A model-based 3D patient-specific pre-treatment QA method for VMAT using the EPID.

This study reports the development and validation of a model-based, 3D patient dose reconstruction method for pre-treatment quality assurance using EPID images. The method is also investigated for sensitivity to potential MLC delivery errors. Each cine-mode EPID image acquired during plan delivery was processed using a previously developed back-projection dose reconstruction model providing a 3D dose estimate on the CT simulation data. Validation was carried out using 24 SBRT-VMAT patient plans by comparing: (1) ion chamber point dose measurements in a solid water phantom, (2) the treatment planning system (TPS) predicted 3D dose to the EPID reconstructed 3D dose in a solid water phantom, and (3) the TPS predicted 3D dose to the EPID and our forward predicted reconstructed 3D dose in the patient (CT data). AAA and AcurosXB were used for TPS predictions. Dose distributions were compared using 3%/3 mm (95% tolerance) and 2%/2 mm (90% tolerance) γ-tests in the planning target volume (PTV) and 20% dose volumes. The average percentage point dose differences between the ion chamber and the EPID, AcurosXB, and AAA were 0.73 ± 1.25%, 0.38 ± 0.96% and 1.06 ± 1.34% respectively. For the patient (CT) dose comparisons, seven (3%/3 mm) and nine (2%/2 mm) plans failed the EPID versus AAA. All plans passed the EPID versus Acuros XB and the EPID versus forward model γ-comparisons. Four types of MLC sensitive errors (opening, shifting, stuck, and retracting), of varying magnitude (0.2, 0.5, 1.0, 2.0 mm), were introduced into six different SBRT-VMAT plans. γ-comparisons of the erroneous EPID dose and original predicted dose were carried out using the same criteria as above. For all plans, the sensitivity testing using a 3%/3 mm γ-test in the PTV successfully determined MLC errors on the order of 1.0 mm, except for the single leaf retraction-type error. A 2%/2 mm criteria produced similar results with two more additional detected errors.

An in vivo dose verification method for SBRT-VMAT delivery using the EPID.

PURPOSE: Radiation treatments have become increasingly more complex with the development of volumetric modulated arc therapy (VMAT) and the use of stereotactic body radiation therapy (SBRT). SBRT involves the delivery of substantially larger doses over fewer fractions than conventional therapy. SBRT-VMAT treatments will strongly benefit from in vivo patient dose verification, as any errors in delivery can be more detrimental to the radiobiology of the patient as compared to conventional therapy. Electronic portal imaging devices (EPIDs) are available on most commercial linear accelerators (Linacs) and their documented use for dosimetry makes them valuable tools for patient dose verification. In this work, the authors customize and validate a physics-based model which utilizes on-treatment EPID images to reconstruct the 3D dose delivered to the patient during SBRT-VMAT delivery. METHODS: The SBRT Linac head, including jaws, multileaf collimators, and flattening filter, were modeled using Monte Carlo methods and verified with measured data. The simulation provides energy spectrum data that are used by their "forward" model to then accurately predict fluence generated by a SBRT beam at a plane above the patient. This fluence is then transported through the patient and then the dose to the phosphor layer in the EPID is calculated. Their "inverse" model back-projects the EPID measured focal fluence to a plane upstream of the patient and recombines it with the extra-focal fluence predicted by the forward model. This estimate of total delivered fluence is then forward projected onto the patient's density matrix and a collapsed cone convolution algorithm calculates the dose delivered to the patient. The model was tested by reconstructing the dose for two prostate, three lung, and two spine SBRT-VMAT treatment fractions delivered to an anthropomorphic phantom. It was further validated against actual patient data for a lung and spine SBRT-VMAT plan. The results were verified with the treatment planning system (TPS) (ECLIPSE AAA) dose calculation. RESULTS: The SBRT-VMAT reconstruction model performed very well when compared to the TPS. A stringent 2%/2 mm χ-comparison calculation gave pass rates better than 91% for the prostate plans, 88% for the lung plans, and 86% for the spine plans for voxels containing 80% or more of the prescribed dose. Patient data were 86% for the lung and 95% for the spine. A 3%/3 mm χ-comparison was also performed and gave pass rates better than 93% for all plan types. CONCLUSIONS: The authors have customized and validated a robust, physics-based model that calculates the delivered dose to a patient for SBRT-VMAT delivery using on-treatment EPID images. The accuracy of the results indicates that this approach is suitable for clinical implementation. Future work will incorporate this model into both offline and real-time clinical adaptive radiotherapy.

