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BACKGROUND: Studies using stereotactic body radiotherapy (SBRT) dose escalation in in low- and intermediate-risk prostate cancer patients have indicated favorable outcomes. OBJECTIVE: To evaluate tolerance and tumor control outcomes in low- and intermediate-risk prostate cancer patients treated with high-dose SBRT following our phase 1 trial. DESIGN, SETTING, AND PARTICIPANTS: A total of 551 patients with low- or intermediate-risk prostate cancer were treated with SBRT. INTERVENTION: Treatment with 37.5–40 Gy SBRT in five fractions directed to the prostate and seminal vesicles. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Outcome measurements included acute toxicities (3 mo after RT) and tumor control evaluation (prostate-specific antigen [PSA] levels at 3–6-mo intervals and post-treatment prostate biopsy at 2 yr). RESULTS AND LIMITATIONS: Acute grade 2 gastrointestinal (GI) toxicities occurred in 1.8% of patients, and late grade 2 and 3 GI toxicities were observed in 3.4% and 0.4% of patients, respectively. Acute grade 2 genitourinary (GU) toxicities occurred in 10% of patients, and grade 3–5 acute GU toxicities were observed in 0.7% of patients. Late grade 2 and 3 GU toxicities were observed in 21.1% and 2.5% of patients, respectively. The use of a hydrogel rectal spacer was significantly associated with reduced late GI toxicity and lower odds of developing late GU toxicity. The median follow-up was 17 mo, and 53% of those with at least 2 yr of follow-up (103/193) had a biopsy performed. The 5-yr cumulative incidence of PSA failure was 2.1%, and the incidence of a positive 2-yr treatment biopsy was 12%. Limitations to this report include its retrospective nature and short follow-up time. CONCLUSIONS: Favorable short-term outcomes were achieved with high-dose SBRT for low- and intermediate-risk disease. Severe late toxicities were observed and favorable tumor control was found. PATIENT SUMMARY: We utilized stereotactic body radiotherapy, a form of external beam radiotherapy that delivers highly targeted high-dose treatment to the prostate, to treat over 500 localized prostate cancer patients in five sessions over 1.5 wk. Treatments were well tolerated without significant urinary or rectal side effects. Nearly 90% of those who underwent biopsies after treatment did not demonstrate residual active disease.

Background and purpose Magnetic Resonance (MR)-only planning has been implemented clinically for radiotherapy of prostate cancer. However, fewer studies exist regarding the overall success rate of MR-only workflows. We report on successes and challenges of implementing MR-only workflows for prostate. Materials and methods A total of 585 patients with prostate cancer underwent an MR-only simulation and planning between 06/2016 – 06/2018. MR simulation included images for contouring, synthetic-CT generation and fiducial identification. Workflow interruptions occurred that required a backup CT, a re-simulation or an update to our current quality assurance (QA) process. The challenges were prospectively evaluated and classified into synthetic-CT generation, motion/artifacts in the MRs, fiducial QA and bowel preparation guidelines. Results MR-only simulation was successful in 544 (93.2%) patients. In seventeen patients (2.9%), reconstruction of synthetic-CT failed due to patient size, femur angulation, or failure to determine the body contour. Twenty-four patients (4.1%) underwent a repeat/backup CT scan because of artifacts on the MR such as image blur due to patient motion or biopsy/surgical artifacts that hampered identification of the implanted fiducial markers. In patients requiring large coverage due to nodal involvement, inhomogeneity artifacts were resolved by using a two-stack acquisition and adaptive inhomogeneity correction. Bowel preparation guidelines were modified to address frequent rectum/gas issues due to longer MR scan time. Conclusions MR-only simulation has been successfully implemented for a majority of patients in the clinic. However, MR-CT or CT-only pathway may still be needed for patients where MR-only solution fails or patients with MR contraindications.

Purpose This study reports clinical experience using a linear accelerator-based MV-kV imaging system for intrafraction motion management during prostate stereotactic body radiation therapy (SBRT). Methods and Materials From June 2016 to August 2018, 193 prostate SBRT patients were treated using MV-kV motion management (median dose 40 Gy in 5 fractions). Patients had 3 fiducials implanted then simulated and treated with a full bladder and empty rectum. Pretreatment orthogonal kVs and cone beam computed tomography were used to position patients and evaluate internal anatomy. Motion was tracked during volumetric modulated arc therapy delivery using simultaneously acquired kV and MV images from standard on-board systems. Treatment was interrupted to reposition patients when motion >1.5-2 mm was detected. Motion traces were analyzed and compared with Calypso traces from a previously treated similar patient cohort. To evaluate “natural motion” (ie, if we had not interrupted treatment and repositioned), intrafraction couch corrections were removed from all traces. Clinical effectiveness of the MV-kV system was explored by evaluating toxicity (Common Terminology Criteria for Adverse Events v3.0) and biochemical recurrence rates (nadir + 2 ng/mL). Results Median number of interruptions for patient repositioning was 1 per fraction (range, 0-9). Median overall treatment time was 8.2 minutes (range, 4.2-44.8 minutes). Predominant motion was inferior and posterior, and probability of motion increased with time. Natural motion >3 mm and >5 mm in any direction was observed in 32.3% and 10.2% of fractions, respectively. Calypso monitoring (n = 50) demonstrated similar motion results. In the 151 MV-kV patients with ≥3-month follow-up (median, 9.5 months; range, 3-26.5 months), grade ≥2 acute genitourinary/gastrointestinal and late genitourinary/gastrointestinal toxicity was observed in 9.9%/2.0% and 11.9%/2.7%, respectively. Biochemical control was 99.3% with a single failure in a high-risk patient. Conclusions The MV-kV system is an effective method to manage intrafraction prostate motion during SBRT, offering the opportunity to correct for prostate clinical target volume displacements that would have otherwise extended beyond typical planning target volume margins.

Purpose To assess the performance and optimize the MR image quality when using a custom-built flexible radiofrequency (RF) spine coil array fitted between the immobilization device and the patient for spine radiotherapy treatment planning. Methods A 32 channel flexible custom-designed receive-only coil array has been developed for spine radiotherapy simulation for a 3 T Philips MR scanner. Coil signal-to-noise performance and interactions with standard vendor hardware were assessed. In four volunteers, immobilization molds were created with a dummy version of the array within the mold, and subjects were scanned using the custom array in the mold. Phantoms and normal volunteers were scanned with both the custom spine coil array and the vendor's FDA-approved in-table posterior coil array to compare performance. Results The superior-inferior field of view for the custom spine array was ~30 cm encompassing at least 10 vertebrae. A noise correlation matrix showed at least 25 dB isolation between all coil elements. Signal-to-noise ratio (SNR) calculated on a phantom scan at the depth of the spinal cord was a factor of 3 higher with the form-fit spine array as compared to the vendor's posterior coil array. The body coil B1 transmit map was equivalent with and without the spine array in place demonstrating that the elements are decoupled from the body coil. Volunteer imaging showed improved SNR as compared to the vendor's posterior coil array. The custom array permitted a high degree of acceleration making possible the acquisition of isotropic high-resolution 1.1 × 1.1 × 1.1 mm3 three-dimensional data set over a 30-cm section of the spine in less than 5 min. Conclusion The custom-designed form-fitting flexible spine coil array provided enhanced SNR and increased acceleration compared to the vendor's posterior array. Future studies will assess MR-based spinal cord imaging with the custom coil in comparison to CT myelogram.

Purpose The plan check tool (PCT) is the result of a multi‐institutional collaboration to jointly develop a flexible automated plan checking framework designed with the versatility to be shared across collaborating facilities while supporting the individual differences between practices. We analyze the effect that PCT has had on the efficiency and effectiveness of initial chart checks at our institution. Methods and Materials Data on errors identified during initial chart checks were acquired during two time periods: before the introduction of PCT in the clinic (6/24/2015 to 7/31/2015, 187 checks) and post‐clinical release (4/14/2016 to 5/2/2016, 186 checks). During each time period, human plan checkers were asked to record all issues that they either manually detected or that were detected by PCT as well as the amount of time, less breaks, or interruptions, it took to check each plan. Results After the clinical release of PCT, there was a statistically significant decrease in the number of issues recorded by the human plan checkers both related to checks explicitly performed by PCT (13 vs 50, P

This study reports the impact of using a centralized database system for major equipment quality assurance (QA) at a large institution.A centralized database system has been implemented for radiation therapy machine QA in our institution at 6 campuses with 11 computed tomographies and 22 linear accelerators (LINACs). The database system was customized to manage monthly and annual computed tomography and LINAC QA. This includes providing the same set of QA procedures across the enterprise, digitally storing all measurement records, and generating trend analyses. Compared with conventional methods (ie, paper forms), the effectiveness of the database system was quantified by changes in the compliance of QA tests and perceptions of staff to the efficiency of data retrieval and analyses. An anonymized questionnaire was provided to physicists enterprise-wide to assess workflow changes.With the implementation of the database system, the compliance of QA test completion improved from 80% to99% for the entire institution. This resonates with the 56% of physicists who found the database system helpful in guiding them through QA, and 25% of physicists found the contrary, and 19% reported no difference (n = 16). Meanwhile, 40% of physicists reported longer times needed to record data using the database system compared with conventional methods, and another 40% suggested otherwise. In addition, 87% and 80% found the database more efficient to analyze and retrieve previous data, respectively. This was also reflected by the shorter time taken to generate year-end QA statistics using the software (5 vs 30 min per LINAC). Overall, 94% of physicists preferred the centralized database system over conventional methods and endorsed continued use of the system.A centralized database system is useful and can improve the effectiveness and efficiency of QA management in a large institution. With consistent data collection and proper data storage using a database, high-quality data can be obtained for failure modes and effects analyses as per TG 100.

