Image-guided Radiotherapy Research Articles

Patient Selection is Critical When Evaluating Candidates for 5-Fraction Stereotactic MRI-Guided Adaptive Radiotherapy (SMART) for Locally Advanced Pancreatic Cancer

Stereotactic magnetic resonance image-guided adaptive radiotherapy (SMART) allows for the safe delivery of biologically effective doses (BED10 ∼ 100 Gy) to patients with pancreatic cancer who otherwise have limited therapeutic avenues. In this study, we analyze long-term outcomes in the largest cohort of patients with borderline-resectable (BR), locally advanced (LA), or medically inoperable (MI) pancreatic cancer treated with a 5-fraction SMART technique. A single institution analysis of patients with BR, LA, or MI pancreatic cancer treated with SMART between 2015 and 2021 was performed. Patients with locally recurrent disease, non-adenocarcinoma histology, de-novo metastatic disease, or who did not receive induction chemotherapy were excluded. Baseline and treatment characteristics were collected. Local control (LC), progression free survival (PFS), and overall survival (OS) were calculated using the Kaplan-Meier method, and factors associated with outcomes were evaluated using Cox regression analyses. Oncologic outcomes measured from time of initial diagnosis; local control defined as freedom from local progression. A total of 129 patients were reviewed. Median age at diagnosis was 67 years. The majority were male (60%) and White (84%). 23% of patients had an ECOG 2. Most patients had LA disease (66%), followed by BR (20%) and MI (14%). Median follow up was 17.0 months (6-61 months). Median LC was not reached, and LC was 81%, 54%, and 48% at 1, 2, and 3-years, respectively. Median PFS was 12.9 months [95% confidence interval 11.8-14.71] with 1, 2, and 3-year PFS of 60%, 20%, and 7%, respectively. Median OS was 17.7 months [15.7-19.7] with 1, 2, and 3-year OS of 78%, 28%, 11%, respectively. On univariate analysis, increased duration of induction chemotherapy had a statistically significant impact on PFS and OS. Those receiving equal to or greater than 4 months of induction chemotherapy had a median OS of 19.2 months [17.2-21.2] as compared to 13.6 [11.9-15.3] for those with less than 4 months. In this patient population which included a large portion of patients with ECOG of 2 or greater and those deemed MI, a 5-fraction SMART regimen yielded durable long-term LC. The impact of increasing duration of induction chemotherapy underlies the importance of patient selection and improved understanding of tumor-specific biology when selecting patient's with locally advanced pancreatic cancer for aggressive local therapy.

The Feasibility of Dose-Escalated Radiation Therapy for Glioblastoma Using Biological Image Guided Adaptive Radiotherapy (BIGART)

Radiotherapy dose escalation (DE) for glioblastoma (GBM) has been an area of active research. We aimed to study the imaging changes within residual gross tumor volumes (GTV) through the course of concurrent chemo-radiotherapy (CCRT) using multiparametric magnetic resonance imaging (mpMRI). Diffusion, perfusion and chemical exchange saturation transfer (CEST) characteristics of the tumor and its microenvironment were investigated to identify a GTV subvolume potentially associated with radio resistance. We used biological image-guided adaptive radiotherapy (BIGART) to study the feasibility of DE to this GTV subvolume using either photon or proton beam therapy (PBT). We prospectively identified GBM patients with >5cc residual tumor post-resection who were candidates for radical CCRT (60 Gy in 30 daily fractions over 6-weeks with concurrent temozolomide 75mg/m2 daily). We observed the imaging changes with serial mpMRI scans done at baseline, after 2, 4 and 6-weeks of CCRT. Regions of interest (ROIs) within the GTV associated with the following abnormal values at week 2 were identified: apparent diffusion coefficient (ADC): 750-1000 ×10-6 mm2/s; relative cerebral blood volume (rCBV): 1.75-6; and APT-w CEST signal intensity >1.79%. The overlap regions of these ROIs were defined as a novel biological target volume (BTV), identifying the potential area of maximal radioresistance. An in silico study was performed using a technology company's treatment planning system to evaluate the feasibility of planning adaptive treatment to the BTV to total dose of 75 Gy in 30 fractions. This is given in two phases: 30 Gy/15# to the whole PTV as per standard practice, followed by a simultaneous integrated boost (SIB) of 45 Gy/15 fractions while maintaining the dose to the rest of the of the PTV to 60 Gy. Either photons or PBT were used to keep doses to organs at risk (OARs) within standard clinical tolerances. Nine patients were recruited for this analysis and a total of 27 mpMRI scans were studied. Median BTVs to GTVs ratio was 35% (range 22-47%). Volumetric-modulated arc (VMAT) photon and PBT adaptive plans for dose escalation to BTVs were created in all cases whilst maintaining OAR tolerances. Both VMAT and PBT provided acceptable target coverage with average BTV-PTV D98% of 73 Gy (range 71.5-73.8 Gy) and average D2% of 76 Gy (range 75.4-77 Gy) while effectively sparing OARs. Sharper dose gradient between DE-BTV and PTV was achieved with VMAT. PBT was particularly advantageous in minimizing the low-dose spillage outside the BTV. We hereby propose a platform for adaptive radiotherapy to GBM tumors with biological-image guidance through the utilization of mpMRI to evaluate the tumor and its microenvironment during CCRT. We identified thresholds for tumor sub volumes showing the most resistant imaging features and created precise BTVs that allowed for dose escalation. PBT represents an additional useful tool for BIGART planning that will be investigated further in our ongoing work.

