Search

IMPORTANCE: Spine metastasis can be treated with high-dose radiation therapy with advanced delivery technology for long-term tumor and pain control. OBJECTIVE: To assess whether patient-reported pain relief was improved with stereotactic radiosurgery (SRS) as compared with conventional external beam radiotherapy (cEBRT) for patients with 1 to 3 sites of vertebral metastases. DESIGN, SETTING, AND PARTICIPANTS: In this randomized clinical trial, patients with 1 to 3 vertebral metastases were randomized 2:1 to the SRS or cEBRT groups. This NRG 0631 phase 3 study was performed as multi-institutional enrollment within NRG Oncology. Eligibility criteria included the following: (1) solitary vertebral metastasis, (2) 2 contiguous vertebral levels involved, or (3) maximum of 3 separate sites. Each site may involve up to 2 contiguous vertebral bodies. A total of 353 patients enrolled in the trial, and 339 patients were analyzed. This analysis includes data extracted on March 9, 2020. INTERVENTIONS: Patients randomized to the SRS group were treated with a single dose of 16 or 18 Gy (to convert to rad, multiply by 100) given to the involved vertebral level(s) only, not including any additional spine levels. Patients assigned to cEBRT were treated with 8 Gy given to the involved vertebra plus 1 additional vertebra above and below. MAIN OUTCOMES AND MEASURES: The primary end point was patient-reported pain response defined as at least a 3-point improvement on the Numerical Rating Pain Scale (NRPS) without worsening in pain at the secondary site(s) or the use of pain medication. Secondary end points included treatment-related toxic effects, quality of life, and long-term effects on vertebral bone and spinal cord. RESULTS: A total of 339 patients (mean [SD] age of SRS group vs cEBRT group, respectively, 61.9 [13.1] years vs 63.7 [11.9] years; 114 [54.5%] male in SRS group vs 70 [53.8%] male in cEBRT group) were analyzed. The baseline mean (SD) pain score at the index vertebra was 6.06 (2.61) in the SRS group and 5.88 (2.41) in the cEBRT group. The primary end point of pain response at 3 months favored cEBRT (41.3% for SRS vs 60.5% for cEBRT; difference, −19 percentage points; 95% CI, −32.9 to −5.5; 1-sided P = .99; 2-sided P = .01). Zubrod score (a measure of performance status ranging from 0 to 4, with 0 being fully functional and asymptomatic, and 4 being bedridden) was the significant factor influencing pain response. There were no differences in the proportion of acute or late adverse effects. Vertebral compression fracture at 24 months was 19.5% with SRS and 21.6% with cEBRT (P = .59). There were no spinal cord complications reported at 24 months. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, superiority of SRS for the primary end point of patient-reported pain response at 3 months was not found, and there were no spinal cord complications at 2 years after SRS. This finding may inform further investigation of using spine radiosurgery in the setting of oligometastases, where durability of cancer control is essential. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00922974

4D-CBCT is a powerful tool to provide respiration-resolved images for the moving target localization. However, projections in each respiratory phase are intrinsically under-sampled under the clinical scanning time and imaging dose constraints. Images reconstructed by compressed sensing (CS)-based methods suffer from blurred edges. Introducing the average-4D-image constraint to the CS-based reconstruction, such as prior-image-constrained CS (PICCS), can improve the edge sharpness of the stable structures. However, PICCS can lead to motion artifacts in the moving regions. In this study, we proposed a dual-encoder convolutional neural network (DeCNN) to realize the average-image-constrained 4D-CBCT reconstruction. The proposed DeCNN has two parallel encoders to extract features from both the under-sampled target phase images and the average images. The features are then concatenated and fed into the decoder for the high-quality target phase image reconstruction. The reconstructed 4D-CBCT using of the proposed DeCNN from the real lung cancer patient data showed: 1) qualitatively, clear and accurate edges for both stable and moving structures; 2) quantitatively, low-intensity errors, high peak signal-to-noise ratio, and high structural similarity compared to the ground truth images; and 3) superior quality to those reconstructed by several other state-of-the-art methods, including the back-projection, CS total variation, PICCS, and the single-encoder convolutional neural network. Overall, the proposed DeCNN is effective in exploiting the average-image constraint to improve the 4D-CBCT image quality.

Motion artifacts induced by breathing variations are common in 4D-MRI images. This study aims to reduce the motion artifacts by developing a novel, robust 4D-MRI sorting method based on anatomic feature matching and applicable in both cine and sequential acquisition.

Byline: Raj. Panta, Paul. Segars, Fang-Fang. Yin, Jing. Cai Aims: To establish a framework to implement the 4D integrated extended cardiac torso (XCAT) digital phantom for 4D radiotherapy (RT) research. [...]

