Feasibility study of surface motion tracking with millimeter wave technology during radiotherapy.

PURPOSE: Continuous monitoring of patient movement is crucial to administering safe radiation therapy (RT). Conventional optical approaches often cannot be used when the patient's surface is blocked by immobilization devices. Millimeter waves (mmWaves) are capable of penetrating nonconductive objects. In this study, we investigated using mmWave technology to monitor patient surface displacements, as well as breathing and cardiac phases, through clothing and body fixtures. METHODS: A mmWave device was mounted inside the bore of a ring-based radiotherapy linear accelerator and pointed at a reflective surface on top of the couch. Measurements were obtained at displacements of 10, 7.5, 5.0, 2.5, and 1.0 mm at heights 100, 150, and 200 mm below isocenter. Submillimeter displacements were performed at a height of 200 mm. Additionally, millimeter and submillimeter displacements were measured with and without a gown and body mold placed between the surface and the sensor. The device was programmed to transmit chirp signals at 77-81 GHz. The subject's surface was detected by fast Fourier transform (FFT) of the reflected chirp signal within a rough range bin. Fine displacements within that range bin were calculated through phase extraction and phase demodulation. The displacement data were sent through two separate bandpass filters with passbands of 0.1-0.6 and 0.8-2.0 Hz to obtain the subject's breathing and cardiac waveforms, respectively. The breathing and cardiac measurements were compared to those of a Vernier Respiration Monitor Belt and an electrocardiogram (EKG), respectively, to assess validity. RESULTS: The device was able to detect millimeter and submillimeter displacements as small as 0.1 mm, as well as monitor displacement with an accuracy within 1 mm in the presence of an obstructive object. The device's breathing and cardiac waveforms exhibited a strong phase correlation between the respiration monitor belt (ρ = 0.9156) and EKG (ρ = 0.7895), respectively. CONCLUSIONS: The mmWave device can monitor surface displacements with an accuracy better than 0.1 mm without obstructions and better than 1 mm with obstructions. It can also provide real-time monitoring of breathing and cardiac waveforms simultaneously with high correlation with traditional respiratory and cardiac monitoring devices. Overall, mmWave technology demonstrates potential for motion monitoring in the field of radiation oncology.

Validation of a Monte Carlo simulation for Microbeam Radiation Therapy on the Imaging and Medical Beamline at the Australian Synchrotron.

Microbeam Radiation Therapy (MRT) is an emerging cancer treatment modality characterised by the use of high-intensity synchrotron-generated x-rays, spatially fractionated by a multi-slit collimator (MSC), to ablate target tumours. The implementation of an accurate treatment planning system, coupled with simulation tools that allow for independent verification of calculated dose distributions are required to ensure optimal treatment outcomes via reliable dose delivery. In this article we present data from the first Geant4 Monte Carlo radiation transport model of the Imaging and Medical Beamline at the Australian Synchrotron. We have developed the model for use as an independent verification tool for experiments in one of three MRT delivery rooms and therefore compare simulation results with equivalent experimental data. The normalised x-ray spectra produced by the Geant4 model and a previously validated analytical model, SPEC, showed very good agreement using wiggler magnetic field strengths of 2 and 3 T. However, the validity of absolute photon flux at the plane of the Phase Space File (PSF) for a fixed number of simulated electrons was unable to be established. This work shows a possible limitation of the G4SynchrotronRadiation process to model synchrotron radiation when using a variable magnetic field. To account for this limitation, experimentally derived normalisation factors for each wiggler field strength determined under reference conditions were implemented. Experimentally measured broadbeam and microbeam dose distributions within a Gammex RMI457 Solid Water® phantom were compared to simulated distributions generated by the Geant4 model. Simulated and measured broadbeam dose distributions agreed within 3% for all investigated configurations and measured depths. Agreement between the simulated and measured microbeam dose distributions agreed within 5% for all investigated configurations and measured depths.

The ideal couch tracking system-Requirements and evaluation of current systems.

