W. Laub

On the sensitivity of common gamma-index evaluation methods to MLC misalignments in Rapidarc quality assurance

PURPOSE In this study the effects of small systematic MLC misalignments and gravitational errors on the quality of Rapidarc treatment plan delivery are investigated with respect to verification measurements with two detector arrays and the evaluation of clinical significance of the error-induced deviations. METHODS Five prostate and six head and neck plans were modified by means of three error types: (1) both MLC banks are opened, respectively, in opposing directions, resulting in larger fields; (2) both MLC banks are closed, resulting in smaller fields; and (3) both MLC banks are shifted for lateral gantry angles, respectively, in the same direction to simulate the effects of gravity on the leaves. Measurements were evaluated with respect to a gamma-index of 3%/3 mm and 2%/2 mm. Dose in the modified plans was recalculated and the resulting dose volume histograms for target and critical structures were compared to those of the unaltered plans. RESULTS The smallest introduced leaf position deviations which fail the >90% criterion for a gamma-index of 2%/2 mm are: (1) 1 mm; (2) 0.5 mm for prostate and 1.0 mm for head and neck cases; and (3) 3 mm corresponding to the error types, respectively. These errors would lead to significant changes in mean PTV dose and would not be detected with the more commonly used 3%/3 mm gamma-index criterion. CONCLUSIONS A stricter gamma-index (2%/2 mm) is necessary in order to detect positional errors of the MLC. Nevertheless, the quality assurance procedure of Rapidarc treatment plans must include a thorough examination of where dose discrepancies occur, and professional judgment is needed when interpreting the gamma-index analysis, since even a >90% passing rate using the 2%/2 mm gamma-index criterion does not guarantee the absence of clinically significance dose deviation.

Clinical radiation therapy measurements with a new commercial synthetic single crystal diamond detector

A commercial version of a synthetic single crystal diamond detector (SCDD) in a Schottky diode configuration was recently released as the new type 60019 microDiamond detector (PTW‐Freiburg, Germany). In this study we investigate the dosimetric properties of this detector to independently confirm that findings from the developing group of the SCDDs still hold true for the commercial version of the SCDDs. We further explore if the use of the microDiamond detector can be expanded to high‐energy photon beams of up to 15 MV and to large field measurements. Measurements were performed with an Elekta Synergy linear accelerator delivering 6, 10, and 15 MV X‐rays, as well as 6, 9, 12, 15, and 20 MeV electron beams. The dependence of the microdiamond detector response on absorbed dose after connecting the detector was investigated. Furthermore, the dark current of the diamond detector was observed after irradiation. Results are compared to similar results from measurements with a diamond detector type 60003. Energy dependency was investigated, as well. Photon depth‐dose curves were measured for field sizes 3×3,10×10, and 30×30cm2. PDDs were measured with the Semiflex type 31010 detector, microLion type 31018 detector, P Diode type 60016, SRS Diode type 60018, and the microDiamond type 60019 detector (all PTW‐Freiburg). Photon profiles were measured at a depth of 10 cm. Electron depth‐dose curves normalized to the dose maximum were measured with the 14×14cm2 electron cone. PDDs were measured with a Markus chamber type 23343, an E Diode type 60017 and the microDiamond type 60019 detector (all PTW‐Freiburg). Profiles were measured with the E Diode and microDiamond at half of D90,D90,D70, and D50 depths and for electron cone sizes of 6×6cm2, 14×14cm2, and 20×20cm2. Within a tolerance of 0.5% detector response of the investigated detector was stable without any preirradiation. After preirradition with approximately 250 cGy the detector response was stable within 0.1%. A dark current after irradiation was not observed. The microDiamond detector shows no energy dependence in high energy photon or electron dosimetry. Electron PDD measurements with the E Diode and microDiamond are in good agreement. However, compared to E Diode measurements, dose values in the bremsstrahlungs region are about 0.5% lower when measured with the microDiamond detector. Markus detector measurements agree with E Diode measurements in the bremsstrahlungs region. For depths larger than dmax, depth‐dose curves of photon beams measured with the microDiamond detector are in close agreement to those measured with the microLion detector for small fields and with those measured with a Semiflex 0.125 cc ionization chamber for large fields. Differences are in the range of 0.25% and less. For profile measurements, microDiamond detector measurements agree well with microLion and P Diode measurements in the high‐dose region of the profile and the penumbra region. For areas outside the open field, P Diode measurements are about 0.5%–1.0% higher than microDiamond and microLion measurements. Thus it becomes evident that the investigated diamond detector (type 60019) is suitable for a wide range of applications in high‐energy photon and electron dosimetry and is interesting for relative, as well as absolute, dosimetry. PACS numbers: 00.06, 80.87

