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Most of the treatment units, both new and old models, are equipped with a megavoltage portal imager but its use for volumetric imaging is limited. This is mainly due to the poor image quality produced by the high‐energy treatment beam (>6 MV). A linac at our center is equipped with a prototype 2.5 MV imaging beam. This study evaluates the feasibility of low‐dose megavoltage cone‐beam imaging with the 2.5 MV beam and a thick cesium iodide detector, which is a high‐efficiency imager. Basic imaging properties such as spatial resolution and modulation transfer function were assessed for the 2.5 MV prototype imaging system. For image quality and imaging dose, a series of megavoltage cone‐beam scans were acquired for the head, thorax, and pelvis of an anthropomorphic phantom and were compared to kilovoltage cone‐beam and 6X megavoltage cone‐beam images. To demonstrate the advantage of MV imaging, a phantom with metallic inserts was scanned and the image quality was compared to CT and kilovoltage cone‐beam scans. With a lower energy beam and higher detector efficiency, the 2.5 MV imaging system generally yields better image quality than does the 6 MV imaging system with the conventional MV imager. In particular, with the anthropomorphic phantom studies, the contrast to noise of bone to tissue is generally improved in the 2.5 MV images compared to 6 MV. With an image quality sufficient for bony alignment, the imaging dose for 2.5 MV cone‐beam images is 2.4−3.4 MU compared to 26 MU in 6 MV cone‐beam scans for the head, thorax, and pelvis regions of the phantom. Unlike kilovoltage cone‐beam, the 2.5 MV imaging system does not suffer from high‐Z image artifacts. This can be very useful for treatment planning in cases where high‐Z prostheses are present. PACS number(s): 87.57.Q‐

Aim: The aim of work is to explore a quick, efficient, and effective patient-specific intensity-modulated radiation therapy (IMRT) quality assurance (QA). Materials and Methods: Software tools were developed to extract and analyze the multi-leaf collimator (MLC) leaf positions (LPs) from electronic portal imaging device (EPID) images for Varian C-series machine and TrueBeam, to extract useful data from MLC log file of C-series linear accelerator (LINAC), to extract useful information from the trajectory log binary file of TrueBeam LINAC, to compare LPs derived from EPID images with log file/trajectory log data, and to analyze IMRT treatment files using the MATLAB programming language. The difference in LP determined from the trajectory log and EPID images was proposed for patient-specific QA. Results: It was found that the differences in LP for regular radiation fields generated using stationary leaves are

Purpose: To develop a new method for accurate measurement of dynamic respiratory tidal volume, we investigate the feasibility of measuring torso volume change using optical surfaceimaging (OSI). Methods: Based on a validated volume conservation theory, the tidal volume is equal to the volume change of the torso during quiet respiration (Li et al, PMB, 54:1693, 2009). A clinical OSI system was employed to acquire surfaceimages of seven geometric phantoms and two ‘deformable’ torso phantoms. The mesh surfaceimages were converted into contours for volume calculation using a treatment planning system. For geometric phantoms, their volumes under the incomplete surfaceimages were calculated with aid of their symmetry. The results were compared with theoretical calculation and water containment experiments. For deformable torso phantoms, we created volume‐controlled deformation stages by placing deformable PlayDoh (DPD) materials on top of rigid Rando/Thorax phantoms, mimicking respiration‐induced torso surface elevation and volume change. The volume difference under the surfaces with and without the DPD padding was calculated with aid of a common posterior line to enclose the region of interest. Three different volumes of DPD padding (>500cc) were mounted on the torso phantoms and CT scanned for volume measurements. Results: For geometric phantoms, the OSI measured volume had accuracy (±1s) of 0.0%±1.6% (vs. geometric volume calculation) and 0.6%±3.8% (vs. water containment experiment). For deformable torso phantoms, the volume change was measured using OSI with an accuracy of 1.5%±2.5% against the measured volume using CTimaging.Linear regression showed a one‐to‐one relationship between the OSI volumes and CT volumes with a slope of 1.003 (r2=0.999). Conclusions: The optical surfaceimaging system can accurately measure the volume of geometric phantoms and the volume change of deformable torso phantoms. The accuracy is about 3% against standard volume measurement methods. Further study on human subjects is under investigation. Memorial Sloan‐Kettering Cancer Center has a reserach agreement with Vision RT, Inc.

Aim of the Study: Statistical analysis of pre-treatment dose verification of intensity-modulated radiotherapy (IMRT) fields to assess the quality of the IMRT practice at different radiotherapy centers. Materials and Methods: The dose verification data acquired by the institutional physicist of 10 different hospitals for various types of patients were collected and analyzed for mean, median, standard deviation (SD), range, minimum and maximum % deviation. The percentage of cases having positive and negative dose differences as well dose differences within ± 3% were also determined. Results: The mean values of percentage variation in difference between treatment planning systems calculated dose and difference between measured dose (D TPS and D Meas ) are found to be from – 1.79 to 1.48 and median from – 1.79 to 1.51. The SDs are found to be from 0.76 to 3.70. The range of variation at these centers varies from 3.99 to 16.45 while minimum and maximum values of percentage variation in difference between D TPS and D Meas ranges from – 10.33 to 13.38. The percentage of cases having positive dose difference ranges from 8 to 94 and cases having negative dose difference ranges from 6 to 92. The percentage of cases having dose difference within ± 3% varies from 57 to 100. Conclusion: IMRT centers are having random and biased (skewed towards over or under dose) distribution of the percentage variation in difference between measured and planned doses. The analysis of results of the IMRT pre-treatment dose verification reveals that there are systematic errors in the chain of IMRT treatment process at a few centers. The dosimetry quality audit prior to commissioning of IMRT may play an important role in avoiding such discrepancies.

PURPOSE To establish a new clinical procedure in frameless stereotactic radiosurgery (SRS) for patient setup verification at treatment couch angles as well as for head-motion monitoring during treatment using video-based optical surface imaging (OSI). METHODS A video-based three-dimensional (3D) OSI system with three ceiling-mounted camera pods was employed to verify setup at treatment couch angles as well as to monitor head motion during treatment. A noninvasive head immobilization device was utilized, which includes an alpha head mold and a dental mouthpiece with vacuum suction; both were locked to the treatment couch. Cone beam computed tomography (CBCT) was used as the standard for image-guided setup. Orthogonal 2D-kV imaging was applied for setup verification before treatment, between couch rotations, and after treatment at zero couch angle. At various treatment couch angles, OSI setup verification was performed, relative to initial OSI setup verification at zero couch angle after CBCT setup through a coordinate transformation. For motion monitoring, the setup uncertainty was decoupled by taking an on-site surface image as new reference to detect motion-induced misalignment in near real-time (1-2 frames per second). Initial thermal instability baseline of the real-time monitoring was corrected. An anthropomorphous head phantom and a 1D positioning platform were used to assess the OSI accuracy in motion detection in longitudinal and lateral directions. Two hypofractionated (9 Gy x 3 and 6 Gy x 5) frameless stereotactic radiotherapy (SRT) patients as well as two single-fraction (21 and 18 Gy) frameless SRS patients were treated using this frameless procedure. For comparison, 11 conventional frame-based SRS patients were monitored using the OSI to serve as clinical standards. Multiple noncoplanar conformal beams were used for planning both frameless and frame-based SRS with a micromultileaf collimator. RESULTS The accuracy of the OSI in 1D motion detection was found to be 0.1 mm with uncertainty of +/- 0.1 mm using the head phantom. The OSI registration against simulation computed tomography (CT) external contour was found to be dependent on the CT skin definition with -0.4 mm variation. For frame-based SRS patients, head-motion magnitude was detected to be

Our goal is to determine an optimized image‐guided setup by comparing setup errors determined by two‐dimensional (2D) and three‐dimensional (3D) image guidance for head and neck cancer (HNC) patients immobilized by customized thermoplastic masks. Nine patients received weekly imaging sessions, for a total of 54, throughout treatment. Patients were first set up by matching lasers to surface marks (initial) and then translationally corrected using manual registration of orthogonal kilovoltage (kV) radiographs with DRRs (2D‐2D) on bony anatomy. A kV cone beam CT (kVCBCT) was acquired and manually registered to the simulation CT using only translations (3D‐3D) on the same bony anatomy to determine further translational corrections. After treatment, a second set of kVCBCT was acquired to assess intrafractional motion. Averaged over all sessions, 2D‐2D registration led to translational corrections from initial setup of 3.5±2.2 (range 0–8) mm. The addition of 3D‐3D registration resulted in only small incremental adjustment (0.8±1.5mm). We retrospectively calculated patient setup rotation errors using an automatic rigid‐body algorithm with 6 degrees of freedom (DoF) on regions of interest (ROI) of in‐field bony anatomy (mainly the C2 vertebral body). Small rotations were determined for most of the imaging sessions; however, occasionally rotations >3° were observed. The calculated intrafractional motion with automatic registration was