Purpose To evaluate pix2pix and CycleGAN and to assess the effects of multiple combination strategies on accuracy for patch-based synthetic computed tomography (sCT) generation for magnetic resonance (MR)-only treatment planning in head and neck (HN) cancer patients. Materials and methods Twenty-three deformably registered pairs of CT and mDixon FFE MR datasets from HN cancer patients treated at our institution were retrospectively analyzed to evaluate patch-based sCT accuracy via the pix2pix and CycleGAN models. To test effects of overlapping sCT patches on estimations, we (a) trained the models for three orthogonal views to observe the effects of spatial context, (b) we increased effective set size by using per-epoch data augmentation, and (c) we evaluated the performance of three different approaches for combining overlapping Hounsfield unit (HU) estimations for varied patch overlap parameters. Twelve of twenty-three cases corresponded to a curated dataset previously used for atlas-based sCT generation and were used for training with leave-two-out cross-validation. Eight cases were used for independent testing and included previously unseen image features such as fused vertebrae, a small protruding bone, and tumors large enough to deform normal body contours. We analyzed the impact of MR image preprocessing including histogram standardization and intensity clipping on sCT generation accuracy. Effects of mDixon contrast (in-phase vs water) differences were tested with three additional cases. The sCT generation accuracy was evaluated using mean absolute error (MAE) and mean error (ME) in HU between the plan CT and sCT images. Dosimetric accuracy was evaluated for all clinically relevant structures in the independent testing set and digitally reconstructed radiographs (DRRs) were evaluated with respect to the plan CT images. Results The cross-validated MAEs for the whole-HN region using pix2pix and CycleGAN were 66.9 ± 7.3 vs 82.3 ± 6.4 HU, respectively. On the independent testing set with additional artifacts and previously unseen image features, whole-HN region MAEs were 94.0 ± 10.6 and 102.9 ± 14.7 HU for pix2pix and CycleGAN, respectively. For patients with different tissue contrast (water mDixon MR images), the MAEs increased to 122.1 ± 6.3 and 132.8 ± 5.5 HU for pix2pix and CycleGAN, respectively. Our results suggest that combining overlapping sCT estimations at each voxel reduced both MAE and ME compared to single-view non-overlapping patch results. Absolute percent mean/max dose errors were 2% or less for the PTV and all clinically relevant structures in our independent testing set, including structures with image artifacts. Quantitative DRR comparison between planning CTs and sCTs showed agreement of bony region positions to Conclusions The dosimetric and MAE based accuracy, along with the similarity between DRRs from sCTs, indicate that pix2pix and CycleGAN are promising methods for MR-only treatment planning for HN cancer. Our methods investigated for overlapping patch-based HU estimations also indicate that combining transformation estimations of overlapping patches is a potential method to reduce generation errors while also providing a tool to potentially estimate the MR to CT aleatoric model transformation uncertainty. However, because of small patient sample sizes, further studies are required.

The use of magnetic resonance imaging (MRI) for radiation therapy simulation is growing because of its ability to provide excellent delineation of target tissue and organs at risk. With the use of hypofractionated schemes in prostate cancer, urethral sparing is essential; however, visualization of the prostatic urethra can be challenging because of the presence of benign prostatic hyperplasia as well as respiratory motion artifacts. The goal of this study was to compare the utility of 2 motion-insensitive, T2-weighted MRI pulse sequences for urethra visualization in the setting of MRI-based simulation.Twenty-two patients undergoing MRI simulation without Foley catheters were imaged on a 3 Tesla MRI scanner between October 2018 and January 2019. Sagittal multislice data were acquired using (1) MultiVane XD radial sampling with parallel imaging acceleration (MVXD) and (2) single-shot fast-spin-echo (SSFSE) sequences with acquisition times of 2 to 3 minutes per sequence. For each examination, 2 genitourinary radiologists scored prostatic urethra visibility on a 1-to-5 scale and rated the signal-to-noise ratio and the presence of artifacts in each series.Urethral visibility was scored higher in the MVXD series than in the SSFSE series in 18 of 22 cases (Reader 1) and 17 of 22 cases (Reader 2). The differences in scores between MVXD and SSFSE were statistically significant for both readers (P .0001 for both, paired Student's t-test) and interobserver agreement was high (Cohen's kappa = 0.67). Both readers found the signal-to-noise ratio of the MVXD sequence to be superior in all cases. The MVXD sequence was found to generate more artifacts than the SSFSE sequence, but these tended to appear in the periphery and did not affect the ability to visualize the urethra.A radial T2-weighted multislice pulse sequence was superior to an SSFSE sequence for visualization of the urethra in the setting of magnetic resonance simulation for prostate cancer.

Pulmonary perfusion with dynamic contrast‐enhanced (DCE‐) MRI is typically assessed using a single‐input tracer kinetic model. Preliminary studies based on perfusion CT are indicating that dual‐input perfusion modeling of lung tumors may be clinically valuable as lung tumors have a dual blood supply from the pulmonary and aortic system. This study aimed to investigate the feasibility of fitting dual‐input tracer kinetic models to DCE‐MRI datasets of thoracic malignancies, including malignant pleural mesothelioma (MPM) and nonsmall cell lung cancer (NSCLC), by comparing them to single‐input (pulmonary or systemic arterial input) tracer kinetic models for the voxel‐level analysis within the tumor with respect to goodness‐of‐fit statistics. Fifteen patients (five MPM, ten NSCLC) underwent DCE‐MRI prior to radiotherapy. DCE‐MRI data were analyzed using five different single‐ or dual‐input tracer kinetic models: Tofts‐Kety (TK), extended TK (ETK), two compartment exchange (2CX), adiabatic approximation to the tissue homogeneity (AATH) and distributed parameter (DP) models. The pulmonary blood flow (BF), blood volume (BV), mean transit time (MTT), permeability‐surface area product (PS), fractional interstitial volume (v I), and volume transfer constant (K Trans) were calculated for both single‐ and dual‐input models. The pulmonary arterial flow fraction (γ), pulmonary arterial blood flow (BFPA) and systemic arterial blood flow (BFA) were additionally calculated for only dual‐input models. The competing models were ranked and their Akaike weights were calculated for each voxel according to corrected Akaike information criterion (cAIC). The optimal model was chosen based on the lowest cAIC value. In both types of tumors, all five dual‐input models yielded lower cAIC values than their corresponding single‐input models. The 2CX model was the best‐fitted model and most optimal in describing tracer kinetic behavior to assess microvascular properties in both MPM and NSCLC. The dual‐input 2CX‐model‐derived BFA was the most significant parameter in differentiating adenocarcinoma from squamous cell carcinoma histology for NSCLC patients.

Purpose To evaluate clinical utility of respiratory‐correlated (RC) four‐dimensional magnetic resonance imaging (4DMRI) for lung tumor delineation and motion assessment, in comparison with the current clinical standard of 4D computed tomography (4DCT). Methods and Materials A prospective T2‐weighted (T2w) RC‐4DMRI technique was applied to acquire coronal 4DMRI images for 14 lung cancer patients (16 lesions) during free breathing (FB) under an IRB‐approved protocol, together with a breath‐hold (BH) T1w 3DMRI and axial 4DMRI. Clinical simulation CT and 4DCT were acquired within 2 h. An internal navigator was applied to trigger amplitude‐binned 4DMRI acquisition whereas a bellows or real‐time position management (RPM) was used in the 4DCT reconstruction. Six radiation oncologists manually delineated the gross and internal tumor volumes (GTV and ITV) in 399 3D images using programmed clinical workflows under a tumor delineation guideline. The ITV was the union of GTVs within the breathing cycle without margin. Average GTV and motion range were assessed and ITV variation between 4DMRI and 4DCT was evaluated using the Dice similarity index, mean distance agreement (MDA), and volume difference. Results The mean tumor volume is similar between 4DCT (GTV4DCT = 1.0, as the reference) and T2w‐4DMRI (GTVT2wMR = 0.97), but smaller in T1w MRI (GTVT1wMR = 0.76), suggesting possible peripheral edema around the tumor. Average GTV variation within the breathing cycle (22%) in 4DMRI is slightly greater than 4DCT (17%). GTV motion variation (−4 to 12 mm) and ITV variation (∆VITV=−25 to 95%) between 4DCT and 4DMRI are large, confirmed by relatively low ITV similarity (Dice = 0.72 ± 0.11) and large MDA = 2.9 ± 1.5 mm. Conclusion Average GTVs are similar between T2w‐4DMRI and 4DCT, but smaller by 25% in T1w BH MRI. Physician training and breathing coaching may be necessary to reduce ITV variability between 4DMRI and 4DCT. Four‐dimensional magnetic resonance imaging is a promising and viable technique for clinical lung tumor delineation and motion assessment.

