Microplastic in Dredged Sediments: From Databases to Strategic Responses.

Microplastics (MPs) accumulate in sediments, yet guidelines for evaluating MP risks in dredged sediments are lacking. The objective of this study was to review existing literature on MPs in sediments to improve fundamental knowledge of MP exposures and develop a publicly available database of MPs in sediments. Twelve percent of the reviewed papers (nine studies) included sediment core samples with MP concentrations generally decreasing with depth, peaking in the top 15 cm. The remaining papers evaluated surficial grab samples (0 to 15 cm depth) from various water bodies with MPs detected in almost every sample. Median MP concentrations (items/kg dry sediment) increased in this order: lakes and reservoirs (184), estuarine (263), Great Lakes nearshore areas and tributaries (290), riverine (410), nearshore marine areas (487), dredge activities (817), and harbors (948). Dredging of recurrent shoaling sediments could be expected to contain MPs at various depths with concentrations influenced by the time elapsed since the last dredging event. These results offer key insights into the presence and variability of MPs in dredged sediments, informing environmental monitoring and risk assessment strategies.

Patient individual phase gating for stereotactic radiation therapy of early stage non-small cell lung cancer (NSCLC).

Stereotactic body radiotherapy (SBRT) applies high doses and requires advanced techniques to spare surrounding tissue in the presence of organ motion. In this work patient individual phase gating is investigated. We studied peripheral and central primary lung tumors. The internal target volume (ITV) was defined including different numbers of phases picked from a 4D Computed tomography (CT) defining the gating window (gw). Planning target volume (PTV) reductions depending on the gw were analyzed. A treatment plan was calculated on a reference phase CT (rCT) and the dose for each breathing phase was calculated and accumulated on the rCT. We compared the dosimetric results with the dose calculated when all breathing phases were included for ITV definition. GWs including 1 to 10 breathing phases were analyzed. We found PTV reductions up to 38.4%. The mean reduction of the lung volume receiving 20 Gy due to gating was found to be 25.7% for peripheral tumors and 16.7% for central tumors. Gating considerably reduced esophageal doses. However, we found that simple reduction of the gw does not necessarily influence the dose in a clinically relevant range. Thus, we suggest a patient individual definition of the breathing phases included within the gw.

Helical tomotherapy: Comparison of Hi-ART and Radixact clinical patient treatments at the Technical University of Munich.

The helical tomotherapy (HT) Hi-ART system was installed at our department in April 2007. In July 2018 the first Radixact system in Germany has been launched for clinical use. We present differences, advantages and disadvantages and show future perspectives in patient treatment using two HT devices. We investigate patient characteristics, image quality, radiotherapy treatment specifications and analyze the time effort for treatments with the Hi-ART system from April 2010 until May 2017 and compare it to the data acquired in the first nine months of usage of the Radixact system. Comparing the Hi-ART and Radixact system, the unique option of integrated MVCT image acquisition has experienced distinct improvement in image quality. Time effort for irradiation treatment could be improved resulting in a mean beam on time for craniospinal axis treatment of 636.2 s for the Radixact system compared to 915.9 s for the Hi-ART system. The beneficial use of tomotherapy for complex target volumes is demonstrated by a head and neck tumor case and craniospinal axis treatment. With the Radixact system MVCT image quality has been improved allowing for fast and precise interfraction dose adaptation. The improved time effort for patient treatment could increase the accessibility for clinical usage.

MRI-based high-precision irradiation in an orthotopic pancreatic tumor mouse model : A treatment planning study.

BACKGROUND AND PURPOSE: Recently, imaging and high-precision irradiation devices for preclinical tumor models have been developed. Image-guided radiation therapy (IGRT) including innovative treatment planning techniques comparable to patient treatment can be achieved in a translational context. The study aims to evaluate magnetic resonance imaging/computed tomography (MRI/CT)-based treatment planning with different treatment techniques for high-precision radiation therapy (RT). MATERIALS AND METHODS: In an orthotopic pancreatic cancer model, MRI/CT-based radiation treatment planning was established. Three irradiation techniques (rotational, 3D multifield, stereotactic) were performed with the SARRP system (Small Animal Radiation Research Platform, Xstrahl Ltd., Camberley, UK). Dose distributions in gross tumor volume (GTV) and organs at risk (OAR) were analyzed for each treatment setting. RESULTS: MRI with high soft tissue contrast improved imaging of GTV and OARs. Therefore MRI-based treatment planning enables precise contouring of GTV and OARs, thus, providing a perfect basis for an improved dose distribution and coverage of the GTV for all advanced radiation techniques. CONCLUSION: An MRI/CT-based treatment planning for high-precision IGRT using different techniques was established in an orthotopic pancreatic tumor model. Advanced radiation techniques allow considering perfect coverage of GTV and sparing of OARs in the preclinical setting and reflect clinical treatment plans of pancreatic cancer patients.