Enhanced Peroxide Fluxes and Radiosensitization in Colorectal Tumors but Not Normal Enterocytes from the Combination of Superoxide Dismutase Mimetics and Pharmacological Ascorbate

Selective superoxide dismutase mimetics (DMs), including GC4419 and GC4711, are radiation (RT) modulators which induce opposite effects in tumors and normal tissues and may be ideally suited for locally advanced rectal cancer. However, their tumor radiosensitization effect is limited at RT doses relevant to rectal cancer (2-5 Gy). Over this dose range, they protect normal mucosal tissues, but we and others have shown they do not reliably enhance tumor radiosensitization at doses < 8-15 Gy. We hypothesize that combining DMs and other therapies which also target redox metabolism may effectively sensitize tumors to clinically relevant RT doses for rectal cancer while maintaining their normal tissue sparing effects. Like DMs, pharmacological ascorbate (P-AscH) selectively increases lethal hydrogen peroxide (H2O2) fluxes in tumors, but it does so through distinct mechanisms which are potentially complimentary with DMs (particularly at low RT doses). Human HCT116, SW480, and HT29 colorectal tumor models and non-malignant FHs74 intestinal epithelial cells were used. Clonogenic survival was assessed following single-fraction RT (2-5 Gy) +/- P-AscH (5 pmol/cell) +/- GC4711 (20 µM). Dependency on H202 fluxes was tested by adding bovine catalase with drug and RT treatments. Oxygen consumption in culture media was measured using a Clark electrode. Rectal toxicity was assessed in vivo using IHC in fixed rectal tissues following fractionated, image-guided rectal RT (5-9 Gy x 3). Tumor growth delay was assessed following RT (5 Gy x 3) +/- P-AscH (4 g/kg) +/- GC4419 (10 mg/kg) in animals with unilateral HCT116 flank tumors. Combination therapy with P-AscH and GC4711 potently radiosensitized all tumor lines in vitro whereas neither agent significantly decreased clonogenic survival as a monotherapy. Neither drug nor combination treatment sensitized FHs74 epithelial cells. P-AscH increased oxygen consumption and H2O2 production in culture media and the addition of GC4711 significantly increased both more than P-AscH alone. Co-treatment with exogenous catalase inhibited cancer cell killing with combination therapy +/- RT. In vivo, combination therapy significantly enhanced tumor growth delay and survival. Both agents significantly decreased markers of acute rectal RT injury as monotherapies. Co-treatment with DMs and P-AscH selectively enhanced tumor radiosensitization by increasing oxygen consumption and H202 fluxes even in tumor models which are known to be resistant to oxidative stressors (HT29). In contrast, each agent conferred a radioprotective effect in the rectum. Combination therapy with DMs and P-AscH may represent a novel, potent approach to target dysregulated redox metabolism in colorectal tumors.

