Feasibility study of ultrasound imaging for stereotactic body radiation therapy with active breathing coordinator in pancreatic cancer.

PURPOSE: Stereotactic body radiation therapy (SBRT) allows for high radiation doses to be delivered to the pancreatic tumors with limited toxicity. Nevertheless, the respiratory motion of the pancreas introduces major uncertainty during SBRT. Ultrasound imaging is a non-ionizing, non-invasive, and real-time technique for intrafraction monitoring. A configuration is not available to place the ultrasound probe during pancreas SBRT for monitoring. METHODS AND MATERIALS: An arm-bridge system was designed and built. A CT scan of the bridge-held ultrasound probe was acquired and fused to ten previously treated pancreatic SBRT patient CTs as virtual simulation CTs. Both step-and-shoot intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) planning were performed on virtual simulation CT. The accuracy of our tracking algorithm was evaluated by programmed motion phantom with simulated breath-hold 3D movement. An IRB-approved volunteer study was also performed to evaluate feasibility of system setup. Three healthy subjects underwent the same patient setup required for pancreas SBRT with active breath control (ABC). 4D ultrasound images were acquired for monitoring. Ten breath-hold cycles were monitored for both phantom and volunteers. For the phantom study, the target motion tracked by ultrasound was compared with motion tracked by the infrared camera. For the volunteer study, the reproducibility of ABC breath-hold was assessed. RESULTS: The volunteer study results showed that the arm-bridge system allows placement of an ultrasound probe. The ultrasound monitoring showed less than 2 mm reproducibility of ABC breath-hold in healthy volunteers. The phantom monitoring accuracy is 0.14 ± 0.08 mm, 0.04 ± 0.1 mm, and 0.25 ± 0.09 mm in three directions. On dosimetry part, 100% of virtual simulation plans passed protocol criteria. CONCLUSIONS: Our ultrasound system can be potentially used for real-time monitoring during pancreas SBRT without compromising planning quality. The phantom study showed high monitoring accuracy of the system, and the volunteer study showed feasibility of the clinical workflow.

Dosimetric Impact of Source Displacement in GammaTile Surgically Targeted Radiation Therapy for Gliomas.

Background This study aims to evaluate dosimetric changes that happened during the first month after GammaTile surgically targeted radiation therapy (STaRT) for gliomas due to Cesium-131 (Cs-131) seed displacement caused by cavity shrinkage in brain brachytherapy. Methodology In this study, 10 glioma patients had 4-11 GammaTiles placed along the resection bed after maximal safe resection during craniotomy. Each GammaTile is composed of four Cs-131 seeds embedded in a biodegradable collagen sponge to minimize seed movement and maintain seed-to-cavity surface distance. The Cs-131 seed positions were identified using VariSeed on day one. On day 30, post-implant computed tomography (CT) images and dosimetry parameters were calculated. An iterative closest point (ICP) algorithm was used to compute rigid transformation between the day one and day 30 seed clouds. The seed displacement was calculated after registration. The volume receiving 100% of the prescription dose (V100), the dose received by 90% of the planning target volume (D90_PTV), the planning target volume receiving 100% of the prescription dose (V100_PTV), and the dose to organs at risk (OARs) were calculated for both CT images to determine the dosimetric changes from any seed displacement. Results The mean seed displacement of 1.8 ± 1.0 mm for all patients was observed between day one and day 30. The maximum seed displacement for each patient ranged from 2.3 mm to 7.3 mm. The mean V100 difference between day one and day 30 was 2.5 cc (range = 0.5-6.5 cc). The mean D90_PTVs were 95.5% (range = 69.0%-131.0%) and 98.1% (range = 19.9%-149.0%) on day one and day 30, respectively. The mean V100_PTVs were 88.4% (range = 81.3%-99.1%) and 87.9% (range = 47.0%-99.7%) on day one and day 30, respectively. On day one, the brainstem dose was 63.5 Gy for one case and 28.1 Gy for another case; while on day 30, the brainstem dose was 55.8 Gy and 20.6 Gy for the same patients, contributing to 7.7 Gy (12.8%) and 7.5 Gy (12.5%) dose reductions to brainstem for these patients, respectively. Only two patients received a dose to the optic nerves (34.1 Gy and 5.2 Gy). There were small changes (1.8 Gy and 0.5 Gy, respectively) in the dose to optic nerves when comparing the dose calculated on day one and the dose calculated on day 30 CT images. The same two patients received 30.4 Gy and 6.8 Gy to the chiasm, respectively. Small changes in the dose to the chiasm (≤1.1 Gy) were noted between day one and day 30. Conclusions A maximum seed displacement of up to 7.3 mm and a mean seed displacement of 1.8 mm caused by cavity shrinkage were observed during the first month after GammaTile STaRT for gliomas. There were noticeable changes in dosimetry parameters. Changes in the doses to OARs, particularly the brainstem, were large (up to 12.8% of the prescription dose). These changes in dosimetry should be considered when evaluating treatment outcomes and planning future GammaTile treatments.

