bluuebunny/crossref_metadata_2025 huggingface dataset:
WE‐C‐L100E‐01: Mammography QA Workshop I & II
Authors: Geiser W , Wu T , Spahn G , Jacobson D
Published: July 2007

Purpose: To explore the impact of digital mammography on the practice of medical physics. Historical and new methods for providing scheduled and unscheduled mammography services for facilities using digital mammography will be presented. Method and Materials: Clinical medical physics services provided for digital mammography facilities from various manufacturers will be presented. Quality control activities approved by the FDA for each individual manufacturer will be compared. The status of a proposed “Alternative Standard” to allow for a more uniform approach to medical physics mammography services will be reviewed. Case studies will be presented demonstrating methods and cost considerations for providing medical physics services under the “minimum standard” (prescribed by MQSA regulations) and “best practices” model. Results: Medical physics services provided in the “minimum standard” and “best practices” model have implications for the quality and cost of mammography services. Conclusion: Medical physics services may be provided in a professional and valuable manner, using combinations of the minimum standard of practice and the “best practices” model. The professional medical physicist should consider multiple parameters when determining the appropriate model under which to deliver services.
WE‐D‐L100J‐01: In Vivo PET Imaging of Angiogenesis in Tumor Mice Model with 64Cu Labeled Avastin
Authors: Chang T , Wang Z
Published: July 2007

Purpose: Using angiogenesis principle to develop a new PET contrast agent for tumor detection with higher tumor specificity and decrease the background spots shown in 18FDG imaging. Method and Materials: Bevacizumab (Avastin; Genentech) is the antibody of the vascular endothelial growth factor (VEGF), an angiogenesis factor. Avastin was conjugated to a macrocyclic ligand (DOTA) and labeled with a positron emitter, . Briefly, 1,4,7,10‐tetraazacyclododecane‐N, N′,N″,N‴‐tetraacetic acid mono‐N‐hydroxysuccinimide ester (DOTA‐NHS‐ester) was reacted with Avastin in 0.1 M buffer of pH 7.5 at 4°C for 12 h. After conjugation, the reaction mixture was centrifuged repeatedly through an YM‐30 centricon with 50 mM ammonium citrate buffer of pH 6.5 in order to remove small molecules. The Avastin‐DOTA conjugate was labeled with at 43°C for 1h and purified with Bio‐Spin 6 column. The microPET/CT imaging was conducted on xenograft models of pancreatic adenocarcinoma established from MiaPaca2 cell line. ‐Avastin was administered i.v. at a dose of 240μCi/40μg Ab into a xenograft pancreatic cancer model. The mouse was imaged with microPET/CT scanner (Gamma Medica Ideas, Inc.) at 1h, 4h and 24h post‐injection. Results: The radiolabeling of Avastin was successfully carried out in our lab which gave a radiochemical purity of >92%. The serum challenge studies have demonstrated that 85% of radiolabeled antibody was still intact, even at 24 hour. The images confirmed high accumulation of radiolabeled ‐DOTA‐Avastin conjugate in tumors located in the both left and right flank of animal as well as in the head and neck. The image also shows that the conventional hot spots of 18FDG image such as, brain, kidneys and bladder do not appear on the image. Conclusion: ‐DOTA‐Avastin can be used as a tumor detection agent for PET scan and effectively decrease the background spots in image compared to 18FDG image.
WE‐D‐L100J‐08: Application of Volumetric Molecular Breast Imaging with a Dedicated SPECT‐CT Mammotomograph
Authors: Tornai M , Madhav P , Crotty D , Cutler S , Perez K , McKinley R , Bowsher J
Published: July 2007

Purpose: Clinical 2D‐scintimammography therapeutic response monitoring results imply that fully‐3D molecular imaging could benefit early response prediction. Capabilities of prototype functional SPECT and anatomical x‐ray CT integrated imaging subsystems, dedicated to whole breast and chest wall diagnostic imaging of normalcy, disease and therapeutic response are demonstrated. The system provides patient comfort while imaging the pendant, uncompressed breast and anterior chest wall in common fields‐of‐view, yielding inherently registered, volumetric images. Method and Materials: The high‐performance SPECT system has 2.5mm CZT multi‐element pixelation and 6.7% FWHM energy resolution at 140keV; the subsystem gantry can sweep the camera about a hemisphere with simple/complex trajectories. The CT subsystem has 15% FWHM quasi‐monochromatic x‐ray cone beam at 36keV and 127micron CsI micro‐columnar pixelation. Both subsystems rotate on a common azimuthal stage. The CT system is equatorially restricted, though fully 3D positioning mobilization is possible for both subsystems on the same hybrid gantry. Emission SPECT data are iteratively reconstructed using OSEM, and transmission CT data using iterative OSTR. Rigid body transformations employing mixed emission/transmission fiducial markers around the breast help register and fuse the reconstructed data. Results: Initial cross contamination studies indicated transmission scatter contamination of SPECT images was negligible (<1%). Emission contamination of CT images was greater, degrading reconstructed image SNR by 20–30%. Use of a radio‐opaque patient bed reduces emission contamination. Registered and fused data yield high‐resolution images of geometrical and anthropomorphic phantoms. New designs of the fully flexible hybrid system will allow for nearly complete sampling by both subsystems. Conclusion: A hybrid SPECT‐CT mammotomography system was successfully implemented for use in breast diagnostics. Conflict of Interest: MPT and JEB are inventors of this technology, and are named as inventors on the patent for this technology applied for by Duke. If this technology becomes commercially successful, they and Duke could benefit financially.
WE‐D‐M100F‐01: Introduction of Imaging for Treatment Assessment
Authors: Cao Y
Published: July 2007

