Comparing organ-at-risk doses for high-dose-rate vaginal brachytherapy between three different planning workflows.

PURPOSE: The aim of this study was to compare the organ-at-risk doses to the rectum and the bladder in postoperative endometrial cancer patients who receive high-dose-rate vaginal brachytherapy (HDR-VB), when using three different methods of treatment planning: (Workflow A) individualized treatment planning before every fraction, (Workflow B) individualized treatment planning for first fraction only), and (Workflow C) using a template plan based on applicator choice and prescription specifics without patient-specific imaging or planning (standardized template approach). METHODS AND MATERIALS: Alternative plans were retrospectively created using workflows B and C for 22 patients who previously received postoperative HDR-VB using a vaginal cylinder and planned using Workflow A for endometrial cancer. The rectum and bladder were contoured on the CTs used for each fraction for dose comparison between the three methods. D50, D2cc, D1cc, D0.1cc, and V100 of the bladder and the rectum were compared using the two-sided Wilcoxon signed-rank test. RESULTS: A total of 123 fractions were available for comparison. For Workflow A vs. Workflow B, there was no significant difference for any rectal or bladder dosimetric parameter. For Workflow A vs. Workflow C, Workflow A delivered a significantly higher median dose to the rectum than Workflow C for D50, D2cc, D1cc, and V100. Workflow C delivered a significantly higher dose to the bladder than Workflow A: D2cc, D1cc, D0.1cc, and V100. However, the magnitudes of the differences were small; the dose index difference was >75 cGy for only two fractions. CONCLUSION: Plan standardization in HDR-VB may result in considerable time and cost savings with minimal organ-at-risk dose differences.

RAC1 GTPase promotes the survival of breast cancer cells in response to hyper-fractionated radiation treatment.

Radiation therapy is a staple approach for cancer treatment, whereas radioresistance of cancer cells remains a substantial clinical problem. In response to ionizing radiation (IR) induced DNA damage, cancer cells can sustain/activate pro-survival signaling pathways, leading to apoptotic resistance and induction of cell cycle checkpoint/DNA repair. Previous studies show that Rac1 GTPase is overexpressed/hyperactivated in breast cancer cells and is associated with poor prognosis. Studies from our laboratory reveal that Rac1 activity is necessary for G2/M checkpoint activation and cell survival in response to IR exposure of breast and pancreatic cancer cells. In this study, we investigated the effect of Rac1 on the survival of breast cancer cells treated with hyper-fractionated radiation (HFR), which is used clinically for cancer treatment. Results in this report indicate that Rac1 protein expression is increased in the breast cancer cells that survived HFR compared with parental cells. Furthermore, this increase of Rac1 is associated with enhanced activities of extracellular signal-regulated kinases 1 and 2 (ERK1/2) and nuclear factor-κB (NF-κB) signaling pathways and increased levels of anti-apoptotic protein Bcl-xL and Mcl-1, which are downstream targets of ERK1/2 and NF-κB signaling pathways. Using Rac1-specific inhibitor and dominant-negative mutant N17Rac1, here we demonstrate that Rac1 inhibition decreases the phosphorylation of ERK1/2 and inhibitory κBα (IκBα), as well as the levels of Bcl-xL and Mcl-1 protein in the HFR-selected breast cancer cells. Moreover, inhibition of Rac1 using either small molecule inhibitor or dominant-negative N17Rac1 abrogates clonogenic survival of HFR-selected breast cancer cells and decreases the level of intact poly(ADP-ribose) polymerase, which is indicative of apoptosis induction. Collectively, results in this report suggest that Rac1 signaling is essential for the survival of breast cancer cells subjected to HFR and implicate Rac1 in radioresistance of breast cancer cells. These studies also provide the basis to explore Rac1 as a therapeutic target for radioresistant breast cancer cells.

A new variable for SRS plan quality evaluation based on normal tissue sparing: the effect of prescription isodose levels.

