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We establish an open framework for developing plan optimization models for knowledge-based planning (KBP) in radiotherapy. Our framework includes reference plans for 100 patients with head-and-neck cancer and high-quality dose predictions from 19 KBP models that were developed by different research groups during the OpenKBP Grand Challenge. The dose predictions were input to four optimization models to form 76 unique KBP pipelines that generated 7600 plans. The predictions and plans were compared to the reference plans via: dose score, which is the average mean absolute voxel-by-voxel difference in dose a model achieved; the deviation in dose-volume histogram (DVH) criterion; and the frequency of clinical planning criteria satisfaction. We also performed a theoretical investigation to justify our dose mimicking models. The range in rank order correlation of the dose score between predictions and their KBP pipelines was 0.50 to 0.62, which indicates that the quality of the predictions is generally positively correlated with the quality of the plans. Additionally, compared to the input predictions, the KBP-generated plans performed significantly better (P, 19 pages, 7 tables, 6 figures

Background Adjuvant radiation therapy improves the overall survival and loco-regional control in patients with breast cancer. However, radiation-induced heart disease, which occurs after treatment from incidental radiation exposure to the cardiac organ, is an emerging challenge. This study aimed to generate synthetic contrast-enhanced computed tomography (SCECT) from non-contrast CT (NCT) using deep learning (DL) and investigate its role in contouring cardiac substructures. We also aimed to determine its applicability for a retrospective study on the substructure volume-dose relationship for predicting radiation-induced heart disease. Methods We prepared NCT-CECT cardiac scan pairs of 59 patients. Of these, 35, 4, and 20 pairs were used for training, validation, and testing, respectively. We adopted conditional generative adversarial network as a framework to generate SCECT. SCECT was validated in the following three stages: (1) The similarity between SCECT and CECT was evaluated; (2) Manual contouring was performed on SCECT and CECT with sufficient intervals and based on this, the geometric similarity of cardiac substructures was measured between them; (3) The treatment plan was quantitatively analyzed based on the contours of SCECT and CECT. Results While the mean values (± standard deviation) of the mean absolute error, peak signal-to-noise ratio, and structural similarity index measure between SCECT and CECT were 20.66 ± 5.29, 21.57 ± 1.85, and 0.77 ± 0.06, those were 23.95 ± 6.98, 20.67 ± 2.34, and 0.76 ± 0.07 between NCT and CECT, respectively. The Dice similarity coefficients and mean surface distance between the contours of SCECT and CECT were 0.81 ± 0.06 and 2.44 ± 0.72, respectively. The dosimetry analysis displayed error rates of 0.13 ± 0.27 Gy and 0.71 ± 1.34% for the mean heart dose and V5Gy, respectively. Conclusion Our findings displayed the feasibility of SCECT generation from NCT and its potential for cardiac substructure delineation in patients who underwent breast radiation therapy.

Purpose To study the performance of a proposed deep learning-based autocontouring system in delineating organs at risk (OARs) in breast radiotherapy with a group of experts. Methods Eleven experts from two institutions delineated nine OARs in 10 cases of adjuvant radiotherapy after breast-conserving surgery. Autocontours were then provided to the experts for correction. Overall, 110 manual contours, 110 corrected autocontours, and 10 autocontours of each type of OAR were analyzed. The Dice similarity coefficient (DSC) and Hausdorff distance (HD) were used to compare the degree of agreement between the best manual contour (chosen by an independent expert committee) and each autocontour, corrected autocontour, and manual contour. Higher DSCs and lower HDs indicated a better geometric overlap. The amount of time reduction using the autocontouring system was examined. User satisfaction was evaluated using a survey. Results Manual contours, corrected autocontours, and autocontours had a similar accuracy in the average DSC value (0.88 vs. 0.90 vs. 0.90). The accuracy of autocontours ranked the second place, based on DSCs, and the first place, based on HDs among the manual contours. Interphysician variations among the experts were reduced in corrected autocontours, compared to variations in manual contours (DSC: 0.89–0.90 vs. 0.87–0.90; HD: 4.3–5.8 mm vs. 5.3–7.6 mm). Among the manual delineations, the breast contours had the largest variations, which improved most significantly with the autocontouring system. The total mean times for nine OARs were 37 min for manual contours and 6 min for corrected autocontours. The results of the survey revealed good user satisfaction. Conclusions The autocontouring system had a similar performance in OARs as that of the experts’ manual contouring. This system can be valuable in improving the quality of breast radiotherapy and reducing interphysician variability in clinical practice.