INTRODUCTION: Intrafractional motion can cause substantial uncertainty in precision radiotherapy. Traditionally, the target volume is defined to be sufficiently large to cover the tumor in every position. With the robotic treatment couch, a real-time motion compensation can improve tumor coverage and organ at risk sparing. However, this approach poses additional requirements, which are systematically developed and which allow the ideal robotic couch to be specified. METHODS AND MATERIALS: Data of intrafractional tumor motion were collected and analyzed regarding motion range, frequency, speed, and acceleration. Using this data, ideal couch requirements were formulated. The four robotic couches Protura, Perfect Pitch, RoboCouch, and RPSbase were tested with respect to these requirements. RESULTS: The data collected resulted in maximum speed requirements of 60 mm/s in all directions and maximum accelerations of 80 mm/s2 in the longitudinal, 60 mm/s2 in the lateral, and 30 mm/s2 in the vertical direction. While the two robotic couches RoboCouch and RPSbase completely met the requirements, even these two showed a substantial residual motion (40% of input amplitude), arguably due to their time delays. CONCLUSION: The requirements for the motion compensation by an ideal couch are formulated and found to be feasible for currently available robotic couches. However, the performance these couches can be improved further regarding the position control if the demanded speed and acceleration are taken into account as well.

Toward a pre-clinical irradiator using clinical infrastructure.

PURPOSE: Pre-clinical irradiation systems use kilovoltage x-ray systems to deliver small fields of radiation in static beam arrangements or arcs. The systems are costly and the radiobiological effectiveness of kilovoltage beams is known to differ from the megavoltage photon beams used clinically. This work used Developer mode on the Varian TrueBeam STx linear accelerator to create a pre-clinical irradiator capable of treating millimeter-sized targets. MATERIALS AND METHODS: A treatment field defined by a single opposed leaf pair was used to deliver arc-based treatments. Dynamic couch trajectories were used to create a shortened virtual isocentre. Initially, a pre-treatment imaging procedure was used to quantify target misalignment at control points along the arcs and determine appropriate couch positional corrections. This was followed by the treatment arcs in which the positional corrections were implemented. Monte Carlo simulations and radiochromic film were used to calculate and measure dose distributions. RESULTS: A 1 mm leaf separation produced the optimal dose distributions. Couch position corrections up to 2.1 mm were required to maintain a target at virtual isocentre. Application of couch corrections reduced non-coplanar arc treatments dose profile by 1.2 mm at 30% of the maximum dose. Treatment of a 1 mm diameter target would result in falloff distances to the 80%, 50% and 25% of the 90% prescription line of 0.3 mm, 0.5 mm and 1.3 mm from the target edge respectively. CONCLUSIONS: This work has demonstrated that it is possible to deliver highly compact dose distributions using megavoltage photon beams from existing clinical infrastructure.

Output factors of ionization chambers and solid state detectors for mobile intraoperative radiotherapy (IORT) accelerator electron beams.

PURPOSE: The electron energy characteristics of mobile intraoperative radiotherapy (IORT) accelerator LIAC® differ from commonly used linear accelerators, thus some of the frequently used detectors can give less accurate results. The aim of this study is to evaluate the output factors (OFs) of several ionization chambers (IC) and solid state detectors (SS) for electron beam energies generated by LIAC® and compare with the output factor of Monte Carlo model (MC) in order to determine the adequate detectors for LIAC® . METHODS: The OFs were measured for 6, 8, 10, and 12 MeV electron energies with PTW 23343 Markus, PTW 34045 Advanced Markus, PTW 34001 Roos, IBA PPC05, IBA PPC40, IBA NACP-02, PTW 31010 Semiflex, PTW 31021 Semiflex 3D, PTW 31014 Pinpoint, PTW 60017 Diode E, PTW 60018 Diode SRS, SNC Diode EDGE, and PTW 60019 micro Diamond detectors. Ion recombination factors (ksat ) of IC were measured for all applicator sizes and OFs were corrected according to ksat . The measured OFs were compared with Monte Carlo output factors (OFMC ). RESULTS: The measured OFs of IBA PPC05, PTW Advanced Markus, PTW Pinpoint, PTW microDiamond, and PTW Diode E detectors are in good agreement with OFMC . The maximum deviations of IBA PPC05 OFs to OFMC are -1.6%, +1.5%, +1.5%, and +2.0%; for PTW Advanced Markus +1.0%, +1.5%, +2.0%, and +2.0%; for PTW Pinpoint +2.0%, +1.6%, +4.0%, and +2.0%; for PTW microDiamond -1.6%, +2%, +1.1%, and +1.0%; and for PTW Diode E -+1.7%, +1.7%, +1.3%, and +2.5% for 6, 8, 10, and 12 MeV, respectively. PTW Roos, PTW Markus, IBA PPC40, PTW Semiflex, PTW Semiflex 3D, SNC Diode Edge measured OFs with a maximum deviation of +5.6%, +4.5%, +5.6%, +8.1%, +4.8%, and +9.6% with respect to OFMC , while PTW Diode SRS and IBA NACP-02 were the least accurate (with highest deviations -37.1% and -18.0%, respectively). CONCLUSION: The OFs results of solid state detectors PTW microDiamond and PTW Diode E as well as the ICs with small electrode spacing distance such as IBA PPC05, PTW Advanced Markus and PTW Pinpoint are in excellent agreement with OFMC . The measurements of the other detectors evaluated in this study are less accurate, thus they should be used with caution. Particularly, PTW Diode SRS and IBA NACP-02 are not suitable and their use should be avoided in relative dosimetry measurements under high dose per pulsed (DPP) electron beams.