OBJECTIVE: A new dosimetric variable, dose-dropping speed (DDS), was proposed and used to evaluate normal tissue sparing among stereotactic radiosurgery (SRS) plans with different prescription isodose lines. METHODS: 40 plans were generated for 8 intracranial SRS cases, prescribing to isodose levels (IDLs) ranging from 50% to 90% in 10% increments. Whilst maintaining similar coverage and conformity, plans at different IDLs were evaluated in terms of normal tissue sparing using the proposed DDS. The DDS was defined as the greater decay coefficient in a double exponential decay fit of the dose drop-off outside the planning target volume (PTV), which models the steep portion of the drop-off. Provided that the prescription dose covers the whole PTV, a greater DDS indicates better normal tissue sparing. RESULTS: Among all plans, the DDS was found to be the lowest for the prescription at 90% IDL and the highest for the prescription at 60% or 70%. The beam profile slope change in the penumbra and its field size dependence were explored and given as the physical basis of the findings. CONCLUSION: A variable was proposed for SRS plan quality evaluation. Using this measure, prescriptions at 60% and 70% IDLs were found to provide best normal tissue sparing. ADVANCES IN KNOWLEDGE: A new variable was proposed based on which normal tissue sparing was quantitatively evaluated, comparing different prescription IDLs in SRS.

SU-E-J-122: Quantification of Respiratory-Induced Pancreatic Head Tumor Rotation and Deformation Using 4DCT and Fiducial Markers.

PURPOSE: To quantify pancreatic head tumor rotation and deformation due to the respiration using 4DCT and fiducial markers. METHODS: This study included seventeen pancreatic head tumor patients who were treated with gated SBRT using Novalis system in our institution. Each patient had two 5-mm-long fiducial markers placed in pancreatic head approximately 2 cm apart for the gating treatment. All patients had 4DCT scans of 3mm-slice thickness using a CT scanner (SENSATION, SIEMENS) under free breathing condition to create the internal target volume (ITV). The respiratory curve was generated through a pressure sensor placed on the patient's abdomen. The 4DCT image data sets were binned into 8 phases: 0% inhale (end of exhale), 25% inhale, 50% inhale, 75% inhale, 100% inhale (end of inhale), 75% exhale, 50% exhale, and 25% exhale. The fiducial markers were contoured on each phase of 4DCT images, and the 3D coordinates (x,y,z) of centroid of the fiducial marker were recorded. The distance between two markers was calculated for each phase, and its variation on eight phases indicated the pancreatic head deformation. The orientation change of the two markers on eight phases indicated the pancreatic head rotation. Student t-test was performed for the statistical analysis. RESULTS: Pancreatic head rotation and deformation were observed through the breathing cycle. The largest rotation and deformation happened to the course from 0% inhale to 100% inahle. The rotation was 8.0±6.2 degree ranging from 2 to 20 degree. The deformation was 2.0±2.4 mm ranging from 0 to 6.6 mm. Both were statistically significant with p<10-4 for rotation and p=0.0033 for deformation. CONCLUSIONS: The 4DCT images showed significant pancreatic head rotation and deformation due to respiration, and both rotation and deformation were highly variable between patients. For patients receiving SBRT with tight margin, rotation and deformation need to be considered, and individualized margin may be necessary.

SU-E-T-206: Standardization in Documentation Format Can Significantly Reduce Manual Data Entry Error in Patient Chart.

PURPOSE: To demonstrate that standardization in documentation format can significantly reduce manual data entry error in patient chart. METHOD AND MATERIALS: Due to lack of direct data link between CT on rail imaging registration software and patient R&V system, therapists have to manually enter translation correction of patient position into R&V system after performing imaging registration between CT image taken just before treatment delivery and treatment planning CT image. Approximately six months after CT on rail was placed into clinical service, we started requiring therapists to use a standard format to document the shifts when they manually enter data to reduce manual data entry error rate. The therapist manual data entry errors in R&V system before (551 entries) and after the format standardization (1645 entries) are the subjects of statistical analysis. The errors are divided into two categories (recoverable and non-recoverable errors) depending on whether a human being can recover the translation shifts in lateral, longitudinal, and vertical directions from the therapist notes. Fisher's exact test is performed to test the statistical significance of therapist's data entry error reduction after our imposing the documentation format requirement. Temporal information on when the errors were made is also analyzed to find out when errors are more likely to happen. RESULTS: Statistical analysis indicated that reductions in the numbers of recoverable, non-recoverable, and total errors after standardization in document format are all statistically significant with p values less than 0.05. CONCLUSION: A simple and low cost measure like standardization in document format can significantly reduce the errors operators introduce to patient R&V system when they perform manual data entry. We hope our experience will convince people to follow more disciplined documentation rule to reduce the error rate and therefore potentially can improve the quality of patient care when manual data entry is involved.

Dose volume histogram comparison between ADAC Pinnacle and Nomos Corvus systems for IMRT.

