Proton Depth Dose Distribution Research Articles

Investigation of the effects of biomaterials on proton Bragg peak and secondary neutron production by the Monte Carlo method in the slab head phantom

Interest in proton therapy has increased in the last decade, as protons are effective to treat deeply located tumors, cause less damage to healthy tissue and allow controlling the energy to be transferred in a target-oriented manner (or energy transfer within target limits). It is known that secondary particles such as neutrons are produced by a result of nuclear interactions of protons with the target. Secondary neutrons can cause an uncontrolled dose increase in healthy tissue near the target site, and because they have a high radiobiological effectiveness, they raise the risk of secondary cancer. There are not enough studies examining the effect of biomaterials on secondary neutron production (SNP) in proton therapy. This study aims to investigate the effect of biomaterials used as implants instead of cranium in the skull on proton depth dose distribution and SNP with Monte Carlo-based PHITS code. Therefore, Bragg peaks and SNPs for 40–140 MeV energy protons were calculated and compared with the literature in a slab head phantom containing stainless steel, CoCrMo (CCM) alloy, alumina, polytetrafluoroethylene, Ti alloy, and NiTi alloy biomaterials used in cranioplasty. It was observed that the most compatible biomaterial compared to cranium for all energies is polytetrafluoroethylene. When polytetrafluoroethylene biomaterial was placed instead of the cranium in the skull, the Bragg peak position of the 100 MeV protons was decreased by 5.04% compared to that in the cranium. In this case, the energy absorbed in the polytetrafluoroethylene biomaterial increased by approximately 28% compared to the cranium, while it decreased by approx. 4% in the brain tissue. It was also observed that while SNP was 0.0501 in the cranium, it increased by almost 18% in PTFE.

3D Dosimetry Based on LiMgPO4 OSL Silicone Foils: Facilitating the Verification of Eye-Ball Cancer Proton Radiotherapy.

A direct verification of the three-dimensional (3D) proton clinical treatment plan prepared for tumor in the eyeball, using the Eclipse Ocular Proton Planning system (by Varian Medical Systems), has been presented. To achieve this, a prototype of the innovative two-dimensional (2D) circular silicone foils, made of a polymer with the embedded optically stimulated luminescence (OSL) material in powder form (LiMgPO4), and a self-developed optical imaging system, consisting of an illuminating light source and a high-sensitive CCD camera has been applied. A specially designed lifelike eyeball phantom has been used, constructed from 40 flat sheet LMP-based silicone foils stacked and placed together behind a spherical phantom made by polystyrene, all to reflect the curvature of the real eyeball. Two-dimensional OSL signals were captured and further analyzed from each single silicone foil after irradiation using a dedicated patient collimator and a 58.8 MeV modulated proton beam. The reconstructed 3D proton depth dose distribution matches very well with the clinical treatment plan, allowing for the consideration of the new OSL system for further 3D dosimetry applications within the proton radiotherapy area.

Simulation of dose distribution and secondary particle production in proton therapy of brain tumor.

The aim of this study is simulation of the proton depth-dose distribution and dose evaluation of secondary particles in proton therapy of brain tumor using the GEANT4 and FLUKA Monte Carlo codes. Proton therapy is a treatment method for variety of tumors such as brain tumor. The most important feature of high energy proton beams is the energy deposition as a Bragg curve and the possibility of creating the spread out Bragg peak (SOBP) for full coverage of the tumor. A spherical tumor with the radius of 1 cm in the brain is considered. A SNYDER head phantom has been irradiated with 30-130 MeV proton beam energy. A PMMA modulator wheel is used for covering the tumor. The simulations are performed using the GEANT4 and FLUKA codes. Using a modulator wheel, the Spread Out Bragg Peak longitudinally and laterally covers the tumor. Flux and absorbed dose of secondary particles produced by nuclear interactions of protons with elements in the head are considerably small compared to protons. Using 76.85 MeV proton beam and a modulator wheel, the tumor can be treated accurately in the 3-D, so that the distribution of proton dose in the surrounding tissues is very low. The results show that more than 99% of the total dose of secondary particles and protons is absorbed in the tumor.

Two-dimensional radiation dosimetry based on LiMgPO4 powder embedded into silicone elastomer matrix

Two-dimensional (2D) spatial radiation dosimetry based on optically stimulated luminescence (OSL) phenomena is presented. By embedding OSL active particles (LiMgPO4) into the transparent and flexible silicone elastomer matrix (polydimethylsiloxane silicone), the favorable dosimetric properties of the OSL material are exploited towards real 2D OSL signal. Direct measurement of the 2D OSL dose distribution using prototype flat foils, irradiated with beta radiation, stimulated with blue light (470 nm) and read out using a high-sensitive CCD camera has been obtained. Basic dosimetric parameters, including repeatability, dose-response, and fading has been measured. A separate experiment was dedicated to measure the real 2D proton depth dose distribution, using unmodulated and collimated 58.8 MeV proton beam used for proton radiotherapy at the IFJ PAN.