Respiration-induced tumor motion during intensity-modulated radiotherapy (IMRT) of non-small-cell lung cancer (NSCLC) could cause substantial differences between planned and delivered doses. While it has been shown that, for conventionally fractionated IMRT, motion effects average out over the course of many treatments, this might not be true for hypofractionated IMRT (IMHFRT). Numerical simulations were performed for nine NSCLC patients (11 tumors) to evaluate this problem. Dose distributions to the Clinical Target Volume (CTV) and Internal Target Volume (ITV) were retrospectively calculated using the previously-calculated leaf motion files but with the addition of typical periodic motion (i.e. amplitude 0.36-1.26cm, 3-8sec period). A typical IMHFRT prescription of 20Gy x 3 fractions was assumed. For the largest amplitude (1.26 cm), the average +/- standard deviation of the ratio of simulated to planned mean dose, minimum dose, D95 and V95 were 0.98+/-0.01, 0.88 +/- 0.09, 0.94 +/- 0.05 and 0.94 +/- 0.07 for the CTV, and 0.99 +/-0.01, 0.99 +/- 0.03, 0.98 +/- 0.02 and 1.00 +/- 0.01 for the ITV, respectively. There was minimal dependence on period or initial phase. For typical tumor geometries and respiratory amplitudes, changes in target coverage are minimal but can be significant for larger amplitudes, faster beam delivery, more highly-modulated fields, and smaller field margins.

Digital tomosynthesis (DTS) with a linear accelerator-mounted imaging system provides a means of reconstructing tomographic images from radiographic projections over a limited gantry arc, thus requiring only a few seconds to acquire. Its application in the thorax, however, often results in blurred images from respiration-induced motion. This work evaluates the feasibility of respiration-correlated (RC) DTS for soft-tissue visualization and patient positioning. Image data acquired with a gantry-mounted kilovoltage imaging system while recording respiration were retrospectively analyzed from patients receiving radiotherapy for non-small-cell lung carcinoma. Projection images spanning an approximately 30 degrees gantry arc were sorted into four respiration phase bins prior to DTS reconstruction, which uses a backprojection, followed by a procedure to suppress structures above and below the reconstruction plane of interest. The DTS images were reconstructed in planes at different depths through the patient and normal to a user-selected angle close to the center of the arc. The localization accuracy of RC-DTS was assessed via a comparison with CBCT. Evaluation of RC-DTS in eight tumors shows visible reduction in image blur caused by the respiratory motion. It also allows the visualization of tumor motion extent. The best image quality is achieved at the end-exhalation phase of the respiratory motion. Comparison of RC-DTS with respiration-correlated cone-beam CT in determining tumor position, motion extent and displacement between treatment sessions shows agreement in most cases within 2-3 mm, comparable in magnitude to the intraobserver repeatability of the measurement. These results suggest the method's applicability for soft-tissue image guidance in lung, but must be confirmed with further studies in larger numbers of patients.

A novel IMRT phantom was designed and fabricated using Acrylonitrile Butadiene Styrene (ABS) plastic. Physical properties of ABS plastic related to radiation interaction and dosimetry were compared with commonly available phantom materials for dose measurements in radiotherapy. The ABS IMRT phantom has provisions to hold various types of detectors such as ion chambers, radiographic/radiochromic films, TLDs, MOSFETs, and gel dosimeters. The measurements related to pretreatment dose verification in IMRT of carcinoma prostate were carried out using ABS and Scanditronix‐Wellhofer RW3 IMRT phantoms for five different cases. Point dose data were acquired using ionization chamber and TLD discs, while Gafchromic EBT and radiographic EDR2 films were used for generating 2D dose distributions. Treatment planning system (TPS) calculated and measured doses in ABS plastic and RW3 IMRT phantom were in agreement within ± 2%. The dose values at a point in a given patient acquired using ABS and RW3 phantoms were found comparable within 1%. Fluence maps and dose distributions of these patients generated by TPS and measured in ABS IMRT phantom were also found comparable both numerically and spatially. This study indicates that ABS plastic IMRT phantom is a tissue‐equivalent phantom and, dosimetrically, it is similar to solid/plastic water IMRT phantoms. Although this material is demonstrated for IMRT dose verification, it can also be used as a tissue‐equivalent phantom material for other dosimetry purposes in radiotherapy. PACS number: 87.53Kn, 87.55Qr, 87.53Bn and 87.55Km

To report toxicity and preliminary biochemical outcomes with high-dose intensity-modulated radiation therapy (IMRT) to a dose of 86.4 Gy for localized prostate cancer.Between August 1997 and March 2004, 478 patients were treated with 86.4 Gy using a 5- to 7-field IMRT technique. To adhere to normal tissue constraints, the mean D95 and V100 for the planning target volume were 83 Gy and 87%, respectively. Toxicity data were scored according to the Common Terminology Criteria for Adverse Events Version 3.0. Freedom from biochemical relapse was calculated. The median follow-up was 53 months.Thirty-seven patients (8%) experienced acute Grade 2 gastrointestinal (GI) toxicity. There was no acute Grade 3 or 4 GI toxicity. One hundred and five patients (22%) experienced acute Grade 2 genitourinary (GU) toxicity and three patients (0.6%) had Grade 3 GU toxicity. There was no acute Grade 4 GU toxicity. Sixteen patients (3%) developed late Grade 2 GI toxicity and two patients (1%) developed late Grade 3 GI toxicity. Sixty patients (13%) had late Grade 2 GU toxicity and 12 (3%) experienced late Grade 3 GU toxicity. The 5-year actuarial PSA relapse-free survival according to the nadir plus 2 ng/mL definition was 98%, 85% and 70% for the low, intermediate, and high risk NCCN prognostic groups.This report represents the largest data set of patients treated to ultra-high radiation dose levels of 86.4 Gy using IMRT for localized prostate cancer. Our findings indicate that this treatment is well tolerated and the early excellent biochemical control rates are encouraging.

Intensity-modulated radiation therapy (IMRT) is an advanced treatment delivery technique that can improve the therapeutic dose ratio. Its use in the treatment of inoperable non-small cell lung cancer (NSCLC) has not been well studied. This report reviews our experience with IMRT for patients with inoperable NSCLC.We performed a retrospective review of 55 patients with stage I-IIIB inoperable NSCLC treated with IMRT at our institution between 2001 and 2005. The study endpoints were toxicity, local control, and overall survival.With a median follow-up of 26 months, the 2-year local control and overall survival rates for stage I/II patients were 50% and 55%, respectively. For the stage III patients, 2-year local control and overall survival rates were 58% and 58%, respectively, with a median survival time of 25 months. Six patients (11%) experienced grade 3 acute pulmonary toxicity. There were no acute treatment-related deaths. Two patients (4%) had grade 3 or worse late treatment-related pulmonary toxicity.IMRT treatment resulted in promising outcomes for inoperable NSCLC patients.

Purpose: To evaluate the use of megavoltage cone-beam computed tomography (MV CBCT) to measure interfractional variation in lung tumor position. Methods and Materials: Eight non–small-cell lung cancer patients participated in the study, 4 with respiratory gating and 4 without. All patients underwent MV CBCT scanning at weekly intervals. Contoured planning CT and MV CBCT images were spatially registered based on vertebral anatomy, and displacements of the tumor centroid determined. Setup error was assessed by comparing weekly portal orthogonal radiographs with digitally reconstructed radiographs generated from planning CT images. Hypothesis testing was performed to test the statistical significance of the volume difference, centroid displacement, and setup uncertainty. Results: The vertebral bodies and soft tissue portions of tumor within lung were visible on the MV CBCT scans. Statistically significant systematic volume decrease over the course of treatment was observed for 1 patient. The average centroid displacement between simulation CT and MV CBCT scans were 2.5 mm, −2.0 mm, and −1.5 mm with standard deviations of 2.7 mm, 2.7 mm, and 2.6 mm in the right–left, anterior–posterior and superior–inferior directions. The mean setup errors were smaller than the centroid shifts, while the standard deviations were comparable. In most cases, the gross tumor volume (GTV) defined on the MV CBCT was located on average at least 5 mm inside a 10 mm expansion of the GTV defined on the planning CT scan. Conclusions: The MV CBCT technique can be used to image lung tumors and may prove valuable for image-guided radiotherapy. Our conclusions must be verified in view of the small patient number.