Purpose To determine the impact of using fiducial match for daily image‐guidance on pelvic lymph node (PLN) coverage for prostate cancer patients receiving stereotactic body radiation therapy (SBRT). Methods Thirty patients underwent SBRT treatment to the prostate and PLN from 2014 to 2016. Each patient received either 800cGy × 5 or 500cGy × 5 to the prostate and 500cGy × 5 to the PLN. A 5 mm clinical target volume (CTV)‐to‐planning target volume (PTV) margin around the PLN was used for planning. Two registrations with planning computed tomography (PCT) for each of the daily cone beam CTs (CBCTs) were performed: a rigid registration to fiducials and to the bony anatomy. The average translational difference between fiducial and bony match as well as percentage of fractions with differences > 5mm were calculated. Changes in bladder and rectal volume as well as center‐of‐mass (COM) position from simulation parameters, and their correlation with translational difference were also evaluated. The dosimetric impact of the translational differences was calculated by shifting the plan isocenter. Results The average translational difference between fiducial and bony match was 0.06 ± 0.82, 2.1 ± 4.1, −2.8 ± 4.3, and 5.5 ± 4.2 mm for lateral, vertical, longitudinal, and vector directions. The average change in bladder and rectal volume from simulation was −67.2 ± 163.04 cc (−12 ± 52%) and −1.6 ± 18.75 (−2 ± 30%) cc. The average change in COM of bladder from the simulation position was 0.34 ± 2.49, 4.4 ± 8.1, and −3.9 ± 7.5 mm along the LR, AP, and SI directions. The corresponding COM change for the rectum was 0.17 ± 1.9, 1.34 ± 3.5, and −0.6 ± 5.2 mm. Conclusions The 5 mm margin covered ~75% of fractions receiving PLN irradiation with SBRT, daily CBCT and fiducial‐guided setup. The dosimetric impact on PLN coverage was significant in 19% of fractions or 25% of patients. A larger translational shift was due to variation in rectal volume and changes in COM position of the bladder and rectum. A consistent bladder positioning and/or rectum filling compared with presimulation volume were essential for adequate coverage of PLN in a hypofractionated treatment regime.

Background To evaluate inter-fractional variations in bladder and rectum during prostate stereotactic body radiation therapy (SBRT) and determine dosimetric and clinical consequences. Methods Eighty-five patients with 510 computed tomography (CT) images were analyzed. Median prescription dose was 40 Gy in 5 fractions. Patients were instructed to maintain a full bladder and empty rectum prior to simulation and each treatment. A single reviewer delineated organs at risk (OARs) on the simulation (Sim-CT) and Cone Beam CTs (CBCT) for analyses. Results Bladder and rectum volume reductions were observed throughout the course of SBRT, with largest mean reductions of 86.9 mL (19.0%) for bladder and 6.4 mL (8.7%) for rectum noted at fraction #5 compared to Sim-CT (P P P P = 0.28). The mean bladder trigone displacement was in the anterior direction (+ 4.02 ± 6.59 mm) with a corresponding decrease in mean trigone dose (− 3.6 ± 9.6%; P P P P = 0.04). No significant correlations were found between relative bladder volume changes, bladder trigone displacements, or rectum volume changes with rates of genitourinary or rectal toxicities. Conclusions Despite smaller than expected bladder and rectal volumes at the time of treatment compared to the planning scans, dosimetric impact was minimal and not predictive of detrimental clinical outcomes. These results cast doubt on the need for excessively strict bladder filling and rectal emptying protocols in the context of image guided prostate SBRT and prospective studies are needed to determine its necessity.

Purpose To evaluate two three‐dimensional (3D)/3D registration platforms, one two‐dimensional (2D)/3D registration method, and one 3D surface registration method (3DS). These three technologies are available to perform six‐dimensional (6D) registrations for image‐guided radiotherapy treatment. Methods Fiducial markers were asymmetrically placed on the surfaces of an anthropomorphic head phantom (n = 13) and a body phantom (n = 8), respectively. The point match (PM) solution to the six‐dimensional (6D) transformation between the two image sets [planning computed tomography (CT) and cone beam CT (CBCT)] was determined through least‐square fitting of the fiducial positions using singular value decomposition (SVD). The transformation result from SVD was verified and was used as the gold standard to evaluate the 6D accuracy of 3D/3D registration in Varian’s platform (3D3DV), 3D/3D and 2D/3D registration in the BrainLab ExacTrac system (3D3DE and 2D3D), as well as 3DS in the AlignRT system. Image registration accuracy from each method was quantitatively evaluated by root mean square of target registration error (rmsTRE) on fiducial markers and by isocenter registration error (IRE). The Wilcoxon signed‐rank test was utilized to compare the difference of each registration method with PM. A P

PURPOSE: Real-time tumor tracking through active correction by the multileaf collimator or treatment couch offers a promising strategy to mitigate delivery uncertainty due to intrafractional tumor motion. This study evaluated the performance of MLC and couch tracking using the prototype iTools Tracking system in TrueBeam Developer Mode and the application for abdominal cancer treatments. METHODS: Experiments were carried out using a phantom with embedded Calypso transponders and a motion simulation platform. Geometric evaluations were performed using a circular conformal field with sinusoidal traces and pancreatic tumor motion traces. Geometric tracking accuracy was retrospectively calculated by comparing the compensational MLC or couch motion extracted from machine log files to the target motion reconstructed from real-time MV and kV images. Dosimetric tracking accuracy was measured with radiochromic films using clinical abdominal VMAT plans and pancreatic tumor traces. RESULTS: Geometrically, the root-mean-square errors for MLC tracking were 0.5 mm and 1.8 mm parallel and perpendicular to leaf travel direction, respectively. Couch tracking on the other hand showed an average of 0.8 mm or less geometric error in all directions. Dosimetrically, both MLC and couch tracking reduced motion-induced local dose errors compared to no tracking. Evaluated with five pancreatic tumor motion traces, the average 2%/2mm global gamma pass rate of eight clinical abdominal VMAT plans was 67.4% (range: 26.4% – 92.7%) without tracking, which was improved to 86.0% (range: 67.9% – 95.6%) with MLC tracking, and 98.1% (range: 94.9% – 100.0%) with couch tracking. In sixteen out of forty deliveries with different plans and motion traces, MLC tracking did not achieve clinically acceptable dosimetric accuracy with 3%/3mm gamma pass rate below 95%. CONCLUSIONS: This study demonstrated the capability of MLC and couch tracking to reduce motion-induced dose errors in abdominal cases using a prototype tracking system. Clinically significant dose errors were observed with MLC tracking for certain plans which could be attributed to the inferior MLC tracking accuracy in the direction perpendicular to leaf travel, as well as the interplay between motion tracking and plan delivery for highly modulated plans. Couch tracking outperformed MLC tracking with consistently high dosimetric accuracy in all plans evaluated, indicating its clinical potential in the treatment of abdominal cancers.

