Commissioning and clinical implementation of the first commercial independent Monte Carlo 3D dose calculation to replace CyberKnife M6™ patient-specific QA measurements.

PURPOSE: To report on the commissioning and clinical validation of the first commercially available independent Monte Carlo (MC) three-dimensional (3D) dose calculation for CyberKnife robotic radiosurgery system® (Accuray, Sunnyvale, CA). METHODS: The independent dose calculation (IDC) by SciMoCa® (Scientific RT, Munich, Germany) was validated based on water measurements of output factors and dose profiles (unshielded diode, field-size dependent corrections). A set of 84 patient-specific quality assurance (QA) measurements for multi-leaf collimator (MLC) plans, using an Octavius two-dimensional SRS1000 array (PTW, Freiburg, Germany), was compared to results of respective calculations. Statistical process control (SPC) was used to detect plans outside action levels. RESULTS: Of all output factors for the three collimator systems of the CyberKnife, 99% agreed within 2% and 81% within 1%, with a maximum deviation of 3.2% for a 5-mm fixed cone. The profiles were compared using a one-dimensional gamma evaluation with 2% dose difference and 0.5 mm distance-to-agreement (Γ(2,0.5)). The off-centre ratios showed an average pass rate >99% (92-100%). The agreement of the depth dose profiles depended on field size, with lowest pass rates for the smallest MLC field sizes. The average depth dose pass rate was 88% (35-99%). The IDCs showed a Γ(2,1) pass rate of 98%. Statistical process control detected six plans outside tolerance levels in the measurements, all of which could be attributed the measurement setup. Independent dose calculations showed problems in five plans, all due to differences in the algorithm between TPS and IDC. Based on these results changes were made in the class solution for treatment plans. CONCLUSION: The first commercially available MC 3D dose IDC was successfully commissioned and validated for the CyberKnife and replaced all routine patient-specific QA measurements in our clinic.

Practical implications for the quality assurance of modulated radiation therapy techniques using point detector arrays.

PURPOSE: Linac parameters potentially influencing the delivery quality of IMRT and VMAT plans are investigated with respect to threshold ranges, consequently to be considered in a linac based quality assurance procedure. Three commercially available 2D arrays are used to further investigate the influence of the measurement device. METHODS: Using three commercially available 2D arrays (Mx: MatriXXevolution , Oc: Octavius1500 , Mc: MapCHECK2), simple static measurements, measurements for MLC characterization and dynamic interplay of gantry movement, MLC movement and variable dose rate were performed. The results were evaluated with respect to each single array as well as among each other. RESULTS: Simple static measurements showed different array responses to dose, dose rate and profile homogeneity and revealed instabilities in dose delivery and profile shape during linac ramp up. Using the sweeping gap test, all arrays were able to detect small leaf misalignments down to ±0.1 mm, but this test also demonstrated up to 15% dose deviation due to profile instabilities and fast accelerating leaves during linac ramp up. Tests including gantry rotation showed different stability of gantry mounts for each array. Including gantry movement and dose rate variability, differences compared to static delivery were smaller compared to dose differences when simultaneously controling interplay of gantry movement, leaf movement and dose rate variability. CONCLUSION: Linac based QA is feasible with the tested commercially available 2D arrays. Limitations of each array and the linac ramp up characteristics should be carefully considered during individual plan generation and regularly checked in linac QA. Especially the dose and dose profile during linac ramp up should be checked regularly, as well as MLC positioning accuracy using a sweeping gap test. Additionally, dynamic interplay tests including various gantry rotation speeds and angles, various leaf speeds and various dose rates should be included.

Intra-fractional bladder motion and margins in adaptive radiotherapy for urinary bladder cancer.