Rapid Unpaired CBCT-Based Synthetic CT for CBCT-Guided Adaptive Radiotherapy

Quantitative cone beam CT (CBCT) is the foundation for image-guided radiation therapy, improving treatment setup, tumor delineation and dose calculation. However, CBCT images suffer from severe artifacts, limiting clinical utility. Deep learning can overcome these limitations, boosting radiographic and dosimetric quality critical for online adaptive radiotherapy (ART). We hypothesize adapted contrastive unpaired translation (CUT), a recent method for image-to-image translation of photographic images, can improve CBCT quality while reducing compute time, demonstrating utility for ART. Same-day CBCT and quality assurance CT (QACT) images acquired from 79 patients receiving proton therapy for prostate cancer between 2019 and 2020 at a single institution were retrospectively collected. QACT images were acquired for quality assurance in accordance with institutional policy. Seventy-nine patients yielded 102 non-contrast CBCT-QACT image sets. Each QACT image was rigidly registered to the corresponding CBCT and resampled to 1 × 1 × 2 mm to establish uniform voxel size and spacing. CBCT images were randomly shuffled prior to input to the CUT model for unsupervised training and QACT-quality synthetic CT images were generated as outputs. We compared mean absolute error (MAE), structural similarity index measure (SSIM), and Fréchet inception distance (FID) against same-day QACT. MAE, SSIM, and FID were compared for the CycleGAN and CUT data relative to input QACT and are reported as the mean across five-fold cross-validation ± standard error. CUT achieved superior performance in MAE (19.5 ± 3.9 HU vs. cycleGAN 47.1 ± 25.4) and FID (31.5 ± 6.6 vs cycleGAN 75.9 ± 41.3). MAE indicates pixel-level correspondence to QACT HU intensity values, making the synthetic outputs of CUT useful for dose calculations during ART. FID further demonstrates perceptual visual similarity. SSIM for CycleGAN (0.7 ± 0.2) and CUT (0.8 ± 0.0) were similar, indicating acceptable reproducibility of global structure. CUT was faster and lighter than CycleGAN. CycleGAN contained a total of 28,286,000 parameters; CUT contained 14,703,000, approximately half that of CycleGAN. As a result, CycleGAN computes on a single CT image slice over 0.33s while CUT requires just 0.18s. The contrastive method investigated here was demonstrated to be faster and more accurate than CycleGAN, requiring fewer networks and parameters to achieve superior performance. We demonstrated anatomic boundary preservation and HU fidelity superior to cycleGAN while significantly reducing compute time. We plan to investigate the use of these synthetic CT images in automated segmentation prior to exploration of CUT in a prospective setting.

ARTIA-Bladder: Daily Online Adaptive Short-Course Radiation Therapy (RT) and Concurrent Chemotherapy for Muscle-Invasive Bladder Cancer (MIBC): A Prospective Trial of an Individualized Approach for Reducing Bowel and Bladder Toxicity

Concurrent chemo-radiotherapy is commonly prescribed for muscle-invasive bladder cancer (MIBC). Post hoc analysis of two large, randomized trials found that hypofractionation improves loco-regional control (LRC) vs. standard fractionation in this population. A challenge in traditional image-guided radiotherapy of the bladder is that daily changes in bladder position and size requires large margins to ensure target coverage. This makes it difficult to spare uninvolved bladder from high-dose treatment, increases the risk of bowel toxicity, and results in historical rates of acute G3+ toxicity exceeding 20-30%. Daily online adaptive RT (ART) may enable reduced, personalized margins that maintain target coverage while reducing dose to OARs. This prospective clinical trial will test whether: 1) participants undergoing ART for MIBC have a lower rate of acute G3+ GI/GU toxicity compared with the 31% historical control rate (Stage III BC2001 trial), and 2) 2-year LRC with ART will be non-inferior to historical controls (75%). This multi-national trial will enroll 165 adult subjects with stage cT2-T4aN0M0 urothelial MIBC. Subjects will have undergone an attempt at maximal transurethral resection of bladder tumor. Patients with clinically involved nodes or G2+ GI or G3+ GU symptoms/conditions at baseline are ineligible. Concurrent with chemotherapy, participants will receive (at the discretion of the investigator) either 55 Gy in 20 fx to whole-bladder or 46 Gy in 20 fx to whole-bladder plus simultaneous in-field boost of 55 Gy in 20 fx to tumor bed. A personalized ITV will be derived for each subject based on bladder expansion, as assessed on two CT simulations separated by 30 min. Daily ART will be attempted for all subjects. The primary endpoint is acute G3+ GI/GU toxicity. Secondary endpoints are LRC; quality of life (EORTC QLQ-BLM30, EPIC 26 bowel and urinary); global function (EQ-5D-5L ); 2-year disease-free, bladder intact event-free, and overall survival; 2-year bladder cancer-specific mortality; NTCP model of acute GI toxicity for hypofractionated bladder RT; workflow feasibility of ART; improved target coverage ± reduced dose to critical OARs vs. non-ART dosimetry; acute G3+ GI/GU toxicity rate in subjects with ≥75% of their treatments as ART; and acute G3+ GI/GU toxicity in the cohort treated with partial bladder boost. Exploratory translational and correlative endpoints will also be examined. This trial opened to enrollment on Feb 2, 2023; the study duration is expected to be 4-5 years. This prospective clinical trial will provide robust clinical data to inform healthcare providers' decisions on the use of daily online ART and hypofractionation as a bladder preservation strategy for this population.

Recent Advances and Adaptive Strategies in Image Guidance for Cervical Cancer Radiotherapy.

