Optimization of treatment workflow for 0.35T MR-Linac system.

PURPOSE: This study presents a novel and comprehensive framework for evaluating magnetic resonance guided radiotherapy (MRgRT) workflow by integrating the Failure Modes and Effects Analysis (FMEA) approach with Time-Driven Activity-Based Costing (TDABC). We assess the workflow for safety, quality, and economic implications, providing a holistic understanding of the MRgRT implementation. The aim is to offer valuable insights to healthcare practitioners and administrators, facilitating informed decision-making regarding the 0.35T MRIdian MR-Linac system's clinical workflow. METHODS: For FMEA, a multidisciplinary team followed the TG-100 methodology to assess the MRgRT workflow's potential failure modes. Following the mitigation of primary failure modes and workflow optimization, a treatment process was established for TDABC analysis. The TDABC was applied to both MRgRT and computed tomography guided RT (CTgRT) for typical five-fraction stereotactic body RT (SBRT) treatments, assessing total workflow and costs associated between the two treatment workflows. RESULTS: A total of 279 failure modes were identified, with 31 categorized as high-risk, 55 as medium-risk, and the rest as low-risk. The top 20% risk priority numbers (RPN) were determined for each radiation oncology care team member. Total MRgRT and CTgRT costs were assessed. Implementing technological advancements, such as real-time multi leaf collimator (MLC) tracking with volumetric modulated arc therapy (VMAT), auto-segmentation, and increasing the Linac dose rate, led to significant cost savings for MRgRT. CONCLUSION: In this study, we integrated FMEA with TDABC to comprehensively evaluate the workflow and the associated costs of MRgRT compared to conventional CTgRT for five-fraction SBRT treatments. FMEA analysis identified critical failure modes, offering insights to enhance patient safety. TDABC analysis revealed that while MRgRT provides unique advantages, it may involve higher costs. Our findings underscore the importance of exploring cost-effective strategies and key technological advancements to ensure the widespread adoption and financial sustainability of MRgRT in clinical practice.

Generation of tissues outside the field of view (FOV) of radiation therapy simulation imaging based on machine learning and patient body outline (PBO).

BACKGROUND: It is not unusual to see some parts of tissues are excluded in the field of view of CT simulation images. A typical mitigation is to avoid beams entering the missing body parts at the cost of sub-optimal planning. METHODS: This study is to solve the problem by developing 3 methods, (1) deep learning (DL) mechanism for missing tissue generation, (2) using patient body outline (PBO) based on surface imaging, and (3) hybrid method combining DL and PBO. The DL model was built upon a Globally and Locally Consistent Image Completion to learn features by Convolutional Neural Networks-based inpainting, based on Generative Adversarial Network. The database used comprised 10,005 CT training slices of 322 lung cancer patients and 166 CT evaluation test slices of 15 patients. CT images were from the publicly available database of the Cancer Imaging Archive. Since existing data were used PBOs were acquired from the CT images. For evaluation, Structural Similarity Index Metric (SSIM), Root Mean Square Error (RMSE) and Peak signal-to-noise ratio (PSNR) were evaluated. For dosimetric validation, dynamic conformal arc plans were made with the ground truth images and images generated by the proposed method. Gamma analysis was conducted at relatively strict criteria of 1%/1 mm (dose difference/distance to agreement) and 2%/2 mm under three dose thresholds of 1%, 10% and 50% of the maximum dose in the plans made on the ground truth image sets. RESULTS: The average SSIM in generation part only was 0.06 at epoch 100 but reached 0.86 at epoch 1500. Accordingly, the average SSIM in the whole image also improved from 0.86 to 0.97. At epoch 1500, the average values of RMSE and PSNR in the whole image were 7.4 and 30.9, respectively. Gamma analysis showed excellent agreement with the hybrid method (equal to or higher than 96.6% of the mean of pass rates for all scenarios). CONCLUSIONS: It was first demonstrated that missing tissues in simulation imaging could be generated with high similarity, and dosimetric limitation could be overcome. The benefit of this study can be significantly enlarged when MR-only simulation is considered.

NRG Oncology Assessment of Artificial Intelligence Deep Learning-Based Auto-segmentation for Radiation Therapy: Current Developments, Clinical Considerations, and Future Directions.