Purpose: To investigate the potential benefits of a micromultileaf collimator (μMLC) –based intensity-modulated stereotactic radiotherapy (IMSRT) in skull-base meningiomas. Methods and Materials: Seven patients with inoperable or recurrent small-volume (1.7–15.5 cc) skull-base meningiomas were treated with IMSRT to 54 Gy in 30 fractions using a μMLC in the dynamic mode. IMSRT plan quality was evaluated in comparison with the conformal stereotactic radiotherapy technique, using the same beam arrangement and static delivery with the μMLC. Plans were compared using multiple dose distributions and dose–volume histograms for the planning target volume and organs at risk. The conformity and uniformity metrics, as well as normal-tissue complication probabilities, were calculated for the two techniques. Follow-up with MRI and clinical examination was performed at regular intervals. Results: With a mean follow-up of 17 months, local control has been achieved in all cases, and no treatment-related toxicities have been noted. For cavernous sinus tumors overlapping with optic apparatus, IMSRT has improved the dose uniformity within the target on average by 8%, which resulted in a reduction of the estimated chiasm normal-tissue complication probability by up to 65%. Conclusions: Intensity-modulated stereotactic radiotherapy can be safely delivered to improve the dose distributions in select skull-base meningiomas with an appreciable concomitant dose reduction to involved critical structures. Longer follow-up with a larger patient group is necessary to demonstrate sustained tumor control and low morbidity with IMSRT for small inoperable, recurrent, or subtotally resected meningiomas.

Howard I. Amols, David A. Jaffray, and Colin G. Orton Citation: Medical Physics 33, 3583 (2006); doi: 10.1118/1.2211707 View online: http://dx.doi.org/10.1118/1.2211707 View Table of Contents: http://scitation.aip.org/content/aapm/journal/medphys/33/10?ver=pdfcov Published by the American Association of Physicists in Medicine Articles you may be interested in Frontiers of Radiation Therapy and Oncology, Vol. 40: IMRT, IGRT, SBRT: Advances in the Treatment Planningand Delivery of Radiotherapy Med. Phys. 35, 3822 (2008); 10.1118/1.2957612 The Modern Technology of Radiation Oncology, Volume 2 Med. Phys. 33, 249 (2006); 10.1118/1.2142595 Image-guided adaptive radiation therapy (IGART): Radiobiological and dose escalation considerations forlocalized carcinoma of the prostate Med. Phys. 32, 2193 (2005); 10.1118/1.1935775 The value of PETCT is being over-sold as a clinical tool in radiation oncology Med. Phys. 32, 1457 (2005); 10.1118/1.1924458 Role of multimodality imaging in radiotherapy planning Med. Phys. 31, 1645 (2004); 10.1118/1.1738171

We have previously described a low-dose megavoltage cone beam computed tomography (MV CBCT) system capable of producing projection image using one beam pulse. In this study, we report on its integration with respiratory gating for gated radiotherapy. The respiratory gating system tracks a reflective marker on the patient's abdomen midway between the xiphoid and umbilicus, and disables radiation delivery when the marker position is outside predefined thresholds. We investigate two strategies for acquiring gated scans. In the continuous rotation-gated acquisition, the linear accelerator(LINAC) is set to the fixed x-ray mode and the gantry makes a 5 min , 360 ° continuous rotation, during which the gating system turns the radiation beam on and off, resulting in projection images with an uneven distribution of projection angles (e.g., in 70 arcs each covering 2 ° ). In the gated rotation-continuous acquisition, the LINAC is set to the dynamic arc mode, which suspends the gantry rotation when the gating system inhibits the beam, leading to a slightly longer ( 6 – 7 min ) scan time, but yielding projection images with more evenly distributed projection angles (e.g., ∼ 0.8 ° between two consecutive projection angles). We have tested both data acquisition schemes on stationary (a contrast detail and a thoracic) phantoms and protocol lung patients. For stationary phantoms, a separate motion phantom not visible in the images is used to trigger the RPM system. Frame rate is adjusted so that approximately 450 images (13 MU) are acquired for each scan and three-dimensional tomographic imagesreconstructed using a Feldkamp filtered backprojection algorithm. The gated rotation-continuous acquisition yield reconstructions free of breathing artifacts. The tumor in parenchymal lung and normal tissues are easily discernible and the boundary between the diaphragm and the lung sharply defined. Contrast-to-noise ratio(CNR) is not degraded relative to nongated scans of stationary phantoms. The continuous rotation-gated acquisition scan also yields tomographic images with discernible anatomic features; however, streak artifacts are observed and CNR is reduced by approximately a factor of 4. In conclusion, we have successfully developed a gated MV CBCT system to verify the patient positioning for gated radiotherapy.

Summary We evaluated the ability of a commercial respiratory gating system to assure the reproducibility of internal anatomy in respiration synchronized CT (RS-CT) scans. This passive system uses an infrared sensitive camera to track the motion of reflective markers mounted on the abdomen. Eighteen patients, nine with lung tumors and nine with liver tumors, were selected for evaluation of the Varian Real-Time Position Monitor respiratory gating system. Liver tumors were chosen as surrogate for lower lobe tumors. Each patient underwent at least two identical RS-CT scans, at end-inspiration (EI) or end-expiration (EE), to assess intra-fraction reproducibility. Twelve patients also underwent a free breathing scan and an opposed-respiration phase synchronized scan (EI if the two first were an EE and vice versa). On each CT, a physician contoured the liver, the kidneys, the spleen, and the diaphragms for the liver patients; and similarly, the lungs, the gross tumor volume (GTV), the trachea, the heart and the diaphragms for the lung patients. After registering the different CT images using bony anatomy, the changes of each structure between the respective data sets were quantified in terms of its volume, the displacement of its center of mass (COM), and an “index” coefficient of reproducibility. An analysis of the CT scans obtained at EI and EE phases yielded an average superior–inferior (SI) difference of the diaphragm position of 14.4 mm (range: 45.9–0.9). A similar analysis of CT scans acquired at the same breathing phase yielded 0.7 mm (range: 3.1–0, p = 0.0001). Similar conclusions were derived in analysis of COM positions of the following structures: lungs, heart, lung's GTV, liver, spleen and kidneys. Evaluation of volume changes for lungs, liver, and spleen confirmed reproducibility of RS-CT while the “index” coefficient confirmed reproducibility of RS-CT of all organs. A commercial gating system using external markers for RS-CT significantly improves the positional reproducibility of thoracic and upper abdominal structures. This reproducible decrease in organ motion will allow a reduction of the margin of expansion facilitating increase in target dose beyond that allowed by conventional radiation treatments.

The recently developed GATE (GEANT4 application for tomographic emission) Monte Carlo package, designed to simulate positron emission tomography (PET) and single photon emission computed tomography (SPECT) scanners, provides the ability to model and account for the effects of photon noncollinearity, off-axis detector penetration, detector size and response, positron range, photon scatter, and patient motion on the resolution and quality of PET images. The objective of this study is to validate a model within GATE of the General Electric (GE) Advance/Discovery Light Speed (LS) PET scanner. Our three-dimensional PET simulation model of the scanner consists of 12 096 detectors grouped into blocks, which are grouped into modules as per the vendor's specifications. The GATE results are compared to experimental data obtained in accordance with the National Electrical Manufactures Association/Society of Nuclear Medicine (NEMA/SNM), NEMA NU 2-1994, and NEMA NU 2-2001 protocols. The respective phantoms are also accurately modeled thus allowing us to simulate the sensitivity, scatter fraction, count rate performance, and spatial resolution. In-house software was developed to produce and analyze sinograms from the simulated data. With our model of the GE Advance/Discovery LS PET scanner, the ratio of the sensitivities with sources radially offset 0 and 10 cm from the scanner's main axis are reproduced to within 1% of measurements. Similarly, the simulated scatter fraction for the NEMA NU 2-2001 phantom agrees to within less than 3% of measured values (the measured scatter fractions are 44.8% and 40.9 +/- 1.4% and the simulated scatter fraction is 43.5 +/- 0.3%). The simulated count rate curves were made to match the experimental curves by using deadtimes as fit parameters. This resulted in deadtime values of 625 and 332 ns at the Block and Coincidence levels, respectively. The experimental peak true count rate of 139.0 kcps and the peak activity concentration of 21.5 kBq/cc were matched by the simulated results to within 0.5% and 0.1% respectively. The simulated count rate curves also resulted in a peak NECR of 35.2 kcps at 10.8 kBq/cc compared to 37.6 kcps at 10.0 kBq/cc from averaged experimental values. The spatial resolution of the simulated scanner matched the experimental results to within 0.2 mm.