In vivo biomedical imaging for assessment of therapeutic response is becoming an increasingly important field. Early assessment and prediction of treatment response allow for individualized re‐optimization of therapy, which represents a novel concept and a paradigm shift from conventional clinical trials. Recent Phase I/II trials have shown that biomedical imaging, including CT, MRI, PET, can provide an indication of therapeutic response, and possibly prior to the radiographic changes. In vivo biomedical imaging for assessment of therapeutic response is a dynamic and fast growing field. Many new trials are ongoing or in the design phase. The complicity of imaging technologies provides an opportunity for more AAPM members to engage in either single center trials or multi‐center trials in coming years. This symposium will provide overviews on PET/SPECT, MRI/MRS and the integration of multimodality imaging in clinical trials for assessment of treatment response.

The objectives of this symposium are:

1. What imaging modalities have shown potential value in phase I/II trials for assessment of therapeutic responses;

2. What are the advantages and limitations of using in vivo functional and metabolic imaging in clinical trials compared to conventional paradigms;
WE‐D‐M100F‐02: PET for Chemo/radiation Therapy Response Assessment
Authors: Jeraj R
Published: July 2007

The most commonly used method to assess treatment response relies on measuring tumor sizes before and after treatment and classifying tumor anatomical shrinkage according to RECIST or WHO criteria. However, there is a considerable variability between individual studies and the same response rate can be associated with completely different survival rates. Furthermore, it is known that changes in tumor biological function significantly precede gross anatomical tumor changes. Positron emission tomography (PET) is the most sensitive, specific and versatile imaging modality that can be used for this purpose.

‐Fluoro‐deoxyglucose (FDG) is the most commonly used PET imaging agent for treatment assessment. FDG shows regions of active glucose metabolism, which are typically decreased after tumor cells die in response to antineoplastic therapies. Besides FDG, several other PET agents exist, which are more specific in cell targeting, and can image different aspects of biological response to therapy. Cell proliferation, apoptosis and angiogenesis are processes that are typically affected by antineoplastic therapies. Currently, the most promising non‐FDG agent is ‐Fluorodeoxythymidine (FLT) as a marker of cell proliferation. PET imaging agents of apoptosis and angiogenesis are still mostly limited to preclinical studies. Use of PET imaging for treatment assessment imposes special requirements on image acquisition, reconstruction and analysis.

FDG‐PET has shown an extreme promise to assess treatment efficacy, both after, as well as during the course of therapy. Depending on the metabolic response, it is possible to classify patients into metabolic responders, which have typically much longer survival rates than metabolic non‐responders. Unfortunately, FDG is not without problems. Two of the most severe are (1) radiation‐induced inflammation during radiation therapy and (2) metabolic flare that occurs early after the start of some chemotherapies. FLT‐PET, which assesses proliferative response, seems to overcome these problems; however, more clinical studies are needed to prove its wider applicability. Reproducible and accurate PET image acquisition, reconstruction and analysis are the key components required for quantitative PET imaging, which provides foundation for treatment assessment.

This symposium reviews the status of treatment assessment studies that involve repeat PET imaging during and after therapy. It discusses advantages and disadvantages of FDG and non‐FDG‐PET imaging for treatment assessment. It also emphasizes importance of the appropriate PET imaging acquisition, reconstruction and analysis that forms the basis for PET image quantification.

Educational Objectives:

1. Overview of FDG‐PET imaging for treatment assessment.

2. Overview of non‐FDG‐PET imaging for treatment assessment.

3. Review PET image acquisition, reconstruction and analysis for treatment assessment.

4. Discuss future of PET imaging for treatment assessment.
WE‐D‐M100F‐04: Integration of Multi‐modality Imaging in Clinical Trials
Authors: Lawrence T
Published: July 2007

Treatment responses and late normal tissue injury are conventionally assessed months or years after the completion of therapy by standard clinical endpoints, such as local progression free survival or late fibrosis. This conventional paradigm presents two major weaknesses. First, at the time of the treatment outcomes being determined, it is often too late to change the outcome of patients. Secondly, takes a large number of patients and a long time to determine the efficacy of the tested treatment. It is urgent for clinical scientists to change this conventional paradigm and to assess the therapeutic response early, i.e. prior to the end of planned therapy. For early assessment of therapeutic responses, conventional clinical endpoints are no longer adequate. Functional, metabolic, and molecular imaging could provide a means or a marker for early assessment of normal tissue injury or of treatment responses prior to anatomic measurements of disease progression, thereby permitting re‐optimization of individual patient treatment strategies. This lecture will provide examples how to integrate multi‐modality imaging in clinical trials for early assessment of treatment response and normal tissue toxicity. The implications of the results will also be discussed.