Purpose The superior soft-tissue contrast achieved using magnetic resonance imaging (MRI) compared to x-ray computed tomography (CT) has led to the popularization of MRI-guided radiation therapy (MR-IGRT), especially in recent years with the advent of first and second generation MRI-based therapy delivery systems for MR-IGRT. The expanding use of these systems is driving interest in MRI-only RT workflows in which MRI is the sole imaging modality used for treatment planning and dose calculations. To enable such a workflow, synthetic CT (sCT) data must be generated based on a patient's MRI data so that dose calculations may be performed using the electron density information derived from CT images. In this study, we propose a novel deep spatial pyramid convolutional framework for the MRI-to-CT image-to-image translation task and compare its performance to the well established U-Net architecture in a generative adversarial network (GAN) framework. Methods Our proposed framework utilizes atrous convolution in a method named atrous spatial pyramid pooling (ASPP) to significantly reduce the total number of parameters required to describe the model while effectively capturing rich, multi-scale structural information in a manner that is not possible in the conventional framework. The proposed framework consists of a generative model composed of stacked encoders and decoders separated by the ASPP module, where atrous convolution is applied at increasing rates in parallel to encode large-scale features. The performance of the proposed method is compared to that of the conventional GAN framework in terms of the time required to train the model and the image quality of the generated sCT as measured by the root mean square error (RMSE), structural similarity index (SSIM), and peak signal-to-noise ratio (PSNR) depending on the size of the training data set. Dose calculations based on sCT data generated using the proposed architecture are also compared to clinical plans to evaluate the dosimetric accuracy of the method. Results Significant reductions in training time and improvements in image quality are observed at every training data set size when the proposed framework is adopted instead of the conventional framework. Over 1042 test images, values of 17.7 ± 4.3 HU, 0.9995 ± 0.0003, and 71.7 ± 2.3 are observed for the RMSE, SSIM, and PSNR metrics, respectively. Dose distributions calculated based on sCT data generated using the proposed framework demonstrate passing rates equal to or greater than 98% using the 3D gamma index with a 2%/2 mm criterion. Conclusions The deep spatial pyramid convolutional framework proposed here demonstrates improved performance compared to the conventional GAN framework that has been applied to the image-to-image translation task of sCT generation. Adopting the method is a first step toward an MRI-only RT workflow that enables widespread clinical applications for MR-IGRT including online adaptive therapy.

MR-guided radiotherapy (MRgRT) systems provide excellent soft tissue imaging immediately prior to and in real time during radiation delivery for cancer treatment. However, 2D cine MRI often has limited spatial resolution due to high temporal resolution. This work applies a super resolution machine learning framework to 3.5 mm pixel edge length, low resolution (LR), sagittal 2D cine MRI images acquired on a MRgRT system to generate 0.9 mm pixel edge length, super resolution (SR), images originally acquired at 4 frames per second (FPS). LR images were collected from 50 pancreatic cancer patients treated on a ViewRay MR-LINAC. SR images were evaluated using three methods. 1) The first method utilized intrinsic image quality metrics for evaluation. 2) The second used relative metrics including edge detection and structural similarity index (SSIM). 3) Finally, automatically generated tumor contours were created on both low resolution and super resolution images to evaluate target delineation and compared with DICE and SSIM. Intrinsic image quality metrics all had statistically significant improvements for SR images versus LR images, with mean (±1 SD) BRISQUE scores of 29.65 ± 2.98 and 42.48 ± 0.98 for SR and LR, respectively. SR images showed good agreement with LR images in SSIM evaluation, indicating there was not significant distortion of the images. Comparison of LR and SR images with paired high resolution (HR) 3D images showed that SR images had a mean (±1 SD) SSIM value of 0.633 ± 0.063 and LR a value of 0.587 ± 0.067 (p ≪ 0.05). Contours generated on SR images were also more robust to noise addition than those generated on LR images. This study shows that super resolution with a machine learning framework can generate high spatial resolution images from 4fps low spatial resolution cine MRI acquired on the ViewRay MR-LINAC while maintaining tumor contour quality and without significant acquisition or post processing delay.