Patient-specific quality assurance for proton depth dose distribution using a multi-layer ionization chamber in a single-ring wobbling method.

The use of a multi-layer ionization chamber, Zebra, in patient-specific quality assurance (QA) for proton depth dose distributions in a single-ring wobbling method is investigated. The depth dose distributions measured using Zebra are compared with those calculated using the treatment planning system (TPS), XiO-M, and measured using an ionization chamber with a motorized water phantom system. Because the TPS only provides point doses, the average doses are calculated using in-house software. The detector size-corrected depth dose distributions are obtained by determining the average of the dose distributions from the TPS over a cylindrical region similar to the size of the Zebra detectors. The calculated depth dose distributions from the cases with a simple compensator shape are in good agreement with those obtained from the TPS without performing volume averaging; however, a 15% difference was shown when compared with those from the cases with a complex compensator shape. Then, the measurements are compared with the detector size-corrected depth dose distributions, showing an improved agreement within 3% for the highly steep dose gradient regions. Although there are some field size limitations, the Zebra system is a useful device for the fast measurement of patient-specific QA for depth dose distributions in wobbled proton beams. However, careful consideration is required for complex dose distribution fields, because the measurements obtained using Zebra cannot be directly compared to the depth dose distributions from the TPS owing to the finite detector size of the Zebra chamber.

Research Facility for Radiobiological Studies at the University Proton Therapy Dresden.

In order to take full advantage of proton radiotherapy, the biological effect of protons in normal and tumor tissue should be investigated and understood in detail. The ongoing discussion on variable relative biological effectiveness along the proton depth dose distribution (eg, Paganetti 2015), and also the administration of concomitant treatments, demands dedicated in vitro trials that prepare the translation into the clinics. Therefore, a setup for radiobiological studies and the corresponding dosimetry should be established that enables in vitro experiments at a horizontal proton beam and a clinical 6 MV photon linear accelerator (Linac) as reference. The experimental proton beam at the University Proton Therapy Dresden is characterized by high beam availability and reliability throughout the day in parallel to patient treatment. For cell irradiation, a homogeneous 10 × 10 cm2 proton field with an optional spread-out Bragg-peak can be formed. A water-filled phantom was installed that allows for precise positioning of different sample geometries along the proton path. Depth-dose profiles within the phantom and dose homogeneity over different cell samples were characterized for the proton beam and the photon reference source. A daily quality assurance protocol was implemented that provides absolute dose information required for significant and reproducible in vitro experiments. Cell survival test experiments were performed to demonstrate the feasibility of such experiments. In the experimental room of the University Proton Therapy Dresden, clinically relevant conditions for proton in vitro experiments have been realized. The established cell phantom and dosimetry facilitate irradiation in an aqueous environment and are transferable to other proton, photon and ion beam facilities. Precise positioning and easy exchange of cell samples, monitor unit-based dose delivery, and high beam availability allow for systematic in vitro experiments. The close vicinity to the radiotherapy and radiobiology departments provides access to clinical linacs and the interdisciplinary basis for further translational steps.

Optimization of beam arrangements in proton minibeam radiotherapy by cell survival simulations.

Proton minibeam radiotherapy using submillimeter beam dimensions allows to enhance tissue sparing in the entrance channel by spatial fractionation additionally to advantageous proton depth dose distribution. In the entrance channel, spatial fractionation leads to reduced side effects compared to conventional proton therapy. The submillimeter sized beams widen with depth due to small angle scattering and enable therefore, in contrary to x-ray microbeam radiation therapy (MRT), the homogeneous irradiation of a tumor. Proton minibeams can either be applied as planar minibeams or pencil shaped with an additional possibility to vary between a quadratic and a hexagonal arrangement for pencil minibeams. The purpose of this work is to deduce interbeam distances to achieve a homogeneous dose distribution for different tumor depths and tumor thicknesses. Furthermore, we aim for a better understanding of the sparing effect on the basis of surviving cells calculated by the linear-quadratic model. Two-dimensional dose distributions are calculated for proton minibeams of different shapes and arrangements. For a tumor in 10-15cm depth, treatment plans are calculated with initial beam size of σ0 =0.2mm in a water phantom. Proton minibeam depth dose distributions are finally converted into cell survival using a linear-quadratic model. Inter proton beam distances are maximized under the constraint of dose homogeneity in the tumor for tumor depths ranging from 4 to 15cm and thickness ranging from 0.5 to 10cm. Cell survival calculations for a 5cm thick tumor covered by 10cm healthy tissue show less cell death by up to 85%, especially in the superficial layers, while keeping the cell death in the tumor as in conventional therapy. In the entrance channel, the pencil minibeams result in higher cell survival in comparison to the planar minibeams while all proton minibeam irradiations show higher cell survival than conventional broadbeam irradiation. The deduced constraints for interbeam distances simplify treatment planning for proton minibeam radiotherapy applications in future studies. The cell survival results indicate that proton minibeam radiotherapy reduces side effects but keeps tumor control as in conventional proton therapy. It makes proton minibeam, especially pencil minibeam radiotherapy a potentially attractive new approach for radiation therapy.