Learning Objectives:

1. Understand the time courses of response and toxicity.

2. Appreciate windows of opportunity for early assessment.

3. Introduce clinical trial design issues for early assessment.
WE‐D‐AUD‐01: Clincal Evaluation of An Independent Dose Check Algorithm for Helical TomoTherapy
Authors: Gibbons J , Smith K , Cheek D , Rosen I
Published: July 2007

Purpose: To determine the clinical acceptability of an algorithm developed to independently verify doses calculated by the TomoTherapy treatment planning system. Method and Materials: Point doses from treatment plans for 97 patients treated on a TomoTherapy system were compared to an independent dose calculation algorithm developed at our facility. All patient plans for which treatment sinograms were available were included in the comparison, which represented a variety of treatment sites and plan parameters. For each treatment plan, the calculation point was selected to be in the geometric center of the primary PTV, where beam modulation and high dose‐gradients were expected to be minimal. If this process put the point into a high dose‐gradient region or very near a tissue interface region, the point was manually repositioned. Results: Comparisons of our calculation to the TomoTherapy‐predicted point doses for the patient treatment plans showed good agreement. For sites other than lung and superficial PTVs, agreement between the calculations was within 2% for 94% of the patient calculations (64 of 68). Our independent calculations within the lung or superficial PTVs overestimated the dose by an average of 3.1% (σ =2.4%) and 3.2% (σ=2.2%), respectively. Conclusion: Systematic errors at points within lung are probably the result of the known weakness of the radiological path length method for correcting for missing tissue and/or tissue density heterogeneities. Errors encountered at points within superficial PTVs are probably the result of our algorithm overestimating the scatter dose at points near the surface of the patient. For the majority of cases, the algorithm demonstrates sufficient accuracy for clinical use and may be used to independently verify patient treatment plans.

Supported in part by a research agreement with TomoTherapy, Inc.
WE‐D‐AUD‐02: Retrospective IMRT Dose Reconstruction Based On Cone‐Beam Computed Tomography (CBCT) and the MLC Positional Log‐File Recorded During Treatment
Authors: Lee K , Le Q , Xing L
Published: July 2007

Purpose: Most CBCTs performed nowadays are only used for setup correction. In reality, CBCT‐derived 3D patient model can also be used for dose reconstruction to reflect the delivered dose taking into account the inter‐fraction organ motion/deformation. The purpose of this work is to establish a methodology to reconstruct the delivered IMRT dose by using on‐treatment CBCT images and the actual dynamic leaf positions recorded during the treatment. Method and Materials: A CT phantom with different inserts was scanned using planning CT (pCT) and CBCT, respectively, and the corresponding electron density calibration curves were established. Five head‐and‐neck (HN) patients were selected and, for each patient, three CBCT scans with the patient at his/her treatment positions were taken at different fractions during the course of radiation therapy. The target and organ contours were mapped from the pCT onto the co‐registered CBCT for DVH analysis. The actual leaf positions in IMRT delivery were recorded by the MLC workstation and the log‐files were retrieved to reconstruct the fluence maps for the corresponding treatment fraction. The delivered dose was then obtained using the reconstructed fluence maps and the CBCT data, and the results were compared to the original pCT‐based treatment plan. Results: A retrospective dose reconstruction procedure has been implemented and applied to 5 HN cases. For cases in which the tumor shrinkage is not obvious, the reconstructed and planned doses are consistent to within 3% in high dose region. The DVHs of the target and other organs do not have significant differences. Large dosimetric changes (5–8%) were observed, however, for a case with tumor shrinkage, indicating the need for re‐planning or adaptive radiation therapy in this situation. Conclusion: IMRT dose reconstruction provides a powerful way to examine the actual patient dose delivery at a particular fraction and represents an essential step toward adaptive radiotherapy.
WE‐D‐AUD‐04: Dose Engine Verification of a Dual‐Level MMLC‐Based Treatment Planning System Benchmarked by MCNPX and Pinnacle
Authors: Liu Y , Shi C , Stathakis S , Papanikolaou N
Published: July 2007

Purpose: To evaluate and verify a dose engine by comparing 3D dose matrices calculated by a dual‐level micro multileaf collimator based treatment planning system (TPS) benchmarked by MCNPX and Pinnacle3 TPS Method and Materials: An irregular aperture shape was created by a dual‐level micro multileaf collimator (mMLC) and dose was delivered through the aperture to a cylindrical solid water phantom with a 6MV Varian 600C linear accelerator. A Monte Carlo model was designed by using MCNPX according to the configurations of the linac source, jaws, aperture shape and phantom. The computed dose matrices from CrossPlan, a specially design TPS for mMLC, and MCNPX were compared against each other and the radiographic films. The isodose distributions, profiles, and gamma analysis were parameters used for comparison. 3D dose matrices from CrossPlan and MCNPX were converted and exported to Pinnacle3 TPS for further comparison. Results: The isodose overlay, gamma analysis, and dose profiles generated by both CrossPlan and MCNPX closely matched each other. The mean dose difference was less than 1.4%, and the gamma index values were less than one. The computed dose images from CrossPlan and MCNPX matched well with the radiographic films. The isodose and DVH comparisons by Pinnacle3 further demonstrate the agreement of the 3D dose matrices from CrossPlan and MCNPX. Conclusion: The good agreement between the computed dose from CrossPlan and MCNPX compared with the radiographic films indicated that both CrossPlan and MCNPX dose engines produce reliable and accurate dose distributions. The CrossPlan based dual‐level micro‐MLC is capable of precise aperture shaping, potentially allowing for an improved intensity modulated radiation therapy (IMRT) plan and delivery. Conflict of Interest: Supported by Initia Medical Technology.
WE‐D‐AUD‐05: Clinical Implementation of Portal Dosimetry — Establishing Action Levels
Authors: Howell R , Smith I Nogueira , Jarrio C
Published: July 2007

