S Shen

Phase I Single-Dose Study of Intracavitary-Administered Iodine-131-TM-601 in Adults With Recurrent High-Grade Glioma

PURPOSEnTM-601 binds to malignant brain tumor cells with high affinity and does not seem to bind to normal brain tissue. Preclinical studies suggest that iodine-131 (131I) -TM-601 may be an effective targeted therapy for the treatment of glioma. We evaluated the safety, biodistribution, and dosimetry of intracavitary-administered 131I-TM-601 in patients with recurrent glioma.nnnPATIENTS AND METHODSnEighteen adult patients (17 with glioblastoma multiforme and one with anaplastic astrocytoma) with histologically documented recurrent glioma and a Karnofsky performance status of > or = 60% who were eligible for cytoreductive craniotomy were enrolled. An intracavitary catheter with subcutaneous reservoir was placed in the tumor cavity during surgery. Two weeks after surgery, patients received a single dose of 131I-TM-601 from one of three dosing panels (0.25, 0.50, or 1.0 mg of TM-601), each labeled with 10 mCi of 131I.nnnRESULTSnIntracavitary administration was well tolerated, with no dose-limiting toxicities observed. 131I-TM-601 bound to the tumor periphery and demonstrated long-term retention at the tumor with minimal uptake in any other organ system. Nonbound peptide was eliminated from the body within 24 to 48 hours. Only minor adverse events were reported during the 22 days after administration. At day 180, four patients had radiographic stable disease, and one had a partial response. Two of these patients further improved and were without evidence of disease for more than 30 months.nnnCONCLUSIONnA single dose of 10 mCi 131I-TM-601 was well tolerated for 0.25 to 1.0 mg TM-601 and may have an antitumoral effect. Dosimetry and biodistribution from this first trial suggest that phase II studies of 131I-TM-601 are indicated.

Radiation dosimetry of 131I-chlorotoxin for targeted radiotherapy in glioma-bearing mice.

Chlorotoxin, or TM-601, is a peptide derived from the venom of the scorpionLeiurus Quinquestriatus that specifically binds to malignant brain tumors, but not to normal tissues. Targeted radiotherapy using 131I-Chlorotoxin is promising for post-surgery treatment of brain tumors. This study reports dosimetry results of 131I-Chlorotoxin in athymic nude mice with intracranially implanted human glioma xenografts and projected radiation doses in patients receiving 370 MBq of 131I-Chlorotoxin. 125I/131I-Chlorotoxin were injected into the right brain where D54 MG xenografts were implanted. Mice were sacrificed 24–96 h later. The blood, normal organs, and tumors were weighed and counted to determine 131I-Chlorotoxin concentration. The radiation dose from 131I was calculated based on non-penetrating radiation in the mouse model. Assuming similar tissue uptake in mice and patients, radiation doses for patients were extrapolated. Distributions of 125I/131I-Chlorotoxin were only significant in tumor, stomach, kidneys, and brain (injection site), reflecting non-specific uptake of Chlorotoxin in normal tissues. Mean radiation dose (cGy/37u2009kBq) was 58.2 for tumor, 17.9 for brains, 1.8 for marrow, 27.1 for stomach, 16.0 for kidneys in mice. For intracranial injection of 370u2009MBq 131I-Chlorotoxin in patients, extrapolated patient dose (cGy) was 70 for brains, 6 for marrow, 35 for stomach, 60 to kidneys, 227 to tumor, suggesting that 3.7u2009GBq of 131I-Chlorotoxin can be safely administrated to patients. These promising results demonstrated potential in improving patient survival using this novel targeting agent.

SU‐DD‐A1‐06: RapidArc Patient Specific Quality Assurance: Comparison with DMLC IMRT

