.10 keV/µm at WED = 5 cm, and y¯D=9.24±0.73 keV/µm at WED = 17.6 cm. CONCLUSIONS: We performed microdosimetric measurements with a novel solid-state, silicon-on-insulator microdosimeter in a clinical spot-scanning proton beam of small spot size and unmodified beam current. For all of the proton field sizes and energies considered, the measurements of y¯D were in agreement with expected trends. Furthermore, we obtained measurements with a spatial resolution of 10 µm in the beam direction. This spatial resolution greatly exceeded that possible with a conventional gaseous tissue-equivalent proportional counter and allowed us to perform a high-resolution investigation within the Bragg peak region. The MicroPlus probe is therefore suitable for applications in proton radiotherapy.

Characterization of proton pencil beam scanning and passive beam using a high spatial resolution solid-state microdosimeter.

PURPOSE: This work aims to characterize a proton pencil beam scanning (PBS) and passive double scattering (DS) systems as well as to measure parameters relevant to the relative biological effectiveness (RBE) of the beam using a silicon on insulator (SOI) microdosimeter with well-defined 3D sensitive volumes (SV). The dose equivalent downstream and laterally outside of a clinical PBS treatment field was assessed and compared to that of a DS beam. METHODS: A novel silicon microdosimeter with well-defined 3D SVs was used in this study. It was connected to low noise electronics, allowing for detection of lineal energies as low as 0.15 keV/µm. The microdosimeter was placed at various depths in a water phantom along the central axis of the proton beam, and at the distal part of the spread-out Bragg peak (SOBP) in 0.5 mm increments. The RBE values of the pristine Bragg peak (BP) and SOBP were derived using the measured microdosimetric lineal energy spectra as inputs to the modified microdosimetric kinetic model (MKM). Geant4 simulations were performed in order to verify the calculated depth-dose distribution from the treatment planning system (TPS) and to compare the simulated dose-mean lineal energy to the experimental results. RESULTS: For a 131 MeV PBS spot (124.6 mm R90 range in water), the measured dose-mean lineal energy yD¯ increased from 2 keV/µm at the entrance to 8 keV/µm in the BP, with a maximum value of 10 keV/µm at the distal edge. The derived RBE distribution for the PBS beam slowly increased from 0.97 ± 0.14 at the entrance to 1.04 ± 0.09 proximal to the BP, then to 1.1 ± 0.08 in the BP, and steeply rose to 1.57 ± 0.19 at the distal part of the BP. The RBE distribution for the DS SOBP beam was approximately 0.96 ± 0.16 to 1.01 ± 0.16 at shallow depths, and 1.01 ± 0.16 to 1.28 ± 0.17 within the SOBP. The RBE significantly increased from 1.29 ± 0.17 to 1.43 ± 0.18 at the distal edge of the SOBP. CONCLUSIONS: The SOI microdosimeter with its well-defined 3D SV has applicability in characterizing proton radiation fields and can measure relevant physical parameters to model the RBE with submillimeter spatial resolution. It has been shown that for a physical dose of 1.82 Gy at the BP, the derived RBE based on the MKM model increased from 1.14 to 1.6 in the BP and its distal part. Good agreement was observed between the experimental and simulation results, confirming the potential application of SOI microdosimeter with 3D SV for quality assurance in proton therapy.

Development of a large-area silicon α-particle detector.

Circular ion-implanted silicon detector of α-particles with a large, 5-cm(2), sensitive area has been developed. An advantage of the detector is that the detector surface is easily cleanable with chemicals. The hardened surface of the detector shows no signs of deterioration of the spectroscopic and electrical characteristics upon repeated cleaning. The energy resolution along the diameters of the detector was (1.0±0.1)% for the 5.486-MeV α-particles. Detailed tests of the charge collection efficiency and uniformity of the detector entrance window were also performed with a 5.5-MeV He(2+) microbeam.

A comparison of X-ray and proton beam low energy secondary electron track structures using the low energy models of Geant4.

PURPOSE: Lethal cell damage by ionising radiation is generally initiated by the formation of complex strand breaks, resulting from ionisation clusters in the DNA molecule. A better understanding of the effect of the distribution of ionisation clusters within the cell and particularly in regard to DNA segments could be beneficial to radiation therapy treatment planning. Low energy X-rays generate an abundance of low energy electrons similar to that associated with MeV protons. The study and comparison of the track structure of photon and proton beams could permit the substitution of photon microbeams for single cell ion irradiations at proton facilities used to predict the relative biological effectiveness (RBE) of charged particle fields. MATERIALS AND METHODS: The track structure of X-ray photons is compared with proton pencil beams in voxels of approximate DNA strand size (2 × 2 × 5 nm). The Very Low Energy extension models of the Monte Carlo simulation toolkit GEometry ANd Tracking 4 (Geant4) is used. Simulations were performed in a water phantom for an X-ray and proton beam of energies 100 keV and 20 MeV, respectively. RESULTS: The track structure of the photon and proton beams are evaluated using the ionisation cluster size distribution as well as the radial dose deposition of the beam. CONCLUSIONS: A comparative analysis of the ionisation cluster distribution and radial dose deposition obtained is presented, which suggest that low energy X-rays could produce similar ionisation cluster distributions to MeV protons on the DNA scale of size at depths greater than ∼10 µm and at distances greater than ∼1 µm from the beam centre. Here the ionisation cluster size for each beam is less than ∼100. The radial dose deposition is also approximately equal at large depths and at distances greater than 10 µm from the beam centre.