Background and purpose: Magnetic resonance (MR) only radiation therapy for prostate treatment provides superior contrast for defining targets and organs-at-risk (OARs). This study aims to develop a deep learning model to leverage this advantage to automate the contouring process. Materials and methods: Six structures (bladder, rectum, urethra, penile bulb, rectal spacer, prostate and seminal vesicles) were contoured and reviewed by a radiation oncologist on axial T2-weighted MR image sets from 50 patients, which constituted expert delineations. The data was split into a 40/10 training and validation set to train a two-dimensional fully convolutional neural network, DeepLabV3+, using transfer learning. The T2-weighted image sets were pre-processed to 2D false color images to leverage pre-trained (from natural images) convolutional layers’ weights. Independent testing was performed on an additional 50 patient’s MR scans. Performance comparison was done against a U-Net deep learning method. Algorithms were evaluated using volumetric Dice similarity coefficient (VDSC) and surface Dice similarity coefficient (SDSC). Results: When comparing VDSC, DeepLabV3+ significantly outperformed U-Net for all structures except urethra (P

Purpose To design a convolutional recurrent neural network (CRNN) that calculates three-dimensional (3D) positions of lung tumors from continuously acquired cone beam computed tomography (CBCT) projections, and facilitates the sorting and reconstruction of 4D-CBCT images. Method Under an IRB-approved clinical lung protocol, kilovoltage (kV) projections of the setup CBCT were collected in free-breathing. Concurrently, an electromagnetic signal-guided system recorded motion traces of three transponders implanted in or near the tumor. Convolutional recurrent neural network was designed to utilize a convolutional neural network (CNN) for extracting relevant features of the kV projections around the tumor, followed by a recurrent neural network for analyzing the temporal patterns of the moving features. Convolutional recurrent neural network was trained on the simultaneously collected kV projections and motion traces, subsequently utilized to calculate motion traces solely based on the continuous feed of kV projections. To enhance performance, CRNN was also facilitated by frequent calibrations (e.g., at 10° gantry rotation intervals) derived from cross-correlation-based registrations between kV projections and templates created from the planning 4DCT. Convolutional recurrent neural network was validated on a leave-one-out strategy using data from 11 lung patients, including 5500 kV images. The root-mean-square error between the CRNN and motion traces was calculated to evaluate the localization accuracy. Result Three-dimensional displacement around the simulation position shown in the Calypso traces was 3.4 ± 1.7 mm. Using motion traces as ground truth, the 3D localization error of CRNN with calibrations was 1.3 ± 1.4 mm. CRNN had a success rate of 86 ± 8% in determining whether the motion was within a 3D displacement window of 2 mm. The latency was 20 ms when CRNN ran on a high-performance computer cluster. Conclusions CRNN is able to provide accurate localization of lung tumors with aid from frequent recalibrations using the conventional cross-correlation-based registration approach, and has the potential to remove reliance on the implanted fiducials.

Purpose To investigate the potential of an atlas‐based approach in generation of synthetic CT for pelvis anatomy. Methods Twenty‐three matched pairs of computed tomography (CT) and magnetic resonance imaging (MRI) scans were selected from a pool of prostate cancer patients. All MR scans were preprocessed to reduce scanner‐ and patient‐induced intensity inhomogeneities and to standardize their intensity histograms. Ten (training dataset) of 23 pairs were then utilized to construct the coregistered CT‐MR atlas. The synthetic CT for a new patient is generated by appropriately weighting the deformed atlas of CT‐MR onto the new patient MRI. The training dataset was used as an atlas to generate the synthetic CT for the rest of the patients (test dataset). The mean absolute error (MAE) between the deformed planning CT and synthetic CT was computed over the entire CT image, bone, fat, and muscle tissues. The original treatment plans were also recomputed on the new synthetic CTs and dose–volume histogram metrics were compared. The results were compared with a commercially available synthetic CT Software (MRCAT) that is routinely used in our clinic. Results MAE errors (±SD) between the deformed planning CT and our proposed synthetic CTs in the test dataset were 47 ± 5, 116 ± 12, 36 ± 6, and 47 ± 5 HU for the entire image, bone, fat, and muscle tissues respectively. The MAEs were 65 ± 5, 172 ± 9, 43 ± 7, and 42 ± 4 HU for the corresponding tissues in MRCAT CT. The dosimetric comparison showed consistent results for all plans using our synthetic CT, deformed planning CT and MRCAT CT. Conclusion We investigated the potential of a multiatlas approach to generate synthetic CT images for the pelvis. Our results demonstrate excellent results in terms of HU value assignment compared to the original CT and dosimetric consistency.

Purpose Localizing lung tumors during treatment delivery is critical for managing respiratory motion, ensuring tumor coverage, and reducing toxicities. The purpose of this project is to develop a real-time system that performs markerless tracking of lung tumors using simultaneously acquired MV and kV images during radiotherapy of lung cancer with volumetric modulated arc therapy. Method Continuous MV/kV images were simultaneously acquired during dose delivery. In the subsequent analysis, a gantry angle-specific region of interest was defined according to the treatment aperture. After removing imaging artifacts, processed MV/kV images were directly registered to the corresponding daily setup cone-beam CT (CBCT) projections that served as reference images. The registration objective function consisted of a sum of normalized cross-correlation, weighted by the contrast-to-noise ratio of each MV and kV image. The calculated 3D shifts of the tumor were corrected by the displacements between the CBCT projections and the planning respiratory correlated CT (RCCT) to generate motion traces referred to a specific respiratory phase. The accuracy of the algorithm was evaluated on both anthropomorphic phantom and patient studies. The phantom consisted of localizing a 3D printed tumor, embedded in a thorax phantom, in an arc delivery. In an IRB-approved study, data were obtained from VMAT treatments of two lung cancer patients with three electromagnetic (Calypso) beacon transponders implanted in airways near the lung tumor. Result In the phantom study, the root mean square error (RMSE) between the registered and actual (programmed couch movement) target position was 1.2 mm measured by the MV/kV imaging system, which was smaller compared to the MV or kV alone, of 4.1 and 1.3 mm, respectively. In the patient study, the mean and standard deviation discrepancy between electromagnetic-based tumor position and the MV/KV-markerless approach was -0.2 ± 0.6 mm, 0.2 ± 1.0 mm, and -1.2 ± 1.5 mm along the superior-inferior, anterior-posterior, and left-right directions, respectively; resulting in a 3D displacement discrepancy of 2.0 ± 1.1 mm. Poor contrast around the tumor was the main contribution to registration uncertainties. Conclusion The combined MV/kV imaging system can provide real-time 3D localization of lung tumor, with comparable accuracy to the electromagnetic-based system when features of tumors are detectable. Careful design of a registration algorithm and a VMAT plan that maximizes the tumor visibility are key elements for a successful MV/KV localization strategy.

Purpose To compare single-shot echo-planar (SS-EPI)-based and turbo spin-echo (SS-TSE)-based diffusion-weighted imaging (DWI) in Non-Small Cell Lung Cancer (NSCLC) patients and to characterize the distributions of apparent diffusion coefficient (ADC) values generated by the two techniques. Methods Ten NSCLC patients were enrolled in a prospective IRB-approved study to compare and optimize DWI using EPI and TSE-based techniques for radiotherapy planning. The imaging protocol included axial T2w, EPI-based DWI and TSE-based DWI on a 3 T Philips scanner. Both EPI-based and TSE-based DWI sequences used three b values (0, 400, and 800 s/mm2 ). The acquisition times for EPI-based and TSE-based DWI were 5 and 8 min, respectively. DW-MR images were manually coregistered with axial T2w images, and tumor volume contoured on T2w images were mapped onto the DWI scans. A pixel-by-pixel fit of tumor ADC was calculated based on monoexponential signal behavior. Tumor ADC mean, standard deviation, kurtosis, and skewness were calculated and compared between EPI and TSE-based DWI. Image distortion and ADC values between the two techniques were also quantified using fieldmap analysis and a NIST traceable ice-water diffusion phantom, respectively. Results The mean ADC for EPI and TSE-based DWI were 1.282 ± 0.42 × 10-3 and 1.211 ± 0.31 × 10-3 mm2 /s. The average skewness and kurtosis were 0.14 ± 0.4 and 2.43 ± 0.40 for DWI-EPI and -0.06 ± 0.69 and 2.89 ± 0.62 for DWI-TSE. Fieldmap analysis showed a mean distortion of 13.72 ± 8.12 mm for GTV for DWI-EPI and 0.61 ± 0.4 mm for DWI-TSE. ADC values obtained using the diffusion phantom for the two techniques were within 0.03 × 10-3 mm2 /s with respect to each other as well as the established values. Conclusions Diffusion-weighted turbo spin-echo shows better geometrical accuracy compared to DWI-EPI. Mean ADC values were similar with both acquisitions but the shape of the histograms was different based on the skewness and kurtosis values. The impact of differences in respiratory technique on ADC values requires further investigation.

Purpose To correlate semiquantitative parameters derived from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) for non-small cell lung cancer (NSCLC). Methods and Materials Twenty-four NSCLC patients who underwent pretreatment 18F-FDG-PET and DCE-MRI were analyzed. The maximum standardized uptake value (SUVmax) was measured from 18F-FDG-PET. Dynamic contrast-enhanced MRI was obtained on a 3T MRI scanner using 4-dimensional T1-weighted high-resolution imaging with a volume excitation sequence. The DCE-MRI parameters, consisting of mean, median, standard deviation (SD), and median absolute deviation (MAD) of peak enhancement, time to peak (TTP), time to half peak (TTHP), wash-in slope (WIS), wash-out slope (WOS), initial gradient, wash-out gradient, signal enhancement ratio, and initial area under the relative signal enhancement curve taken up to 30, 60, 90, 120, 150, and 180 seconds, TTP, and TTHP (IAUCtthp), were calculated for each lesion. Univariate analysis (UVA) was performed using Spearman correlation. A linear regression model to predict SUVmax from DCE-MRI parameters was developed by multivariate analysis (MVA) using least absolute shrinkage selection operator in combination with leave-one-out cross-validation (LOOCV). Results In UVA, mean(WOS) (ρ = −0.456, P = .025), mean(IAUCtthp) (ρ = −0.439, P = .032), median(IAUCtthp) (ρ = −0.543, P = .006), and MAD(IAUCtthp) (ρ = −0.557, P = .005) were statistically significant; all these parameters were negatively correlated with SUVmax. In MVA, a linear combination of SD(WIS), SD(TTP), MAD(TTHP), and MAD(IAUCtthp) was statistically significant for predicting SUVmax (LOOCV-based adjusted R2 = 0.298, P = .0006). A decrease in SD(WIS), MAD(TTHP), and MAD(IAUCtthp) and an increase in SD(TTP) were associated with a significant increase in SUVmax. Conclusion An association was found between SUVmax, the SD, and MAD of DCE-MRI metrics derived during contrast uptake in NSCLC, reflecting that intratumoral heterogeneity in wash-in contrast kinetics is associated with tumor metabolism. Although MAD(IAUCtthp) was a significant feature in both UVA and MVA, the LASSO-based multivariate regression model yielded better predictability of SUVmax than a univariate regression model using MAD(IAUCtthp). This study will facilitate understanding of the complex relationship between tumor vascularization and metabolism and eventually help in guiding targeted therapy.