Deep learning neural networks (DLNN) in Artificial intelligence (AI) have been extensively explored for automatic segmentation in radiotherapy (RT). In contrast to traditional model-based methods, data-driven AI-based models for auto-segmentation have shown high accuracy in early studies in research settings and controlled environment (single institution). Vendor-provided commercial AI models are made available as part of the integrated treatment planning system (TPS) or as a stand-alone tool that provides streamlined workflow interacting with the main TPS. These commercial tools have drawn clinics' attention thanks to their significant benefit in reducing the workload from manual contouring and shortening the duration of treatment planning. However, challenges occur when applying these commercial AI-based segmentation models to diverse clinical scenarios, particularly in uncontrolled environments. Contouring nomenclature and guideline standardization has been the main task undertaken by the NRG Oncology. AI auto-segmentation holds the potential clinical trial participants to reduce interobserver variations, nomenclature non-compliance, and contouring guideline deviations. Meanwhile, trial reviewers could use AI tools to verify contour accuracy and compliance of those submitted datasets. In recognizing the growing clinical utilization and potential of these commercial AI auto-segmentation tools, NRG Oncology has formed a working group to evaluate the clinical utilization and potential of commercial AI auto-segmentation tools. The group will assess in-house and commercially available AI models, evaluation metrics, clinical challenges, and limitations, as well as future developments in addressing these challenges. General recommendations are made in terms of the implementation of these commercial AI models, as well as precautions in recognizing the challenges and limitations.

Automated Lung Cancer Segmentation Using a PET and CT Dual-Modality Deep Learning Neural Network.

PURPOSE: To develop an automated lung tumor segmentation method for radiation therapy planning based on deep learning and dual-modality positron emission tomography (PET) and computed tomography (CT) images. METHODS AND MATERIALS: A 3-dimensional (3D) convolutional neural network using inputs from diagnostic PETs and simulation CTs was constructed with 2 parallel convolution paths for independent feature extraction at multiple resolution levels and a single deconvolution path. At each resolution level, the extracted features from the convolution arms were concatenated and fed through the skip connections into the deconvolution path that produced the tumor segmentation. Our network was trained/validated/tested by a 3:1:1 split on 290 pairs of PET and CT images from patients with lung cancer treated at our clinic, with manual physician contours as the ground truth. A stratified training strategy based on the magnitude of the gross tumor volume (GTV) was investigated to improve performance, especially for small tumors. Multiple radiation oncologists assessed the clinical acceptability of the network-produced segmentations. RESULTS: The mean Dice similarity coefficient, Hausdorff distance, and bidirectional local distance comparing manual versus automated contours were 0.79 ± 0.10, 5.8 ± 3.2 mm, and 2.8 ± 1.5 mm for the unstratified 3D dual-modality model. Stratification delivered the best results when the model for the large GTVs (>25 mL) was trained with all-size GTVs and the model for the small GTVs (<25 mL) was trained with small GTVs only. The best combined Dice similarity coefficient, Hausdorff distance, and bidirectional local distance from the 2 stratified models on their corresponding test data sets were 0.83 ± 0.07, 5.9 ± 2.5 mm, and 2.8 ± 1.4 mm, respectively. In the multiobserver review, 91.25% manual versus 88.75% automatic contours were accepted or accepted with modifications. CONCLUSIONS: By using an expansive clinical PET and CT image database and a dual-modality architecture, the proposed 3D network with a novel GTVbased stratification strategy generated clinically useful lung cancer contours that were highly acceptable on physician review.

A data-driven approach to optimal beam/arc angle selection for liver stereotactic body radiation therapy treatment planning.

BACKGROUND: Stereotactic body radiation therapy (SBRT) for liver cancer has shown promising therapeutic effects. Effective treatment relies not only on the precise delivery provided by image-guided radiation therapy (IGRT) but also high dose gradient formed around the treatment volume to spare functional liver tissue, which is highly dependent on the beam/arc angle selection. In this study, we aim to develop a decision support model to learn human planner's beam navigation approach for beam angle/arc angle selection for liver SBRT. METHODS: A total of 27 liver SBRT/HIGRT patients (10 IMRT, 17 VMAT/DCA) were included in this study. A dosimetric budget index was defined for each beam angle/control point considering dose penetration through the patient body and liver tissue. Optimal beam angle setting (beam angles for IMRT and start/terminal angle for VMAT/DCA) was determined by minimizing the loss function defined as the sum of total dosimetric budget index and beam span penalty function. Leave-one-out validation was exercised on all 27 cases while weighting coefficients in the loss function was tuned in nested cross validation. To compare the efficacy of the model, a model plan was generated using automatically generated beam setting while retaining the original optimization constraints in the clinical plan. Model plan was normalized to the same planning target volume (PTV) V100% as the clinical plans. Dosimetric endpoints including PTV D98%, D2%, liver V20Gy and total MU were compared between two plan groups. Wilcoxon Signed-Rank test was performed with the null hypothesis being that no difference exists between two plan groups. RESULTS: Beam setting prediction was instantaneous. Mean PTV D98% was 91.3% and 91.3% (P=0.566), while mean PTV D2% was 107.9% and 108.1% (P=0.164) for clinical plan and model plan respectively. Liver V20Gy showed no significant difference (P=0.590) with 23.3% for clinical plan and 23.4% for the model plan. Total MU is comparable (P=0.256) between the clinical plan (avg. 2,389.6) and model plan (avg. 2,319.6). CONCLUSIONS: The evidence driven beam setting model yielded similar plan quality as hand-crafted clinical plan. It is capable of capturing human's knowledge in beam selection decision making. This model could facilitate decision making for beam angle selection while eliminating lengthy trial-and-error process of adjusting beam setting during liver SBRT treatment planning.