PURPOSE Applications of deep learning (DL) are essential to realizing an effective adaptive radiotherapy (ART) workflow. Despite the promise demonstrated by DL approaches in several critical ART tasks, there remain unsolved challenges to achieve satisfactory generalizability of a trained model in a clinical setting. Foremost among these is the difficulty of collecting a task-specific training dataset with high-quality, consistent annotations for supervised learning applications. In this study, we propose a tailored DL framework for patient-specific performance that leverages the behavior of a model intentionally overfitted to a patient-specific training dataset augmented from the prior information available in an ART workflow-an approach we term Intentional Deep Overfit Learning (IDOL). METHODS Implementing the IDOL framework in any task in radiotherapy consists of two training stages: (1) training a generalized model with a diverse training dataset of N patients, just as in the conventional DL approach, and (2) intentionally overfitting this general model to a small training dataset-specific the patient of interest ( N+1 ) generated through perturbations and augmentations of the available task- and patient-specific prior information to establish a personalized IDOL model. The IDOL framework itself is task-agnostic and is, thus, widely applicable to many components of the ART workflow, three of which we use as a proof of concept here: the autocontouring task on replanning CTs for traditional ART, the MRI super-resolution (SR) task for MRI-guided ART, and the synthetic CT (sCT) reconstruction task for MRI-only ART. RESULTS In the replanning CT autocontouring task, the accuracy measured by the Dice similarity coefficient improves from 0.847 with the general model to 0.935 by adopting the IDOL model. In the case of MRI SR, the mean absolute error (MAE) is improved by 40% using the IDOL framework over the conventional model. Finally, in the sCT reconstruction task, the MAE is reduced from 68 to 22 HU by utilizing the IDOL framework. CONCLUSIONS In this study, we propose a novel IDOL framework for ART and demonstrate its feasibility using three ART tasks. We expect the IDOL framework to be especially useful in creating personally tailored models in situations with limited availability of training data but existing prior information, which is usually true in the medical setting in general and is especially true in ART.

PURPOSE Adjuvant radiotherapy (RT) has been performed to reduce locoregional failure (LRF) following radical cystectomy for locally advanced bladder cancer; however, its efficacy has not been well established. We analyzed the locoregional recurrence patterns of post-radical cystectomy to identify patients who could benefit from adjuvant RT and determine the optimal target volume. MATERIALS AND METHODS We retrospectively reviewed 160 patients with stage ≥ pT3 bladder cancer who were treated with radical cystectomy between January 2006 and December 2015. The impact of pathologic findings, including the stage, lympho-vascular invasion, perineural invasion, margin status, nodal involvement, and the number of nodes removed on failure patterns, was assessed. RESULTS Median follow-up period was 27.7 months. LRF was observed in 55 patients (34.3%), 12 of whom presented with synchronous local and regional failures as the first failure. The most common failure pattern was distant metastasis (40%). Among LRFs, the most common recurrence site was the cystectomy bed (15.6%). Patients with positive resection margins had a significantly higher recurrence rate compared to those without (28% vs. 10%, p=0.004). The pelvic nodal recurrence rate was < 5% in pN0 patients; the rate of recurrence in the external and common iliac nodes was 12.5% in pN+ patients. The rate of recurrence in the common iliac nodes was significantly higher in pN2-3 patients than in pN0-1 patients (15.2% vs. 4.4%, p=0.04). CONCLUSION Pelvic RT could be beneficial especially for those with positive resection margins or nodal involvement after radical cystectomy. Radiation fields should be optimized based on the patient-specific risk factors.

