Characterization of the IDENTIFYTM surface scanning system for radiation therapy setup on a closed-bore linac.

PURPOSE: In radiation therapy, surface guidance can be used for patient setup and intra-fraction motion monitoring. The surface guided radiation therapy (SGRT) system from Varian Medical systems, IDENTIFYTM, consists of three pods, including cameras and a random pattern projector, mounted on the ceiling. The information captured by the cameras is used to make a reconstruction of the surface. The aim of the study was to assess the technical performance of this SGRT system on a closed-bore linac. METHODS: Phantom measurements were performed to assess the accuracy, precision, reproducibility and temporal stability of the system, both in align and in load position. Translations of the phantoms in lateral, longitudinal, and vertical direction, and rotations around three axes (pitch, roll and yaw) were performed with an accurate, in-house built, positioning stage. Different phantom geometries and different surface colors were used, and various ambient light intensities were tested. RESULTS: The accuracy of the IDENTIFYTM system at the closed-bore linac was 0.07 mm and 0.07 degrees at load position, and 0.06 mm and 0.01 degrees at align position for the white head phantom. The precision was 0.02 mm and 0.02 degrees in load position, and 0.01 mm and 0.02 degrees in align position. The accuracy for the Penta-Guide phantom was comparable to the white head phantom, with 0.06 mm and 0.01 degrees in align position. The system was slightly less accurate for translations of the CIRS lung phantom in align position (0.20 mm, 0.05 degrees). Reproducibility measurements showed a variation of 0.02 mm in load position. Regarding the temporal stability, the maximum drift over 30 min was 0.33 mm and 0.02 degrees in load position. No effect of ambient light level on the accuracy of the IDENTIFYTM system was observed. Regarding different surface colors, the accuracy of the system for a black phantom was slightly worse compared to a white surface, but not clinical relevant. CONCLUSION: The IDENTIFYTM system can adequately be used for motion monitoring on a closed-bore linac with submillimeter accuracy. The results of the performed measurements meet the clinical requirements described in the guidelines of the AAPM and the ESTRO.

Comparing adaptation strategies in MRI-guided online adaptive radiotherapy for prostate cancer: Implications for treatment margins.

PURPOSE: To quantify the difference in accuracy of adapt-to-position (ATP), adapt-to-rotation (ATR) and adapt-to-shape (ATS) workflows used in MRI-guided online adaptive radiotherapy for prostate carcinoma (PCa) by evaluating the margins required to accommodate intra-fraction motion of the clinical target volumes for prostate (CTVpros), prostate including seminal vesicles (CTVpros + sv) and gross tumor volume (GTV). MATERIALS AND METHODS: Clinical delineations of the CTVpros, CTVpros + sv and GTV of 24 patients with intermediate- and high-risk PCa, treated using ATS on a 1.5 T MR-Linac, were used for analysis. Delineations were available pre- and during beam-on. To simulate ATP and ATR workflows, we automatically generated the structures associated with these workflows using rigid transformations from the planning-MRI to the daily online MRIs. Clinical GTVs were analyzed as ATR GTVs and only ATP GTVs were simulated. Planning target volumes (PTVs) were generated with isotropic margins ranging 0.0-5.0 mm. The volumetric overlap was calculated between these PTVs and their corresponding clinical delineation on the MRI acquired during beam-on and averaged over all treatment fractions. RESULTS: The PTV margin required to cover > 95% of the CTVpros was equal (2.5 mm) for all workflows. For the CTVpros + sv, this margin increased to 5.0, 4.0 and 3.5 mm in the ATP, ATR and ATS workflow, respectively. GTV coverage improved from ATP to ATR for margins up to 4.0 mm. CONCLUSION: ATP, ATR and ATS workflows ensure equal coverage of the CTVpros for the current clinical margins. For the CTVpros + sv, ATS showed optimal performance. GTV coverage improves by additional adaptations to prostate rotations.

Dose coverage and breath-hold analysis of breast cancer patients treated with surface-guided radiotherapy.

