Divergent Clinical Equivalence Findings from DVH and NTCP Metrics for Alternative OAR Delineations with Increasing Setup Variability in Head-and-Neck Radiotherapy.

PURPOSE: This study quantifies the variation in dose-volume histogram (DVH) and normal tissue complication probability (NTCP) metrics for head-and-neck (HN) cancer patients when alternative organ-at-risk (OAR) delineations are used for treatment planning and for treatment plan evaluation. We particularly focus on the effects of daily patient positioning/setup variations (SV) in relation to treatment technique and delineation variability. MATERIALS AND METHODS: We generated two-arc VMAT, 5-beam IMRT, and 9-beam IMRT treatment plans for a cohort of 209 HN patients. These plans incorporated five different OAR delineation sets, including manual and four automated algorithms. Each treatment plan was assessed under various simulated per-fraction patient setup uncertainties, evaluating the potential clinical impacts through DVH and NTCP metrics. RESULTS: The study demonstrates that increasing setup variability generally reduces differences in DVH metrics between alternative delineations. However, in contrast, differences in NTCP metrics tend to increase with higher setup variability. This pattern is observed consistently across different treatment plans and delineator combinations, illustrating the intricate relationship between SV and delineation accuracy. Additionally, the need for delineation accuracy in treatment planning is shown to be case-specific and dependent on factors beyond geometric variations. CONCLUSIONS: The findings highlight the necessity for comprehensive quality assurance programs in radiotherapy, incorporating both dosimetric impact analysis and geometric variation assessment to ensure optimal delineation quality. The study emphasizes the complex dynamics of treatment planning in radiotherapy, advocating for personalized, case-specific strategies in clinical practice to enhance patient care quality and efficacy in the face of varying SV and delineation accuracies.

OpenKBP-Opt: an international and reproducible evaluation of 76 knowledge-based planning pipelines.

Objective.To establish an open framework for developing plan optimization models for knowledge-based planning (KBP).Approach.Our framework includes radiotherapy treatment data (i.e. reference plans) for 100 patients with head-and-neck cancer who were treated with intensity-modulated radiotherapy. That data also includes high-quality dose predictions from 19 KBP models that were developed by different research groups using out-of-sample data during the OpenKBP Grand Challenge. The dose predictions were input to four fluence-based dose mimicking models to form 76 unique KBP pipelines that generated 7600 plans (76 pipelines × 100 patients). The predictions and KBP-generated plans were compared to the reference plans via: the dose score, which is the average mean absolute voxel-by-voxel difference in dose; the deviation in dose-volume histogram (DVH) points; and the frequency of clinical planning criteria satisfaction. We also performed a theoretical investigation to justify our dose mimicking models.Main results.The range in rank order correlation of the dose score between predictions and their KBP pipelines was 0.50-0.62, which indicates that the quality of the predictions was generally positively correlated with the quality of the plans. Additionally, compared to the input predictions, the KBP-generated plans performed significantly better (P< 0.05; one-sided Wilcoxon test) on 18 of 23 DVH points. Similarly, each optimization model generated plans that satisfied a higher percentage of criteria than the reference plans, which satisfied 3.5% more criteria than the set of all dose predictions. Lastly, our theoretical investigation demonstrated that the dose mimicking models generated plans that are also optimal for an inverse planning model.Significance.This was the largest international effort to date for evaluating the combination of KBP prediction and optimization models. We found that the best performing models significantly outperformed the reference dose and dose predictions. In the interest of reproducibility, our data and code is freely available.

Knowledge-based quality control of organ delineations in radiation therapy.

