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Introduction: The purpose of this study is to develop the predictive models for epidermal growth factor receptor (EGFR) mutation status and subtypes [exon 21-point mutation (L858R) and exon 19 deletion mutation (19Del)] and validate the clinical effectiveness.Methods: Total 172 patients with lung adenocarcinoma were enrolled. The analysis of variance and the least absolute shrinkage were used feature selection from plain computed tomography images. Then, radiomic score (rad-score) was calculated for the training and test cohorts. Two machine learning (ML) models with 5-fold were applied to construct the predictive models with rad-score and clinical features and evaluated by the area under the curve (AUC) of receiver operating characteristic curve. The nomogram was developed using rad-score and clinical features, then evaluated by the C-index. Finally, decision curve analysis (DCA) was performed using the best ML and nomogram models.Results: The AUC of the best ML models and the C-index of the nomogram models were 0.82, 0.73 and 0.84, 0.78 in the EGFR mutation groups, 0.83, 0.83 and 0.83, 0.80 in the L858R mutation groups, and 0.84, 0.77 and 0.85, 0.69 in the 19Del groups, respectively in the training and test cohorts. DCA showed that nomogram models have more benefits than ML models.Conclusion: We constructed two predictive models for EGFR mutation status and subtypes. The nomogram models had more clinical usefulness than ML models.

Purpose We evaluated the tumor residual volumes considering six degrees-of-freedom (6DoF) patient setup errors in stereotactic radiotherapy (SRT) with multicomponent mathematical model using single-isocenter irradiation for brain metastases. Methods Simulated spherical gross tumor volumes (GTVs) with 1.0 (GTV 1), 2.0 (GTV 2), and 3.0 (GTV 3)-cm diameters were used. The distance between the GTV center and isocenter (d) was set at 0–10 cm. The GTV was simultaneously translated within 0–1.0 mm (T) and rotated within 0°–1.0° (R) in the three axis directions using affine transformation. We optimized the tumor growth model parameters using measurements of non-small cell lung cancer cell lines' (A549 and NCI-H460) growth. We calculated the GTV residual volume at the irradiation's end using the physical dose to the GTV when the GTV size, d, and 6DoF setup error varied. The d-values that satisfy tolerance values (10%, 35%, and 50%) of the GTV residual volume rate based on the pre-irradiation GTV volume were determined. Results The larger the tolerance value set for both cell lines, the longer the distance to satisfy the tolerance value. Conclusions In GTV residual volume evaluations based on the multicomponent mathematical model on SRT with single-isocenter irradiation, the smaller the GTV size and the larger the distance and 6DoF setup error, the shorter the distance that satisfies the tolerance value might need to be.

PURPOSE Current radiotherapy planning procedures are generally designed based on anatomical information only and use computed tomography (CT) images that do not incorporate organ-functional information. In this study, we developed a method for estimating liver elasticity using the finite element method (FEM) and four-dimensional CT (4DCT) images acquired during radiotherapy planning, and we subsequently evaluated its feasibility as a biomarker for liver fibrosis. MATERIALS AND METHODS Twenty patients who underwent 4DCT and ultrasound-based transient elastography (UTE) were enrolled. All patients had chronic liver disease or cirrhosis. Liver elasticity measurements of the UTE were performed on the right lobe of the patient's liver in 20 patients. The serum biomarkers of the aspartate aminotransferase (AST)-to-platelet ratio index (APRI) and fibrosis-4 index (FIB-4) were available in 18 of the 20 total patients, which were measured within 1 week after undergoing 4DCT. The displacement between the 4DCT images obtained at the endpoints of exhalation and inspiration was determined using the actual (via deformable image registration) and simulated (via FEM) respiration-induced displacement. The elasticity of each element of the liver model was optimized by minimizing the error between the actual and simulated respiration-induced displacement. Then, each patient's estimated liver elasticity was defined as the mean Young's modulus of the liver's right lobe and that of the whole liver using the estimated elasticity map. The estimated liver elasticity was evaluated for correlations with the elasticity obtained via UTE and with two serum biomarkers (APRI and FIB-4). RESULTS The mean ± standard deviation (SD) of the errors between the actual and simulated respiration-induced displacement in the liver model was 0.54 ± 0.33 mm. The estimated liver's right lobe elasticity was statistically significantly correlated with the UTE (r = 0.87, P

PURPOSE This study aimed to develop a six degrees-of-freedom (6DoF) robotic moving phantom for evaluating the dosimetric impact of intrafraction rotation during respiratory-gated radiotherapy with real-time tumor monitoring in the lung. MATERIALS AND METHODS Fifteen patients who had undergone respiratory-gated stereotactic body radiotherapy (SBRT) with the SyncTraX system for lung tumors were enrolled in this study. A water-equivalent phantom (WEP) was set at the tip of the robotic arm. A log file that recorded the three-dimensional positions of three fiducial markers implanted near the lung tumor was used as the input to the 6DoF robotic moving phantom. Respiratory-gated radiotherapy was performed for the WEP, which was driven using translational and rotational motions of the lung tumor. The accuracy of the 6DoF robotic moving phantom was calculated as the difference between the actual and the measured positions. To evaluate the dosimetric impact of intrafraction rotation, the absolute dose distributions under conditions involving gating and movement were compared with those under static conditions. RESULTS For the sinusoidal patterns, the mean ± standard deviation (SD) of the root mean square errors (RMSEs) of the translation and rotation positional errors was