Our purpose was to investigate polymeric gels for use as a highly transparent radiotherapy bolus and determine the relevant physical and dosimetric properties. We first quantified tensile properties (maximum stress, strain, and Young modulus) for various polymeric gels, along with a commercial bolus product in order to illustrate the wide variety of potential materials. For a select polymeric gel with tensile properties similar to currently used radiotherapy bolus, we also evaluated mass and electron density, effective atomic number, optical transparency, and percent depth dose in clinical megavoltage photon and electron beams. For this polymeric gel, mass density was 872 ± 12 and 896 ± 13 g/cm3when measured via weight/volume and computed tomography Hounsfield units, respectively. Electron density was 2.95 ± 0.04 ×1023electrons/cm3. Adding fused silica (9% by weight) increases density to that of water. The ratio of the effective atomic number to that of water without and with added silica was 0.780 and 0.835 at 1 MeV, 0.767 and 0.826 at 6 MeV, and 0.746 and 0.809 at 20 MeV. Percent depth dose for 6 MV photons was within 2% of water within the first 2.5 cm and after scaling by the density coincided within 1% out to >7 cm. For 6 and 20 MeV electrons, after scaling for density D80%was within 1.3 and 1.5 mm of water, respectively. The high transparency and mechanical flexibility of polymeric gels indicate potential for use as a radiotherapy bolus; differences in density from water may be managed via either using “water equivalent thickness” or by incorporating fused silica into the material.

Objective: The objective of this study is to theoretically and experimentally evaluate the dosimetry in the microscopic disease regions surrounding the tumor under stereotactic body radiation therapy of lung cancer.Methods: For simplicity, the tumor was considered moving along 1 dimension with a periodic function. The probability distribution function of the tumor position was generated according to the motion pattern and was used to estimate the delivered dose in the microscopic disease region. An experimental measurement was conducted to validate both the estimated dose with a probability function and the calculated dose from 4-dimensional computed tomography data using a dynamic thorax phantom. Four tumor motion patterns were simulated with cos4(x) and sin(x), each with 2 different amplitudes: 10 mm and 5 mm. A 7-field conformal plan was created for treatment delivery. Both films (EBT2) and optically stimulated luminescence detectors were inserted in and around the target of the phantom to measure the delivered doses. Dose differences were evaluated using gamma analysis with 3%/3 mm.Results: The average gamma index between measured doses using film and calculated doses using average intensity projection simulation computed tomography was 80.8% ± 0.9%. In contrast, between measured doses using film and calculated doses accumulated from 10 sets of 4-dimensional computed tomography data, it was 98.7% ± 0.6%. The measured doses using optically stimulated luminescence detectors matched very well (within 5% of the measurement uncertainty) with the theoretically calculated doses using probability distribution function at the corresponding position. Respiratory movement caused inadvertent irradiation exposure, with 70% to 80% of the dose line wrapped around the 10 mm region outside the target.Conclusion: The use of static dose calculation in the treatment planning system could substantially underestimate the actual delivered dose in the microscopic disease region for a moving target. The margin for microscopic disease may be substantially reduced or even eliminated for lung stereotactic body radiation therapy.

Background and Purpose: Compared to cone-beam computed tomography, digital tomosynthesis imaging has the benefits of shorter scanning time, less imaging dose, and better mechanical clearance for tumor localization in radiation therapy. However, for lung tumors, the localization accuracy of the conventional digital tomosynthesis technique is affected by the lack of depth information and the existence of lung tumor motion. This study investigates the clinical feasibility of using an orthogonal-view phase-matched digital tomosynthesis technique to improve the accuracy of lung tumor localization.Materials and Methods: The proposed orthogonal-view phase-matched digital tomosynthesis technique benefits from 2 major features: (1) it acquires orthogonal-view projections to improve the depth information in reconstructed digital tomosynthesis images and (2) it applies respiratory phase-matching to incorporate patient motion information into the synthesized reference digital tomosynthesis sets, which helps to improve the localization accuracy of moving lung tumors. A retrospective study enrolling 14 patients was performed to evaluate the accuracy of the orthogonal-view phase-matched digital tomosynthesis technique. Phantom studies were also performed using an anthropomorphic phantom to investigate the feasibility of using intratreatment aggregated kV and beams’ eye view cine MV projections for orthogonal-view phase-matched digital tomosynthesis imaging. The localization accuracy of the orthogonal-view phase-matched digital tomosynthesis technique was compared to that of the single-view digital tomosynthesis techniques and the digital tomosynthesis techniques without phase-matching.Results: The orthogonal-view phase-matched digital tomosynthesis technique outperforms the other digital tomosynthesis techniques in tumor localization accuracy for both the patient study and the phantom study. For the patient study, the orthogonal-view phase-matched digital tomosynthesis technique localizes the tumor to an average (± standard deviation) error of 1.8 (0.7) mm for a 30° total scan angle. For the phantom study using aggregated kV–MV projections, the orthogonal-view phase-matched digital tomosynthesis localizes the tumor to an average error within 1 mm for varying magnitudes of scan angles.Conclusion: The pilot clinical study shows that the orthogonal-view phase-matched digital tomosynthesis technique enables fast and accurate localization of moving lung tumors.