Comportamiento dosimétrico de un sistema de planificación mediante curvas de calibración de densidades electrónicas relativas / Dosimetric behaviour of a planning system through calibration curves of relative electron density

En esta investigación se planteó como objetivo la verificación del comportamiento dosimétrico del Sistema de Planificación de Tratamiento (TPS) de Radioterapia mediante las curvas de calibración de Densidades Electrónicas Relativas (DER). Este estudio se realizó en el Hospital de la Sociedad de Lucha Contra el Cáncer (SOLCA) Núcleo Loja, usando un fantoma antropomorfo CIRS 062M y un tomógrafo Toshiba Activion 16. Para determinar la nueva curva de calibración DER se tomaron los valores de densidades electrónicas especificadas en el manual del fantoma y las Unidades Hounsfield de la imagen tomográfica. Se realizó controles de calidad dosimétricos y verificación dosimétrica en tres casos clínicos: tórax, pelvis y cráneo; para realizar las pruebas dosimétricas se utilizó un acelerador CLINAC CX, cámara de ionización PTW tipo Farmer con volumen sensible de 0,6 cm3 y un electrómetro PTW UNIDOS E. Los resultados mostraron que las medidas para cada inserto del fantoma en ningún caso excedieron los límites establecidos de ± 20 UH, para el tomógrafo y el TPS; las pruebas de control de calidad no superaron el límite máximo de desviaciones en el cálculo de dosis absorbida por el TPS y la obtenida por medición de ± 4 % establecida por la IAEA y las verificaciones dosimétricas en tórax, pelvis y cráneo, determinaron que las desviaciones en el cálculo de la dosis absorbida por el TPS y la obtenida por medición no superaban la tolerancia del ± 5 % establecida por la ICRU.

In this research, the aim was to verify the dosimetric behavior of the Radiotherapy Treatment Planning System (TPS) using the Relative Electron Density (DER) calibration curves. This study was carried out at the SOLCA (Society of Fight Against Cancer) hospital in Loja, using an CIRS model 062M anthropomorphic phantom and a Toshiba Activion 16 tomograph. To determine the new DER calibration curve, the values of the electron densities specified in the manual of the phantom and the Hounsfield Units of the tomographic image were taken. Dosimetric quality controls were made in the location of three clinical cases: thorax pelvis and skull; used a CLINAC CX accelerator was used to perform the dosimetric tests, PTW ionization chamber type Farmer with sensitive volume of 0.6 cm3 and a PTW UNIDOS E electrometer. The results showed that the measurements for each insert of the phantom in no case exceeded the established limits of ± 20 UH, for the tomograph and the TPS; the quality control tests did not exceed the maximum limit of deviations in the calculation of dose absorbed by the TPS and the one obtained by measurement of ± 4% established by the IAEA and the clinical planning in the thorax, pelvis and skull, determine that the deviations in the calculation of the dose absorbed by the TPS and that obtained by measurement, they do not exceed the tolerance of ± 5% established by the ICR.

Body motion during dynamic couch tracking with healthy volunteers.