An efficient planning technique for low dose whole lung radiation therapy for covid-19 pandemic patients.

This study aimed to establish an efficient planning technique for low dose whole lung treatment that can be implemented rapidly and safely. The treatment technique developed here relied only on chest radiograph and a simple empirical monitor unit calculation formula. The 3D dose calculation in real patient anatomy, including both nonCOVID and COVID-19 patients, which took into account tissue heterogeneity showed that the dose delivered to lungs had reasonable uniformity even with this simple and quick setup.

Lung IMRT planning with automatic determination of beam angle configurations.

Beam angle configuration is a major planning decision in intensity modulated radiation treatment (IMRT) that has a significant impact on dose distributions and thus quality of treatment, especially in complex planning cases such as those for lung cancer treatment. We propose a novel method to automatically determine beam configurations that incorporates noncoplanar beams. We then present a completely automated IMRT planning algorithm that combines the proposed method with a previously reported OAR DVH prediction model. Finally, we validate this completely automatic planning algorithm using a set of challenging lung IMRT cases. A beam efficiency index map is constructed to guide the selection of beam angles. This index takes into account both the dose contributions from individual beams and the combined effect of multiple beams by introducing a beam-spread term. The effect of the beam-spread term on plan quality was studied systematically and the weight of the term to balance PTV dose conformity against OAR avoidance was determined. For validation, complex lung cases with clinical IMRT plans that required the use of one or more noncoplanar beams were re-planned with the proposed automatic planning algorithm. Important dose metrics for the PTV and OARs in the automatic plans were compared with those of the clinical plans. The results are very encouraging. The PTV dose conformity and homogeneity in the automatic plans improved significantly. And all the dose metrics of the automatic plans, except the lung V5 Gy, were statistically better than or comparable with those of the clinical plans. In conclusion, the automatic planning algorithm can incorporate non-coplanar beam configurations in challenging lung cases and can generate plans efficiently with quality closely approximating that of clinical plans.

Outlier identification in radiation therapy knowledge-based planning: A study of pelvic cases.

PURPOSE: The purpose of this study was to apply statistical metrics to identify outliers and to investigate the impact of outliers on knowledge-based planning in radiation therapy of pelvic cases. We also aimed to develop a systematic workflow for identifying and analyzing geometric and dosimetric outliers. METHODS: Four groups (G1-G4) of pelvic plans were sampled in this study. These include the following three groups of clinical IMRT cases: G1 (37 prostate cases), G2 (37 prostate plus lymph node cases) and G3 (37 prostate bed cases). Cases in G4 were planned in accordance with dynamic-arc radiation therapy procedure and include 10 prostate cases in addition to those from G1. The workflow was separated into two parts: 1. identifying geometric outliers, assessing outlier impact, and outlier cleaning; 2. identifying dosimetric outliers, assessing outlier impact, and outlier cleaning. G2 and G3 were used to analyze the effects of geometric outliers (first experiment outlined below) while G1 and G4 were used to analyze the effects of dosimetric outliers (second experiment outlined below). A baseline model was trained by regarding all G2 cases as inliers. G3 cases were then individually added to the baseline model as geometric outliers. The impact on the model was assessed by comparing leverages of inliers (G2) and outliers (G3). A receiver-operating-characteristic (ROC) analysis was performed to determine the optimal threshold. The experiment was repeated by training the baseline model with all G3 cases as inliers and perturbing the model with G2 cases as outliers. A separate baseline model was trained with 32 G1 cases. Each G4 case (dosimetric outlier) was subsequently added to perturb the model. Predictions of dose-volume histograms (DVHs) were made using these perturbed models for the remaining 5 G1 cases. A Weighted Sum of Absolute Residuals (WSAR) was used to evaluate the impact of the dosimetric outliers. RESULTS: The leverage of inliers and outliers was significantly different. The Area-Under-Curve (AUC) for differentiating G2 (outliers) from G3 (inliers) was 0.98 (threshold: 0.27) for the bladder and 0.81 (threshold: 0.11) for the rectum. For differentiating G3 (outlier) from G2 (inlier), the AUC (threshold) was 0.86 (0.11) for the bladder and 0.71 (0.11) for the rectum. Significant increase in WSAR was observed in the model with 3 dosimetric outliers for the bladder (P < 0.005 with Bonferroni correction), and in the model with only 1 dosimetric outlier for the rectum (P < 0.005). CONCLUSIONS: We established a systematic workflow for identifying and analyzing geometric and dosimetric outliers, and investigated statistical metrics for outlier detection. Results validated the necessity for outlier detection and clean-up to enhance model quality in clinical practice.