Evaluation of radiation-related invasion in primary patient-derived glioma cells and validation with established cell lines: impact of different radiation qualities with differing LET.

PURPOSE: Glioblastoma multiforme (GBM) is the most common primary brain tumor and has a very poor overall prognosis. Multimodal treatment is still inefficient and one main reason is the invasive nature of GBM cells, enabling the tumor cells to escape from the treatment area causing tumor progression. This experimental study describes the effect of low- and high-LET irradiation on the invasion of primary GBM cells with a validation in established cell systems. METHODS: Seven patient derived primary GBM as well as three established cell lines (LN229, LN18 and U87) were used in this study. Invasion was investigated using Matrigel® coated transwell chambers. Irradiation was performed with low- (X-ray) and high-LET (alpha particles) radiation. The colony formation assay was chosen to determine the corresponding alpha particle dose equivalent to the X-ray dose. RESULTS: 4 Gy X-ray irradiation increased the invasive potential of six patient derived GBM cells as well as two of the established lines. In contrast, alpha particle irradiation with an equivalent dose of 1.3 Gy did not show any effect on the invasive behavior. The findings were validated with established cell lines. CONCLUSION: Our results show that in contrast to low-LET irradiation high-LET irradiation does not enhance the invasion of established and primary glioblastoma cell lines. We therefore suggest that high-LET irradiation could become an alternative treatment option. To fully exploit the benefits of high-LET irradiation concerning the invasion of GBM further molecular studies should be performed.

BioXmark for high-precision radiotherapy in an orthotopic pancreatic tumor mouse model : Experiences with a liquid fiducial marker.

BACKGROUND AND PURPOSE: High-precision radiotherapy (RT) requires precise positioning, particularly with high single doses. Fiducial markers in combination with onboard imaging are excellent tools to support this. The purpose of this study is to establish a pancreatic cancer mouse model for high-precision image-guided RT (IGRT) using the liquid fiducial marker BioXmark (Nanovi, Kongens Lyngby, Denmark). METHODS: In an animal-based cancer model, different volumes of BioXmark (10-50 µl), application forms, and imaging modalities-cone-beam computer tomography (CBCT) incorporated in either the Small Animal Radiation Research Platform (SARRP) or the small-animal micro-CT Scanner (SkyScan; Bruker, Brussels, Belgium)-as well as subsequent RT with the SARRP system were analyzed to derive recommendations for BioXmark. RESULTS: Even small volumes (10 µl) of BioXmark could be detected by CBCT (SARRP and Skyscan). Larger volumes (50 µl) led to hardening artefacts. The position of BioXmark was monitored at least weekly by CBCT and was stable over 4 months. BioXmark was shown to be well tolerated; no changes in physical condition or toxic side effects were observed in comparison to control mice. BioXmark enabled an exact fusion with the original treatment plan with less hardening artefacts, and minimized the application of contrast agent for fractionated RT. CONCLUSION: An orthotopic pancreatic tumor mouse model was established for high-precision IGRT using a fiducial marker. BioXmark was successfully tested and provides the perfect basis for improved imaging in high-precision RT. BioXmark enables a unique application method and optimal targeted precision in fractionated RT. Therefore, preclinical trials evaluating novel fractionation regimens and/or combination treatment with high-end RT can be performed.

A light-weight compact proton gantry design with a novel dose delivery system for broad-energetic laser-accelerated beams.