Optimal parameters for clinical implementation of breast cancer patient setup using Varian DTS software.

Digital tomosynthesis (DTS) was evaluated as an alternative to cone-beam computed tomography (CBCT) for patient setup. DTS is preferable when there are constraints with setup time, gantry-couch clearance, and imaging dose using CBCT. This study characterizes DTS data acquisition and registration parameters for the setup of breast cancer patients using nonclinical Varian DTS software. DTS images were reconstructed from CBCT projections acquired on phantoms and patients with surgical clips in the target volume. A shift-and-add algorithm was used for DTS volume reconstructions, while automated cross-correlation matches were performed within Varian DTS software. Triangulation on two short DTS arcs separated by various angular spread was done to improve 3D registration accuracy. Software performance was evaluated on two phantoms and ten breast cancer patients using the registration result as an accuracy measure; investigated parameters included arc lengths, arc orientations, angular separation between two arcs, reconstruction slice spacing, and number of arcs. The shifts determined from DTS-to-CT registration were compared to the shifts based on CBCT-to-CT registration. The difference between these shifts was used to evaluate the software accuracy. After findings were quantified, optimal parameters for the clinical use of DTS technique were determined. It was determined that at least two arcs were necessary for accurate 3D registration for patient setup. Registration accuracy of 2 mm was achieved when the reconstruction arc length was > 5° for clips with HU ≥ 1000; larger arc length (≥ 8°) was required for very low HU clips. An optimal arc separation was found to be ≥ 20° and optimal arc length was 10°. Registration accuracy did not depend on DTS slice spacing. DTS image reconstruction took 10-30 seconds and registration took less than 20 seconds. The performance of Varian DTS software was found suitable for the accurate setup of breast cancer patients. Optimal data acquisition and registration parameters were determined.

A phantom-based analysis for tracking intra-fraction pancreatic tumor motion by ultrasound imaging during radiation therapy.

Purpose: In this study, we aim to further evaluate the accuracy of ultrasound tracking for intra-fraction pancreatic tumor motion during radiotherapy by a phantom-based study. Methods: Twelve patients with pancreatic cancer who were treated with stereotactic body radiation therapy were enrolled in this study. The displacement points of the respiratory cycle were acquired from 4DCT and transferred to a motion platform to mimic realistic breathing movements in our phantom study. An ultrasound abdominal phantom was placed and fixed in the motion platform. The ground truth of phantom movement was recorded by tracking an optical tracker attached to this phantom. One tumor inside the phantom was the tracking target. In the evaluation of the results, the monitoring results from the ultrasound system were compared with the phantom motion results from the infrared camera. Differences between infrared monitoring motion and ultrasound tracking motion were analyzed by calculating the root-mean-square error. Results: The 82.2% ultrasound tracking motion was within a 0.5 mm difference value between ultrasound tracking displacement and infrared monitoring motion. 0.7% ultrasound tracking failed to track accurately (a difference value > 2.5 mm). These differences between ultrasound tracking motion and infrared monitored motion do not correlate with respiratory displacements, respiratory velocity, or respiratory acceleration by linear regression analysis. Conclusions: The highly accurate monitoring results of this phantom study prove that the ultrasound tracking system may be a potential method for real-time monitoring targets, allowing more accurate delivery of radiation doses.