PURPOSE: To reduce the likelihood of errors in organ delineations used for radiotherapy treatment planning, a knowledge-based quality control (KBQC) system, which discriminates between valid and anomalous delineations is developed. METHOD AND MATERIALS: The KBQC is comprised of a group-wise inference system and anomaly detection modules trained using historical priors from 296 locally advanced lung and prostate cancer patient computational tomographies (CTs). The inference system discriminates different organs based on shape, relational, and intensity features. For a given delineated image set, the inference system solves a combinatorial optimization problem that results in an organ group whose relational features follow those of the training set considering the posterior probabilities obtained from support vector machine (SVM), discriminant subspace ensemble (DSE), and artificial neural network (ANN) classifiers. These classifiers are trained on nonrelational features with a 10-fold cross-validation scheme. The anomaly detection module is a bank of ANN autoencoders, each corresponding with an organ, trained on nonrelational features. A heuristic rule detects anomalous organs that exceed predefined organ-specific tolerances for the feature reconstruction error and the classifier's posterior probabilities. Independent data sets with anomalous delineations were used to test the overall performance of the KBQC system. The anomalous delineations were manually manipulated, computer-generated, or propagated based on a transformation obtained by imperfect registrations. Both peer-review-based scoring system and shape similarity coefficient (DSC) were used to label regions of interest (ROIs) as normal or anomalous in two independent test cohorts. RESULTS: The accuracy of the classifiers was ≥ $\ge$ 99.8%, and the minimum per-class F1-scores were 0.99, 0.99, and 0.98 for SVM, DSE, and ANN, respectively. The group-wise inference system reduced the miss-classification likelihood for the test data set with anomalous delineations compared to each individual classifier and a fused classifier that used the average posterior probability of all classifiers. For 15 independent locally advanced lung patients, the system detected > $>$ 79% of the anomalous ROIs. For 1320 auto-segmented abdominopelvic organs, the anomaly detection system identified anomalous delineations, which also had low Dice similarity coefficient values with respect to manually delineated organs in the training data set. CONCLUSION: The KBQC system detected anomalous delineations with superior accuracy compared to classification methods that judge only based on posterior probabilities.

An Automated Workflow to Improve Efficiency in Radiation Therapy Treatment Planning by Prioritizing Organs at Risk.

PURPOSE: Manual delineation (MD) of organs at risk (OAR) is time and labor intensive. Auto-delineation (AD) can reduce the need for MD, but because current algorithms are imperfect, manual review and modification is still typically used. Recognizing that many OARs are sufficiently far from important dose levels that they do not pose a realistic risk, we hypothesize that some OARs can be excluded from MD and manual review with no clinical effect. The purpose of this study was to develop a method that automatically identifies these OARs and enables more efficient workflows that incorporate AD without degrading clinical quality. METHODS AND MATERIALS: Preliminary dose map estimates were generated for n = 10 patients with head and neck cancers using only prescription and target-volume information. Conservative estimates of clinical OAR objectives were computed using AD structures with spatial expansion buffers to account for potential delineation uncertainties. OARs with estimated dose metrics below clinical tolerances were deemed low priority and excluded from MD and/or manual review. Final plans were then optimized using high-priority MD OARs and low-priority AD OARs and compared with reference plans generated using all MD OARs. Multiple different spatial buffers were used to accommodate different potential delineation uncertainties. RESULTS: Sixty-seven out of 201 total OARs were identified as low-priority using the proposed methodology, which permitted a 33% reduction in structures requiring manual delineation/review. Plans optimized using low-priority AD OARs without review or modification met all planning objectives that were met when all MD OARs were used, indicating clinical equivalence. CONCLUSIONS: Prioritizing OARs using estimated dose distributions allowed a substantial reduction in required MD and review without affecting clinically relevant dosimetry.

Dose escalation in the definite target volume.