The standard of care for locally advanced cervical cancer is external beam radiotherapy (EBRT) with simultaneous chemotherapy followed by an internal radiation boost. New imaging methods such as positron-emission tomography and magnetic resonance imaging have been implemented into daily practice for better tumor delineation in radiotherapy planning. The method of delivering radiation has changed with technical advances in qualitative imaging and treatment delivery. Image-guided radiotherapy (IGRT) plays an important role in minimizing treatment toxicity of pelvic radiation and provides a superior conformality for sparing the organs at risk (OARs) such as bone marrow, bowel, rectum, and bladder. Similarly, three-dimensional image-guided adaptive brachytherapy (3D-IGABT) with computed tomography (CT) or magnetic resonance imaging (MRI) has been reported to improve target coverage and reduce the dose to normal tissues. Brachytherapy is a complementary part of radiotherapy treatment for cervical cancer and, over the past 20 years, 3D-image-based brachytherapy has rapidly evolved and established itself as the gold standard. With new techniques and adaptive treatment in cervical cancer, the concept of personalized medicine is introduced with an enhanced comprehension of the therapeutic index not only in terms of volume (three-dimensional) but during treatment too (four-dimensional). Current data show promising results with integrated IGRT and IGABT in clinical practice and, therefore, better local control and overall survival while reducing treatment-related morbidity. This review gives an overview of the substantial impact that occurred in the progress of image-guided adaptive external beam radiotherapy and brachytherapy.

Retracted: Research on Improving Radiotherapy Accuracy Based on Image-Guided Radiotherapy.

[This retracts the article DOI: 10.1155/2022/9696403.].

Feasibility of artificial intelligence-driven interfractional monitoring of organ changes by mega-voltage computed tomography in intensity-modulated radiotherapy of prostate cancer.

High-dose radiotherapy (RT) for localized prostate cancer requires careful consideration of target position changes and adjacent organs-at-risk (OARs), such as the rectum and bladder. Therefore, daily monitoring of target position and OAR changes is crucial in minimizing interfractional dosimetric uncertainties. For efficient monitoring of the internal condition of patients, we assessed the feasibility of an auto-segmentation of OARs on the daily acquired images, such as megavoltage computed tomography (MVCT), via a commercial artificial intelligence (AI)-based solution in this study. We collected MVCT images weekly during the entire course of RT for 100 prostate cancer patients treated with the helical TomoTherapy system. Based on the manually contoured body outline, the bladder including prostate area, and rectal balloon regions for the 100 MVCT images, we trained the commercially available fully convolutional (FC)-DenseNet model and tested its auto-contouring performance. Based on the optimally determined hyperparameters, the FC-DenseNet model successfully auto-contoured all regions of interest showing high dice similarity coefficient (DSC) over 0.8 and a small mean surface distance (MSD) within 1.43 mm in reference to the manually contoured data. With this well-trained AI model, we have efficiently monitored the patient's internal condition through six MVCT scans, analyzing DSC, MSD, centroid, and volume differences. We have verified the feasibility of utilizing a commercial AI-based model for auto-segmentation with low-quality daily MVCT images. In the future, we will establish a fast and accurate auto-segmentation and internal organ monitoring system for efficiently determining the time for adaptive replanning.

Split-filter dual energy computed tomography radiotherapy: From calibration to image guidance

Background and purposeDual-energy computed tomography (DECT) is an emerging technology in radiotherapy (RT). Here, we investigate split-filter DECT throughout the RT treatment chain as compared to single-energy CT (SECT). Materials and methodsDECT scans were acquired with a tin-gold split-filter at 140 kV resulting in a low- and high-energy CT reconstruction (recon). Ten cancer patients (four head-and-neck (HN)​, three rectum​, two anal/pelvisand one abdomen) were DECT scanned without and with iodine administered. A cylindrical and an anthropomorphic HN phantom were scanned with DECT and 120 kV SECT. The DECT images generated were: 120 kV SECT-equivalent (CTmix), virtual monoenergetic images (VMIs), iodine map, virtual non-contrast (VNC), effective atomic number (Zeff), and relative electron density (ρe,w). The clinical utility of these recons was investigated for calibration, delineation, dose calculation and image-guided RT (IGRT). ResultsA calibration curve for 75 keV VMI had a root-mean-square-error (RMSE) of 34 HU in closest agreement with the RSME of SECT calibration. This correlated with a phantom-based dosimetric agreement to SECT of γ1%1mm > 98%. A 40 keV VMI recon was most promising to improve tumor delineation accuracy with an average evaluation score of 1.6 corresponding to “partial improvement”. The dosimetric impact of iodine was in general < 2%. For this setup, VNC vs. non-contrast CTmix based dose calculations are considered equivalent. SECT- and DECT-based IGRT was in agreement within the setup uncertainty. ConclusionsDECT-based RT could be a feasible alternative to SECT providing additional recons to support the different steps of the RT workflow.