In precision radiotherapy, the intrafractional motion can cause a considerable uncertainty of the location of the tumor to be treated. An established approach is the expansion of the target volume to account for the motion. An alternative approach is couch-tracking, in which the patient is continually moved to compensate the intrafractional motion. However, couch-tracking itself might induce uncertainty of the patient's body position, because the body is non-rigid. One hundred healthy volunteers were positioned supine on a robotic couch. Optical markers were placed on the torso of the volunteers as well as on the couch, and their positions were tracked with an optical surface measurement system. Using these markers, the uncertainty of the body position relative to the couch position was estimated while the couch was static or moving. Over the included 83 healthy volunteers, the median of the uncertainty increased by 0.8 mm (SI), 0.4 mm (LR) and 0.4 mm (AP) when the couch moved. Couch motion was found to increase the uncertainty of the body position relative to the couch. However, this uncertainty is one order of magnitude smaller than the intrafractional tumor motion amplitudes to be compensated. Therefore, even with body motion present, the couch-tracking approach is a viable option. The study was registered at ClinicalTrials.gov (NCT02820532) and the Swiss national clinical trials portal (SNCTP000001878).

A generic multimodule phantom for testing geometry of a linac c-arm as a part of quality control in radiotherapy.

PURPOSE: To develop an assumption-free methodology for testing geometry of linacs. METHODS: The problem of projecting a fiducial positioned in a predefined point in a 3D space and attached rigidly to a treatment table of a radiotherapeutic device onto an imaging plane with unknown characteristics from a source with unknown coordinates is formulated. The problem of determining these unknowns is formulated as an optimization problem. The problem of determining the gantry/the collimator rotation axis and angle from projection of additional fiducials is also formulated and solved. Analytical methodology is developed for determining isocenter position and an error of estimating isocenter position. The developed methodology is tested in simulations. RESULTS: Very good agreement between preset and calculated values of quantities of interest was found in the simulations. In all cases, the proposed schemes enabled determination of the geometric characteristics of a radiotherapeutic device with accuracy better than one hundredth of a millimeter and one hundredth of a degree. CONCLUSIONS: A concept of a multimodule multifiducial phantom has been introduced. Analytical framework has been developed to extract geometric characteristics of radiotherapy devices from projection images of a phantom. The phantom design and the methodology developed have been tested in simulations.

Demand for radiotherapy in Spain

Aim. Assessing the demand for radiotherapy in Spain based on existing evidence to estimate the human resources and equipment needed so that every person in Spain has access to high-quality radiotherapy when they need it. Material and methods. We used data from the European Cancer Observatory on the estimated incidence of cancer in Spain in 2012, along with the evidence-based indications for radiotherapy developed by the Australian CCORE project, to obtain an optimal radiotherapy utilisation proportion (OUP) for each tumour. Results. About 50.5 % of new cancers in Spain require radiotherapy at least once over the course of the disease. Additional demand for these services comes from reradiation therapy and non-melanoma skin cancer. Approximately, 25-30 % of cancer patients with an indication for radiotherapy do not receive it due to factors that include access, patient preference, familiarity with the treatment among physicians, and especially resource shortages, all of which contribute to its underutilisation. Conclusions. Radiotherapy is underused in Spain. The increasing incidence of cancer expected over the next decade and the greater frequency of reradiations necessitate the incorporation of radiotherapy demand into need-based calculations for cancer services planning (AU)

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A preclinical microbeam facility with a conventional x-ray tube.

PURPOSE: Microbeam radiation therapy is an innovative treatment approach in radiation therapy that uses arrays of a few tens of micrometer wide and a few hundreds of micrometer spaced planar x-ray beams as treatment fields. In preclinical studies these fields efficiently eradicated tumors while normal tissue could effectively be spared. However, development and clinical application of microbeam radiation therapy is impeded by a lack of suitable small scale sources. Until now, only large synchrotrons provide appropriate beam properties for the production of microbeams. METHODS: In this work, a conventional x-ray tube with a small focal spot and a specially designed collimator are used to produce microbeams for preclinical research. The applicability of the developed source is demonstrated in a pilot in vitro experiment. The properties of the produced radiation field are characterized by radiochromic film dosimetry. RESULTS: 50 µm wide and 400 µm spaced microbeams were produced in a 20 × 20 mm2 sized microbeam field. The peak to valley dose ratio ranged from 15.5 to 30, which is comparable to values obtained at synchrotrons. A dose rate of up to 300 mGy/s was achieved in the microbeam peaks. Analysis of DNA double strand repair and cell cycle distribution after in vitro exposures of pancreatic cancer cells (Panc1) at the x-ray tube and the European Synchrotron leads to similar results. In particular, a reduced G2 cell cycle arrest is observed in cells in the microbeam peak region. CONCLUSIONS: At its current stage, the source is restricted to in vitro applications. However, moderate modifications of the setup may soon allow in vivo research in mice and rats.