Background To determine if reduced dose delivery uncertainty is associated with daily image-guidance (IG) and Prostate Specific Antigen Relapse Free Survival (PRFS) in intensity-modulated radiotherapy (IMRT) of high-risk prostate cancer (PCa). Methods Planning data for consecutive PCa patients treated with IMRT (n = 67) and IG-IMRT (n = 35) was retrieved. Using computer simulations of setup errors, we estimated the patient-specific uncertainty in accumulated treatment dose distributions for the prostate and for posterolateral aspects of the gland that are at highest risk for extra-capsular disease. Multivariate Cox regression for PRFS considering Gleason score, T-stage, pre-treatment PSA, number of elevated clinical risk factors (T2c+, GS7+ and PSA10+), nomogram-predicted risk of extra-capsular disease (ECD), and dose metrics was performed. Results For IMRT vs. IG-IMRT, plan dosimetry values were similar, but simulations revealed uncertainty in delivered dose external to the prostate was significantly different, due to positioning uncertainties. A patient-specific interaction term of the risk of ECD and risk of low dose to the ECD (p = 0.005), and the number of elevated clinical risk factors (p = 0.008), correlate with reduced PRFS. Conclusions Improvements in PSA outcomes for high-risk PCa using IG-IMRT vs. IMRT without IG may be due to improved dosimetry for ECD. Electronic supplementary material The online version of this article (10.1186/s13014-018-0978-1) contains supplementary material, which is available to authorized users.

Background and Purpose This study summarizes the cranial stereotactic radiosurgery (SRS) volumetric modulated arc therapy (VMAT) procedure at our institution. Materials and Methods Volumetric modulated arc therapy plans were generated for 40 patients with 188 lesions (range 2–8, median 5) in Eclipse and treated on a TrueBeam STx. Limitations of the custom beam model outside the central 2.5 mm leaves necessitated more than one isocenter pending the spatial distribution of lesions. Two to nine arcs were used per isocenter. Conformity index (CI), gradient index (GI) and target dose heterogeneity index (HI) were determined for each lesion. Dose to critical structures and treatment times are reported. Results Lesion size ranged 0.05–17.74 cm3 (median 0.77 cm3), and total tumor volume per case ranged 1.09–26.95 cm3 (median 7.11 cm3). For each lesion, HI ranged 1.2–1.5 (median 1.3), CI ranged 1.0–2.9 (median 1.2), and GI ranged 2.5–8.4 (median 4.4). By correlating GI to PTV volume a predicted GI = 4/PTV0.2 was determined and implemented in a script in Eclipse and used for plan evaluation. Brain volume receiving 7 Gy (V 7 Gy) ranged 10–136 cm3 (median 42 cm3). Total treatment time ranged 24–138 min (median 61 min). Conclusions Volumetric modulated arc therapy provide plans with steep dose gradients around the targets and low dose to critical structures, and VMAT treatment is delivered in a shorter time than conventional methods using one isocenter per lesion. To further improve VMAT planning for multiple cranial metastases, better tools to shorten planning time are needed. The most significant improvement would come from better dose modeling in Eclipse, possibly by allowing for customizing the dynamic leaf gap (DLG) for a special SRS model and not limit to one DLG per energy per treatment machine and thereby remove the limitation on the Y‐jaw and allow planning with a single isocenter.

For positioning a moving target, a maximum intensity projection (MIP) or average intensity projection (AIP) image derived from 4DCT is often used as the reference image which is matched to free breathing cone-beam CT (FBCBCT) before treatment. This method can be highly accurate if the respiratory motion of the patient is stable. However, a patient’s breathing pattern is often irregular. The purpose of this study is to investigate the effects of irregular respiration on positioning accuracy for a moving target aligned with FBCBCT. Nine patients’ respiratory motion curves were selected to drive a Quasar motion phantom with one embedded cubic and two spherical targets. A 4DCT of the phantom was acquired on a CT scanner (Philips Brilliance 16) equipped with a Varian RPM system. The phase binned 4DCT images and the corresponding MIP and AIP images were transferred into Eclipse for analysis. FBCBCTs of the phantom driven by the same respiratory curves were also acquired on a Varian TrueBeam and fused such that both CBCT and MIP/AIP images share the same target zero positions. The sphere and cube volumes and centroid differences (alignment error) determined by MIP, AIP and FBCBCT images were calculated, respectively. Compared to the volume determined by MIP, the volumes of the cube, large sphere, and small sphere in AIP and FBCBCT images were smaller. The alignment errors for the cube, large sphere and small sphere with center to center matches between MIP and FBCBCT were 2.5 ± 1.8 mm, 2.4 ± 2.1 mm, and 3.8 ± 2.8 mm, and the alignment errors between AIP and FBCBCT were 0.5 ± 1.1 mm, 0.3 ± 0.8 mm, and 1.8 ± 2.0 mm, respectively. AIP images appear to be superior reference images to MIP images. However, irregular respiratory pattern could compromise the positioning accuracy, especially for smaller targets.

Purpose To describe the details and experience of implementing a MR-only workflow in the clinic for simulation and planning of prostate cancer patients. Methods Forty-eight prostate cancer patients from June 2016 - Dec 2016 receiving external beam radiotherapy were scheduled to undergo MR-only simulation. MR images were acquired for contouring (T2w axial, coronal, sagittal), synthetic-CT generation (3D FFE-based) and fiducial identification (3D bFFE-based). The total acquisition time was 25 min. Syn-CT was generated at the console using commercial software called MRCAT. As part of acceptance testing of the MRCAT package, external laser positioning system QA (< 2 mm) and geometric fidelity QA (< 2 mm within 50 cm LR and 30 cm AP) were performed and baseline values were set. Our current combined CT + MR simulation process was modified to accommodate a MRCAT-based MR-only simulation workflow. An automated step-by-step process using a MIM™ workflow was created for contouring on the MR images. Patient setup for treatment was achieved by matching the MRCAT DRRs with the orthogonal KV radiographs based on either fiducial ROIs or bones. 3-D CBCTs were acquired and compared with the MR/syn-CT to assess the rectum and bladder filling compared to simulation conditions. Results Forty-two patients successfully underwent MR-only simulation and met all of our institutional dosimetric objectives that were developed based on a CT + MR-based workflow. The remaining six patients either had a hip prosthesis or their large body size fell outside of the geometric fidelity QA criteria and thus they were not candidates for MR-only simulation. A total time saving of ~15 min was achieved with MR-based simulation as compared to CT + MR-based simulation. An automated and organized MIM workflow made contouring on MR much easier, quicker and more accurate compared with combined CT + MR images because the temporal variations in normal structure was minimal. 2D and 3D treatment setup localization based on bones/fiducials using a MRCAT reference image was successfully achieved for all cases. Conclusions MR-only simulation and planning with equivalent or superior target delineation, planning and treatment setup localization accuracy is feasible in a clinical setting. Future work will focus on implementing a robust 3D isotropic acquisition for contouring. Electronic supplementary material The online version of this article (doi:10.1186/s13014-017-0854-4) contains supplementary material, which is available to authorized users.

