Impact of irradiation setup in proton spot scanning brain therapy on organ doses from secondary radiation.

A Monte Carlo model of a proton spot scanning pencil beam was used to simulate organ doses from secondary radiation produced from brain tumour treatments delivered with either a lateral field or a vertex field to one adult and one paediatric patient. Absorbed doses from secondary neutrons, photons and protons and neutron equivalent doses were higher for the vertex field in both patients, but the differences were low in absolute terms. Absorbed doses ranged between 0.1 and 43 µGy.Gy-1 in both patients with the paediatric patient receiving higher doses. The neutron equivalent doses to the organs ranged between 0.5 and 141 µSv.Gy-1 for the paediatric patient and between 0.2 and 134 µSv.Gy-1 for the adult. The highest neutron equivalent dose from the entire treatment was 7 mSv regardless of field setup and patient size. The results indicate that different field setups do not introduce large absolute variations in out-of-field doses produced in patients undergoing proton pencil beam scanning of centrally located brain tumours.

Out-of-field doses from secondary radiation produced in proton therapy and the associated risk of radiation-induced cancer from a brain tumor treatment.

PURPOSE: To determine out-of-field doses produced in proton pencil beam scanning (PBS) therapy using Monte Carlo simulations and to estimate the associated risk of radiation-induced second cancer from a brain tumor treatment. METHODS: Simulations of out-of-field absorbed doses were performed with MCNP6 and benchmarked against measurements with tissue-equivalent proportional counters (TEPC) for three irradiation setups: two irradiations of a water phantom using proton energies of 78-147 MeV and 177-223 MeV, and one brain tumor irradiation of a whole-body phantom. Out-of-field absorbed and equivalent doses to organs in a whole-body phantom following a brain tumor treatment were subsequently simulated and used to estimate the risk of radiation-induced cancer. Additionally, the contribution of absorbed dose originating from radiation produced in the nozzle was calculated from simulations. RESULTS: Out-of-field absorbed doses to the TEPC ranged from 0.4 to 135 µGy/Gy. The average deviation between simulations and measurements of the water phantom irradiations was about 17%. The absorbed dose contribution from radiation produced in the nozzle ranged between 0 and 70% of the total dose; the contribution was however small in absolute terms. The absorbed and equivalent doses to the organs ranged between 0.2 and 60 µGy/Gy and 0.5-151 µSv/Gy. The estimated lifetime risk of radiation-induced second cancer was approximately 0.01%. CONCLUSIONS: The agreement of out-of-field absorbed doses between measurements and simulations was good given the sources of uncertainties. Calculations of out-of-field organ doses following a brain tumor treatment indicated that proton PBS therapy of brain tumors is associated with a low risk of radiation-induced cancer.

Organ doses from a proton gantry-mounted cone-beam computed tomography system characterized with MCNP6 and GATE.

PURPOSE: To determine organ doses from a proton gantry-mounted cone-beam computed tomography (CBCT) system using two Monte Carlo codes and to study the influence on organ doses from different acquisition modes and repeated imaging. METHODS: The CBCT system was characterized with MCNP6 and GATE using measurements of depth doses in water and spatial profiles in air. The beam models were validated against absolute dose measurements and used to simulate organ doses from CBCT imaging with head, thorax and pelvis protocols. Anterior and posterior 190° scans were simulated and the resulting organ doses per mAs were compared to those from 360° scans. The influence on organ doses from repeated imaging with different imaging schedules was also investigated. RESULTS: The agreement between MCNP6, GATE and measurements with regard to depth doses and beam profiles was within 4% for all protocols and the corresponding average agreement in absolute dose validation was 4%. Absorbed doses for in-field organs from 360° scans ranged between 6 and 8 mGy, 15-17 mGy and 24-54 mGy for the head, thorax and pelvis protocols, respectively. Cumulative organ doses from repeated CBCT imaging ranged between 0.04 and 0.32 Gy for weekly imaging and 0.2-1.6 Gy for daily imaging. The anterior scans resulted in an average increase in dose per mAs of 24% to the organs of interest relative to the 360° scan, while the posterior scan showed a 37% decrease. CONCLUSIONS: A proton gantry-mounted CBCT system was accurately characterized with MCNP6 and GATE. Organ doses varied greatly depending on acquisition mode, favoring posterior scans.

