Evaluation of energy deposition and secondary particle production in proton therapy of brain using a slab head phantom

AimEvaluation of energy deposition of protons in human brain and calculation of the secondary neutrons and photons produced by protons in proton therapy.BackgroundRadiation therapy is one of the main methods of treating localized cancer tumors. The use of high energy proton beam in radiotherapy was proposed almost 60 years ago. In recent years, there has been a revival of interest in this subject in the context of radiation therapy. High energy protons suffer little angular deflection and have a well-defined penetration range, with a sharp increase in the energy loss at the end of their trajectories, namely the Bragg peak.Materials and methodsA slab head phantom was used for the purpose of simulating proton therapy in brain tissue. In this study simulation was carried out using the Monte Carlo MCNPX code.ResultsBy using mono energetic proton pencil beams, energy depositions in tissues, especially inside the brain, as well as estimating the neutron and photon production as a result of proton interactions in the body, together with their energy spectra, were calculated or obtained. The amount of energy escaped from the head by secondary neutrons and photons was determined.ConclusionsIt was found that for high energy proton beams the amount of escaped energy by neutrons is almost 10 times larger than that by photons. We estimated that at 110 MeV beam energy, the overall proton energy “leaked” from the head by secondary photons and neutrons to be around 1%.     

Cancer risk after breast proton therapy considering physiological and radiobiological uncertainties

BackgroundThe reduced normal tissue dose burden from protons can reduce the risk of second cancer for breast cancer patients. Breathing motion and the impact of variable relative biological effectiveness (RBE) are however concerns for proton dose distributions. This study aimed to quantify the impact of these factors on risk predictions from proton and photon therapy.Materials and methodsTwelve patients were planned in free breathing with protons and photons to deliver 50 Gy (RBE) in 25 fractions (assuming RBE = 1.1 for protons) to the left breast. Second cancer risk was evaluated with several models for the lungs, contralateral breast, heart and esophagus as organs at risk (OARs). Plans were recalculated on CT-datasets acquired in extreme phases to account for breathing motion. Proton plans were also recalculated assuming variable RBE for a range of radiobiological parameters.ResultsThe OARs received substantially lower doses from protons compared to photons. The highest risks were for the lungs (average second cancer risks of 0.31% and 0.12% from photon and proton plans, respectively). The reduced risk with protons was maintained, even when breathing and/or RBE variation were taken into account. Furthermore, while the total risks from the photon plans were seen to increase with the integral dose, no such correlation was observed for the proton plans.ConclusionsProtons have an advantage over the photons with respect to the induction of cancer. Uncertainties in physiological movements and radiobiological parameters affected the absolute risk estimates, but not the general trend of lower risk associated with proton therapy.     

What can particle therapy add to the treatment of prostate cancer?

The treatment of prostate cancer with either protons or carbon ions is not a novelty, and several thousands of patients were treated with hadrontherapy in the past decades. The standard treatment approach consisted in two lateral opposed fields for both protons and carbon ions, mostly delivered with scattered beams and using conventional fractionation and hypofractionation for protons and carbon ions, respectively. Similar (RBE-weighted and BED) doses to photon therapy (XRT) have been delivered, with comparable results in terms of both local control and toxicity. The advancements in dose deposition and image guidance of the early ‘00s that improved the quality of XRT treatments and then allowed for hypofractionation, are being matched with some delay by hadrontherapy in these very years. Pencil beam scanning is now the norm in proton therapy, and volumetric image guidance is being developed in all new hadrontherapy facilities. There is therefore the possibility of truly taking advantage of superior dose distributions of hadrons and safely apply it to innovative treatment protocols, such as an intraprostatic boost and the treatment of larger volume for advanced stage disease. This full integration between the best of technology and new clinical approaches is probably necessary in order to obtain clinical results that are truly superior to the current state of the art of XRT.     

COTS Silicon diodes as radiation detectors in proton and heavy charged particle radiotherapy 1

Modern radiotherapy facilities for cancer treatment such as the Heavy Ion Therapy Center (HIT) in Heidelberg, Germany, allow for sub-millimeter precision in dose deposition. For measurement of such dose distributions and characterization of the particle beams, detectors with high spatial resolution are necessary. Here, a detector based on the commercially available COTS photodiode (BPW-34) is presented. When applied in hadronic beams of protons and carbon ions, the detector reproduces dose distribution well, but its response decreases rapidly by radiation damage. However, for MeV photon beams, the detector exhibits a similar behavior as found in diode detectors usually applied in radiotherapy.     