Cell-Cycle Dependent Expression of a Translocation-Mediated Fusion Oncogene Mediates Checkpoint Adaptation in Rhabdomyosarcoma

Rhabdomyosarcoma is the most commonly occurring soft-tissue sarcoma in childhood. Most rhabdomyosarcoma falls into one of two biologically distinct subgroups represented by alveolar or embryonal histology. The alveolar subtype harbors a translocation-mediated PAX3:FOXO1A fusion gene and has an extremely poor prognosis. However, tumor cells have heterogeneous expression for the fusion gene. Using a conditional genetic mouse model as well as human tumor cell lines, we show that that Pax3:Foxo1a expression is enriched in G2 and triggers a transcriptional program conducive to checkpoint adaptation under stress conditions such as irradiation in vitro and in vivo. Pax3:Foxo1a also tolerizes tumor cells to clinically-established chemotherapy agents and emerging molecularly-targeted agents. Thus, the surprisingly dynamic regulation of the Pax3:Foxo1a locus is a paradigm that has important implications for the way in which oncogenes are modeled in cancer cells.

Impact of irradiation and immunosuppressive agents on immune system homeostasis in rhesus macaques

In this study we examined the effects of non‐myeloablative total body irradiation (TBI) in combination with immunosuppressive chemotherapy on immune homeostasis in rhesus macaques. Our results show that the administration of cyclosporin A or tacrolimus without radiotherapy did not result in lymphopenia. The addition of TBI to the regimen resulted in lymphopenia as well as alterations in the memory/naive ratio following reconstitution of lymphocyte populations. Dendritic cell (DC) numbers in whole blood were largely unaffected, while the monocyte population was altered by immunosuppressive treatment. Irradiation also resulted in increased levels of circulating cytokines and chemokines that correlated with T cell proliferative bursts and with the shift towards memory T cells. We also report that anti‐thymocyte globulin (ATG) treatment and CD3 immunotoxin administration resulted in a selective and rapid depletion of naive CD4 and CD8 T cells and increased frequency of memory T cells. We also examined the impact of these treatments on reactivation of latent simian varicella virus (SVV) infection as a model of varicella zoster virus (VZV) infection of humans. None of the treatments resulted in overt SVV reactivation; however, select animals had transient increases in SVV‐specific T cell responses following immunosuppression, suggestive of subclinical reactivation. Overall, we provide detailed observations into immune modulation by TBI and chemotherapeutic agents in rhesus macaques, an important research model of human disease.

Allogeneic stem cell transplantation in fully MHC-matched Mauritian cynomolgus macaques recapitulates diverse human clinical outcomes

Allogeneic hematopoietic stem cell transplantation (HSCT) is a critically important therapy for hematological malignancies, inborn errors of metabolism, and immunodeficiency disorders, yet complications such as graft-vs.-host disease (GvHD) limit survival. Development of anti-GvHD therapies that do not adversely affect susceptibility to infection or graft-vs.-tumor immunity are hampered by the lack of a physiologically relevant, preclinical model of allogeneic HSCT. Here we show a spectrum of diverse clinical HSCT outcomes including primary and secondary graft failure, lethal GvHD, and stable, disease-free full donor engraftment using reduced intensity conditioning and mobilized peripheral blood HSCT in unrelated, fully MHC-matched Mauritian-origin cynomolgus macaques. Anti-GvHD prophylaxis of tacrolimus, post-transplant cyclophosphamide, and CD28 blockade induces multi-lineage, full donor chimerism and recipient-specific tolerance while maintaining pathogen-specific immunity. These results establish a new preclinical allogeneic HSCT model for evaluation of GvHD prophylaxis and next-generation HSCT-mediated therapies for solid organ tolerance, cure of non-malignant hematological disease, and HIV reservoir clearance.Rhesus macaques are not ideal for studying response to allogeneic hematopoietic stem cell transplant (allo-HSCT) owing to complex MHC genetics that prevent full MHC-matching. Here the authors show that inbred Mauritian-origin cynomolgus macaques are a superior preclinical model of allogeneic stem cell transplantation that mimics diverse clinical outcomes of human allo-HSCT.