Purpose: To compare RapidArc (Varian Medical Systems) intensity modulated arc therapy and dynamic multileaf collimated IMRT (DMLC) delivery accuracy using patient specific quality assurance measurements. Method and Materials: We selected 6 cases (head and neck, para‐aortic lymph nodes, and 4 prostates) that were treated using both DMLC and RapidArc. The DMLC and RapidArc plans were equivalent with respect to target and critical structure dosimetry. Absolute dose measurements were made with an ionization chamber in a custom acrylic phantom, which was positioned such that the chamber was located in a high‐dose, low‐gradient region of the dose distribution. Film was used to obtain the dose distribution in a coronal plane at the level of the ionization chamber. A 2D ionization chamber array (Matrixx, IBA Dosimetry) was used to obtain a second measurement in the same coronal plane. The gamma index was calculated for both the film and 2D array measurements using the criteria of 3%/3mm. Results: The mean difference between the ionization chamber measurements and the calculations was 1.0% for both RapidArc and DMLC. The ranges were 0.6% to 1.6% and 0.0% to 2.3%, respectively. The mean fraction of pixels with gamma > 1 for the film was 4.3% (range 0.8% to 6.9%) for RapidArc and 10.4% (range 5.4% to 17.3%) for DMLC. For the 2D array the mean fraction of pixels with gamma > 1 was 0.5% (range 0.0% to 1.1%) for RapidArc and 1.6% (range 0.5% to 4.1%) for DMLC. Conclusion: The results demonstrate that RapidArc delivery is at least as accurate as that for DMLC. The mean fraction of pixels with gamma >1 and the range of fractions for both film and the 2D chamber array suggests that RapidArc may be modestly more accurate than DMLC. Conflict of Interest: Research sponsored by Varian Medical Systems.

SU‐E‐T‐227: Feasibility of Collision Avoidance Using In Room 3D Camera

Purpose: To determine the feasibility of detecting potential collisions between hardware and patient without the need of a CT scan. Methods: A 3D camera (Kinect for Windows, Microsoft) was mounted onto an on board imaging arm and 3 depth images at different angles were taken of an anthropomorphic phantom in a treatment position. A convex hull was then calculated from the depth vertices for use in a computer collision simulation. Positive collisions were then determined by manually moving the couch and gantry over a sample of their motion ranges. The results were compared with a computer simulation that calculated the positive collisions from the scanned geometry. Results: The simulation calculated 64,620 collision potential configurations of the phantom/couch and gantry at 1 degree increments in 4.36 sec using an Intel Core i3 processor with 8GB of ram. The accuracy of the calculation was assessed by dividing up the results into four different groups: true positive (correctly predicted collision), true negative (correctly predicted no collision), false positive (wrongly predicted collision), false negative (wrongly predicted no collision). There were 3949 measured data points, which resulted in TP = 1131, TN = 2437, FN = 275, and FP = 106 points. The receiver operating curve accuracy metric (TP+TN)/(TP+TN+TN+FN)) was then calculated from these groups as 90.35 %. Conclusion: We have successfully demonstrated a framework that could be used to scan patient geometry on the treatment table for use in collision avoidance. This could also be used in the simulation step of treatment to avoid planning geometrically infeasible setups. Collision prediction inaccuracies are attributed to inadequate point cloud data to accurately describe phantom geometry. Better sampling with improved reconstruction software should enable the ability to completely avoid planning of non‐deliverable beams or collisions during treatment.

SU‐E‐P‐14: A Practical Approach of Small Field Dosimetry Measurement for Patient‐Specific IMRT/SRS/SBRT

PURPOSEnTo design and implement a small-field IMRT/SRS/SBRT dosimetry measurement with a regular-size ion chamber and films.nnnMETHODSnAn acrylic phantom was constructed and commissioned to sandwich a Kodak EDR2 radiographic film. After a patient QA plan was delivered, the phantom was shifted superiorly by 10 cm and a reference plan was delivered on the same film. The reference plan has four-field-box beam geometry with 4 × 4 cm2 field size. Since the dose distribution of the reference plan was uniform and large, the absolute dose of the reference plan can be accurately measured separately with a regular-size ion chamber (diameter: 0.6 cm). After normalization, a two-dimensional absolute dose distribution can be obtained and compared to that calculated by Eclipse Treatment Planning System. An in-house software written in MATLAB was used to analyze films. Two-dimensional gamma indexes were calculated to evaluate patient QA plans.nnnRESULTSnThree patient-specific IMRT/SRS/SBRT QA plans were used to verify the feasibility of the method. The prescription dose of the reference plan was 3.5 Gy. The scatter dose from one plan to the other plan (which is 10 cm or more away) is very small (<1 cGy) and can be ignored. Compared with Eclipse calculation, the measured dose errors of the reference plan were -0.1-, -0.3%, and -0.8%, respectively. For the three patient-specific QA plans, the point dose measurement errors were 2.1%, 0.8% and 0.2%, respectively, and the γ>1 failure rates were 0.2%, 0.2%, and 0.1%, respectively.nnnCONCLUSIONnSince the scatter dose from another plan 10 cm (or more) away was very small, this method allows one to measure the dose of any small target with a regular-size ion chamber and films without volume limitation.