1H magnetic resonance spectroscopic imaging (MRSI) can improve the accuracy of target delineation for gliomas, but it lacks the anatomic resolution needed for image fusion. This paper presents a simple protocol for fusing simulation computer tomography (CT) and MRSI images for glioma intensity-modulated radiotherapy (IMRT), including a retrospective study of 12 patients. Each patient first underwent whole-brain axial fluid-attenuated-inversion-recovery (FLAIR) MRI (3 mm slice thickness, no spacing), followed by three-dimensional (3D) MRSI measurements (TE/TR: 144/1000 ms) of a user-specified volume encompassing the extent of the tumor. The nominal voxel size of MRSI ranged from 8 x 8 x 10 mm3 to 12 x 12 x 10 mm3. A system was developed to grade the tumor using the choline-to-creatine (Cho/Cr) ratios from each MRSI voxel. The merged MRSI images were then generated by replacing the Cho/Cr value of each MRSI voxel with intensities according to the Cho/Cr grades, and resampling the poorer-resolution Cho/Cr map into the higher-resolution FLAIR image space. The FUNCTOOL processing software was also used to create the screen-dumped MRSI images in which these data were overlaid with each FLAIR MRI image. The screen-dumped MRSI images were manually translated and fused with the FLAIR MRI images. Since the merged MRSI images were intrinsically fused with the FLAIR MRI images, they were also registered with the screen-dumped MRSI images. The position of the MRSI volume on the merged MRSI images was compared with that of the screen-dumped MRSI images and was shifted until agreement was within a predetermined tolerance. Three clinical target volumes (CTVs) were then contoured on the FLAIR MRI images corresponding to the Cho/Cr grades. Finally, the FLAIR MRI images were fused with the simulation CT images using a mutual-information algorithm, yielding an IMRT plan that simultaneously delivers three different dose levels to the three CTVs. The image-fusion protocol was tested on 12 (six high-grade and six low-grade) glioma patients. The average agreement of the MRSI volume position on the screen-dumped MRSI images and the merged MRSI images was 0.29 mm with a standard deviation of 0.07 mm. Of all the voxels with Cho/Cr grade one or above, the distribution of Cho/Cr grade was found to correlate with the glioma grade from pathologic finding and is consistent with literature results indicating Cho/Cr elevation as a marker for malignancy. In conclusion, an image-fusion protocol was developed that successfully incorporates MRSI information into the IMRT treatment plan for glioma.

Because of the proximity of the spinal cord, effective radiotherapy of paraspinal tumors to high doses requires highly conformal dose distributions, accurate patient setup, setup verification, and patient immobilization. An immobilization cradle has been designed to facilitate the rapid setup and radiation treatment of patients with paraspinal disease. For all treatments, patients were set up to within 2.5 mm of the design using an amorphous silicon portal imager. Setup reproducibility of the target using the cradle and associated clinical procedures was assessed by measuring the setup error prior to any correction. From 350 anterior/posterior images, and 303 lateral images, the standard deviations, as determined by the imaging procedure, were 1.3 m, 1.6 m, and 2.1 in the ant/post, right/left, and superior/inferior directions. Immobilization was assessed by measuring patient shifts between localization images taken before and after treatment. From 67 ant/post image pairs and 49 lateral image pairs, the standard deviations were found to be less than 1 mm in all directions. Careful patient positioning and immobilization has enabled us to develop a successful clinical program of high dose, conformal radiotherapy of paraspinal disease using a conventional Linac equipped with dynamic multileaf collimation and an amorphous silicon portal imager.

We have studied the feasibility of a low-dose megavoltage cone beam computed tomography (MV CBCT) system for visualizing the gross tumor volume in respiratory gated radiation treatments of nonsmall-cell lung cancer. The system consists of a commercially available linear accelerator (LINAC), an amorphous silicon electronic portal imaging device, and a respiratory gating system. The gantry movement and beam delivery are controlled using dynamic beam delivery toolbox, a commercial software package for executing scripts to control the LINAC. A specially designed interface box synchronizes the LINAC, image acquisition electronics, and the respiratory gating system. Images are preprocessed to remove artifacts due to detector sag and LINAC output fluctuations. We report on the output, flatness, and symmetry of the images acquired using different imaging parameters. We also examine the quality of three-dimensional (3D) tomographic reconstruction with projection images of anthropomorphic thorax, contrast detail, and motion phantoms. The results show that, with the proper choice of imaging parameters, the flatness and symmetry are reasonably good with as low as three beam pulses per projection image. Resolution of 5% electron density differences is possible in a contrast detail phantom using 100 projections and 30 MU. Synchronization of image acquisition with simulated respiration also eliminated motion artifacts in a moving phantom, demonstrating the system's capability for imaging patients undergoing gated radiation therapy. The acquisition time is limited by the patient's respiration (only one image per breathing cycle) and is under 10 min for a scan of 100 projections. In conclusion, we have developed a MV CBCT system using commercially available components to produce 3D reconstructions, with sufficient contrast resolution for localizing a simulated lung tumor, using a dose comparable to portal imaging.

Accurate knowledge of gantry angle is essential in megavoltage cone beam imaging (MVCBI) with an electronic portal imager. We present a method for determining the gantry angle by detectingmultileaf collimator(MLC) leaf positions in projection images. During image acquisition the gantry moves continuously and the MLC operates in dynamic arc mode. Our algorithm detects the leaf positions in the images and compares them with a stationary reference leaf. Comparison of the algorithm against angles determined from the locations of fiducial markers shows the accuracy ( 0.26 ° rms error) to be sufficient for MVCBI.

BACKGROUND The objective of this study was to report the results of a Phase I dose-escalation study using three-dimensional conformal radiation therapy (3D-CRT) for the treatment of patients with nonsmall cell lung carcinoma (NSCLC). METHODS Between 1991 and 2003, 104 patients were enrolled for 3D-CRT at Memorial Sloan-Kettering Cancer Center. The median patient age was 69 years. Twenty-eight percent of patients had Stage I–II NSCLC, 33% of patients had Stage IIIA NSCLC, 32% of patients had Stage IIIB NSCLC, and 6% of patients had recurrent NSCLC. Induction chemotherapy was received by 16% of patients. Radiation was delivered in daily fractions of 1.8 grays (Gy) for doses ≤ 81.0 Gy and in daily fractions of 2.0 Gy for higher doses. Accrual at a dose level was complete when 10 patients received the intended dose without unacceptable acute morbidity. RESULTS After an incident of fatal acute radiation pneumonitis at the starting dose of 70.2 Gy, the protocol was modified to limit normal tissue complication probabilities (NTCP) to < 25%. The dose was then escalated from 70.2 Gy, to 75.6 Gy, 81.0 Gy, and 84.0 Gy, with at least 10 patients treated at each dose level. Unacceptable pulmonary toxicity occurred at 90.0 Gy. Subsequently, another 10 patients were accrued at the 84.0 Gy level with acceptable toxicity. Thus, 84.0 Gy was the maximum tolerated dose (MTD). The crude late pulmonary toxicity rate was 7%, the 2-year local control rate was 52%, the disease-free survival rate was 33%, and the overall survival rate was 40%. The median survival was 21.1 months. Overall survival was improved significantly in patients who received ≥ 80.0 Gy. CONCLUSIONS The MTD of 3D-CRT for NSCLC with an NTCP constraint of 25% was 84.0 Gy in the current study. There was a suggestion of improved survival in patients who received 80.0 Gy. Cancer 2005. © 2005 American Cancer Society.

Tumor motion due to respiration during radiation therapy for non-small cell lung cancer is a significant problem. This article reports on two techniques used to control tumor motion: respiratory gating and the deep inspiration breath hold technique. This technique was implemented in 40 patients without significant difficulties and there are encouraging clinical outcomes.