Purpose: To develop a 4-dimensional computerized magnetic resonance imaging phantom with image textures extracted from real patient scans for liver motion studies.Methods: The proposed phantom was developed based on the current version of 4-dimensional extended cardiac-torso computerized phantom and a clinical magnetic resonance scan. Initially, the extended cardiac-torso phantom was voxelized in abdominal–chest region at the end of exhalation phase. Structures/tissues were classified into 4 categories: (1) Seven key textured organs, including liver, gallbladder, spleen, stomach, heart, kidneys, and pancreas, were mapped from a clinical T1-weighted liver magnetic resonance scan using deformable registration. (2) Large textured soft tissue volumes were simulated via an iterative pattern generation method using the same magnetic resonance scan. (3) Lung and intestine structures were generated by assigning uniform intensity with proper noise modeling. (4) Bony structures were generated by assigning the magnetic resonance values. A spherical hypointensity tumor was inserted into the liver. Other respiratory phases of the 4-dimensional phantom were generated using the backward deformation vector fields exported by the extended cardiac-torso program, except that bony structures were generated separately for each phase. A weighted image filtering process was utilized to improve the overall tissue smoothness at each phase.Results: Three 4-dimensional series with different motion amplitudes were generated. The developed motion phantom produced good illustrations of abdominal–chest region with anatomical structures in key organs and texture patterns in large soft tissue volumes. In a standard series, the tumor volume was measured as 13.90 ± 0.11 cm3in a respiratory cycle and the tumor’s maximum center-of-mass shift was 2.95 cm/1.84 cm on superior–inferior/anterior–posterior directions. The organ motion during the respiratory cycle was well rendered. The developed motion phantom has the flexibility of motion pattern variation, organ geometry variation, and tumor modeling variation.Conclusions: A 4-D computerized phantom was developed and could be used to produce image series with synthetic magnetic resonance textures for magnetic resonance imaging research of liver motion.

Purpose: To investigate the feasibility of using undersampled k-space data and an iterative image reconstruction method with total generalized variation penalty in the quantitative pharmacokinetic analysis for clinical brain dynamic contrast-enhanced magnetic resonance imaging.Methods: Eight brain dynamic contrast-enhanced magnetic resonance imaging scans were retrospectively studied. Two k-space sparse sampling strategies were designed to achieve a simulated image acquisition acceleration factor of 4. They are (1) a golden ratio–optimized 32-ray radial sampling profile and (2) a Cartesian-based random sampling profile with spatiotemporal-regularized sampling density constraints. The undersampled data were reconstructed to yield images using the investigated reconstruction technique. In quantitative pharmacokinetic analysis on a voxel-by-voxel basis, the rate constant Ktransin the extended Tofts model and blood flow FBand blood volume VBfrom the 2-compartment exchange model were analyzed. Finally, the quantitative pharmacokinetic parameters calculated from the undersampled data were compared with the corresponding calculated values from the fully sampled data. To quantify each parameter’s accuracy calculated using the undersampled data, error in volume mean, total relative error, and cross-correlation were calculated.Results: The pharmacokinetic parameter maps generated from the undersampled data appeared comparable to the ones generated from the original full sampling data. Within the region of interest, most derived error in volume mean values in the region of interest was about 5% or lower, and the average error in volume mean of all parameter maps generated through either sampling strategy was about 3.54%. The average total relative error value of all parameter maps in region of interest was about 0.115, and the average cross-correlation of all parameter maps in region of interest was about 0.962. All investigated pharmacokinetic parameters had no significant differences between the result from original data and the reduced sampling data.Conclusion: With sparsely sampled k-space data in simulation of accelerated acquisition by a factor of 4, the investigated dynamic contrast-enhanced magnetic resonance imaging pharmacokinetic parameters can accurately estimate the total generalized variation-based iterative image reconstruction method for reliable clinical application.

Purpose: This study aimed to detect the sensitivity of Delt 4 on ordinary field multileaf collimator misalignments, system misalignments, random misalignments, and misalignments caused by gravity of the multileaf collimator in stereotactic body radiation therapy.Methods: (1) Two field sizes, including 2.00 cm (X) × 6.00 cm (Y) and 7.00 cm (X) × 6.00 cm (Y), were set. The leaves of X1 and X2 in the multileaf collimator were simultaneously opened. (2) Three cases of stereotactic body radiation therapy of spinal tumor were used. The dose of the planning target volume was 1800 cGy with 3 fractions. The 4 types to be simulated included (1) the leaves of X1 and X2 in the multileaf collimator were simultaneously opened, (2) only X1 of the multileaf collimator and the unilateral leaf were opened, (3) the leaves of X1 and X2 in the multileaf collimator were randomly opened, and (4) gravity effect was simulated. The leaves of X1 and X2 in the multileaf collimator shifted to the same direction. The difference between the corresponding 3-dimensional dose distribution measured by Delt 4 and the dose distribution in the original plan made in the treatment planning system was analyzed with γ index criteria of 3.0 mm/3.0%, 2.5 mm/2.5%, 2.0 mm/2.0%, 2.5 mm/1.5%, and 1.0 mm/1.0%.Results: (1) In the field size of 2.00 cm (X) × 6.00 cm (Y), the γ pass rate of the original was 100% with 2.5 mm/2.5% as the statistical standard. The pass rate decreased to 95.9% and 89.4% when the X1 and X2 directions of the multileaf collimator were opened within 0.3 and 0.5 mm, respectively. In the field size of 7.00 (X) cm × 6.00 (Y) cm with 1.5 mm/1.5% as the statistical standard, the pass rate of the original was 96.5%. After X1 and X2 of the multileaf collimator were opened within 0.3 mm, the pass rate decreased to lower than 95%. The pass rate was higher than 90% within the 3 mm opening. (2) For spinal tumor, the change in the planning target volume V18under various modes calculated using treatment planning system was within 1%. However, the maximum dose deviation of the spinal cord was high. In the spinal cord with a gravity of −0.25 mm, the maximum dose deviation minimally changed and increased by 6.8% than that of the original. In the largest opening of 1.00 mm, the deviation increased by 47.7% than that of the original. Moreover, the pass rate of the original determined through Delt 4 was 100% with 3 mm/3% as the statistical standard. The pass rate was 97.5% in the 0.25 mm opening and higher than 95% in the 0.5 mm opening A, 0.25 mm opening A, whole gravity series, and 0.20 mm random opening. Moreover, the pass rate was higher than 90% with 2.0 mm/2.0% as the statistical standard in the original and in the 0.25 mm gravity. The difference in the pass rates was not statistically significant among the −0.25 mm gravity, 0.25 mm opening A, 0.20 mm random opening, and original as calculated using SPSS 11.0 software with P> .05.Conclusions: Different analysis standards of Delt 4 were analyzed in different field sizes to improve the detection sensitivity of the multileaf collimator position on the basis of 90% throughout rate. In stereotactic body radiation therapy of spinal tumor, the 2.0 mm/2.0% standard can reveal the dosimetric differences caused by the minor multileaf collimator position compared with the 3.0 mm/3.0% statistical standard. However, some position derivations of the misalignments that caused high dose amount to the spinal cord cannot be detected. However, some misalignments were not detected when a large number of multileaf collimator were administered into the spinal cord.

