Evaluation of monte carlo to support commissioning of the treatment planning system of new pencil beam scanning proton therapy facilities.

Objective. To demonstrate the potential of Monte Carlo (MC) to support the resource-intensive measurements that comprise the commissioning of the treatment planning system (TPS) of new proton therapy facilities.Approach. Beam models of a pencil beam scanning system (Varian ProBeam) were developed in GATE (v8.2), Eclipse proton convolution superposition algorithm (v16.1, Varian Medical Systems) and RayStation MC (v12.0.100.0, RaySearch Laboratories), using the beam commissioning data. All models were first benchmarked against the same commissioning data and validated on seven spread-out Bragg peak (SOBP) plans. Then, we explored the use of MC to optimise dose calculation parameters, fully understand the performance and limitations of TPS in homogeneous fields and support the development of patient-specific quality assurance (PSQA) processes. We compared the dose calculations of the TPSs against measurements (DDTPSvs.Meas.) or GATE (DDTPSvs.GATE) for an extensive set of plans of varying complexity. This included homogeneous plans with varying field-size, range, width, and range-shifters (RSs) (n= 46) and PSQA plans for different anatomical sites (n= 11).Main results. The three beam models showed good agreement against the commissioning data, and dose differences of 3.5% and 5% were found for SOBP plans without and with RSs, respectively. DDTPSvs.Meas.and DDTPSvs.GATEwere correlated in most scenarios. In homogeneous fields the Pearson's correlation coefficient was 0.92 and 0.68 for Eclipse and RayStation, respectively. The standard deviation of the differences between GATE and measurements (±0.5% for homogeneous and ±0.8% for PSQA plans) was applied as tolerance when comparing TPSs with GATE. 72% and 60% of the plans were within the GATE predicted dose difference for both TPSs, for homogeneous and PSQA cases, respectively.Significance. Developing and validating a MC beam model early on into the commissioning of new proton therapy facilities can support the validation of the TPS and facilitate comprehensive investigation of its capabilities and limitations.

Development of optimised tissue-equivalent materials for proton therapy.

Objective. In proton therapy there is a need for proton optimised tissue-equivalent materials as existing phantom materials can produce large uncertainties in the determination of absorbed dose and range measurements. The aim of this work is to develop and characterise optimised tissue-equivalent materials for proton therapy.Approach. A mathematical model was developed to enable the formulation of epoxy-resin based tissue-equivalent materials that are optimised for all relevant interactions of protons with matter, as well as photon interactions, which play a role in the acquisition of CT numbers. This model developed formulations for vertebra bone- and skeletal muscle-equivalent plastic materials. The tissue equivalence of these new materials and commercial bone- and muscle-equivalent plastic materials were theoretical compared against biological tissue compositions. The new materials were manufactured and characterised by their mass density, relative stopping power (RSP) measurements, and CT scans to evaluate their tissue-equivalence.Main results. Results showed that existing tissue-equivalent materials can produce large uncertainties in proton therapy dosimetry. In particular commercial bone materials showed to have a relative difference up to 8% for range. On the contrary, the best optimised formulations were shown to mimic their target human tissues within 1%-2% for the mass density and RSP. Furthermore, their CT-predicted RSP agreed within 1%-2% of the experimental RSP, confirming their suitability as clinical phantom materials.Significance. We have developed a tool for the formulation of tissue-equivalent materials optimised for proton dosimetry. Our model has enabled the development of proton optimised tissue-equivalent materials which perform better than existing tissue-equivalent materials. These new materials will enable the advancement of clinical proton phantoms for accurate proton dosimetry.

Determination of beam quality correction factors for the Roos plane-parallel ionisation chamber exposed to very high energy electron (VHEE) beams using Geant4.