The relative inability of conventional radiotherapy to control localized prostate cancer results from resistance of subpopulations of tumor clonogens to dose levels of 65 to 70 Gy, the maximum feasible with traditional two-dimensional (2D) treatment planning and delivery techniques. Several technological advances have enhanced the precision and improved the outcome of external-beam radiotherapy. The three-dimensional conformal radiotherapy (3D-CRT) approach has permitted significant increases in the tumor dose to levels beyond those feasible with conventional techniques. Intensity-modulated radiotherapy (IMRT), an advanced form of conformal radiotherapy, has resulted in reduced rectal toxicity, permitting tumor dose escalation to previously unattainable levels with a concomitant improvement in local tumor control and disease-free survival. The combination of androgen deprivation and conventional-dose radiotherapy, tested mainly in patients with locally advanced disease, has also produced significant outcome improvements. Whether androgen deprivation will preclude the need for dose escalation or whether high-dose radiotherapy will obviate the need for androgen deprivation remains unknown. In some patients, both approaches may be necessary to maximize the probability of cure. In view of the favorable benefit-risk ratio of high-dose IMRT, the design of clinical trials to resolve these critical questions is essential.

Conventional radiation therapy has had limited success in curing inoperable lung cancer due to poor local control. There is evidence to suggest that higher doses of radiation will improve local control. In order to safely deliver higher doses of thoracic radiation, advanced treatment techniques are required. Different biologic indices have been utilized to determine whether dose escalation can be safely accomplished, and the results have been reported from many institutions. Tumor motion control aids in treatment since it allows radiation oncologists to more accurately target tumors and therefore to spare more normal tissue from the radiation field. The imaging information from 18-FDG-PET scans also improves target delineation. Advanced treatment delivery techniques, such as three-dimensional conformal radiation therapy, intensity modulated radiation therapy, and stereotactic radiosurgery are also being used to safely escalate the radiation dose. This article explores the current literature on these issues and other advanced radiation therapy techniques.

Purpose: To design and implement a noninvasive stereotactic immobilization technique with daily CT image-guided positioning to treat patients with paraspinal lesions accurately and to quantify the systematic and random patient setup errors occurring with this method. Methods and Materials: A stereotactic body frame (SBF) was developed for “rigid” immobilization of paraspinal patients. The inherent accuracy of this system for stereotactic CT-guided treatment was evaluated with phantom studies. Seven patients with thoracic and lumbar spine lesions were immobilized with the SBF and positioned for 33 treatment fractions using daily CT scans. For all 7 patients, the daily setup errors, as assessed from the daily CT scans, were corrected at each treatment fraction. A retrospective analysis was also performed to assess what the impact on patient treatment would have been without the CT-based corrections (i.e., if patient setup had been performed only with the SBF). Results: The average magnitude of systematic and random errors from uncorrected patient setups using the SBF was approximately 2 mm and 1.5 mm (1 SD), respectively. For fixed phantom targets, the system accuracy for the SBF localization and treatment was shown to be within 1 mm (1 SD) in any direction. Dose-volume histograms incorporating these uncertainties for an intensity-modulated radiotherapy plan for lumbar spine lesions were generated, and the effects on the dose-volume histograms were studied. Conclusion: We demonstrated a very accurate and precise method of patient immobilization and treatment delivery based on a noninvasive SBF and daily image guidance for paraspinal lesions. The SBF provides excellent immobilization for paraspinal targets, with setup accuracy better than 2 mm (1 SD). However, for highly conformal paraspinal treatments, uncorrected systematic and random errors of 2 mm in magnitude can result in a significantly greater (>100%) dose to the spinal cord than planned, even though the planned target coverage may not change substantially. With daily CT guidance using the SBF, we showed that the maximal spinal cord dose is ensured to be within 10–15% of the planned value.

Purpose: Megavoltage cone-beam computed tomography (MVCBCT) has been proposed for treatment verification in conformal radiotherapy. However, the doses required for such imaging may compromise the quality of the delivered dose distribution. The present paper explores the effect of cone-beam imaging on dose homogeneity and critical organ dose and the use of our new tool, adapted intensity-modulated radiation therapy (AIMRT). Methods and Materials: Three types of treatment plans were devised (3D-CRT [three-dimensional conformal radiotherapy], IMRT [intensity-modulated radiotherapy], and AIMRT) based on 4 patients with thoracic malignancies. MVCBCT fields were then integrated into the plans. The MVCBCT technique used 21 imaging portals at 10° intervals. The MVCBCT apertures were shaped to conform to the planning target volume with a 6-mm margin. In a second set of plans, the field size was expanded by a further 2 cm. The unoptimized MVCBCT dose distribution was incorporated into the IMRT plan using AIMRT. Results: Normal-tissue complication probability with MVCBCT is acceptable for all plans at the 66.6 Gy level, but exceeds tolerance for both 3D-CRT alone and 3D-CRT with MVCBCT at higher doses. In contrast, the use of AIMRT planning with MVCBCT allowed safe dose escalation to 85 Gy. Expanding the MVCBCT aperture provided better anatomic visibility with an acceptable lung dose. The results using IMRT with MVCBCT fell between the values measured for 3D-CRT and AIMRT with MVCBCT. Conclusion: The present study is the first to demonstrate that MVCBCT can be incorporated into 3D-CRT and IMRT planning with minimal effect on planning target volume homogeneity and dose to critical structures. This paves the way for highly conformal radiotherapy at greater doses delivered with increased confidence and safety.

Purpose : To evaluate and develop optimum inverse treatment planning strategies for the treatment of concave targets adjacent to normal tissue structures. Methods and Materials : Optimized dose distributions were designed using an idealized geometry consisting of a cylindrical phantom with a concave kidney-shaped target (PTV) and cylindrical normal tissues (NT) placed 5–13 mm from the target. Targets with radii of curvature from 1 to 2.75 cm were paired with normal tissues with radii between 0.5 and 2.25 cm. The target was constrained to a prescription dose of 100% and minimum and maximum doses of 95% and 105% with relative penalties of 25. Maximum dose constraint parameters for the NT varied from 10% to 70% with penalties from 10 to 1000. Plans were evaluated using the PTV uniformity index (PTV Dmax/PTV D95) and maximum normal tissue doses (NT Dmax/PTV D95). Results : In nearly all situations, the achievable PTV uniformity index and the maximum NT dose exceeded the corresponding constraints. This was particularly true for small PTV-NT separations (5–8 mm) or strict NT dose constraints (10%–30%), where the achievable doses differed from the requested by 30% or more. The same constraint parameters applied to different PTV-NT separations yielded different dose distributions. For most geometries, a range of constraints could be identified that would lead to acceptable plans. The optimization results were fairly independent of beam energy and radius of curvature, but improved as the number of beams increased, particularly for small PTV-NT separations or strict dose constraints. Conclusion : Optimized dose distributions are strongly affected by both the constraint parameters and target-normal tissue geometry. Standard site-specific constraint templates can serve as a starting point for optimization, but the final constraints must be determined iteratively for individual patients. A strategy whereby NT constraints and penalties are modified until the highest acceptable PTV uniformity index is achieved is discussed. This strategy can be used, in simple patient geometries, to ensure the lowest possible normal tissue dose. Strategies for setting the optimum dose constraints and penalties may vary for different optimization algorithms and objective functions. Increasing the number of beams can significantly improve normal tissue dose and target uniformity in situations where the PTV-NT separation is small or the normal tissue dose limits are severe. Setting unrealistically severe constraints in such situations often results in dose distributions that are inferior to plans achieved with more lenient constraints.

Purpose: To compare intensity-modulated radiotherapy (IMRT) and conventional three-dimensional conformal radiotherapy (3D-CRT) for the boost treatment of new-onset nasopharyngeal carcinoma (NPC) or the salvage treatment of locally recurrent NPC. Methods and Materials: Between January 14 and February 23, 2000, 5-field 3D-CRT treatment plans were generated for 14 consecutive NPC patients using the ADAC Pinnacle planning system in Chang Gung Memorial Hospital, Kaohsiung, Taiwan. The planning data of these patients were later transferred to Memorial Sloan-Kettering Cancer Center, where new IMRT plans, also using 5–7 radiation fields were created for each patient using an inverse treatment planning system. The IMRT and 3D-CRT plans were compared for all 14 patients. The relationship between the anatomic shapes and locations of targets and the results of different plans were studied. Results: Target doses were more homogeneous in IMRT plans. The average maximal brainstem dose (D 05 , the dose received by 5% of the brainstem volume) decreased from 30.9% of the prescription dose with 3D-CRT to 15.3% and 14.7% with 5- and 7-field IMRT, respectively ( p = 0.004 and 0.003, respectively, compared with 3D-CRT, paired Student's t test). Five anatomic factors were found that predicted greater benefits with IMRT. These factors were ( 1 ) vertical length of target >7 cm, ( 2 ) minimal distance between target and brainstem 3 ) maximal AP overlap of target and brainstem >0.6 cm, ( 4 ) maximal AP overlap of target and spinal cord >1 cm, and ( 5 ) vertical overlap of target and eyes >0 cm. For the 7 patients with at least 1 of these 5 anatomic factors, the benefits achieved by IMRT planning would have been greater than the benefits for the other 7 patients ( p = 0.005, Fisher's exact test). Conclusion: For boost or salvage treatment of NPC, lower normal tissue doses and more homogeneous target doses were achieved with IMRT plans. For NPC patients with at least 1 of the 5 anatomic factors, IMRT is highly recommended.