A solar flare simulation and dosimetry facility at a proton therapy cyclotron

During extravehicular activities (EVA) astronauts are exposed to intense radiation from solar flare events (SFE). Hence, the radiation shielding efficacy of space suits, in particular the helmets and extra vehicular visor assembly (EVVA) are imperative to safety of astronauts and ultimate success of the space mission. At West German Proton Therapy Centre Essen (WPE) we have replicated the historical solar flare spectra by manipulating the treatment planning system (TPS) of the 230 MeV proton-therapy cyclotron and developed novel proton irradiation and dosimetry methods for the testing of space borne devices as mentioned above. We have used a single foil of radiochromic film (type EBT 2) to estimate the proton depth dose distribution in the human eye. The optimal thickness of EVVA (acryl glass) for the protection from solar flares was estimated to be 2.35 cm. A maximum SFE proton dose up to 20 Gy found to be well assessed using the EBT 2 films.

Fan‐beam intensity modulated proton therapy

This paper presents a concept for a proton therapy system capable of delivering intensity modulated proton therapy using a fan beam of protons. This system would allow present and future gantry-based facilities to deliver state-of-the-art proton therapy with the greater normal tissue sparing made possible by intensity modulation techniques. A method for producing a divergent fan beam of protons using a pair of electromagnetic quadrupoles is described and particle transport through the quadrupole doublet is simulated using a commercially available software package. To manipulate the fan beam of protons, a modulation device is developed. This modulator inserts or retracts acrylic leaves of varying thickness from subsections of the fan beam. Each subsection, or beam channel, creates what effectively becomes a beam spot within the fan area. Each channel is able to provide 0-255 mm of range shift for its associated beam spot, or stop the beam and act as an intensity modulator. Results of particle transport simulations through the quadrupole system are incorporated into the MCNPX Monte Carlo transport code along with a model of the range and intensity modulation device. Several design parameters were investigated and optimized, culminating in the ability to create topotherapy treatment plans using distal-edge tracking on both phantom and patient datasets. Beam transport calculations show that a pair of electromagnetic quadrupoles can be used to create a divergent fan beam of 200 MeV protons over a distance of 2.1 m. The quadrupole lengths were 30 and 48 cm, respectively, with transverse field gradients less than 20 T/m, which is within the range of water-cooled magnets for the quadrupole radii used. MCNPX simulations of topotherapy treatment plans suggest that, when using the distal edge tracking delivery method, many delivery angles are more important than insisting on narrow beam channel widths in order to obtain conformal target coverage. Overall, the sharp distal falloff of a proton depth-dose distribution was found to provide sufficient control over the dose distribution to meet objectives, even with coarse lateral resolution and channel widths as large as 2 cm. Treatment plans on both phantom and patient data show that dose conformity suffers when treatments are delivered from less than approximately ten angles. Treatment time for a sample prostate delivery is estimated to be on the order of 10 min, and neutron production is estimated to be comparable to that found for existing collimated systems. Fan beam proton therapy is a method of delivering intensity modulated proton therapy which may be employed as an alternative to magnetic scanning systems. A fan beam of protons can be created by a set of quadrupole magnets and modified by a dual-purpose range and intensity modulator. This can be used to deliver inversely planned treatments, with spot intensities optimized to meet user defined dose objectives. Additionally, the ability of a fan beam delivery system to effectively treat multiple beam spots simultaneously may provide advantages as compared to spot scanning deliveries.