TH‐E‐BRE‐07: Development of Dose Calculation Error Predictors for a Widely Implemented Clinical Algorithm

PURPOSE Several shortcomings of the current implementation of the analytic anisotropic algorithm (AAA) may lead to dose calculation errors in highly modulated treatments delivered to highly heterogeneous geometries. Here we introduce a set of dosimetric error predictors that can be applied to a clinical treatment plan and patient geometry in order to identify high risk plans. Once a problematic plan is identified, the treatment can be recalculated with more accurate algorithm in order to better assess its viability. METHODS Here we focus on three distinct sources dosimetric error in the AAA algorithm. First, due to a combination of discrepancies in smallfield beam modeling as well as volume averaging effects, dose calculated through small MLC apertures can be underestimated, while that behind small MLC blocks can overestimated. Second, due the rectilinear scaling of the Monte Carlo generated pencil beam kernel, energy is not properly transported through heterogeneities near, but not impeding, the central axis of the beamlet. And third, AAA overestimates dose in regions very low density (< 0.2 g/cm3 ). We have developed an algorithm to detect the location and magnitude of each scenario within the patient geometry, namely the field-size index (FSI), the heterogeneous scatter index (HSI), and the lowdensity index (LDI) respectively. RESULTS Error indices successfully identify deviations between AAA and Monte Carlo dose distributions in simple phantom geometries. Algorithms are currently implemented in the MATLAB computing environment and are able to run on a typical RapidArc head & neck geometry in less than an hour. CONCLUSION Because these error indices successfully identify each type of error in contrived cases, with sufficient benchmarking, this method can be developed into a clinical tool that may be able to help estimate AAA dose calculation errors and when it might be advisable to use Monte Carlo calculations.

SU‐E‐I‐39: Experimental Study On the Performance of the OMAR CT Artifact Correction Algorithm Near Titanium and Stainless Steel

PURPOSE Implants with high atomic numbers produce star-like artifacts in CT-images. When coupled in pairs, a black window appears in between. The Philips OMAR algorithm approaches these artifacts by post processing the images. In this study, measurements were performed with radiochromic EBT2 films in order to verify, whether the OMAR algorithm contributes to the accuracy of treatment plans in implant regions. METHODS Two sets of titanium and stainless steel rods with diameters of 1inch and 0.5inch were centered in a water phantom either single or in pairs. The phantom was scanned in a Philips Bigbore Brilliance scanner, which provides the OMAR correction algorithm. A set of uncorrected CT data was kept in addition to the post processed data. The treatment plans were calculated with AAA in Eclipse. The Hounsfield units in the volume of the metal rods were set to match the relative electron density with the conversion table extended accordingly. A 10×12 field at 90 degrees gantry rotation and 400MU was calculated using on a 1mm grid. The plans were irradiated using a Varian Novalis-TX linac with EBT3 films placed on the sides of the single rod setup or between the rods in the two rod setups. The FilmQA Pro Software was used for evaluation of the films. RESULTS With one inhomogeneity present in the phantom, the difference between the plans based on the uncorrected data and the plans based on the post processed data is small. With paired inhomogeneities and the associated increased artifact, the difference becomes more significant and the OMAR algorithm improves the accuracy. High Z scattering effects cause considerable deviation from the planned dose profiles near the rods. CONCLUSION The OMAR-algorithm improves the accuracy of the dose calculations. The dose profiles across implant regions are calculated accurately, if the Hounsfield units are defined accordingly.