Proton beams may provide superior dose-conformity in radiation therapy. However, the large sizes and costs limit the widespread use of proton therapy (PT). The recent progress in proton acceleration via high-power laser systems has made it a compelling alternative to conventional accelerators, as it could potentially reduce the overall size and cost of the PT facilities. However, the laser-accelerated beams exhibit different characteristics than conventionally accelerated beams, i.e. very intense proton bunches with large divergences and broad-energy spectra. For the application of laser-driven beams in PT, new solutions for beam transport, such as beam capture, integrated energy selection, beam shaping and delivery systems are required due to the specific beam parameters. The generation of these beams are limited by the low repetition rate of high-power lasers and this limitation would require alternative solutions for tumour irradiation which can efficiently utilize the available high proton fluence and broad-energy spectra per proton bunch to keep treatment times short. This demands new dose delivery system and irradiation field formation schemes. In this paper, we present a multi-functional light-weight and compact proton gantry design for laser-driven sources based on iron-less pulsed high-field magnets. This achromatic design includes improved beam capturing and energy selection systems, with a novel beam shaping and dose delivery system, so-called ELPIS. ELPIS system utilizes magnetic fields, instead of physical scatterers, for broadening the spot-size of broad-energetic beams while capable of simultaneously scanning them in lateral directions. To investigate the clinical feasibility of this gantry design, we conducted a treatment planning study with a 3D treatment planning system augmented for the pulsed beams with optimizable broad-energetic widths and selectable beam spot sizes. High quality treatment plans could be achieved with such unconventional beam parameters, deliverable via the presented gantry and ELPIS dose delivery system. The conventional PT gantries are huge and require large space for the gantry to rotate the beam around the patient, which could be reduced up to 4 times with the presented pulse powered gantry system. The further developments in the next generation petawatt laser systems and laser-targets are crucial to reach higher proton energies. However, if proton energies required for therapy applications are reached it could be possible in future to reduce the footprint of the PT facilities, without compromising on clinical standards.

Rapid implementation of the repair-misrepair-fixation (RMF) model facilitating online adaption of radiosensitivity parameters in ion therapy.

INTRODUCTION: Treatment planning for ion therapy must account for physical properties of the beam as well as differences in the relative biological effectiveness (RBE) of ions compared to photons. In this work, we present a fast RBE calculation approach, based on the decoupling of physical properties and the [Formula: see text] ratio commonly used to describe the radiosensitivity of irradiated cells or organs. MATERIAL AND METHODS: In the framework of the mechanistic repair-misrepair-fixation (RMF) model, the biological modeling can be decoupled from the physical dose. This was implemented into a research treatment planning system for carbon ion therapy. RESULTS: The presented implementation of the RMF model is very fast, allowing online changes of [Formula: see text]. For example, a change of [Formula: see text] including a complete biological modeling and a recalculation of RBE for [Formula: see text] voxel takes 4 ms on a 4 CPU, 3.2 GHz workstation. DISCUSSION AND CONCLUSION: The derived decoupling within the RMF model allows fast changes in [Formula: see text], facilitating online adaption by the user. This provides new options for radiation oncologists, facilitating online variations of the radiobiological input parameters during the treatment plan evaluation process as well as uncertainty and sensitivity analyses.

Quantification of the uncertainties of a biological model and their impact on variable RBE proton treatment plan optimization.

PURPOSE: In proton radiation therapy, a relative biological effectiveness (RBE) equal to 1.1 is currently assumed, although biological experiments show that it is not constant. The purpose of this study was to quantify the uncertainties of a published biological model and explore their impact on variable RBE treatment plan (TP) optimization. METHODS: Two patient cases with a high and a low (α/ß)x tumor were investigated. Firstly, intensity modulated proton therapy TPs assuming constant RBE were derived, and subsequently the variable RBE weighted dose (RWD), including the uncertainty originating in the fit to the experimental data and the uncertainty of the (α/ß)x, were calculated. Secondly, TPs optimized for uniform biological effect assuming a variable RBE were created using the worst case tissue specific (α/ß)x. RESULTS: For the nasopharyngeal cancer patient, the uncertainty of (α/ß)x corresponded to a CTV D98 confidence interval (CI) of (-2, +4)% while for the fit parameter CI was (-2,+1)%. For the standard fractionation prostate case the (α/ß)x CI was (-7,+5)% and the fit parameter CI was (-3,+3)%. For the hypofractionated case both CIs were (-1,+1)%. In both patient cases, the RBE in most organs at risk (OARs) was significantly underestimated by the constant RBE approximation, whereas the situation was not as definite in the target volumes. Overdosage of OARs was reduced by using the biological effect optimization. CONCLUSION: For the two patient cases, the RWD uncertainty from the fit parameter in the biological model contributed non-negligibly to the total uncertainty, depending on the patient case and the organ. The presented optimization strategy is a basic method for robust biological effect optimization to reduce potential consequences caused by the (α/ß)x uncertainty.

Development and clinical evaluation of an ionization chamber array with 3.5 mm pixel pitch for quality assurance in advanced radiotherapy techniques.