BACKGROUND: Surface-guided radiotherapy (SGRT) is used to ensure a reproducible patient set-up and for intra-fraction motion monitoring. The arm position of breast cancer patients is important, since this is related to the position of the surrounding lymph nodes. The aim of the study was to investigate the set-up accuracy of the arm of patients positioned using SGRT. Moreover, the actual delivered dose was investigated and an extensive breath-hold analysis was performed. METHODS: 84 patients who received local or locoregional breast radiation therapy were positioned and monitored using SGRT. The accuracy of the arm position, represented by the clavicle position, was studied on the anterior-posterior kV-image. To investigate the effect of changes in anatomy and patient set-up, the actual delivered dose was calculated on cone-beam CT-scans (CBCT). A deformable registration of the CT to the CBCT was applied to deform the structures of the CT onto the CBCT. The minimum dose in percentage of the prescribed dose that was received by 98% of different CTV volumes (D98) was determined. An extensive breath-hold analysis was performed and definitions for relevant parameters were given. RESULTS: The arm position of 77 out of 84 patients in total was successful, based on the clavicle rotation. The mean clavicle rotation was 0.4° (± 2.0°). For 89.8% of the patients who were irradiated on the whole-breast D98 was larger than 95% of the prescribed dose (D98 > 95%). D98 > 95% applied for 70.8% of the patients irradiated on the chest wall. Concerning the lymph node CTVs, D98 > 95% for at least 95% of the patients. The breath-hold analysis showed a mean residual setup error of - 0.015 (± 0.90), - 0.18 (± 0.82), - 0.58 (± 1.1) mm in vertical, lateral, and longitudinal direction, respectively. The reproducibility and stability of the breath-hold was good, with median 0.60 mm (95% confidence interval (CI) [0.66-0.71] mm) and 0.20 mm (95% CI 0.21-0.23] mm), respectively. CONCLUSIONS: Using SGRT we were able to position breast cancer patients successfully, with focus on the arm position. The actual delivered dose calculated on the CBCT was adequate and no relation between clavicle rotation and actual delivered dose was found. Moreover, breath-hold analysis showed a good reproducibility and stability of the breath-hold. Trial registration CCMO register NL69214.028.19.

Evaluation of two independent dose prediction methods to personalize the automated radiotherapy planning process for prostate cancer.

BACKGROUND AND PURPOSE: Currently, automatic approaches for radiotherapy planning are widely used, however creation of high quality treatment plans is still challenging. In this study, two independent dose prediction methods were used to personalize the initial settings for the automated planning template for optimizing prostate cancer treatment plans. This study evaluated the dose metrics of these plans comparing both methods with the current clinical automated prostate cancer treatment plans. MATERIAL AND METHODS: Datasets of 20 high-risk prostate cancer treatment plans were taken from our clinical database. The prescription dose for these plans was 70 Gy given in fractions of 2.5 Gy. Plans were replanned using the current clinical automated treatment and compared with two personalized automated planning methods. The feasibility dose volume histogram (FDVH) and modified filter back projection (mFBP) methods were used to calculate independent dose predictions. Parameters for the initial objective values of the planning template were extracted from these predictions and used to personalize the optimization of the automated planning process. RESULTS: The current automated replanned clinical plans and the automated plans optimized with the personalized template methods fulfilled the clinical dose criteria. For both methods a reduction in the average mean dose of the rectal wall was found, from 22.5 to 20.1 Gy for the FDVH and from 22.5 to 19.6 Gy for the mFBP method. CONCLUSIONS: With both dose-prediction methods the initial settings of the template could be personalized. Hereby, the average dose to the rectal wall was reduced compared to the standard template method.

Geometrical analysis for motion monitoring of rigid bodies with optical surface scanning in radiation oncology.