NOD-SCID mice irradiation with medical accelerators: Dosimetric and radiobiological results.

PURPOSE: Preclinical studies normally requires dedicated instruments due to the small anatomical scales involved, but the possibility of using clinical devices for this purpose may be of economical, scientific and translational interest. In the present work the accurate description of treatment planning, dosimetric results, radiotoxicity and tumor response of the irradiation of NOD-SCID mice were presented. Two medical linear accelerators, TrueBeam STx and Tomotherapy Hi-ART, were compared. NOD-SCID mice irradiation with Tomotherapy is a novelty, as well as the comparison of different irradiation techniques, devices and dose fractionations. METHODS: Human derived glioblastoma multiforme neurospheres were injected in immunocompromised NOD-SCID mice to establish xenograft models. Mice were anaesthetized and placed in a plexiglas cage pieboth to perform CT scan for treatment planning purposes and for the irradiation. Three fractionation schedules were evaluated: 4Gy/1 fraction, 4Gy/2 fractions and 6Gy/3 fractions. Tomotherapy planning parameters, the presence of a bolus layer and the irradiation time were reported. After irradiation, mice were examined daily and sacrificed when they showed signs of suffering or when tumor volume reached the established endpoint. Outcomes regarding both radiotoxicity and tumor response were evaluated comparing irradiated mice as respect to their controls. RESULTS: Survival analysis showed that Tomotherapy irradiation with 6Gy/3 fractions with a bolus layer prolong mice survival (log-rank test, p<0.02). Tumor volume and mice survival were significantly different in irradiated xenografts as compared to their controls (t-test, p<0.03; log-rank, p<0.05). CONCLUSION: The radiobiological potential of Tomotherapy in inducing tumor growth stabilization is demonstrated.

Towards clinical application: prompt gamma imaging of passively scattered proton fields with a knife-edge slit camera.

Prompt γ-ray imaging with a knife-edge shaped slit camera provides the possibility of verifying proton beam range in tumor therapy. Dedicated experiments regarding the characterization of the camera system have been performed previously. Now, we aim at implementing the prototype into clinical application of monitoring patient treatments. Focused on this goal of translation into clinical operation, we systematically addressed remaining challenges and questions. We developed a robust energy calibration routine and corresponding quality assurance protocols. Furthermore, with dedicated experiments, we determined the positioning precision of the system to 1.1 mm (2σ). For the first time, we demonstrated the application of the slit camera, which was intentionally developed for pencil beam scanning, to double scattered proton beams. Systematic experiments with increasing complexity were performed. It was possible to visualize proton range shifts of 2-5 mm with the camera system in phantom experiments in passive scattered fields. Moreover, prompt γ-ray profiles for single iso-energy layers were acquired by synchronizing time resolved measurements to the rotation of the range modulator wheel of the treatment system. Thus, a mapping of the acquired profiles to different anatomical regions along the beam path is feasible and additional information on the source of potential range shifts can be obtained. With the work presented here, we show that an application of the slit camera in clinical treatments is possible and of potential benefit.

Technical aspects of real time positron emission tracking for gated radiotherapy.

