Cem Altunbas

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.

Hedgehog signaling drives radioresistance and stroma-driven tumor repopulation in head and neck squamous cancers

Local control and overall survival in patients with advanced head and neck squamous cell cancer (HNSCC) remains dismal. Signaling through the Hedgehog (Hh) pathway is associated with epithelial-to-mesenchymal transition, and activation of the Hh effector transcription factor Gli1 is a poor prognostic factor in this disease setting. Here, we report that increased GLI1 expression in the leading edge of HNSCC tumors is further increased by irradiation, where it contributes to therapeutic inhibition. Hh pathway blockade with cyclopamine suppressed GLI1 activation and enhanced tumor sensitivity to radiotherapy. Furthermore, radiotherapy-induced GLI1 expression was mediated in part by the mTOR/S6K1 pathway. Stroma exposed to radiotherapy promoted rapid tumor repopulation, and this effect was suppressed by Hh inhibition. Our results demonstrate that Gli1 that is upregulated at the tumor-stroma intersection in HNSCC is elevated by radiotherapy, where it contributes to stromal-mediated resistance, and that Hh inhibitors offer a rational strategy to reverse this process to sensitize HNSCC to radiotherapy.

Dosimetric errors during treatment of centrally located lung tumors with stereotactic body radiation therapy: Monte Carlo evaluation of tissue inhomogeneity corrections.

Early experience with stereotactic body radiation therapy (SBRT) of centrally located lung tumors indicated increased rate of high-grade toxicity in the lungs. These clinical results were based on treatment plans that were computed using pencil beam-like algorithms and without tissue inhomogeneity corrections. In this study, we evaluated the dosimetric errors in plans with and without inhomogeneity corrections and with planning target volumes (PTVs) that were within the zone of the proximal bronchial tree (BT). For 10 patients, the PTV, lungs, and sections of the BT either inside or within 2cm of the PTV were delineated. Two treatment plans were generated for each patient using the following dose-calculation methods: (1) pencil beam (PB) algorithm without inhomogeneity correction (IC) (PB - IC) and (2) PB with inhomogeneity correction (PB + IC). Both plans had identical beam geometry but different beam segment shapes and monitor units (MU) to achieve similar conformal dose coverage of PTV. To obtain the baseline dose distributions, each plan was recalculated using a Monte Carlo (MC) algorithm by keeping MUs the same in the respective plans. The median maximum dose to the proximal BT and PTV dose coverage in the PB + IC plans were overestimated by 8% and 11%, respectively. However, the median maximum dose to the proximal BT and PTV dose coverage in PB - IC plans were underestimated by 15% and 9%. Similar trends were observed in low-dose regions of the lung within the irradiated volume. Our study indicates that dosimetric bias introduced by unit tissue density plans cannot be characterized as underestimation or overestimation of dose without taking the tumor location into account. This issue should be considered when analyzing clinical toxicity data from early lung SBRT trials that utilized unit tissue density for dose calculations.

Optimized dynamic contrast-enhanced cone-beam CT for target visualization during liver SBRT

The pharmacokinetic behavior of iodine contrast agents makes it difficult to achieve significant enhancement during contrast-enhanced cone-beam CT (CE-CBCT). This study modeled this dynamic behavior to optimize CE-CBCT and improve the localization of liver lesions for SBRT. We developed a model that allows for controlled study of changing iodine concentrations using static phantoms. A projection database consisting of multiple phantom images of differing iodine/scan conditions was built. To reconstruct images of dynamic hepatic concentrations, hepatic contrast enhancement data from conventional CT scans were used to re-assemble the projections to match the expected amount of contrast. In this way the effect of various parameters on image quality was isolated, and using our dynamic model we found parameters for iodine injection, CBCT scanning, and injection/scanning timing which optimize contrast enhancement. Increasing the iodine dose, iodine injection rate, and imaging dose led to significant increases in signal-to-noise ratio (SNR). Reducing the CBCT imaging time also increased SNR, as the image can be completed before the iodine exits the liver. Proper timing of image acquisition played a significant role, as a 30 second error in start time resulted in a 40% SNR decrease. The effect of IV contrast is severely degraded in CBCT, but there is promise that, with optimization of the injection and scan parameters to account for iodine pharmacokinetics, CE-CBCT which models venous-phase blood flow kinetics will be feasible for accurate localization of liver lesions.