In this study, we assess a developed novel dynamic moving phantom system that can reproduce patient three‐dimensional (3D) tumor motion and patient anatomy, and perform patient‐specific quality assurance (QA) of respiratory‐gated radiotherapy using SyncTraX. Three patients with lung cancer were enrolled in a study. 3D printing technology was adopted to obtain individualized lung phantoms using CT images. A water‐equivalent phantom (WEP) with the 3D‐printed plate lung phantom was set at the tip of the robotic arm. The log file that recorded the 3D positions of the lung tumor was used as the input to the dynamic robotic moving phantom. The WEP was driven to track 3D respiratory motion. Respiratory‐gated radiotherapy was performed for driving the WEP. The tracking accuracy was calculated as the differences between the actual and measured positions. For the absolute dose and dose distribution, the differences between the planned and measured doses were calculated. The differences between the planned and measured absolute doses were

To quantify dose delivery errors for high-dose-rate image-guided brachytherapy (HDR-IGBT) using an independent end-to-end dose delivery quality assurance test at multiple institutions. The novelty of our study is that this is the first multi-institutional end-to-end dose delivery study in the world.The postal audit used a polymer gel dosimeter in a cylindrical acrylic container for the afterloading system. Image acquisition using computed tomography, treatment planning, and irradiation were performed at each institution. Dose distribution comparison between the plan and gel measurement was performed. The percentage of pixels satisfying the absolute-dose gamma criterion was reviewed.Thirty-five institutions participated in this study. The dose uncertainty was 3.6% ± 2.3% (mean ± 1.96σ). The geometric uncertainty with a coverage factor of k = 2 was 3.5 mm. The tolerance level was set to the gamma passing rate of 95% with the agreement criterion of 5% (global)/3 mm, which was determined from the uncertainty estimation. The percentage of pixels satisfying the gamma criterion was 90.4% ± 32.2% (mean ± 1.96σ). Sixty-six percent (23/35) of the institutions passed the verification. Of the institutions that failed the verification, 75% (9/12) had incorrect inputs of the offset between the catheter tip and indexer length in treatment planning and 17% (2/12) had incorrect catheter reconstruction in treatment planning.The methodology should be useful for comprehensively checking the accuracy of HDR-IGBT dose delivery and credentialing clinical studies. The results of our study highlight the high risk of large source positional errors while delivering dose for HDR-IGBT in clinical practices.

Objective. This study aimed to produce a three-dimensional liver elasticity map using the finite element method (FEM) and respiration-induced motion captured by T1-weighted magnetic resonance images (FEM-E-map) and to evaluate whether FEM-E-maps can be an imaging biomarker comparable to magnetic resonance elastography (MRE) for assessing the distribution and severity of liver fibrosis. Approach. We enrolled 14 patients who underwent MRI and MRE. T1-weighted MR images were acquired during shallow inspiration and expiration breath-holding, and the displacement vector field (DVF) between two images was calculated using deformable image registration. FEM-E-maps were constructed using FEM and DVF. First, three Poisson’s ratio settings (0.45, 0.49, and 0.499995) were validated and optimized to minimize the difference in liver elasticity between the FEM-E-map and MRE. Then, the whole and regional liver elasticity values estimated using FEM-E-maps were compared with those obtained from MRE using Pearson’s correlation coefficients. Spearman rank correlations and chi-square histograms were used to compare the voxel-level elasticity distribution. Main results. The optimal Poisson’s ratio was 0.49. Whole liver elasticity estimated using FEM-E-maps was strongly correlated with that measured using MRE (r = 0.96). For regional liver elasticity, the correlation was 0.84 for the right lobe and 0.82 for the left lobe. Spearman analysis revealed a moderate correlation for the voxel-level elasticity distribution between FEM-E-maps and MRE (0.61 ± 0.10). The small chi-square distances between the two histograms (0.11 ± 0.07) indicated good agreement. Significance. FEM-E-maps represent a potential imaging biomarker for visualizing the distribution of liver fibrosis using only T1-weighted images obtained with a common MR scanner, without any additional examination or special elastography equipment. However, additional studies including comparisons with biopsy findings are required to verify the reliability of this method for clinical application.

In this study, we investigated the possibility of predicting expression levels of programmed death-ligand 1 (PD-L1) using radiomic features of intratumoral and peritumoral tumors on computed tomography (CT) images. We retrospectively analyzed 161 patients with non-small cell lung cancer. We extracted radiomic features for intratumoral and peritumoral regions on CT images. The null importance, least absolute shrinkage, and selection operator model were used to select the optimized feature subset to build the prediction models for the PD-L1 expression level. LightGBM with five-fold cross-validation was used to construct the prediction model and evaluate the receiver operating characteristics. The corresponding area under the curve (AUC) was calculated for the training and testing cohorts. The proportion of ambiguously clustered pairs was calculated based on consensus clustering to evaluate the validity of the selected features. In addition, Radscore was calculated for the training and test cohorts. For expression level of PD-L1 above 1%, prediction models that included radiomic features from the intratumoral region and a combination of radiomic features from intratumoral and peritumoral regions yielded an AUC of 0.83 and 0.87 and 0.64 and 0.74 in the training and test cohorts, respectively. In contrast, the models above 50% prediction yielded an AUC of 0.80, 0.97, and 0.74, 0.83, respectively. The selected features were divided into two subgroups based on PD-L1 expression levels≥50% or≥1%. Radscore was statistically higher for subgroup one than subgroup two when radiomic features for intratumoral and peritumoral regions were combined. We constructed a predictive model for PD-L1 expression level using CT images. The model using a combination of intratumoral and peritumoral radiomic features had a higher accuracy than the model with only intratumoral radiomic features.