Safety and efficacy of GammaTile intracranial brachytherapy implanted during awake craniotomy.

INTRODUCTION: GammaTile intracranial brachytherapy (cesium-131 seeds) has demonstrated encouraging safety and local control results, and recently received Food and Drug Administration clearance for newly diagnosed and recurrent brain tumors. The authors present the first reported case of GammaTile intraoperative brachytherapy performed during an awake craniotomy. METHODS: A 50-year-old man had a biopsy-proven, 2.8 cm left lateral frontal glioblastoma lesion nearing Broca's area on MRI. Despite several interventions (craniotomy, adjuvant chemoradiation, tumor treating fields) tumor progression occurred near the left parietal resection cavity. Re-resection was planned with awake craniotomy and language mapping. A preoperative planning session involving Radiation Oncology and Neurosurgery identified the area of the expected postoperative bed, and consequently five GammaTiles were ordered, each containing 4 cesium-131 3.5 U seeds. RESULTS: During surgery, tumor mapping and bipolar stimulation were performed while the patient spoke in complete sentences. Speech arrest occurred upon stimulation at the posterior edge of the gyrus, indicative of language cortex. Microsurgical maximal safe resection subsequently occurred, and areas at risk for residual/recurrence disease were determined in consultation with Radiation Oncology. Subsequently, Neurosurgery placed all five GammaTiles (20 cesium-131 seeds total) after which closure was completed and radioactive surveys of the room remained within state statue. Postoperative dosimetry yielded excellent coverage. CONCLUSIONS: The first reported case of GammaTile intraoperative brachytherapy during awake craniotomy supports the safety and feasibility of this treatment strategy. This case indicates that for patients with tumors adjacent to eloquent cortex, awake craniotomy can allow for custom implantation of intraoperative brachytherapy following maximum safe resection.

Evaluation of MatriXX for IMRT and VMAT dose verifications in peripheral dose regions.

PURPOSE: MatriXX is a two-dimensional ion chamber array designed for IMRT/VMAT (RapidArc, IMAT, etc.) dose verifications. Its dosimetric properties have been characterized for megavoltage beams in a number of studies; however, to the best of the authors' knowledge, there is still a lack of an investigation into its performance in the peripheral or low dose regions. In this work, the authors have carried out a systematic study on this issue. METHODS: The authors compare the performance of MatriXX with a cylindrical ion chamber in solid water phantoms in the peripheral dose regions. The comparisons are performed for a number of typical irradiation conditions that involve different gantry and/or MLC motions, field sizes, and distances to the target including static gantry/open fields, static gantry/sweeping MLC gap (mimicking an IMRT delivery), dynamic gantry/oscillating sweeping MLC gap (mimicking a VMAT delivery), as well as clinical IMRT and VMAT plans. RESULTS: MatriXX, when used according to the manufacturer's recommendations, is found to disagree with an ion chamber in peripheral dose regions. This disagreement has been attributed to four types of MatriXX errors, namely, positive bias, over-response to scattered doses, round-off error, and angular dependence, all of which contribute to dose inaccuracies in the peripheral regions. The positive bias, which is independent of the dose level, is cumulative when MatriXX operates in the movie mode. The accumulation is proportional to the number of movie frames (snaps) when the sampling time is greater than 500 ms and is proportional to the overall movie time for a sampling time shorter than 500 ms. This behavior suggests multiple sources of the bias. MatriXX is also found to over-respond to peripheral doses by about 2.0% for the regions investigated in this work (3-15 cm from the field edge), where phantom scatter and collimator scatter dominate. Round-off error is determined to be due to insufficient precision in conversion of the raw signals to MatriXX software data for low doses. Angular dependence is defined as the dose response of MatriXX at different gantry angles. Up to 8% difference in detector response has been observed between 0 degree and 180 degrees. Possible sources of these errors are discussed and a correction method is suggested. With corrections, MatriXX shows good agreement with the ion chamber in all cases involving different gantry and/or MLC dynamics, as well as the clinical plans. For both primary and peripheral doses, MatriXX shows dose linearity down to 2 cGy with an accuracy of within 1% of the local dose. CONCLUSIONS: The performance of MatriXX has been systematically evaluated in the peripheral dose regions. Major sources of error associated with MatriXX are identified and a correction method is suggested. This method has been successfully tested using both experimental and clinical plans. In all cases, good agreements between MatriXX and an ion chamber are achieved after corrections. The authors conclude that with proper corrections, MatriXX can be reliably used for peripheral dose measurements within the ranges studied.