PURPOSE: To introduce the definite target volume (DTV) and evaluate dosimetric consequences of boosting dose to this region of high clinical target volume (CTV)- and low organs at risk (OAR)-probability. METHODS: This work defines the DTV via occupancy probability and via contraction of the CTV by margin M less any planning risk volume (PRV) volumes. The equivalence to within varying occupancy probability of the two methods is established for spherical target volumes. We estimate a margin for four radiation treatment sites based on modern images guided radiation therapy-literature utilizing repeat volumetric imaging. Based on margins and patient-specific DTV targets, the ability to dose escalate the DTV including the effects of spatial uncertainty was evaluated. We simulate delivery assuming violation of the underlying spatial uncertainty of 130%. RESULTS: Contracting the planning target volume (PTV) by M and excluding PRV volumes, the DTV ranged from 7.3 to 93.6 cc. In a brain treatment, DTV-Dmax increased to 66.8 Gy (145% of prescription isodose); in advanced lung DTV-Dmax increased to 122.2 Gy (204% of prescription isodose), in a pancreatic case DTV-Dmax was boosted up to 87.3 Gy (173% or prescription isodose), and in retroperitoneal sarcoma to 74.6 Gy (249% of prescription isodose). The high point doses were not associated with increased dose to OARs, even when considering the effects of spatial uncertainty. Simulated delivery at 130% of assumed spatial uncertainties revealed DTV-based planning can result in minor increases in OAR Dmean/Dmax of 2.7 ± 2.1 Gy/1.8 ± 2.2 Gy with duodenum Dmax > 110% of prescription isodose in the pancreatic case. These dose increases were consistent with simulation of clinical, homogenous PTV-dose distributions. CONCLUSION: We have proposed and tested a method to deliver extremely high doses to subvolumes of target volumes in multiple treatment sites by defining a new target volume, the DTV. Based on simulated delivery, the method does not result in significant increases in dose to OARs if spatial uncertainty can be estimated.

Multiobjective, Multidelivery Optimization for Radiation Therapy Treatment Planning.

PURPOSE: To introduce multiobjective, multidelivery optimization (MODO), which generates alternative patient-specific plans emphasizing dosimetric trade-offs and conformance to quasi-constrained (QC) conditions for multiple delivery techniques. METHODS AND MATERIALS: For M delivery techniques and N organs at risk (OARs), MODO generates M (N + 1) alternative treatment plans per patient. For 30 locally advanced lung cancer cases, the algorithm was investigated based on dosimetric trade-offs to 4 OARs: each lung, heart, and esophagus (N = 4) and 4 delivery techniques (4-field coplanar intensity modulated radiation therapy [IMRT], 9-field coplanar IMRT, 27-field noncoplanar IMRT, and noncoplanar arc IMRT) and conformance to QC conditions, including dose to 95% (D95) of the planning target volume (PTV), maximum dose (Dmax) to PTV (PTV-Dmax), and spinal cord Dmax. The MODO plan set was evaluated for conformance to QC conditions while simultaneously revealing dosimetric trade-offs. Statistically significant dosimetric trade-offs were defined such that the coefficient of determination was >0.8 with dosimetric indices that varied by at least 5 Gy. RESULTS: Plans varied mean dose by >5 Gy to ipsilateral lung for 24 of 30 patients, contralateral lung for 29 of 30 patients, esophagus for 29 of 30 patients, and heart for 19 of 30 patients. In the 600 plans, average PTV-D95 = 67.6 ± 2.1 Gy, PTV-Dmax = 79.8 ± 5.2 Gy, and spinal cord Dmax among all plans was 51.4 Gy. Statistically significant dosimetric trade-offs reducing OAR mean dose by >5 Gy were evident in 19 of 30 patients, including multiple OAR trade-offs of at least 5 Gy in 7 of 30 cases. The most common statistically significant trade-off was increasing PTV-Dmax to reduce dose to OARs (15 of 30). The average 4-field plan reduced total lung V20 by 10.4% ± 8.3% compared with 9-field plans, 7.7% ± 7.9% compared with 27-field noncoplanar plans, and 11.7% ± 10.3% compared with 2-arc noncoplanar plans, with corresponding increases in PTV-Dmax of 5.3 ± 5.9 Gy, 4.6 ± 5.6 Gy, and 9.3 ± 7.3 Gy. CONCLUSIONS: The proposed optimization method produces clinically relevant treatment plans that meet QC conditions and demonstrate variations in OAR doses.

Beam modeling and beam model commissioning for Monte Carlo dose calculation-based radiation therapy treatment planning: Report of AAPM Task Group 157.