Technical note: Preprocessing of portal images to improve image quality of VMAT-CT.

The concept of volumetric modulated arc therapy-computed tomography (VMAT-CT) was proposed more than a decade ago. However, its application has been very limited mainly due to the poor image quality. More specifically, the blurred areas in electronic portal imaging device (EPID) images collected during VMAT heavily degrade the image quality of VMAT-CT. The goal of this study was to propose systematic methods to preprocess EPID images and improve the image quality of VMAT-CT. Online region-based active contour method was introduced to binarize portal images. Multi-leaf collimator (MLC) motion modeling was developed to remove the MLC motion blur. Outlier filtering was then applied to replace the remaining artifacts with plausible data. To assess the impact of these preprocessing methods on the image quality of VMAT-CT, 44 clinical VMAT plans for several treatment sites (lung, esophagus, and head & neck) were delivered to a Rando phantom, and several real-patient cases were also acquired. VMAT-CT reconstruction was attempted for all the cases, and image quality was evaluated. All three preprocessing methods could effectively remove the blurred edges of EPID images. The combined preprocessing methods not only saved VMAT-CT from distortions and artifacts, but also increased the percentage of VMAT plans that can be reconstructed. The systematic preprocessing of portal images improves the image quality of VMAT-CT significantly, and facilitates the application of VMAT-CT as an effective image guidance tool.

Development and Quality Assurance of Multileaf Collimator (MLC) Auto-Feathering Junctions for Multi-Isocenter Supine Volumetric Modulated Arc Therapy (VMAT) Craniospinal Axis Irradiation on Halcyon.

Currently, there is alack of methods and tools that efficiently evaluate the auto-feathering junctions created by multileaf collimator (MLCs) for supine volumetric modulated arc therapy (VMAT) craniospinalirradiation (CSI) plans. We have investigated the feasibility of stitching together multi-isocenter fluence maps to then analyze the feathered junctions for patient-specific quality assurance (QA). Furthermore, we investigated the capability of Halcyon for the treatment of CSI patients.Three patients, who previously underwent VMAT CSI treatment on TrueBeam (6-MV flattening filter-free (FFF)) for 36 Gy in 20 fractionswerereplanned for Halcyon. A multi-isocenter approach with only translational superior-inferior shifts was used for both platforms. Each isocenter consists of two full arcs with anterior avoidance sectors, ±5° collimator rotations between arcs, and 5-8 cm of overlapping MLC auto-feathering junctions. All plans were QA'd via electronicportalimaging device (EPID) portal dosimetry and analyzed with a gamma criteria of 3%/3 mm. A variety of plan quality metrics were analyzed to evaluate dose distributions to the target, doses to organs at risk (OARs), and integral dose to the patient. A MATLAB script was developed to stitch the calculated and measured fluence maps in order to perform patient-specific QA for the composite fluence.The Halcyon plans provided highly conformal and homogenous dose distributions to the entire CSI target, superior to the clinical TrueBeam plans, while sparing critical organs with significantly lower values of V10Gy and V18Gy by up to 2% and 2.5%, respectively.Qualitative depictions of vertical dose profiles from the stitched DICOM of the entire CSI target for both planned and delivered fluence maps demonstrated equivalency, with slightly lower average pass rates with Halcyon (97%) compared to TrueBeam(99.9%). This approach to stitch multiple measured versus calculated EPID fluence maps has shown to be a feasible and accurate method and will be helpful for comprehensive VMAT CSI QA on both platforms. Further implementation of this script will be used in examining dosimetric impacts of daily patient positioning errors at MLC auto-feathering junctions.