PURPOSE: To characterize a new air vented ionization chamber technology, suitable to build detector arrays with small pixel pitch and independence of sensitivity on dose per pulse. METHODS: The prototype under test is a linear array of air vented ionization chambers, consisting of 80 pixels with 3.5 mm pixel pitch distance and a sensitive volume of about 4 mm(3). The detector has been characterized with (60)Co radiation and MV x rays from different linear accelerators (with flattened and unflattened beam qualities). Sensitivity dependence on dose per pulse has been evaluated under MV x rays by changing both the source to detector distance and the beam quality. Bias voltage has been varied in order to evaluate the charge collection efficiency in the most critical conditions. Relative dose profiles have been measured for both flattened and unflattened distributions with different field sizes. The reference detectors were a commercial array of ionization chambers and an amorphous silicon flat panel in direct conversion configuration. Profiles of dose distribution have been measured also with intensity modulated radiation therapy (IMRT), stereotactic radiosurgery (SRS), and volumetric modulated arc therapy (VMAT) patient plans. Comparison has been done with a commercial diode array and with Gafchromic EBT3 films. RESULTS: Repeatability and stability under continuous gamma irradiation are within 0.3%, in spite of low active volume and sensitivity (∼200 pC/Gy). Deviation from linearity is in the range [0.3%, -0.9%] for a dose of at least 20 cGy, while a worsening of linearity is observed below 10 cGy. Charge collection efficiency with 2.67 mGy/pulse is higher than 99%, leading to a ±0.9% sensitivity change in the range 0.09-2.67 mGy/pulse (covering all flattened and unflattened beam qualities). Tissue to phantom ratios show an agreement within 0.6% with the reference detector up to 34 cm depth. For field sizes in the range 2 × 2 to 15 × 15 cm(2), the output factors are in agreement with a thimble chamber within 2%, while with 25 × 25 cm(2) field size, an underestimation of 4.0% was found. Agreement of field and penumbra width measurements with the flat panel is of the order of 1 mm down to 1 × 1 cm(2) field size. Flatness and symmetry values measured with the 1D array and the reference detectors are comparable, and differences are always smaller than 1%. Angular dependence of the detector, when compared to measurements taken with a cylindrical chamber in the same phantom, is as large as 16%. This includes inhomogeneity and asymmetry of the design, which during plan verification are accounted for by the treatment planning system (TPS). The detector is capable to reproduce the dose distributions of IMRT and VMAT plans with a maximum deviation from TPS of 3.0% in the target region. In the case of VMAT and SRS plans, an average (maximum) deviation of the order of 1% (4%) from films has been measured. CONCLUSIONS: The investigated technology appears to be useful both for Linac QA and patient plan verification, especially in treatments with steep dose gradients and nonuniform dose rates such as VMAT and SRS. Major limitations of the present prototype are the linearity at low dose, which can be solved by optimizing the readout electronics, and the underestimation of output factors with large field sizes. The latter problem is presently not completely understood and will require further investigations.

Local weighting of nanometric track structure properties in macroscopic voxel geometries for particle beam treatment planning.

The research project BioQuaRT within the European Metrology Research Programme aimed at correlating ion track structure characteristics with the biological effects of radiation and developed measurement and simulation techniques for determining ion track structure on different length scales from about 2 nm to about 10 µm. Within this framework, we investigated methods to translate track-structure quantities derived on a nanometre scale to macroscopic dimensions. Here we make use of parameterizations that link the energy of the projectile to the ionization pattern of the track using nanodosimetric ionization cluster size distributions. They were defined with data generated by simulations of ion tracks in liquid water using the Geant4 Monte Carlo toolkit with the Geant4-DNA processes. For the clinical situation with a mixed radiation field, where particles of various energies hit a cell from several directions, we have to find macroscopic relevant mean values. They can be determined by appropriate local weighting functions for the identified parameterization. We show that a stopping power weighted mean value of the mentioned track structure properties can describe the overall track structure in a cell exposed to a mixed radiation field. The parameterization, together with the presented stopping power weighting approach, show how nanometric track structure properties could be integrated into treatment planning systems without the need to perform time consuming simulations on the nanometer level for each individual patient.

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.

Investigation of EBT2 and EBT3 films for proton dosimetry in the 4-20 MeV energy range.