Dose calculation plays an important role in the accuracy of radiotherapy treatment planning and beam delivery. The Monte Carlo (MC) method is capable of achieving the highest accuracy in radiotherapy dose calculation and has been implemented in many commercial systems for radiotherapy treatment planning. The objective of this task group was to assist clinical physicists with the potentially complex task of acceptance testing and commissioning MC-based treatment planning systems (TPS) for photon and electron beam dose calculations. This report provides an overview on the general approach of clinical implementation and testing of MC-based TPS with a specific focus on models of clinical photon and electron beams. Different types of beam models are described including those that utilize MC simulation of the treatment head and those that rely on analytical methods and measurements. The trade-off between accuracy and efficiency in the various source-modeling approaches is discussed together with guidelines for acceptance testing of MC-based TPS from the clinical standpoint. Specific recommendations are given on methods and practical procedures to commission clinical beam models for MC-based TPS.

Robust radiotherapy planning.

Motion and uncertainty in radiotherapy is traditionally handled via margins. The clinical target volume (CTV) is expanded to a larger planning target volume (PTV), which is irradiated to the prescribed dose. However, the PTV concept has several limitations, especially in proton therapy. Therefore, robust and probabilistic optimization methods have been developed that directly incorporate motion and uncertainty into treatment plan optimization for intensity modulated radiotherapy (IMRT) and intensity modulated proton therapy (IMPT). Thereby, the explicit definition of a PTV becomes obsolete and treatment plan optimization is directly based on the CTV. Initial work focused on random and systematic setup errors in IMRT. Later, inter-fraction prostate motion and intra-fraction lung motion became a research focus. Over the past ten years, IMPT has emerged as a new application for robust planning methods. In proton therapy, range or setup errors may lead to dose degradation and misalignment of dose contributions from different beams - a problem that cannot generally be addressed by margins. Therefore, IMPT has led to the first implementations of robust planning methods in commercial planning systems, making these methods available for clinical use. This paper first summarizes the limitations of the PTV concept. Subsequently, robust optimization methods are introduced and their applications in IMRT and IMPT planning are reviewed.

Quality assurance tool for organ at risk delineation in radiation therapy using a parametric statistical approach.

PURPOSE: To develop a quality assurance (QA) tool that identifies inaccurate organ at risk (OAR) delineations. METHODS: The QA tool computed volumetric features from prior OAR delineation data from 73 thoracic patients to construct a reference database. All volumetric features of the OAR delineation are computed in three-dimensional space. Volumetric features of a new OAR are compared with respect to those in the reference database to discern delineation outliers. A multicriteria outlier detection system warns users of specific delineation outliers based on combinations of deviant features. Fifteen independent experimental sets including automatic, propagated, and clinically approved manual delineation sets were used for verification. The verification OARs included manipulations to mimic common errors. Three experts reviewed the experimental sets to identify and classify errors, first without; and then 1 week after with the QA tool. RESULTS: In the cohort of manual delineations with manual manipulations, the QA tool detected 94% of the mimicked errors. Overall, it detected 37% of the minor and 85% of the major errors. The QA tool improved reviewer error detection sensitivity from 61% to 68% for minor errors (P = 0.17), and from 78% to 87% for major errors (P = 0.02). CONCLUSIONS: The QA tool assists users to detect potential delineation errors. QA tool integration into clinical procedures may reduce the frequency of inaccurate OAR delineation, and potentially improve safety and quality of radiation treatment planning.

Dose to mass for evaluation and optimization of lung cancer radiation therapy.

