Single isocenter HyperArc treatment of multiple intracranial metastases: Targeting accuracy.

PURPOSE/OBJECTIVES: (A) To examine the alignment accuracy of CBCT guidance for brain metastases with off centered isocenters, (B) to test dose delivery and targeting accuracy for single isocenter treatments with multiple brain metastases. We report the results of the end-to-end test for Truebeam stereotactic radiosurgery (SRS). MATERIALS/METHODS: An anthropomorphic CT head phantom was drilled with five MOSFET inserts and two PTW Pinpoint chamber inserts. The phantom was simulated, planned, and delivered. For the purpose of comparing the accuracy of alignment, CBCTs were acquired with the isocenter centered and offset superiorly 8 cm, inferiorly 8 cm, anteriorly 7 cm, posteriorly 7 cm, and right 5 cm. There were six degrees of freedom corrections applied to the plans, as well as intentional rotational and translational errors for dose comparisons. Dose accuracy checks were performed with MOSFET and PTW Pinpoint chamber, and targeting accuracy was assessed with GafChromic films. RESULT: (A) Compared to centered CBCT, off-centered CBCT scan showed some alignment errors, with a maximum difference of 0.6-degree pitch and 0.9 mm translation when the phantom was placed 8 cm inferior off center. (B) For the single isocenter plan, measured doses of the five MOSFET were 95%-100% of the planned dose, whereas the multiple isocenter plans were 96%-100%. With intentional setup errors of 1-degree pitch, doses were 97.1%-100.4% compared to the perfect setup. The same was found for the two pinpoint chamber readings with 1-degree rotation and 1 mm translation. (C) Targeting accuracy for targets at the isocenter is 0.67 mm, within the machine specification of 0.75 mm. Targeting accuracy for isocenters 6-12 cm away from the target is in the range 0.67-1.18 mm. CONCLUSION: (A) Single isocenter HyperArc treatments for multiple brain metastases are feasible and targeting accuracy is clinically acceptable. (B) The vertex in a cranial scan is very important for proper alignment.

Diagnosing atmospheric communication of a sealed monitor chamber.

Daily output variations of up to ±2% were observed for a protracted time on a Varian TrueBeam® STx; these output variations were hypothesized to be the result of atmospheric communication of the sealed monitor chamber. Daily changes in output relative to baseline, measured with an ionization chamber array (DQA3) and the amorphous silicon flat panel detector (IDU) on the TrueBeam®, were compared with daily temperature-pressure corrections (PTP ) determined from sensors within the DQA3. Output measurements were performed using a Farmer® ionization chamber over a 5-hour period, during which there was controlled variation in the monitor chamber temperature. The root mean square difference between percentage output change from baseline measured with the DQA3 and IDU was 0.50% over all measurements. Over a 7-month retrospective review of daily changes in output and PTP , weak correlation (R2  = 0.30) was observed between output and PTP for the first 5 months; for the final 2 months, daily output changes were linearly correlated with changes in PTP , with a slope of 0.84 (R2  = 0.89). Ionization measurements corrected for ambient temperature and pressure during controlled heating and cooling of the monitor chamber differed from expected values for a sealed monitor chamber by up to 4.6%, but were consistent with expectation for an air-communicating monitor chamber within uncertainty (1.3%, k = 2). Following replacement of the depressurized monitor chamber, there has been no correlation between daily percentage change in output and PTP (R2  = 0.09). The utility of control charts is demonstrated for earlier identification of changes in the sensitivity of a sealed monitor chamber.

Improved Total-Body Irradiation Survival by Delivery of Two Radiation Mitigators that Target Distinct Cell Death Pathways.

The acute lethality of total-body irradiation (TBI) involves damage to multiple organs, including bone marrow and intestine. Ionizing radiation mitigators that are effective when delivered 24 h or later after TBI include the anti-apoptotic drug, JP4-039 and the anti-necroptotic drug, necrostatin-1. In contrast to effective delivery of JP4-039 at 24 h after TBI, necrostatin-1 is most effective when delivery is delayed until 48 h, a time that correlates with the elevation of necroptosis-inducing inflammatory cytokines and necroptosis-induced serine phosphorylation of receptor-interacting serine/threonine-protein kinase-3 (RIP3) in tissues. The goal of this work was to determine whether administration of JP4-039 influenced the optimal delivery time for necrostatin-1. We measured daily levels of 33 proteins in plasma compared to intestine and bone marrow of C57BL/6NTac female mice over a 7-day time period after 9.25 Gy TBI (LD50/30). Protein responses to TBI in plasma were different from those measured in intestine or bone marrow. In mice that were given JP4-039 at 24 h after TBI, we delayed necrostatin-1 delivery for 72 h after TBI based on measured delay in RIP-3 kinase elevation in marrow and intestine. Sequential delivery of these two radiation mitigator drugs significantly increased survival compared to single drug administration.

Comparison of the recommendations of the AAPM TG-51 and TG-51 addendum reference dosimetry protocols.