Evaluation of clip localization for different kilovoltage imaging modalities as applied to partial breast irradiation setup.

Surgical clip localization and image quality were evaluated for different types of kilovoltage cone beam imaging modalities as applied to partial breast irradiation (PBI) setup. These modalities included (i) clinically available radiographs and cone beam CT (CB-CT) and (ii) various alternative modalities based on partial/sparse/truncated CB-CT. An anthropomorphic torso-breast phantom with surgical clips was used for the imaging studies. The torso phantom had artificial lungs, and the attached breast phantom was a mammographic phantom with realistic shape and tissue inhomogeneities. Three types of clips of variable size were used in two orthogonal orientations to assess their in-/cross-plane characteristics for image-guided setup of the torso-breast phantom in supine position. All studies were performed with the Varian on-board imaging (OBI, Varian) system. CT reconstructions were calculated with the standard Feldkamp-Davis-Kress algorithm. First, the radiographs were studied for a wide range of viewing angles to characterize image quality for various types of body anatomy in the foreground/background of the clips. Next, image reconstruction quality was evaluated for partial/sparse/truncated CB-CT. Since these modalities led to reconstructions with strong artifacts due to insufficient input data, a knowledge-based CT reconstruction method was also tested. In this method, the input data to the reconstruction algorithm were modified by combining complementary data sets selected from the treatment and reference projections. Different partial/sparse/truncated CB-CT scan types were studied depending on the total are angle, angular increment between the consequent views (CT projections), orientation of the arc center with respect to the imaged breast and chest wall, and imaging field size. The central angles of the viewing arcs were either tangential or orthogonal to the chest wall. Several offset positions of the phantom with respect to the reference position were studied. The acquired and reconstructed image data sets were analyzed using home-built software focusing on the ability to localize clips in 3D. Streaking and leakage reconstruction artifacts and spatial distortions of breast surface were analyzed as well. Advantages and disadvantages of each kilovoltage CB imaging modality as applied to partial breast setup evaluation based on clips are presented. Because clips were found to be difficult to recognize in radiographs, 3D reconstructions were preferred. Even though it was possible to localize clips with about +/-1 mm accuracy based on reconstructions for short arcs of 40 degrees and incremental angle up to about 5 degrees, identification of clips in such reconstructions is difficult. Reconstructions obtained for arcs of as low as 80 degrees and incremental angle of as high as 3 degrees were suggested for easier clip identification. For more severely undersampled data, iterative CB-CT reconstruction is recommended to decrease the artifacts.

Phase II study of intraoperative dosimetry for prostate brachytherapy using registered ultrasound and fluoroscopy.

PURPOSE: To assess the performance of a system of intraoperative dosimetry and obtain estimates of dosimetry outcomes achieved when utilizing the system in a Phase II clinical trial. METHODS AND MATERIALS: Forty-five patients undergoing permanent Pd-103 seed implantation for prostate cancer were prospectively enrolled. Seed implantation was performed and dose was tracked intraoperatively using intraoperative registered ultrasound and fluoroscopy (iRUF). Three-dimensional seed locations were computed from X-rays and registered to ultrasound for intraoperative dosimetry, followed by adaptive plan modification to achieve prostate V100 ≥95% and ≥95% D90. Time required for iRUF was recorded. Postoperative CT/MRI scans were performed 1 day after the implantation and used as reference for dosimetric analysis. Dosimetric parameters for the prostate and urethra were compared between standard ultrasound-based dosimetry (USD), iRUF, and postoperative CT/MRI. RESULTS: Mean total time for iRUF was <30 min. A mean of four seeds (0-12) were added per implant to correct cold spots discovered by iRUF. Day 1 CT/MRI prostate V100 was ≥95% for 44/45 patients; 1 patient had Day 1 V100 93%. No patient had rectal V100 exceeding 1 cc. Compared to CT/MRI, iRUF dosimetry had significantly smaller mean differences and higher correlations for all prostate and urethral dosimetric parameters examined than USD. Both USD and iRUF tended to overestimate dose, but with less bias in iRUF than USD. CONCLUSIONS: Intraoperative dosimetry utilizing iRUF was associated with acceptable increase in procedure time and enabled very high rates of achieving excellent prostate dose coverage. iRUF intraoperative dosimetry approximated postoperative CT/MRI dosimetry to a greater degree than USD for the prostate and urethra.