Clinical experiences with online adaptive radiotherapy of vulvar carcinoma

Background and purpose Radiotherapy for vulvar carcinoma is challenging due to relatively high risk of locoregional disease recurrence, a technically challenging target, and postoperative lymphocele, and a high risk radiation sequelae. We aim to explore, if it is possible to reduce dose to normal tissue, while maintaining CTV coverage for this patient group with online adaptive radiotherapy. Materials and methods 20 patients with vulvar carcinoma (527 fractions) were treated with online adaptation on a Varian Ethos accelerator. Setup CBCTs were acquired daily for adaptive planning. Verification CBCTs were acquired immediately prior to dose delivery. CTV dose coverage and dose to bladder and rectum were extracted from the scheduled and adapted plans as well as from adapted plans recalculated based on verification CBCTs. In addition, analysis of the decision of the adaptive procedure was performed for 17 patients (465 fractions). Results Mean CTV D95% and standard deviation was 98% ± 5% for the scheduled plan compared to 100.0 ± 0.3% and 100.0 ± 0.8% for the adapted plan on the setup and verification CBCT respectively. Dose to OARs varied substantially and did not show any benefit from adaption itself, however a margin reduction was implemented after the first patients treated. The adapted plan was chosen for 63.5% of the fractions and dominant reasons for not adapting were ‘no significant dosimetric gain’ (75 fractions, 14%) and ‘Medical doctor (MD) not available for treatment’ (50 fractions, 9.5%). The median adaption time was 15 min and the 25th and 75th percentile was 12 and 17 min, respectively. Conclusion CTVs and PTVs dose coverage were significantly improved with adaptation compared to image-guided RT. This gain was robust during the treatment time.

Image-guided superficial radiation therapy has superior 2-year recurrence probability to Mohs micrographic surgery

IntroductionNon-melanoma skin cancers (NMSCs) are the most common cancers in the USA, and their incidence is rising. Mohs micrographic surgery (MMS) is commonly performed to excise NMSCs. MMS replaced superficial radiotherapy (SRT) as a first line treatment, given its superior efficacy. Image-guided superficial radiation therapy (IGSRT) was invented to improve the precision of SRT. This study investigates how the 2-year recurrence probability of IGSRT-treated NMSCs compares to that of MMS-treated lesions. MethodsThis retrospective cohort study compared the 2-year recurrence probability of early stage NMSCs (squamous and basal cell carcinomas (SCCs and BCCs)) treated by IGSRT (2,286 lesions) to data on NMSCs treated by MMS (5,391 lesions) via one sample proportion tests. Medical Subject Headings were used to search PubMed for reports of 2-year recurrence probability rates of NMSCs treated by MMS. Seventeen studies were screened; 14 studies were excluded for lack of 2-year time to event analysis, or irrelevant patient population (non-BCC/SCC study, advanced disease), leaving 3 studies for comparison. ResultsIGSRT-treated NMSCs have a statistically significantly improved 2-year recurrence probability than those treated by MMS, P < 0.001 for pooled data. ConclusionThe 2-year recurrence probability IGSRT-treated NMSCs is superior to MMS-treated and supports IGSRT as an effective treatment option for individuals with early stage NMSCs.

Investigation of uncertainty in internal target volume definition for lung stereotactic body radiotherapy

This study evaluated the validity of internal target volumes (ITVs) defined by three- (3DCT) and four-dimensional computed tomography (4DCT), and subsequently compared them with actual movements during treatment. Five patients with upper lobe lung tumors were treated with stereotactic body radiotherapy (SBRT) at 48 Gy in four fractions. Planning 3DCT images were acquired with peak-exhale and peak-inhale breath-holds, and 4DCT images were acquired in the cine mode under free breathing. Cine images were acquired using an electronic portal imaging device during irradiation. Tumor coverage was evaluated based on the manner in which the peak-to-peak breathing amplitude on the planning CT covered the range of tumor motion (± 3 SD) during irradiation in the left–right, anteroposterior, and cranio-caudal (CC) directions. The mean tumor coverage of the 4DCT-based ITV was better than that of the 3DCT-based ITV in the CC direction. The internal margin should be considered when setting the irradiation field for 4DCT. The proposed 4DCT-based ITV can be used as an efficient approach in free-breathing SBRT for upper-lobe tumors of the lung because its coverage is superior to that of 3DCT.

Evaluation of a Scintillating Plastic Optical Fiber Device for Measuring kV-Cone Beam Computed Tomography Dose.

Justification of imaging procedures such as cone beam computed tomography (CBCT) in radiotherapy makes no doubt. However, the CBCT composite dose is rarely reported or optimized, even though the repeated CBCT cumulative dose can be up to 3% of the prescription dose. This study aimed to evaluate the performance and utility of a new plastic scintillating optical fiber dosimeter for CBCT dosimetric quality assurance (QA) applications before a potential application in patient composite CBCT dosimetry. The dosimeter, made of 1 mm diameter plastic fiber, was installed under a linear accelerator treatment table and linked to photodetectors. The fiber impact on the fluence and dose delivered was respectively assessed with an electronic portal imaging device (EPID) and EBT3 Gafchromic® film. The presence of artifacts was visually evaluated on kV images. The dosimeter performances were determined for various acquisition parameters by comparison with ionization chamber values. The maximum impact of the fiber on the fluence measured by the EPID was -1.2% for the 6 MV flattening filter-free beam. However, the fiber did not alter the film dose profile when measured for all the beams tested. The fiber was not visible at energies ≥ 80 kV and was merely visible on the CBCT images. When the rate of images per second or mA was changed, the maximum relative difference between the device and the ionization chamber CTDIs was <5%. Changing collimation led to a -7.2% maximum relative difference with an absolute dose difference that was insignificant (-0.3 mGy). Changing kV was associated with a -8.7% maximum relative difference, as published in the literature. The dosimeter may be a promising device for CBCT recurrent dosimetry quality control or dose optimization. According to these results, further developments are in progress in order to adapt the solution to the measurement of patient composite CBCT doses.