Hidekazu Tanaka,1 Taiki Ono,1 Yuki Manabe,1 Miki Kajima,1 Koya Fujimoto,1 Yuki Yuasa,1 Takehiro Shiinoki,1 Yoshikazu Yamaji,2 Kazuto Matsunaga2 1Department of Radiation Oncology, Yamaguchi University Graduate School of Medicine, Ube, Japan; 2Department of Respiratory Medicine and Infectious Disease, Yamaguchi University Graduate School of Medicine, Ube, JapanCorrespondence: Hidekazu Tanaka 1-1-1 Minamikogushi, Ube, 755-8505, JapanTel +81 836 22 2966Fax +81 836 22 2471Email h-tanaka@yamaguchi-u.ac.jpPurpose: Anemia has been associated with poor prognosis in patients with cancer across several cancer types. It has been identified as a prognostic factor in patients with non-small cell lung cancer (NSCLC) who have undergone surgery or chemoradiotherapy. However, there are only a few reports that have evaluated the prognostic significance of anemia in patients with NSCLC undergoing stereotactic body radiation therapy (SBRT).Patients and Methods: A total of 77 patients were enrolled in this study. The pretreatment hemoglobin (Hb) levels, within 2 weeks before SBRT, were available for all patients. The median age of the participants (56 men, 21 women) was 80 (range, 50– 90) years. The median Hb level was 12.8 (range, 7.8– 18.3) g/dL. The median follow-up period was 24 (range, 1– 87) months.Results: Local recurrence was observed in 8 (10.4%) cases during the follow-up period. The 1- and 2-year local control (LC) rates were 94.8% and 86.4%, respectively. Seventeen (22.1%) patients died during the follow-up period. The 1- and 2-year overall survival (OS) rates were 93.1% and 85.2%, respectively. Univariate analysis identified anemia and body mass index as significant prognostic factors for predicting OS. On multivariate analysis, anemia was confirmed to be the only significant factor (p = 0.02469).Conclusion: Our data suggest that anemia is a prognostic factor for predicting the OS rate in patients with early-stage NSCLC treated with SBRT.Keywords: anemia, hemoglobin, non-small cell lung cancer, stereotactic body radiation therapy, stereotactic ablative body radiotherapy

Purpose This study aimed to quantify the respiration‐induced motion in each pancreatic region during motion mitigation strategies and to characterize the correlations between this motion and that of the surrogate signals in cine‐magnetic resonance imaging (MRI). We also aimed to evaluate the effects of these motion mitigation strategies in each pancreatic region. Methods Sagittal and coronal two‐dimensional cine‐MR images were obtained in 11 healthy volunteers, eight of whom also underwent imaging with abdominal compression (AC). For each pancreatic region, the magnitude of pancreatic motion with and without motion mitigation and the positional error between the actual and predicted pancreas motion based on surrogate signals were evaluated. Results The magnitude of pancreatic motion with and without AC in the left–right (LR) and superior–inferior (SI) directions varied depending on the pancreatic region. In respiratory gating (RG) assessments based on a surrogate signal, although the correlation was reasonable, the positional error was large in the pancreatic tail region. Furthermore, motion mitigation in the anterior‐posterior and SI directions with RG was more effective than was that with AC in the head region. Conclusions This study revealed pancreatic region‐dependent variations in respiration‐induced motion and their effects on motion mitigation outcomes during AC or RG. The magnitude of pancreatic motion with or without AC and the magnitude of the positional error with RG varied depending on the pancreatic region. Therefore, during radiation therapy for pancreatic cancer, it is important to consider that the effects of motion mitigation during AC or RG may differ depending on the pancreatic region.

Purpose The aim of the current study was to evaluate the backscatter dose and energy spectrum from the Lipiodol with flattening filter (FF) and flattening filter‐free (FFF) beams. Moreover, the backscatter range, that was defined as the backscatter distance (BD) are revealed. Methods 6 MVX FF and FFF beams were delivered by TrueBeam. Two dose calculation methods with Monte Carlo calculation were used with a virtual phantom in which the Lipiodol (3 × 3 × 3 cm3) was located at a depth of 5.0 cm in a water‐equivalent phantom (20 × 20 × 20 cm3). The first dose calculation was an analysis of the dose and energy spectrum with the complete scattering of photons and electrons, and the other was a specified dose analysis only with scattering from a specified region. The specified dose analysis was divided into a scattering of primary photons and a scattering of electrons. Results The lower‐energy photons contributed to the backscatter, while the high‐energy photons contributed the difference of the backscatter dose between the FF and FFF beams. Although the difference in the dose from the scattered electrons between the FF and FFF beams was within 1%, the difference of the dose from the scattered photons between the FF and FFF beams was 5.4% at a depth of 4.98 cm. Conclusions The backscatter range from the Lipiodol was within 3 mm and depended on the Compton scatter from the primary photons. The backscatter dose from the Lipiodol can be useful in clinical applications in cases where the backscatter region is located within a tumor.