Establishing the feasibility of the dosimetric compliance criteria of RTOG 1308: phase III randomized trial comparing overall survival after photon versus proton radiochemotherapy for inoperable stage II-IIIB NSCLC.

BACKGROUND: To establish the feasibility of the dosimetric compliance criteria of the RTOG 1308 trial through testing against Intensity Modulation Radiation Therapy (IMRT) and Passive Scattering Proton Therapy (PSPT) plans. METHODS: Twenty-six lung IMRT and 26 proton PSPT plans were included in the study. Dose Volume Histograms (DVHs) for targets and normal structures were analyzed. The quality of IMRT plans was assessed using a knowledge-based engineering tool. RESULTS: Most of the RTOG 1308 dosimetric criteria were achieved. The deviation unacceptable rates were less than 10 % for most criteria; however, a deviation unacceptable rate of more than 20 % was computed for the planning target volume minimum dose compliance criterion. Dose parameters for the target volume were very close for the IMRT and PSPT plans. However, the PSPT plans led to lower dose values for normal structures. The dose parameters in which PSPT plans resulted in lower values than IMRT plans were: lung V5Gy (%) (34.4 in PSPT and 47.2 in IMRT); maximum spinal cord dose (31.7 Gy in PSPT and 43.5 Gy in IMRT); heart V5Gy (%) (19 in PSPT and 47 in IMRT); heart V30Gy (%) (11 in PSPT and 19 in IMRT); heart V45Gy (%) (7.8 in PSPT and 12.1 in IMRT); heart V50% (Gy) (7.1 in PSPT and 9.8 in IMRT) and mean heart dose (7.7 Gy in PSPT and 14.9 Gy in IMRT). CONCLUSIONS: The revised RTOG 1308 dosimetric compliance criteria are feasible and achievable.

Utilizing knowledge from prior plans in the evaluation of quality assurance.

Increased interest regarding sensitivity of pre-treatment intensity modulated radiotherapy and volumetric modulated arc radiotherapy (VMAT) quality assurance (QA) to delivery errors has led to the development of dose-volume histogram (DVH) based analysis. This paradigm shift necessitates a change in the acceptance criteria and action tolerance for QA. Here we present a knowledge based technique to objectively quantify degradations in DVH for prostate radiotherapy. Using machine learning, organ-at-risk (OAR) DVHs from a population of 198 prior patients' plans were adapted to a test patient's anatomy to establish patient-specific DVH ranges. This technique was applied to single arc prostate VMAT plans to evaluate various simulated delivery errors: systematic single leaf offsets, systematic leaf bank offsets, random normally distributed leaf fluctuations, systematic lag in gantry angle of the mutli-leaf collimators (MLCs), fluctuations in dose rate, and delivery of each VMAT arc with a constant rather than variable dose rate.Quantitative Analyses of Normal Tissue Effects in the Clinic suggests V75Gy dose limits of 15% for the rectum and 25% for the bladder, however the knowledge based constraints were more stringent: 8.48 ± 2.65% for the rectum and 4.90 ± 1.98% for the bladder. 19 ± 10 mm single leaf and 1.9 ± 0.7 mm single bank offsets resulted in rectum DVHs worse than 97.7% (2σ) of clinically accepted plans. PTV degradations fell outside of the acceptable range for 0.6 ± 0.3 mm leaf offsets, 0.11 ± 0.06 mm bank offsets, 0.6 ± 1.3 mm of random noise, and 1.0 ± 0.7° of gantry-MLC lag.Utilizing a training set comprised of prior treatment plans, machine learning is used to predict a range of achievable DVHs for the test patient's anatomy. Consequently, degradations leading to statistical outliers may be identified. A knowledge based QA evaluation enables customized QA criteria per treatment site, institution and/or physician and can often be more sensitive to errors than criteria based on organ complication rates.