Purpose: To establish clinical action levels and methods to improve agreement between the measured dose and the portal dose prediction (PDP) for IMRT QA using Portal Dosimetry. Method and Materials: 1152 treatment fields were evaluated. The maximum gamma (γmax), average gamma (γavg), and percent of the field area with a gamma value greater than 1.0 (γ% > 1) were documented for each treatment field. The mean values for each parameter and associated standard deviations (SD) were tabulated. Several strategies were considered to improve agreement between measured dose and PDP. Results: Clinical action levels were based on the mean parameters for our institution. Clinical Action Levels: 1) The average γmax, γavg, and γ% > 1 for all fields for a given treatment plan must be within 1SD of the mean institutional values, and 2) No more than 25% of the fields for a given treatment plan can have γmax, γavg, or γ% > 1 values in excess of 2SDs from the institutional mean. If the plan fails either of the above conditions, the QA must be repeated after applying one of the below troubleshooting techniques. Effective Trouble Shooting Techniques: 1) Verify linac output. 2) Portal dosimeter can be recalibrated. 3) The plan can be recalculated at a lower dose rate—effective for plans with significant modulation and a small number of monitor units. 4) On rare occasions, a completely new plan is required. Conclusion: These data have been used in our clinic to set clinical tolerance limits for evaluating IMRT QA using Portal Dosimetry; They also provide valuable trouble‐shooting tools to improve the results of IMRT QA for individual patients. IMRT fields which are not within the tolerances must be evaluated very carefully to ascertain the nature of the disagreement and whether it is acceptable to treat a patient with those fields.
WE‐D‐AUD‐08: Analysis of 1200 Delivery QA Measurements and Patient Plan Parameters in Helical Tomotherapy
Authors: West M , Sen A , Movahed A , Ingram G , Lollar D
Published: July 2007

Purpose: We have treated over 1200 patients on different anatomic sites using available beams widths. Every patient plan was verified with a delivery QA plan on a cylindrical water‐equivalent phantom. This study analyzes the variations of the delivery QA results and attempts to find some correlations with the patient plan parameters. Method and Materials: Following approval of an IMRT plan, a dose verification plan was generated for delivery on a Cheese phantom. An EDR2 film was placed in the central coronal plane of the phantom. An #a1SL ion chamber was placed 5 mm below the film for simultaneous point dose measurement. After appropriate setup and irradiation of the phantom with the delivery QA plan, the recorded charge was converted to dose and the film processed for dose distribution analysis. The films were scanned with a Vidar scanner and transferred to the Tomotherapy planning station for comparison of the delivered and planned dose distribution. Altogether 903 patient plans have been analyzed of which 11 are on 1 cm beam, 196 are on 2.5 cm beam and 696 are on 5 cm beam. Results: The difference between measured and calculated doses for all beam widths correlates (R2 = 0.87) with a normal distribution (μ = 0.6, σ = 3.152). The 2.5 cm and 5.0 cm beams independently are (μ,σ,R2) 2.15, 2.93, 0.85 and 0.338, 2.92, 0.87, respectively. The 1.0 cm beam measurements had μ = −0.9, σ = 3.8. No treatment planning parameters (pitch, treatment time, modulation factor) were found to correlate with the percent difference. Conclusions: The results are randomly distributed and planning parameters do not appear to affect the delivery QA results. The random nature indicates variation in machine output, phantom positioning, and position within the treatment field.
WE‐D‐M100J‐01: Enhancement of Cell Killing by X‐Ray Irradiation in the Presence of Gold Nanoparticles
Authors: Kulkarni R , Sramek B , Lisle A , Boote E , Caldwell C , Katti K
Published: July 2007

Purpose: This investigation was initiated to determine the radiobiologic enhancement for x‐ray irradiation of cells in the presence of citrate‐stabilized gold nanoparticles. Method and materials: Citrate‐stabilized gold nanoparticles were added to a strain of lymphoma cells in suspension at a concentration of 0.017 mg of gold per ml. Cell suspensions prepared included a two sham controls, and two samples with gold nanoparticles. One sham and one gold nanoparticle based sample were irradiated with x‐ray photons from a clinical x‐ray device (120 kVp, 6.67 mm Al equivalent beam). A total dose of 0.91 Gy was delivered in two approximately equal parts (24 hour separation). The non‐irradiated cell suspensions were treated identically. Cell survival for non‐irradiated cell suspensions and irradiated cell suspensions were determined over 72 hours using methylene blue dye exclusion. Results: The ratio of live:dead cells for all cell suspensions was 7.5:1 at the start of the experiment. After 72 hours, the irradiated cells exhibited a ratio approximately 50% lower than the non‐irradiated cells. The irradiated cell suspension with gold nanoparticles showed enhanced cell killing. Conclusions: Even at the low gold concentration and low x‐ray energy, gold nanoparticles exhibit some enhancement of cell killing. Further studies are ongoing using increasing gold concentrations and varying radiation doses. It is likely that the presence of higher Z materials contributes to secondary electron dose in a way that may be described only through microdosimetry methods.

