Dosimetric evaluation and beam characterization of pair production enhanced radiotherapy (PPER) with the use of organometallics.

The current study evaluates dosimetric and spectral effects when platinum (Pt)-based chemotherapeutics and less toxic tungstophosphoric-acid (TPA) organometallics are present during x-ray radiotherapy. We hypothesize that the use of high energy photon beams (i.e. 18 MV) will increase absorbed dose due to increased pair production from high-Z elements and thus result in additional tumor cell kill. EGSnrc code was used to examine the contribution of pair production to dose in the presence of the high-Z material (TPA, Pt mixtures and tungsten, W) as a function of beam energy. Variables included different concentrations (100 µmolar, 1 mmolar), depths (5 mm, 10 cm), thicknesses (5 mm, 5 cm) and energies (6, 18 MV). Overall, for the deeper depth, the 511 keV photon fluence increase was up 31% (18 MV-1 mmolar) while at 6 MV it was between 10%-11% depending on the concentration. For the shallower depth, 18 MV fluence increase was up 14.6% (1 mmolar) and 18.6% (1 mmolar) for the 6 MV. The dose enhancement effect due to pair production was up 25%-30% and a total 33%-58% depending on the depth. The benefit related to pair production was more for 18 MV and under conditions that simulated a realistic clinical setup. While part of the effect could be attributed to photoabsorption, a significant contribution of dose could result from pair production. Experimental clonogenic survival assay was consistent with the theory in that the low dose shoulder region of a cell survival curve was reduced using TPA and 18 MV compared with TPA and 6 MV or compared with no TPA and 18 MV; RBE was approximately 2 at the dose commonly used in conventional fractionated clinical radiotherapy. This suggests a potential new strategy for dose enhancement based on pair production using higher energy beamlines.

Technical Note: Evaluation of the systematic accuracy of a frameless, multiple image modality guided, linear accelerator based stereotactic radiosurgery system.

PURPOSE: To evaluate the total systematic accuracy of a frameless, image guided stereotactic radiosurgery system. METHODS: The localization accuracy and intermodality difference was determined by delivering radiation to an end-to-end prototype phantom, in which the targets were localized using optical surface monitoring system (OSMS), electromagnetic beacon-based tracking (Calypso®), cone-beam CT, "snap-shot" planar x-ray imaging, and a robotic couch. Six IMRT plans with jaw tracking and a flattening filter free beam were used to study the dosimetric accuracy for intracranial and spinal stereotactic radiosurgery treatment. RESULTS: End-to-end localization accuracy of the system evaluated with the end-to-end phantom was 0.5 ± 0.2 mm with a maximum deviation of 0.9 mm over 90 measurements (including jaw, MLC, and cone measurements for both auto and manual fusion) for single isocenter, single target treatment, 0.6 ± 0.4 mm for multitarget treatment with shared isocenter. Residual setup errors were within 0.1 mm for OSMS, and 0.3 mm for Calypso. Dosimetric evaluation based on absolute film dosimetry showed greater than 90% pass rate for all cases using a gamma criteria of 3%/1 mm. CONCLUSIONS: The authors' experience demonstrates that the localization accuracy of the frameless image-guided system is comparable to robotic or invasive frame based radiosurgery systems.

Extracting the normal lung dose-response curve from clinical DVH data: a possible role for low dose hyper-radiosensitivity, increased radioresistance.

In conventionally fractionated radiation therapy for lung cancer, radiation pneumonitis' (RP) dependence on the normal lung dose-volume histogram (DVH) is not well understood. Complication models alternatively make RP a function of a summary statistic, such as mean lung dose (MLD). This work searches over damage profiles, which quantify sub-volume damage as a function of dose. Profiles that achieve best RP predictive accuracy on a clinical dataset are hypothesized to approximate DVH dependence.Step function damage rate profiles R(D) are generated, having discrete steps at several dose points. A range of profiles is sampled by varying the step heights and dose point locations. Normal lung damage is the integral of R(D) with the cumulative DVH. Each profile is used in conjunction with a damage cutoff to predict grade 2 plus (G2+) RP for DVHs from a University of Michigan clinical trial dataset consisting of 89 CFRT patients, of which 17 were diagnosed with G2+ RP.Optimal profiles achieve a modest increase in predictive accuracy--erroneous RP predictions are reduced from 11 (using MLD) to 8. A novel result is that optimal profiles have a similar distinctive shape: enhanced damage contribution from low doses (<20 Gy), a flat contribution from doses in the range ~20-40 Gy, then a further enhanced contribution from doses above 40 Gy. These features resemble the hyper-radiosensitivity / increased radioresistance (HRS/IRR) observed in some cell survival curves, which can be modeled using Joiner's induced repair model.A novel search strategy is employed, which has the potential to estimate RP dependence on the normal lung DVH. When applied to a clinical dataset, identified profiles share a characteristic shape, which resembles HRS/IRR. This suggests that normal lung may have enhanced sensitivity to low doses, and that this sensitivity can affect RP risk.

Changes realized from extended bit-depth and metal artifact reduction in CT.