Detailed characterisation of the Roos secondary standard plane-parallel ionisation chamber has been conducted in a novel 200 MeV Very High Energy Electron (VHEE) beam with reference to the standard 12 MeV electron calibration beam used in our experimental work. Stopping-power-ratios and perturbation factors have been determined for both beams and used to calculated the beam quality correction factor using the Geant4 general purpose MC code. These factors have been calculated for a variety of charged particle transport parameters available in Geant4 which were found to pass the Fano cavity test. Stopping-power-ratios for the 12 MeV electron calibration beam quality were found to agree within uncertainties to that quoted by current dosimetry protocols. Perturbation factors were found to vary by up-to 4% for the calibration beam depending on the parameter configuration, compared with only 0.8% for the VHEE beam. Beam quality correction factors were found to describe an approximately 10% lower dose than would be originally calculated if a beam quality correction were not accounted for. Moreover, results presented here largely resolve unphysical chamber measurements, such as collection efficiencies greater than 100%, and assist in the accurate determination of absorbed dose and ion recombination in secondary standard ionisation chambers.

Development of a heterogeneous phantom to measure range in clinical proton therapy beams.

PURPOSE: In particle therapy, determination of range by measurement or calculation can be a significant source of uncertainty. This work investigates the development of a bespoke Range Length Phantom (RaLPh) to allow independent determination of proton range in tissue. This phantom is intended to be used as an audit device. METHOD: RaLPh was designed to be compact and allows different configurations of tissue substitute slabs, to facilitate measurement of range using radiochromic film. Fourteen RaLPh configurations were tested, using two types of proton fluence optimised water substitutes, two types of bone substitute, and one lung substitute slabs. These were designed to mimic different complex tissue interfaces. Experiments were performed using a 115 MeV mono-energetic scanning proton beam to investigate the proton range for each configuration. Validation of the measured film ranges was performed via Monte Carlo simulations and ionisation chamber measurements. The phantom was then assessed as an audit device, by comparing film measurements with Treatment Planning System (TPS) predicted ranges. RESULTS: Varying the phantom slab configurations allowed for measurable range differences, and the best combinations of heterogeneous material gave agreement between film and Monte Carlo on average within 0.2% and on average within 0.3% of ionisation chamber measurements. Results against the TPS suggest a material density override is currently required to enable the phantom to be an audit device. CONCLUSION: This study found that a heterogeneous phantom with radiochromic film can provide range verification as part of a dedicated audit for clinical proton therapy beams.

A Geant4 Fano test for novel very high energy electron beams.

Objective.The boundary crossing algorithm available in Geant4 10.07-p01 general purpose Monte Carlo code has been investigated for a 12 and 200 MeV electron source by the application of a Fano cavity test.Approach.Fano conditions were enforced through all simulations whilst varying individual charged particle transport parameters which control particle step size, ionisation and single scattering.Main Results.At 12 MeV, Geant4 was found to return excellent dose consistency within 0.1% even with the default parameter configurations. The 200 MeV case, however, showed significant consistency issues when default physics parameters were employed with deviations from unity of more than 6%. The effect of the inclusion of nuclear interactions was also investigated for the 200 MeV beam and was found to return good consistency for a number of parameter configurations.Significance.The Fano test is a necessary investigation to ensure the consistency of charged particle transport available in Geant4 before detailed detector simulations can be conducted.

Identifying Surrogates for Heart and Ipsilateral Lung Dose to Guide Field Placement and Treatment Modality Selection during Virtual Simulation of Breast Radiotherapy.