Purpose The growing use of magnetic resonance imaging (MRI) as a substitute for computed tomography-based treatment planning requires the development of effective algorithms to generate electron density maps for treatment planning and patient setup verification. The purpose of this work was to develop a method to synthesize computerized tomography (CT) for MR-only radiotherapy of head and neck cancer patients. Methods The algorithm is based on registration of multiple patient datasets containing both MRI and CT images (a “multi-atlas” algorithm). Twelve matched pairs of good quality CT and MRI scans (those without apparent motion and blurring artifacts) were selected from a pool of head and neck cancer patients to form the atlas. All atlas MRI scans were pre-processed to reduce scanner- and patient-induced intensity inhomogeneities and to standardize their intensity histograms. Atlas CT and MRIs were co-registered using a novel bone-to-air replacement technique applied to the CT scans that improves the similarity between CTs and MRIs and facilitates the registration process. For each new patient, all atlas MRIs are deformed initially onto the new patients’ MRI. We introduce a generalized registration error (GRE) metric that automatically measures the goodness of local registration between MRI pairs. The final synthetic CT value at each point is a nonlinear GRE-weighted average of the atlas CTs. For evaluation, the leave-one-out technique was used for synthetic CT generation and the mean absolute error (MAE) between the original and synthetic CT was computed over the entire CT image. The impact of our proposed CT-MR registration scheme on the accuracy of the final synthetic CT was also studied. The original treatment plans were also recomputed on the new synthetic CTs and dose-volume histogram metrics were compared. In addition, the two-dimensional (2D) gamma analysis at 1%/1mm and 2%/2 mm dose difference/distance to agreement was also performed to study the dose distribution at the isocenter. Results MAE error (± standard deviation) between the original and the synthetic CTs was 64 ± 10, 113 ± 12, and 130 ± 28 Hounsfield Unit (HU) for the entire image, air, and bone regions, respectively. Our results showed that our proposed bone-suppression based CT-MR fusion and GRE-weighted strategy could lower the overall MAE error between the original and synthetic CTs by ~69% and ~34%, respectively. Dose re-calculation comparison showed highly consistent results between plans based on the synthetic vs. the original CTs. The 2D gamma analysis revealed the pass rate of 95.44 ± 2.5 and 99.36 ± 0.71 for 1%/1mm and 2%/2 mm criteria, respectively. Due to local registration weighting, the method is robust with respect to MRI imaging artifacts. Conclusion We developed a novel image analysis technique to synthesize CT for head and neck anatomy. Novel methods were introduced to accurately register atlas CTs and MRIs as well as to weight the final electron density maps using local registration goodness estimates. The resulting accuracy is clinically acceptable, at least for these atlas patients. This article is protected by copyright. All rights reserved.

Purpose To compare the image quality of amplitude-binned 4-dimensional magnetic resonance imaging (4DMRI) reconstructed using 2 concurrent respiratory (navigator and bellows) waveforms. Methods and Materials A prospective, respiratory-correlated 4DMRI scanning program was used to acquire T2-weighted single-breath 4DMRI images with internal navigator and external bellows. After a 10-second training waveform of a surrogate signal, 2-dimensional MRI acquisition was triggered at a level (bin) and anatomic location (slice) until the bin-slice table was completed for 4DMRI reconstruction. The bellows signal was always collected, even when the navigator trigger was used, to retrospectively reconstruct a bellows-rebinned 4DMRI. Ten volunteers participated in this institutional review board–approved 4DMRI study. Four scans were acquired for each subject, including coronal and sagittal scans triggered by either navigator or bellows, and 6 4DMRI images (navigator-triggered, bellows-rebinned, and bellows-triggered) were reconstructed. The simultaneously acquired waveforms and resulting 4DMRI quality were compared using signal correlation, bin/phase shift, and binning motion artifacts. The consecutive bellows-triggered 4DMRI scan was used for indirect comparison. Results Correlation coefficients between the navigator and bellows signals were found to be patient-specific and inhalation-/exhalation-dependent, ranging from 0.1 to 0.9 because of breathing irregularities (>50% scans) and commonly observed bin/phase shifts (−1.1 ± 0.6 bin) in both 1-dimensional waveforms and diaphragm motion extracted from 4D images. Navigator-triggered 4DMRI contained many fewer binning motion artifacts at the diaphragm than did the bellows-rebinned and bellows-triggered 4DMRI scans. Coronal scans were faster than sagittal scans because of the fewer slices and higher achievable acceleration factors. Conclusions Navigator-triggered 4DMRI contains substantially fewer binning motion artifacts than bellows-rebinned and bellows-triggered 4DMRI, primarily owing to the deviation of the external from the internal surrogate. The present study compared 2 concurrent surrogates during the same 4DMRI scan and their resulting 4DMRI quality. The navigator-triggered 4DMRI scanning protocol should be preferred to the bellows-based, especially for coronal scans, for clinical respiratory motion simulation.

Purpose We report on the clinical performance of a fully automated approach to treatment planning based on a Pareto optimal, constrained hierarchical optimization algorithm, named Expedited Constrained Hierarchical Optimization (ECHO). Methods and materials From April 2017 to October 2018, ECHO produced 640 treated plans for 523 patients who underwent stereotactic body radiation therapy (RT) for paraspinal and other metastatic tumors. A total of 182 plans were for 24 Gy in a single fraction, 387 plans were for 27 Gy in 3 fractions, and the remainder were for other prescriptions or fractionations. Of the plans, 84.5% were for paraspinal tumors, with 69, 302, and 170 in the cervical, thoracic, and lumbosacral spine, respectively. For each case, after contouring, a template plan using 9 intensity modulated RT fields based on disease site and tumor location was sent to ECHO through an application program interface plug-in from the treatment planning system. ECHO returned a plan that satisfied all critical structure hard constraints with optimal target volume coverage and the lowest achievable normal tissue doses. Upon ECHO completion, the planner received an e-mail indicating the plan was ready for review. The plan was accepted if all clinical criteria were met. Otherwise, a limited number of parameters could be adjusted for another ECHO run. Results The median planning target volume size was 84.3 cm3 (range, 6.9-633.2). The median time to produce 1 ECHO plan was 63.5 minutes (range, 11-340 minutes) and was largely dependent on the field sizes. Of the cases, 79.7% required 1 run to produce a clinically accepted plan, 13.3% required 1 additional run with minimal parameter adjustments, and 7.0% required ≥2 additional runs with significant parameter modifications. All plans met or bettered the institutional clinical criteria. Conclusions We successfully implemented automated stereotactic body RT paraspinal and other metastatic tumors planning. ECHO produced high-quality plans, improved planning efficiency and robustness, and enabled expedited treatment planning at our clinic.

Purpose To develop and implement a fully automated approach to intensity modulated radiation therapy (IMRT) treatment planning. Method The optimization algorithm is developed based on a hierarchical constrained optimization technique and is referred internally at our institution as expedited constrained hierarchical optimization (ECHO). Beamlet contributions to regions-of-interest are precomputed and captured in the influence matrix. Planning goals are of two classes: hard constraints that are strictly enforced from the first step (e.g., maximum dose to spinal cord), and desirable goals that are sequentially introduced in three constrained optimization problems (better planning target volume (PTV) coverage, lower organ at risk (OAR) doses, and smoother fluence map). After solving the optimization problems using external commercial optimization engines, the optimal fluence map is imported into an FDA-approved treatment planning system (TPS) for leaf sequencing and accurate full dose calculation. The dose-discrepancy between the optimization and TPS dose calculation is then calculated and incorporated into optimization by a novel dose correction loop technique using Lagrange multipliers. The correction loop incorporates the leaf sequencing and scattering effects into optimization to improve the plan quality and reduce the calculation time. The resultant optimal fluence map is again imported into TPS for leaf sequencing and final dose calculation for plan evaluation and delivery. The workflow is automated using application program interface (API) scripting, requiring user interaction solely to prepare the contours and beam arrangement prior to launching the ECHO plug-in from the TPS. For each site, parameters and objective functions are chosen to represent clinical priorities. The first site chosen for clinical implementation was metastatic paraspinal lesions treated with stereotactic body radiotherapy (SBRT). As a first step, 75 ECHO paraspinal plans were generated retrospectively and compared with clinically treated plans generated by planners using VMAT (volumetric modulated arc therapy) with 4 to 6 partial arcs. Subsequently, clinical deployment began in April, 2017. Results In retrospective study, ECHO plans were found to be dosimetrically superior with respect to tumor coverage, plan conformity, and OAR sparing. For example, the average PTV D95%, cord and esophagus max doses, and Paddick Conformity Index were improved, respectively, by 1%, 6%, 14%, and 15%, at a negligible 3% cost of the average skin D10cc dose. Conclusion Hierarchical constrained optimization is a powerful and flexible tool for automated IMRT treatment planning. The dosimetric correction step accurately accounts for detailed dosimetric multileaf collimator and scattering effects. The system produces high-quality, Pareto optimal plans and avoids the time-consuming trial-and-error planning process.