Depth absorbed dose and LET distributions of therapeutic 1H, 4He, 7Li, and 12C beams.

The depth absorbed dose and LET (linear energy transfer) distribution of different ions of clinical interest such as 1H, 4He, 7Li, and 12C ions have been investigated using the Monte Carlo code SHIELD-HIT. The energies of the projectiles correspond to ranges in water and soft tissue of approximately 260 mm. The depth dose distributions of the primary particles and their secondaries have been calculated and separated with regard to their low and high LET components. A LET value below 10 eV/nm can generally be regarded as low LET and sparsely ionizing like electrons and photons. The high LET region may be assumed to start at 20 eV/nm where on average two double-strand breaks can be formed when crossing the periphery of a nucleosome, even though strictly speaking the LET limits are not sharp and ought to vary with the charge and mass of the ion. At the Bragg peak of a monoenergetic high energy proton beam, less than 3% of the total absorbed dose is comprised of high LET components above 20 eV/nm. The high LET contribution to the total absorbed dose in the Bragg peak is significantly larger with increasing ion charge as a natural result of higher stopping power and lower range straggling. The fact that the range straggling and multiple scattering are reduced by half from hydrogen to helium increases the possibility to accurately deposit only the high LET component in the tumor with negligible dose to organs at risk. Therefore, the lateral penumbra is significantly improved and the higher dose gradients of 7Li and 12C ions both longitudinally and laterally will be of major advantage in biological optimized radiation therapy. With increasing charge of the ion, the high LET absorbed dose in the beam entrance and the plateau regions where healthy normal tissues are generally located is also increased. The dose distribution of the high LET components in the 7Li beam is only located around the Bragg peak, characterized by a Gaussian-type distribution. Furthermore, the secondary particles produced by high energy 7Li ions in tissuelike media have mainly low LET character both in front of and beyond the Bragg peak.

Design of a fast multileaf collimator for radiobiological optimized IMRT with scanned beams of photons, electrons, and light ions.

Intensity modulated radiation therapy is rapidly becoming the treatment of choice for most tumors with respect to minimizing damage to the normal tissues and maximizing tumor control. Today, intensity modulated beams are most commonly delivered using segmental multileaf collimation, although an increasing number of radiation therapy departments are employing dynamic multileaf collimation. The irradiation time using dynamic multileaf collimation depends strongly on the nature of the desired dose distribution, and it is difficult to reduce this time to less than the sum of the irradiation times for all individual peak heights using dynamic leaf collimation [Svensson et al., Phys. Med. Biol. 39, 37-61 (1994)]. Therefore, the intensity modulation will considerably increase the total treatment time. A more cost-effective procedure for rapid intensity modulation is using narrow scanned photon, electron, and light ion beams in combination with fast multileaf collimator penumbra trimming. With this approach, the irradiation time is largely independent of the complexity of the desired intensity distribution and, in the case of photon beams, may even be shorter than with uniform beams. The intensity modulation is achieved primarily by scanning of a narrow elementary photon pencil beam generated by directing a narrow well focused high energy electron beam onto a thin bremsstrahlung target. In the present study, the design of a fast low-weight multileaf collimator that is capable of further sharpening the penumbra at the edge of the elementary scanned beam has been simulated, in order to minimize the dose or radiation response of healthy tissues. In the case of photon beams, such a multileaf collimator can be placed relatively close to the bremsstrahlung target to minimize its size. It can also be flat and thin, i.e., only 15-25 mm thick in the direction of the beam with edges made of tungsten or preferably osmium to optimize the sharpening of the penumbra. The low height of the collimator will minimize edge scatter from glancing incidence. The major portions of the collimator leafs can then be made of steel or even aluminum, so that the total weight of the multileaf collimator will be as low as 10 kg, which may even allow high-speed collimation in real time in synchrony with organ movements. To demonstrate the efficiency of this collimator design in combination with pencil beam scanning, optimal radiobiological treatments of an advanced cervix cancer were simulated. Different geometrical collimator designs were tested for bremsstrahlung, electron, and light ion beams. With a 10 mm half-width elementary scanned photon beam and a steel collimator with tungsten edges, it was possible to make as effective treatments as obtained with intensity modulated beams of full resolution, i.e., here 5 mm resolution in the fluence map. In combination with narrow pencil beam scanning, such a collimator may provide ideal delivery of photons, electrons, or light ions for radiation therapy synchronized to breathing and other organ motions. These high-energy photon and light ion beams may allow three-dimensional in vivo verification of delivery and thereby clinical implementation of the BioArt approach using Biologically Optimized three-dimensional in vivo predictive Assay based adaptive Radiation Therapy [Brahme, Acta Oncol. 42, 123-126 (2003)].