AIMS: Virtual simulation (VSim) of tangential photon fields is a common method of field localisation for breast radiotherapy. Heart and ipsilateral lung dose is unknown until the dosimetric plan is produced. If heart and ipsilateral lung tolerance doses are exceeded, this can prolong the pre-treatment pathway, particularly if a change of technique is required. The aim of this study was to identify predictive surrogates for heart and ipsilateral lung dose during VSim to aid optimum field placement and treatment modality selection. MATERIALS AND METHODS: Computed tomography data from 50 patients referred for left breast/chest wall radiotherapy were retrospectively analysed (model-building cohort). The prescribed dose was 40.05 Gy in 15 fractions using a tangential photon technique. The heart and ipsilateral lung contours were duplicated, cropped to within the field borders and labelled heart-in-field (HIF) and ipsilateral lung-in-field (ILF). The percentage of HIF (%HIF) and ILF (%ILF) was calculated and correlated with mean heart dose (MHD) and volume of the ipsilateral lung receiving 18 Gy (V18Gy). Linear regression models were calculated. A validation cohort of 10 left- and 10 right-sided cases with an anterior supraclavicular fossa (SCF) field, and 10 left- and 10 right-sided cases including the internal mammary nodes using a wide tangential technique and anterior SCF field, tested the predictive model. Threshold values for %HIF and %ILF were calculated for clinically relevant MHD and ipsilateral lung V18Gy tolerance doses. RESULTS: For the model-building cohort, the median %HIF and MHD were 2.6 (0.4-16.7) and 2.3 (1.2-8) Gy. The median %ILF and ipsilateral lung V18Gy were 12.1 (2.8-33.6) and 12.6 (3.3-35) %. There was a statistically significant strong positive correlation of %HIF with MHD (r2 = 0.97, P < 0.0001) and of %ILF with ipsilateral lung V18Gy (r2 = 0.99, P < 0.0001). For the validation cohort, the median %HIF and MHD were 3.9 (0.6-8) and 2.5 (1.4-4.7) Gy. The median %ILF and ipsilateral lung V18Gy were 20.1 (12.4-32.0) and 20.9 (12.4-34.4) %. The validation cohort confirmed that %HIF and %ILF continue to be predictive surrogates for heart and ipsilateral lung dose during VSim of left- and right-sided cases when including the SCF ± internal mammary nodes with a three-field photon technique. DISCUSSION: The ability to VSim breast radiotherapy (±nodal targets) and accurately predict the heart and ipsilateral lung doses on the dosimetric plan will ensure that tolerance doses are not exceeded, and identify early in the pre-treatment pathway those cases where alternative techniques or modalities should be considered.

Pencil Beam Scanning Proton Therapy Case Selection for Paediatric Abdominal Neuroblastoma: Effects of Tumour Location and Bowel Gas.

AIMS: Pencil beam scanning (PBS) proton therapy is an increasingly used radiation modality for childhood malignancies due to its ability to minimise dose to surrounding organs. However, the dosimetry is extremely sensitive to anatomical and density changes. The aims of this study were to investigate if there is a dosimetric benefit or detriment with PBS for paediatric abdominal neuroblastoma, assess gastrointestinal air variability and its dosimetric consequences, plus identify if there are factors that could assist case selection for PBS referral. MATERIALS AND METHODS: Twenty neuroblastoma cases were double-planned with PBS and intensity-modulated arc therapy (IMAT). Cases were divided into unilateral, midline unilateral and midline bilateral locations in relation to the kidneys. Plans were recalculated after the gastrointestinal volume was simulated as air (Hounsfield Units -700) and water (Hounsfield Units 0), then compared with nominal plans (recalculated - nominal, ΔD). Forty-three weekly cone beam computed tomography scans were analysed to quantify gastrointestinal air variability during treatment. RESULTS: PBS reduced the mean dose to normal tissues at all tumour locations, particularly unilateral tumours. However, 15% had better dosimetry with IMAT, all of which were midline tumours. Increased gastrointestinal air caused significant compromises to PBS versus IMAT plans for midline tumours [median/maximum ΔD95% clinical target volume (CTV) -2.4%/-15.7% PBS versus 1.4%/0% IMAT, P = 0.003], whereas minimal impact was observed for unilateral tumours (ΔD95% CTV -0.5%/-1.9% PBS versus 0.5%/-0.5% IMAT, P = 0.008). D95% CTV was significantly decreased in PBS plans if planning target volume (PTV) ≥400 cm3 (median -4.1%, P = 0.001) or PTV extension ≥60% anterior to vertebral body (-2.1%, P = 0.002). A larger variation in gastrointestinal air was observed in patients treated under general anaesthesia (median 38.4%) versus awake (11.5%); P = 0.004. CONCLUSION: In this planning study, tumours at the unilateral location consistently showed improved dose reductions to normal tissue with minimal dose degradation from increased gastrointestinal air with PBS plans. Tumour location, PTV volume and anterior extension of PTV are useful characteristics in facilitating patient selection for PBS.