Background In breast cancer patients receiving radiotherapy (RT), accurate target delineation and reduction of radiation doses to the nearby normal organs is important. However, manual clinical target volume (CTV) and organs-at-risk (OARs) segmentation for treatment planning increases physicians’ workload and inter-physician variability considerably. In this study, we evaluated the potential benefits of deep learning-based auto-segmented contours by comparing them to manually delineated contours for breast cancer patients. Methods CTVs for bilateral breasts, regional lymph nodes, and OARs (including the heart, lungs, esophagus, spinal cord, and thyroid) were manually delineated on planning computed tomography scans of 111 breast cancer patients who received breast-conserving surgery. Subsequently, a two-stage convolutional neural network algorithm was used. Quantitative metrics, including the Dice similarity coefficient (DSC) and 95% Hausdorff distance, and qualitative scoring by two panels from 10 institutions were used for analysis. Inter-observer variability and delineation time were assessed; furthermore, dose-volume histograms and dosimetric parameters were also analyzed using another set of patient data. Results The correlation between the auto-segmented and manual contours was acceptable for OARs, with a mean DSC higher than 0.80 for all OARs. In addition, the CTVs showed favorable results, with mean DSCs higher than 0.70 for all breast and regional lymph node CTVs. Furthermore, qualitative subjective scoring showed that the results were acceptable for all CTVs and OARs, with a median score of at least 8 (possible range: 0–10) for (1) the differences between manual and auto-segmented contours and (2) the extent to which auto-segmentation would assist physicians in clinical practice. The differences in dosimetric parameters between the auto-segmented and manual contours were minimal. Conclusions The feasibility of deep learning-based auto-segmentation in breast RT planning was demonstrated. Although deep learning-based auto-segmentation cannot be a substitute for radiation oncologists, it is a useful tool with excellent potential in assisting radiation oncologists in the future. Trial registration Retrospectively registered.

Objective. Owing to the superior soft tissue contrast of MRI, MRI-guided adaptive radiotherapy (ART) is well-suited to managing interfractional changes in anatomy. An MRI-only workflow is desirable, but producing synthetic CT (sCT) data through paired data-driven deep learning (DL) for abdominal dose calculations remains a challenge due to the highly variable presence of intestinal gas. We present the preliminary dosimetric evaluation of our novel approach to sCT reconstruction that is well suited to handling intestinal gas in abdominal MRI-only ART.Approach. We utilize a paired data DL approach enabled by the intensity projection prior, in which well-matching training pairs are created by propagating air from MRI to corresponding CT scans. Evaluations focus on two classes: patients with (1) little involvement of intestinal gas, and (2) notable differences in intestinal gas presence between corresponding scans. Comparisons between sCT-based plans and CT-based clinical plans for both classes are made at the first treatment fraction to highlight the dosimetric impact of the variable presence of intestinal gas.Main results. Class 1 patients (n= 13) demonstrate differences in prescribed dose coverage of the PTV of 1.3 ± 2.1% between clinical plans and sCT-based plans. Mean DVH differences in all structures for Class 1 patients are found to be statistically insignificant. In Class 2 (n= 20), target coverage is 13.3 ± 11.0% higher in the clinical plans and mean DVH differences are found to be statistically significant.Significance. Significant deviations in calculated doses arising from the variable presence of intestinal gas in corresponding CT and MRI scans result in uncertainty in high-dose regions that may limit the effectiveness of adaptive dose escalation efforts. We have proposed a paired data-driven DL approach to sCT reconstruction for accurate dose calculations in abdominal ART enabled by the creation of a clinically unavailable training data set with well-matching representations of intestinal gas.