BACKGROUND AND PURPOSE: Surface guided radiotherapy can be used to improve patient setup and for accurate intra-fraction motion monitoring in correspondence to the isocenter. For a clinical relevant motion analysis the actual displacement of the entire clinical target volume (CTV) is necessary. Therefore, the aim of this study was to develop a novel assessment method for intra-fraction motion for rigid body structures based on motion data and a geometrical analysis. MATERIALS AND METHODS: A threshold value on the volume coverage (VC(t)) of the CTV by the planning target volume (PTV) was proposed as online motion monitoring method. Moreover, offline analysis was performed by using heat maps and by calculating VCx, the volume coverage for at least x% of treatment time. The method was applied retrospectively to patient treatment data for whole brain radiation treatment without a thermoplastic mask. RESULTS: In 132 out of 142 fractions in total the proportion of the CTV that was inside the PTV for at least 99% of the time (VC99) was more than 95%, for a CTV-to-PTV margin of 5 mm. The source-voxel heat map showed which part of the CTV had a reduced coverage and the target heat map showed the movement of the CTV. CONCLUSION: Instead of using an action threshold on the movements of the isocenter, a threshold on the VC(t) of the CTV by the PTV was proposed. The heat maps and resulting values of VCx can be used to adapt the VC(t) threshold or the CTV-to-PTV margin for subsequent fractions.

Exogenous ketosis increases blood and muscle oxygenation but not performance during exercise in hypoxia.

Available evidence indicates that elevated blood ketones are associated with improved hypoxic tolerance in rodents. From this perspective, we hypothesized that exogenous ketosis by oral intake of the ketone ester (R)-3-hydroxybutyl (R)-3-hydroxybutyrate (KE) may induce beneficial physiological effects during prolonged exercise in acute hypoxia. As we recently demonstrated KE to deplete blood bicarbonate, which per se may alter the physiological response to hypoxia, we evaluated the effect of KE both in the presence and absence of bicarbonate intake (BIC). Fourteen highly trained male cyclists performed a simulated cycling race (RACE) consisting of 3-h intermittent cycling (IMT180') followed by a 15-min time-trial (TT15') and an all-out sprint at 175% of lactate threshold (SPRINT). During RACE, fraction of inspired oxygen ([Formula: see text]) was gradually decreased from 18.6% to 14.5%. Before and during RACE, participants received either 1) 75 g of ketone ester (KE), 2) 300 mg/kg body mass bicarbonate (BIC), 3) KE + BIC, or 4) a control drink in addition to 60 g of carbohydrates/h in a randomized, crossover design. KE counteracted the hypoxia-induced drop in blood ([Formula: see text]) and muscle oxygenation by ∼3%. In contrast, BIC decreased [Formula: see text] by ∼2% without impacting muscle oxygenation. Performance during TT15' and SPRINT were similar between all conditions. In conclusion, KE slightly elevated the degree of blood and muscle oxygenation during prolonged exercise in moderate hypoxia without impacting exercise performance. Our data warrant to further investigate the potential of exogenous ketosis to improve muscular and cerebral oxygenation status, and exercise tolerance in extreme hypoxia.

Evaluation of optimization workflow using custom-made planning through predicted dose distribution for head and neck tumor treatment.

PURPOSE: Lack of a reference dose distribution is one of the challenges in the treatment planning used in volumetric modulated arc therapy because numerous manual processes result from variations in the location and size of a tumor in different cases. In this study, a predicted dose distribution was generated using two independent methods. Treatment planning using the predicted distribution was compared with the clinical value, and its efficacy was evaluated. METHODS: Computed tomography scans of 81 patients with oropharynx or hypopharynx tumors were acquired retrospectively. The predicted dose distributions were determined using a modified filtered back projection (mFBP) and a hierarchically densely connected U-net (HD-Unet). Optimization parameters were extracted from the predicted distribution, and the optimized dose distribution was obtained using a commercial treatment planning system. RESULTS: In the test data from ten patients, significant differences between the mFBP and clinical plan were observed for the maximum dose of the brain stem, spinal cord, and mean dose of the larynx. A significant difference between the dose distributions from the HD-Unet dose and the clinical plan was observed for the mean dose of the left parotid gland. In both cases, the equivalent coverage and flatness of the clinical plan were observed for the tumor target. CONCLUSIONS: The predicted dose distribution was generated using two approaches. In the case of the mFBP approach, no prior learning, such as deep learning, is required; therefore, the accuracy and efficiency of treatment planning will be improved even for sites where sufficient training data are unavailable.