The dynamic tumor tracking radiotherapy (DTT-RT) is the cutting-edge technology that attempts to track and irradiates the moving tumor continuously. Prediction of the 50 -500 ms future position of the tumor is necessary for successful implementation of DTT-RT to compensate for the positioning lag of the multi-leaf collimator (MLC). It is known that lung tumor exhibits respiratory induced motion. Precise prediction of lung tumor motion is known to be a very difficult problem since it exhibits large variation both on the amplitude and the phase of the trajectory, although it is induced by respiration of a patient that is nearly periodic. This paper proposes a prediction model of a lung tumor motion. The proposed model utilizes the high-order repetitive control to generate prediction corresponding to periodic baseline of the trajectory and the long-short term memory to cope with the remaining portion. We have developed nine personalized prediction models for nine patients who underwent respiratory gated stereotactic body radiotherapy in Yamaguchi University Hospital to predict 666 ms ahead 3D tumor position for each patient. The average 3D RMS position error for the nine patients was 2.18 mm (±1.66).

Purpose To develop a novel biological dosimetric margin (BDM) and to create a biological conversion factor (BCF) that compensates for the difference between physical dosimetric margin (PDM) and BDM, which provides a novel scheme of a direct estimation of the BDM from the physical dose (PD) distribution. Methods The offset to isocenter was applied in 1-mm steps along left-right (LR), anterior-posterior (AP), and cranio-caudal (CC) directions for 10 treatment plans of lung stereotactic body radiation therapy (SBRT) with a prescribed dose of 48 Gy. These plans were recalculated to biological equivalent dose (BED) by the linear-quadratic model for the dose per fraction (DPF) of d = 3-20 Gy/fr and α / β = 3 - 10 . BDM and PDM were defined so that the region that satisfied that the dose covering 95% (or 98%) of the clinical target volume was greater than or equal to the 90% of the prescribed PD and BED, respectively. An empirical formula of the BCF was created as a function of the DPF. Results There was no significant difference between LR and AP directions for neither the PDM nor BDM. On the other hand, BDM and PDM in the CC direction were significantly larger than in the other directions. BCFs of D95% and D98% were derived for the transverse (LR and AP) and longitudinal (CC) directions. Conclusions A novel scheme to directly estimate the BDM using the BCF was developed. This technique is expected to enable the BED-based SBRT treatment planning using PD-based treatment planning systems.

Purpose/Objective(s) The monocyte-to-lymphocyte ratio (MLR), a kind of systemic inflammation biomarker, has been evaluated in relation to several types of cancer and has been found to predict responses to therapy and patient outcomes. Determining the MLR is inexpensive and can be easily derived from complete blood counts. The purpose of this study was to determine whether there are association between the MLR and local control rates (LC) and cause-specific survival rates (CSS) of patients with lung cancer treated with stereotactic body radiation therapy (SBRT). Materials/Methods Patients treated in two hospitals were enrolled in this study. The inclusion criteria were as follows: patients with localized non-small-cell lung cancer (NSCLC), with N0M0 disease, who were medically inoperable or refused to undergo surgery, were treated with SBRT, and for whom blood count data were available within 2 weeks prior to SBRT. In total, 194 patients met these criteria. Univariate and multivariate Cox proportional hazard regression models were used to estimate LC and CSS. Variables of which the P-values Results The median age of the 194 participants (144 male, 50 female) was 80 (range, 50-96) years. Patients presented with performance status (PS) 0/1/2/3 were 92/86/14/2. The median diameter of the tumor was 20 (range, 7-52) mm. The number of patients with pathological confirmation of lung cancer was 89 (45.9%). The remaining patients were diagnosed based on the observation of increasing size and abnormal uptake on PET. In principle, the prescribed dose to peripheral tumors was 48 Gy in 4 fractions (n = 130) or 50 Gy in 5 fractions (n = 51). The tumors with central lesions located near organs at risk were treated with 60 Gy in 8 fractions (n = 11). The calculated median MLR was 0.2605 (0.095-1.113). The optimal cut-off values for the MLR in LC and CSS rates were 0.198 and 0.340, respectively. Univariate Cox proportional hazards regression analysis determined the MLR, PS and tumor diameter as significant factor for LC. Multivariate analysis determined the MLR and tumor diameter as significant factor (P = 0.04105 and 0.03071), respectively. Although the MLR tends to predict the CSS in univariate analysis (P = 0.08616), none of the parameters was a significant factor to predict the CSS. However, the MLR as a continuous variable was a significant factor for CSS in univariate analysis (P = 0.003693). Conclusion Our data suggest that the MLR is correlated with LC and CSS rates in patients with NSCLC treated by SBRT.