BACKGROUND: The bladder is a tumour site well suited for adaptive radiotherapy (ART) due to large inter-fractional changes, but it also displays considerable intra-fractional motion. The aim of this study was to assess target coverage with a clinically applied method for plan selection ART and to estimate population-based and patient-specific intra-fractional margins, also relevant for a future re-optimisation strategy. MATERIAL AND METHODS: Nine patients treated in a clinical phase II ART trial of daily plan selection for bladder cancer were included. In the library plans, 5 mm isotropic margins were added to account for intra-fractional changes. Pre-treatment and weekly repeat magnetic resonance imaging (MRI) series were acquired in which a full three-dimensional (3D) volume was scanned every second min for 10 min (a total of 366 scans in 61 series). Initially, the bladder clinical target volume (CTV) was delineated in all scans. The t = 0 min scan was then rigidly registered to the planning computed tomography (CT) and plan selections were simulated using the CTV_0 (at t = 0 min). To assess intra-fractional motion, coverage of the CTV_10 (at t = 10 min) was quantified using the applied PTV. Population-based margins were calculated using the van Herk margin recipe while patient-specific margins were calculated using a linear model. RESULTS: For 49% of the cases, the CTV_10 extended more than 5 mm outside the CTV_0. However, in 58 of the 61 cases (97%) CTV_10 was covered by the selected PTV. Population-based margins of 14 mm Sup/Ant, 9 mm Post and 5 mm Inf/Lat were sufficient to cover the bladder. Using patient-specific margins, the overlap between PTV and bowel-cavity was reduced from 137 cm(3) with the plan selection strategy to 24 cm(3). CONCLUSION: In this phase II ART trial, 5 mm isotropic margin for intra-fractional motion was sufficient even though considerable intra-fractional motion was observed. In online re-optimised ART, population-based margin can be applied although patient-specific margins are preferable.

Technical evaluation of different respiratory monitoring systems used for 4D CT acquisition under free breathing.

Respiratory monitoring systems are required to supply CT scanners with information on the patient's breathing during the acquisition of a respiration-correlated computer tomography (RCCT), also referred to as 4D CT. The information a respiratory monitoring system has to provide to the CT scanner depends on the specific scanner. The purpose of this study is to compare two different respiratory monitoring systems (Anzai Respiratory Gating System; C-RAD Sentinel) with respect to their applicability in combination with an Aquilion Large Bore CT scanner from Toshiba. The scanner used in our clinic does not make use of the full time dependent breathing signal, but only single trigger pulses indicating the beginning of a new breathing cycle. Hence the attached respiratory monitoring system is expected to deliver accurate online trigger pulse for each breathing cycle. The accuracy of the trigger pulses sent to the CT scanner has to be ensured by the selected respiratory monitoring system. Since a trigger pulse (output signal) of a respiratory monitoring system is a function of the measured breathing signal (input signal), the typical clinical range of the input signal is estimated for both examined respiratory monitoring systems. Both systems are analyzed based on the following parameters: time resolution, signal amplitude, noise, signal-to-noise ratio (SNR), signal linearity, trigger compatibility, and clinical examples. The Anzai system shows a better SNR (≥ 28 dB) than the Sentinel system (≥ 14.6 dB). In terms of compatibility with the cycle-based image sorting algorithm of the Toshiba CT scanner, the Anzai system benefits from the possibility to generate cycle-based triggers, whereas the Sentinel system is only able to generate amplitude-based triggers. In clinical practice, the combination of a Toshiba CT scanner and the Anzai system will provide better results due to the compatibility of the image sorting and trigger release methods.

Adaptive radiotherapy in locally advanced prostate cancer using a statistical deformable motion model.

UNLABELLED: Daily treatment plan selection from a plan library is a major adaptive radiotherapy strategy to account for individual internal anatomy variations. This strategy depends on the initial input images being representative for the variations observed later in the treatment course. Focusing on locally advanced prostate cancer, our aim was to evaluate if residual motion of the prostate (CTV-p) and the elective targets (CTV-sv, CTV-ln) can be prospectively accounted for with a statistical deformable model based on images acquired in the initial part of treatment. METHODS: Thirteen patients with locally advanced prostate cancer, each with 9-10 repeat CT scans, were included. Displacement vectors fields (DVF) obtained from contour-based deformable registration of delineations in the repeat- and planning CT scans were used to create patient-specific statistical motion models using principal component analysis (PCA). For each patient and CTV, four PCA-models were created: one with all 9-10 DVF as input in addition to models with only four, five or six DVFs as input. Simulations of target shapes from each PCA-model were used to calculate iso-coverage levels, which were converted to contours. The levels were analyzed for sensitivity and precision. RESULTS: A union of the simulated shapes was able to cover at least 97%, 97% and 95% of the volumes of the evaluated CTV shapes for PCA-models using six, five and four DVFs as input, respectively. There was a decrease in sensitivity with higher iso-coverage levels, with a sharper decline for greater target movements. Apart from having the steepest decline in sensitivity, CTV-sv also displayed the greatest influence on the number of geometries used in the PCA-model. CONCLUSIONS: PCA-based simulations of residual motion derived from four to six DVFs as input could account for the majority of the target shapes present during the latter part of the treatment. CTV-sv displayed the greatest range in both sensitivity and precision.