The clinical impact of uncertainties in the mean excitation energy of human tissues during proton therapy

Uncertainties in the estimated mean excitation energies (I-values) needed for calculating proton stopping powers can be in the order of 10–15%, which introduces a fundamental limitation in the accuracy of proton range determination. Previous efforts have quantified shifts in proton depth dose distributions due to I-value uncertainties in water and homogenous tissue phantoms. This study is the first to quantify the clinical impact of I-value uncertainties on proton dose distributions within patient geometries. A previously developed Geant4 based Monte Carlo code was used to simulate a proton treatment plan for three patients (prostate, pancreases, and liver) with varying tissue I-values. A uniform variation study was conducted in which the tissue I-values were varied by ±5% and ±10% of the nominal values as well as a probabilistic variation study in which the I-values were randomly sampled according to a normal distribution with the mean equal to the nominal I-value and a standard deviation of 5 and 10% of the nominal values. Modification of tissue I-values impacted both the proton range and SOBP width. R90 range shifts up to 7.7 mm (4.4.%) and R80 range shifts up to 4.8 mm (1.9%) from the nominal range were recorded. Modulating the tissue I-values by 10% the nominal value resulted in up to a 3.5% difference mean dose in the target volumes and organs at risk compared to the nominal case. The range and dose differences were the largest for the deeper-seated prostate and pancreas cases. The treatments that were simulated with randomly sampled I-values resulted in range and dose differences that were generally within the upper and lower bounds set by the 10% uniform variations. This study demonstrated the impact of I-value uncertainties on patient dose distributions. Clearly, sub-millimeter precision in proton therapy would necessitate a reduction in I-value uncertainties to ensure an efficacious clinical outcome.

Variations in the RBE for Cell Killing Along the Depth-Dose Profile of a Modulated Proton Therapy Beam

Considerable evidence now exists to show that that the relative biological effectiveness (RBE) changes considerably along the proton depth-dose distribution, with progressively higher RBE values at the distal part of the modulated, or spread out Bragg peak (SOBP) and in the distal dose fall-off (DDF). However, the highly variable nature of the existing studies (with regards to cell lines, and to the physical properties and dosimetry of the various proton beams) precludes any consensus regarding the RBE weighting factor at any position in the depth-dose profile. We have thus conducted a systematic study on the variation in RBE for cell killing for two clinical modulated proton beams at Indiana University and have determined the relationship between the RBE and the dose-averaged linear energy transfer (LETd) of the protons at various positions along the depth-dose profiles. Clonogenic assays were performed on human Hep2 laryngeal cancer cells and V79 cells at various positions along the SOBPs of beams with incident energies of 87 and 200 MeV. There was a marked variation in the radiosensitivity of both cell lines along the SOBP depth-dose profile of the 87 MeV proton beam. Using Hep2 cells, the D(0.1) isoeffect dose RBE values (normalized against (60)Co) were 1.46 at the middle of SOBP, 2.1 at the distal end of the SOBP and 2.3 in the DDF. For V79 cells, the D(0.1) isoeffect RBE for the 87 MEV beam were 1.23 for the proximal end of the SOBP: 1.46 for the distal SOBP and 1.78 for the DDF. Similar D(0.1) isoeffect RBE values were found for Hep2 cells irradiated at various positions along the depth-dose profile of the 200 MeV beam. Our experimentally derived RBE values were significantly correlated (P = 0.001) with the mean LETd of the protons at the various depths, which confirmed that proton RBE is highly dependent on LETd. These in vitro data suggest that the RBE of the proton beam at certain depths is greater than 1.1, a value currently used in most treatment planning algorithms. Thus, the potential for increased cell killing and normal tissue damage in the distal regions of the proton SOBP may be greater than originally thought.

WE‐C‐BRB‐06: Clinical Impact of Uncertainties in the Mean Excitation Energy of Human Tissues during Proton Therapy

Purpose: Uncertainties in the estimated mean excitation energies (I‐value) needed forcalculating proton stopping power can be in the order of 10–15%, which introduces afundamental limitation in the accuracy of proton range determination. Previous efforts havequantified shifts in proton depth dose distributions due to I‐value uncertainties in homogenoustissue phantoms. This study is the first to quantify the clinical impact of I‐value uncertainties onproton dose distributions within patient geometries. Methods: A previously developed Geant4 based Monte Carlo code was used to simulate aproton treatment plan for prostate cancer with varying tissue I‐values. A total of five cases weresimulated using nominal I‐values as well as I‐values modified by ±5% and ±10% of the nominalvalues. Dose volume histograms were generated for the GTV, CTV, PTV and relevant organs‐at‐risk (OARs). Results: Modification of tissue I‐values impacted both the proton range and SOBP width. D90range shifts up to 4 mm from the nominal range were recorded whereas D80 range shiftsreached up to 2 mm. For an increase in I‐value of 10% of the nominal value, the increase inrange and SOBP width resulted in a 1.4% decrease in the CTV mean dose. Inversely, decreasing the I‐value by 10% increased the CTV mean dose by 0.8%. The difference in themean dose to the OARs was relatively small except for the rectum that differedby up to 5%. Conclusions: This study demonstrated that the impact of I‐value uncertainties on patient dosedistributions. Clearly, sub‐millimeter precision in proton therapy would necessitate reduction in I‐value uncertainties to ensure an efficacious clinical outcome.