Single-dose preoperative stereotactic body radiotherapy is a novel radiotherapy technique for the early-stage breast cancer, and the treatment response pattern of this technique needs to be investigated on a quantitative basis. In this work, dynamic contrast-enhanced magnetic resonance imaging and diffusion-weighted magnetic resonance imaging were used to study the treatment response pattern in a unique cohort of patients with early-stage breast cancer treated with preoperative radiation. Fifteen female qualified patients received single-dose preoperative radiotherapy with 1 of the 3 prescription doses: 15 Gy, 18 Gy, and 21 Gy. Magnetic resonance imaging scans including both diffusion-weighted magnetic resonance imaging and dynamic contrast-enhanced magnetic resonance imaging were acquired before radiotherapy for planning and after radiotherapy but before surgical resection. In diffusion-weighted magnetic resonance imaging, the regional averaged apparent diffusion coefficient was calculated. In dynamic contrast-enhanced magnetic resonance imaging, quantitative parameters Ktransand vewere evaluated using the standard Tofts model based on the average contrast agent concentration within the region of interest, and the semiquantitative initial area under the concentration curve (iAUC6min) was also recorded. These parameters’ relative changes after radiotherapy were calculated for gross tumor volume, clinical target volume, and planning target volume. The initial results showed that after radiotherapy, initial area under the concentration curve significantly increased in planning target volume (P< .006) and clinical target volume (P< .006), and vesignificantly increased in planning target volume (P< .05) and clinical target volume (P< .05). Statistical studies suggested that linear correlations between treatment dose and the observed parameter changes exist in most examined tests, and among these tests, the change in gross tumor volume regional averaged apparent diffusion coefficient (P< .012) and between treatment dose and planning target volume Ktrans(P< .029) were found to be statistically significant. Although it is still preliminary, this pilot study may be useful to provide insights for future works.

Purpose: Scatter significantly limits the application of the dual-source cone-beam computed tomography by inducing scatter artifacts and degrading contrast-to-noise ratio, Hounsfield-unit accuracy, and image uniformity. Although our previously developed interleaved acquisition mode addressed the cross scatter between the 2 X-ray sources, it doubles the scanning time and doesn’t address the forward scatter issue. This study aims to develop a prepatient grid system to address both forward scatter and cross scatter in the dual-source cone-beam computed tomography.Methods: Grids attached to both X-ray sources provide physical scatter reduction during the image acquisition. Image data were measured in the unblocked region, while both forward scatter and cross scatter were measured in the blocked region of the projection for postscan scatter correction. Complementary projections were acquired with grids at complementary locations and were merged to form complete projections for reconstruction. Experiments were conducted with different phantom sizes, grid blocking ratios, image acquisition modes, and reconstruction algorithms to investigate their effects on the scatter reduction and correction. The image quality improvement by the prepatient grids was evaluated both qualitatively through the artifact reduction and quantitatively through contrast-to-noise ratio, Hounsfield-unit accuracy, and uniformity using a CATphan 504 phantom.Results: Scatter artifacts were reduced by scatter reduction and were removed by scatter correction method. Contrast-to-noise ratio, Hounsfield-unit accuracy, and image uniformity were improved substantially. The simultaneous acquisition mode achieved comparable contrast-to-noise ratio as the interleaved and sequential modes after scatter reduction and correction. Higher grid blocking ratio and smaller phantom size led to higher contrast-to-noise ratio for the simultaneous mode. The iterative reconstruction with total variation regularization was more effective than the Feldkamp, Davis, and Kress method in reducing noise caused by the scatter correction to enhance contrast-to-noise ratio.Conclusion: The prepatient grid system is effective in removing the scatter effects in the simultaneous acquisition mode of the dual-source cone-beam computed tomography, which is useful for scanning time reduction or dual energy imaging.