Simulation of secondary particle production and absorbed dose to tissue in light ion beams.

During radiation therapy with an ion beam, the production of secondary particles like neutrons, protons and heavier ions contribute to the dose delivered to tumour and healthy tissues outside the treated volume. Also, the secondary particles leaving the patient are of interest for radiation background around the ion-therapy facility. Calculations of secondary particle production and the dose absorbed by water, soft tissue and a multi-material phantom simulating the heterogeneous media of the patient body were performed for protons, helium, lithium and carbon ions in the energy range up to 400 MeV u(-1). The Monte Carlo code SHIELD-HIT for transport of protons and light ions in tissue-like media was used in these studies. The neutron ambient dose-equivalent, H*(10), was determined for neutrons leaving the water phantom irradiated with different light ion beams. The comparison of calculated secondary particle production in the water and PMMA phantoms irradiated with helium and carbon ions shows satisfactory agreement with experimental data.

Radiation transport calculations for 50 MV photon therapy beam using the Monte Carlo code GEANT4.

A new thin transmission target technique for fast dose delivery using narrow scanned photon beams has been developed. High-energy, 50-100 MeV, electron beams of low emittance incident on thin low-Z targets produce narrow and intense high-energy bremsstrahlung beams. However, electrons transmitted through the target are bent from the therapeutic beam by a purging magnet and have to be effectively absorbed in a dedicated electron collector. The electron-photon transport through a treatment head has been studied using the Monte Carlo simulation toolkit Geant4. The Geant4 electromagnetic physics processes have been compared with experimental data of radial dose profiles. The differences between calculated and measured radial dose distributions are approximately 2-10%. Preliminary investigations of the collector design have been carried out in order to minimise secondary electron and photon contamination of the therapeutic beam. The toolkit presented here is promising for further development of narrow photon beam therapy.

Cellular parameters and RBE-LET dependences for modelling heavy-ion radiotherapy.

Sets of four parameters (m, E0, sigma0 and kappa) of the cellular track structure model of Katz have been fitted to recently published data concerning human melanoma (AA) and mammalian (V79) cells exposed to a variety of lighter ions and to mixed ion-Co60 and ion-ion irradiation. Using these parameters, model predictions of V79 survival were verified against experimental data. RBE-LET dependences were calculated and compared with experimental data obtained for V79 cells after exposure to 3He, 12C and 20Ne ion beams. The presented track-segment approach used in track structure calculations, while satisfactory for heavier ions, may be of limited value for predicting the RBE-LET dependence of proton and helium radiotherapy beams in regions close to the distal range of these particles. We discuss the predictive capability of this model and propose standards in reporting cellular radiobiology data for application in modelling heavy ion beam radiotherapy.

Ion beam transport in tissue-like media using the Monte Carlo code SHIELD-HIT.