Manual segmentation is the gold standard method for radiation therapy planning; however, it is time-consuming and prone to inter- and intra-observer variation, giving rise to interests in auto-segmentation methods. We evaluated the feasibility of deep learning-based auto-segmentation (DLBAS) in comparison to commercially available atlas-based segmentation solutions (ABAS) for breast cancer radiation therapy. This study used contrast-enhanced planning computed tomography scans from 62 patients with breast cancer who underwent breast-conservation surgery. Contours of target volumes (CTVs), organs, and heart substructures were generated using two commercial ABAS solutions and DLBAS using fully convolutional DenseNet. The accuracy of the segmentation was assessed using 14 test patients using the Dice Similarity Coefficient and Hausdorff Distance referencing the expert contours. A sensitivity analysis was performed using non-contrast planning CT from 14 additional patients. Compared to ABAS, the proposed DLBAS model yielded more consistent results and the highest average Dice Similarity Coefficient values and lowest Hausdorff Distances, especially for CTVs and the substructures of the heart. ABAS showed limited performance in soft-tissue-based regions, such as the esophagus, cardiac arteries, and smaller CTVs. The results of sensitivity analysis between contrast and non-contrast CT test sets showed little difference in the performance of DLBAS and conversely, a large discrepancy for ABAS. The proposed DLBAS algorithm was more consistent and robust in its performance than ABAS across the majority of structures when examining both CTVs and normal organs. DLBAS has great potential to aid a key process in the radiation therapy workflow, helping optimise and reduce the clinical workload.

Objective. Real-time imaging is highly desirable in image-guided radiotherapy, as it provides instantaneous knowledge of patients’ anatomy and motion during treatments and enables online treatment adaptation to achieve the highest tumor targeting accuracy. Due to extremely limited acquisition time, only one or few x-ray projections can be acquired for real-time imaging, which poses a substantial challenge to localize the tumor from the scarce projections. For liver radiotherapy, such a challenge is further exacerbated by the diminished contrast between the tumor and the surrounding normal liver tissues. Here, we propose a framework combining graph neural network-based deep learning and biomechanical modeling to track liver tumor in real-time from a single onboard x-ray projection. Approach. Liver tumor tracking is achieved in two steps. First, a deep learning network is developed to predict the liver surface deformation using image features learned from the x-ray projection. Second, the intra-liver deformation is estimated through biomechanical modeling, using the liver surface deformation as the boundary condition to solve tumor motion by finite element analysis. The accuracy of the proposed framework was evaluated using a dataset of 10 patients with liver cancer. Main results. The results show accurate liver surface registration from the graph neural network-based deep learning model, which translates into accurate, fiducial-less liver tumor localization after biomechanical modeling (Significance. The method demonstrates its potentiality towards intra-treatment and real-time 3D liver tumor monitoring and localization. It could be applied to facilitate 4D dose accumulation, multi-leaf collimator tracking and real-time plan adaptation. The method can be adapted to other anatomical sites as well.

PURPOSE Deep learning (DL)-based super-resolution (SR) reconstruction for magnetic resonance imaging (MRI) has recently been receiving attention due to the significant improvement in spatial resolution compared to conventional SR techniques. Challenges hindering the widespread implementation of these approaches remain, however. Low-resolution (LR) MRIs captured in the clinic exhibit complex tissue structures obfuscated by noise that are difficult for a simple DL framework to handle. Moreover, training a robust network for a SR task requires abundant, perfectly matched pairs of LR and high-resolution (HR) images that are often unavailable or difficult to collect. The purpose of this study is to develop a novel SR technique for MRI based on the concept of cascaded DL that allows for the reconstruction of high-quality SR images in the presence of insufficient training data, an unknown translation model, and noise. METHODS The proposed framework, based on the concept named cascaded deep learning, consists of three components: (a) a denoising autoencoder (DAE) trained using clinical LR noisy MRI scans that have been processed with a nonlocal means filter that generates denoised LR data; (b) a down-sampling network (DSN) trained with a small amount of paired LR/HR data from volunteers that allows for the generation of perfectly paired LR/HR data for the training of a generative model; and (c) the proposed SR generative model (p-SRG) trained with data generated by the DSN that maps from LR inputs to HR outputs. After training, LR clinical images may be fed through the DAE and p-SRG to yield SR reconstructions of the LR input. The application of this framework was explored in two settings: 3D breath-hold MRI axial SR reconstruction from LR axial scans (