Analysis of Geometry Verification of X, Y, Z Correction Values with Megavoltage Computed Tomography Using Lower Extremity Positioning System in Prostate Cancer

The immobilization tool is used to minimize the movement caused while doing irradiation, one of the immobilization tools is the Lower Extremity Positioning System (LEPS) which is used to minimize movement in the Pelvis area. This research was conducted at Dr. Cipto Mangunkusumo Central General Hospital. The type of this research is analytics quantitative. This research used 15 samples with secondary data, which were selected based on inclusion and exclusion criteria’s. The secondary data will be analyzed namely the consistency between the Set-Up value (Couch Position before verification) and the MVCT (Couch Position after verification) value using the Non-Parametric Wilcoxon statistical test, and evaluating the shifting values of X, Y and Z with tolerance standards from AAPM TG-148 which is 2 mm. The results obtained are based on statistical analysis of the Set-Up value with the MVCT results obtained that there is no significant difference, and based on the overall substance, the total that exceeds the tolerance of X coordinates is 92 times with a percentage of 68%, from Y coordinates that is 80 times with a percentage of 59%, from the Z coordinate which is 51 times with a percentage of 38% there is a shift that exceeds tolerance. The conclusion is that the results of MVCT verification still occur that exceed the tolerance standard so that LEPS is still not effective in preventing shifts that occur during radiation therapy.

Dual-energy head cone-beam CT using a dual-layer flat-panel detector: Hybrid material decomposition and a feasibility study.

Flat panel detector (FPD) based cone-beam computed tomography (CT) has made tremendous progress in the last two decades, with many new and advanced medical and industrial applications keeping emerging from diagnostic imaging and image guidance for radiotherapy and interventional surgery. The current cone-beam CT (CBCT), however, is still suboptimal for head CT scan which requires a high standard of image quality. While the dual-layer FPD technology is under extensive development and is promising to further advance CBCT from qualitative anatomic imaging to quantitative dual-energy CT, its potential of enabling head CBCT applications has not yet been fullyinvestigated. The relatively moderate energy separation from the dual-layer FPD and the overall low signal level especially at the bottom-layer detector, could raise significant challenges in performing high-quality dual-energy material decomposition (MD). In this work, we propose a hybrid, physics and model guided, MD algorithm that attempts to fully use the detected x-ray signals and prior-knowledge behind head CBCT using dual-layer FPD. Firstly, a regular projection-domain MD is performed as initial results of our approach and for comparison as conventional method. Secondly, based on the combined projection, a dual-layer multi-material spectral correction (dMMSC) is applied to generate beam hardening free images. Thirdly, the dMMSC corrected projections are adopted as a physics-model based guidance to generate a hybrid MD. A set of physics experiments including fan-beam scan and cone-beam scan using a head phantom and a Gammex Multi-Energy CT phantom are conducted to validate our proposedapproach. The combined reconstruction could reduce noise by about 10% with no visible resolution degradation. The fan-beam studies on the Gammex phantom demonstrated an improved MD performance, with the averaged iodine quantification error for the 5-15 mg/ml iodine inserts reduced from about 5.6% to 3.0% by the hybrid method. On fan-beam scan of the head phantom, our proposed hybrid MD could significantly reduce the streak artifacts, with CT number nonuniformity (NU) in the selected regions of interest (ROIs) reduced from 23 Hounsfield Units (HU) to 4.2 HU, and the corresponding noise suppressed from 31 to 6.5 HU. For cone-beam scan, after scatter correction (SC) and cone-beam artifact reduction (CBAR), our approach can also significantly improve image quality, with CT number NU in the selected ROI reduced from 24.2 to 6.6 HU and the noise level suppressed from 22.1 to 8.2HU. Our proposed physics and model guided hybrid MD for dual-layer FPD based head CBCT can significantly improve the robustness of MD and suppress the low-signal artifact. This preliminary feasibility study also demonstrated that the dual-layer FPD is promising to enable head CBCT spectralimaging.