Purpose A commercially available bolus (“commercial-bolus”) does not make complete contact with the irregularly shaped patient skin. This study aims to customise a patient-specific three-dimensional (3D) bolus using a 3D printing technique (“3D-bolus”) and to evaluate its clinical feasibility for photon radiotherapy. Methods The 3D-bolus was designed using a treatment planning system (TPS) in Digital Imaging and Communications in Medicine-Radiotherapy (DICOM-RT) format, and converted to stereolithographic format for printing. To evaluate its physical characteristics, treatment plans were created for water-equivalent phantoms that were bolus-free, or had a flat-form printed 3D-bolus, a TPS-designed bolus (“virtual-bolus”), or a commercial-bolus. These plans were compared based on the percentage depth dose (PDD) and target-volume dose volume histogram (DVH) measurements. To evaluate the clinical feasibility, treatment plans were created for head phantoms that were bolus-free or had a 3D-bolus, a virtual-bolus, or a commercial-bolus. These plans were compared based on the target volume DVH. Results In the physical evaluation, the 3D-bolus provided effective dose coverage in the build-up region, which was equivalent to the commercial-bolus. With regard to the clinical feasibility, the air gaps were lesser with the 3D-bolus when compared to the commercial-bolus. Furthermore, the prescription dose could be delivered appropriately to the target volume. The 3D-bolus has potential use for air-gap reduction compared to the commercial-bolus and facilitates target-volume dose coverage and homogeneity improvement. Conclusions A 3D-bolus produced using a 3D printing technique is comparable to a commercial-bolus applied to an irregular-shaped skin surface.

Rationale: Although the development of CT imaging can help us to understand the complex pathophysiology of lung diseases, the association with physical activity (PA) and multiple CT metrics remain unknown. The aim of the study is to investigate whether inspiratory-to-expiratory CT imaging show promise for use as biomarkers in PA. Methods: Parametric response mapping(PRM), expiratory/inspiratory mean lung density ratio (E/I) and expiratory/inspiratory mean normal lung density ratio (ND-E/I) through the use of inspiratory and expiratory CT scan and PA by use of a triaxial accelerometer was evaluated in healthy(n=6), asthmatics(n=27) and COPD(n=14). PRM classifies lung as normal, functional small airway disease (PRMfSAD), and emphysema (PRMEMPH). Exercise (Ex) was calculated by metabolic equivalents (METs) multiplied by PA duration and low activity (LA) was defined exercise as Ex below 1.5. Results: 6 patients were classified as the LA group and 41 patients as the activity maintenance (MA) group. LA group was more likely to be heavy smokers, have low pulmonary function and hyperinflation. Moreover, LA group show higher PRMfSAD (41.6 vs 29.8, p Conclusion: Quantitative inspiratory-to-expiratory CT imaging can be biomarker to detect physical activity levels.

The aim of our study is to evaluate the metal artefact reduction techniques with the same contrast scale for different vendors’ dual-energy CT (DECT): kV-CT image with metal artefact reduction method and monoenergetic CT image using Canon’s DECT, and monoenergetic CT image with metal artefact reduction method using GE’s DECT. The kV-CT image and DECT scans were performed with the water-based polymethyl methacrylate phantom with various metal materials (brass, aluminium, copper, stainless steel, steel, lead, and titanium). Two types of metal artefact reduction (MAR) algorithm with the monoenergetic CT images were used. Smart MAR implemented by GE and the kV-CT images with MAR algorithms. Single-energy metal artefact reduction (SEMAR), implemented by Canon, was reconstructed. The artefact index was evaluated using the converted electron density values from the kV-CT and DECT images. The artefact index with all material inserts in the monoenergetic CT images were smallest at 70–90 keV for Canon and 140 keV for GE. The artefact index without SEMAR was larger than that with SEMAR for the 80 and 135-kV CT images. In the comparison of the artefact index for the converted electron density images from the 80 and 135-kV CT images with SEMAR, as well as the monoenergetic CT images with and without MAR, the monoenergetic CT image at 140 keV with MAR showed a reduction. In the comparison of the monoenergetic CT images at 140 keV and other energy ranges without and with Smart MAR, there was no statistically significant difference (P

This technical note discloses our implementation of a six degree-of-freedom (DOF) high-precision robotic phantom on a commercially available industrial robot manipulator. These manipulators are designed to optimize their set point tracking accuracy as it is the most important performance metric for industrial manipulators. Their in-house controllers are tuned to suppress its error less than a few tens of micrometers. However, the use of industrial robot manipulators in six DOF robotic phantom can be a difficult problem since their in-house controller are not optimized for continuous path tracking in general. Although instantaneous tracking error in a continuous path tracking task will not exceed five millimeters during motion with the in-house controller, it seriously matters for a robotic phantom, as the tracking error should remain within one millimeter in three dimensional space for all time during motion. The difficulty of the task is further increased since the reference trajectory of a robotic phantom, which is a six DOF tumor motion of a patient, cannot be as smooth as the ones used in factories. The present study presents a feedforward controller for a feedback-controlled industrial six DOF robotic manipulator to be used as a six DOF robotic phantom to drive the water equivalent phantom (WEP). We first trained a set of six recurrent neural networks (RNNs) to capture the six DOF input/output behavior of the robotic manipulator controlled by its in-house controller, and we proceed to formulate an iterative learning control (ILC) using the trained model to generate an augmented reference trajectory for a specific patient that enables very high tracking accuracy to that trajectory. Experimental evaluation results demonstrate clear improvements in the accuracy of the proposed robotic phantom compared to our previous robotic phantom, which uses the same manipulator but is driven by a different corrected reference trajectory.