PURPOSE: Respiratory motion can lead to treatment errors in the delivery of radiotherapy treatments. Respiratory gating can assist in better conforming the beam delivery to the target volume. We present a study of the technical aspects of a real time positron emission tracking system for potential use in gated radiotherapy. METHODS: The tracking system, called PeTrack, uses implanted positron emission markers and position sensitive gamma ray detectors to track breathing motion in real time. PeTrack uses an expectation-maximization algorithm to track the motion of fiducial markers. A normalized least mean squares adaptive filter predicts the location of the markers a short time ahead to account for system response latency. The precision and data collection efficiency of a prototype PeTrack system were measured under conditions simulating gated radiotherapy. The lung insert of a thorax phantom was translated in the inferior-superior direction with regular sinusoidal motion and simulated patient breathing motion (maximum amplitude of motion ±10 mm, period 4 s). The system tracked the motion of a (22)Na fiducial marker (0.34 MBq) embedded in the lung insert every 0.2 s. The position of the was marker was predicted 0.2 s ahead. For sinusoidal motion, the equation used to model the motion was fitted to the data. The precision of the tracking was estimated as the standard deviation of the residuals. Software was also developed to communicate with a Linac and toggle beam delivery. In a separate experiment involving a Linac, 500 monitor units of radiation were delivered to the phantom with a 3 × 3 cm photon beam and with 6 and 10 MV accelerating potential. Radiochromic films were inserted in the phantom to measure spatial dose distribution. In this experiment, the period of motion was set to 60 s to account for beam turn-on latency. The beam was turned off when the marker moved outside of a 5-mm gating window. RESULTS: The precision of the tracking in the IS direction was 0.53 mm for a sinusoidally moving target, with an average count rate ∼250 cps. The average prediction error was 1.1 ± 0.6 mm when the marker moved according to irregular patient breathing motion. Across all beam deliveries during the radiochromic film measurements, the average prediction error was 0.8 ± 0.5 mm. The maximum error was 2.5 mm and the 95th percentile error was 1.5 mm. Clear improvement of the dose distribution was observed between gated and nongated deliveries. The full-width at halfmaximum of the dose profiles of gated deliveries differed by 3 mm or less than the static reference dose distribution. Monitoring of the beam on/off times showed synchronization with the location of the marker within the latency of the system. CONCLUSIONS: PeTrack can track the motion of internal fiducial positron emission markers with submillimeter precision. The system can be used to gate the delivery of a Linac beam based on the position of a moving fiducial marker. This highlights the potential of the system for use in respiratory-gated radiotherapy.

Flattening filter free beams from TrueBeam and Versa HD units: Evaluation of the parameters for quality assurance.

PURPOSE: Flattening filter free (FFF) beams generated by medical linear accelerators are today clinically used for stereotactical and non-stereotactical radiotherapy treatments. Such beams differ from the standard flattened beams (FF) in the high dose rate and the profile shape peaked on the beam central axis. Definition of new parameters as unflatness and slope for FFF beams has been proposed based on a renormalization factor for FFF profiles. The present study aims to assess the dosimetric differences between FFF beams generated by linear accelerators from different vendors, and to provide renormalization and parameter data of the two kinds of units. METHODS: Dosimetric data from two Varian TrueBeam and two Elekta Versa HD linear accelerators, all with 6 and 10 MV nominal accelerating potentials, FF and FFF modes have been collected. Renormalization factors and related fit parameters according to Fogliata et al. ["Definition of parameters for quality assurance of flattening filter free (FFF) photon beams in radiation therapy," Med. Phys. 39, 6455-6464 (2012)] have been evaluated for FFF beams of both units and energies. Unflatness and slope parameters from profile curves were evaluated. Dosimetric differences in terms of beam penetration and near-the-surface dose were also assessed. RESULTS: FFF profile parameters have been updated; renormalization factors and unflatness from the Varian units are consistent with the published data. Elekta FFF beam qualities, different from the Varian generated beams, tend to express similar behaviour as the FF beam of the corresponding nominal energy. TPR20,10 for 6 and 10 MV FF and FFF TrueBeam beams are 0.665, 0.629 (6 MV) and 0.738, 0.703 (10 MV). The same figures for Versa HD units are 0.684, 0.678 (6 MV) and 0.734, 0.721 (10 MV). CONCLUSIONS: Renormalization factor and unflatness parameters evaluated from Varian and Elekta FFF beams are provided, in particular renormalization factors table and fit parameters.

Low Z target switching to increase tumor endothelial cell dose enhancement during gold nanoparticle-aided radiation therapy.