Independent knowledge-based treatment planning QA to audit Pinnacle autoplanning.

BACKGROUND AND PURPOSE: With the advent of automatic treatment planning options like Pinnacle's Autoplanning (PAP), the challenge arises how to assess the quality of a plan that no dosimetrist did work on. The aim of this study was to assess plan quality consistency of PAP prostate cancer patients in clinical practice. MATERIALS AND METHODS: 100 prostate cancer patients were included from NKI and 129 from RadboudUMC (RUMC). Per institute a previously developed [1] treatment planning QA model, based on overlap volume histograms, was trained on PAP plans to predict achievable dose metrics which were then compared to the clinical PAP plans. A threshold of 3 Gy (DVH dose parameters)/3% (DVH volume parameters) was used to detect outliers. For the outlier plans, the PAP technique was adjusted with the aim of meeting the threshold. RESULTS: The average difference between the prediction and the clinically achieved value was <0.5 Gy (mean dose parameters) and <1.2% (volume parameters), with standard deviation of 1.9 Gy/1.5% respectively. We found 8% (NKI)/25% (RUMC) of patients to exceed the 3 Gy/3% threshold, with deviations up to 6.7 Gy (mean dose rectum) and 6% (rectal wall V64Gy). In all cases the plans could be improved to fall within the thresholds, without compromising the other dose metrics. CONCLUSION: Independent treatment planning QA was used successfully to assess the quality of clinical PAP in a multi-institutional setting. Respectively 8% and 25% suboptimal clinical PAP plans were detected that all could be improved with replanning. Therefore we recommend the use of independent treatment plan QA in combination with PAP for prostate cancer patients.

Dosimetric comparison of five different techniques for craniospinal irradiation across 15 European centers: analysis on behalf of the SIOP-E-BTG (radiotherapy working group).

PURPOSE: Conventional techniques (3D-CRT) for craniospinal irradiation (CSI) are still widely used. Modern techniques (IMRT, VMAT, TomoTherapy®, proton pencil beam scanning [PBS]) are applied in a limited number of centers. For a 14-year-old patient, we aimed to compare dose distributions of five CSI techniques applied across Europe and generated according to the participating institute protocols, therefore representing daily practice. MATERIAL AND METHODS: A multicenter (n = 15) dosimetric analysis of five different techniques for CSI (3D-CRT, IMRT, VMAT, TomoTherapy®, PBS; 3 centers per technique) was performed using the same patient data, set of delineations and dose prescription (36.0/1.8 Gy). Different treatment plans were optimized based on the same planning target volume margin. All participating institutes returned their best treatment plan applicable in clinic. RESULTS: The modern radiotherapy techniques investigated resulted in superior conformity/homogeneity-indices (CI/HI), particularly in the spinal part of the target (CI: 3D-CRT:0.3 vs. modern:0.6; HI: 3D-CRT:0.2 vs. modern:0.1), and demonstrated a decreased dose to the thyroid, heart, esophagus and pancreas. Dose reductions of >10.0 Gy were observed with PBS compared to modern photon techniques for parotid glands, thyroid and pancreas. Following this technique, a wide range in dosimetry among centers using the same technique was observed (e.g., thyroid mean dose: VMAT: 5.6-24.6 Gy; PBS: 0.3-10.1 Gy). CONCLUSIONS: The investigated modern radiotherapy techniques demonstrate superior dosimetric results compared to 3D-CRT. The lowest mean dose for organs at risk is obtained with proton therapy. However, for a large number of organs ranges in mean doses were wide and overlapping between techniques making it difficult to recommend one radiotherapy technique over another.

Real-time beam monitoring for error detection in IMRT plans and impact on dose-volume histograms : A multi-center study.