A potential method for in vivo range verification in proton therapy treatment

Proton therapy potentially offers excellent dose conformality and reduction in integral dose. The superior dose distribution is, however, much more sensitive to the radiological depth along the beam path than for photon fields. Variations in this depth due to inaccurate planning calculation, setup uncertainty, respiration-induced organ motion, etc, could result in either an ‘undershooting’, missing the distal portion of the target volume entirely, or an ‘overshooting’, delivering the full prescription dose to the normal tissue beyond the target volume. In vivo dose verification plays an important role in the quality assurance of the treatments. The point dose measurements widely used for photon treatments are, however, insufficient for protons due to the particular characteristics of the proton depth–dose distribution. In this work, we explore a method for in vivo range verifications in proton treatments using range-modulated passive scattering fields. The method utilizes the time dependence of the dose distribution delivered by these fields. By measuring the time dependence of the dose rate at any point in the target volume, the residual range of the beam at this point can be obtained with millimeter accuracy.

Out‐of‐field dose equivalents delivered by proton therapy of prostate cancer

Measurements were performed to assess the dose equivalent outside a primary proton treatment field, using a silicon-on-insulator (SOI) microdosimeter. The SOI microdosimeter was placed on the surface of an anthropomorphic phantom and dose equivalents were determined as a function of lateral distance from a typical passively scattered and modulated prostate treatment field. Measurements were also completed within a polystyrene plate phantom as a function of depth for a distance of 5 cm from the field edge, as function of lateral distance from field edge at two different depths, and as a function of distance from the distal edge on the central beam axis. The dose equivalent at the surface of the anthropomorphic phantom decreases from 3.9 to 0.18 mSv/Gy when the lateral distance from the proton field edge increases from 2.5 to 60 cm. Measurements along the proton depth dose distribution at a constant distance of 5 cm from the primary field edge indicate a decrease in dose equivalent as a function of depth, with a 38% decrease relative to the surface dose at a depth of 5 cm in polystyrene. Measurements completed as a function of lateral distance from the primary field at two separate depths within polystyrene illustrate a convergence of the dose equivalent at approximately 20 cm from the primary field edge. Past the distal edge of the spread-out Bragg peak dose equivalents decrease exponentially for increasing distance, with an initial value of 1.6 mSv/Gy at 0.6 cm from the distal edge. Silicon microdosimetry measurements were also compared with published results obtained utilizing different measurement techniques. This study demonstrates the applicability of SOI microdosimetry in determining the dose equivalent outside proton treatment fields, and provides valuable information on the dose equivalent both at the surface and at depth experienced by prostate cancer patients treated with protons.

Application of an imaging plate to dose distribution measurement of proton beam

The linearity between proton dose to photostimulated luminescence was maintained between 0.0 to 1.3 cGy. Proton depth dose distributions measured by photostimulated luminescence and by Si diode in water were proportional.

A proton profile monitor using an amorphous silicon photodiode array

An amorphous silicon photodiode array originally manufactured for facsimile has been applied to an imaging system for proton beam measurements. A Gd/sub 2/O/sub 2/S phosphor sheet and a CsI(Tl) scintillator strip for proton-to-light conversion were tested to obtain good sensitivity. Proton depth dose distribution measurements for cancer therapy are presented. >

Degradation of the Bragg peak due to inhomogeneities

The rapid fall-off of dose at the end of range of heavy charged particle beams has the potential in therapeutic applications of sparing critical structures just distal to the target volume. The effects of highly inhomogeneous regions on this desirable depth-dose characteristic are explored. The proton depth-dose distribution behind a lucite-air interface parallel to the beam was bimodal. A second experiment showed little significant effect on the distal depth-dose of protons having passed through a mosaic of teflon and lucite. Anatomic studies demonstrated significant effects of complex fine inhomogeneities on the end of range characteristics. Monoenergetic protons passing through the petrous ridges and mastoid air cells in the base of the skull showed a dramatic degradation of the distal Bragg peak. Heavy ions showed a corresponding degradation in their ends of range. In the worst case in the base of the skull region, a monoenergetic neon beam showed a broadening of the full width at half maximum of the Bragg peak to over 15 mm. A similar effect was found with carbon ions in the abdomen. The authors address the implications of these data for dose computation with heavy charged particles.