A quantitative CBCT pipeline based on 2D antiscatter grid and grid-based scatter sampling for image-guided radiation therapy.

Quantitative accuracy is critical for expanding the role of cone beam CT (CBCT) imaging from target localization to quantitative treatment monitoring and plan adaptations in radiation therapy. Despite advances in CBCT image quality improvement methods, quantitative accuracy gap between CBCT and multi-detector CT (MDCT) remains. In this work, a physics-driven approach was investigated that combined robust scatter rejection, raw data correction and iterative image reconstruction to further improve CBCT image quality and quantitative accuracy, referred to as quantitative CBCT (qCBCT). QCBCT approach includes tungsten 2D antiscatter grid hardware, residual scatter correction with grid-based scatter sampling, image lag, and beam hardening correction for offset detector geometry linac-mounted CBCT. Images were reconstructed with iterative image reconstruction to reduce image noise. qCBCT was evaluated using a variety of phantoms to investigate the effect of object size and its composition on image quality, and image quality was benchmarked against clinical CBCT and gold standard MDCT images used for treatment planning. QCBCT provided statistically significant improvement in CT number accuracy and reduced image artifacts when compared to clinical CBCT images. When compared to gold standard MDCT, mean HU errors in qCBCT and clinical CBCT were 17±9 and 38±29 HU, respectively. Magnitude of phantom size dependent HU variations were comparable between MDCT and qCBCT images. With iterative reconstruction, contrast-to-noise ratio improved by 25% when compared to clinical CBCT protocols. Combination of novel scatter suppression techniques and other data correction methods in qCBCT provided CT number accuracy comparable to gold standard MDCT used for treatment planning. This approach may potentially improve CBCT's promise in fulfilling the tasks that demand high quantitative accuracy, such as online dose calculations and treatment response assessment, in image guided radiation therapy.

Real-Time Motion Analysis With 4D Deep Learning for Ultrasound-Guided Radiotherapy.

Motion compensation in radiation therapy is a challenging scenario that requires estimating and forecasting motion of tissue structures to deliver the target dose. Ultrasound offers direct imaging of tissue in real-time and is considered for image guidance in radiation therapy. Recently, fast volumetric ultrasound has gained traction, but motion analysis with such high-dimensional data remains difficult. While deep learning could bring many advantages, such as fast data processing and high performance, it remains unclear how to process sequences of hundreds of image volumes efficiently and effectively. We present a 4D deep learning approach for real-time motion estimation and forecasting using long-term 4D ultrasound data. Using motion traces acquired during radiation therapy combined with various tissue types, our results demonstrate that long-term motion estimation can be performed markerless with a tracking error of 0.35±0.2 mm and with an inference time of less than 5 ms. Also, we demonstrate forecasting directly from the image data up to 900 ms into the future. Overall, our findings highlight that 4D deep learning is a promising approach for motion analysis during radiotherapy.

Endoscopically placed fiducial markers for image-guided radiotherapy in preoperative gastric cancer: Technical feasibility and potential benefit.

Background and study aims Fiducial markers have demonstrated clinical value in radiotherapy in several organs, but little is known about markers in the stomach. Here, we assess the technical feasibility of endoscopic placement of markers in gastric cancer patients and their potential benefit for image-guided radiotherapy (IGRT). Patients and methods In this prospective feasibility study, 14 gastric cancer patients underwent endoscopy-guided gold (all patients) and liquid (7 patients) marker placements distributed throughout the stomach. Technical feasibility, procedure duration, and potential complications were evaluated. Assessed benefit for IGRT comprised marker visibility on acquired imaging (3-4 computed tomography [CT] scans and 19-25 cone-beam CTs [CBCTs] per patient) and lack of migration. Marker visibility was compared per marker type and location (gastroesophageal junction (i.e., junction/cardia), corpus (corpus/antrum/fundus), and pylorus). Results Of the 93 marker implantation attempts, 59 were successful, i.e., marker in stomach wall and present during entire 5-week radiotherapy course (2-6 successfully placed markers per patient), with no significant difference (Fisher's exact test; P >0.05) in success rate between gold (39/66=59%) and liquid (20/27=74%). Average procedure duration was 24.4 min (range 16-38). No procedure-related complications were reported. All successfully placed markers were visible on all CTs, with 81% visible on ≥95% of CBCTs. Five markers were poorly visible (on <75% of CBCTs), possibly due to small marker volume and peristaltic motion since all five were liquid markers located in the corpus. No migration was observed. Conclusions Endoscopic placement of fiducial markers in the stomach is technically feasible and safe. Being well visible and positionally stable, markers provide a potential benefit for IGRT.