Interventional Radiation Oncology (IRO): Transition of a magnetic resonance simulator to a brachytherapy suite.

PURPOSE: As a core component of a new gynecologic cancer radiation program, we envisioned, structured, and implemented a novel Interventional Radiation Oncology (IRO) unit and magnetic resonance (MR)-brachytherapy environment in an existing MR simulator. METHODS AND MATERIALS: We describe the external and internal processes required over a 6-8 month time frame to develop a clinical and research program for gynecologic brachytherapy and to successfully convert an MR simulator into an IRO unit. RESULTS: Support of the institution and department resulted in conversion of an MR simulator to a procedural suite. Development of the MR gynecologic brachytherapy program required novel equipment, staffing, infrastructural development, and cooperative team development with anesthetists, nurses, therapists, physicists, and physicians to ensure a safe and functional environment. Creation of a separate IRO unit permitted a novel billing structure. CONCLUSIONS: The creation of an MR-brachytherapy environment in an MR simulator is feasible. Developing infrastructure includes several collaborative elements. Unique to the field of radiation oncology, formalizing the space as an Interventional Radiation Oncology unit permits a sustainable financial structure.

Stereotactic body radiation therapy in pancreatic cancer: the new frontier.

Pancreatic cancer (PCA) remains a disease with a poor prognosis. The majority of PCA patients are unable to undergo surgical resection, which is the only potentially curative option at this time. A combination of chemotherapy and chemoradiation (CRT) are standard options for patients with locally advanced, unresectable disease, however, local control and patient outcomes remains poor. Stereotactic body radiation therapy (SBRT) is an emerging treatment option for PCA. SBRT delivers potentially ablative doses to the pancreatic tumor plus a small margin over a short period of time. Early studies with single-fraction SBRT demonstrated excellent tumor control with high rates of toxicity. The implementation of SBRT (3-5 doses) has demonstrated promising outcomes with favorable tumor control and toxicity rates. Herein we discuss the evolving role of SBRT in PCA treatment.

Automation of clip localization in Digital Tomosynthesis for setup of breast cancer patients.

The objective of this study is to develop an automatic clip localization procedure for breast cancer patient setup based on Digital Tomosynthesis (DTS) and to characterize its performance with respect to the overall registration accuracy and robustness. The study was performed under an IRB-approved protocol for 12 breast cancer patients with surgical clips implanted around the tumor cavity. The registration of DTS images to planning CTs was performed using an automatic algorithm developed to overcome specific challenges of localization and registration of clips in the breast setup images. The automatic method consisted of auto-segmentation (intensity-based thresholding with a priori knowledge about clip size and location to distinguish clips from bony features) and auto-registration of the segmented clip clusters. To determine the inherent accuracy and robustness of the registration algorithm, additional simulated DTS data was analyzed. The developed algorithm is efficient in removing false positives and negatives and provides an accuracy of better than 2.3mm for 60° and 3.3mm for 40° DTS. When incorporated in clinical software, this algorithm helps to facilitate fast and accurate setup evaluation with minimal dose delivered to patients.

Localization of a portion of an endorectal balloon for prostate image-guided radiation therapy using cone-beam tomosynthesis: a feasibility study.