This work quantified differences between recommendations of the TG-51 and TG-51 addendum reference dosimetry protocols. Reference dosimetry was performed for flattened photon beams with nominal energies of 6, 10, 15, and 23 MV, as well as flattening-filter free (FFF) beam energies of 6 and 10 MV, following the recommendations of both the TG-51 and TG-51 addendum protocols using both a Farmer® ionization chamber and a scanning ionization chamber with calibration coefficients traceable to absorbed dose-to-water (Dw ) standards. Differences in Dw determined by the two protocols were 0.1%-0.3% for beam energies with a flattening filter, and up to 0.2% and 0.8% for FFF beams measured with the scanning and Farmer® ionization chambers, respectively, due to kQ determination, volume-averaging correction, and collimator jaw setting. Combined uncertainty was between 0.91% and 1.2% (k = 1), varying by protocol and detector.

Development and characterization of a three-dimensional radiochromic film stack dosimeter for megavoltage photon beam dosimetry.

PURPOSE: Three-dimensional (3D) dosimeters are particularly useful for verifying the commissioning of treatment planning and delivery systems, especially with the ever-increasing implementation of complex and conformal radiotherapy techniques such as volumetric modulated arc therapy. However, currently available 3D dosimeters require extensive experience to prepare and analyze, and are subject to large measurement uncertainties. This work aims to provide a more readily implementable 3D dosimeter with the development and characterization of a radiochromic film stack dosimeter for megavoltage photon beam dosimetry. METHODS: A film stack dosimeter was developed using Gafchromic(®) EBT2 films. The dosimeter consists of 22 films separated by 1 mm-thick spacers. A Virtual Water™ phantom was created that maintains the radial film alignment within a maximum uncertainty of 0.3 mm. The film stack dosimeter was characterized using simulations and measurements of 6 MV fields. The absorbed-dose energy dependence and orientation dependence of the film stack dosimeter were investigated using Monte Carlo simulations. The water equivalence of the dosimeter was determined by comparing percentage-depth-dose (PDD) profiles measured with the film stack dosimeter and simulated using Monte Carlo methods. Film stack dosimeter measurements were verified with thermoluminescent dosimeter (TLD) microcube measurements. The film stack dosimeter was also used to verify the delivery of an intensity-modulated radiation therapy (IMRT) procedure. RESULTS: The absorbed-dose energy response of EBT2 film differs less than 1.5% between the calibration and film stack dosimeter geometries for a 6 MV spectrum. Over a series of beam angles ranging from normal incidence to parallel incidence, the overall variation in the response of the film stack dosimeter is within a range of 2.5%. Relative to the response to a normally incident beam, the film stack dosimeter exhibits a 1% under-response when the beam axis is parallel to the film planes. Measured and simulated PDD profiles agree within a root-mean-square difference of 1.3%. In-field film stack dosimeter and TLD measurements agree within 5%, and measurements in the field penumbra agree within 0.5 mm. Film stack dosimeter and TLD measurements have expanded (k = 2) overall measurement uncertainties of 6.2% and 5.8%, respectively. Film stack dosimeter measurements of an IMRT dose distribution have 98% agreement with the treatment planning system dose calculation, using gamma criteria of 3% and 2 mm. CONCLUSIONS: The film stack dosimeter is capable of high-resolution, low-uncertainty 3D dose measurements, and can be readily incorporated into an existing film dosimetry program.

Characterizing the marker-dye correction for Gafchromic(®) EBT2 film: a comparison of three analysis methods.

PURPOSE: Gafchromic(®) EBT2 film has a yellow marker dye incorporated into the active layer of the film that can be used to correct the film response for small variations in thickness. This work characterizes the effect of the marker-dye correction on the uniformity and uncertainty of dose measurements with EBT2 film. The effect of variations in time postexposure on the uniformity of EBT2 is also investigated. METHODS: EBT2 films were used to measure the flatness of a (60)Co field to provide a high-spatial resolution evaluation of the film uniformity. As a reference, the flatness of the (60)Co field was also measured with Kodak EDR2 films. The EBT2 films were digitized with a flatbed document scanner 24, 48, and 72 h postexposure, and the images were analyzed using three methods: (1) the manufacturer-recommended marker-dye correction, (2) an in-house marker-dye correction, and (3) a net optical density (OD) measurement in the red color channel. The field flatness was calculated from orthogonal profiles through the center of the field using each analysis method, and the results were compared with the EDR2 measurements. Uncertainty was propagated through a dose calculation for each analysis method. The change in the measured field flatness for increasing times postexposure was also determined. RESULTS: Both marker-dye correction methods improved the field flatness measured with EBT2 film relative to the net OD method, with a maximum improvement of 1% using the manufacturer-recommended correction. However, the manufacturer-recommended correction also resulted in a dose uncertainty an order of magnitude greater than the other two methods. The in-house marker-dye correction lowered the dose uncertainty relative to the net OD method. The measured field flatness did not exhibit any unidirectional change with increasing time postexposure and showed a maximum change of 0.3%. CONCLUSIONS: The marker dye in EBT2 can be used to improve the response uniformity of the film. Depending on the film analysis method used, however, application of a marker-dye correction can improve or degrade the dose uncertainty relative to the net OD method. The uniformity of EBT2 was found to be independent of the time postexposure.