Clinical evaluation of an anatomy-based patient specific quality assurance system

The Delta4DVH Anatomy 3D quality assurance (QA) system (ScandiDos), which converts the measured detector dose into the dose distribution in the patient geometry was evaluated. It allows a direct comparison of the calculated 3D dose with the measured back-projected dose. In total, 16 static and 16 volumetric-modulated arc therapy (VMAT) fields were planned using four different energies. Isocenter dose was measured with a pinpoint chamber in homogeneous phantoms to investigate the dose prediction by the Delta4DVH Anatomy algorithm for static fields. Dose distributions of VMAT fields were measured using GAFCHROMIC film. Gravitational gantry errors up to 10° were introduced into all VMAT plans to study the potential of detecting errors. Additionally, 20 clinical treatment plans were verified. For static fields, the Delta4DVH Anatomy predicted the isocenter dose accurately, with a deviation to the measured phantom dose of 1.1% ± 0.6%. For VMAT fields the predicted Delta4DVH Anatomy dose in the isocenter plane corresponded to the measured dose in the phantom, with an average gamma agreement index (GAI) (3 mm/3%) of 96.9± 0.4%. The Delta4DVH Anatomy detected the induced systematic gantry error of 10° with a relative GAI (3 mm/3%) change of 5.8% ± 1.6%. The conventional Delta4PT QA system detected a GAI change of 4.2%± 2.0%. The conventional Delta4PT GAI (3 mm/3%) was 99.8% ± 0.4% for the clinical treatment plans. The mean body and PTV-GAI (3 mm/5%) for the Delta4DVH Anatomy were 96.4% ± 2.0% and 97.7%± 1.8%; however, this dropped to 90.8%± 3.4% and 87.1% ± 4.1% for passing criteria of 3 mm/3%. The anatomy-based patient specific quality assurance system predicts the dose distribution correctly for a homogeneous case. The limiting factor for the error detection is the large variability in the error-free plans. The dose calculation algorithm is inferior to that used in the TPS (Eclipse)

Cardiac fibrosis can be attenuated by blocking the activity of transglutaminase 2 using a selective small-molecule inhibitor

Cardiac fibrosis is implicit in all forms of heart disease but there are no effective treatments. In this report, we investigate the role of the multi-functional enzyme Transglutaminase 2 (TG2) in cardiac fibrosis and assess its potential as a therapeutic target. Here we describe the use a highly selective TG2 small-molecule inhibitor to test the efficacy of TG2 inhibition as an anti-fibrotic therapy for heart failure employing two different in vivo models of cardiac fibrosis: Progressively induced interstitial cardiac fibrosis by pressure overload using angiotensin II infusion: Acutely induced focal cardiac fibrosis through myocardial infarction by ligation of the left anterior descending coronary artery (AMI model). In the AMI model, in vivo MRI showed that the TG2 inhibitor 1–155 significantly reduced infarct size by over 50% and reduced post-infarct remodelling at 20 days post insult. In both models, Sirius red staining for collagen deposition and levels of the TG2-mediated protein crosslink ε(γ-glutamyl)lysine were significantly reduced. No cardiac rupture or obvious signs of toxicity were observed. To provide a molecular mechanism for TG2 involvement in cardiac fibrosis, we show that both TGFβ1-induced transition of cardiofibroblasts into myofibroblast-like cells and TGFβ1- induced EndMT, together with matrix deposition, can be attenuated by the TG2 selective inhibitor 1–155, suggesting a new role for TG2 in regulating TGFβ1 signalling in addition to its role in latent TGFβ1 activation. In conclusion, TG2 has a role in cardiac fibrosis through activation of myofibroblasts and matrix deposition. TG2 inhibition using a selective small-molecule inhibitor can attenuate cardiac fibrosis

Commissioning of photon beams of a flattening filter-free linear accelerator and the accuracy of beam modeling using an anisotropic analytical algorithm

PURPOSE: To investigate dosimetric characteristics of a new linear accelerator designed to deliver flattened, as well as flattening filter-free (FFF), beams. To evaluate the accuracy of beam modeling under physical conditions using an anisotropic analytical algorithm. METHODS AND MATERIALS: Dosimetric data including depth dose curves, profiles, surface dose, penumbra, out-of-field dose, output, total and scatter factors were examined for four beams (X6, X6FFF, X10, and X10FFF) of Varian's TrueBeam machine. Beams modeled by anisotropic analytical algorithm were compared with measured dataset. RESULTS: FFF beams have lower mean energy (tissue-phantom ratio at the depths of 20 and 10 cm (TPR 20/10): X6, 0.667; X6FFF, 0.631; X10, 0.738; X10FFF, 0.692); maximum dose is located closer to the surface; and surface dose increases by 10%. FFF profiles have sharper but faster diverging penumbra. For small fields and shallow depths, dose outside a field is lower for FFF beams; however, the advantage fades with increasing phantom scatter. Output increases 2.26 times for X6FFF and 4.03 times for X10FFF and is less variable with field size; collimator exchange effect is reduced. A good agreement between modeled and measured data is observed. Criteria of 2% depth-dose and 2-mm distance-to-agreement are always met. CONCLUSION: Reference dosimetric characteristics of TrueBeam photon bundles were obtained, and successful modeling of the beams was achieved. Copyright © 2011 Elsevier Inc. All rights reserved

Ion-recombination correction for different ionization chambers in high dose rate flattening-filter-free photon beams

Recently, there has been an increased interest in flattening-filter-free (FFF) linear accelerators. Removal of the filter results in available dose rates up to 24 Gy min(-1) (for nominal energy 10 MV in depth of maximum dose, a source-surface distance of 100 cm and a field size of 10×10 cm2). To guarantee accurate relative and reference dosimetry for the FFF beams, we investigated the charge collection efficiency of multiple air-vented and one liquid ionization chamber for dose rates up to 31.9 Gy min(-1). For flattened beams, the ion-collection efficiency of all air-vented ionization chambers (except for the PinPoint chamber) was above 0.995. By removing the flattening filter, we found a reduction in collection efficiency of approximately 0.5-0.9% for a 10 MV beam. For FFF beams, the Markus chamber showed the largest collection efficiency of 0.994. The observed collection efficiencies were dependent on dose per pulse, but independent of the pulse repetition frequency. Using the liquid ionization chamber, the ion-collection efficiency for flattened beams was above 0.990 for all dose rates. However, this chamber showed a low collection efficiency of 0.940 for the FFF 10 MV beam at a dose rate of 31.9 Gy min(-1). All investigated air-vented ionization chambers can be reliably used for relative dosimetry of FFF beams. The order of correction for reference dosimetry is given in the manuscript. Due to their increased saturation in high dose rate FFF beams, liquid ionization chambers appear to be unsuitable for dosimetry within these contexts