The development of the Monte Carlo code SHIELD-HIT (heavy ion transport) for the simulation of the transport of protons and heavier ions in tissue-like media is described. The code SHIELD-HIT, a spin-off of SHIELD (available as RSICC CCC-667), extends the transport of hadron cascades from standard targets to that of ions in arbitrary tissue-like materials, taking into account ionization energy-loss straggling and multiple Coulomb scattering effects. The consistency of the results obtained with SHIELD-HIT has been verified against experimental data and other existing Monte Carlo codes (PTRAN, PETRA), as well as with deterministic models for ion transport, comparing depth distributions of energy deposition by protons, 12C and 20Ne ions impinging on water. The SHIELD-HIT code yields distributions consistent with a proper treatment of nuclear inelastic collisions. Energy depositions up to and well beyond the Bragg peak due to nuclear fragmentations are well predicted. Satisfactory agreement is also found with experimental determinations of the number of fragments of a given type, as a function of depth in water, produced by 12C and 14N ions of 670 MeV u(-1), although less favourable agreement is observed for heavier projectiles such as 16O ions of the same energy. The calculated neutron spectra differential in energy and angle produced in a mimic of a Martian rock by irradiation with 12C ions of 290 MeV u(-1) also shows good agreement with experimental data. It is concluded that a careful analysis of stopping power data for different tissues is necessary for radiation therapy applications, since an incorrect estimation of the position of the Bragg peak might lead to a significant deviation from the prescribed dose in small target volumes. The results presented in this study indicate the usefulness of the SHIELD-HIT code for Monte Carlo simulations in the field of light ion radiation therapy.

Secondary particle production in tissue-like and shielding materials for light and heavy ions calculated with the Monte-Carlo code SHIELD-HIT.

The Monte Carlo code SHIELD has been modified into a version named SHIELD-HIT which extends the transport of hadron cascades in shielding materials to that of ions in tissue-like materials, and includes ion energy-loss straggling, multiple scattering, track-length calculations and production of secondary particles, which includes all generations, for ion interactions with the media. Calculations using SHIELD-HIT have been performed for 1H, 12C and 26Fe ions with energies up to 1000 MeV/u transported through water, soft tissue and aluminium. These have been validated by comparing Monte Carlo results with experimental data and results from other Monte Carlo codes for ion transport. Good agreement has been found for depth-dose distributions of protons and 12C ions in water up to depths well beyond the Bragg peak, where nuclear fragmentation effects dominate and for the production of secondary particles at different depths. Detailed track-length fluence spectra of secondary particles have been calculated for various combinations of projectiles and targets of interest for space radiation and radiotherapy applications. The secondary particle spectra in water from carbon ions have been used for calculations of stopping-power ratios for ionization chamber dosimetry, confirming the values recommended by the IAEA Code of Practice for radiotherapy dosimetry with heavy ions.

Simulations of microdosimetric quantities with the Monte Carlo code FLUKA for carbon ions at therapeutic energies.

PURPOSE: Microdosimetric quantities can be used to estimate the biological effectiveness of radiation fields. This study evaluates the capability of the general-purpose Monte Carlo code FLUKA to simulate microscopic patterns of energy depositions for mixed radiation fields which are created by carbon ions at therapeutic energies in phantoms. MATERIALS AND METHODS: Measured lineal energy spectra and linear energy transfer (LET) spectra produced by carbon ions of about 300 MeV/n at different depths in phantoms representing human tissue were chosen from published literature and were compared with results from simulations of the measurement set-ups with FLUKA. RESULTS: Simulations of the dose-weighted lineal energy spectra yd(y) and dose-weighted LET spectra describe the main features of the respective measured spectra. All simulated frequency mean and dose mean lineal energy values are, respectively, within 21% and 11% of the measured ones. A slight underestimation of fragment fluences is notable. It is shown that the simultaneous detection of several charged fragments in the TEPC ('V effect') has considerable impact on the measured lineal energy spectra of fragments. CONCLUSIONS: Agreement between measurements and FLUKA results is encouraging and shows that FLUKA can predict microdosimetric spectra of mixed radiation fields created by therapeutic carbon ions in phantoms reasonably well.

A Monte Carlo evaluation of carbon and lithium ions dose distributions in water.