PURPOSE: Previous studies have introduced gold nanoparticles as vascular-disrupting agents during radiation therapy. Crucial to this concept is the low energy photon content of the therapy radiation beam. The authors introduce a new mode of delivery including a linear accelerator target that can toggle between low Z and high Z targets during beam delivery. In this study, the authors examine the potential increase in tumor blood vessel endothelial cell radiation dose enhancement with the low Z target. METHODS: The authors use Monte Carlo methods to simulate delivery of three different clinical photon beams: (1) a 6 MV standard (Cu/W) beam, (2) a 6 MV flattening filter free (Cu/W), and (3) a 6 MV (carbon) beam. The photon energy spectra for each scenario are generated for depths in tissue-equivalent material: 2, 10, and 20 cm. The endothelial dose enhancement for each target and depth is calculated using a previously published analytic method. RESULTS: It is found that the carbon target increases the proportion of low energy (<150 keV) photons at 10 cm depth to 28% from 8% for the 6 MV standard (Cu/W) beam. This nearly quadrupling of the low energy photon content incident on a gold nanoparticle results in 7.7 times the endothelial dose enhancement as a 6 MV standard (Cu/W) beam at this depth. Increased surface dose from the low Z target can be mitigated by well-spaced beam arrangements. CONCLUSIONS: By using the fast-switching target, one can modulate the photon beam during delivery, producing a customized photon energy spectrum for each specific situation.

Development and evaluation of a short-range applicator for treating superficial moving tumors with respiratory-gated spot-scanning proton therapy using real-time image guidance.

Treatment of superficial tumors that move with respiration (e.g. lung tumors) using spot-scanning proton therapy (SSPT) is a high-priority research area. The recently developed real-time image-gated proton beam therapy (RGPT) system has proven to be useful for treating moving tumors deep inside the liver. However, when treating superficial tumors, the proton's range is small and so is the sizes of range straggling, making the Bragg-peaks extremely sharp compared to those located in deep-seated tumors. The extreme sharpness of Bragg-peaks is not always beneficial because it necessitates a large number of energy layers to make a spread-out Bragg-peak, resulting in long treatment times, and is vulnerable to motion-induced dose deterioration. We have investigated a method to treat superficial moving tumors in the lung by the development of an applicator compatible with the RGPT system. A mini-ridge filter (MRF) was developed to broaden the pristine Bragg-peak and, accordingly, decrease the number of required energy layers to obtain homogeneous irradiation. The applicator position was designed so that the fiducial marker's trajectory can be monitored by fluoroscopy during proton beam-delivery. The treatment plans for three lung cancer patients were made using the applicator, and four-dimensional (4D) dose calculations for the RGPT were performed using patient respiratory motion data. The effect of the MRF on the dose distributions and treatment time was evaluated. With the MRF, the number of energy layers was decreased to less than half of that needed without it, whereas the target volume coverage values (D99%, D95%, D50%, D2%) changed by less than 1% of the prescribed dose. Almost no dose distortion was observed after the 4D dose calculation, whereas the treatment time decreased by 26%-37%. Therefore, we conclude that the developed applicator compatible with RGPT is useful to solve the issue in the treatment of superficial moving tumors with SSPT.

Three-dimensional conformal arc radiotherapy using a C-arm linear accelerator with a computed tomography on-rail system for prostate cancer: clinical outcomes.

BACKGROUND: We report the feasibility and treatment outcomes of image-guided three-dimensional conformal arc radiotherapy (3D-CART) using a C-arm linear accelerator with a computed tomography (CT) on-rail system for localized prostate cancer. METHODS AND MATERIALS: Between 2006 and 2011, 282 consecutive patients with localized prostate cancer were treated with in-room CT-guided 3D-CART. Biochemical failure was defined as a rise of at least 2.0 ng/ml beyond the nadir prostate-specific antigen level. Toxicity was scored according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. RESULTS: A total of 261 patients were analyzed retrospectively (median follow-up: 61.6 months). The median prescribed 3D-CART dose was 82 Gy (2 Gy/fraction, dose range: 78-86 Gy), and 193 of the patients additionally received hormonal therapy. The 5-year overall survival rate was 93.9 %. Among low-, intermediate-, and high-risk patients, 5-year rates of freedom from biochemical failure were 100, 91.5 and 90.3 %, respectively. Rates of grade 2-3 late gastrointestinal and genitourinary toxicities were 2.3 and 11.4 %, respectively. No patient experienced late grade 4 or higher toxicity. CONCLUSIONS: In-room CT-guided 3D-CART was feasible and effective for localized prostate cancer. Treatment outcomes were comparable to those previously reported for intensity-modulated radiotherapy.