This paper compares dose volume histograms (DVHs) generated by the ADAC Pinnacle and the Nomos Corvus planning systems. Seven prostate cases and seven head and neck cases were selected for review. Plans computed on both systems possessed exactly the same anatomical contours and IMRT segments. The Pinnacle system used the collapsed cone convolution superposition, while Corvus employed a finite size pencil beam (FSPB) convolution. Prostate DVH results demonstrated similar DVH curves from both systems. For each structure, the ratio of Pinnacle dose value divided by Corvus value was calculated. The high dose structures (which might contain tumour) had ratios close to unity, while the low dose structures (the critical organs) had ratios farther away from unity. Almost all ratios were less than unity, indicating a systematic difference that Pinnacle calculated doses were lower than Corvus ones. Head and neck data provided similar findings. A possible cause for this discrepancy could be the beam modelling. The difference in DVH parameters that we discovered between the two systems was about the same order of magnitude as the measurement-computation difference. When low dose is critical, such difference may affect the clinical planning decision.

Effect of affinity for droplet surfaces on the fraction of analyte molecules charged during electrospray droplet fission.

The effect of uneven fissioning of mass and charge from electrospray droplets on the amount of analyte charged during the electrospray process was explored. A surface selectivity factor (S) was developed to describe the affinity of an analyte for the droplet surface, and both theoretical and experimental response curves were compared for analytes with various S values. The theoretical response curves were generated by calculating the overlap between the charge and analyte spawned from parent droplets to determine the amount of analyte charged. This overlap was then graphed as a function of analyte concentration. Differences in the amount of analyte charged during droplet fission were predicted for analytes of varying surface affinities. The issue of analyte partitioning between the surface and interior phases of the ESI droplet was also included in the discussion. This was accomplished by applying the equilibrium partitioning model to a set of offspring droplets to determine the amount of analyte on their surfaces and then calculating the overlap between fissioning analyte and excess charge. Experimental response curves resembled theoretical ones, and S values predicted from theory were in excellent agreement with those predicted on the basis of the structural characteristics of the analytes.

Commissioning and quality assurance for MLC-based IMRT.

The commissioning and quality assurance (QA) associated with the implementation of linear accelerator multileaf collimator (MLC)-based intensity-modulated radiation therapy (IMRT) at the University of Nebraska Medical Center are described. Our MLC-based IMRT is implemented using the PRIMUS linear accelerator interface through the IMPAC record and verification system to the CORVUS treatment planning system. The "step-and-shoot" technique is used for this MLC-based IMRT. Commissioning process requires the verification of predefined parameters available on the CORVUS and the collection of some machine data. The machine data required are output factor in air and output factor in phantom, and percent depth dose for a number of field sizes. In addition, inplane and crossplane dose profiles of 4 x 4 cm and 20 x 20 cm field sizes and diagonal dose profiles of a large field size have to be measured. Validation of connectivity and dose model includes the use of uniform intensity bar strips, triangular-shaped nonuniform intensity bar strip, and N-shaped target. QA procedure follows the recommendation of the AAPM Task Group No. 40 report. In addition, the leaf position accuracy and reproducibility of the MLC should be checked at regular intervals. The dose validation is implemented through the hybrid plan where the patient beam parameters are applied to a flat phantom. Independent dose calculation method is used to confirm the dose delivery plan and data input to the CORVUS.

Independent dose calculations for the corvus MLC IMRT.

Two independent dose calculation methods have been explored to validate MLC-based IMRT plans from the NOMOS CORVUS system. After the plan is generated on the CORVUS planning system, the beam parameters are imported into an independent workstation. The beam parameters consist of intensity maps at each gantry angle. In addition, CT scans of the patient are imported into the independent workstation to obtain the external contour of the patient. The coordinate system is defined relative to the alignment point chosen in the CORVUS plan. The 2 independent calculation methods are based on a pencil beam kernel convolution and a Clarkson-type differential scatter summation, respectively. The pencil beam data for a 1 x 1-cm beam, as formed by the multileaf collimator, were measured for the 6-MV photon beam from a Siemens PRIMUS linear accelerator using film dosimetry. In the pencil beam method, the dose at a point is calculated using the depth and off-axis distance from a given pencil beam, corrected for beam intensity. The scatter summation method used the conversion of measured depth dose data into scatter maximum ratios. In this method, the differential scatter from each pencil beam is corrected for the beam intensity. Isodose distributions were generated using the independent dose calculations and compared to the CORVUS plans. Although isodose distributions from both methods show good agreement with the CORVUS plan, our implementation of the differential scatter summation approach seems more favorable. The 2 independent dose calculation algorithms are described in this paper.