PURPOSE: To compare dose distributions on the central- and off-axis for (12)C and (7)Li ion beams simulated by the codes SHIELD-HIT (Heavy Ion Transport) and FLUKA (FLUKtuierende KAskade), and compare with experimental data for 300 MeV/u (12)C and 185 MeV/u (7)Li ion beams. MATERIALS AND METHODS: The general purpose Monte Carlo codes, SHIELD-HIT10 and FLUKA 2008.3d.1 were used for the ion dose distribution calculations. SHIELD-HIT transports hadrons and atomic nuclei of arbitrary charge and mass number in an energy range from 1 keV/u up to 1 GeV/u. Similarly, FLUKA transports charged hadrons in an energy range from 100 keV up to 20 TeV. Neutrons are transported down to thermal energies in both codes. Inelastic nuclear interactions are modelled in SHIELD-HIT by the Many Stage Dynamical Model (MSDM), whereas in FLUKA the Pre-Equilibrium Approach to Nuclear Thermalisation (PEANUT) package which includes a Generalized Intra-Nuclear Cascade model was used. RESULTS: The dose distributions in water irradiated with 300 MeV/u (12)C and 185 MeV/u (7)Li ion beams were simulated with the two codes. Studies were performed of the energy deposition both on the central axis and at lateral distances up to 10 cm off-axis. The dose distributions calculated by SHIELD-HIT and FLUKA were compared with published experimental data. The dose mean lineal energy [Formula: see text], frequency mean lineal energy [Formula: see text], dose mean specific energy [Formula: see text], and frequency mean specific energy [Formula: see text] were calculated with the ion track-structure code PITS99 (Positive Ion Track Structure 99), coupled with the electron code KURBUC for the primary and secondary ions average energies at 1 mm before the Bragg peak. CONCLUSION: The Monte Carlo codes show good agreement with experimental results for off-axis dose distributions. The disagreements in the Bragg peak region for the central-axis dose distributions imply that further improvements especially in the nuclear interaction models are required to increase the accuracy of the codes.

Evaluation of nuclear reaction cross-sections and fragment yields in carbon beams using the SHIELD-HIT Monte Carlo code. Comparison with experiments.

In light ion therapy, the knowledge of the spectra of both primary and secondary particles in the target volume is needed in order to accurately describe the treatment. The transport of ions in matter is complex and comprises both atomic and nuclear processes involving primary and secondary ions produced in the cascade of events. One of the critical issues in the simulation of ion transport is the modeling of inelastic nuclear reaction processes, in which projectile nuclei interact with target nuclei and give rise to nuclear fragments. In the Monte Carlo code SHIELD-HIT, inelastic nuclear reactions are described by the Many Stage Dynamical Model (MSDM), which includes models for the different stages of the interaction process. In this work, the capability of SHIELD-HIT to simulate the nuclear fragmentation of carbon ions in tissue-like materials was studied. The value of the parameter κ, which determines the so-called freeze-out volume in the Fermi break-up stage of the nuclear interaction process, was adjusted in order to achieve better agreement with experimental data. In this paper, results are shown both with the default value κ = 1 and the modified value κ = 10 which resulted in the best overall agreement. Comparisons with published experimental data were made in terms of total and partial charge-changing cross-sections generated by the MSDM, as well as integral and differential fragment yields simulated by SHIELD-HIT in intermediate and thick water targets irradiated with a beam of 400 MeV u(-1) (12)C ions. Better agreement with the experimental data was in general obtained with the modified parameter value (κ = 10), both on the level of partial charge-changing cross-sections and fragment yields.

Secondary absorbed doses from light ion irradiation in anthropomorphic phantoms representing an adult male and a 10 year old child.

Secondary organ absorbed doses were calculated by Monte Carlo simulations with the SHIELD-HIT07 code coupled with the mathematical anthropomorphic phantoms CHILD-HIT and ADAM-HIT. The simulated irradiations were performed with primary (1)H, (4)He, (7)Li, (12)C and (16)O ion beams in the energy range 100-400 MeV/u which were directly impinging on the phantoms, i.e. approximating scanned beams, and with a simplified beamline for (12)C irradiation. The evaluated absorbed doses to the out-of-field organs were in the range 10(-6) to 10(-1) mGy per target Gy and with standard deviations 0.5-20%. While the contribution to the organ absorbed doses from secondary neutrons dominated in the ion beams of low atomic number Z, the produced charged fragments and their subsequent charged secondaries of higher generations became increasingly important for the secondary dose delivery as Z of the primary ions increased. As compared to the simulated scanned (12)C ion beam, the implementation of a simplified beamline for prostate irradiation with (12)C ions resulted in an increase of 2-50 times in the organ absorbed doses depending on the distance from the target volume. Comparison of secondary organ absorbed doses delivered by (1)H and (12)C beams showed smaller differences when the RBE for local tumor control of the ions was considered and normalization to the RBE-weighted dose to the target was performed.