PURPOSE: To evaluate potential organ at risk dose-sparing by using dose-mass-histogram (DMH) objective functions compared with dose-volume-histogram (DVH) objective functions. METHODS: Treatment plans were retrospectively optimized for 10 locally advanced non-small cell lung cancer patients based on DVH and DMH objectives. DMH-objectives were the same as DVH objectives, but with mass replacing volume. Plans were normalized to dose to 95% of the PTV volume (PTV-D95v) or mass (PTV-D95m). For a given optimized dose, DVH and DMH were intercompared to ascertain dose-to-volume vs. dose-to-mass differences. Additionally, the optimized doses were intercompared using DVH and DMH metrics to ascertain differences in optimized plans. Mean dose to volume, Dv‾, mean dose to mass, DM‾, and fluence maps were intercompared. RESULTS: For a given dose distribution, DVH and DMH differ by >5% in heterogeneous structures. In homogeneous structures including heart and spinal cord, DVH and DMH are nearly equivalent. At fixed PTV-D95v, DMH-optimization did not significantly reduce dose to OARs but reduced PTV-Dv‾ by 0.20±0.2Gy (p=0.02) and PTV-DM‾ by 0.23±0.3Gy (p=0.02). Plans normalized to PTV-D95m also result in minor PTV dose reductions and esophageal dose sparing (Dv‾ reduced 0.45±0.5Gy, p=0.02 and DM‾ reduced 0.44±0.5Gy, p=0.02) compared to DVH-optimized plans. Optimized fluence map comparisons indicate that DMH optimization reduces dose in the periphery of lung PTVs. CONCLUSIONS: DVH- and DMH-dose indices differ by >5% in lung and lung target volumes for fixed dose distributions, but optimizing DMH did not reduce dose to OARs. The primary difference observed in DVH- and DMH-optimized plans were variations in fluence to the periphery of lung target PTVs, where low density lung surrounds tumor.

Clinical adequacy assessment of autocontours for prostate IMRT with meaningful endpoints.

PURPOSE: To determine if radiation treatment plans created based on autosegmented (AS) regions-of-interest (ROI)s are clinically equivalent to plans created based on manually segmented ROIs, where equivalence is evaluated using probabilistic dosimetric metrics and probabilistic biological endpoints for prostate IMRT. METHOD AND MATERIALS: Manually drawn contours and autosegmented ROIs were created for 167 CT image sets acquired from 19 prostate patients. Autosegmentation was performed utilizing Pinnacle's Smart Probabilistic Image Contouring Engine. For each CT set, 78 Gy/39 fraction 7-beam IMRT treatment plans with 1 cm CTV-to-PTV margins were created for each of the three contour scenarios; PMD using manually delineated (MD) ROIs, PAS using autosegmented ROIs, and PAM using autosegmented organ-at-risks (OAR)s and the manually drawn target. For each plan, 1000 virtual treatment simulations with different systematic errors for each simulation and a different random error for each fraction were performed. The statistical probability of achieving dose-volume metrics (coverage probability (CP)), expectation values for normal tissue complication probability (NTCP), and tumor control probability (TCP) metrics for all possible cross-evaluation pairs of ROI types and planning scenarios were reported. In evaluation scenarios, the root mean square loss (RMSL) and maximum absolute loss (MAL) of coverage probability of dose-volume objectives, E[TCP], and E[NTCP] were compared with respect to the base plan created and evaluated with manually drawn contours. RESULTS: Femoral head dose objectives were satisfied in all situations, as well as the maximum dose objectives for all ROIs. Bladder metrics were within the clinical coverage tolerances except D35Gy for the autosegmented plan evaluated with the manual contours. Dosimetric indices for CTV and rectum could be highly compromised when the definition of the ROIs switched from manually delineated to autosegmented. Seventy-two percent of CT image sets satisfied the worst-case CP thresholds for all dosimetric objectives in all scenarios, the percentage dropped to 50% if biological indices were taken into account. Among evaluation scenarios, (MD,PAM ) bore the highest resemblance to (MD,PMD ) where 99% and 88% of cases met all CP thresholds for bladder and rectum, respectively. CONCLUSIONS: When including daily setup variations in prostate IMRT, the dose-volume metric CP, and biological indices of ROIs were approximately equivalent for the plans created based on manually drawn targets and autosegmented OARs in 88% of cases. The accuracy of autosegmented prostates and rectums are impediment to attain statistically equivalent plans created based on manually drawn ROIs.

A Swiss cheese error detection method for real-time EPID-based quality assurance and error prevention.