A lack of appetite for information and computation. Simple heuristics in food choice.

The predominant, but largely untested, assumption in research on food choice is that people obey the classic commandments of rational behavior: they carefully look up every piece of relevant information, weight each piece according to subjective importance, and then combine them into a judgment or choice. In real world situations, however, the available time, motivation, and computational resources may simply not suffice to keep these commandments. Indeed, there is a large body of research suggesting that human choice is often better accommodated by heuristics-simple rules that enable decision making on the basis of a few, but important, pieces of information. We investigated the prevalence of such heuristics in a computerized experiment that engaged participants in a series of choices between two lunch dishes. Employing MouselabWeb, a process-tracing technique, we found that simple heuristics described an overwhelmingly large proportion of choices, whereas strategies traditionally deemed rational were barely apparent in our data. Replicating previous findings, we also observed that visual stimulus segments received a much larger proportion of attention than any nutritional values did. Our results suggest that, consistent with human behavior in other domains, people make their food choices on the basis of simple and informationally frugal heuristics.

Sensitivity and specificity of Monte Carlo based independent secondary dose computation for detecting modulation-related dose errors in intensity modulated radiotherapy.

BACKGROUND: The recent availability of Monte Carlo based independent secondary dose calculation (ISDC) for patient-specific quality assurance (QA) of modulated radiotherapy requires the definition of appropriate, more sensitive action levels, since contemporary recommendations were defined for less accurate ISDC dose algorithms. PURPOSE: The objective is to establish an optimum action level and measure the efficacy of a Monte Carlo ISDC software for pre-treatment QA of intensity modulated radiotherapy treatments. METHODS: The treatment planning system and the ISDC were commissioned by their vendors from independent base data sets, replicating a typical real-world scenario. In order to apply Receiver-Operator-Characteristics (ROC), a set of treatment plans for various case classes was created that consisted of 190 clinical treatment plans and 190 manipulated treatment plans with dose errors in the range of 1.5-2.5%. All 380 treatment plans were evaluated with ISDC in the patient geometry. ROC analysis was performed for a number of Gamma (dose-difference/distance-to-agreement) criteria. QA methods were ranked according to Area under the ROC curve (AUC) and optimum action levels were derived via Youden's J statistics. RESULTS: Overall, for original treatment plans, the mean Gamma pass rate (GPR) for Gamma(1%, 1 mm) was close to 90%, although with some variation across case classes. The best QA criterion was Gamma(2%, 1 mm) with GPR > 90% and an AUC of 0.928. Gamma criteria with small distance-to-agreement had consistently higher AUC. GPR of original treatment plans depended on their modulation degree. An action level in terms of Gamma(1%, 1 mm) GPR that decreases with modulation degree was the most efficient criterion with sensitivity = 0.91 and specificity = 0.95, compared with Gamma(3%, 3 mm) GPR > 99%, sensitivity = 0.73 and specificity = 0.91 as a commonly used action level. CONCLUSIONS: ISDC with Monte Carlo proves highly efficient to catch errors in the treatment planning process. For a Monte Carlo based TPS, dose-difference criteria of 2% or less, and distance-to-agreement criteria of 1 mm, achieve the largest AUC in ROC analysis.

Does moral commitment predict resistance to corruption? experimental evidence from a bribery game.

Corruption is ubiquitous in practice and has severe negative consequences for organizations and societies at large. Drawing on a laboratory experiment, we propose that individuals high in moral commitment are less likely to engage in corrupt behaviors and prefer foregoing financial benefits. Specifically, we posit that individuals refrain from corruption (i) the more they endorse integrity (incorruptibility) as a protected value and (ii) the higher their level of Honesty-Humility. The results of a two-step experiment largely support our expectations: people who treat compromises to integrity as unacceptable were less willing to accept bribes, and Honesty-Humility decreased bribe-giving. The findings are robust to demographic variables (e.g., age, gender, cultural background) and additional personal characteristics (e.g., risk tolerance, dispositional greed) and have important implications for ongoing theory-building efforts and business practice.