Stereotactic radiosurgery (SRS) has been an effective treatment method for brain tumors; however, few data are available regarding radiation-induced white matter (WM) damage by SRS. In this work, diffusion tensor imaging (DTI) was used to investigate WM changes following SRS. Fifteen patients with gliomas were enrolled, with prescription doses ranging 18–25 Gy. Patients were scanned with magnetic resonance imaging (MRI) including DTI before and after SRS. Diffusion tensors were calculated and fiber tracking was performed. Non-irradiated WM volumes and irradiated WM volumes receiving =12 Gy and =5 Gy were contoured as volumes of interest (VOI). Apparent diffusion coefficient (), fractional anisotropy (FA) and number of fibers (NF) were calculated and assessed using the Wilcoxon signed-rank test. Compared with those of non-irradiated VOIs, FA and NF decreased considerably after two months of SRS in the irradiated WM VOIs. The variation in was however small and was not statistically significant. The preliminary results suggested that FA and NF might potentially be more sensitive indicators than in measuring radiation-induced WM changes and DTI could be a valuable tool to assess radiation-induced WM changes in SRS. Although it is still preliminary, this pilot study may be useful to provide insights for future studies.

The administration of high-precision radiotherapy, termed stereotactic body radiotherapy (SBRT), delivers high doses of radiation to tumours without greatly affecting adjacent normal tissues. SBRT can affect the disease course for properly selected patients with metastatic cancer with improved palliation, disease response, and long-term disease control. In this Review, the biology, practical aspects of delivery and emerging clinical opportunities for SBRT in limited metastatic cancer patients are discussed.

The purpose of this investigation was to study apparatus-dependent dose distribution differences specific to spine stereotactic body radiotherapy (SBRT) treatment planning. This multi-institutional study was performed evaluating an image-guided robotic radiosurgery system (CK), intensity modulated protons (IMP), multileaf collimator (MLC) fixed-field IMRT with 5 mm (11 field), 4 mm (9 field), and 2.5 mm (8- and 9-field) leaf widths and intensity modulated volumetric arc therapy (IMVAT) with a 2.5 mm MLC. Treatment plans were systematically developed for targets consisting of one, two and three consecutive thoracic vertebral bodies (VBs) with the esophagus and spinal cord contoured as the organs at risk. It was found that all modalities achieved acceptable treatment planning constraints. However, following normalization fixed field IMRT with a 2.5 mm MLC, IMVAT and IMP systems yielded the smallest ratio of maximum dose divided by the prescription dose (MD/PD) for one-, two- and three-VB PTVs (ranging from 1.1–1.16). The 2.5 mm MLC 9-field IMRT, IMVAT and CK plans resulted in the least dose to 0.1 cc volumes of spinal cord and esophagus. CK plans had the greatest degree of target dose inhomogeneity. As the level of complexity increased with an increasing number of vertebral bodies, distinct apparatus features such as the use of a high number of beams and a finer leaf size MLC were favored. Our study quantified apparatus-dependent dose-distribution differences specific to spine SBRT given strict, but realistic, constraints and highlights the need to benchmark physical dose distributions for multi-institutional clinical trials.

Stereotactic radiosurgery (SRS) refers to a single radiation treatment delivering a high dose to an intra-cranial target localized in three-dimensions by CT and/or MRI imaging. Traditionally, immobilization of the patient's head has been achieved using a rigid stereotactic head frame as the key step in allowing for accurate dose delivery. SRS has been delivered by both Cobalt-60 (Gamma Knife®) and linear accelerator (linac) technologies for many decades. The focus of this review is to highlight recent advances and major innovations in SRS technologies relevant to clinical practice and developments allowing for non-invasive frame SRS.

This report describes the technique and initial experience using cone beam CT (CBCT) for localization of treatment targets in patients undergoing stereotactic body radiation therapy (SBRT). Patients selected for SBRT underwent 3-D or 4-D CT scans in a customized immobilization cradle. GTV, CTV, ITV, and PTV were defined. Intensity-modulated radiation beams, multiple 3-D conformal beams, or dynamic conformal arcs were delivered using a Varian 21EX with 120-leaf MLC. CBCT images were obtained prior to each fraction, and registered to the planning CT by using soft tissue and bony structures to assure accurate isocenter localization. Patients were repositioned for treatment based on the CBCT images. Radiographic images (kV, MV, or CBCT) were taken before and after beam delivery to further assess set-up accuracy. Ten patients with lung, liver, and spine lesions received 29 fractions of treatment using this technique. The prescription doses ranged 1250 ~ 6000 cGy in 1 ~ 5 fractions. Compared to traditional 2-D matching using bony structures, CBCT corrects target deviation from 1 mm to 15 mm, with an average of 5 mm. Comparison of pre-treatment to post-treatment radiographic images demonstrated an average 2 mm deviation (ranging from 0–4 mm). Improved immobilization may enhance positioning accuracy. Typical total “in-room” times for the patients are approximately 1 hour. CBCT-guided SBRT is feasible and enhances setup accuracy using 3-D anatomical information.