A Monte Carlo tool for evaluating VMAT and DIMRT treatment deliveries including planar detectors.

The aim of this work is to describe and validate a new general research tool that performs Monte Carlo (MC) simulations for volumetric modulated arc therapy (VMAT) and dynamic intensity modulated radiation therapy (DIMRT), simultaneously tracking dose deposition in both the patient CT geometry and an arbitrary planar detector system. The tool is generalized to handle either entrance or exit detectors and provides the simulated dose for the individual control-points of the time-dependent VMAT and DIMRT deliveries. The MC simulation tool was developed with the EGSnrc radiation transport. For the individual control point simulation, we rotate the patient/phantom volume only (i.e. independent of the gantry and planar detector geometries) using the gantry angle in the treatment planning system (TPS) DICOM RP file such that each control point has its own unique phantom file. After MC simulation, we obtained the total dose to the phantom by summing dose contributions for all control points. Scored dose to the sensitive layer of the planar detector is available for each control point. To validate the tool, three clinical treatment plans were used including VMAT plans for a prostate case and a head-and-neck case, and a DIMRT plan for a head-and-neck case. An electronic portal imaging device operated in 'movie' mode was used with the VMAT plans delivered to cylindrical and anthropomorphic phantoms to validate the code using an exit detector. The DIMRT plan was delivered to a novel transmission detector, to validate the code using an entrance detector. The total MC 3D absolute doses in patient/phantom were compared with the TPS doses, while 2D MC doses were compared with planar detector doses for all individual control points, using the gamma evaluation test with 3%/3 mm criteria. The MC 3D absolute doses demonstrated excellent agreement with the TPS doses for all the tested plans, with about 95% of voxels having γ <1 for the plans. For planar dosimetry image comparisons, we defined an acceptable pass rate of >90% of percentage pixels with γ <1. We found that over 90% of control points in the plans passed this criterion. In general, our results indicate that the simulation tool is suitable for accurately calculating both patient/phantom doses and planar doses for VMAT dose delivery. The tool will be valuable to check performance and advance the development of in vivo planar detectors for use in measurement-based VMAT dose verification. In addition, the tool can be useful as an independent research tool for VMAT commissioning of the TPS and delivery system.

Investigation of the spatial resolution of an online dose verification device.