Leaf sequencing techniques for MLC-based IMRT.

The nonuniform fields required by intensity-modulation radiation therapy (IMRT) can be delivered using conventional multileaf collimators (MLC) as beam modulators. In MLC-based IMRT, the nonuniform field is initially converted into an intensity map represented as a matrix of beam intensities. The intensity map is then decomposed into a series of subfields or segments of uniform intensities. Although there are many ways of segmenting the beam intensity matrix, a resulting subfield is only deliverable if it satisfies the constraints imposed by the MLC. These constraints exist as a result of the design of the MLC. The simplest constraint of the MLC is that its pairs of leaves can only move in and out in one dimension. Additional constraints include collision of opposing leaves and the need to match the tongue-and-groove to reduce interleaf leakage. The practical aspect of MLC-based IMRT requires that an optimized algorithm decomposes the nonuniform field into the least number of segments and therefore reduces the delivery time. This paper examines the static use and the dynamic use of MLCs to perform MLC-based IMRT.

Electrospray ionization detection of inherently nonresponsive epoxides by peptide binding.

A small organic molecule that is inherently nonresponsive to electrospray analysis, 1,3-butadiene diepoxide, was analyzed via electrospray ionization (ESI) by binding it to various peptides and observing the product at the characteristic mass shift. The epoxide reacted only with peptides with arginines in their sequence, most likely through a base-catalyzed ring opening to form a covalently bound product. A calibration curve linear over 3 orders of magnitude was generated for the butadiene diepoxide/peptide adduct. Several other epoxides were also reacted with the peptide of choice (angiotensin II), and adducts of these epoxides with the peptide were observed as well, demonstrating the versatility of this method for the analysis of small epoxides. This study demonstrates the possibility of assaying epoxides bound to peptides or proteins in biological samples. Furthermore, it demonstrates an important concept that could be applied to other analytical problems in electrospray: the ability to react an analyte that is nonresponsive to electrospray analysis with an analyte well suited for the technique, and accomplish quantitation based on the adduct formed between the two.

Independent dose calculations for the PEACOCK System.

An independent dose calculation method has been developed to validate intensity-modulated radiation therapy (IMRT) plans from the NOMOS PEACOCK System. After the plan is generated on the CORVUS planning system, the beam parameters are imported into an independent workstation. The beam parameters consist of intensity maps at each gantry angle and each arc position. In addition, CT scans of the patient are imported into the independent workstation to obtain the external contour of the patient. The coordinate system is defined relative to the alignment point chosen in the CORVUS plan. The independent calculation uses the pencil beam data viz tissue maximum ratio (TMR) and beam profiles for a single 1 x 0.8-cm beamlet formed by the NOMOS multileaf intensity-modulating collimator (MIMiC) leaf. The pencil beam data were measured for the 6-MV photon beam from Siemens PRIMUS linear accelerator using film dosimetry. The dose at a point is calculated using the depth and off-axis distance from a given pencil beam, corrected for its beam intensity. Isodose distributions are generated using the independent dose calculations and compared to the CORVUS plans. Isodose distributions show good agreement with the CORVUS plans for a number of clinical cases. The independent dose calculation algorithm is described in this paper.

Commissioning of Peacock System for intensity-modulated radiation therapy.

The Peacock System was introduced to perform tomographic intensity-modulated radiation therapy (IMRT). Commissioning of the Peacock System included the alignment of the multileaf intensity-modulating collimator (MIMiC) to the beam axis, the alignment of the RTA device for immobilization, and checking the integrity of the CRANE for indexing the treatment couch. In addition, the secondary jaw settings, couch step size, and transmission through the leaves were determined. The dosimetric data required for the CORVUS planning system were divided into linear accelerator-specific and MIMiC-specific. The linear accelerator-specific dosimetric data were relative output in air, relative output in phantom, percent depth dose for a range of field sizes, and diagonal dose profiles for a large field size. The MIMiC-specific dosimetric data were the in-plane and cross-plane dose profiles of a small and a large field size to derive the penumbra fit. For each treatment unit, the Beam Utility software requires the data be entered into the CORVUS planning system in modular forms. These modules were treatment unit information, angle definition, configuration, gantry and couch angles range, dosimetry, results, and verification plans. After the appropriate machine data were entered, CORVUS created a dose model. The dose model was used to create known simple dose distribution for evaluation using the verification tools of the CORVUS. The planned doses for phantoms were confirmed using an ion chamber for point dose measurement and film for relative dose measurement. The planning system calibration factor was initially set at 1.0 and will be changed after data on clinical cases are acquired. The treatment unit was released for clinical use after the approval icon was checked in the verification plans module.