A combined system comprising the TrueBeam linear accelerator and a new real-time tumour-tracking radiotherapy system, SyncTraX, was installed at our institution. The objectives of this study are to develop a method for the verification of respiratory-gated radiotherapy with SyncTraX using cine electronic portal image device (EPID) images and a log file and to verify this treatment in clinical cases. Respiratory-gated radiotherapy was performed using TrueBeam and the SyncTraX system. Cine EPID images and a log file were acquired for a phantom and three patients during the course of the treatment. Digitally reconstructed radiographs (DRRs) were created for each treatment beam using a planning CT set. The cine EPID images, log file, and DRRs were analysed using a developed software. For the phantom case, the accuracy of the proposed method was evaluated to verify the respiratory-gated radiotherapy. For the clinical cases, the intra- and inter-fractional variations of the fiducial marker used as an internal surrogate were calculated to evaluate the gating accuracy and set-up uncertainty in the superior-inferior (SI), anterior-posterior (AP), and left-right (LR) directions. The proposed method achieved high accuracy for the phantom verification. For the clinical cases, the intra- and inter-fractional variations of the fiducial marker were ⩽3 mm and ±3 mm in the SI, AP, and LR directions. We proposed a method for the verification of respiratory-gated radiotherapy with SyncTraX using cine EPID images and a log file and showed that this treatment is performed with high accuracy in clinical cases.

Purpose: The purposes of this study were to estimate accumulated kV X-ray imaging dose throughout dynamic tumor tracking (DTT) irradiation by Vero 4DRT system and to address an analytical skin dose formula for well-balanced kV X-ray imaging conditions between skin dose and image noise. Method: First, skin dose was measured using kV X-ray tube, chamber, and water-equivalent phantoms. Next, imaging dose for six patients in DTT treatment was computed using log files. Subsequently, scattered dose ratio was calculated by amount of ionization in front of flat panel detector (FPD) for fields with size of maximum and the chamber for 0 - 200 mm-thickness phantoms and tube voltage of 60, 80, 100, 120 kV, respectively. Furthermore, image noise was computed from FPD images. Results: The skin dose was greater by a factor of 1.4 - 1.6 than those in Synergy XVI system. The image noise in FPD, was expressed as N = 0.045×(1/QFPDen)0.479, where QFPDen denotes amount of ionization in front of FPD. Then, skin dose, D (N, t, v) was formulated as (0.045/N)(1/0.479)/QFPDen/mAs (t, v) ×D/mAs (v), where QFPDen/mAs (t, v) and D/mAs (v) denote amount of ionization in front of FPD and skin dose per mAs, respectively. Using the formulae, it has been demonstrated that skin dose with 120 kV has become lower than any other tube voltage in this study. Conclusion: Using skin doses for the phantom, the skin dose throughout DTT irradiation was estimated as 0.50 Gy. Furthermore, skin dose by kV X-ray imaging was described as a function of image noise, phantom thickness, and tube voltage, suggesting image noise may be reduced with higher X-ray tube voltage in this phantom study.

A combined system comprising the TrueBeam linear accelerator and a new real-time, tumor-tracking radiotherapy system, SyncTraX, was installed in our institution. The goals of this study were to assess the capability of SyncTraX in measuring the position of a fiducial marker using color fluoroscopic images, and to evaluate the dosimetric and geometric accuracy of respiratory-gated radiotherapy using this combined system for the simple geometry. For the fundamental evaluation of respiratory-gated radiotherapy using SyncTraX, the following were performed:1) determination of dosimetric and positional characteristics of sinusoidal patterns using a motor-driven base for several gating windows; 2) measurement of time delay using an oscilloscope; 3) positional verification of sinusoidal patterns and the pattern in the case of a lung cancer patient; 4) measurement of the half-value layer (HVL in mm AL), effective kVp, and air kerma, using a solid-state detector for each fluoroscopic condition, to determine the patient dose. The dose profile in a moving phantom with gated radiotherapy having a gating window ≤ 4 mm was in good agreement with that under static conditions for each photon beam. The total time delay between TrueBeam and SyncTraX was < 227 ms for each photon beam. The mean of the positional tracking error was < 0.4 mm for sinusoidal patterns and for the pattern in the case of a lung cancer patient. The air-kerma rates from one fluoroscopy direction were 1.93 ± 0.01, 2.86 ± 0.01, 3.92 ± 0.04, 5.28 ± 0.03, and 6.60 ± 0.05 mGy/min for 70, 80, 90, 100, and 110 kV X-ray beams at 80 mA, respectively. The combined system comprising TrueBeam and SyncTraX could track the motion of the fiducial marker and control radiation delivery with reasonable accuracy; therefore, this system provides significant dosimetric improvement. However, patient exposure dose from fluoroscopy was not clinically negligible.