We describe a fast, PC‐based optimization planning system for a planar permanent‐seed implant. Sites where this system is applicable include brain, lung, and head and neck. The system described here allowsplacing ribbons of different strengths and of different lengths along and across the implant plane. The program takes full advantage of the availability of different source strengths in inventory, and attempts to find configurations of ribbons that result in optimal dose uniformity over the prescription plane. Dosimetry is based on the AAPM TG 43 Report [R. Nath et al., Med. Phys. 22, 209–234 (1995)]. Compared with TG 43 parameters, the classical tables underestimate the I‐125 source strengths needed by 40%. The use of several source strengths improves the plan. Typical optimization yields dose uniformity of 10%, and computing times are within 2–3 min No further enhancement is obtained if ribbons are placed in a grid pattern as opposed to the (simpler) arrangement along parallel lines. Nor is it valuable to have variable ribbon lengths. For an I‐125 implant the optimization system described here is a practical alternative to the (strictly speaking inapplicable) classical systems. It calculates correctly the total source strengths, and ‐ most notably ‐ generates plans with optimal dose uniformity. The fast computing time is well suited for planning during surgery in the operating room. PACS number(s): 87.53Jw, 87.53.Tf

The BANG (MGS Research Inc., Guilford, CT) polymer gel has been used as a dosimeter to determine the three‐dimensional (3D) dose distribution of a ruthenium‐106 (Ru‐106) ophthalmologic applicator. An eye phantom made of the BANG gel was irradiated with the Ru‐106 source for up to 1 h. The phantom and a set of calibration vials were scanned simultaneously in a GE 1.5 T MR imager using the Hahn spin‐echo pulse sequence with a TR of 2000 ms and two TEs of 20 ms and 100 ms. The T2 values were evaluated on a pixel‐by‐pixel basis using custom‐built software on a DEC alpha workstation and converted to dose using calibration data. Depth doses and isodose lines of the Ru‐106 eye‐plaque were generated. It is concluded that the BANG gel dosimetry offers the potential for measuring the 3D dose distributions of an ophthalmologic applicator, with high spatial resolution and relatively good accuracy. PACS number(s): 87.66.–a, 87.90.+y

Extraskeletal chondrosarcoma of the leg is a rare, malignant neoplasm with very few cases having been reported in the literature. In this study we investigate the possibility of using intensity modulated radiotherapy (IMRT) for this type of disease and demonstrate its advantages over conventional three-dimensional (3D) conformal treatment. A case was presented of a patient with extraskeletal chondrosarcoma of the lateral compartment of the leg in which the target volume was 50 cm in length and twisted around the surrounding bones. Both the 3D conformal plan and IMRT plan were designed using the Memorial Sloan-Kettering Cancer Center planning system. The IMRT plan produced a superior dose distribution to the patient as compared to the 3D conformal plan both in terms of dose conformity and homogeneity in the target volumes, and reduction of the maximum dose to the bone. The planning time of the IMRT plan was about 35 times shorter than that of the 3D conformal plan. It was demonstrated that the IMRT technique can be used not just for small tumors, but also for large and spiral-shaped tumors close to critical organs. The IMRT method requires less planning time, and provides better target coverage with more sparing of critical structures. When planning patients with multiple target volumes receiving different prescribed doses, the IMRT technique can more easily meet this requirement. 2001 American College of Medical Physics.

Purpose: We describe computer software that performs, quickly and accurately, secondary dose calculations for high-dose-rate (HDR) treatment plans, including those employed for prostate treatments. Methods: The program takes as primary input the data file used by the HDR remote afterloader console for treatment. Dosimetric calculations are performed using the Meisberger polynomial and the anisotropy table for the HDR Iridium-192 source. For standard applicators, treatment geometry is automatically reconstructed and the dose is calculated at relevant reference point(s). Template-based treatment plans (e.g., prostate) require additional user input; the dose calculation is then performed at user-selected reference points. A total dwell time calculation for volume and planar implants using the Manchester tables was also implemented. Results: For fixed-geometry HDR procedures, secondary dose calculations are within 2% of the treatment plan, and results are available for review instantly. For more general applications, the calculated and planned doses are typically within 3% at the prescription isodose line. The Manchester-based dwell time calculation is within 10% of the planned time.

Purpose: Recent studies have demonstrated that magnetic-resonance spectroscopic imaging (MRSI) of the prostate may effectively distinguish between regions of cancer and normal prostatic epithelium. This diagnostic imaging tool takes advantage of the increased choline plus creatine versus citrate ratio found in malignant compared to normal prostate tissue. The purpose of this study is to describe a novel brachytherapy treatment-planning optimization module using an integer programming technique that will utilize biologic-based optimization. A method is described that registers MRSI to intraoperative-obtained ultrasound images and incorporates this information into a treatment-planning system to achieve dose escalation to intraprostatic tumor deposits. Methods: MRSI was obtained for a patient with Gleason 7 clinically localized prostate cancer. The ratios of choline plus creatine to citrate for the prostate were analyzed, and regions of high risk for malignant cells were identified. The ratios representing peaks on the MR spectrum were calculated on a spatial grid covering the prostate tissue. A procedure for mapping points of interest from the MRSI to the ultrasound images is described. An integer-programming technique is described as an optimization module to determine optimal seed distribution for permanent interstitial implantation. MRSI data are incorporated into the treatment-planning system to test the feasibility of dose escalation to positive voxels with relative sparing of surrounding normal tissues. The resultant tumor control probability (TCP) is estimated and compared to TCP for standard brachytherapy-planned implantation. Results: The proposed brachytherapy treatment-planning system is able to achieve a minimum dose of 120% of the 144 Gy prescription to the MRS positive voxels using 125 I seeds. The preset dose bounds of 100–150% to the prostate and 100–120% to the urethra were maintained. When compared to a standard plan without MRS-guided optimization, the estimated TCP for the MRS-optimized plan is superior. The enhanced TCP was more pronounced for smaller volumes of intraprostatic tumor deposits compared to estimated TCP values for larger lesions. Conclusions: Using this brachytherapy-optimization system, we could demonstrate the feasibility of MRS-optimized dose distributions for 125 I permanent prostate implants. Based on probability estimates of anticipated improved TCP, this approach may have an impact on the ability to safely escalate dose and potentially improve outcome for patients with organ-confined but aggressive prostatic cancers. The magnitude of the TCP enhancement, and therefore the risks of ignoring the MR data, appear to be more substantial when the tumor is well localized; however, the gain achievable in TCP may depend quite considerably on the MRS tumor-detection efficiency.

Purpose. Intracoronary gamma or beta radiation from centrally located sources at the time of overstretch balloon injury inhibits neointimal proliferation. In an effort to deliver homogeneous, centered radiation fields in a technically straightforward fashion, we studied the effects of a beta-emitting solution used as a balloon inflation fluid to deliver radiation at the time of coronary injury. Methods. Twenty-one coronary arteries in 13 juvenile swine underwent irradiation (control and 11 or 25 Gy media dose). Radiation was delivered using a perfusion balloon inflated with an Re-188 solution. Subsequently, overdilatation percutaneous transluminal coronary angioplasty was performed at the pretreated segment. Histopathologic and histomorphometric analysis was performed at 30 days after injury on the entire irradiated artery. Results. Balloon overdilation was associated with significant vascular injury and marked neointimal proliferation in control and low-dose (11 Gy)-treated arteries. High-dose radiation (25 Gy) significantly inhibited neointima formation compared with controls (neointimal area: 0.49 ± 0.29 mm 2 vs. 1.51 ± 0.22 mm 2 , respectively; p = 0.02) and low-dose radiation (neointimal area 1.75 ± 0.54 mm 2 , p > 0.1 compared with controls). Conclusions. Liquid Re-188 is an effective beta-emitting vehicle to deliver intracoronary radiation and prevent restenosis in this model. Intracoronary radiation treatment using aqueous radioisotope sources is technically straightforward and provides the optimally achievable radiation dose distribution.