The optimal balance between quality and efficiency in proton radiography imaging technique at various proton beam energies: A Monte Carlo study

Proton radiography is a novel imaging modality that allows direct measurement of the proton energy loss in various tissues. Currently, due to the conversion of so-called Hounsfield units from X-ray Computed Tomography (CT) into relative proton stopping powers (RPSP), the uncertainties of RPSP are 3–5% or higher, which need to be minimized down to 1% to make the proton treatment plans more accurate.In this work, we simulated a proton radiography system, with position-sensitive detectors (PSDs) and a residual energy detector (RED). The simulations were built using Geant4, a Monte Carlo simulation toolkit. A phantom, consisting of several materials was placed between the PSDs of various Water Equivalent Thicknesses (WET), corresponding to an ideal detector, a gaseous detector, silicon and plastic scintillator detectors. The energy loss radiograph and the scattering angle distributions of the protons were studied for proton beam energies of 150 MeV, 190 MeV and 230 MeV. To improve the image quality deteriorated by the multiple Coulomb scattering (MCS), protons with small angles were selected. Two ways of calculating a scattering angle were considered using the proton’s direction and position.A scattering angle cut of 8.7 mrad was applied giving an optimal balance between quality and efficiency of the radiographic image. For the three proton beam energies, the number of protons used in image reconstruction with the direction method was half the number of protons kept using the position method.     

Evaluation of Gafchromic® EBT3 films characteristics in therapy photon,electron and proton beams

PurposeTo evaluate the uncertainties and characteristics of radiochromic film-based dosimetry system using the EBT3 model Gafchromic^® film in therapy photon, electron and proton beams.Material and methodsEBT3 films were read using an EPSON Expression 10000XL/PRO scanner. They were irradiated in five beams, an Elekta SL25 6 MV and 18 MV photon beam, an IBA 100 MeV 5 × 5 cm² proton beam delivered by pencil-beam scanning, a 60 MeV fixed proton beam and an Elekta SL25 6 MeV electron beam. Reference dosimetry was performed using a FC65-G chamber (Elekta beam), a PPC05 (IBA beam) and both Markus 1916 and PPC40 Roos ion-chambers (60 MeV proton beam). Calibration curves of the radiochromic film dosimetry system were acquired and compared within a dose range of 0.4–10 Gy. An uncertainty budget was estimated on films irradiated by Elekta SL25 by measuring intra-film and inter-film reproducibility and uniformity; scanner uniformity and reproducibility; room light and film reading delay influences.ResultsThe global uncertainty on acquired optical densities was within 0.55% and could be reduced to 0.1% by placing films consistently at the center of the scanner. For all beam types, the calibration curves are within uncertainties of measured dose and optical densities. The total uncertainties on calibration curve due to film reading and fitting were within 1.5% for photon and proton beams. For electrons, the uncertainty was within 2% for dose superior to 0.8 Gy.ConclusionsThe low combined uncertainty observed and low beam and energy-dependence make EBT3 suitable for dosimetry in various applications.     

Proton microbeam radiotherapy with scanned pencil-beams – Monte Carlo simulations

Irradiation, delivered by a synchrotron facility, using a set of highly collimated, narrow and parallel photon beams spaced by 1 mm or less, has been termed Microbeam Radiation Therapy (MRT). The tolerance of healthy tissue after MRT was found to be better than after standard broad X-ray beams, together with a more pronounced response of malignant tissue. The microbeam spacing and transverse peak-to-valley dose ratio (PVDR) are considered to be relevant biological MRT parameters. We investigated the MRT concept for proton microbeams, where we expected different depth-dose profiles and PVDR dependences, resulting in skin sparing and homogeneous dose distributions at larger beam depths, due to differences between interactions of proton and photon beams in tissue. Using the FLUKA Monte Carlo code we simulated PVDR distributions for differently spaced 0.1 mm (sigma) pencil-beams of entrance energies 60, 80, 100 and 120 MeV irradiating a cylindrical water phantom with and without a bone layer, representing human head. We calculated PVDR distributions and evaluated uniformity of target irradiation at distal beam ranges of 60–120 MeV microbeams. We also calculated PVDR distributions for a 60 MeV spread-out Bragg peak microbeam configuration. Application of optimised proton MRT in terms of spot size, pencil-beam distribution, entrance beam energy, multiport irradiation, combined with relevant radiobiological investigations, could pave the way for hypofractionation scenarios where tissue sparing at the entrance, better malignant tissue response and better dose conformity of target volume irradiation could be achieved, compared with present proton beam radiotherapy configurations.     