Retrospective Planning Study of Patients with Superior Sulcus Tumours Comparing Pencil Beam Scanning Protons to Volumetric-Modulated Arc Therapy.

AIMS: Twenty per cent of patients with non-small cell lung cancer present with stage III locally advanced disease. Precision radiotherapy with pencil beam scanning (PBS) protons may improve outcomes. However, stage III is a heterogeneous group and accounting for complex tumour motion is challenging. As yet, it remains unclear as to whom will benefit. In our retrospective planning study, we explored if patients with superior sulcus tumours (SSTs) are a select cohort who might benefit from this treatment. MATERIALS AND METHODS: Patients with SSTs treated with radical radiotherapy using four-dimensional planning computed tomography between 2010 and 2015 were identified. Tumour motion was assessed and excluded if greater than 5 mm. Photon volumetric-modulated arc therapy (VMAT) and PBS proton single-field optimisation plans, with and without inhomogeneity corrections, were generated retrospectively. Robustness analysis was assessed for VMAT and PBS plans involving: (i) 5 mm geometric uncertainty, with an additional 3.5% range uncertainty for proton plans; (ii) verification plans at maximal inhalation and exhalation. Comparative dosimetric and robustness analyses were carried out. RESULTS: Ten patients were suitable. The mean clinical target volume D95 was 98.1% ± 0.4 (97.5-98.8) and 98.4% ± 0.2 (98.1-98.9) for PBS and VMAT plans, respectively. All normal tissue tolerances were achieved. The same four PBS and VMAT plans failed robustness assessment. Inhomogeneity corrections minimally impacted proton plan robustness and made it worse in one case. The most important factor affecting target coverage and robustness was the clinical target volume entering the spinal canal. Proton plans significantly reduced the mean lung dose (by 21.9%), lung V5, V10, V20 (by 47.9%, 36.4%, 12.1%, respectively), mean heart dose (by 21.4%) and thoracic vertebra dose (by 29.2%) (P < 0.05). CONCLUSIONS: In this planning study, robust PBS plans were achievable in carefully selected patients. Considerable dose reductions to the lung, heart and thoracic vertebra were possible without compromising target coverage. Sparing these lymphopenia-related organs may be particularly important in this era of immunotherapy.

The challenge of ionisation chamber dosimetry in ultra-short pulsed high dose-rate Very High Energy Electron beams.

High dose-rate radiotherapy, known as FLASH, has been shown to increase the differential response between healthy and tumour tissue. Moreover, Very High Energy Electrons (VHEEs) provide more favourable dose distributions than conventional radiotherapy electron and photon beams. Plane-parallel ionisation chambers are the recommended secondary standard systems for clinical reference dosimetry of electrons, therefore chamber response to these high energy and high dose-per-pulse beams must be well understood. Graphite calorimetry, the UK primary standard, has been employed to measure the dose delivered from a 200 MeV pulsed electron beam. This was compared to the charge measurements of a plane-parallel ionisation chamber to determine the absolute collection efficiency and infer the ion recombination factor. The dose-per-pulse measured by the calorimeter ranged between 0.03 Gy/pulse and 5.26 Gy/pulse, corresponding to collection efficiencies between 97% and 4%, respectively. Multiple recombination models currently available have been compared with experimental results. This work is directly applicable to the development of standard dosimetry protocols for VHEE radiotherapy, FLASH radiotherapy and other high dose-rate modalities. However, the use of secondary standard ionisation chambers for the dosimetry of high dose-per-pulse VHEEs has been shown to require large corrections for charge collection inefficiency.

Edoxaban for treatment of venous thromboembolism in patient groups with different types of cancer: Results from the Hokusai VTE Cancer study.