PURPOSE: This study aimed to test the sensitivity of a transmission detector for online dose monitoring of intensity-modulated radiation therapy (IMRT) for detecting small delivery errors. Furthermore, the correlation of changes in detector output induced by small delivery errors with other metrics commonly employed to quantify the deviations between calculated and delivered dose distributions was investigated. METHODS: Transmission detector measurements were performed at three institutions. Seven types of errors were induced in nine clinical step-and-shoot (S&S) IMRT plans by modifying the number of monitor units (MU) and introducing small deviations in leaf positions. Signal reproducibility was investigated for short- and long-term stability. Calculated dose distributions were compared in terms of γ passing rates and dose-volume histogram (DVH) metrics (e.g., Dmean, Dx%, Vx%). The correlation between detector signal variations, γ passing rates, and DVH parameters was investigated. RESULTS: Both short- and long-term reproducibility was within 1%. Dose variations down to 1 MU (∆signal 1.1 ± 0.4%) as well as changes in field size and positions down to 1 mm (∆signal 2.6 ± 1.0%) were detected, thus indicating high error-detection sensitivity. A moderate correlation of detector signal was observed with γ passing rates (R2 = 0.57-0.70), while a good correlation was observed with DVH metrics (R2 = 0.75-0.98). CONCLUSION: The detector is capable of detecting small delivery errors in MU and leaf positions, and is thus a highly sensitive dose monitoring device for S&S IMRT for clinical practice. The results of this study indicate a good correlation of detector signal with DVH metrics; therefore, clinical action levels can be defined based on the presented data.

Influence of the Integral Quality Monitor transmission detector on high energy photon beams: A multi-centre study.

PURPOSE: The influence of the Integral Quality Monitor (IQM) transmission detector on photon beam properties was evaluated in a preclinical phase, using data from nine participating centres: (i) the change of beam quality (beam hardening), (ii) the influence on surface dose, and (iii) the attenuation of the IQM detector. METHODS: For 6 different nominal photon energies (4 standard, 2 FFF) and square field sizes from 1×1cm2 to 20×20cm2, the effect of IQM on beam quality was assessed from the PDD20,10 values obtained from the percentage dose depth (PDD) curves, measured with and without IQM in the beam path. The change in surface dose with/without IQM was assessed for all available energies and field sizes from 4×4cm2 to 20×20cm2. The transmission factor was calculated by means of measured absorbed dose at 10cm depth for all available energies and field sizes. RESULTS: (i) A small (0.11-0.53%) yet statistically significant beam hardening effect was observed, depending on photon beam energy. (ii) The increase in surface dose correlated with field size (p<0.01) for all photon energies except for 18MV. The change in surface dose was smaller than 3.3% in all cases except for the 20×20cm2 field and 10MV FFF beam, where it reached 8.1%. (iii) For standard beams, transmission of the IQM showed a weak dependence on the field size, and a pronounced dependence on the beam energy (0.9412 for 6MV to 0.9578 for 18MV and 0.9440 for 6MV FFF; 0.9533 for 10MV FFF). CONCLUSIONS: The effects of the IQM detector on photon beam properties were found to be small yet statistically significant. The magnitudes of changes which were found justify treating IQM either as tray factors within the treatment planning system (TPS) for a particular energy or alternatively as modified outputs for specific beam energy of linear accelerators, which eases the introduction of the IQM into clinical practice.

Cross-institutional knowledge-based planning (KBP) implementation and its performance comparison to Auto-Planning Engine (APE).

BACKGROUND AND PURPOSE: To investigate (1) whether a plan library established at one institution can be applied for another institution's knowledge-based planning (KBP); (2) the performance of cross-institutional KBP compared to Auto-Planning Engine (APE). MATERIAL AND METHODS: Radboud University Medical Center (RUMC) provided 35 oropharyngeal cancer patients (68Gy to PTV68 and 50.3Gy to PTV50.3) with clinically-delivered and comparative APE plans. The Johns Hopkins University (JHU) contributed a three-dose-level plan library consisting of 179 clinically-delivered plans. MedStar Georgetown University Hospital (MGUH) contributed a KBP approach employing overlap-volume histogram (OVH-KBP), where the JHU library was used for guiding RUMC patients' KBP. Since clinical protocols adopted at RUMC and JHU are different and both approaches require protocol-specific planning parameters as initial input, 10 randomly selected patients from RUMC were set aside for deriving them. The finalized parameters were applied to the remaining 25 patients for OVH-KBP and APE plan generation. A Wilcoxon rank-sum test was used for statistical comparison. RESULTS: PTV68 and PTV50.3's V95 in OVH-KBP and APE were similar (p>0.36). Cord's D0.1 cc in OVH-KBP was reduced by 5.1Gy (p=0.0001); doses to other organs were similar (p>0.2). CONCLUSION: APE and OVH-KBP's plan quality is comparable. Institutional-protocol differences can be addressed to allow cross-institutional library sharing.