Statistical breathing curve sampling to quantify interplay effects of moving lung tumors in a 4D Monte Carlo dose calculation framework.

PURPOSE: The interplay between respiratory tumor motion and dose application by intensity modulated radiotherapy (IMRT) techniques can potentially lead to undesirable and non-intuitive deviations from the planned dose distribution. We developed a 4D Monte Carlo (MC) dose recalculation framework featuring statistical breathing curve sampling, to precisely simulate the dose distribution for moving target volumes aiming at a comprehensive assessment of interplay effects. METHODS: We implemented a dose accumulation tool that enables dose recalculations of arbitrary breathing curves including the actual breathing curve of the patient. This MC dose recalculation framework is based on linac log-files, facilitating a high temporal resolution up to 0.1 s. By statistical analysis of 128 different breathing curves, interplay susceptibility of different treatment parameters was evaluated for an exemplary patient case. To facilitate prospective clinical application in the treatment planning stage, in which patient breathing curves or linac log-files are not available, we derived a log-file free version with breathing curves generated by a random walk approach. Interplay was quantified by standard deviations σ in D5%, D50% and D95%. RESULTS: Interplay induced dose deviations for single fractions were observed and evaluated for IMRT and volumetric arc therapy (σD95% up to 1.3 %) showing a decrease with higher fraction doses and an increase with higher MU rates. Interplay effects for conformal treatment techniques were negligible (σ<0.1%). The log-file free version and the random walk generated breathing curves yielded similar results (deviations in σ< 0.1 %) and can be used as substitutes for interplay assessment. CONCLUSION: It is feasible to combine statistically sampled breathing curves with MC dose calculations. The universality of the presented framework allows comprehensive assessment of interplay effects in retrospective and prospective clinically relevant scenarios.

Special report: workshop on 4D-treatment planning in actively scanned particle therapy--recommendations, technical challenges, and future research directions.

This article reports on a 4D-treatment planning workshop (4DTPW), held on 7-8 December 2009 at the Paul Scherrer Institut (PSI) in Villigen, Switzerland. The participants were all members of institutions actively involved in particle therapy delivery and research. The purpose of the 4DTPW was to discuss current approaches, challenges, and future research directions in 4D-treatment planning in the context of actively scanned particle radiotherapy. Key aspects were addressed in plenary sessions, in which leaders of the field summarized the state-of-the-art. Each plenary session was followed by an extensive discussion. As a result, this article presents a summary of recommendations for the treatment of mobile targets (intrafractional changes) with actively scanned particles and a list of requirements to elaborate and apply these guidelines clinically.

Volumetric and actuarial analysis of brain necrosis in proton therapy using a novel mixture cure model.

BACKGROUND AND PURPOSE: High-dose fractionated radiotherapy is often necessary to achieve long-term tumor control in several types of tumors involving or within close proximity to the brain. There is limited data to guide on optimal constraints to the adjacent nontarget brain. This investigation explored the significance of the three-dimensional (3D) dose distribution of passive scattering proton therapy to the brain with other clinicopathological factors on the development of symptomatic radiation necrosis. MATERIALS AND METHODS: All patients with head and neck, skull base, or intracranial tumors who underwent proton therapy (minimum prescription dose of 59.4 Gy(RBE)) with collateral moderate to high dose radiation exposure to the nontarget brain were retrospectively reviewed. A mixture cure model with respect to necrosis-free survival was used to derive estimates for the normal tissue complication probability (NTCP) model while adjusting for potential confounding factors. RESULTS: Of 179 identified patients, 83 patients had intracranial tumors and 96 patients had primary extracranial tumors. The optimal dose measure obtained to describe the occurrence of radiation necrosis was the equivalent uniform dose (EUD) with parameter a = 9. The best-fit parameters of logistic NTCP models revealed D50 = 57.7 Gy for intracranial tumors, D50 = 39.5 Gy for extracranial tumors, and γ50 = 2.5 for both tumor locations. Multivariable analysis revealed EUD and primary tumor location to be the strongest predictors of brain radiation necrosis. CONCLUSION: In the current clinical volumetric data analyses with multivariable modelling, EUD was identified as an independent and strong predictor for brain radiation necrosis from proton therapy.