PURPOSE: To develop a robust and efficient process that detects relevant dose errors (dose errors of ≥5%) in external beam radiation therapy and directly indicates the origin of the error. The process is illustrated in the context of electronic portal imaging device (EPID)-based angle-resolved volumetric-modulated arc therapy (VMAT) quality assurance (QA), particularly as would be implemented in a real-time monitoring program. METHODS: A Swiss cheese error detection (SCED) method was created as a paradigm for a cine EPID-based during-treatment QA. For VMAT, the method compares a treatment plan-based reference set of EPID images with images acquired over each 2° gantry angle interval. The process utilizes a sequence of independent consecutively executed error detection tests: an aperture check that verifies in-field radiation delivery and ensures no out-of-field radiation; output normalization checks at two different stages; global image alignment check to examine if rotation, scaling, and translation are within tolerances; pixel intensity check containing the standard gamma evaluation (3%, 3 mm) and pixel intensity deviation checks including and excluding high dose gradient regions. Tolerances for each check were determined. To test the SCED method, 12 different types of errors were selected to modify the original plan. A series of angle-resolved predicted EPID images were artificially generated for each test case, resulting in a sequence of precalculated frames for each modified treatment plan. The SCED method was applied multiple times for each test case to assess the ability to detect introduced plan variations. To compare the performance of the SCED process with that of a standard gamma analysis, both error detection methods were applied to the generated test cases with realistic noise variations. RESULTS: Averaged over ten test runs, 95.1% of all plan variations that resulted in relevant patient dose errors were detected within 2° and 100% within 14° (<4% of patient dose delivery). Including cases that led to slightly modified but clinically equivalent plans, 89.1% were detected by the SCED method within 2°. Based on the type of check that detected the error, determination of error sources was achieved. With noise ranging from no random noise to four times the established noise value, the averaged relevant dose error detection rate of the SCED method was between 94.0% and 95.8% and that of gamma between 82.8% and 89.8%. CONCLUSIONS: An EPID-frame-based error detection process for VMAT deliveries was successfully designed and tested via simulations. The SCED method was inspected for robustness with realistic noise variations, demonstrating that it has the potential to detect a large majority of relevant dose errors. Compared to a typical (3%, 3 mm) gamma analysis, the SCED method produced a higher detection rate for all introduced dose errors, identified errors in an earlier stage, displayed a higher robustness to noise variations, and indicated the error source.

Benefits of adaptive radiation therapy in lung cancer as a function of replanning frequency.

PURPOSE: To quantify the potential benefit associated with daily replanning in lung cancer in terms of normal tissue dose sparing and to characterize the tradeoff between adaptive benefit and replanning frequency. METHODS: A set of synthetic images and contours, derived from weekly active breathing control images of 12 patients who underwent radiation therapy treatment for nonsmall cell lung cancer, is generated for each fraction of treatment using principal component analysis in a way that preserves temporal anatomical trends (e.g., tumor regression). Daily synthetic images and contours are used to simulate four different treatment scenarios: (1) a "no-adapt" scenario that simulates delivery of an initial plan throughout treatment, (2) a "midadapt" scenario that implements a single replan for fraction 18, (3) a "weekly adapt" scenario that simulates weekly adaptations, and (4) a "full-adapt" scenario that simulates daily replanning. An initial intensity modulated radiation therapy plan is created for each patient and replanning is carried out in an automated fashion by reoptimizing beam apertures and weights. Dose is calculated on each image and accumulated to the first in the series using deformable mappings utilized in synthetic image creation for comparison between simulated treatments. RESULTS: Target coverage was maintained and cord tolerance was not exceeded for any of the adaptive simulations. Average reductions in mean lung dose (MLD) and volume of lung receiving 20 Gy or more (V20lung) were 65 ± 49 cGy (p = 0.000 01) and 1.1% ± 1.2% (p = 0.0006), respectively, for all patients. The largest reduction in MLD for a single patient was 162 cGy, which allowed an isotoxic escalation of the target dose of 1668 cGy. Average reductions in cord max dose, mean esophageal dose (MED), dose received by 66% of the heart (D66heart), and dose received by 33% of the heart (D33heart), were 158 ± 280, 117 ± 121, 37 ± 77, and 99 ± 120 cGy, respectively. Average incremental reductions in MLD for the midadapt, weekly adapt, and full-adapt treatments were 38, 18, and 8 cGy, respectively. Incremental reductions in MED for the same treatments were 57, 37, and 23 cGy. Reductions in MLD and MED for the full-adapt treatment were correlated with the absolute decrease in the planning target volume (r = 0.34 and r = 0.26). CONCLUSIONS: Adaptive radiation therapy for lung cancer yields clinically relevant reductions in normal tissue doses for frequencies of adaptation ranging from a single replan up to daily replanning. Increased frequencies of adaptation result in additional benefit while magnitude of benefit decreases.