Registration Guided Simulation of Prostate Movement for Radiation Therapy

Developing an accurate dosage plan for radiation therapy is crucial to the success of the treatment, yet many obstacles still exist in spite of the application of the modern technology. One such challenge is revealed in registering CT scans and MRI images, that capture the location and geometry of the prostate. Due to bodily functions and breathing of the patients, the prostate moves with respect to different images. Relying solely on computer vision techniques such as the demons algorithm, can at best give a quantitative measurement of the differences between images. How the differences are created remains unknown. We develop a pipeline in which we first employ simulations of the movement and deformation of the rectum to depict its influence on the position variation of the prostate, then calculate the displacement fields using demons image registration algorithm, and lastly use the displacement field to correct the simulations to match with the target image. Potentially, physicians can better devise dosage planning knowing how the prostate moves during the treatment.

TH-C-19A-06: Measurements with a New Commercial Synthetic Single Crystal Diamond Detector

PURPOSE A commercial version of a synthetic single crystal diamond detector in a Scottky diode configuration was recently released as the new type 60019 microDiamond detector (PTW-Freiburg). In this study we investigate the dosimetric properties of this detector and explore if the use of the microDiamond detector can be expanded to high energy photon beams of up to 15MV and to large field measurements. METHODS Energy dependency was investigated. Photon and electron depth-dose curves were measured. Photon PDDs were measured with the Semiflex type 31010, microLion type 31018, P-Diode type 60016, SRS Diode type 60018, and the microDiamond type 60019 detector. Electron depth-dose curves were measured with a Markus chamber type 23343, an E Diode type 60017 and the microDiamond type 60019 detector (all PTW-Freiburg). Profiles were measured with the E-Diode and microDiamond at dose maximum depths. RESULTS The microDiamond detector shows no energy dependence in high energy photon or electron dosimetry. Electron PDD measurements with the E-Diode and microDiamond are in good agreement except for the bremsstrahlungs region, where values are about 0.5 % lower with the microDiamond detector. Markus detector measurements agree with E-Diode measurements in this region. For depths larger than dmax, depth-dose curves of photon beams measured with the microDiamond detector are in close agreement to those measured with the microLion detector for small fields and with those measured with a Semiflex 0.125cc ionization chamber for large fields. For profile measurements, microDiamond detector measurements agree well with microLion and P-Diode measurements in the high-dose region and the penumbra region. For areas outside the open field, P-Diode measurements are about 0.5-1.0% higher than microDiamond and microLion measurements. CONCLUSION The investigated diamond detector is suitable for a wide range of applications in high energy photon and electron dosimetry and is interesting for relative as well as absolute dosimetry.

SU‐E‐T‐136: Novel Secondary Quality Assurance Procedure for the INTRABEAM System Ion Chamber Using Commercial OSLDs

PURPOSE In recent events, our clinic has experienced a soft x-ray ion chamber calibration drift of 8%. For the INTRABEAMTM system which relies on an ion chamber measurement to deduce a dose rate correction factor for treatment, such an ion chamber change results in a large deviation between the planned patient dose and the treatment dose. We present a cross calibration method between an ion chamber and commercially available optically stimulated luminescent dosimeters (OSLDs) to monitor the consistency of the soft x-ray ion chamber. METHODS Our method uses the INTRABEAM™ system dose rate determined by a PTW soft x-ray ion chamber (model 23342) under normal quality assurance procedures to produce the counts per dose rate for irradiated nanoDot™ OSLDs. The procedure replaces the ion chamber with an OSLD at the same position which is obtained with a fabricated stage of the same dimension as the ion chamber stage. Upon replacement of the ion chamber, the QA procedure is repeated irradiating a nanoDot™ OSLD for approximately two minutes with low energy kV x-rays of energy 20 keV with 0.64 mm Al HVL. The QA procedure is repeated three times with a new OSLD for each irradiation. A ten minute waiting period is invoked prior to reading each nanoDot™ OSLD a total of three times. RESULTS This method produces an average counts per dose rate for all nanoDot™ OSLDs with a 1-sigma standard deviation of 1.7%. The low standard deviation gives this method the ability to detect an ion chamber measurement change in dose rate greater than 3.5% incorporating the positional uncertainty and sensitivity change. CONCLUSION In the advent of complete equipment failure, a system can degrade and report erroneous measurements. Our quick secondary check for equipment drift provides a necessary tool to ensure patient safety.