The goal of this study is to investigate the Pareto optimal tradeoffs between target coverage and hippocampal sparing using knowledge-based multicriteria optimization (MCO). Ten prior clinical cases were selected that were treated with hippocampal avoidance whole brain radiotherapy (HA-WBRT) using VMAT. A new, balanced plan was generated for each case using an in-house RapidPlan model in the Eclipse V16.1 treatment planning system. The MCO decision support tool was used to create 4 Pareto optimal plans. The Pareto optimal plans were created using PTV Dmin and hippocampus Dmax as tradeoff criteria. The tradeoff plans were generated for each patient by adjusting PTV Dmin from the value achieved by the corresponding balanced plan in fixed intervals as follows: -4 Gy, -2 Gy, +2 Gy, and +4 Gy. All plans were normalized so that 95% of the PTV was covered by the prescription dose. A 1-way ANOVA, with Geisser-Greenhouse correction, was used for statistical analysis. When evaluating the achieved PTV Dmin and D98%, the results showed the dose to the hippocampus decreased as coverage lowered and in comparison, D98% was higher when the PTV coverage was increased. When comparing multiple tradeoffs, the p-value for PTV D98% was 0.0026, and the p-values for PTV D2%, PTV Dmin, Hippocampus Dmax, Dmin, and Dmean were all less than 0.0001, indicating that the tradeoff plans achieved statistically significant differences. The results also showed that Pareto optimal plans failed to reduce hippocampal dose beyond a certain point, indicating more limited achievability of the MCO-navigated plans than the interface suggested. This study presents valuable data for planning results for HA-WBRT using MCO. MCO has shown to be mostly effective in adjusting the tradeoff between PTV coverage and hippocampal dose.

To evaluate the effects of arc geometry on lung stereotactic body radiation therapy (SBRT) plan quality, using collision check software to select safe beam angles. Thirty lung SBRT cases were replanned 10Gy x 5 using 4 volumetric modulated arc therapy (VMAT) geometries: coplanar lateral (cpLAT), coplanar oblique (cpOBL), noncoplanar lateral (ncpLAT) and noncoplanar oblique (ncpOBL). Lateral arcs spanned 180° on the affected side whereas the 180° oblique arcs crossed midline to spare healthy tissues. Couch angles were separated by 30° on noncoplanar plans. Clearance was verified with Radformation CollisionCheck software. Optimization objectives were the same across the four plans for each case. Planning target volume (PTV) coverage was set to 95% and then plans were evaluated for dose conformity, healthy tissue doses, and monitor units. Clinically treated plans were used to benchmark the results. The volumes of the 25%, 50% and 75% isodoses were smaller with noncoplanar than coplanar arcs. The volume of the 50% isodose line relative to the PTV (CI50%) was as follows: clinical 3.75±0.72, cpLAT 3.39 ± 0.37, cpOBL 3.36 ± 0.34, ncpLAT 3.02 ± 0.21 and ncpOBL 3.02 ± 0.22. The Wilcoxon signed rank test with Bonferroni correction showed p < 0.005 in all CI50% comparisons except between the cpLat and cpObl arcs and between the ncpLat and ncpObl arcs. The best lung sparing was achieved using ncpObl arcs, which was statistically significant (p < 0.001) compared with the other four plans at V12.5Gy, V13.5Gy and V20Gy. Chest wall V30Gy was significantly better using noncoplanar arcs in comparison to the other plan types (p < 0.001). The best heart sparing at V10Gy from the ncpOBL arcs was significant compared with the clinical and cpLat plans (p < 0.005). Arc geometry has a substantial effect on lung SBRT plan quality. Noncoplanar arcs were superior to coplanar arcs at compacting the dose distribution at the 25%, 50% and 75% isodose levels, thereby reducing the dose to healthy tissues. Further healthy tissue sparing was achieved using oblique arcs that minimize the pathlength through healthy tissues and avoid organs at risk. The dosimetric advantages of the noncoplanar and oblique arcs require careful beam angle selection during treatment planning to avoid collisions during treatment, which may be facilitated by commercial software.