Immobilization devices for intensity-modulated radiation therapy (IMRT).

Three-dimensional conformal radiation therapy (3DCRT) and intensity-modulated radiation therapy (IMRT) plans show radiation dose distribution that is highly conformal to the target volume. The successful clinical implementation of these radiotherapy modalities requires precise positioning of the target to avoid a geographical miss. Effective reduction in target positional inaccuracies can be achieved with the proper use of immobilization devices. This paper reviews some of the immobilization devices that have been used and/or have the potential of being used for IMRT. The immobilization devices being reviewed include stereotactic frame, Talon system, thermoplastic molds, Alpha Cradles, and Vac-Lok system. The implementation of these devices at various anatomical sites is discussed.

Quality assurance procedures for the Peacock system.

The Peacock system is the product of technological innovations that are changing the practice of radiotherapy. It uses dynamic beam modulation technique and inverse planning algorithm, both of which are new methodologies, to perform intensity-modulation radiation therapy (IMRT). The quality assurance (QA) procedure established by Task Group No. 40 did not adequately consider these emerging modalities. A review of literature indicates that published articles on QA procedures concentrate primarily on the verification of dose delivered to phantom during commissioning of the system and dose delivered to phantom before treating patients. Absolute dose measurements using ion chambers and relative dose measurements using film dosimetry have been used to verify delivered doses. QA on equipment performance and equipment safety is limited. This paper will discuss QA on equipment performance, equipment safety, and patient setup reproducibility.

Predicting electrospray response from chromatographic retention time.

The relationship between electrospray ionization response and HPLC retention time was explored. For the series of small peptides studied, higher ESI response was observed for analytes with longer reversed-phase HPLC retention times. This correlation existed for both experimentally measured retention times and those calculated from amino acid retention coefficients. This study is useful t

Practical implications of some recent studies in electrospray ionization fundamentals.

In accomplishing successful electrospray ionization analyses, it is imperative to have an understanding of the effects of variables such as analyte structure, instrumental parameters, and solution composition. Here, we review some fundamental studies of the ESI process that are relevant to these issues. We discuss how analyte chargeability and surface activity are related to ESI response, and how accessible parameters such as nonpolar surface area and reversed phase HPLC retention time can be used to predict relative ESI response. Also presented is a description of how derivitizing agents can be used to maximize or enable ESI response by improving the chargeability or hydrophobicity of ESI analytes. Limiting factors in the ESI calibration curve are discussed. At high concentrations, these factors include droplet surface area and excess charge concentration, whereas at low concentrations ion transmission becomes an issue, and chemical interference can also be limiting. Stable and reproducible non-pneumatic ESI operation depends on the ability to balance a number of parameters, including applied voltage and solution surface tension, flow rate, and conductivity. We discuss how changing these parameters can shift the mode of ESI operation from stable to unstable, and how current-voltage curves can be used to characterize the mode of ESI operation. Finally, the characteristics of the ideal ESI solvent, including surface tension and conductivity requirements, are discussed. Analysis in the positive ion mode can be accomplished with acidified methanol/water solutions, but negative ion mode analysis necessitates special constituents that suppress corona discharge and facilitate the production of stable negative ions.

Simple cylindrical ion mirror with three elements.

A new cylindrical ion mirror has been designed to create an electric field that is non-linear or curved along the flight path axis for general-purpose time-of-flight mass spectrometers. The inclusion of one or two grids is found to improve the radial field homogeneity especially around the aperture. Only three cylindrical electrodes are used in the design. Changing the electrode dimensions and voltages affects the electric field distribution. Once the electrode dimensions are fixed, there are only two adjustable parameters for achieving optimum nonlinear electric field shape. Resolving powers of 7,000 and 16,100 have been achieved with kinetic energy variations of 34 and 10.5%, respectively. Simulations show that the electric field homogeneity in the radial direction enables the use of ion beam diameters up to 15 mm with only modest loss of resolving power. Increasing the mirror diameter could further increase the practical ion beam diameter. This article details the electric field distribution within the cylindrical mirror in both axial and radial directions. The voltages of the middle and rear electrodes affect the resolving power and the kinetic energy range over which focus can be achieved. The predicted arrival time spread for a single m/z value is narrower than that caused by the turn-around time of ions in a gas-phase ion source. In this case, the broad energy range over which good focus is achieved enables the use of higher extraction fields for turn-around time reduction.