A virtual simulator designed for collision prevention in proton therapy.

PURPOSE: In proton therapy, collisions between the patient and nozzle potentially occur because of the large nozzle structure and efforts to minimize the air gap. Thus, software was developed to predict such collisions between the nozzle and patient using treatment virtual simulation. METHODS: Three-dimensional (3D) modeling of a gantry inner-floor, nozzle, and robotic-couch was performed using SolidWorks based on the manufacturer's machine data. To obtain patient body information, a 3D-scanner was utilized right before CT scanning. Using the acquired images, a 3D-image of the patient's body contour was reconstructed. The accuracy of the image was confirmed against the CT image of a humanoid phantom. The machine components and the virtual patient were combined on the treatment-room coordinate system, resulting in a virtual simulator. The simulator simulated the motion of its components such as rotation and translation of the gantry, nozzle, and couch in real scale. A collision, if any, was examined both in static and dynamic modes. The static mode assessed collisions only at fixed positions of the machine's components, while the dynamic mode operated any time a component was in motion. A collision was identified if any voxels of two components, e.g., the nozzle and the patient or couch, overlapped when calculating volume locations. The event and collision point were visualized, and collision volumes were reported. RESULTS: All components were successfully assembled, and the motions were accurately controlled. The 3D-shape of the phantom agreed with CT images within a deviation of 2 mm. Collision situations were simulated within minutes, and the results were displayed and reported. CONCLUSIONS: The developed software will be useful in improving patient safety and clinical efficiency of proton therapy.

Pharmacokinetic digital phantoms for accuracy assessment of image-based dosimetry in (177)Lu-DOTATATE peptide receptor radionuclide therapy.

Patient-specific image-based dosimetry is considered to be a useful tool to limit toxicity associated with peptide receptor radionuclide therapy (PRRT). To facilitate the establishment and reliability of absorbed-dose response relationships, it is essential to assess the accuracy of dosimetry in clinically realistic scenarios. To this end, we developed pharmacokinetic digital phantoms corresponding to patients treated with (177)Lu-DOTATATE. Three individual voxel phantoms from the XCAT population were generated and assigned a dynamic activity distribution based on a compartment model for (177)Lu-DOTATATE, designed specifically for this purpose. The compartment model was fitted to time-activity data from 10 patients, primarily acquired using quantitative scintillation camera imaging. S values for all phantom source-target combinations were calculated based on Monte-Carlo simulations. Combining the S values and time-activity curves, reference values of the absorbed dose to the phantom kidneys, liver, spleen, tumours and whole-body were calculated. The phantoms were used in a virtual dosimetry study, using Monte-Carlo simulated gamma-camera images and conventional methods for absorbed-dose calculations. The characteristics of the SPECT and WB planar images were found to well represent those of real patient images, capturing the difficulties present in image-based dosimetry. The phantoms are expected to be useful for further studies and optimisation of clinical dosimetry in (177)Lu PRRT.

Robotic real-time translational and rotational head motion correction during frameless stereotactic radiosurgery.

PURPOSE: To develop a control system to correct both translational and rotational head motion deviations in real-time during frameless stereotactic radiosurgery (SRS). METHODS: A novel feedback control with a feed-forward algorithm was utilized to correct for the coupling of translation and rotation present in serial kinematic robotic systems. Input parameters for the algorithm include the real-time 6DOF target position, the frame pitch pivot point to target distance constant, and the translational and angular Linac beam off (gating) tolerance constants for patient safety. Testing of the algorithm was done using a 4D (XY Z + pitch) robotic stage, an infrared head position sensing unit and a control computer. The measured head position signal was processed and a resulting command was sent to the interface of a four-axis motor controller, through which four stepper motors were driven to perform motion compensation. RESULTS: The control of the translation of a brain target was decoupled with the control of the rotation. For a phantom study, the corrected position was within a translational displacement of 0.35 mm and a pitch displacement of 0.15° 100% of the time. For a volunteer study, the corrected position was within displacements of 0.4 mm and 0.2° over 98.5% of the time, while it was 10.7% without correction. CONCLUSIONS: The authors report a control design approach for both translational and rotational head motion correction. The experiments demonstrated that control performance of the 4D robotic stage meets the submillimeter and subdegree accuracy required by SRS.