Comparison of planned dose on different CT image sets to four-dimensional Monte Carlo dose recalculation using the patient's actual breathing trace for lung stereotactic body radiation therapy.

PURPOSE: The need for four-dimensional (4D) treatment planning becomes indispensable when it comes to radiation therapy for moving tumors in the thoracic and abdominal regions. The primary purpose of this study is to combine the actual breathing trace during each individual treatment fraction with the Linac's log file information and Monte Carlo 4D dose calculations. We investigated this workflow on multiple computed tomography (CT) datasets in a clinical environment for stereotactic body radiation therapy (SBRT) treatment planning. METHODS: We have developed a workflow, which allows us to recalculate absorbed dose to a 4DCT dataset using Monte Carlo calculation methods and accumulate all 4D doses in order to compare them to the planned dose using the Linac's log file, a 4DCT dataset, and the patient's actual breathing curve for each individual fraction. For five lung patients, three-dimensional-conformal radiation therapy (3D-CRT) and volumetric modulated arc treatment (VMAT) treatment plans were generated on four different CT image datasets: a native free-breathing 3DCT, an average intensity projection (AIP) and a maximum intensity projection (MIP) CT both obtained from a 4DCT, and a 3DCT with density overrides based on the 3DCT (DO). The Monte Carlo 4D dose has been calculated on each 4DCT phase using the Linac's log file and the patient's breathing trace as a surrogate for tumor motion and dose was accumulated to the gross tumor volume (GTV) at the 50% breathing phase (end of exhale) using deformable image registration. RESULTS: Δ D 98 % and Δ D 2 % between 4D dose and planned dose differed largely for 3DCT-based planning and also for DO in three patients. Least dose differences between planned and recalculated dose have been found for AIP and MIP treatment planning which both tend to be superior to DO, but the results indicate a dependency on the breathing variability, tumor motion, and size. An interplay effect has not been observed in the small patient cohort. CONCLUSIONS: We have developed a workflow which, to our best knowledge, is the first incorporation of the patient breathing trace over the course of all individual treatment fractions with the Linac's log file information and 4D Monte Carlo recalculations of the actual treated dose. Due to the small patient cohort, no clear recommendation on which CT can be used for SBRT treatment planning can be given, but the developed workflow, after adaption for clinical use, could be used to enhance a priori 4D Monte Carlo treatment planning in the future and help with the decision on which CT dataset treatment planning should be carried out.

Model-independent, multimodality deformable image registration by local matching of anatomical features and minimization of elastic energy.

With respect to the demands of adaptive and 4D-radiotherapy applications, an algorithm is proposed for a fully automatic, multimodality deformable registration that follows the concept of translational relocation of regularly distributed image subvolumes governed by local anatomical features. Thereby, the problem of global deformable registration is broken down to multiple independent local registration steps which allows for straightforward parallelization of the algorithm. In a subsequent step, possible local misregistrations are corrected for by minimization of the elastic energy of the displacement field under consideration of image information. The final displacement field results from interpolation of the subvolume shift vectors. The algorithm can employ as a similarity measure both the correlation coefficient and mutual information. The latter allows the application to intermodality deformable registration problems. The typical calculation time on a modern multiprocessor PC is well below 1 min, which facilitates almost-interactive, "online" usage. CT-to-MRI and CT-to-cone-beam-CT registrations of head-and-neck data sets are presented, as well as inhale-to-exhale registrations of lung CT data sets. For quantitative evaluation of registration accuracy, a virtual thorax phantom was developed; additionally, a landmark-based evaluation on four lung respiratory-correlated CT data sets was performed. This consistently resulted in average registration residuals on the order of the voxel size or less (3D-residuals approximately 1-2 mm). Summarizing, the presented algorithm allows an accurate multimodality deformable registration with calculation times well below 1 min, and thus bears promise as a versatile basic tool in adaptive and 4D-radiotherapy applications.

Validation of the Acuros XB dose calculation algorithm versus Monte Carlo for clinical treatment plans.