The effectiveness of 20 mev protons at nanosecond pulse lengths in producing chromosome aberrations in human-hamster hybrid cells

Laser accelerated radiotherapy is a potential cancer treatment with proton and carbon-ion beams that is currently under development. Ultra-fast high-energy laser pulses will accelerate ion beams that deliver their dose to a patient in a "pulsed mode" that is expected to differ from conventional irradiation by increasing the dose delivery rate to a tissue voxel by approximately 8 orders of magnitude. In two independently performed experiments at the ion microprobe SNAKE of the 14 MV Munich tandem accelerator, A(L) cells were exposed either to protons with 1-ns pulse durations or to protons applied over 150 ms in continuous irradiation mode. A slightly but consistently lower aberration yield was observed for the pulsed compared to the continuous mode of proton irradiation. This difference was not statistically significant when each aberration type was analyzed separately (P values between 0.61 and 0.85 in experiment I and P values between 0.32 and 0.64 in experiment II). However, excluding the total aberrations, which were not analyzed as independent radiation-induced effects, the mean ratio of the yields of dicentrics, centric rings and excess acentrics scored together showed (with 95% CI) a significant difference of 0.90 (0.81; 0.98) between the pulsed and the continuous irradiation modes. A similar tendency was also determined for the corresponding RBE values relative to 70 kV X rays. Since the different findings for the comparisons of individual chromosome aberration types and combined comparisons could be explained by different sample sizes with the consequence that the individual comparisons had less statistical power to identify a difference, it can be concluded that 20 MeV protons may be slightly less effective in the pulsed mode.     

Heavy particle beams (proton) in oncology (35-year practice of N.N. Blokhin Cancer Research Centre)

Clinically proved "alternative breast-preserving method" applicable for patients with locally advanced nodal breast cancer. These patients refuse to go in to surgery or have indications for surgery (183 patients--T(1-4)N(0-3)M(0-1)). This method consists of the combination of the traditional method of the whole breast and/or nodal photon irradiation with local highly concentrated proton irradiation in the dosage iso-equivalent to tumor (proton with energy from 130 to 180 MeV, with stop in the target in notice depth). We used the irradiation of the adenohypophysis with narrow proton beams energy 200 MeV. The aim of the first combination of the components is the selectively influence on the target and the channeling to the tumor and its subclinical substances the dosages sufficient for the total irradiation of tumor with sparing surrounding tissues and parts of body. The goal of irradiation of adenohypophysis with protons is the normalization of its hormonal activity and elimination of factors stimulating growth of tumor cells in case of dishormonal cancer. The suggested method didu't only improve the results of the treatment of locally advanced breast cancer, but also contributed to the reducing of the emotional stress. We received high results of the patients with locally advanced nodal breast cancer of criteria: local control rate (96%), long remission (more then 40%) and 5-year actuarial survival rate (83%). The patients examined during 5 and 18 years. It made a good cosmetic effect and high quality life of the patients with breast cancer.     

Monte carlo model and output factors of elekta infinity™ 6 and 10 MV photon beam

AimThis study aimed to commission the Elekta Infinity™ working in 6 and 10 MV photon beam installed in Concord International Hospital, Singapore, and compare the OFs between MC simulation and measurement using PTW semiflex and microDiamond detector for small field sizes.Material and MethodsThere are two main steps in this study: modelling of Linac 6 and 10 MV photon beam and analysis of the output factors for field size 2 × 2–10 × 10 cm². The EGSnrc/BEAMnrc-DOSXYZnrc code was used to model and characterize the Linac and to calculate the dose distributions in a water phantom. The dose distribution and OFs were compared to the measurement data in the same condition.ResultsThe commissioning process was only conducted for a 10 × 10 cm² field size. The PDD obtained from MC simulation showed a good agreement with the measurement. The local dose difference of PDDs was less than 2% for 6 and 10 MV. The initial electron energy was 5.2 and 9.4 MeV for 6 and 10 MV photon beam, respectively. This Linac model can be used for dose calculation in other situations and different field sizes because this Linac has been commissioned and validated using Monte Carlo simulation. The 10 MV Linac produces higher electron contamination than that of 6 MV.ConclusionsThe Linac model in this study was acceptable. The most important result in this work comes from OFs resulted from MC calculation. This value was more significant than the OFs from measurement using semiflex and microDiamond for all beam energy and field sizes because of the CPE phenomenon.     