BACKGROUND: The safety and efficacy of edoxaban and dalteparin is unclear for several cancer groups. METHODS: We evaluated the occurrence of the primary outcome in large cancer groups. The primary outcome was the composite of recurrent VTE or major bleeding over 12 months. RESULTS: In patients with gastrointestinal cancer, the primary outcome occurred in 19.4% patients given edoxaban and in 15.0% given dalteparin (risk difference [RD], 4.4%; 95%-CI, -4.1% to 12.8%). The corresponding rates for edoxaban and dalteparin were 10.4% and 10.7% for lung cancer (RD, -0.3%; 95%-CI, -10.0% to 9.5%), 13.6% and 12.5% for urogenital cancer (RD, 1.1; 95%-CI, -10.1-12.4), 3.1% and 11.7% for breast cancer (RD, -8.6; 95%-CI, -19.3-2.2), 8.9% and 10.9% for hematological malignancies (RD, -2.0; 95%-CI, -13.1-9.1), and 10.4% and 17.4% for gynecological cancer (RD, -7.0; 95%-CI, -19.8-5.7). In the subgroup of gastrointestinal cancer, edoxaban was associated with a 3.5% lower absolute risk of recurrent VTE and a 7.9% higher risk of major bleeding. CONCLUSION: Edoxaban has a similar risk-benefit ratio to dalteparin in most cancer groups. In those with gastrointestinal cancer, the lower risk of recurrent VTE and the advantages of oral therapy need to be balanced against the increased risk of major bleeding.

The impact of proton LET/RBE modeling and robustness analysis on base-of-skull and pediatric craniopharyngioma proton plans relative to VMAT.

Purpose: Pediatric craniopharyngioma, adult base-of-skull sarcoma and chordoma cases are all regarded as priority candidates for proton therapy. In this study, a dosimetric comparison between volumetric modulated arc therapy (VMAT) and intensity modulated proton therapy (IMPT) was first performed. We then investigated the impact of physical and biological uncertainties. We assessed whether IMPT plans remained dosimetrically superior when such uncertainty estimates were considered, especially with regards to sparing organs at risk (OARs).Methodology: We studied 10 cases: four chondrosarcoma, two chordoma and four pediatric craniopharyngioma. VMAT and IMPT plans were created according to modality-specific protocols. For IMPT, we considered (i) variable RBE modeling using the McNamara model for different values of (α/ß)x, and (ii) robustness analysis with ±3 mm set-up and 3.5% range uncertainties.Results: When comparing the VMAT and IMPT plans, the dosimetric advantages of IMPT were clear: IMPT led to reduced integral dose and, typically, improved CTV coverage given our OAR constraints. When physical robustness analysis was performed for IMPT, some uncertainty scenarios worsened the CTV coverage but not usually beyond that achieved by VMAT. Certain scenarios caused OAR constraints to be exceeded, particularly for the brainstem and optical chiasm. However, variable RBE modeling predicted even more substantial hotspots, especially for low values of (α/ß)x. Variable RBE modeling often prompted dose constraints to be exceeded for critical structures.Conclusion: For base-of-skull and pediatric craniopharyngioma cases, both physical and biological robustness analyses should be considered for IMPT: these analyses can substantially affect the sparing of OARs and comparisons against VMAT. All proton RBE modeling is subject to high levels of uncertainty, but the clinical community should remain cognizant possible RBE effects. Careful clinical and imaging follow-up, plus further research on end-of-range RBE mitigation strategies such as LET optimization, should be prioritized for these cohorts of proton patients.

Evaluation of the water-equivalence of plastic materials in low- and high-energy clinical proton beams.