Standardized beam bouquets for lung IMRT planning.

The selection of the incident angles of the treatment beams is a critical component of intensity modulated radiation therapy (IMRT) planning for lung cancer due to significant variations in tumor location, tumor size and patient anatomy. We investigate the feasibility of establishing a small set of standardized beam bouquets for planning. The set of beam bouquets were determined by learning the beam configuration features from 60 clinical lung IMRT plans designed by experienced planners. A k-medoids cluster analysis method was used to classify the beam configurations in the dataset. The appropriate number of clusters was determined by maximizing the value of average silhouette width of the classification. Once the number of clusters had been determined, the beam arrangements in each medoid of the clusters were designated as the standardized beam bouquet for the cluster. This standardized bouquet set was used to re-plan 20 cases randomly selected from the clinical database. The dosimetric quality of the plans using the beam bouquets was evaluated against the corresponding clinical plans by a paired t-test. The classification with six clusters has the largest average silhouette width value and hence would best represent the beam bouquet patterns in the dataset. The results shows that plans generated with a small number of standardized bouquets (e.g. 6) have comparable quality to that of clinical plans. These standardized beam configuration bouquets will potentially help improve plan efficiency and facilitate automated planning.

From active shape model to active optical flow model: a shape-based approach to predicting voxel-level dose distributions in spine SBRT.

Prediction of achievable dose distribution in spine stereotactic body radiation therapy (SBRT) can help in designing high-quality treatment plans to maximally protect spinal cords and to effectively control tumours. Dose distributions at spinal cords are primarily affected by the shapes of adjacent planning target volume (PTV) contours. In this work, we estimate such contour effects and predict dose distributions by exploring active optical flow model (AOFM) and active shape model (ASM). We first collect a sequence of dose sub-images and PTV contours near spinal cords from fifteen SBRT plans in the training dataset. The data collection is then classified into five groups according to the PTV locations in relation to spinal cords. In each group, we randomly choose a dose sub-image as the reference and register all other sub-images to the reference using an optical flow method. AOFM is then constructed by importing optical flow vectors and dose values into the principal component analysis (PCA). Similarly, we build ASM by using PCA on PTV contour points. The correlation between ASM and AOFM is estimated via a stepwise multiple regression model. When predicting dose distribution of a new case, the group is first determined based on the PTV contour. The prediction model of the selected group is used to estimate dose distributions by mapping the PTV contours from the ASM space to the AOFM space. This method was validated on fifteen SBRT plans in the testing dataset. Analysis of dose-volume histograms revealed that the important D2%, D5%, D10% and D0.1cc dosimetric parameters of spinal cords between the prediction and the clinical plans were 11.7 ± 1.7 Gy versus 11.8 ± 1.7 Gy (p = 0.95), 10.9 ± 1.7 Gy versus 11.1 ± 1.9 Gy (p = 0.8295), 10.2 ± 1.6 Gy versus 10.1 ± 1.7 (p = 0.9036) and 11.2 ± 2.0 Gy versus 11.1 ± 2.2 Gy (p = 0.5208), respectively. Here, the 'cord' is the spinal cord proper (not the thecal sac) extended 5 mm inferior and superior to the involved vertebral bodies, and the 'PTV' is the involved segment of the vertebral body expanded uniformly by 2 mm but excluding the spinal cord volume expanded by 2 mm (Ref. RTOG 0631). These results suggested that the AOFM-based approach is a promising tool for predicting accurate spinal cord dose in clinical practice. In this work, we demonstrated the feasibility of using AOFM and ASM models derived from previously treated patients to estimate the achievable dose distributions for new patients.

Impact of dose calculation accuracy during optimization on lung IMRT plan quality.