PURPOSE: The two distinct dose computation paradigms of Boltzmann equation solvers and Monte Carlo simulation both promise in principle maximum accuracy. In practice, clinically acceptable calculation times demand approximations and numerical short-cuts on one hand, and modeling the beam characteristics of a real linear accelerator to the required accuracy on the other. A thorough benchmark of both algorithm types therefore needs to start with beam modeling, and needs to include a number of clinically challenging treatment plans. METHODS: The Acuros XB (v 13.7, Varian Medical Systems) and SciMoCa (v 1.0, Scientific RT) algorithms were commissioned for the same Varian Clinac accelerator for beam qualities 6 and 15 MV. Beam models were established with water phantom measurements and MLC calibration protocols. In total, 25 patients of five case classes (lung/three-dimensional (3D) conformal, lung/IMRT, head and neck/VMAT, cervix/IMRT, and rectum/VMAT) were randomly selected from the clinical database and computed with both algorithms. Statistics of 3D gamma analysis for various dose/distance-to-agreement (DTA) criteria and differences in selected DVH parameters were analyzed. RESULTS: The percentage of points fulfilling a gamma evaluation was scored as the gamma agreement index (GAI), denoted as G(ΔD, DTA). G(3,3), G(2,2), and G(1,1) were evaluated for the full body, PTV, and selected organs at risk (OARs). For all patients, G(3,3) ≥ 99.9% and G(2,2) > 97% for the body. G(1,1) varied among the patients. However, for all patients, G(1,1) > 70% and G(1,1) > 80% for 68% of the patients. For each patient, the mean dose deviation was ΔD < 1% for the body, PTV, and all evaluated OARs, respectively. In dense bone and at off-axis distance > 10 cm, the Acuros algorithm yielded slightly higher doses. In the first layer of voxels of the patient surface, the calculated doses deviated between the algorithms. However, at the second voxel, good agreement was observed. The differences in D(98%PTV) were <1.9% between the two algorithms and for 76% of the patients, deviations were below 1%. CONCLUSIONS: Overall, an outstanding agreement was found between the Boltzmann equation solver and Monte Carlo. High-accuracy dose computation algorithms have matured to a level that their differences are below common experimental detection thresholds for clinical treatment plans. Aside from residual differences which could be traced back to implementation details and fundamental cross-section data, both algorithms arrive at identical dose distributions.

Clinical workflow optimization to improve 4DCT reconstruction for Toshiba Aquilion CT scanners.

Respiratory motion remains a source of major uncertainties in radiotherapy. Respiratory correlated computed tomography (referred to as 4DCT) serves as one way of reducing breathing artifacts in 3D-CTs and allows the investigation of tumor motion over time. The quality of the 4DCT images depends on the data acquisition scheme, which in turn is dependent on the vendor. Specifically, the only way Toshiba Aquilion LB CT scanners can reconstruct 4DCTs is a cycle-based reconstruction using triggers provided by an external surrogate signal. The accuracy is strongly dependent on the method of trigger generation. Two consecutive triggers are used to define a breathing cycle which is divided into respiratory phases of equal duration. The goal of this study is to identify if there are advantages in the usage of local-amplitude based sorting (LAS) of the respiration motion states, in order to reduce image artifacts and improve 4DCT quality. Furthermore, this study addresses the generation and optimization of a clinical workflow using as surrogate motion monitoring system the Sentinel™ (C-RAD AB, Sweden) optical surface scanner in combination with a Toshiba Aquilion LB CT scanner. For that purpose, a phantom study using 10 different breathing waveforms and a retrospective patient study using the 4DCT reconstructions of 10 different patients has been conducted. The error in tumor volume has been reduced from 2.9±3.7% to 2.7±2.6% using optimal cycle-based triggers (manipulated CBS) and to 2.7±2.2% using LAS in the phantom study. Moreover, it was possible to decrease the tumor volume variability from 5.0±3.6% using the original cycle-based triggers (original CBS) to 3.5±2.5% using the optimal triggers and to 3.7±2.7% using LAS in the patient data analysis. We therefore propose the usage of the manipulated CBS, also with regard to an accurate and safe clinical workflow.

Evaluation of machine log files/MC-based treatment planning and delivery QA as compared to ArcCHECK QA.