Coverage-based treatment planning to accommodate delineation uncertainties in prostate cancer treatment.

PURPOSE: To compare two coverage-based planning (CP) techniques with fixed margin-based (FM) planning for high-risk prostate cancer treatments, with the exclusive consideration of the dosimetric impact of delineation uncertainties of target structures and normal tissues. METHODS: In this work, 19-patient data sets were involved. To estimate structure dose for each delineated contour under the influence of interobserver contour variability and CT image quality limitations, 1000 alternative structures were simulated by an average-surface-of-standard-deviation model, which utilized the patient-specific information of delineated structure and CT image contrast. An IMRT plan with zero planning-target-volume (PTV) margin on the delineated prostate and seminal vesicles [clinical-target-volume (CTV prostate) and CTVSV] was created and dose degradation due to contour variability was quantified by the dosimetric consequences of 1000 alternative structures. When D98 failed to achieve a 95% coverage probability objective D98,95 ≥ 78 Gy (CTV prostate) or D98,95 ≥ 66 Gy (CTVSV), replanning was performed using three planning techniques: (1) FM (PTV prostate margin = 4,5,6 mm and PTVSV margin = 4,5,7 mm for RL, PA, and SI directions, respectively), (2) CPOM which optimized uniform PTV margins for CTV prostate and CTVSV to meet the D98,95 objectives, and (3) CPCOP which directly optimized coverage-based objectives for all the structures. These plans were intercompared by computing percentile dose-volume histograms and tumor-control probability/normal tissue complication probability (TCP/NTCP) distributions. RESULTS: Inherent contour variability resulted in unacceptable CTV coverage for the zero-PTV-margin plans for all patients. For plans designed to accommodate contour variability, 18/19 CP plans were most favored by achieving desirable D98,95 and TCP/NTCP values. The average improvement of probability of complication free control was 9.3% for CPCOP plans and 3.4% for CPOM plans. CONCLUSIONS: When the delineation uncertainties need to be considered for prostate patients, CP techniques can produce more desirable plans than FM plans for most patients. The relative advantages between CPCOP and CPOM techniques are patient specific.

Safety and feasibility of STAT RAD: Improvement of a novel rapid tomotherapy-based radiation therapy workflow by failure mode and effects analysis.

PURPOSE: The clinical challenge of radiation therapy (RT) for painful bone metastases requires clinicians to consider both treatment efficacy and patient prognosis when selecting a radiation therapy regimen. The traditional RT workflow requires several weeks for common palliative RT schedules of 30 Gy in 10 fractions or 20 Gy in 5 fractions. At our institution, we have created a new RT workflow termed "STAT RAD" that allows clinicians to perform computed tomographic (CT) simulation, planning, and highly conformal single fraction treatment delivery within 2 hours. In this study, we evaluate the safety and feasibility of the STAT RAD workflow. METHODS AND MATERIALS: A failure mode and effects analysis (FMEA) was performed on the STAT RAD workflow, including development of a process map, identification of potential failure modes, description of the cause and effect, temporal occurrence, and team member involvement in each failure mode, and examination of existing safety controls. A risk probability number (RPN) was calculated for each failure mode. As necessary, workflow adjustments were then made to safeguard failure modes of significant RPN values. After workflow alterations, RPN numbers were again recomputed. RESULTS: A total of 72 potential failure modes were identified in the pre-FMEA STAT RAD workflow, of which 22 met the RPN threshold for clinical significance. Workflow adjustments included the addition of a team member checklist, changing simulation from megavoltage CT to kilovoltage CT, alteration of patient-specific quality assurance testing, and allocating increased time for critical workflow steps. After these modifications, only 1 failure mode maintained RPN significance; patient motion after alignment or during treatment. CONCLUSIONS: Performing the FMEA for the STAT RAD workflow before clinical implementation has significantly strengthened the safety and feasibility of STAT RAD. The FMEA proved a valuable evaluation tool, identifying potential problem areas so that we could create a safer workflow.