The purpose of this study was to evaluate the effect of dose calculation accuracy and the use of an intermediate dose calculation step during the optimization of intensity-modulated radiation therapy (IMRT) planning on the final plan quality for lung cancer patients. This study included replanning for 11 randomly selected free-breathing lung IMRT plans. The original plans were optimized using a fast pencil beam convolution algorithm. After optimization, the final dose calculation was performed using the analytical anisotropic algorithm (AAA). The Varian Treatment Planning System (TPS) Eclipse v11, includes an option to perform intermediate dose calculation during optimization using the AAA. The new plans were created using this intermediate dose calculation during optimization with the same planning objectives and dose constraints as in the original plan. Differences in dosimetric parameters for the planning target volume (PTV) dose coverage, organs-at-risk (OARs) dose sparing, and the number of monitor units (MU) between the original and new plans were analyzed. Statistical significance was determined with a p-value of less than 0.05. All plans were normalized to cover 95% of the PTV with the prescription dose. Compared with the original plans, the PTV in the new plans had on average a lower maximum dose (69.45 vs. 71.96Gy, p = 0.005), a better homogeneity index (HI) (0.08 vs. 0.12, p = 0.002), and a better conformity index (CI) (0.69 vs. 0.59, p = 0.003). In the new plans, lung sparing was increased as the volumes receiving 5, 10, and 30 Gy were reduced when compared to the original plans (40.39% vs. 42.73%, p = 0.005; 28.93% vs. 30.40%, p = 0.001; 14.11%vs. 14.84%, p = 0.031). The volume receiving 20 Gy was not significantly lower (19.60% vs. 20.38%, p = 0.052). Further, the mean dose to the lung was reduced in the new plans (11.55 vs. 12.12 Gy, p = 0.024). For the esophagus, the mean dose, the maximum dose, and the volumes receiving 20 and 60 Gy were lower in the new plans than in the original plans (17.91 vs. 19.24 Gy, p = 0.004; 57.32vs. 59.81 Gy, p = 0.020; 39.34% vs. 41.59%, p = 0.097; 12.56%vs. 15.35%, p = 0.101). For the heart, the mean dose, the maximum dose, and the volume receiving 40 Gy were also lower in new plans (11.07 vs. 12.04 Gy, p = 0.007; 56.41 vs. 57.7 Gy, p = 0.027; 7.16% vs. 9.37%, p= 0.012). The maximum dose to the spinal cord in the new plans was significantly lower than in the original IMRT plans (29.1 vs. 31.39Gy, p = 0.014). Difference in MU between the IMRT plans was not significant (1216.90 vs. 1198.91, p = 0.328). In comparison to the original plans, the number of iterations needed to meet the optimization objectives in the new plans was reduced by a factor of 2 (2-3 vs. 5-6 iterations). Further, optimization was 30% faster corresponding to an average time savings of 10-15 min for the reoptimized plans. Accuracy of the dose calculation algorithm during optimization has an impact on planning efficiency, as well as on the final plan dosimetric quality. For lung IMRT treatment planning, utilizing the intermediate dose calculation during optimization is feasible for dose homogeneity improvement of the PTV and for improvement of optimization efficiency.

Incorporating single-side sparing in models for predicting parotid dose sparing in head and neck IMRT.

PURPOSE: Sparing of single-side parotid gland is a common practice in head-and-neck (HN) intensity modulated radiation therapy (IMRT) planning. It is a special case of dose sparing tradeoff between different organs-at-risk. The authors describe an improved mathematical model for predicting achievable dose sparing in parotid glands in HN IMRT planning that incorporates single-side sparing considerations based on patient anatomy and learning from prior plan data. METHODS: Among 68 HN cases analyzed retrospectively, 35 cases had physician prescribed single-side parotid sparing preferences. The single-side sparing model was trained with cases which had single-side sparing preferences, while the standard model was trained with the remainder of cases. A receiver operating characteristics (ROC) analysis was performed to determine the best criterion that separates the two case groups using the physician's single-side sparing prescription as ground truth. The final predictive model (combined model) takes into account the single-side sparing by switching between the standard and single-side sparing models according to the single-side sparing criterion. The models were tested with 20 additional cases. The significance of the improvement of prediction accuracy by the combined model over the standard model was evaluated using the Wilcoxon rank-sum test. RESULTS: Using the ROC analysis, the best single-side sparing criterion is (1) the predicted median dose of one parotid is higher than 24 Gy; and (2) that of the other is higher than 7 Gy. This criterion gives a true positive rate of 0.82 and a false positive rate of 0.19, respectively. For the bilateral sparing cases, the combined and the standard models performed equally well, with the median of the prediction errors for parotid median dose being 0.34 Gy by both models (p = 0.81). For the single-side sparing cases, the standard model overestimates the median dose by 7.8 Gy on average, while the predictions by the combined model differ from actual values by only 2.2 Gy (p = 0.005). Similarly, the sum of residues between the modeled and the actual plan DVHs is the same for the bilateral sparing cases by both models (p = 0.67), while the standard model predicts significantly higher DVHs than the combined model for the single-side sparing cases (p = 0.01). CONCLUSIONS: The combined model for predicting parotid sparing that takes into account single-side sparing improves the prediction accuracy over the previous model.