In high-precision radiotherapy, absolute and relative doses are evaluated for patient-specific intensity-modulated radiation therapy (IMRT) quality assurance (QA). In our institution, we use GAFCHROMIC EBT3 (EBT3) for relative dose evaluation in IMRT QA. We usually use two directional film configurations, which are in the axial and sagittal planes. The QA in our institution shows some differences between the gamma pass rates in the axial and sagittal directions. The purpose of this study was to evaluate the incident directional dependence of EBT3 by using the percent depth dose (PDD) and the off-center ratio (OCR) between EBT3 films positioned perpendicular to the beam axis and along the beam axis. Furthermore, we compared the PDD in EBT3 films positioned perpendicular to the beam axis and the PDD by using an ionization chamber. In addition, PDDs in water phantoms with and without EBT3 films were calculated by Monte Carlo simulation. The results showed that the PDD in EBT3 films positioned perpendicular to the beam axis increased with the depth from the phantom surface. Monte Carlo simulation showed the same trend as did the film measurements. The OCR results were slightly different at dose levels below 20 %. The OCR in EBT3 films positioned along the beam axis was higher than that perpendicular to the beam axis. Thus, we conclude that EBT3 film has incident directional dependence. In IMRT QA, the gamma analysis results may be affected by the incident directional dependence of EBT3 film.

BACKGROUND: Previously, the physical dose-enhancement factor (D(phys)EF) enhancement was introduced. However, the dose enhancement considering the biological effectiveness was not shown. PURPOSE: The aim of the current study was to evaluate the biological dose-enhancement factor (D(bio)EF) by the dose rate and to compare the D(phys)EF and the D(bio)EF in Lipiodol for liver Stereotactic Body Radiation Therapy (SBRT). MATERIALS AND METHODS: Flattening-filter-free (FFF) 6-MV (6MVX) and 10MVX beams were delivered by TrueBeam. A virtual inhomogeneity phantom and a liver SBRT patient-treatment plan were used. The D(phys)EF and lineal energy distribution ([Formula: see text]) distribution was calculated from Monte Carlo simulations. Using a microdosimetric-kinetic (MK) model that is estimated based on the linear-quadratic formula for Lipiodol using human liver hepatocellular cells (HepG2), the biological dose and biological dose enhancement factor (D(bio)EF) were calculated. The dose rate in the simulation was changed from 0.1 to 24 Gy/min. RESULTS: The D(bio)EF (DR:2Gy/min) and D(phys)EF with 10MVX FFF beam were 23.2% and 19.1% at maximum and 12.8% and 11.1% on average in the Lipiodol. In the comparison of the D(bio)EF between 0.1–24 Gy/min, the D(bio)EF was 21.2% and 11.1% with 0.1 Gy/min for 6MVX and 10 MVX, respectively. The D(bio)EF was larger than DEF for the 6MVX and 10MVX FFF beams. In clinical cases with the 10MVX FFF beam, the D(bio)EF and D(phys)EF in the Lipiodol region can increase the in-tumor dose by approximately 11% and 10%, respectively, without increasing the dose to normal tissue. CONCLUSIONS: The lower-energy and higher-dose-rate beams were contributed to the biological dose. The Lipiodol caused the enhancement of the physical dose and biological effectiveness. ADVANCES IN KNOWLEDGE: The biological dose enhancement (D(bio)EF) should be considered in the high-density material such as the Lipiodol.

OBJECTIVES: The aim of the current study is to evaluate the accuracy and the precision of raw-data-based relative electron density (RED(raw)) and the calibration-based RED (RED(cal)) at a range of low-RED to high-RED for tissue-equivalent phantom materials by comparing them with reference RED (RED(ref)) and to present the difference of RED(raw) and RED(cal) for the contrast medium using dual-energy CT (DECT). METHODS: The RED(raw) images were reconstructed by raw-data-based decomposition using DECT. For evaluation of the accuracy of the RED(raw), RED(ref) was calculated for the tissue-equivalent phantom materials based on their specified density and elemental composition. The RED(cal) images were calculated using three models: Lung-Bone model, Lung-Ti model and Lung-Ti (SEMAR) model which used single-energy metal artifact reduction (SEMAR). The difference between RED(raw) and RED(cal) was calculated. RESULTS: In the titanium rod core, the deviations of RED(raw) and RED(cal) (Lung-Bone model, Lung-Ti model and Lung-Ti model with SEMAR) from RED(ref) were 0.45%, 50.8%, 15.4% and 15.0%, respectively. The largest differences between RED(raw) and RED(cal) (Lung-Bone model, Lung-Ti model and Lung-Ti model with SEMAR) in the contrast medium phantom were 8.2%, −23.7%, and 28.7%, respectively. However, the differences between RED(raw) and RED(cal) values were within 10% at 20 mg/ml. The standard deviation of the RED(raw) was significantly smaller than the RED(cal) with three models in the titanium and the materials that had low CT numbers. CONCLUSION: The RED(cal) values could be affected by beam hardening artifacts and the RED(cal) was less accurate than RED(raw) for high-Z materials as titanium. ADVANCES IN KNOWLEDGE: The raw-data-based reconstruction method could reduce the beam hardening artifact compared with image-based reconstruction and increase the accuracy for the RED estimation in high-Z materials, such as titanium and iodinated contrast medium.