Is the risk for secondary cancers after proton therapy enhanced distal to the Planning Target Volume? A two-case report with possible explanations

It is often assumed that radiation-induced secondary cancer after proton therapy forms preferentially close to the distal fall-off of the spread-out Bragg peak because of an increased relative biological effectiveness (RBE) with regard to cancer induction of low-energy protons. In this study we analyze to what extent dose gradients distal to the Planning Target Volume (PTV) may, independently from the RBE, contribute to enhanced radiation carcinogenesis. The study is based on two dogs which, out of 30 dogs treated with proton therapy at the Paul Scherrer Institute (PSI), developed a secondary cancer. Both dogs were originally diagnosed and treated for a fibrosarcoma and developed an osteosarcoma 48 and almost 60 months, respectively, after radiotherapy. From the dose distributions of the initial radiotherapy for both dogs three-dimensional maps of secondary cancer complication probability (SCCP) were computed. The SCCP maps were analyzed in the regions where the dogs developed a secondary cancer. The SCCP maps showed an enhanced risk in the regions of the femur where the secondary cancers were detected, as compared to the SCCP of the total femur. Excess risk of radiation-induced cancer at the distal part of proton radiation fields can thus be explained using SCCP calculations on the basis of the physical dose distributions. Therefore, the occurrence of secondary cancer close to the distal dose gradients of proton therapy is not necessarily due to an increased RBE of low-energy protons. More extensive studies based on more patients will be necessary to further elucidate the factors influencing the development of secondary tumors.     

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

AimThe 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.BackgroundProton 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.Materials and methodsA 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.ResultsUsing 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.ConclusionsUsing 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.     

Improved normal tissue protection by proton and X-ray microchannels compared to homogeneous field irradiation

The risk of developing normal tissue injuries often limits the radiation dose that can be applied to the tumour in radiation therapy. Microbeam Radiation Therapy (MRT), a spatially fractionated photon radiotherapy is currently tested at the European Synchrotron Radiation Facility (ESRF) to improve normal tissue protection. MRT utilizes an array of microscopically thin and nearly parallel X-ray beams that are generated by a synchrotron. At the ion microprobe SNAKE in Munich focused proton microbeams (“proton microchannels”) are studied to improve normal tissue protection. Here, we comparatively investigate microbeam/microchannel irradiations with sub-millimetre X-ray versus proton beams to minimize the risk of normal tissue damage in a human skin model, in vitro. Skin tissues were irradiated with a mean dose of 2 Gy over the irradiated area either with parallel synchrotron-generated X-ray beams at the ESRF or with 20 MeV protons at SNAKE using four different irradiation modes: homogeneous field, parallel lines and microchannel applications using two different channel sizes. Normal tissue viability as determined in an MTT test was significantly higher after proton or X-ray microchannel irradiation compared to a homogeneous field irradiation. In line with these findings genetic damage, as determined by the measurement of micronuclei in keratinocytes, was significantly reduced after proton or X-ray microchannel compared to a homogeneous field irradiation. Our data show that skin irradiation using either X-ray or proton microchannels maintain a higher cell viability and DNA integrity compared to a homogeneous irradiation, and thus might improve normal tissue protection after radiation therapy.     

The radiolysis and racemization of leucine on proton irradiation

D- and L-Leucine have been subjected to 39-55 percent radiolysis using 0-11 MeV protons, both with the proton beam passing through the sample or being absorbed by it, and with quenching the sample immediately on completion of irradiation or after a 21-day interval. Racemization was small (1.1-1.7 percent) and comparable in all cases, suggesting that radioracemization and secondary degradative effects were not important factors in our recent unsuccessful attempts to induce optical activity in DL-leucine by partial radiolysis using 0-11 MeV longitudinally polarized protons.     

Changes in cellular response to the damage induced in PC-3 prostate cancer cells by proton microbeam irradiation

The aim of this research was to find out whether the passage number effect may influence on the PC-3 cells (the human prostate cancer line derived from bone metastases) response to proton radiation. 2 MeV horizontally focused proton microbeam was used as a radiation source. The cells were treated with a counted number of H(+) ions (50-8000) corresponding to doses of 1.3-209 Gy/cell. For comparison, cell death was also induced by UVC radiation. All cells were stained with Hoechst 33342 and propidium iodide and visualized under a fluorescence microscope. Necrosis was observed at: a) 8000 protons per cell (corresponding to ～209 Gy/cell) after 2-4 passages, b) 3200 protons per cell (corresponding to ～84 Gy/cell) for cells after 11-14 passages and c) only 800 protons per cell (corresponding to ～2 Gy/cell ) after 47-50 passages. Apoptosis was efficiently induced, by protons, only in cells after 50 passages. The results showed that the laboratory conditions affected cellular response of PC-3 cell line to the proton irradiation. The cellular response to the radiation treatment strongly depends on number of passages.     