Gold nanoparticle‐enhanced radiation therapy is a possible outcome of this work. Additional effort is directed toward functionalized gold nanoparticles using targeting moieties for specific cancers. This work contributes toward an understanding of the therapeutic enhancement that may be expected with specific concentrations of gold nanoparticles.

Supported by: NIH R01 CA119412‐01.
WE‐D‐M100J‐02: A Closed Form of Linear‐Quadratic Model with Reciprocal‐Time for Radiation Damage Repair
Authors: Wang J , Zhang D , Mayr N , Zhang H , Gupta N , Li K , Montebello J
Published: July 2007

Purpose: Repair of sublethal damage plays an important role in radiation therapy. Conventional radiobiology concepts are based on the assumption that the repair rate remains constant during the entire radiation course. However, increasing evidence from animal experiments report that the repair process may slow down with time and the data does not fit an exponential pattern. To address this dilemma, we developed a new closed form of Linear‐Quadratic (LQ) model based on the repair pattern with a reciprocal time. The new formulas were tested with published experimental data. Methods and Materials: The LQ model has been widely used in radiation therapy, . The parameter G represents the repair process of sublethal damage with Tr as the repair half‐time: in the reciprocal pattern. A closed form of G was derived analytically for arbitrary radiation schemes: dose rate . A set of published animal data was adopted to test the reciprocal formulas, in which rat foot skin was irradiated in split‐doses with increasing time intervals (0–22h). The complication data of moist desquamation were analyzed using the generalized LQ model. Results: A closed form of the LQ model to describe the repair process in a reciprocal pattern was obtained: , where function . Formulas for special cases were derived from this general form. The reciprocal model showed a better fit to the animal data than the exponential model, especially for the ED50 data (reduced of 2.0 vs. 4.3, p=0.11 vs. 0.006), with the following LQ parameters: α/β = 2.6–4.8Gy, Tr= 3.2–3.9h. Conclusions: The repair process following a reciprocal‐time has been investigated in this study and a closed form of the generalized LQ model was presented and validated. These formulas can be used to analyze the experimental and clinical data, where a slowing‐down repair process appears during the radiation course.
WE‐D‐M100J‐03: A Neural Network Model to Predict Lung Radiation‐Induced Pneumonitis
Authors: Chen S , Zhou S , Zhang J , Marks L , Das S
Published: July 2007

Purpose: To build and test a feed‐forward neural network model to predict the occurrence of lung radiation‐induced Grade 2+ pneumonitis. Method and Materials: The database comprised 235 patients with lung cancer treated using radiotherapy (34 diagnosed with pneumonitis). The neural network was constructed using a unique algorithm that alternately grew and pruned it, starting from the smallest possible network, until a satisfactory solution was found. The weights and biases of the network were computed using the error back‐propagation approach. The network was tested using ten‐fold cross‐validation, wherein 1/10th of the data were tested, in turn, using the model built with the remaining 9/10th of the data. Results: The network was constructed with input features selected from dose and non‐dose variables. The selected input features were: lung volume receiving > 16 Gy (V16), mean lung dose, generalized equivalent uniform dose (gEUD) for the exponent a=3.5, free expiratory volume in 1s (FEV1), diffusion capacity of Carbon Monoxide (DLCO%), and whether or not the patient underwent chemotherapy prior to radiotherapy. With the exception of FEV1, all input features were found to be individually significant (p < 0.05). The area under the Receiver Operating Characteristics (ROC) curve for cross‐validated testing was 0.76 (sensitivity: 68%, specificity: 69%). To gauge the impact of non‐dose variables on model predictive capability, a second network was constructed with input features selected only from lung dose‐volume histogram variables. The area under the ROC curve for cross‐validation was 0.67 (sensitivity: 53%, specificity: 69%). The network constructed from dose and non‐dose variables was statistically superior (p=0.020), indicating that the addition of non‐dose features significantly improves the generalization capability of the network. Conclusions: The neural network constructed from dose and non‐dose variables can be used to prospectively predict radiotherapy‐induced pneumonitis and, thereby, appropriately alter radiotherapy plans to reduce this possibility.
WE‐D‐M100J‐06: Hypofractionation Results in a Decrease in Tumor Cell Killing Compared to Standard Fractionation as a Result of Tumor Hypoxia
Authors: Carlson DJ , Keall PJ , Brown JM
Published: July 2007