PURPOSE: A treatment planning/delivery QA tool using linac log files (LF) and Monte Carlo (MC) dose calculation is investigated as a standalone alternative to phantom-based patient-specific QA (ArcCHECK (AC)). METHODS: Delivering a variety of fields onto MapCHECK2 and ArcCHECK, diode sensitivity dependence on dose rate (in-field) and energy (primarily out-of-field) was quantified. AC and LF QAs were analyzed with respect to delivery complexity by delivering 12 × 12 cm static fields/arcs comprised of varying numbers of abutting sub-fields onto ArcCHECK. About 11 clinical dual-arc VMAT patients planned using Pinnacle's convolution-superposition (CS) were delivered on ArcCHECK and log file dose (LF-CS and LF-MC) calculated. To minimize calculation time, reduced LF-CS sampling (1/2/3/4° control point spacing) was investigated. Planned ("Plan") and LF-reconstructed CS and MC doses were compared with each other and AC measurement via statistical [mean ± StdDev(σ)] and gamma analyses to isolate dosimetric uncertainties and quantify the relative accuracies of AC QA and MC-based LF QA. RESULTS: Calculation and ArcCHECK measurement differed by up to 1.5% in-field due to variation in dose rate and up to 5% out-of-field. For the experimental segment-varying plans, despite CS calculation deviating by as much as 13% from measurement, Plan-MC and LF-MC doses generally matched AC measurement within 3%. Utilizing 1° control point spacing, 2%/2 mm LF-CS vs AC pass rates (97%) were slightly lower than Plan-CS vs AC pass rates (97.5%). Utilizing all log file samples, 2%/2 mm LF-MC vs AC pass rates (97.3%) were higher than Plan-MC vs AC (96.5%). Phantom-dependent, calculation algorithm-dependent (MC vs CS), and delivery error-dependent dose uncertainties were 0.8 ± 1.2%, 0.2 ± 1.1%, and 0.1 ± 0.9% respectively. CONCLUSION: Reconstructing every log file sample with no increase in computational cost, MC-based LF QA is faster and more accurate than CS-based LF QA. Offering similar dosimetric accuracy compared to AC measurement, MC-based log files can be used for treatment planning QA.

Statistical motion modelling for robust evaluation of clinically delivered accumulated dose distributions after curative radiotherapy of locally advanced prostate cancer.

BACKGROUND AND PURPOSE: Planned doses are used as surrogate for the actually delivered dose in radiotherapy. We have estimated the delivered dose in a dose-escalation trial of locally advanced prostate cancer by statistical dose-accumulation and by DVH-summation, and compared to planned dose. MATERIALS AND METHOD: Prescribed dose-escalation to the prostate was 67.5 Gy/25fr., corresponding to 81GyEQD2 assuming α/ß = 1.5. The 21 patients had three targets (i.e. CTV67.5 + 2 mm, CTV60 + 5 mm, CTV50 + 10 mm) irradiated by a simultaneous-integrated-boost technique. Analysis was based on 213 CT scans and 5-years of follow-up. For statistical dose-accumulation, we modelled 10000 possible treatment courses based on planned dose and deformation-vector-fields from contour-based registration. For DVH-summation we recalculated dose on repeat-CTs and estimated median D98%/EUD. Groups with/without disease recurrence were compared. RESULTS: Discrepancies between planned and accumulated dose were mostly seen for CTV67.5, where under-dosage was found at different locations in the prostate in 12/21 patients. Delivered dose-escalation (D98%) was on average 73.9GyEQD2 (range: 68.3-78.7GyEQD2). No significant difference in accumulated-D98% was found in patients with (n = 8) and without (n = 13) recurrence (p > 0.05). Average D98%/EUD with statistical dose-accumulation vs DVH-summation was significantly different in CTV60, CTV50, rectum and bladder but not in CTV67.5. CONCLUSION: The planned dose escalation was not received by more than half-of-the patients. Robustness of the prostate target (CTV67.5) should therefore be better prioritized in these patients given the low toxicity profile. Estimates of delivered dose were less conservative for dose-accumulation due to interaction of random organ motion with the dose matrix.

Principal component analysis-based pattern analysis of dose-volume histograms and influence on rectal toxicity.