Multiple anatomy optimization of accumulated dose.

PURPOSE: To investigate the potential advantages of multiple anatomy optimization (MAO) for lung cancer radiation therapy compared to the internal target volume (ITV) approach. METHODS: MAO aims to optimize a single fluence to be delivered under free-breathing conditions such that the accumulated dose meets the plan objectives, where accumulated dose is defined as the sum of deformably mapped doses computed on each phase of a single four dimensional computed tomography (4DCT) dataset. Phantom and patient simulation studies were carried out to investigate potential advantages of MAO compared to ITV planning. Through simulated delivery of the ITV- and MAO-plans, target dose variations were also investigated. RESULTS: By optimizing the accumulated dose, MAO shows the potential to ensure dose to the moving target meets plan objectives while simultaneously reducing dose to organs at risk (OARs) compared with ITV planning. While consistently superior to the ITV approach, MAO resulted in equivalent OAR dosimetry at planning objective dose levels to within 2% volume in 14/30 plans and to within 3% volume in 19/30 plans for each lung V20, esophagus V25, and heart V30. Despite large variations in per-fraction respiratory phase weights in simulated deliveries at high dose rates (e.g., treating 4/10 phases during single fraction beams) the cumulative clinical target volume (CTV) dose after 30 fractions and per-fraction dose were constant independent of planning technique. In one case considered, however, per-phase CTV dose varied from 74% to 117% of prescription implying the level of ITV-dose heterogeneity may not be appropriate with conventional, free-breathing delivery. CONCLUSIONS: MAO incorporates 4DCT information in an optimized dose distribution and can achieve a superior plan in terms of accumulated dose to the moving target and OAR sparing compared to ITV-plans. An appropriate level of dose heterogeneity in MAO plans must be further investigated.

Coverage-based treatment planning to accommodate deformable organ variations in prostate cancer treatment.

PURPOSE: To compare two coverage-based planning (CP) techniques with standard fixed margin-based planning (FM), considering the dosimetric impact of interfraction deformable organ motion exclusively for high-risk prostate treatments. METHODS: Nineteen prostate cancer patients with 8-13 prostate CT images of each patient were used to model patient-specific interfraction deformable organ changes. The model was based on the principal component analysis (PCA) method and was used to predict the patient geometries for virtual treatment course simulation. For each patient, an IMRT plan using zero margin on target structures, prostate (CTVprostate) and seminal vesicles (CTVSV), were created, then evaluated by simulating 1000 30-fraction virtual treatment courses. Each fraction was prostate centroid aligned. Patients whose D98 failed to achieve 95% coverage probability objective D98,95 ≥ 78 Gy (CTVprostate) or D98,95 ≥ 66 Gy (CTVSV) were replanned using planning techniques: (1) FM (PTVprostate = CTVprostate + 5 mm, PTVSV = CTVSV + 8 mm), (2) CPOM which optimized uniform PTV margins for CTVprostate and CTVSV to meet the coverage probability objective, and (3) CPCOP which directly optimized coverage probability objectives for all structures of interest. These plans were intercompared by computing probabilistic metrics, including 5% and 95% percentile DVHs (pDVH) and TCP/NTCP distributions. RESULTS: All patients were replanned using FM and two CP techniques. The selected margins used in FM failed to ensure target coverage for 8/19 patients. Twelve CPOM plans and seven CPCOP plans were favored over the other plans by achieving desirable D98,95 while sparing more normal tissues. CONCLUSIONS: Coverage-based treatment planning techniques can produce better plans than FM, while relative advantages of CPOM and CPCOP are patient-specific.