Effects of 645 MeV and 9.2 GeV protons on Artemia eggs.

Developmental capacities of Artemia eggs have been studied after exposure to 645 MeV or 9.2 GeV protons. Effects of proton irradiation were studied in comparison with 60Co gamma ray irradiation, endpoints being emergence, hatching and 4-5 day old live nauplii percentages. Effectiveness of 645 MeV protons is greater than that of 9.2 GeV protons. R.b.e. values calculated for nauplius survival is 2.3 for 645 MeV protons and 1.5 for 9.2 GeV protons. These results can be taken into account in radiation hazard estimation during space flights.     

The radiolysis and racemization of leucine on proton irradiation

D- and L-Leucine have been subjected to 39–55 percent radiolysis using 0–11 MeV protons, both with the proton beam passing through the sample or being absorbed by it, and with quenching the sample immediately on completion of irradiation or after a 21-day interval. Racemization was small (1.1–1.7 percent) and comparable in all cases, suggesting that radioracemization and secondary degradative effects were not important factors in our recent unsuccessful attempts to induce optical activity in DL-leucine by partial radiolysis using 0–11 MeV longitudinally polarized protons.     

Clinical application of a gantry-attachable plastic scintillating plate dosimetry system in pencil beam scanning proton therapy beam monitoring

PurposeThe entrance beam fluence of therapeutic proton scanning beams can be monitored using a gantry-attachable plastic scintillating plate (GAPSP). This study evaluated the clinical application of the GAPSP using a method that measures intensity modulated proton therapy (IMPT) beams for patient treatment.MethodsIMPT beams for the treatment of nine patients, at sites that included the spine, head and neck, pelvis, and lung, were measured using the GAPSP, composed of an EJ-212 plastic scintillator and a CMOS camera. All energy layers distinguished by the GAPSP were accumulated to determine the dose distribution of the treatment field. The evaluated fields were compared with reference dose maps verified by quality assurance.ResultsComparison of dose distributions of evaluation treatment fields with reference dose distributions showed that the 3%/1 mm average gamma passing rate was 96.4%, independent of the treatment site, energy range and field size. When dose distributions were evaluated using the same criteria for each energy layer, the average gamma passing rate was 91.7%.ConclusionsThe GAPSP is a suitable, low-cost method for monitoring pencil beam scanning proton therapy, especially for non-spot scanning or additional collimation. The GAPSP can also estimate the treatment beam by the energy layer, a feature not common to other proton dosimetry tools.     

Evaluating the quality of NMR structures by local density of protons

Evaluating the quality of experimentally determined protein structural models is an essential step toward identifying potential errors and guiding further structural refinement. Herein, we report the use of proton local density as a sensitive measure to assess the quality of nuclear magnetic resonance (NMR) structures. Using 256 high-resolution crystal structures with protons added and optimized, we show that the local density of different proton types display distinct distributions. These distributions can be characterized by statistical moments and are used to establish local density Z-scores for evaluating both global and local packing for individual protons. Analysis of 546 crystal structures at various resolutions shows that the local density Z-scores increase as the structural resolution decreases and correlate well with the ClashScore (Word et al. J Mol Biol 1999;285(4):1711-1733) generated by all atom contact analysis. Local density Z-scores for NMR structures exhibit a significantly wider range of values than for X-ray structures and demonstrate a combination of potentially problematic inflation and compression. Water-refined NMR structures show improved packing quality. Our analysis of a high-quality structural ensemble of ubiquitin refined against order parameters shows proton density distributions that correlate nearly perfectly with our standards derived from crystal structures, further validating our approach. We present an automated analysis and visualization tool for proton packing to evaluate the quality of NMR structures.     

Cardiac risk and MCNP/SISCODES doses in RT of the left internal mammary chain with photon and electron portals

Aim

The present study evaluated the increment of cardiac risk (CR) and absorbed dose in radiotherapy of the internal mammary chain (IMC), in particular with photon portals of 4 6?MV, and cobalt therapy (Co60); and, electron portals of 8, 12 and 16?MeV applied in the left breast, considering the adoption of a combined photon (16?Gy) and electron (30?Gy) protocols.