Purpose To develop an Eclipse plug‐in (MLC_MODIFIER) that automatically modifies control points to expose fiducials obscured by MLC during VMAT, thereby facilitating tracking using periodic MV/kV imaging. Method Three‐dimensional fiducial tracking was performed during VMAT by pairing short‐arc (3°) MV digital tomosynthesis (DTS) images to triggered kV images. To evaluate MLC_MODIFIER efficacy, two cohorts of patients were considered. For first 12 patients, plans were manually edited to expose one fiducial marker. Next for 15 patients, plans were modified using MLC_MODIFIER script. MLC_MODIFIER evaluated MLC apertures at appropriate angles for marker visibility. Angles subtended by control points were compressed and low‐dose “imaging” control points were inserted and exposed one marker with 1 cm margin. Patient's images were retrospectively reviewed to determine rate of MV registration failures. Failure categories were poor DTS image quality, MLC blockage of fiducials, or unknown reasons. Dosimetric differences in rectum, bladder, and urethra D1 cc, PTV maximum dose, and PTV dose homogeneity (PTV HI) were evaluated. Statistical significance was evaluated using Fisher's exact and Student's t test. Result Overall MV registration failures, failures due to poor image quality, MLC blockage, and unknown reasons were 33% versus 8.9% (P

Large nodal masses shrink during head-and-neck radiation treatment. If the shrinkage is dramatic, nearby organs at risk (OARs) may receive potentially harmful radiation dose. In an institutional IRB-approved protocol, patients were monitored with weekly T2-weighted MRIs. Gross tumor volumes (GTV) from pre-treatment MRI were propagated to weekly MRIs via deformable image registrations (DIR) for tracking the change of GTV nodal volume and detection of significant shrinkage. This detection method, however, becomes problematic when a significant amount of the nodal mass dissolves during treatment, invalidating the assumption of correspondence between images for accurate deformable registration. We presented a novel method using image saliency to detect whether a involved nodal volume becomes significantly small during the treatment. We adapted a multi-resolution pyramid method and introduced symmetry in calculating image saliency of MRI images. The ratio of mean saliency value (RSal) from the propagated nodal volume on a weekly image to the mean saliency value of the pre-treatment nodal volume was calculated to assess whether the nodal volume shrank significantly. We evaluated our method using 94 MRI scans from 19 patients enrolled in the protocol. We achieved AUC of 0.97 in detection of significant shrinkage (smaller than 30% of the original volume) and the optimal RSal is 0.698.

Purpose We investigated the sources of variability in radiation therapy treatment plan output between planners within a single institution. Methods and materials Forty treatment planners across 5 campuses of an institution created a plan on the same thoracic esophagus patient computed tomography scan and structure set. Plans were scored and ranked based on the planner's adherence to an ordered list of target dose coverage and normal tissue evaluation criteria. A runs test was used to identify whether any of the studied planner qualities influenced the ranking. Spearman rank correlation was used to investigate whether plan score correlated with years of experience or planned monitor units. Results The distribution of scores, ranging from 80.24 to 135.89, was negatively skewed (mean, 128.7; median, 131.5). No statistically significant relationship between plan score and campus ( P = .193), job title ( P = .174), previous outside experience ( P = .611), or number of gantry angles ( P = .156) was discovered. No statistical correlation between plan score and monitor unit or years of experience was found. Conclusions Despite clear and established critical organ dose criteria and well-documented planning guidelines, planning variation still occurs, even among members of the same institution. Because plan consistency does not seem to significantly correlate with experience, career path, or campus, investigation into alternate methods beyond additional education and training to reduce this variation, such as knowledge-based planning or advanced optimization techniques, is necessary.

Background and purpose We investigate whether knowledge based planning (KBP) can identify systematic variations in intensity modulated radiotherapy (IMRT) plans between multiple campuses of a single institution. Material and methods A KBP model was constructed from 58 prior main campus (MC) esophagus IMRT radiotherapy plans and then applied to 172 previous patient plans across MC and 4 regional sites (RS). The KBP model predicts DVH bands for each organ at risk which were compared to the previously planned DVHs for that patient. Results RS1's plans were the least similar to the model with less heart and stomach sparing, and more variation in liver dose, compared to MC. RS2 produced plans most similar to those expected from the model. RS3 plans displayed more variability from the model prediction but overall, the DVHs were no worse than those of MC. RS4 did not present any statistically significant results due to the small sample size ( n =11). Conclusions KBP can retrospectively highlight subtle differences in planning practices, even between campuses of the same institution. This information can be used to identify areas needing increased consistency in planning output and subsequently improve consistency and quality of care.

Purpose: Robust detection of implanted fiducials is essential for monitoring intrafractional motion during hypofractionated treatment. The authors developed a plan optimization strategy to ensure clear visibility of implanted fiducials and facilitate 3D localization during volumetric modulated arc therapy (VMAT). Methods: Periodic kilovoltage (kV) images were acquired at 20° gantry intervals and paired with simultaneously acquired 4.4° short arc megavoltage digital tomosynthesis (MV-DTS) to localize three fiducials during VMAT delivery for hypofractionated prostate cancer treatment. Beginning with the original optimized plan, control point segments where fiducials were consistently blocked by multileaf collimator(MLC) within each 4.4° MV-DTS interval were first identified. For each segment, MLC apertures were edited to expose the fiducial that led to the least increase in the cost function. Subsequently, MLC apertures of all control points not involved with fiducial visualization were reoptimized to compensate for plan quality losses and match the original dose–volume histogram. MV dose for each MV-DTS was also kept above 0.4 MU to ensure acceptable image quality. Different imaging (gantry) intervals and visibility margins around fiducials were also evaluated. Results: Fiducials were consistently blocked by the MLC for, on average, 36% of the imagingcontrol points for five hypofractionated prostate VMAT plans but properly exposed after reoptimization. Reoptimization resulted in negligible dosimetric differences compared with original plans and outperformed simple aperture editing: on average, PTV D98 recovered from 87% to 94% of prescription, and PTV dose homogeneity improved from 9% to 7%. Without violating plan objectives and compromising delivery efficiency, the highest imaging frequency and largest margin that can be achieved are a 10° gantry interval, and 15 mm, respectively. Conclusions: VMAT plans can be made to accommodate MV-kV imaging of fiducials. Fiducial visualization rate and workflow efficiency are significantly improved with an automatic modification and reoptimization approach.

The purpose of this study was to evaluate the accuracy and clinical feasibility of a motion monitoring method employing simultaneously acquired MV and kV images during volumetric‐modulated arc therapy (VMAT). Short‐arc digital tomosynthesis (SA‐DTS) is used to improve the quality of the MV images that are then combined with orthogonally acquired kV images to assess 3D motion. An anthropomorphic phantom with implanted gold seeds was used to assess accuracy of the method under static, typical prostatic, and respiratory motion scenarios. Automatic registration of kV images and single MV frames or MV SA‐DTS reconstructed with arc lengths from 2° to 7° with the appropriate reference fiducial template images was performed using special purpose‐built software. Clinical feasibility was evaluated by retrospectively analyzing images acquired over four or five sessions for each of three patients undergoing hypofractionated prostate radiotherapy. The standard deviation of the registration error in phantom using MV SA‐DTS was similar to single MV images for the static and prostate motion scenarios (σ=0.25 mm). Under respiratory motion conditions, the standard deviation of the registration error increased to 0.7 mm and 1.7 mm for single MV and MV SA‐DTS, respectively. Registration failures were observed with the respiratory scenario only and were due to motion‐induced fiducial blurring. For the three patients studied, the mean and standard deviation of the difference between automatic registration using 4° MV SA‐DTS and manual registration using single MV images results was 0.07±0.52 mm. The MV SA‐DTS results in patients were, on average, superior to single‐frame MV by nearly 1 mm — significantly more than what was observed in phantom. The best MV SA‐DTS results were observed with arc lengths of 3° to 4°. Registration failures in patients using MV SA‐DTS were primarily due to blockage of the gold seeds by the MLC. The failure rate varied from 2% to 16%. Combined MV SA‐DTS and kV imaging is feasible for intratreatment motion monitoring during VMAT of anatomic sites where limited motion is expected, and improves registration accuracy compared to single MV/kV frames. To create a clinically robust technique, further improvements to ensure visualization of fiducials at the desired control points without degradation of the treatment plan are needed. PACS number(s): 87.55.km, 87.55.N‐

Hypofractionated treatments generally increase the complexity of a treatment plan due to the more stringent constraints of normal tissues and target coverage. As a result, treatment plans contain more modulated MLC motions that may require extra efforts for accurate dose calculation. This study explores methods to minimize the differences between in‐house dose calculation and actual delivery of hypofractionated volumetric‐modulated arc therapy (VMAT), by focusing on arc approximation and tongue‐and‐groove (TG) modeling. For dose calculation, the continuous delivery arc is typically approximated by a series of static beams with an angular spacing of 2°. This causes significant error when there is large MLC movement from one beam to the next. While increasing the number of beams will minimize the dose error, calculation time will increase significantly. We propose a solution by inserting two additional apertures at each of the beam angle for dose calculation. These additional apertures were interpolated at two‐thirds’ degree before and after each beam. Effectively, there were a total of three MLC apertures at each beam angle, and the weighted average fluence from the three apertures was used for calculation. Because the number of beams was kept the same, calculation time was only increased by about 6%‐8%. For a lung plan, areas of high local dose differences (>4%) between film measurement and calculation with one aperture were significantly reduced in calculation with three apertures. Ion chamber measurement also showed similar results, where improvements were seen with calculations using additional apertures. Dose calculation accuracy was further improved for TG modeling by developing a sampling method for beam fluence matrix. Single element point sampling for fluence transmitted through MLC was used for our fluence matrix with 1 mm resolution. For Varian HDMLC, grid alignment can cause fluence sampling error. To correct this, transmission volume averaging was applied. For three paraspinal HDMLC cases, the average dose difference was greatly reduced in film and calculation comparisons with our new approach. The gamma (3%, 3 mm) pass rates have improved significantly from 74.1%, 90.0%, and 90.4% to 99.2%, 97.9%, and 97.3% for three cases, for calculation without volume averaging and calculation with volume averaging, respectively. Our results indicate that more accurate MLC leaf position and transmission sampling can improve accuracy and agreement between calculation and measurement, and are particularly important for hypofractionated VMAT that consists of large MLC movement. PACS number(s): 87.55.kd