The aim of this work was to evaluate the water-equivalence of new trial plastics designed specifically for light-ion beam dosimetry as well as commercially available plastics in clinical proton beams. The water-equivalence of materials was tested by computing a plastic-to-water conversion factor, [Formula: see text]. Trial materials were characterized experimentally in 60 MeV and 226 MeV un-modulated proton beams and the results were compared with Monte Carlo simulations using the FLUKA code. For the high-energy beam, a comparison between the trial plastics and various commercial plastics was also performed using FLUKA and Geant4 Monte Carlo codes. Experimental information was obtained from laterally integrated depth-dose ionization chamber measurements in water, with and without plastic slabs with variable thicknesses in front of the water phantom. Fluence correction factors, [Formula: see text], between water and various materials were also derived using the Monte Carlo method. For the 60 MeV proton beam, [Formula: see text] and [Formula: see text] factors were within 1% from unity for all trial plastics. For the 226 MeV proton beam, experimental [Formula: see text] values deviated from unity by a maximum of about 1% for the three trial plastics and experimental results showed no advantage regarding which of the plastics was the most equivalent to water. Different magnitudes of corrections were found between Geant4 and FLUKA for the various materials due mainly to the use of different nonelastic nuclear data. Nevertheless, for the 226 MeV proton beam, [Formula: see text] correction factors were within 2% from unity for all the materials. Considering the results from the two Monte Carlo codes, PMMA and trial plastic #3 had the smallest [Formula: see text] values, where maximum deviations from unity were 1%, however, PMMA range differed by 16% from that of water. Overall, [Formula: see text] factors were deviating more from unity than [Formula: see text] factors and could amount to a few percent for some materials.

Fluence correction factor for graphite calorimetry in a clinical high-energy carbon-ion beam.

The aim of this work is to develop and adapt a formalism to determine absorbed dose to water from graphite calorimetry measurements in carbon-ion beams. Fluence correction factors, [Formula: see text], needed when using a graphite calorimeter to derive dose to water, were determined in a clinical high-energy carbon-ion beam. Measurements were performed in a 290 MeV/n carbon-ion beam with a field size of 11 × 11 cm2, without modulation. In order to sample the beam, a plane-parallel Roos ionization chamber was chosen for its small collecting volume in comparison with the field size. Experimental information on fluence corrections was obtained from depth-dose measurements in water. This procedure was repeated with graphite plates in front of the water phantom. Fluence corrections were also obtained with Monte Carlo simulations through the implementation of three methods based on (i) the fluence distributions differential in energy, (ii) a ratio of calculated doses in water and graphite at equivalent depths and (iii) simulations of the experimental setup. The [Formula: see text] term increased in depth from 1.00 at the entrance toward 1.02 at a depth near the Bragg peak, and the average difference between experimental and numerical simulations was about 0.13%. Compared to proton beams, there was no reduction of the [Formula: see text] due to alpha particles because the secondary particle spectrum is dominated by projectile fragmentation. By developing a practical dose conversion technique, this work contributes to improving the determination of absolute dose to water from graphite calorimetry in carbon-ion beams.

Theoretical and experimental characterization of novel water-equivalent plastics in clinical high-energy carbon-ion beams.

Water-equivalent plastics are frequently used in dosimetry for experimental simplicity. This work evaluates the water-equivalence of novel water-equivalent plastics specifically designed for light-ion beams, as well as commercially available plastics in a clinical high-energy carbon-ion beam. A plastic- to-water conversion factor [Formula: see text] was established to derive absorbed dose to water in a water phantom from ionization chamber readings performed in a plastic phantom. Three trial plastic materials with varying atomic compositions were produced and experimentally characterized in a high-energy carbon-ion beam. Measurements were performed with a Roos ionization chamber, using a broad un-modulated beam of 11 × 11 cm2, to measure the plastic-to-water conversion factor for the novel materials. The experimental results were compared with Monte Carlo simulations. Commercially available plastics were also simulated for comparison with the plastics tested experimentally, with particular attention to the influence of nuclear interaction cross sections. The measured [Formula: see text] correction increased gradually from 0% at the surface to 0.7% at a depth near the Bragg peak for one of the plastics prepared in this work, while for the other two plastics a maximum correction of 0.8%-1.3% was found. Average differences between experimental and numerical simulations were 0.2%. Monte Carlo results showed that for polyethylene, polystyrene, Rando phantom soft tissue and A-150, the correction increased from 0% to 2.5%-4.0% with depth, while for PMMA it increased to 2%. Water-equivalent plastics such as, Plastic Water, RMI-457, Gammex 457-CTG, WT1 and Virtual Water, gave similar results where maximum corrections were of the order of 2%. Considering the results from Monte Carlo simulations, one of the novel plastics was found to be superior in comparison with the plastic materials currently used in dosimetry, demonstrating that it is feasible to tailor plastic materials to be water-equivalent for carbon ions specifically.