Purpose: Tumor hypoxia has been observed in many human cancers and has been shown to correlate with treatment failure in radiotherapy. The purpose of this study is to quantify the effect of radiation fractionation on tumor cell killing assuming a realistic distribution of tumor oxygenation and full reoxygenation between fractions. The sensitivity of the results to variations in the radiobiologically hypoxic fraction, the dose per fraction, and tumor cell intrinsic radiosensitivity is evaluated. Method and Materials: A probability density function for the partial pressure of oxygen in a tumor cell population is quantified as a function of radial distance from the capillary wall. Estimates of the oxygen partial pressures for subpopulations of tumor cells are used to determine the corresponding oxygen enhancement ratios (OERs) for cell killing. The overall surviving fraction of a tumor cell population consisting of maximally resistant cells, cells at intermediate levels of hypoxia, and well‐oxygenated cells is calculated as a function of dose per fraction for an equivalent tumor biological effective dose (BED). Results: Our model predicts that tumor cell killing decreases by a factor of 105 over a radial distance of 130 μm assuming a partial oxygen pressure of 60 mmHg at the capillary wall. For head and neck (α/β = 10 Gy) and prostate (α/β = 3.0 Gy) cancer, the surviving fraction of cells over a full treatment course increases by a factor of 103 as the dose per fraction is increased from 1–24 Gy and 1–18 Gy, respectively. The total dose delivered for each dose per fraction is calculated to achieve equivalent tumor BED values for reference head and neck and prostate treatments. Conclusion: Hypofractionation of a radiotherapy regimen results in reduced tumor cell killing compared to conventional fractionation for tumors with regions of hypoxia.
WE‐D‐M100J‐07: Impact of Hemoglobin On Outcome of Chemo/Radiation Therapy for Cervical Cancer
Authors: Zhang D , Wang J , Mayr N , Montebello J , Yuh W
Published: July 2007

Purpose: Hemoglobin (Hgb) has been considered as an important factor on radiation therapy for cervical cancer. However, recent studies reported that anemia is only a secondary symptom associated with disease stage and tumor volume, but not an independent predictor for outcome. Our study is to investigate whether low Hgb actively influences the effectiveness of radiation therapy or is merely a symptom of tumor burden. Materials/Methods: The study was based on 67 cervical cancer patients (stage IB2‐IVA). Serial Hgb measurements were performed before and during therapy. Tumor volume was obtained from 3D MRI volumetry. Median follow‐up was 2.9 years (range 0.09∼6.4 years). Treatment outcome was evaluated with local tumor‐control and disease‐free survival. Correlations between Hgb parameters and clinical variables were evaluated with Spearman‐rank method. Outcome prediction was based on univariate and multivariate analyses with Cox regression model. Survival analysis was assessed using Kaplan‐Meier method. Results: Hgb levels were not correlated with tumor stage (correlation coefficient −0.1∼ −0.2) and weakly correlated with tumor volume (correlation coefficient −0.4∼ −0.5). In univariate analysis, local tumor‐control was predicted by mean Hgb (p=0.009) and nadir Hgb (p=0.004); disease‐free survival was only predicted by nadir Hgb (p=0.031). In multivariate analysis, Hgb parameters were the best predictors of outcome: local tumor‐control was predicted by mean Hgb (p=0.013) and nadir Hgb (p=0.007); disease‐free survival was only marginally predicted by nadir Hgb (p=0.053). Kaplan‐Meier analysis demonstrated that Hgb (>12g/dl vs <12g/dl) could potentially differentiate patients in terms of local tumor‐control and disease‐free survival. Conclusion: Preliminary results suggest that Hgb may not be associated with tumor burden (volume and stage). This early work suggests that chronically low Hgb during RT course negatively affects outcome. The independent role of Hgb in combination with other factors may be useful in outcome prediction.
WE‐D‐BRA‐03: Cyberknife Experience
Authors: Dieterich S
Published: July 2007

Purpose: The purpose of this presentation is to show in selected case studies where differential dose planning is used in Cyberknife treatments, and which challenges are associated with each approach. Method and Materials: Three case studies were selected to demonstrate different situations were differential dose planning would be used in Cyberknife SRS. Case1: Multiple, anatomically close cranial lesions of varying sizes. As experience with Gammaknife SRS has shown, the risk of complications in treating brain metastasis is correlated with dose and lesion size. Lesions larger than 2 cm in diameter are typically treated with a lower dose. In the situation were multiple lesions of different size are located closely together in the brain, creating separate treatment plans on the Cyberknife would lead to longer treatment times, higher whole‐body dose due to scatter and leakage, and difficulty to asses multiple plan dose overlays.

Case 2: The second situation involved mostly head and neck cancers where the GTV and CTV are treated to different doses as a boost after conventional IMRT treatments. Typically, the GTV encompasses the PET positive areas. Around the GTV, a CTV enclosing the microscopic extension of the disease as determined by the physician based on the case history.

Case 3: Unusual cases. A patient with pituitary adenoma was also diagnosed with Graves disease. Because of the proximity of the lesion and the orbital muscles affected by Graves disease, the tumor and orbital muscles were treated at the same time with different dose. Results: All three categories could be planned to the physicians' satisfaction. In case 1 patients, attention has to be paid to minimizing the dose to the healthy brain between the lesions. This can be achieved by using tuning structures or tuning shells around the tumors. In Case 2, the limiting factor is the dose fall‐off outside the GTV. A fraction of the CTV will be treated at a higher dose than planned. In case 3, the combined planning of the Graves disease and the pituitary adenoma achieved good dose sparing of the optic apparatus. Conclusion: The Cyberknife software is very flexible and allows relatively easy planning for complex situations.
WE‐E‐L100J‐03: Scatter Measurements and Simulations in X‐Ray Cone Beam CT Breast Imaging
Authors: Chen Y , Liu B , O'Connor M , Didier C , Glick S
Published: July 2007