PURPOSE: To assess the feasibility of using cone-beam tomosynthesis (CBTS) to localize the air-tissue interface for the application of prostate image-guided radiation therapy using an endorectal balloon for immobilization and localization. METHODS AND MATERIALS: A Feldkamp-David-Kress-based CBTS reconstruction was applied to selected sets of cone-beam computed tomography (CBCT) projection data to simulate volumetric imaging achievable from tomosynthesis for a limited range of scan angles. Projection data were calculated from planning CT images of 10 prostate cancer patients treated with an endorectal balloon, as were experimental CBCT projections for a pelvic phantom in two patients. More than 50 points at the air-tissue interface were objectively identified by an intensity-based interface-finding algorithm. Using three-dimensional point sets extracted from CBTS images compared with points extracted from corresponding CBCT images, the relative shift resulting from a reduced scan angle was determined. Because the CBCT and CBTS images were generated from the same projection data set, shift identified was presumed to be due to distortions introduced by the tomosynthesis technique. RESULTS: Scans of ≥60° were shown to be able to localize an air-tissue interface near the isocenter with accuracy on the order of a millimeter. The accuracy was quantified in terms of the mean discrepancy as a function of reconstruction angle. CONCLUSION: This work provides an understanding of the effect of scan angle used in localization of a portion of an endorectal balloon by means of CBTS. CBTS with relatively small scan angles is capable of accurately localizing an extended interface near the isocenter and may provide clinically relevant measurements to guide IGRT treatments while reducing imaging radiation to the patient.

An oscillating sweeping gap test for VMAT quality assurance.

The objective of this study was to develop an oscillating sweeping gap test for volumetric modulated arc therapy (VMAT) quality assurance (QA). A novel test was designed and used to simultaneously determine uncertainties associated with linac performance, dose calculation and dosimetric MLC parameters during VMAT delivery. Delivered doses were measured with Matrixx, ionization chamber A12 and EDR2 films, and compared to calculations from the treatment planning system (TPS) Eclipse. A new gantry and MLC motion pattern, called here 'oscillating sweeping gap', is developed as an extension of the standard sweeping gap MLC pattern developed for IMRT QA. Specifically, in the oscillating sweeping gap test, a uniform MLC gap is moving repeatedly back and forth across the field at a constant speed during a full rotation of the gantry. The dose distribution generated by the combined gantry and MLC motion pattern is designed to be quasi-uniform within a cylindrical target volume with a sharp penumbra. The test design allows for an easy detection of dose errors as deviations from the uniform background. MLC gap sizes, gantry and MLC speeds and monitor units (MU) are selected according to a formula determining the magnitude of dose delivered to the target. Both measured and calculated dose distributions were analyzed as a function of the number of control points in the TPS, MLC gap size and magnitude of the gantry angle error. Dose calculation errors due to the insufficient number of control points in the gantry and MLC motion pattern appear as streak artifacts. The magnitude of these artifacts is increasing with the decreased number of control points, and with the decreased MLC gap size. The spatial distribution of dose errors due to the gantry angle errors (unsteady rocking motion) appears as high-frequency noise for higher wobble frequencies and as large hot/cold spots for lower wobble frequencies. The actual MLC leaf position as a function of time (or the gantry angle), determined from the Matrixx snaps (dose images measured per time interval) of the moving gap and compared to the ideal leaf positions, reveal discrepancies in agreement with theoretical calculations. The MLC parameters determined for VMAT with the oscillating sweeping gap test, their uncertainties and the associated dose errors are similar to those determined for IMRT with the standard sweeping gap test. The oscillating sweeping gap test has been developed for the gantry and MLC QA. Applications include commissioning of the planning system for VMAT and performing routine linac QA. The test is sensitive to several errors in dose calculation and delivery.

Optimal gantry angles and field sizes in kilovoltage cone-beam tomosynthesis for set-up of women with breast cancer undergoing radiotherapy treatment.

Optimal beam geometry for kilovoltage cone-beam tomosynthesis (CB-TS) imaging for the set-up of 20 patients with breast cancer was analyzed and presented for prone and supine scenarios. Gantry angles and field sizes that allow maximum clearance and minimum dose to normal organs from kilovoltage imaging were determined for medial and lateral arcs. Optimal CB-TS arc span may vary depending on patient geometry, particularly on the separation between the cavity and the chest wall. CB-TS arc angles 40 degrees were found to be optimal for the cavity to chest wall separation d>3 cm for supine set-up and d>7 cm for prone set-up. Maximum required jaw openings were 20 x 14 cm(2). Recommendations are provided for clinical implementation of CB-TS imaging for breast cancer patients.