Modeling the dosimetry of organ-at-risk in head and neck IMRT planning: an intertechnique and interinstitutional study.

PURPOSE: To build a statistical model to quantitatively correlate the anatomic features of structures and the corresponding dose-volume histogram (DVH) of head and neck (HN) Tomotherapy (Tomo) plans. To study if the model built upon one intensity modulated radiation therapy (IMRT) technique (such as conventional Linac) can be used to predict anticipated organs-at-risk (OAR) DVH of patients treated with a different IMRT technique (such as Tomo). To study if the model built upon the clinical experience of one institution can be used to aid IMRT planning for another institution. METHODS: Forty-four Tomotherapy intensity modulate radiotherapy plans of HN cases (Tomo-IMRT) from Institution A were included in the study. A different patient group of 53 HN fixed gantry IMRT (FG-IMRT) plans was selected from Institution B. The analyzed OARs included the parotid, larynx, spinal cord, brainstem, and submandibular gland. Two major groups of anatomical features were considered: the volumetric information and the spatial information. The volume information includes the volume of target, OAR, and overlapped volume between target and OAR. The spatial information of OARs relative to PTVs was represented by the distance-to-target histogram (DTH). Important anatomical and dosimetric features were extracted from DTH and DVH by principal component analysis. Two regression models, one for Tomotherapy plan and one for IMRT plan, were built independently. The accuracy of intratreatment-modality model prediction was validated by a leave one out cross-validation method. The intertechnique and interinstitution validations were performed by using the FG-IMRT model to predict the OAR dosimetry of Tomo-IMRT plans. The dosimetry of OARs, under the same and different institutional preferences, was analyzed to examine the correlation between the model prediction and planning protocol. RESULTS: Significant patient anatomical factors contributing to OAR dose sparing in HN Tomotherapy plans have been analyzed and identified. For all the OARs, the discrepancies of dose indices between the model predicted values and the actual plan values were within 2.1%. Similar results were obtained from the modeling of FG-IMRT plans. The parotid gland was spared in a comparable fashion during the treatment planning of two institutions. The model based on FG-IMRT plans was found to predict the median dose of the parotid of Tomotherapy plans quite well, with a mean error of 2.6%. Predictions from the FG-IMRT model suggested the median dose of the larynx, median dose of the brainstem and D2 of the brainstem could be reduced by 10.5%, 12.8%, and 20.4%, respectively, in the Tomo-IMRT plans. This was found to be correlated to the institutional differences in OAR constraint settings. Re-planning of six Tomotherapy patients confirmed the potential of optimization improvement predicted by the FG-IMRT model was correct. CONCLUSIONS: The authors established a mathematical model to correlate the anatomical features and dosimetric indexes of OARs of HN patients in Tomotherapy plans. The model can be used for the setup of patient-specific OAR dose sparing goals and quality control of planning results.The institutional clinical experience was incorporated into the model which allows the model from one institution to generate a reference plan for another institution, or another IMRT technique.

Single institution's dosimetry and IGRT analysis of prostate SBRT.