MO‐D‐BRB‐06: JUNIOR INVESTIGATOR WINNER ‐ Fast and Accurate Patient Specific Collision Detection for Radiation Therapy

PURPOSEnTo develop a fast and generalizable method which can identify all possible hardware collisions specific to a given patient setup before treatment planning.nnnMETHODSnAn anthropomorphic phantom placed in a typical breast setup using a wingboard was simulated on a CT scanner and the phantom body contour, table, and gantry geometry were made into polygon meshes using 3D modeling software. In the treatment room, a limited physical search of the collision positive zones was performed using the positioned phantom. A software tool that incorporated a generalized hierarchical bounding box (HBB) collision detection algorithm was developed and used to virtually map out the entire collision space by transforming the positions of the polygonal geometry over a given parameter range.nnnRESULTSnThe geometry containing 47K polygons was mapped over a space of 6480 states with an average transform/collision check of 5.5ms, for a total time of 35.6s on a 3.14GHz dual core computer with 4GB memory. The computed collision space, using receiver operating curve analysis had an accuracy of 96.35%, and a positive predictive value of 91.2%.nnnCONCLUSIONSnThis work demonstrates a framework that can provide a fast and accurate map of the collision free space specific to any patient setup. Differences in physical and simulated collision space is attributed to inaccuracies of the geometrical models used. Future work includes improving the efficiency of the algorithm, enhancing the geometrical models and increasing the dimensions of the search.

SU-F-T-645: To Test Spatial Anddosimetric Accuracy of Small Cranial Target Irradiation Based On 1.5 T MRIscans Using Static Arcs with MLCDefined Fields.

PURPOSEnTo test spatial and dosimetric accuracy of small cranial target irradiation based on 1.5 T MRI scans using static arcs with MLC-defined fields METHODS: A plastic (PMMA) phantom simulating a small brain lesion was mounted on a GammaKnife headframe equipped with MRI localizer. The lesion was a 3 mm long, 3.175 mm diameter cylindrical cavity filled with MRI contrast. Radiochromic film passing through the cavity was marked with pin pricks at the cavity center. The cavity was contoured on an MRI image and fused with CT to simulate treatment of a lesion not visible on CT. The transfer of the target to CT involved registering the MRI contrast cannels of the localizer that were visible on both modalities. Treatments were planned to deliver 800 cGy to the cavity center using multiple static arcs with 5.0×2.4 mm MLC-defined fields. The phantom was aligned on a STx accelerator by registering the conebeam CT with the planning CT. Films from coronal and sagittal planes were scanned and evaluated using ImageJ software RESULTS: Geographic errors in treatment based on 1.5 T scans agreed within 0.33, -0.27 and 1.21 mm in the vertical, lateral and longitudinal dimensions, respectively. The doses delivered to the cavity center were 7.2% higher than planned. The dose distributions were similar to those of a GammaKnife.nnnCONCLUSIONnRadiation can be delivered with an accelerator at mm accuracy to small cranial targets based on 1.5 MRI scans fused to CTs using a standard GammaKnife headframe and MRI localizer. MLC-defined static arcs produce isodose lines very similar to the GammaKnife.

SU-C-201-05: Imaging 212Pb-TCMC-Trastuzumab for Alpha Radioimmunotherapy for Ovarian Cancer

Purpose: To support the phase I trial for toxicity, biodistribution and pharmacokinetics of intra-peritoneal (IP) 212Pb-TCMC-trastuzumab in patients with HER-2 expressing malignancy. A whole body gamma camera imaging method was developed for estimating amount of 212Pb-TCMC-trastuzumab left in the peritoneal cavity. Methods: {sup 212}Pb decays to {sup 212}Bi via beta emission. {sup 212}Bi emits an alpha particle at an average of 6.1 MeV. The 238.6 keV gamma ray with a 43.6% yield can be exploited for imaging. Initial phantom was made of saline bags with 212Pb. Images were collected for 238.6 keV with a medium energy general purpose collimator. There are other high energy gamma emissions (e.g. 511keV, 8%; 583 keV, 31%) that penetrate the septae of the collimator and contribute scatter into 238.6 keV. An upper scatter window was used for scatter correction for these high energy gammas. Results: A small source containing 212Pb can be easily visualized. Scatter correction on images of a small 212Pb source resulted in a ∼50% reduction in the full width at tenth maximum (FWTM), while change in full width at half maximum (FWHM) was 5 cm outside; scatter correction improved imagemorexa0» contrast by removing this scatter around the sources. Patient imaging, in the 1st cohort (n=3) showed little redistribution of 212Pb-TCMC-trastuzumab out of the peritoneal cavity. Compared to the early post-treatment images, the 18-hour post-injection images illustrated the shift to more uniform anterior/posterior abdominal distribution and the loss of intensity due to radioactive decay. Conclusion: Use of medium energy collimator, 15% width of 238.6 keV photopeak, and a 7.5% upper scatter window is adequate for quantification of 212Pb radioactivity inside peritoneal cavity for alpha radioimmunotherapy of ovarian cancer. Research Support: AREVA Med, NIH 1UL1RR025777-01.«xa0less