A set of experiments were conducted to evaluate six similarity measures for intensity-based rigid-body 3D/2D image registration. Similarity measure is an index that measures the similarity between a digitally reconstructed radiograph (DRR) and an x-ray planar image. The registration is accomplished by maximizing the sum of the similarity measures between biplane x-ray images and the corresponding DRRs in an iterative fashion. We have evaluated the accuracy and attraction ranges of the registrations using six different similarity measures on phantom experiments for head, thorax, and pelvis. The images were acquired using Varian Medial System On-Board Imager. Our results indicated that normalized cross correlationand entropy of differenceshowed a wide attraction range (62 degand 83 mmmean attraction range, ωmean), but the worst accuracy (4.2 mmmaximum error, emax). The gradient-based similarity measures, gradient correlationand gradient difference, and the pattern intensityshowed sub-millimeter accuracy, but narrow attraction ranges (ωmean=29 deg, 31 mm). Mutual informationwas in-between of these two groups (emax=2.5 mm, ωmean=48 deg, 52 mm). On the data of 120 x-ray pairs from eight IRB approved prostate patients, the gradient differenceshowed the best accuracy. In the clinical applications, registrations starting with the mutual informationfollowed by the gradient differencemay provide the best accuracy and the most robustness.

Intensity-modulated photon radiation therapy (RT; IMRT) and proton therapy are advanced radiation technologies that permit improved conformation of radiation dose to target structures while limiting irradiation of surrounding normal tissues. Application of these technologies in the treatment of rectal and anal cancer is attractive, based on the potential reduction in radiation treatment toxicities that are frequently incurred in the pelvis and perineum. Furthermore, conformal RT might also allow for dose escalation to target areas, leading to improved tumor control. This review discusses the underlying principles of IMRT. In addition, the rationale and clinical data regarding the efficacy of radiation dose escalation for rectal and anal cancer will be highlighted, as well as tolerance of pelvic organs to RT and chemotherapy. Finally, preliminary results of IMRT in the treatment of lower gastrointestinal tract cancers will be reviewed. The potential and rationale for proton therapy in treatment of these malignances are also discussed.

An adaptive prediction approach was developed to infer internal target position by external marker positions. First, a prediction model (or adaptive neural network) is developed to infer target position from its former positions. For both internal target and external marker motion, two networks with the same type are created. Next, a linear model is established to correlate the prediction errors of both neural networks. Based on this, the prediction error of an internal target position can be reconstructed by the linear combination of the prediction errors of the external markers. Finally, the next position of the internal target is estimated by the network and subsequently corrected by the reconstructed prediction error. In a similar way, future positions are inferred as their previous positions are predicted and corrected. This method was examined by clinical data. The results demonstrated that an improvement (10% on average) of correlation between predicted signal and real internal motion was achieved, in comparison with the correlation between external markers and internal target motion. Based on the clinical data (with correlation coefficient 0.75 on average) observed between external marker and internal target motions, a prediction error (23% on average) of internal target position was achieved. The preliminary results indicated that this method is helpful to improve the predictability of internal target motion with the additional information of external marker signals. A consistent correlation between external and internal signals is important for prediction accuracy.

The basic concept, design and performance of a novel needle-based x-ray system for medical applications are reported. The main principle of the system is based on a two-stage production of x-rays. The system comprises a conventional x-ray tube with an Ag anode, any known type of conditioning optics and a 2.2 mm diameter hollow needle with an interchangeable Mo target. The target can be moved along the needle axis and rotated around the needle axis. The needle x-ray device allows for adjustment in energy and flux intensity of the x-rays emitted by the target. The depth dependence of the intensity, dose rate as well as spatial and energy distribution of the radiation emitted by the target have been experimentally measured. The depth dose rate results have been compared with theoretical calculations using a Monte Carlo simulation of the x-ray production process. These studies have experimentally confirmed that the concept of this x-ray system is correct. Further improvement of the device can increase the dose rate up to the levels required for clinical applications.

Traditional management strategies for patients with spinal tumors have undergone considerable changes during the last 15years. Significant improvements in digital imaging, computer processing, and treatment planning have provided the basis for the application of stereotactic techniques, now the standard of care for intracranial pathology, to spinal pathology. In addition, certain of these improvements have also allowed us to progress from frame-based to frameless systems which now act to accurately assure the delivery of high doses of radiation to a precisely defined target volume while sparing injury to adjacent normal tissues. In this article we will describe the evolution from yesterday’s standards for radiation therapy to the current state of the art for the treatment of patients with spinal tumors. This presentation will include a discussion of radiation dosing and toxicity, the overall process of extracranial radiation delivery, and the current state of the art regarding Cyberknife, Novalis, and tomotherapy. Additional discussion relating current research protocols and future directions for the management of benign tumors of the spine will also be presented.

An artificial intelligence (AI)-guided inverse planning system was developed to optimize the combination of parameters in the objective function for intensity-modulated radiation therapy (IMRT). In this system, the empirical knowledge of inverse planning was formulated with fuzzy if–then rules, which then guide the parameter modification based on the on-line calculated dose. Three kinds of parameters (weighting factor, dose specification, and dose prescription) were automatically modified using the fuzzy inference system (FIS). The performance of the AI-guided inverse planning system (AIGIPS) was examined using the simulated and clinical examples. Preliminary results indicate that the expected dose distribution was automatically achieved using the AI-guided inverse planning system, with the complicated compromising between different parameters accomplished by the fuzzy inference technique. The AIGIPS provides a highly promising method to replace the current trial-and-error approach.