The implementation of knowledge-based planning (KBP) continues to grow in radiotherapy clinics. KBP guides radiation treatment design by generating clinically acceptable plans in a timely and resource-efficient manner. The role of multiple KBP models tailored for variations within a disease site remains undefined in part because of the substantial effort and number of training cases required to create a high-quality KBP model. In this study, our aim was to explore whether site-specific KBP models lead to clinically meaningful differences in plan quality for head-and-neck (HN) patients when compared to a general model. One KBP model was created from prior volumetric-modulated arc therapy (VMAT) cases that treated unilateral HN lymph nodes while another model was created from VMAT cases that treated bilateral HN nodes. Thirty cases from each model (60 cases total) were randomly selected to create a third, general model. These models were applied to 60 HN test cases - 30 unilateral and 30 bilateral - to generate 180 VMAT plans in Eclipse. Clinically relevant dose metrics were compared between models. Paired-sample t-tests were used for statistical analysis, with the threshold for statistical significance set a priori at 0.007, taking into consideration multiple hypothesis testing to avoid type I error. For unilateral test cases, the unilateral model-generated plans had significantly lower spinal cord maximum doses (12.1 Gy vs 19.3 Gy, p < 0.001) and oral cavity mean doses (20.8 Gy vs 23.0 Gy, p < 0.001), compared with the bilateral model-generated plans. The unilateral and general models generated comparable plans for unilateral HN test cases. For bilateral test cases, the bilateral model created plans had significantly lower brainstem maximum doses (10.8 Gy vs 12.2 Gy, p < 0.001) and parotid mean doses (24.0 Gy vs 25.5 Gy, p < 0.001) when compared to the unilateral model. Right parotid mean doses were lower for bilateral model plans compared to general model plans (23.8 Gy vs 24.4 Gy). The general model created plans with significantly lower brainstem maximum doses (10.3 Gy vs 10.8 Gy) and oral cavity mean doses (35.3 Gy vs 36.7 Gy) when compared with bilateral model-generated plans. The general model outperformed the bilateral model in several dose metrics but they were not deemed clinically significant. For both case sets, the unilateral and general model created plans had higher monitor units when compared to the bilateral model, likely due to more stringent constraint settings. All other dose metrics were comparable. This study demonstrates that a balanced general HN model created using carefully curated treatment plans can produce high quality plans comparable to dedicated unilateral and bilateral models.

Radiotherapy (RT) doses to cardiac substructures from the definitive treatment of locally advanced non-small cell lung cancers (NSCLC) have been linked to post-RT cardiac toxicities. With modern treatment delivery techniques, it is possible to focus radiation doses to the planning target volume while reducing cardiac substructure doses. However, it is often challenging to design such treatment plans due to complex tradeoffs involving numerous cardiac substructures. Here, we built a cardiac-substructure-based knowledge-based planning (CS-KBP) model and retrospectively evaluated its performance against a cardiac-based KBP (C-KBP) model and manually optimized patient treatment plans. CS-KBP/C-KBP models were built with 27 previously-treated plans that preferentially spare the heart. While the C-KBP training plans were created with whole heart structures, the CS-KBP model training plans each have 15 cardiac substructures (coronary arteries, valves, great vessels, and chambers of the heart). CS-KBP training plans reflect cardiac-substructure sparing preferences. We evaluated both models on 28 additional patients. Three sets of treatment plans were compared: (1) manually optimized, (2) C-KBP model-generated, and (3) CS-KBP model-generated. Plans were normalized to receive the prescribed dose to at least 95% of the PTV. A two-tailed paired-sample t-test was performed for clinically relevant dose-volume metrics to evaluate the performance of the CS-KBP model against the C-KBP model and clinical plans, respectively. Overall results show significantly improved cardiac substructure sparing by CS-KBP in comparison to C-KBP and the clinical plans. For instance, the average left anterior descending artery volume receiving 15 Gy (V15 Gy) was significantly lower (p < 0.01) for CS-KBP (0.69 ± 1.57 cc) compared to the clinical plans (1.23 ± 1.76 cc) and C-KBP plans (1.05 ± 1.68 cc). In conclusion, the CS-KBP model significantly improved cardiac-substructure sparing without exceeding the tolerances of other OARs or compromising PTV coverage.

Background Knowledge-based planning (KBP) is increasingly implemented clinically because of its demonstrated ability to improve treatment planning efficiency and reduce plan quality variations. However, cases with large dose-volume histogram (DVH) prediction uncertainties may still need manual adjustments by the planner to achieve high plan quality. Purpose The purpose of this study is to develop a data-driven method to detect patients with high prediction uncertainties so that intentional effort is directed to these patients. Methods We apply an anomaly detection method known as the local outlier factor (LOF) to a dataset consisting of the training set and each of the prospective patients considered, to evaluate their likelihood of being an anomaly when compared with the training cases. Features used in the LOF analysis include anatomical features and the model-generated DVH principal component scores. To test the efficacy of the proposed model, 142 prostate patients were retrieved from the clinical database and split into a training dataset of 100 patients and a test dataset of 42 patients. The outlier identification performance was quantified by the difference between the DVH prediction root-mean-squared errors (RMSE) of the identified outlier cases and that of the remaining inlier cases. Results With a predefined LOF threshold of 1.4, the inlier cases achieved average RMSEs of 5.0 and 6.7 for bladder and rectum, while the outlier cases have substantially higher RMSEs of 6.7 and 13.0 in comparison. Conclusions We propose a method that can determine the prospective patient's outlier status. This method can be integrated into existing automated treatment planning workflows to reduce the risk of generating suboptimal treatment plans while providing an upfront alert to the treatment planner.