External beam radiotherapy for prostate cancer is in a period of rapid change and evolution as treatment paradigms shift toward hypofractionated regimens. Technological advances including image guided radiotherapy, volume modulated arc therapy and the use of magnetic resonance imaging for planning, treatment delivery and response assessment have made the move to hypofractionation possible. In this chapter, the treatment planning process applicable to hypofractionated, stereotactic radiotherapy for prostate cancer using a conventional linear accelerator is described with an emphasis on the increasing role of magnetic resonance imaging in simulation and planning. A simulation workflow using MR imaging only is presented and compared with one based on multi-modality imaging (CT and MRI). An overview of volume modulated arc therapy planning is provided with examples for extreme hypofractionation and simultaneous boost treatment of intra-prostatic disease. Further developments of MR-based planning methods to target dominant intra-prostatic lesions, perform on-line adaptive therapy and MR-guided radiotherapy delivery are discussed.

PURPOSE Manual delineation of head and neck (H&N) organ-at-risk (OAR) structures for radiation therapy planning is time consuming and highly variable. Therefore, we developed a dynamic multiatlas selection-based approach for fast and reproducible segmentation. METHODS Our approach dynamically selects and weights the appropriate number of atlases for weighted label fusion and generates segmentations and consensus maps indicating voxel-wise agreement between different atlases. Atlases were selected for a target as those exceeding an alignment weight called dynamic atlas attention index. Alignment weights were computed at the image level and called global weighted voting (GWV) or at the structure level and called structure weighted voting (SWV) by using a normalized metric computed as the sum of squared distances of computed tomography (CT)-radiodensity and modality-independent neighborhood descriptors (extracting edge information). Performance comparisons were performed using 77 H&N CT images from an internal Memorial Sloan-Kettering Cancer Center dataset (N = 45) and an external dataset (N = 32) using Dice similarity coefficient (DSC), Hausdorff distance (HD), 95th percentile of HD, median of maximum surface distance, and volume ratio error against expert delineation. Pairwise DSC accuracy comparisons of proposed (GWV, SWV) vs single best atlas (BA) or majority voting (MV) methods were performed using Wilcoxon rank-sum tests. RESULTS Both SWV and GWV methods produced significantly better segmentation accuracy than BA (P

Purpose: Patients with cancers of oropharynx have a favorable prognosis and are an ideal candidate for adaptive therapy. A replan to improve coverage or escalate/de-escalate dose based on morphological information alone may not be adequate as the grossly involved lymph nodes (LNs) of a subset of these patients tend to become cystic and often do not regress. Functional adaptation may be a better approach when considering replanning for these patients. The purpose of this study was to evaluate the weekly trends in treatment related morphological and physiological changes for these LNs using diffusion-weighted MRI (DW-MRI) and evaluate its implications for adaptive replanning. Methods: Ten patients with histologically proven oropharynx HNSCC undergoing concurrent chemoradiation were analyzed in this study. MR imaging protocol included axial T1w, T2w, and DW-MRI using a 3 T Philips MR scanner. The patients were scanned weekly in radiation treatment planning position using a 16 element phased-array anterior coil and a 44 element posterior coil. A total of 65 DWI and T2w scans were analyzed. DWI was performed using an optimized single-shot echo planar imaging sequence (TR/TE = 5000/65 ms, slice thickness = 5 mm; slices = 28; b values = 0 and 800 s/mm2). Quantification of the DW-MRI images was performed by calculating the apparent diffusion coefficient (ADC). T2w and DWI scans were imported into the Eclipse treatment planning system and gross tumor volumes (GTVs) corresponding to grossly involved LNs were contoured on each axial slice by physician experts. An attempt was made to remove any cystic or necrotic components so that the ADC analysis was of viable tumor only. A pixel-by-pixel fit of signal intensities within the GTVs was performed assuming monoexponential behavior. From each GTV histogram mean, median, standard deviation, skewness, and kurtosis were calculated. Absolute and percent change in weekly ADC histogram parameters and percent change in T2w GTV were also calculated. Results: For all nodes, an immediate change in ADC was observed during first 2–3 weeks after which ADC values either continued to increase or plateaued. A few nodal volumes had a slightly decreased ADC value during later weeks. Percent increase in median ADC from weeks 1 to 6 with respect to baseline was 14%, 25%, 41%, 42%, 45%, and 58%. The corresponding change in median T2 volumes was 8%, 10%, 16%, 22%, 40%, and 42%, respectively. The ADC distribution of the viable tumors was initially highly kurtotic; however, the kurtosis decreased as treatment progressed. The ADC distribution also showed a higher degree of skewness in the first 2 weeks, progressively becoming less skewed as treatment progressed so as to slowly approach a more symmetric distribution. Conclusions: Physiological changes in LNs represented by changes in ADC evaluated using DW-MRI are evident sooner than the morphological changes calculated from T2w MRI. The decisions for adaptive replanning may need to be individualized and should be based primarily on tumor functional information. The authors’ data also suggest that for many patients, week 3 maybe the optimal time to intervene and replan. Larger studies are needed to confirm their findings.

Data visualization technique was applied to analyze the daily QA results of photon and electron beams. Special attention was paid to any trend the beams might display. A Varian Trilogy Linac equipped with dual photon energies and five electron energies was commissioned in early 2010. Daily Linac QA tests including the output constancy, beam flatness and symmetry (radial and transverse directions) were performed with an ionization chamber array device (QA Beam Checker Plus, Standard Imaging). The data of five years were collected and analyzed. For each energy, the measured data were exported and processed for visual trending using an in-house Matlab program. These daily data were cross-correlated with the monthly QA and annual QA results, as well as the preventive maintenance records. Majority of the output were within 1% of variation, with a consistent positive/upward drift for all seven energies (~+0.25% per month). The baseline of daily device is reset annually right after the TG-51 calibration. This results in a sudden drop of the output. On the other hand, the large amount of data using the same baseline exhibits a sinusoidal behavior (period = 12 months; amplitude = 0.8%, 0.5% for photons, electrons, respectively) on symmetry and flatness when normalization of baselines is accounted for. The well known phenomenon of new Linac output drift was clearly displayed. This output drift was a result of the air leakage of the over-pressurized sealed monitor chambers for the specific vendor. Data visualization is a new trend in the era of big data in radiation oncology research. It allows the data to be displayed visually and therefore more intuitive. Based on the visual display from the past, the physicist might predict the trend of the Linac and take actions proactively. It also makes comparisons, alerts failures, and potentially identifies causalities.

PURPOSE: To investigate whether building a knowledge based planning (KBP) model with prostate bed plans constructed from constrained hierarchical optimization (CHO) would result in more efficient model construction with more consistent output than a model built using plans from a traditional, trial-and-error based optimization (TEO) technique. METHODS: Three KBP models were constructed from plans from subsets of fifty-eight post-prostatectomy patients treated with intensity modulated radiation therapy. TEO(54) was built from fifty-four TEO plans, selected to represent typical clinical variations in target and organ-at-risk sizes and shapes. CHO(30) and TEO(30) were built from the same thirty patients populated with CHO and TEO plans, respectively. The three models were each applied to a new set of eighteen patient scans and dose-volume histogram estimates (DVHEs) were generated for rectal and bladder walls and compared for each patient. RESULTS: CHO(30) resulted in a significantly tighter range in DVHEs (p < 0.01) for both the rectal and bladder walls compared with either of the TEO models, indicating less uncertainty in the dose estimation. Plans resulting from KBP optimization using each model were very similar. CONCLUSION: Populating a KBP model with CHO data resulted in a high quality model. Since CHO plans can be generated automatically offline in a process that necessitates little to no user interaction, a CHO-KBP model can quickly adapt to changes in plan evaluation criteria or planning techniques without the need to wait to accrue sufficient numbers of clinical TEO plans. This may facilitate the use of KBP approaches for initial or ongoing quality assurance procedures and plan quality audits.