SU‐D‐12A‐04: Investigation of a 2D Antiscatter Grid for Flat Panel Detectors

PURPOSE To improve CT number accuracy and contrast sensitivity, a novel 2D antiscatter grid (ASG) for flat panel detector (FPD) based CBCT imaging was evaluated. Experiments were performed to characterize the scatter rejection and contrast sensitivity performance of ASG. The reduction in primary transmission for various ASG geometries was also evaluated by a computational model. METHODS The 2D ASG design was based on multi-hole collimators used in Nuclear Medicine. It consisted of abutted hexagon shaped apertures with 2.5 mm pitch and 32 mm height, and separated by 0.25 mm thick lead septa. Scatter-to-primary ratio (SPR), contrast-to-noise ratio (CNR), and mean primary transmission were measured using a benchtop FPD/x-ray source system. Acrylic slabs of varying thicknesses were imaged with a contrast-detail phantom to measure CNR and SPR under different scatter conditions. Primary transmission was also measured by averaging pixel values in flood field images without the phantom. We additionally explored variation of primary transmission with pitch and septum thickness using a computational model of our ASG. RESULTS Our 2D ASG reduced the SPR from 3.3 to 0.12, and improved CNR by 50% in 20 cm thick slab phantom projections acquired at 120 kVp. While the measured primary transmission was 72.8%, our simulations show that primary transmission can be increased to 86% by reducing the septum thickness to 0.1 mm. Primary transmission further increases to 93% if septum thickness of 0.1 mm is used in conjunction with an increased pitch of 4 mm. CONCLUSION The 2D ASG appears to be a promising scatter rejection device, offering both superior scatter rejection and improved contrast sensitivity. Though its lead footprint reduced primary transmission, our work shows that optimization of aperture pitch and septum thickness can significantly improve the primary transmission.

Rotational setup errors in pediatric stereotactic radiation therapy

PURPOSE Stereotactic radiation therapy (SRT) is an increasingly commonly used technique in children. The use of image guidance increases the ability to accurately position patients. With our robotic couch, rotational errors that can be corrected are limited to approximately 3 degrees. Given this limitation, we reviewed the rotational setup errors in our pediatric brain tumor population. METHODS AND MATERIALS We reviewed the rotational corrections for all pediatric (age ≤21 years old) patients treated at our facility from 2009 to 2011. We compared children <5 years old treated to children between 5 and 21 years old (≥5 years old). Also, we analyzed the effect of steroid use and trends in rotational errors over the treatment period in each age group. RESULTS The mean pitch, roll, and yaw rotational setup errors for younger children are -0.70 ± 2.60 degrees, -0.06 ± 1.89 degrees, and 0.69 ± 2.42 degrees, respectively; for children ≥5 years old, they are 0.46 ± 2.09 degrees, -0.06 ± 1.89 degrees, and 0.69 ± 2.42 degrees, respectively. The mean pitch corrections are larger for children <5 years old (P < .001) and the variance of the pitch, roll, and yaw corrections are all larger for children <5 years old (P < .001). The frequency of rotational errors above 3 degrees for pitch, roll, and yaw is 21.7%, 10.6%, and 20.9% for children <5 years old, and 15.6%, 2.1%, and 13.8% for children ≥5 years old. In both age groups, pitch and roll corrections were larger for children treated with steroids. CONCLUSIONS Rotational errors in our pediatric population occur more frequently than previously reported, and are more common in younger children and in children treated with steroids. These rotational set up errors may not be fully correctable due to mechanical and safety limitations. We have altered our planning and treatment process to better account for rotational errors in children receiving SRT.

WE-AB-207A-10: Transmission Characteristics of a Two Dimensional Antiscatter Grid Prototype for CBCT

PURPOSE Scattered radiation remains to be a major contributor to image quality degradation in CBCT. To address the scatter problem, a focused, 2D antiscatter grid (2DASG) prototype was designed, and fabricated using additive manufacturing processes. Its scatter and primary transmission properties were characterized using a linac mounted CBCT system. METHODS The prototype 2DASG was composed of rectangular grid holes separated by tungsten septa, and has a grid pitch of 2.91 mm, grid ratio of 8, and a septal thickness of 0.1 mm. Each grid hole was aligned or focused towards the x-ray source in half-fan (i.e. offset detector) geometry of the Varian TrueBeam CBCT system. Scatter and primary transmission experiments were performed by using acrylic blocks and the beam-stop method. Transmission properties of a radiographic ASG (1DASG) (grid ratio of 10) was also performed by using the identical setup. RESULTS At 30 cm phantom thickness, scatter to primary ratio (SPR) was 4.51 without any ASG device. SPR was reduced to 1.28 with 1DASG, and it was further reduced to 0.28 with 2DASG. Scatter transmission fraction (Ts) of 1DASG was 21%, and Ts was reduced to 5.8% with 2DASG. The average primary transmission fraction (Tp) of 1DASG was 70.6%, whereas Tp increased to 85.1% with 2DASG. Variation of Tp across 40 cm length (the long axis of flat panel detector) was 2.6%. CONCLUSION When compared to conventional ASGs, the focused 2DASG can vastly improve scatter suppression and primary transmission performance. Due to precise alignment of 2DASGs grid holes with respect to beam divergence, high degree of primary transmission through the 2DASG was maintained across the full length of the prototype. We strongly believe that robust scatter rejection and primary transmission characteristics of our 2DASG can translate into both improved quantitative accuracy and soft tissue resolution in linac mounted CBCT systems.