Abstract Purpose Metallic implants have been correlated to local control failure for spinal sarcoma and chordoma patients due to the uncertainty of implant delineation from computed tomography (CT). Such uncertainty can compromise the proton Monte Carlo dose calculation (MCDC) accuracy. A component method is proposed to determine the dimension and volume of the implants from CT images. Methods The proposed component method leverages the knowledge of surgical implants from medical supply vendors to predefine accurate contours for each implant component, including tulips, screw bodies, lockers, and rods. A retrospective patient study was conducted to demonstrate the feasibility of the method. The reference implant materials and samples were collected from patient medical records and vendors, Medtronic and NuVasive. Additional CT images with extensive features, such as extended Hounsfield units and various reconstruction diameters, were used to quantify the uncertainty of implant contours. Results For in vivo patient implant estimation, the reference and the component method differences were 0.35, 0.17, and 0.04 cm3 for tulips, screw bodies, and rods, respectively. The discrepancies by a conventional threshold method were 5.46, 0.76, and 0.05 cm3, respectively. The mischaracterization of implant materials and dimensions can underdose the clinical target volume coverage by 20 cm3 for a patient with eight lumbar implants. The tulip dominates the dosimetry uncertainty as it can be made from titanium or cobalt–chromium alloys by different vendors. Conclusions A component method was developed and demonstrated using phantom and patient studies with implants. The proposed method provides more accurate implant characterization for proton MCDC and can potentially enhance the treatment quality for proton therapy. The current proof‐of‐concept study is limited to the implant characterization for lumbar spine. Future investigations could be extended to cervical spine and dental implants for head‐and‐neck patients where tight margins are required to spare organs at risk.

Purpose: High radiation doses to the heart have been correlated with poor overall survival in patients receiving radiation therapy for stage III non-small cell lung cancer (NSCLC). We built a knowledge-based planning (KBP) tool to limit the dose to the heart during creation of volumetric modulated arc therapy (VMAT) treatment plans for patients being treated to 60 Gy in 30 fractions for stage III NSCLC. Methods and Materials: A previous study at our institution retrospectively delineated intracardiac volumes and optimized VMAT treatment plans to reduce dose to these substructures and to the whole heart. Two RapidPlan (RP) KBP models were built from this cohort, 1 model using the clinical plans and a separate model using the cardiac-optimized plans. Using target volumes and 6 organs at risk (OARs), models were trained to generate treatment plans in a semiautomated process. The cardiac-sparing KBP model was tested in the same cohort used for training, and both models were tested on an external validation cohort of 30 patients. Results: Both RP models produced clinically acceptable plans in terms of target coverage, dose uniformity, and dose to OARs. Compared with the previously created cardiac-optimized plans, cardiac-sparing RPs showed significant reductions in the mean dose to the esophagus and lungs while performing similarly or better in all evaluated heart dose metrics. When comparing the 2 models, the cardiac-sparing RP showed reduced (P < .05) heart mean and maximum doses as well as volumes receiving 60 Gy, 50 Gy, and 30 Gy. Conclusions: By using a set of cardiac-optimized treatment plans for training, the proposed KBP model provided a means to reduce the dose to the heart and its substructures without the need to explicitly delineate cardiac substructures. This tool may offer reduced planning time and improved plan quality and might be used to improve patient outcomes.

Purpose: Increasing radiation dose to the heart is associated with worse survival in stage III nonsmall cell lung cancer. We sought to evaluate the ability of optimized volumetric modulated arc therapy (VMAT) and intensity modulated proton therapy (IMPT) to spare cardiac substructures. We also wanted to determine how a cardiac optimization treatment planning algorithm influences dose distribution to other thoracic organs at risk (OARs). Methods and Materials: Cardiac substructures were retrospectively contoured for all patients with stage III non-small cell lung cancer who were treated at our institution with VMAT to 60 Gy in 2-Gy fractions. The structures included valves, atrioventricular node, coronary arteries, chambers, and great vessels. New cardiac-optimized VMAT plans were created to spare these structures while preserving planning target volume coverage and maintaining standard dose constraints to OARs. Dosimetry variables for the new cardiac-optimized VMAT plans were compared via paired t test with the original VMAT plans. IMPT plans were also created, and the cardiac-optimized VMAT plans were then similarly compared with the IMPT plans. Results: Twenty-six patients who were treated from July 2013 to September 2017 were included. Compared with the original VMAT plans, statistically significant improvements were demonstrated for all cardiac structures for the new cardiac-optimized VMAT plans while maintaining or improving appropriate lung, esophagus, and spinal cord constraints and planning target volume coverage goals. Compared with cardiac-optimized VMAT, IMPT demonstrated additional statistically significant improvements for some cardiac dosimetry metrics while maintaining or improving other thoracic OAR constraints. Conclusions: VMAT is now widely available, and high-quality VMAT plans that incorporate cardiac substructures into the optimization process can provide overall improvements in dose to OARs and, in particular, substantial sparing of critical cardiac structures. IMPT provides some incremental dosimetric improvements beyond cardiac-optimized VMAT, the clinical significance of which remains uncertain. (C) 2019 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.