Purpose: To compare and validate Monte Carlo simulation using the GATE software with experimental measurements for scattered radiation in X‐ray cone beam CT breast imaging . In addition, to determine the scatter distribution for single‐order, and multiple‐order incoherent and coherent scatter using validated Monte Carlo simulation. Methods: This study used a bench‐top cone‐beam CT breast imaging system using a flat‐panel detector. A cylindrical phantom with equivalent composition of 50% fibro‐glandular and 50% adipose tissues was used. Scatter distributions were measured by beam stop and aperture methods. A lead strip was positioned between the X‐ray source and the breast phantom in the beam stop method. Its inverse version was used in the aperture method. We computed the scatter contribution in the breast phantom by subtracting background scatter. The background scatter fraction was measured without the phantom. The Geant4‐based simulation package GATE was used to model X‐ray photon interactions in the phantom and detector. Two implemented electromagnetic interactions packages, standard and low energy models, were compared for computing efficiency and physics ingredients. A structured breast phantom was used in GATE simulations to determine the characteristics of various scatter components which cannot be separated in measurements. Results: Measurements by the two methods are consistent within 5% after background subtraction, and agree with the low energy model simulations. A hybrid model in GATE, with photoelectric process from the standard model and Compton and Rayleigh scattering processes from the low energy model, is computationally efficient while maintaining physics accuracy. The GATE simulations in the Bakic phantom show that the multiple‐order scatter distribution, as well as single‐order Compton scatter, has predominantly low‐frequency characteristics. Single‐order Rayleigh scatter was observed to be the primary contribution to the spatially variant scatter component.
WE‐E‐L100J‐04: Coherent Scatter Imaging for Mammography
Authors: Zhou W , MacDonald C
Published: July 2007

Purpose: To develop a new screening tool for the detection of breast cancer by the wide‐field collection of x‐ray coherent scatter from the human breast, to potentially improve the diagnosis of breast cancer. Method and Materials: Coherent scatter analysis is normally performed using a highly collimated narrow beam. This complicates adding coherent scatter analysis to screening mammography. A technique has been developed which allows broad field discrimination of coherent scatter using standard high ratio Bucky grids. Using the Kα line from a standard Mo tube, the coherent scattering angle (2θ) for normal breast tissue and cancer tissue would be 9 and 13 degrees, respectively. For the first step of work, pork and beef fat (2θ = 9 degrees) were used as a phantom for normal human breast tissue, while graphite (2θ = 12.16 degrees) was used as a phantom for breast cancer tissue. The coherent scatter images were recorded with CR plates. Tests were carried out with a 10:1 grid for a series of tilt angles and sample‐to‐grid distances. Results: The intensity distribution showed that the coherent scatter from the graphite cancer phantom where observable above the fat background at certain grid tilt angles and sample‐to‐grid distances. Theoretical calculations for the intensity distributions were compared to measurements. Conclusion: This work indicates promising potential for including coherent scatter analysis in screening mammography. The patient is not exposed to any additional x‐ray radiation. Coherent scatter is normally present but not collected. This technology provides an entirely new basis for diagnosis, which may improve the sensitivity and specificity of mammography.
WE‐E‐L100J‐06: Simulation Studies On Contrast Enhanced Dual Energy Mammography
Authors: Zheng D , Huang S , Zhou H , Boone J
Published: July 2007

Purpose: Technique optimization for contrast‐enhanced dual energy mammography in a breast CT scanner. Method and Materials: Using kVp accuracy and HVL measurements physically performed on the x‐ray source of a dedicated cone beam breast CT system, a mathematical spectral model was calibrated to have the same spectral and output properties as the physical system. Mathematical breast phantoms were fabricated by generating random sized and randomly placed glandular spheres on an adipose background to approximate the anatomical noise of the breast. The simulated imaging geometry matched that of the breast CT system. Quantum noise was simulated using Poisson model and a validated random number generator. Contrast‐enhanced dual energy mammography was optimized for parameters including kVp, x‐ray spectral filtration, and mAs distribution between high and low energy images. Mean glandular dose to the breast was calculated using dose coefficients generated from previously published Monte Carlo simulations. A figure of merit of the contrast‐to‐noise ratio at constant mean glandular dose was chosen for the optimization task to maximize image quality at minimal radiation dose levels. Optimization was carried out over a range of breast diameters, breast compositions, and iodine concentrations. Results: Spectra study suggested the optimal kVp to be between 120kV and 140kV for the high energy image, and between 50kV and 60kV for the low energy image, for the studied ranges of breast diameters and compositions. Added copper filtration up to 1mm for the high kVp spectra continued to improve CNR at set dose levels. Iodine as diluted as 0.05% of the 350mg/mL standard solution could be detected with a 2.5mGy total dose. Optimized mAs distribution suggested a higher dose proportion for the low kVp image than for the high kVp image. Conclusion: An optimized contrast‐enhanced dual energy mammography can efficiently suppress anatomical noise and significantly improve contrast detection.
WE‐E‐M100F‐02: Interplay Between Image Quality and Temporal Resolution in 4DCT Acquisition Protocols
Authors: Mutaf Y D , Brinkmann D H
Published: July 2007