Radiation dose uncertainty and correction for a mouse orthotopic and xenograft irradiation model

Abstract Purpose In animal irradiation models, reported dose can vary significantly from the actual doses delivered. We describe an effective method for in vivo dose verification. Materials and methods Mice bearing commercially-available cell line or patient-derived tumor cell orthotopic or flank xenografts were irradiated using a 160 kVp, 25 mA X-ray source. Entrance dose was evaluated using optically-stimulated luminescence dosimeters (OSLD) and exit dose was assessed using radiochromic film dosimetry. Results Tumor position within the irradiation field was validated using external fiducial markers. The average entrance dose in orthotopic tumors from 10 OSLDs placed on two different animal irradiation days was 514 ± 37 cGy (range: 437–545). Exit dose measurements taken from seven radiochromic films on two separate days were 341 ± 21 cGy (a 34% attenuation). Flank tumor irradiation doses measured by OSLD were 368 ± 9 cGy compared to exit doses of 330 cGy measured by radiochromic film. Conclusion Variations related to the irradiation model can lead to significant under or overdosing in vivo which can affect tumor control and/or biologic endpoints that are dose-dependent. We recommend that dose measurements be determined empirically based on the mouse model and irradiator used and dose compensation adjustments performed to ensure correct and appropriate doses.

TH‐EF‐BRB‐06: A Method to Synthesize Hybrid KV/MV Projections for Metal Artifact Corrections in CBCT

Purpose: Simultaneous utilization of kV and MV projections is a promising approach to correct metal artifacts in CBCT. However, due to inherent differences in attenuation, beam hardening, and scattering properties of kV and MV beams, it is challenging to employ kV and MV projections in the same CBCT set. To address these limitations, a novel method was developed to generate hybrid kV/MV projections, and to correct metal artifacts in CBCT images. Methods: First, a calibration dataset-based method was developed to correct beam hardening and scatter in kV and MV projections, and to convert MV projections to kV-equivalent attenuation maps. In the next stage, hybrid kV/MV projections were synthesized by weighted summation of corrected kV and MV projections; a user-controlled, generalized logistic curve was utilized as the weighting function, and its shape determined the relative weight of kV and MV projections with respect to relative attenuation differences on a pixel-by-pixel basis. Results: Phantoms with integrated metal hardware were imaged using 125 kVp and 6 MV beams from a linac with on-board KV imaging. CBCT images were reconstructed from KV-only projections and from hybrid kV/MV projections. In kV-only CBCT sets, metal hardware lead to severe artifacts and HU variations. HU values were underestimated by — 400±117 in a Catphan phantom with femoral implants. On the other hand, CBCT reconstructed from hybrid kV/MV projections exhibited significantly less metal artifacts, and the underestimation in HU values was reduced to — 100±73. Similar results were observed in all imaging experiments. Conclusion: Our method was successful in reducing metal artifacts, and improving CT number accuracy in CBCT images. Consistency of corrections appeared to be robust under diverse imaging conditions. The user-controlled weighting function allowed fine tuning the balance between the level of desired metal artifact suppression and the preservation of soft tissue contrast in CBCT images.

Evaluation of threshold and gradient based 18F-fluoro-deoxy-2-glucose hybrid positron emission tomographic image segmentation methods for liver tumor delineation

PURPOSE Image segmentation methods were studied to delineate liver lesions in (18)F-fluoro-2-deoxy-glucose positron emission tomographic (FDG-PET) images. The goal of this study was to identify a clinically practical, semiautomated FDG-PET avid volume segmentation method to improve the accuracy of liver tumor contouring for treatment planning in stereotactic body radiation therapy (SBRT). METHODS AND MATERIALS Pretreatment PET-CT image sets for 26 patients who received SBRT to 28 liver lesions were delineated using the following 3 methods: (1) Percent threshold with respect to background corrected maximum standard uptake values (SUV; threshold values varied from 10% to 50% with 10% increments); (2) threshold 3 standard deviations above mean background SUV (3σ); and (3) a gradient-based method that detects the edge of the FDG-PET avid lesion (edge). For each lesion, semiautomatically generated contours were evaluated with respect to reference contours manually drawn by 3 radiation oncologists. Two similarity metrics, Dice coefficient, and mean minimal distance (MMD), were employed to assess the volumetric overlap and the mean Euclidian distance between semiautomatically and observer-drawn contours. RESULTS Mean Dice and MMD values for 10%, 20%, 30% threshold, 3σ, and edge varied from 0.69 to 0.73, and from 3.44 mm to 3.94 mm, respectively (ideal Dice and MMD values are 1 and 0 mm, respectively). A statistically significant difference was not observed among 10%, 20%, 30% threshold, 3σ, and edge methods, whereas 40% and 50% methods had inferior Dice and MMD values. CONCLUSIONS Three PET segmentation methods were identified above as potential tools to accelerate liver lesion delineation. The edge method appears to be the most practical for clinical implementation as it does not require calculation of SUV statistics. However, the performance of all segmentation methods showed large lesion-to-lesion fluctuations. Therefore, such methods may be suitable for generating initial estimates of FDG-PET avid volumes rather than being surrogates for manual volume delineation.