PURPOSE: The aim of this work is to characterize a new online dose verification device, COMPASS transmission detector array (IBA Dosimetry, Schwarzenbruck, Germany). The array is composed of 1600 cylindrical ionization chambers of 3.8 mm diameter, separated by 6.5 mm center-to-center spacing, in a 40 × 40 arrangement. METHODS: The line spread function (LSF) of a single ion chamber in the detector was measured with a narrow slit collimator for a 6 MV photon beam. The 0.25 × 10 mm(2) slit was formed by two machined lead blocks. The LSF was obtained by laterally translating the detector in 0.25 mm steps underneath the slit over a range of 24 mm and taking a measurement at each step. This measurement was validated with Monte Carlo simulation using BEAMnrc and DOSXYZnrc. The presampling modulation transfer function (MTF), the Fourier transform of the line spread function, was determined and compared to calculated (Monte Carlo and analytical) MTFs. Two head-and-neck intensity modulated radiation therapy (IMRT) fields were measured using the device and were used to validate the LSF measurement. These fields were simulated with the BEAMnrc Monte Carlo model, and the Monte Carlo generated incident fluence was convolved with the 2D detector response function (derived from the measured LSF) to obtain calculated dose. The measured and calculated dose distributions were then quantitatively compared using χ-comparison criteria of 3% dose difference and 3 mm distance-to-agreement for in-field points (defined as those above the 10% maximum dose threshold). RESULTS: The full width at half-maximum (FWHM) of the measured detector response for a single chamber is 4.3 mm, which is comparable to the chamber diameter of 3.8 mm. The pre-sampling MTF was calculated, and the resolution of one chamber was estimated as 0.25 lp∕mm from the first zero crossing. For both examined IMRT fields, the χ-comparison between measured and calculated data show good agreement with 95.1% and 96.3% of in-field points below χ of 1.0 for fields 1 and 2, respectively (with an average χ of 0.29 for IMRT field 1 and 0.24 for IMRT field 2). CONCLUSIONS: The LSF for a new novel online detector has been measured at 6 MV using a narrow slit technique, and this measurement has been validated by Monte Carlo simulation. The detector response function derived from line spread function has been applied to recover measured IMRT fields. The results have shown that the device measures IMRT fields accurately within acceptable tolerance.

Sci-Fri PM: Delivery - 01: Approach to evaluate the accuracy of individual control-points of a VMAT delivery measured by an EPID.

A unique approach that uses Monte Carlo (MC) methods to validate time-resolved measured dose by an electronic portal imaging device (EPID) during delivery of volumetric modulated arc therapy (VMAT) treatments was investigated. Time-resolved dose is simultaneously scored in both the patient and EPID geometries. A RapidArc© verification plan was generated and delivered on a homogeneous cylindrical phantom. Portal images were collected using an aS1000 amorphous-silicon EPID attached to a Varian Clinac 2100ix. The images were acquired in the continuous acquisition mode and in-house analysis software was used to obtain images for each control point. We performed MC simulation and dose calculation of the verification plan using the EGSnrc MC package. The MC phantom file contains both the EPID model and the cylindrical phantom derived from the CT data sets. For the individual control point simulation, we rotate the phantom only using the gantry angle information. For this work, we calculated dose distributions for five control points (out of a total of 177) in the verification plan. The normalized measured and calculated data were compared using the chi comparison (computationally efficient implementation of gamma). The chi comparison between measured and calculated doses for the five control points using criteria of 3% and 3mm revealed an average of 88.7% of all pixels having χ<1. The agreement will improve when the measured portal images are corrected for flood field and support-arm backscatter effects. This approach allows us to obtain both the EPID dose and the phantom/patient dose. These preliminary results demonstrate promising accuracy. With further improvements, this approach will be useful for benchmarking of time-resolved EPID dose applications intended for rotational IMRT QA and adaptive radiation therapy.

A Monte Carlo investigation of contaminant electrons due to a novel in vivo transmission detector.