Radiosurgery can deliver a single, large radiation dose to a localized tumor using a stereotactic approach and hence, requires accurate and precise delivery of radiation to the target. Of the extracranial organ targets, the spine is considered a suitable site for radiosurgery, because there is minimal or no breathing-related organ movement. The authors studied spinal radiosurgery in patients with spinal metastases to determine its accuracy and precision. The spinal radiosurgery program was based on an image-guided and intensity-modulated, shaped-beam radiosurgical unit. It is equipped with micromultileaf collimators for beam shaping and radiation intensity modulation and with a noninvasive, frameless positioning device that uses infrared, passive marker technology together with corroborative image fusion of the digitally reconstructed image from computed tomography (CT) simulation and orthogonal X-ray imagery at the treatment position. These images were compared with the port films that were taken at the time of treatment to determine the accuracy of the isocenter position. Clinical feasibility was tested in 10 patients who had spinal metastasis with or without spinal cord compression. The patients were treated with fractionated external beam radiotherapy followed by single-dose radiosurgery as a boost (6–8 grays) to the most involved portion of the spine or to the site of spinal cord compression. The accuracy for the isocenter was within 1.36 mm ± 0.11 mm, as measured by image fusion of the digitally reconstructed image from CT simulation and the port film. Clinically, the majority of patients had prompt pain relief within 2–4 weeks of treatment. Complete and partial recovery of motor function also was achieved in patients with spinal cord compression. The radiation dose to the spinal cord was minimal. The maximum dose of radiation to the anterior edge of the spinal cord within a transverse section, on average, was 50% of the prescribed dose. There was no acute radiation toxicity detected clinically during the mean follow-up of 6 months. Image-guided, shaped-beam spinal radiosurgery is accurate and precise. Rapid clinical improvement of pain and neurologic function also may be achieved. The results indicate the potential of spinal radiosurgery in the treatment of patients with spinal metastasis, especially those with solitary sites of spine involvement, to increase the prospects of long-term palliation. Cancer 2003;97:2013–8. © 2003 American Cancer Society. DOI 10.1002/cncr.11296

Interpolation is generally needed to visualize medical images from a limited number of sliced tomographic images such as CT. In this paper, a novel gray-scale image interpolation method, for interpolating two-dimensional images accurately and efficiently, called direction-based interpolation, is investigated. In this method, the digital image is considered a sampling of the underlying continuous function, which is also called the image field. If the image is interpolated along the isovalue curves in the image field, instead of along the coordinate axes, both the edges and the internal structures of the objects in the image are well preserved. Initially, the isovalue direction at each point is calculated from the local centered moments of the image. A specific type of image, called the direction image, is composed from the isovalue directions. Then, the direction image is interpolated into a high-resolution direction image. The isovalue curve through any point in the image field is determined from the high-resolution direction image using a path-finding technique. A high-resolution gray-scale image with satisfactory object structure is then generated by interpolating the original image linearly along the isovalue curves. Experiments on a set of CT images show that this method not only preserves the shapes of complicated structures but also has an efficient computation. The comparison between the digitally reconstructed radiographs generated from the interpolated result using the direction-based interpolation method, the traditional linear interpolation method, and the traditional cubic spline interpolation method shows the promise of the proposed method in radiation treatment planning.

Yin F-F, Giger ML, Vyborny CJ, Doi K, Schmidt RA. Comparison of bilateral-subtraction and single-image processing techniques in the computerized detection of mammographic masses. Invest Radiol 1993;28:473–481.

Purpose: To investigate the impact of intra- and inter-fractional esophageal motion on dosimetry and observed toxicity in a phase I dose escalation study of accelerated radiotherapy with concurrent chemotherapy for locally advanced lung cancer.Methods and Materials: Patients underwent computed tomography imaging for radiotherapy treatment planning (CT1 and 4DCT1) and at 2 weeks (CT2 and 4DCT2) and 5 weeks (CT3 and 4DCT3) after initiating treatment. Each computed tomography scan consisted of 10-phase 4DCTs in addition to a static free-breathing or breath-hold computed tomography. The esophagus was independently contoured on all computed tomographies and 4DCTs. Both CT2 and CT3 were rigidly registered with CT1 and doses were recalculated using the original intensity-modulated radiation therapy plan based on CT1 to assess the impact of interfractional motion on esophageal dosimetry. Similarly, 4DCT1 data sets were rigidly registered with CT1 to assess the impact of intrafractional motion. The motion was characterized based on the statistical analysis of slice-by-slice center shifts (after registration) for the upper, middle, and lower esophageal regions, respectively. For the dosimetric analysis, the following quantities were calculated and assessed for correlation with toxicity grade: the percent volumes of esophagus that received at least 20 Gy (V20) and 60 Gy (V60), maximum esophageal dose, equivalent uniform dose, and normal tissue complication probability.Results: The interfractional center shifts were 4.4 ± 1.7 mm, 5.5 ± 2.0 mm and 4.9 ± 2.1 mm for the upper, middle, and lower esophageal regions, respectively, while the intrafractional center shifts were 0.6 ± 0.4 mm, 0.7 ± 0.7 mm, and 0.9 ± 0.7 mm, respectively. The mean V60 (and corresponding normal tissue complication probability) values estimated from the interfractional motion analysis were 7.8% (10%), 4.6% (7.5%), 7.5% (8.6%), and 31% (26%) for grade 0, grade 1, grade 2, and grade 3 toxicities, respectively.Conclusions: Interfractional esophageal motion is significantly larger than intrafractional motion. The mean values of V60 and corresponding normal tissue complication probability, incorporating interfractional esophageal motion, correlated positively with esophageal toxicity grade.