Recent preclinical and clinical studies indicate that irradiation using ionizing radiation in the dose range of 15 to 30 Gy may reduce the occurrence of restenosis in patients who have undergone an angioplasty. Several delivery systems of intravascular brachytherapy have been developed to deliver radiation doses in this range with minimal normal tissue toxicity. In late 1995 the American Association of Physicists in Medicine (AAPM) formed a task group to investigate these issues and to report the current state of the art of intravascular brachytherapy physics. The report of this task group is presented here.

Intraluminal irradiation of coronary and peripheral arteries has been shown to reduce neointimal hyperplasia following balloon angioplasty, thereby inhibiting restenosis. Several irradiation techniques are being investigated, including temporary intravascular insertion of high activity gamma- or beta-emitting seeds and wires; inflation of dilatation balloon catheter with radioactive liquid or gas; insertion of miniature x-ray tubes via coronary catheters; permanent implantation of radioactive stents; and postangioplasty fractionated external beam irradiation. Unlike conventional brachytherapy, intravascular treatment of restenosis requires accurate knowledge of dose at distances of 0.5–5 mm from the radioactive source. This requirement presents special problems with regard to source calibration and dose specification, because dose gradients at such close distances from a radioactive source are extremely large. This makes it virtually impossible to define the characteristics of an ideal radiation source without some knowledge of the location and radiosensitivity of the target tissues, plus the radiotolerance of normal tissues. Hence, the current debate over whether beta or gamma sources are to be preferred. Imprecise knowledge of dose–volume effects for coronary arteries, plus uncertainties in the biological time sequencing of restenosis fuel a second debate on whether external beam treatments may be efficacious, and whether or not permanent radioactive stents may prove superior to high dose, single fraction brachytherapy. We review here the dosimetric properties of the various irradiation techniques and isotopes that have been proposed, including aspects of radiation safety, dose homogeneity, and practical aspects of source delivery.

Purpose. Irradiation of the arterial wall with beta particles has been shown to be effective in inhibiting neointimal hyperplasia following percutaneous transluminal coronary angioplasty (PTCA). In this study, we describe the use of 188 W/ 188 Re generators to obtain 188 Re (half-life 16.9 h, maximal beta energy of 2.12 MeV) as a new candidate radioisotope for endovascular irradiation. We have evaluated two [ 188 Re]-compounds as candidates for use as solution-based radiation sources that would allow conventional liquid-filled balloon inflation for delivery of radiation to the vessel wall. While balloon rupture at nominal inflation pressures is a very rare event, ( 188 Re-labeled compounds that are proposed for intravascular therapy. Materials and Methods. Rhenium-188 was obtained as [ 188 Re]-sodium perrhenate by saline elution of an alumina-based 188 W/ 188 Re generator system (>500 mCi). High specific volume solutions of the [ 188 Re]-sodium perrhenate (>50 mCi/ml) were obtained by postelution concentration of the generator bolus by passage through a tandem silver cation/anion column system. Rhenium-188-labeled benzoylthioacetyltriglycine (MAG3) was prepared by stannous ion reduction of [ 188 Re]-perrhenate in the presence of the benzyl-MAG3 substrate, and was characterized as a single radioactive component. Rhenium-188-perrhenate and [ 188 Re]-MAG3 were administered to separate groups of Fischer rats, which were sacrificed at various times and the tissue distribution of 188 Re determined in the major organs. Excretory products were also collected daily from separate groups of rats for each agent over 7 days. The effects of perchlorate and iodide preblocking and postdisplacement of thyroid uptake of [ 188 Re]-perrhenate were also evaluated. Results. Organ uptake values were modest for both agents [ 188 Re after injection of [ 188 Re]-MAG3 was low (0.16 %ID/gram), uptake after injection of [ 188 Re]-perrhenate was higher and could be blocked by pretreatment with perchlorate (intravenous [IV]) or displaced by perchlorate posttreatment. Also, oral or IV iodide pre- or postadministration could also significantly block or displace thyroid uptake of [ 188 Re]-perrhenate. Both [ 188 Re] agents were excreted primarily via the urinary bladder. The excretion half-life of [ 188 Re]-perrhenate was about 7 h; in contrast, the [ 188 Re]-MAG3 complex showed 50% excretion in less than 2 h. The large intestines received the most significant adsorbed dose, with values of 2.0 cGy/mCi for [ 188 Re]-perrhenate and 4.6 × 10 −3 cGy/mCi for [ 188 Re]-MAG3. Conclusions. Rhenium-188-MAG3 shows more rapid urinary bladder excretion in rats than perrhenate and both agents show low organ uptake. Thyroid uptake of free [ 188 Re]-perrhenate can be blocked or displaced with oral perchlorate administration. For the projected use of [ 188 Re]-MAG3 for balloon inflation required for irradiation of the arterial wall, calculated organ dose values are within acceptable limits in the unlikely event of low pressure balloon rupture. Rhenium-188-MAG3 in solution is thus a new candidate for balloon dilation providing uniform endovascular irradiation following PTCA for restenosis therapy. Published by Elsevier Science Inc.

Background —Intravascular irradiation with β-emitters has been proposed for inhibition of restenosis in coronary arteries after balloon angioplasty or stent implantation. Previous studies have shown the effectiveness of γ-radiation to prevent recurrent restenosis, even in the presence of an implanted stent. The limited range of β-particles compared with γ-radiation, however, opens the question of whether absorption and scattering of β-particles by stent struts will cause significant perturbations in the uniformity and magnitude of the radiation dose, which may in turn compromise treatment. Methods and Results —Nine different stents were deployed with a balloon filled with a β-emitting radioactive liquid. Dose distributions were measured with Gafchromic film. Stents varied significantly in their absorption of β-particles. Some stents, constructed of fine meshed wires, produced minimal dose perturbations. Others, with thicker, high-atomic-number struts, induced cold spots in the dose distribution adjacent to the wires of ≤35%. Average dose reduction varied from 4% to 14% in the presence of various stents. Conclusions —Radiation strategy may have to be tailored to stent design. Stents that minimally perturb the dose distribution may be deployed before irradiation. Those that significantly alter the radiation dose might be better deployed after irradiation. Dose prescriptions may require modification if such perturbations prove clinically significant. Observed dose perturbations, however, decreased rapidly with increasing distance from the stent, which may mitigate the clinical impact of these findings. This, as well as the effects of stents on γ-dose distributions, requires further investigation.

Purpose Treatment plan optimization in radiation oncology entails designing multiple x-ray beams to irradiate a tumor to a dose that will achieve locoregional control while minimizing normal tissue complications. For some anatomical sites, it is possible to estimate tumor control probabilities (TCP) and normal tissue complication probabilities (NTCP) as a function of radiation dose. Thus, treatment plan optimization can be based on biologic end points rather than on dose calculations alone. Given multiple plans with different NTCPs and TCPs, a tradeoff must be made between maximizing TCP and maintaining an acceptable NTCP. How do physicians reach these decisions? Can the process be quantified? Should patients participate in the process? Methods and materials Physicians and patients were asked to rank a series of treatment plans having different combinations of TCP and NTCP. Responses were parametrized into a figure of merit (FM) equation which quantifies predilections of TCP and NTCP. Results Physician-based FM equations are site- and patient-specific. Variations exist among physicians, but treatment plan selection is often conservative in accordance with the primum non nocere dictum. FM equations generated from the responses of patients suggest that some patients may be willing to accept higher treatment toxicity in exchange for increased TCP. Conclusion The term "optimized treatment plan" contains inherently subjective criteria which reflect one's willingness to accept treatment morbidity in exchange for probability of cure. These criteria may differ among patients and/or physicians. A quantifiable FM may permit the design of custom-made treatment plans that include physician and patient input.