Clinical implementation of 3D printing in the construction of patient specific bolus for electron beam radiotherapy for non-melanoma skin cancer.

BACKGROUND AND PURPOSE: Creating an individualized tissue equivalent material build-up (i.e. bolus) for electron beam radiation therapy is complex and highly labour-intensive. We implemented a new clinical workflow in which 3D printing technology is used to create the bolus. MATERIAL AND METHODS: A patient-specific bolus is designed in the treatment planning system (TPS) and a shell around it is created in the TPS. The shell is printed and subsequently filled with silicone rubber to make the bolus. Before clinical implementation we performed a planning study with 11 patients to evaluate the difference in tumour coverage between the designed 3D-print bolus and the clinically delivered plan with manually created bolus. For the first 15 clinical patients a second CT scan with the 3D-print bolus was performed to verify the geometrical accuracy. RESULTS: The planning study showed that the V85% of the CTV was on average 97% (3D-print) vs 88% (conventional). Geometric comparison of the 3D-print bolus to the originally contoured bolus showed a high similarity (DSC=0.89). The dose distributions on the second CT scan with the 3D print bolus in position showed only small differences in comparison to the original planning CT scan. CONCLUSIONS: The implemented workflow is feasible, patient friendly, safe, and results in high quality dose distributions. This new technique increases time efficiency.

Camera-based independent couch height verification in radiation oncology.

For specific radiation therapy (RT) treatments, it is advantageous to use the isocenter-to-couch distance (ICD) for initial patient setup.(1) Since sagging of the treatment couch is not properly taken into account by the electronic readout of the treatment machine, this readout cannot be used for initial patient positioning using the isocenter-to-couch distance (ICD). Therefore, initial patient positioning to the prescribed ICD has been carried out using a ruler prior to each treatment fraction in our institution. However, the ruler method is laborious and logging of data is not possible. The objective of this study is to replace the ruler-based setup of the couch height with an independent, user-friendly, optical camera-based method whereby the radiation technologists have to move only the couch to the correct couch height, which is visible on a display. A camera-based independent couch height measurement system (ICHS) was developed in cooperation with Panasonic Electric Works Western Europe. Clinical data showed that the ICHS is at least as accurate as the application of a ruler to verify the ICD. The camera-based independent couch height measurement system has been successfully implemented in seven treatment rooms, since 10 September 2012. The benefits of this system are a more streamlined workflow, reduction of human errors during initial patient setup, and logging of the actual couch height at the isocenter. Daily QA shows that the systems are stable and operate within the set 1 mm tolerance. Regular QA of the system is necessary to guarantee that the system works correctly.

Modeling kinematics and dynamics of human arm movements.

A central problem in motor control relates to the coordination of the arm's many degrees of freedom. This problem concerns the many arm postures (kinematics) that correspond to the same hand position in space and the movement trajectories between begin and end position (dynamics) that result in the same arm postures. The aim of this study was to compare the predictions for arm kinematics by various models on human motor control with experimental data and to study the relation between kinematics and dynamics. Goal-directed arm movements were measured in 3-D space toward far and near targets. The results demonstrate that arm postures for a particular target depend on previous arm postures, contradicting Donders's law. The minimum-work and minimum-torque-change models, on the other hand, predict a much larger effect of initial posture than observed. These data suggest that both kinematics and dynamics affect postures and that their relative contribution might depend on instruction and task complexity.