Investigation into the effects of high-Z nano materials in proton therapy.

High-Z nano materials have been previously shown to increase the amount of dose deposition within the tumour due to an increase in secondary electrons. This study evaluates the effects of high-Z nano materials in combination with protons, and the impact of proton energy, nanoparticle material and concentration. These effects were studied in silico through Monte Carlo simulation and experimentally through a phantom study, with particular attention to macroscale changes to the Bragg peak in the presence of nanoparticles. Three nanoparticle materials were simulated (gold, silver and platinum) at three concentrations (0.01, 0.1 and 6.5 mg ml(-1)) at two clinical proton energies (60 and 226 MeV). Simulations were verified experimentally using Gafchromic film measurements of gold nanoparticles suspended in water at two available high concentrations (5.5 mg ml(-1) and 1.1 mg ml(-1)). A significant change to Bragg peak features was evident, where at 226 MeV and 6.5 mg ml(-1), simulations of gold showed a 4.7 mm longitudinal shift of the distal edge and experimentally at 5.5 mg ml(-1), a shift of 2.2 mm. Simulations showed this effect to be material dependent, where platinum having the highest physical density caused the greatest shift with increasing concentration. A dose enhancement of 6% ± 0.05 and 5% ± 0.15 (60 MeV and 226 MeV, respectively) was evident with gold at 6.5 mg ml(-1) to water alone, compared to the 21% ± 0.53 observed experimentally as dose to film with 5.5 mg ml(-1) of gold nanoparticles suspended in water at 226 MeV. The introduction of nanoparticles has strong potential to enhance dose in proton therapy, however the changes to the Bragg peak distribution that occur with high concentrations need to be accounted for to ensure tumour coverage.

Photon small-field measurements with a CMOS active pixel sensor.

In this work the dosimetric performance of CMOS active pixel sensors for the measurement of small photon beams is presented. The detector used consisted of an array of 520 × 520 pixels on a 25 µm pitch. Dosimetric parameters measured with this sensor were compared with data collected with an ionization chamber, a film detector and GEANT4 Monte Carlo simulations. The sensor performance for beam profiles measurements was evaluated for field sizes of 0.5 × 0.5 cm(2). The high spatial resolution achieved with this sensor allowed the accurate measurement of profiles, beam penumbrae and field size under lateral electronic disequilibrium. Field size and penumbrae agreed within 5.4% and 2.2% respectively with film measurements. Agreements with ionization chambers better than 1.0% were obtained when measuring tissue-phantom ratios. Output factor measurements were in good agreement with ionization chamber and Monte Carlo simulation. The data obtained from this imaging sensor can be easily analyzed to extract dosimetric information. The results presented in this work are promising for the development and implementation of CMOS active pixel sensors for dosimetry applications.

Spatial distribution of Auger electrons emitted from internalised radionuclides in cancer cells: the photoresist autoradiography (PAR) method.

Microdosimetric evaluation of Auger electron-emitting radionuclides involves a detailed evaluation of energy deposition at a nanometre scale. To perform Monte Carlo modelling of such energy deposition, accurate information regarding the spatial distribution of the radionuclide is required. A recent addition to the methods for determining the spatial distribution of cellular internalised radionuclides is based on detection in a polymer photoresist (e.g. polymethyl methacralate), followed by atomic force microscopy analysis of the resultant 3D pattern. In comparison with present practice, the method offers greater spatial resolution and improved quantification. The volume of the pattern is proportional to the total dose, thereby permitting assessment of variability of accumulated activity, while the variation in depth across the pattern reflects the lateral spatial distribution in the local fluence per unit area. An added advantage is the similarity in response to ionising radiation of an organic polymer compared to that of biological material. A pattern in the resist from radiation emitted by a radionuclide treated cell gives additional spatial information about the energy deposited in the resist.