SU‐E‐T‐291: Dosimetric Accuracy of Multitarget Single Isocenter Radiosurgery

Purpose: To evaluate the accuracy of single-isocenter multiple-target VMAT radiosurgery (SIMT-VMAT-SRS) by analysis of pre-treatment verification measurements. Methods: Our QA procedure used a phantom having a coronal plane for EDR2 film and a 0.125 cm3 ionization chamber. Film measurements were obtained for the largest and smallest targets for each plan. An ionization chamber measurement (ICM) was obtained for sufficiently large targets. Films were converted to dose using a patient-specific calibration curve and compared to treatment planning system calculations. Alignment error was estimated using image registration. The gamma index was calculated for 3%/3 and 3%/1 mm criteria. The median dose in the target region and, for plans having an ICM, the average dose in the central 5 mm was calculated. Results: The average equivalent target diameter of the 48 targets was 15 mm (3–43 mm). Twenty of the 24 plans had an ICM for the plan corresponding to the largest target (diameter 11–43 mm) with a mean ratio of chamber reading to expected dose (ED) and the mean ratio of film to ED (averaged over the central 5 mm) was 1.001 (0.025 SD) and 1.000 (0.029 SD), respectively. For all plans, the mean film to ED (from the median dose in the target region) was 0.997 (0.027 SD). The mean registration vector was (0.15,0.29) mm, with an average magnitude of 0.96 mm. Before (after) registration, the average fraction of pixels having gamma < 1 was 99.3% (99.6%) and 89.1% (97.6%) for 3%/3mm and 3%/1mm, respectively. Conclusion: Our results demonstrate dosimetric accuracy of SIMT-VMAT-SRS for targets as small as 3 mm. Film dosimetry provides accurate assessment of the absolute dose delivered to targets too small for an ionization chamber measurement; however, the relatively large registration vector indicates that image-guidance should replace laser-based setup for patient-specific evaluation of geometric accuracy.

SU-E-J-38: Improved DRR Image Quality Using Polyetheretherketone (PEEK) Fiducial in Image Guided Radiotherapy (IGRT)

Purpose Fiducial-based imaging is often used in IGRT. Traditional gold fiducial marker often has substantial reconstruction artifacts. These artifacts Result in poor image quality of DRR for online kV-to-DRR matching. This study evaluated the image quality of PEEK in DRR in static and moving phantom. Methods CT scan of the Gold and PEEK fiducial (both 1×3 mm) was acquired in a 22 cm cylindrical phantom filled with water. Image artifacts was evaluated with maximum CT value deviated from water due to artifacts; volume of artifacts in 10×10 cm in the center slice; maximum length of streak artifacts from the fiducial. DRR resolution were measured using FWHM and FWTM. 4DCT of PEEK fiducial was acquired with the phantom moving sinusoidally in superior-inferior direction. Motion artifacts were assessed for various 4D phase angles. Results The maximum CT value deviation was −174 for Gold and −24 for PEEK. The volume of artifacts in a 10x10 cm 3 mm slice was 0.369 for Gold and 0.074 cm3 for PEEK. The maximum length of streak artifact was 80mm for Gold and 7 mm for PEEK. PEEK in DRR, FWHM was close to actual (1.0 mm for Gold and 1.1 mm for PEEK). FWTM was 1.8morexa0» mm for Gold and 1.3 mm for PEEK in DRR. Barrel motion artifact of PEEK fiducial was noticeable for free-breathing scan. The apparent PEEK length due to residual motion was in close agreement with the calculated length (13 mm for 30–70 phase, 10 mm in 40–60 phase). Conclusion Streak artifacts on planning CT associated with use of gold fiducial can be significantly reduced by PEEK fiducial, while having adequate kV image contrast. DRR image resolution at FWTM was improved from 1.8 mm to 1.3 mm. Because of this improvement, we have been routinely use PEEK for liver IGRT.«xa0less