Radiochromic films such as Gafchromic EBT2 or EBT3 films are widely used for dose determination in radiation therapy because they offer a superior spatial resolution compared to any other digital dosimetric 2D detector array. The possibility to detect steep dose gradients is not only attractive for intensity-modulated radiation therapy with photons but also for intensity-modulated proton therapy. Their characteristic dose rate-independent response makes radiochromic films also attractive for dose determination in cell irradiation experiments using laser-driven ion accelerators, which are currently being investigated as future medical ion accelerators. However, when using these films in ion beams, the energy-dependent dose response in the vicinity of the Bragg peak has to be considered. In this work, the response of these films for low-energy protons is investigated. To allow for reproducible and background-free irradiation conditions, the films were exposed to mono-energetic protons from an electrostatic accelerator, in the 4-20 MeV energy range. For comparison, irradiation with clinical photons was also performed. It turned out that in general, EBT2 and EBT3 films show a comparable performance. For example, dose-response curves for photons and protons with energies as low as 11 MeV show almost no differences. However, corrections are required for proton energies below 11 MeV. Care has to be taken when correction factors are related to an average LET from depth-dose measurements, because only the dose-averaged LET yields similar results as obtained in mono-energetic measurements.

Future development of biologically relevant dosimetry.

Proton and ion beams are radiotherapy modalities of increasing importance and interest. Because of the different biological dose response of these radiations as compared with high-energy photon beams, the current approach of treatment prescription is based on the product of the absorbed dose to water and a biological weighting factor, but this is found to be insufficient for providing a generic method to quantify the biological outcome of radiation. It is therefore suggested to define new dosimetric quantities that allow a transparent separation of the physical processes from the biological ones. Given the complexity of the initiation and occurrence of biological processes on various time and length scales, and given that neither microdosimetry nor nanodosimetry on their own can fully describe the biological effects as a function of the distribution of energy deposition or ionization, a multiscale approach is needed to lay the foundation for the aforementioned new physical quantities relating track structure to relative biological effectiveness in proton and ion beam therapy. This article reviews the state-of-the-art microdosimetry, nanodosimetry, track structure simulations, quantification of reactive species, reference radiobiological data, cross-section data and multiscale models of biological response in the context of realizing the new quantities. It also introduces the European metrology project, Biologically Weighted Quantities in Radiotherapy, which aims to investigate the feasibility of establishing a multiscale model as the basis of the new quantities. A tentative generic expression of how the weighting of physical quantities at different length scales could be carried out is presented.

Variance-based sensitivity analysis of biological uncertainties in carbon ion therapy.

PURPOSE: Biological models to estimate the relative biological effectiveness (RBE) or the equivalent dose in 2 Gy fractions (EQD2) are needed for treatment planning and plan evaluation in carbon ion therapy. We present a model-independent, Monte Carlo based sensitivity analysis (SA) approach to quantify the impact of different uncertainties on the biological models. METHODS AND MATERIALS: The Monte Carlo based SA is used for the evaluation of variations in biological parameters. The key property of this SA is the high number of simulation runs, each with randomized input parameters, allowing for a statistical variance-based ranking of the input variations. The potential of this SA is shown in a simplified one-dimensional treatment plan optimization. Physical properties of carbon ion beams (e.g. fragmentation) are simulated using the Monte Carlo code FLUKA. To estimate biological effects of ion beams compared to X-rays, we use the Local Effect Model (LEM) in the framework of the linear-quadratic (LQ) model. Currently, only uncertainties in the output of the biological models are taken into account. RESULTS/CONCLUSIONS: The presented SA is suitable for evaluation of the impact of variations in biological parameters. Major advantages are the possibility to access and display the sensitivity of the evaluated quantity on several parameter variations at the same time. Main challenges for later use in three-dimensional treatment plan evaluation are computational time and memory usage. The presented SA can be performed with any analytical or numerical function and hence be applied to any biological model used in carbon ion therapy.

The effects of ultra-high dose rate proton irradiation on growth delay in the treatment of human tumor xenografts in nude mice.