Dose ratio proton radiography using the proximal side of the Bragg peak.

PURPOSE: In recent years, there has been a movement toward single-detector proton radiography, due to its potential ease of implementation within the clinical environment. One such single-detector technique is the dose ratio method in which the dose maps from two pristine Bragg peaks are recorded beyond the patient. To date, this has only been investigated on the distal side of the lower energy Bragg peak, due to the sharp falloff. The authors investigate the limits and applicability of the dose ratio method on the proximal side of the lower energy Bragg peak, which has the potential to allow a much wider range of water-equivalent thicknesses (WET) to be imaged. Comparisons are made with the use of the distal side of the Bragg peak. METHODS: Using the analytical approximation for the Bragg peak, the authors generated theoretical dose ratio curves for a range of energy pairs, and then determined how an uncertainty in the dose ratio would translate to a spread in the WET estimate. By defining this spread as the accuracy one could achieve in the WET estimate, the authors were able to generate lookup graphs of the range on the proximal side of the Bragg peak that one could reliably use. These were dependent on the energy pair, noise level in the dose ratio image and the required accuracy in the WET. Using these lookup graphs, the authors investigated the applicability of the technique for a range of patient treatment sites. The authors validated the theoretical approach with experimental measurements using a complementary metal oxide semiconductor active pixel sensor (CMOS APS), by imaging a small sapphire sphere in a high energy proton beam. RESULTS: Provided the noise level in the dose ratio image was 1% or less, a larger spread of WETs could be imaged using the proximal side of the Bragg peak (max 5.31 cm) compared to the distal side (max 2.42 cm). In simulation, it was found that, for a pediatric brain, it is possible to use the technique to image a region with a square field equivalent size of 7.6 cm(2), for a required accuracy in the WET of 3 mm and a 1% noise level in the dose ratio image. The technique showed limited applicability for other patient sites. The CMOS APS demonstrated a good accuracy, with a root-mean-square-error of 1.6 mm WET. The noise in the measured images was found to be σ = 1.2% (standard deviation) and theoretical predictions with a 1.96σ noise level showed good agreement with the measured errors. CONCLUSIONS: After validating the theoretical approach with measurements, the authors have shown that the use of the proximal side of the Bragg peak when performing dose ratio imaging is feasible, and allows for a wider dynamic range than when using the distal side. The dynamic range available increases as the demand on the accuracy of the WET decreases. The technique can only be applied to clinical sites with small maximum WETs such as for pediatric brains.

Patient-specific stopping power calibration for proton therapy planning based on single-detector proton radiography.

A simple robust optimizer has been developed that can produce patient-specific calibration curves to convert x-ray computed tomography (CT) numbers to relative stopping powers (HU-RSPs) for proton therapy treatment planning. The difference between a digitally reconstructed radiograph water-equivalent path length (DRRWEPL) map through the x-ray CT dataset and a proton radiograph (set as the ground truth) is minimized by optimizing the HU-RSP calibration curve. The function of the optimizer is validated with synthetic datasets that contain no noise and its robustness is shown against CT noise. Application of the procedure is then demonstrated on a plastic and a real tissue phantom, with proton radiographs produced using a single detector. The mean errors using generic/optimized calibration curves between the DRRWEPL map and the proton radiograph were 1.8/0.4% for a plastic phantom and -2.1/ - 0.2% for a real tissue phantom. It was then demonstrated that these optimized calibration curves offer a better prediction of the water equivalent path length at a therapeutic depth. We believe that these promising results are suggestive that a single proton radiograph could be used to generate a patient-specific calibration curve as part of the current proton treatment planning workflow.