Purpose: The accuracy and temporal resolution of 4DCT imaging depends on temporal characteristics of the acquisition protocol like gantry rotation speed and image reconstruction interval, in addition to the spatial and temporal characteristics of the motion itself. Therefore, a generic acquisition protocol might not be suitable for all patients. The aim of this study is to evaluate the interplay between the parameters affecting the accuracy and temporal resolution of 4DCT images. Methods and Materials: Several 4DCT images were acquired of cylindrical phantoms under repetitive motion induced by a translation platform. Acquisition settings were varied with respect to image reconstruction interval, gantry rotation speed and motion period of the phantoms. Reconstructed images were sorted into ten phase bins and compared to CT images of static phantoms at corresponding positions of the respiration phase. Results: Acquisitions with different image reconstruction intervals did not play a significant role in the amount of motion observed in full cycle maximum intensity projection (MIP) images. Single‐phase image integrity was observed to be constant up to a threshold in the value of reconstruction interval, beyond which the image integrity varied somewhat arbitrarily due to the reduced number of images. This threshold is correlated with the number of phase bins and the motion period. Furthermore, image integrity was observed to improve with decreasing gantry rotation periods. Conclusions: Image integrity as evaluated in this study demonstrates relative gains with respect to changes in the temporal resolution parameters of 4DCT acquisition. Due to observed differences, we report that suboptimal settings could result in dramatic target delineation inaccuracies. Optimization of acquisition parameters needs to be performed, assessing the period of motion and limiting factors such as the availability of acquisition settings, image storage and processing power. Conflict of Interest: Sponsored in part by GE Healthcare.
WE‐E‐M100F‐03: Improving Soft Tissue Contrast in Megavoltage Cone‐Beam CT Images for Adaptive Radiotherapy
Authors: Reitz B , Gayou O , Johnson M , Parda D , Miften M
Published: July 2007

Purpose: To investigate image quality improvement in Megavoltage Cone‐Beam CT (MV‐CBCT) images using image filtering techniques for adaptive radiotherapy (ART) protocols. MV‐CBCT imaging is often used for daily patient localization. However, soft tissue contrast in MV‐CBCT images is limited and accurate delineation of targets and organs‐at‐risk is sometimes challenging. Image post‐processing with advanced image filtering techniques can improve the quality without the need to increase the dose exposure for the imaging procedure. Method and Materials: MV‐CBCT images of two image‐quality phantoms and of patients with prostate cancer were post‐processed using noise‐reducing, edge‐preserving image filters. On the phantom images, the contrast‐to‐noise ratio and the spatial resolution before and after filtering were evaluated. The improvement in image quality for the prostate patients was qualitatively judged by physicians based on the ability to delineate the prostate, rectum, bladder and seminal‐vesicle volumes. The optimal combination of MV‐CBCT delivery protocols with different patient doses and filtering techniques was determined for online and offline ART protocols. Results: Using an edge‐preserving noise‐reducing curvature flow image filter, the quality of MV‐CBCT images was improved. The contrast‐to‐noise ratio on the phantoms was improved by up to 30%, while maintaining the spatial resolution. Although the raw cone‐beam image quality of the prostate patients was sufficient for patient treatment localization, the ability to contour anatomical structures was increased on the post‐processed images. Conclusion: Using advanced filtering tools for MV‐CBCT images can improve the image quality, especially soft‐tissue contrast. This allows delineation of organs not clearly visible on the raw images. The tools are potentially beneficial for deformable registration of MV‐CBCT images with planning CTs, for monitoring the delivered dose to targets and organs‐at‐risk, and for ART protocols. Finally using protocols with lower exposure, patient dose from daily imaging procedures can be reduced.
WE‐E‐M100F‐04: Commissioning and Validation of a Beam Model for Calculating Megavoltage CT Dose From Imaging with a Helical Tomotherapy Unit
Authors: Shah A , Langen K , Meeks S , Kupelian P , Staton R , Cox A , Ruchala K
Published: July 2007

Purpose: To commission and validate an MVCT beam model that allows for the calculation of dose received by patients due to megavoltage imaging on a helical tomotherapy unit (Tomotherapy, Inc., Madison, WI). Method and Materials: Percent depth dose and profile data were collected in order to commission a new MVCT beam model. The fluence output for the beam model was adjusted to match the measured dose in phantom. The model was then verified through a series of absorbed dose measurements in three phantoms (20‐cm cylindrical phantom, CIRS anthropomorphic phantom, and 30‐cm “cheese” phantom). The multiple scan average dose was recorded for all three phantoms with various changes to CT collimator pitch and ion chamber location (central versus peripheral points). Results: The delivered doses and the computed doses were on average within 1.5% for all three phantoms, when the ion chamber was centrally located; and within 3.5%, when the chamber was located on the peripheral edge of the phantoms. The measured dose in the anthropomorphic phantom was 2.3 cGy with a pitch of 1.0 (4 mm couch movement per gantry rotation), 1.4 cGy with a pitch 2.0, and 0.90 cGy with a pitch of 3.0, these matched within 1% to the calculated dose. The computed versus measured dose was also within 1% when calculating dose in different tissue densities (lung and bone). Conclusion: This study has shown that with the development of a new MVCT beam model, dose delivered from MVCT imaging can be calculated. Validation measurements, in phantom, have verified that the computed dose can be reported to within 1.5% of the measured dose. The rationale for implementing this MVCT beam model is to provide a future method for calculating patient‐specific MVCT dose. Conflict of Interest: Co‐authors are either funded by a research grant or employed by TomoTherapy, Inc.