Purpose : Recent data indicate that intraluminal irradiation of coronary arteries following balloon angioplastry reduces proliferation of smooth muscle cells, neointima formation, and restenosis. We present calculations for various isotopes and geometries in an attempt to identify suitable source designs for such treatments. Methods and Materials : Analytical calculations of dose distribution and dose rates are presented for 192Ir, 125I, 103Pd, 32P, and 90Sr for use in intracoronary irradiation. The effects of source geometry and positioning accuracy are studied. Result : Accurate source centering, high dose rate, well-defined treatment volume, and radiation safety are all of concern; 15–20 Gy are required to a length of 2–3 cm of vessel wall (2–4 mm diameter). Dose must be confined to the region of the angioplasty, with reduced doses to normal tissues. Beta emitters have radiation safety advantages, but may not have suitable ranges for treating large diameter vessels. Gamma emitters deliver larger doses to normal tissues and to staff. Low energy x-ray emitters such as 125I and 103Pd reduce these risks but are not available at high enough activities. The feasibility of injecting a radioactive liquid directly into the angioplasty balloon is also explored. Conclusion : Accurate source centering is found to be of great importance. If this can be accomplished, then high energy beta emitters such as 90Sr would be ideal sources. Otherwise, gamma emitters such as 192Ir may be optimal, A liquid beta source would have optimal geometry and dose distribution, but available sources, such as 32P are unsafe for use with available balloon catheters.

Purpose:Restenosis after percutaneous transluminal coronary angioplasty represents, in part, a proliferative response of vascular smooth muscle at teh site of injury. We have previously shown that high-dose radiation (20 Gy), delivered via an intracoronary 192Ir source, causes focal medial fibrosis and markedly impairs the restenosis process after balloon angioplasty in swine. This study sought to delineate the dose-response characteristics of this effect. Methods and Materials: Forty juvenile swine underwent coronary angiography; a segment of the left coronary artery was chosen as a target for balloon injury. In 30 swine, a 2 cm ribbon of 192Ir was positioned at the target segment and 20, 15, or 10 Gy were delivered to the vessel wall (10 animals/dose). Subsequently, overdilatation balloon angioplasty was performed at the irradiated segment. In 10 control swine, overdilatation balloon angioplasty was performed without previous irradation. Thirty-eight animals survived until sacrifice at 30 ± 3 days. Histopathological analysis was performed by a pathologist in a blinded manner. The area of maximal luminal compromise within the target segment was analyzed via computer-assisted planimetry. Results: Neointimal area was decreased by 71.4% at 20 Gy and by 58.3% at 15 Gy compared with control animals (p < 0.05). A stimulatory effect on smooth muscle cell proliferation was noted at 10 Gy, with a 123% increase in neointimal area compared with controls (p < 0.05). Mean percent area stenosis was also reduced by 63% at 20 Gy and by 74.8% at 15 Gy compared with controls (p < 0.05 for both). Conclusions: Intracoronary irradiation prior to overstretch balloon angioplasty markedly reduces neointima formation: this effect is dose dependent, with evidence of a significant stimulatory effect at 10 Gy. The effective therapeutic dose range for the prevention of restenosis in this in this model begins at approximatley 15 Gy delivered to the vessel wall.

Recent reports suggest that intraluminal irradiation of coronary arteries in conjunction with balloon angioplasty reduces proliferation of smooth muscle cells and neointima formation, thereby inhibiting restenosis. One possible irradiation technique is to inflate the balloon dilitation catheter with a radioactive solution. This has advantages over other proposed irradiation procedures, in that accurate source positioning and uniform dose to the vessel wall are assured. Several high-energy beta-minus emitters may be suitable for this application. We present experimental measurements and analytical calculations of the dose distribution around a 3-mm-diam by 20-mm-long balloon filled with 90Y-chloride solution. The dose rate at the surface of the balloon is approximately 0.14 cGy/s per mCi/ml (3.78 x 10(-11) Gy/s per Bq/ml), with the dose decreasing to 53% at 0.5 mm, and5% at 3.5-mm radial distance. 90Y and other possible isotopes are currently available at specific concentrationsor = 50 mCi/ml (1.85 x 10(9) Bq/ml), which enables the delivery of 20 Gy in less than 5 min. The dosimetric and radiation safety advantages of this system warrant further feasibility studies. Issues of concern include incorporating the beta-emitter into a suitable chemical form, and assessing organ and whole body doses in the (1 in 10(3)) event of balloon failure.

Background. Ionizing radiation is a lung carcinogen in a variety of settings, including after breast cancer radiation therapy. The authors explored whether cigarette smoking and breast cancer radiation therapy have a multiplicative effect on the risk of subsequent lung cancer. Methods. This case-control study investigated women registered with primary breast cancer in the Connecticut Tumor Registry who developed a second malignancy between 1986 and 1989. Those diagnosed with a subsequent primary lung cancer were compared with those diagnosed with a subsequent nonsmoking, nonradiation-related second malignancy, and age-adjusted odds ratios were calculated with logistic regression. Results. No radiation effects were observed within 10 years of initial primary breast cancer. Among both smokers and nonsmokers diagnosed with second primary cancers more than 10 years after an initial primary breast cancer, radiation therapy was associated with a 3-fold increased risk of lung cancer. A multiplicative effect was observed, with women exposed to both cigarette smoking and breast cancer radiation therapy having a relative risk of 32.7 (95% confidence interval [CI], 6.9–154). The radiation carcinogenic effect was observed only for the ipsilateral lung and not for the contralateral lung both in smokers and nonsmokers. Conclusions. Breast cancer radiation therapy, as delivered before 1980, increased the risk of lung cancer after ten years in nonsmokers, and a multiplicative effect was observed in smokers. For both smokers and non-smokers, this effect was observed only for the ipsilateral lung and not the contralateral lung. Modern techniques, however, significantly decrease the radiation dose to the lungs, which may decrease the risk of lung cancer. Nonetheless, due to the available choices in early-stage breast cancer treatment, current practices may need to be revised for young breast cancer patients who smoke. Cancer 1994: 73:1615–20.

To establish a new clinical procedure in frameless stereotactic radiosurgery (SRS) for patient setup verification at treatment couch angles as well as for head-motion monitoring during treatment using video-based optical surface imaging (OSI).A video-based three-dimensional (3D) OSI system with three ceiling-mounted camera pods was employed to verify setup at treatment couch angles as well as to monitor head motion during treatment. A noninvasive head immobilization device was utilized, which includes an alpha head mold and a dental mouthpiece with vacuum suction; both were locked to the treatment couch. Cone beam computed tomography (CBCT) was used as the standard for image-guided setup. Orthogonal 2D-kV imaging was applied for setup verification before treatment, between couch rotations, and after treatment at zero couch angle. At various treatment couch angles, OSI setup verification was performed, relative to initial OSI setup verification at zero couch angle after CBCT setup through a coordinate transformation. For motion monitoring, the setup uncertainty was decoupled by taking an on-site surface image as new reference to detect motion-induced misalignment in near real-time (1-2 frames per second). Initial thermal instability baseline of the real-time monitoring was corrected. An anthropomorphous head phantom and a 1D positioning platform were used to assess the OSI accuracy in motion detection in longitudinal and lateral directions. Two hypofractionated (9 Gy x 3 and 6 Gy x 5) frameless stereotactic radiotherapy (SRT) patients as well as two single-fraction (21 and 18 Gy) frameless SRS patients were treated using this frameless procedure. For comparison, 11 conventional frame-based SRS patients were monitored using the OSI to serve as clinical standards. Multiple noncoplanar conformal beams were used for planning both frameless and frame-based SRS with a micromultileaf collimator.The accuracy of the OSI in 1D motion detection was found to be 0.1 mm with uncertainty of +/- 0.1 mm using the head phantom. The OSI registration against simulation computed tomography (CT) external contour was found to be dependent on the CT skin definition with -0.4 mm variation. For frame-based SRS patients, head-motion magnitude was detected to be1.0 mm (0.3 +/- 0.2 mm) and1.0 degree (0.2 degrees +/- 0.2 degrees) for 98% of treatment time, with exception of one patient with head rotation1.5 degrees for 98% of the time. For frameless SRT/SRS patients, similar motion magnitudes were observed with an average of 0.3 +/- 0.2 mm and 0.2 degrees +/- 0.1 degree in ten treatments. For 98% of the time, the motion magnitude was1.1 mm and 1.0 degree. Complex head-motion patterns within 1.0 mm were observed for frameless SRT/SRS patients. The OSI setup verification at treatment couch angles was found to be within 1.0 mm.The OSI system is capable of detecting 0.1 +/- 0.1 mm 1D spatial displacement of a phantom in near real time and useful in head-motion monitoring. This new frameless SRS procedure using the mask-less head-fixation system provides immobilization similar to that of conventional frame-based SRS. Head-motion monitoring using near-real-time surface imaging provides adequate accuracy and is necessary for frameless SRS in case of unexpected head motion that exceeds a set tolerance.