Knowledge models in radiotherapy capture the relation between patient anatomy and dosimetry to provide treatment planning guidance. When treatment schemes evolve, existing models struggle to predict accurately. We propose a case-based reasoning framework designed to handle novel anatomies that are of same type but vary beyond original training samples. A total of 105 pelvic intensity-modulated radiotherapy cases were analyzed. Eighty cases were prostate cases while the other 25 were prostate-plus-lymph-node cases. We simulated 4 scenarios: Scarce scenario, Semiscarce scenario, Semiample scenario, and Ample scenario. For the Scarce scenario, a multiple stepwise regression model was trained using 85 cases (80 prostate, 5 prostate-plus-lymph-node). The proposed workflow started with evaluating the feature novelty of new cases against 5 training prostate-plus-lymph-node cases using leverage statistic. The case database was composed of a 5-case dose atlas. Case-based dose prediction was compared against the regression model prediction using sum of squared residual. Mean sum of squared residual of case-based and regression predictions for the bladder of 13 identified outliers were 0.174 ± 0.166 and 0.459 ± 0.508, respectively (P= .0326). For the rectum, the respective mean sum of squared residuals were 0.103 ± 0.120 and 0.150 ± 0.171 for case-based and regression prediction (P= .1972). By retaining novel cases, under the Ample scenario, significant statistical improvement was observed over the Scarce scenario (P= .0398) for the bladder model. We expect that the incorporation of case-based reasoning that judiciously applies appropriate predictive models could improve overall prediction accuracy and robustness in clinical practice.

Purpose: To develop an automated optimization program to generate optimal beam settings for whole-breast radiation therapy driven by clinically oriented goals.Materials and Methods: Forty patients were retrospectively included in this study. Each patient’s planning images, contoured structures of planning target volumes, organs-at-risk, and breast wires were used to optimize for patient-specific–beam settings. Two beam geometries were available tangential beams only and tangential plus supraclavicular beams. Beam parameters included isocenter position, gantry, collimator, couch angles, and multileaf collimator shape. A geometry-based goal function was defined to determine such beam parameters to minimize out-of-field target volume and in-field ipsilateral lung volume. For each geometry, the weighting in the goal function was trained with 10 plans and tested on 10 additional plans. For each query patient, the optimal beam setting was searched for different gantry-isocenter pairs. Optimal fluence maps were generated by an in-house automatic fluence optimization program for target coverage and homogeneous dose distribution, and dose calculation was performed in Eclipse. Automatically generated plans were compared with manually generated plans for target coverage and lung and heart sparing.Results: The program successfully produced a set of beam parameters for every patient. Beam optimization time ranged from 10 to 120 s. The automatic plans had overall comparable plan quality to manually generated plans. For all testing cases, the mean target V95%was 91.0% for the automatic plans and 88.5% for manually generated plans. The mean ipsilateral lung V20Gywas lower for the automatic plans (15.2% vs 17.9%). The heart mean dose, maximum dose of the body, and conformity index were all comparable.Conclusion: We developed an automated goal-driven beam setting optimization program for whole-breast radiation therapy. It provides clinically relevant solutions based on previous clinical practice as well as patient specific anatomy on a substantially faster time frame.

Aim: The aim of the study is to develop a geometrically adaptive and statistically robust plan quality inference method.Methods and Materials: We propose a knowledge-based plan quality inference method that references to similar plans in the historical database for patient-specific plan quality evaluation. First, a novel plan similarity metric with high-dimension geometrical difference quantification is utilized to retrieve similar plans. Subsequently, dosimetric statistical inferences are obtained from the selected similar plans. Two plan quality metrics—dosimetric result probability and dose deviation index—are proposed to quantify plan quality among prior similar plans. To evaluate the performance of the proposed method, we exported 927 clinically approved head and neck treatment plans. Eight organs at risk, including brain stem, cord, larynx, mandible, pharynx, oral cavity, left parotid and right parotid, were analyzed. Twelve suboptimal plans identified by dosimetric result probability were replanned to validate the capability of the proposed methods in identifying inferior plans.Results: After replanning, left and right parotid median doses are reduced by 31.7% and 18.2%, respectively; 83% of these cases would not be identified as suboptimal without the proposed similarity plan selection. Analysis of population plan quality reveals that average parotid sparing has been improving significantly over time (21.7% dosimetric result probability reduction from year 2006-2007 to year 2016-2017). Notably, the increasing dose sparing over time in retrospective plan quality analysis is strongly correlated with the increasing dose prescription ratios to the 2 planning targets, revealing the collective trend in planning conventions.Conclusions: The proposed similar plan retrieval and analysis methodology has been proven to be predictive of the current plan quality. Therefore, the proposed workflow can potentially be applied in the clinics as a real-time plan quality assurance tool. The proposed metrics can also serve the purpose of plan quality analytics in finding connections and historical trends in the clinical treatment planning workflow.