The new technology of laser-driven ion acceleration (LDA) has shown the potential for driving highly brilliant particle beams. Laser-driven ion acceleration differs from conventional proton sources by its ultra-high dose rate, whose radiobiological impact should be investigated thoroughly before adopting current clinical dose concepts. The growth of human FaDu tumors transplanted onto the hind leg of nude mice was measured sonographically. Tumors were irradiated with 20 Gy of 23 MeV protons at pulsed mode with single pulses of 1 ns duration or continuous mode (∼100 ms) in comparison to controls and to a dose-response curve for 6 MV photons. Tumor growth delay and the relative biological effectiveness (RBE) were calculated for all irradiation modes. The mean target dose reconstructed from Gafchromic films was 17.4 ± 0.8 Gy for the pulsed and 19.7 ± 1.1 Gy for the continuous irradiation mode. The mean tumor growth delay was 34 ± 6 days for pulsed, 35 ± 6 days for continuous protons, and 31 ± 7 days for photons 20 ± 1.2 Gy, resulting in RBEs of 1.22 ± 0.19 for pulsed and 1.10 ± 0.18 for continuous protons, respectively. In summary, protons were found to be significantly more effective in reducing the tumor volume than photons (P < 0.05). Together with the results of previous in vitro experiments, the in vivo data reveal no evidence for a substantially different radiobiology that is associated with the ultra-high dose rate of protons that might be generated from advanced laser technology in the future.

Instrumentation for diagnostics and control of laser-accelerated proton (ion) beams.

Suitable instrumentation for laser-accelerated proton (ion) beams is critical for development of integrated, laser-driven ion accelerator systems. Instrumentation aimed at beam diagnostics and control must be applied to the driving laser pulse, the laser-plasma that forms at the target and the emergent proton (ion) bunch in a correlated way to develop these novel accelerators. This report is a brief overview of established diagnostic techniques and new developments based on material presented at the first workshop on 'Instrumentation for Diagnostics and Control of Laser-accelerated Proton (Ion) Beams' in Abingdon, UK. It includes radiochromic film (RCF), image plates (IP), micro-channel plates (MCP), Thomson spectrometers, prompt inline scintillators, time and space-resolved interferometry (TASRI) and nuclear activation schemes. Repetition-rated instrumentation requirements for target metrology are also addressed.

Comparison of Gafchromic EBT2 and EBT3 films for clinical photon and proton beams.

PURPOSE: Dose verification in highly conformal radiation therapy such as IMRT or proton therapy can benefit from the high spatial resolution offered by radio-chromic films such as Gafchromic EBT or EBT2. Recently, a new generation of these films, EBT3, has become available. The composition and thickness of the sensitive layer are the same as for the previous EBT2 films. The most important change is the symmetric layer configuration to eliminate side orientation dependence, which is reported for EBT2 films. METHODS: The general film characteristics such as sensitivity to read-out orientation and postexposure darkening evolution of the new EBT3 film are evaluated. Film response has been investigated in clinical photon and proton beams and compared to former EBT2 films. Quenching effects in the proton Bragg peak region have been studied for both, EBT2 and EBT3 films. RESULTS: The general performance of EBT3 is comparable to EBT2, and the orientation dependence with respect to film side is completely eliminated in EBT3 films. Response differences of EBT2 and EBT3 films are of the same order of magnitude as batch-to-batch variations observed for EBT2 films. No significant difference has been found for both generations of EBT films between photon and proton exposure. Depth dose measurements of EBT2 and EBT3 show an excellent agreement, though underestimating dose by up to 20% in the Bragg peak region. CONCLUSIONS: The symmetric configuration of EBT3 presents a major improvement for film handling. EBT3 has similar dosimetric performance as its precursor EBT2 and can, thus, be applied to dose verification in IMRT in the same way. For dose verification in proton therapy the underresponse in the Bragg peak region has to be taken into account.

Dosimetric effects of energy spectrum uncertainties in radiation therapy with laser-driven particle beams.

Laser-driven particle acceleration is a potentially cost-efficient and compact new technology that might replace synchrotrons or cyclotrons for future proton or heavy-ion radiation therapy. Since the energy spectrum of laser-accelerated particles is rather wide, compared to the monoenergetic beams of conventional machines, studies have proposed the usage of broader spectra for the treatment of at least certain parts of the target volume to make the process more efficient. The thereby introduced additional uncertainty in the applied energy spectrum is analysed in this note. It is shown that the uncertainty can be categorized into a change of the total number of particles, and a change in the energy distribution of the particles. The former one can be monitored by a simple fluence detector and cancels for a high number of statistically fluctuating shots. The latter one, the redistribution of a fixed number of particles to different energy bins in the window of transmitted energies of the energy selection system, only introduces smaller changes to the resulting depth dose curve. Therefore, it might not be necessary to monitor this uncertainty for all applied shots. These findings might enable an easier uncertainty management for particle therapy with broad energy spectra.