PURPOSE: High-Z material in computed tomography (CT) yields metal artifacts that degrade image quality and may cause substantial errors in dose calculation. This study couples a metal artifact reduction (MAR) algorithm with enhanced 16-bit depth (vs standard 12-bit) to quantify potential gains in image quality and dosimetry. METHODS: Extended CT to electron density (CT-ED) curves were derived from a tissue characterization phantom with titanium and stainless steel inserts scanned at 90-140 kVp for 12- and 16-bit reconstructions. MAR was applied to sinogram data (Brilliance BigBore CT scanner, Philips Healthcare, v.3.5). Monte Carlo simulation (MC-SIM) was performed on a simulated double hip prostheses case (Cerrobend rods embedded in a pelvic phantom) using BEAMnrc∕Dosxyz (400,000,0000 histories, 6X, 10 × 10 cm(2) beam traversing Cerrobend rod). A phantom study was also conducted using a stainless steel rod embedded in solid water, and dosimetric verification was performed with Gafchromic film analysis (absolute difference and gamma analysis, 2% dose and 2 mm distance to agreement) for plans calculated with Anisotropic Analytic Algorithm (AAA, Eclipse v11.0) to elucidate changes between 12- and 16-bit data. Three patients (bony metastases to the femur and humerus, and a prostate cancer case) with metal implants were reconstructed using both bit depths, with dose calculated using AAA and derived CT-ED curves. Planar dose distributions were assessed via matrix analyses and using gamma criteria of 2%∕2 mm. RESULTS: For 12-bit images, CT numbers for titanium and stainless steel saturated at 3071 Hounsfield units (HU), whereas for 16-bit depth, mean CT numbers were much larger (e.g., titanium and stainless steel yielded HU of 8066.5 ± 56.6 and 13,588.5 ± 198.8 for 16-bit uncorrected scans at 120 kVp, respectively). MC-SIM was well-matched between 12- and 16-bit images except downstream of the Cerrobend rod, where 16-bit dose was ∼6.4% greater than 12-bit. Absolute film dosimetry in a region downstream of a stainless steel rod revealed that 16-bit calculated dose, with and without MAR, agreed more closely with film results (1%-2% less than film) as compared to 12-bit reconstructions (5.6%-6.5% less than film measurements). Gamma analysis revealed that 16-bit dose calculations were better matched to film results than 12-bit (∼10% higher pass rates for 16-bit). Similar results were observed in two patient cases; the largest discrepancy was observed for a femur case where 12-bit doses, both with and without MAR correction, were 6-7 Gy lower (∼17%-20% of the prescription dose) as compared to 16-bit dose calculations. However, when beams are not directly traversing metal, such as a prostate cancer case with bilateral hip prostheses; the impact of 16-bit reconstruction was diminished. CONCLUSIONS: These results suggest that it may be desirable to implement 16-bit MAR-corrected images for treatment planning purposes, which can provide a more accurate dosimetric approach coupled with improved visualization by suppression of CT artifacts.

Commissioning of the Varian TrueBeam linear accelerator: a multi-institutional study.

PURPOSE: Latest generation linear accelerators (linacs), i.e., TrueBeam (Varian Medical Systems, Palo Alto, CA) and its stereotactic counterpart, TrueBeam STx, have several unique features, including high-dose-rate flattening-filter-free (FFF) photon modes, reengineered electron modes with new scattering foil geometries, updated imaging hardware/software, and a novel control system. An evaluation of five TrueBeam linacs at three different institutions has been performed and this work reports on the commissioning experience. METHODS: Acceptance and commissioning data were analyzed for five TrueBeam linacs equipped with 120 leaf (5 mm width) MLCs at three different institutions. Dosimetric data and mechanical parameters were compared. These included measurements of photon beam profiles (6X, 6XFFF, 10X, 10XFFF, 15X), photon and electron percent depth dose (PDD) curves (6, 9, 12 MeV), relative photon output factors (Scp), electron cone factors, mechanical isocenter accuracy, MLC transmission, and dosimetric leaf gap (DLG). End-to-end testing and IMRT commissioning were also conducted. RESULTS: Gantry/collimator isocentricity measurements were similar (0.27-0.28 mm), with overall couch/gantry/collimator values of 0.46-0.68 mm across the three institutions. Dosimetric data showed good agreement between machines. The average MLC DLGs for 6, 10, and 15 MV photons were 1.33 ± 0.23, 1.57 ± 0.24, and 1.61 ± 0.26 mm, respectively. 6XFFF and 10XFFF modes had average DLGs of 1.16 ± 0.22 and 1.44 ± 0.30 mm, respectively. MLC transmission showed minimal variation across the three institutions, with the standard deviation <0.2% for all linacs. Photon and electron PDDs were comparable for all energies. 6, 10, and 15 MV photon beam quality, %dd(10)x varied less than 0.3% for all linacs. Output factors (Scp) and electron cone factors agreed within 0.27%, on average; largest variations were observed for small field sizes (1.2% coefficient of variation, 10 MV, 2 × 2 cm(2)) and small cone sizes (<1% coefficient of variation, 6 × 6 cm(2) cone), respectively. CONCLUSIONS: Overall, excellent agreement was observed in TrueBeam commissioning data. This set of multi-institutional data can provide comparison data to others embarking on TrueBeam commissioning, ultimately improving the safety and quality of beam commissioning.

A Monte Carlo tutorial and the application for radiotherapy treatment planning.

Monte Carlo-based treatment planning algorithms are advancing rapidly and will certainly be implemented as part of conventional treatment planning systems in the near future. This paper was designed as a basic tutorial for using the Monte Carlo method as applied to radiotherapy treatment planning. The tutorial addresses the basic transport differences between photon and electron transport as well as the sampling distributions. The implementation of a virtual linac source model and the conversion from the Monte Carlo source modeling reference plane into the treatment reference plane is discussed. The implementation of a thresholding algorithm for converting CT electron density to patient specific materials is also presented. A 6-field prostate boost treatment is used to compare a conventional treatment planning algorithm (pencil beam model) with a Monte Carlo simulation algorithm. The agreement between the 2 calculation methods is good based upon the qualitative comparison of the isodose distribution and the dose-volume histograms for the prostate and the rectum. The effects of statistical uncertainty on the Monte Carlo calculation are also presented.