BACKGROUND AND PURPOSE: To report single institution's IGRT and dosimetry analysis on the 37 Gy/5 fraction prostate SBRT clinical trial. MATERIALS/METHODS: The IRB (Duke University Medical Center) approved clinical trial has treated 28 patients with stage T1-T2c prostate cancer with a regimen of 37 Gy in 5 fractions using IMRT and IGRT protocols since 2009. The clinical trial protocol requires CT/MRI imaging for the prostate delineation; a margin of 3 mm in posterior direction and 5 mm elsewhere for planning target volume (PTV); and strict dose constraints for primary organs-at-risks (OARs) including the bladder, the rectum, and the femoral heads. Rigid IGRT process is also an essential part of the protocol. Precise patient and prostate positioning and dynamic tracking of prostate motion are performed with electromagnetic localization device (Calypso) and on-board imaging (OBI) system. Initial patient and target alignment is performed based on fiducials with OBI imaging system and Calypso system. Prior to treatment, cone-beam CT (CBCT) is performed for soft tissue alignment verification. During treatment, per-beam corrections for target motion using translational couch movements is performed before irradiating each field, based on electromagnetic localization or on-board imaging localization. Dosimetric analysis on target coverage and OAR sparing is performed based on key DVH parameters corresponding to protocol guidance. IGRT analysis is focused on the average frequency and magnitude of corrections during treatment, and overall intra-fractional target drift. A margin value is derived using actual target motion data and the margin recipe from Van Herk et al., and is compared to the current one in practice. In addition, cumulative doses with and without per-beam IGRT corrections are compared to assess the benefit of online IGRT. RESULTS: 1. No deviation has been found in 10 of 14 dosimetric constraints, with minor deviations in the rest 4 constraints.2. Online IGRT techniques including Calypso, OBI and CBCT supplement each other to create an effective and reliable system on tracking target and correcting intra-fractional motion.3. On average ½ corrections have been performed per fraction, with magnitude of (0.22 ± 0.11) cm. Average target drift magnitude is (0.7 ± 1.3) mm in one direction during each fraction.4. Benefit from per-beam correction in overall review is small: most differences from no correction are < 0.1 Gy for PTV D1cc/Dmean and < 1%/1.5 cc for OAR parameters. Up to 1.5 Gy reduction was seen in PTV D99% without online correction. Largest differences for OARs are -4.1 cc and +1.6 cc in the V50% for the bladder and the rectum, respectively. However, online IGRT helps to catch unexpected significant target motion.5. Margin derived from actual target motion is 2.5 mm isotropic, consist with current practice. CONCLUSIONS: Clinical experience of the 37 Gy/5-fraction prostate SBRT from a single institution is reported. Dosimetric analysis demonstrated excellent target coverage and OAR sparing for our first 28 patients in this trial. Online IGRT techniques implemented are both effective and reliable. Per-beam correction in general provides a small benefit in dosimetry. Target motion measured by online localization devices confirms that current margin selection is adequate.

Quantitative analysis of the factors which affect the interpatient organ-at-risk dose sparing variation in IMRT plans.

PURPOSE: The authors present an evidence-based approach to quantify the effects of an array of patient anatomical features of the planning target volumes (PTVs) and organs-at-risk (OARs) and their spatial relationships on the interpatient OAR dose sparing variation in intensity modulated radiation therapy (IMRT) plans by learning from a database of high-quality prior plans. METHODS: The authors formulized the dependence of OAR dose volume histograms (DVHs) on patient anatomical factors into feature models which were learned from prior plans by a stepwise multiple regression method. IMRT plans for 64 prostate, 82 head-and-neck (HN) treatments were used to train the models. Two major groups of anatomical features were considered in this study: the volumetric information and the spatial information. The geometry of OARs relative to PTV is represented by the distance-to-target histogram, DTH. Important anatomical and dosimetric features were extracted from DTH and DVH by principal component analysis. The final models were tested by additional 24 prostate and 24 HN plans. RESULTS: Significant patient anatomical factors contributing to OAR dose sparing in prostate and HN IMRT plans have been analyzed and identified. They are: the median distance between OAR and PTV, the portion of OAR volume within an OAR specific distance range, and the volumetric factors: the fraction of OAR volume which overlaps with PTV and the portion of OAR volume outside the primary treatment field. Overall, the determination coefficients R(2) for predicting the first principal component score (PCS1) of the OAR DVH by the above factors are above 0.68 for all the OARs and they are more than 0.53 for predicting the second principal component score (PCS2) of the OAR DVHs except brainstem and spinal cord. Thus, the above set of anatomical features combined has captured significant portions of the DVH variations for the OARs in prostate and HN plans. To test how well these features capture the interpatient organ dose sparing variations in general, the DVHs and specific dose-volume indices calculated from the regression models were compared with the actual DVHs and dose-volume indices from each patient's plan in the validation dataset. The dose-volume indices compared were V99%, V85%, and V50% for bladder and rectum in prostate plans and parotids median dose in HN plans. The authors found that for the bladder and rectum models, 17 out of 24 plans (71%) were within 6% OAR volume error and 21 plans (85%) were within 10% error; For the parotids model, the median dose values for 30 parotids out of 48 (63%) were within 6% prescription dose error and the values in 40 parotids (83%) were within 10% error. CONCLUSIONS: Quantitative analysis of patient anatomical features and their correlation with OAR dose sparing has identified a number of important factors that explain significant amount of interpatient DVH variations in OARs. These factors can be incorporated into evidence-based learning models as effective features to provide patient-specific OAR dose sparing goals.