A novel transmission detector (IBA Dosimetry, Germany) developed as an IMRT quality assurance tool, intended for in vivo patient dose measurements, is studied here. The goal of this investigation is to use Monte Carlo techniques to characterize treatment beam parameters in the presence of the detector and to compare to those of a plastic block tray (a frequently used clinical device). Particular attention is paid to the impact of the detector on electron contamination model parameters of two commercial dose calculation algorithms. The linac head together with the COMPASS transmission detector (TRD) was modeled using BEAMnrc code. To understand the effect of the TRD on treatment beams, the contaminant electron fluence, energy spectra, and angular distributions at different SSDs were analyzed for open and non-open (i.e. TRD and block tray) fields. Contaminant electrons in the BEAMnrc simulations were separated according to where they were created. Calculation of surface dose and the evaluation of contributions from contaminant electrons were performed using the DOSXYZnrc user code. The effect of the TRD on contaminant electrons model parameters in Eclipse AAA and Pinnacle(3) dose calculation algorithms was investigated. Comparisons of the fluence of contaminant electrons produced in the non-open fields versus open field show that electrons created in the non-open fields increase at shorter SSD, but most of the electrons at shorter SSD are of low energy with large angular spread. These electrons are out-scattered or absorbed in air and contribute less to surface dose at larger SSD. Calculated surface doses with the block tray are higher than those with the TRD. Contribution of contaminant electrons to dose in the buildup region increases with increasing field size. The additional contribution of electrons to surface dose increases with field size for TRD and block tray. The introduction of the TRD results in a 12% and 15% increase in the Gaussian widths used in the contaminant electron source model of the Eclipse AAA dose algorithm. The off-axis coefficient in the Pinnacle(3) dose calculation algorithm decreases in the presence of TRD compared to without the device. The electron model parameters were modified to reflect the increase in electron contamination with the TRD, a necessary step for accurate beam modeling when using the device.

Poster - Thurs Eve-33: Initial implementation of a novel, measurement-based IMRT QA method.

Current measurement-based QA for IMRT typically involves a composite dose delivery to a phantom. However, this approach does not allow a direct dosimetric evaluation of the delivered treatment with respect to the patient anatomy. In this work we implement a novel, measurement-based IMRT QA method which provides an accurate reconstruction of the 3D-dose distribution in the patient model. The RPC Head&Neck phantom and two clinical prostate cases have been examined to date. Step & shoot plans were developed satisfying required dose metrics. A 2D-array of dose chambers (MatriXX, IBA Dosimetry) was mounted on a linear accelerator to capture delivered fluence. The measurement data were read directly by the control software (COMPASS, IBA Dosimetry), which also provides the ability to import patient plan data from the TPS. The COMPASS software also includes a dose calculation engine and head fluence model and requires beam commissioning procedures analogous to those of a TPS. Reconstructed doses and DVHs were compared to those calculated by the TPS. The beam model in the COMPASS software was able to predict percentage depth dose and X and Y profiles for MLC-defined apertures ranging from 1×1-20×20 cm∧2 to within 1.5% (depth-dose), 2.0% (in-field profiles), and 2.5% (out-of-field profiles). Reconstructed doses in the test plans were mostly within 2% of those in the TPS. DVHs compared to <1.2%. Reconstructed doses were overlaid on CT data and contoured structures, to enable a clinically useful understanding of discrepancies as compared to the TPS plan. Research partially sponsored by IBA Dosimetry.

Mutation of Cys-67 alters the thermodynamic stability of the human leukocyte antigen HLA0-B*2705.

The B pocket of the class I major histocompatibility complex-encoded protein HLA-B*2705 has recently been suggested to be responsible for the misfolding of this HLA haplotype and thus to induce susceptibility to autoimmune inflammatory diseases. Four mutants of the B*2705 heavy chain were refolded in the presence of three control peptides. The monitoring of the thermal unfolding of the B*2705-peptide complexes by circular dichroism spectroscopy showed that all heterotrimeric mutants were markedly less stable than the corresponding complexes with the wild-type heavy chain. Among the four heavy chain mutations, the C67S change was investigated for unfolding and peptide binding properties because this position may mediate disulfide pair bridging and alter T-cell recognition of HLA-B*2705. Wild-type heterotrimers completely unfold in a single transition at mild acidic pH whereas increase of the pH to mild basic conditions induce only a partial biphasic unfolding. Cys-67 seems to play a crucial role in controlling the thermodynamic stability of the B*2705-peptide complexes as the C67S mutant unfolds faster and with a single transition, independent of pH. Fluorescence polarization and size exclusion chromatography of unfolding intermediates suggest that the peculiar unfolding of the B*2705 wild-type heavy chain cannot be explained by modified peptide binding properties but more likely by the formation of high molecular weight species.