PURPOSE: The variability of dose-volume histogram (DVH) shapes in a patient population can be quantified using principal component analysis (PCA). We applied this to rectal DVHs of prostate cancer patients and investigated the correlation of the PCA parameters with late bleeding. METHODS AND MATERIALS: PCA was applied to the rectal wall DVHs of 262 patients, who had been treated with a four-field box, conformal adaptive radiotherapy technique. The correlated changes in the DVH pattern were revealed as "eigenmodes," which were ordered by their importance to represent data set variability. Each DVH is uniquely characterized by its principal components (PCs). The correlation of the first three PCs and chronic rectal bleeding of Grade 2 or greater was investigated with uni- and multivariate logistic regression analyses. RESULTS: Rectal wall DVHs in four-field conformal RT can primarily be represented by the first two or three PCs, which describe approximately 94% or 96% of the DVH shape variability, respectively. The first eigenmode models the total irradiated rectal volume; thus, PC1 correlates to the mean dose. Mode 2 describes the interpatient differences of the relative rectal volume in the two- or four-field overlap region. Mode 3 reveals correlations of volumes with intermediate doses ( approximately 40-45 Gy) and volumes with doses >70 Gy; thus, PC3 is associated with the maximal dose. According to univariate logistic regression analysis, only PC2 correlated significantly with toxicity. However, multivariate logistic regression analysis with the first two or three PCs revealed an increased probability of bleeding for DVHs with more than one large PC. CONCLUSIONS: PCA can reveal the correlation structure of DVHs for a patient population as imposed by the treatment technique and provide information about its relationship to toxicity. It proves useful for augmenting normal tissue complication probability modeling approaches.

Incidence of late rectal bleeding in high-dose conformal radiotherapy of prostate cancer using equivalent uniform dose-based and dose-volume-based normal tissue complication probability models.

PURPOSE: Accurate modeling of rectal complications based on dose-volume histogram (DVH) data are necessary to allow safe dose escalation in radiotherapy of prostate cancer. We applied different equivalent uniform dose (EUD)-based and dose-volume-based normal tissue complication probability (NTCP) models to rectal wall DVHs and follow-up data for 319 prostate cancer patients to identify the dosimetric factors most predictive for Grade > or = 2 rectal bleeding. METHODS AND MATERIALS: Data for 319 patients treated at the William Beaumont Hospital with three-dimensional conformal radiotherapy (3D-CRT) under an adaptive radiotherapy protocol were used for this study. The following models were considered: (1) Lyman model and (2) logit-formula with DVH reduced to generalized EUD, (3) serial reconstruction unit (RU) model, (4) Poisson-EUD model, and (5) mean dose- and (6) cutoff dose-logistic regression model. The parameters and their confidence intervals were determined using maximum likelihood estimation. RESULTS: Of the patients, 51 (16.0%) showed Grade 2 or higher bleeding. As assessed qualitatively and quantitatively, the Lyman- and Logit-EUD, serial RU, and Poisson-EUD model fitted the data very well. Rectal wall mean dose did not correlate to Grade 2 or higher bleeding. For the cutoff dose model, the volume receiving > 73.7 Gy showed most significant correlation to bleeding. However, this model fitted the data more poorly than the EUD-based models. CONCLUSIONS: Our study clearly confirms a volume effect for late rectal bleeding. This can be described very well by the EUD-like models, of which the serial RU- and Poisson-EUD model can describe the data with only two parameters. Dose-volume-based cutoff-dose models performed worse.

Multi-criterial patient positioning based on dose recalculation on scatter-corrected CBCT images.

BACKGROUND AND PURPOSE: Our aim was to evaluate the feasibility and potential advantages of dose guided patient positioning based on dose recalculation on scatter corrected cone beam computed tomography (CBCT) image data. MATERIAL AND METHODS: A scatter correction approach has been employed to enable dose calculations on CBCT images. A recently proposed tool for interactive multicriterial dose-guided patient positioning which uses interpolation between pre-calculated sample doses has been utilized. The workflow was retrospectively evaluated for two head and neck patients with a total of 39 CBCTs. Dose-volume histogram (DVH) parameters were compared to rigid image registration based isocenter corrections (clinical scenario). RESULTS: The accuracy of the dose interpolation was found sufficient, facilitating the implementation of dose guided patient positioning. Compared to the clinical scenario, the mean dose to the parotid glands could be improved for 2 out of 5 fractions for the first patient while other parameters were preserved. For the second patient, the mean coverage over all fractions of the high dose PTV could be improved by 4%. For this patient, coverage improvements had to be traded against organ at risk (OAR) doses within their clinical tolerance limits. CONCLUSIONS: Dose guided patient positioning using in-room CBCT data is feasible and offers increased control over target coverage and doses to OARs.