Objective: The aim of the current study is to evaluate the effectiveness of reduction metal artifacts using kV-CT image with the single-energy based metal artefact reduction (SEMAR) technique by single-energy reconstruction, monochromatic CT and rED reconstructed by dual-energy reconstruction. Methods: Seven different metal materials (brass, aluminum, copper, stainless, steel, lead and titanium) were placed inside the water-based PMMA phantom. After DECT-based scan, the artefact index (AI) were evaluated with the kV-CT images with and without SEMAR by single-energy reconstruction, and raw-data based electron density (rED), monochromatic CT images by dual-energy reconstruction. Moreover, the AI with evaluated with rED and the converted ED images from the kV-CT and monochromatic CT images. Results: The minimum average value of the AI with all-metal inserts was approximately 80 keV. The AI without SEMAR was larger than that with SEMAR for the 80 kV and 135 kV CT images. In the comparison of the AI for the rED and ED images that were converted from 80 kV and 135 kV CT images with and without SEMAR, the monochromatic CT images of the PMMA phantom with inserted metal materials at 80 keV revealed that the kV-CT with SEMAR reduced the metal artefact substantially. Conclusion: The converted ED from the kV-CT and monochromatic CT images could be useful for a comparison of the AI using the same contrast scale. The kV-CT image with SEMAR by single-energy reconstruction was found to substantially reduce metal artefact. Advances in knowledge: The effectiveness of reduction of metal artifacts using single-energy based metal artefact reduction (SEMAR) technique and dual-energy CT (DECT) was evaluated the electron density conversion techniques.

This paper handles the prediction of the future lung tumor position which exhibits respiratory-induced motion inside the body of the patient. The prediction of the future tumor position is a necessary step for dynamic tumor tracking radiotherapy to compensate the positioning lag of the gantry of the clinical linear accelerator. This lag is known to be almost one second and the objective of the current study is accordingly to generate the one second future position estimate of the tumor with the tolerance of 1mm prediction error in the three-dimensional space. Several researches have been done to calculate predicted position of the tumor by establishing mathematical models. The current study focuses on the development of a mathematical model which provides one-second future position of the tumor using the recurrent neural network (RNN). The result of the numerical validation has been reported to justify the choice of the model structure and to show that the model can be trained to have the sufficient prediction accuracy necessary for use in real-time dynamic tumor tracking radiotherapy.

Metal dental restoration materials cause dose enhancement upstream and dose disturbance downstream of the high‐density inhomogeneous regions in which these materials are used. In this study, we evaluated the impact of a dental metallic crown (DMC) on intensity‐modulated radiotherapy (IMRT) and volumetric‐modulated arc therapy (VMAT) for head and neck cancer. Additionally, the possibility of sparing the oral mucosa from dose enhancement using an individual intraoral mouthpiece was evaluated. An experimental oral phantom was designed to verify the dosimetric impact of a DMC. We evaluated the effect on single beam, parallel opposing beam, arc beam, IMRT, and VMAT treatment plans. To evaluate the utility of a 3‐mm‐thick intraoral mouthpiece, the doses across the mouthpiece were measured. For single beam irradiation, the measured doses at the entrance and exit planes of the DMC were 51% higher and 21% lower than the calculated dose by the treatment planning system, respectively. The maximum dose enhancements were 22% and 46% for parallel opposing beams and the 90° arc rotation beam, respectively. For IMRT and VMAT, the measured doses adjacent to the DMC were 12.2%±6.3% (mean±1.96 SD) and 12.7%±2.5% higher than the calculated doses, respectively. With regard to the performance of the intraoral mouthpiece for the IMRT and VMAT cases, the disagreement between measured and calculated doses at the outermost surface of the mouthpieces were −2.0%, and 2.0%, respectively. Dose enhancements caused by DMC‐mediated radiation scattering occurred during IMRT and VMAT. Because it is difficult to accurately estimate the dose perturbations, careful consideration is necessary when planning head and neck cancer treatments in patients with DMCs. To spare the oral mucosa from dose enhancement, the use of an individual intraoral mouthpiece should be considered. PACS numbers: 87.55.km, 87.55.N‐, 87.55.Qr

This paper discloses the development of a phase oscillator model for radiotherapy which predicts future position of the lung tumor based on the current and past phase of lung tumor, respiration waveform and heartbeat measurements. We assumed that these phases can be measured at the same time, and tried the prediction of 0.15s ahead of time of the superior-inferior direction of a lung tumor motion. The result of offline simulation shows that the proposed model provides the estimated position of the tumor with 1.5mm RMS error.

Purpose: We have recently developed a dynamic tumor tracking irradiation system using Vero4DRT (MHI‐Tm2000). It is needed to create a 4D correlation model between a fiducial marker implanted near a tumor and an external surrogate as a function of time by continuously acquiring both fluoroscopyimages and external surrogate signals. The purpose of this study was to propose a new dosimetry method using Gafchromic XR‐SP2 films to measuresurface dose by fluoroscopyimaging.Methods: First, half‐value layers (HVLs) were measured using aluminum(Al) thicknesses (15 mm) at 40125 kVp. Subsequently, several films were irradiated using various milliampere second values on a solid water phantom. The surface air kerma were also measured using the chamber to calculate the surface doses under the same condition. Then, the calibration curve of dose vs. pixel values was calculated. Finally, surface dose by fluoroscopyimaging was measured using several pieces of film taped on the chest phantom. Orthogonal X‐ray fluoroscopyimaging was simultaneously performed until completion of data acquisition for creating a 4D correlation model. Those films were scanned after irradiation using a flat‐bed scanner and converted to dose by calibration curve. Results: The HVLs for tube voltage within 40125 kVp ranged from 2.35 to 5.98 mm Al. The calibration curve between surface dose and pixel values was reasonably smooth. The differences between the measured and the calibrated doses were less than 3%. The hot spots with the maximum dose of 37.12 mGy were observed around the area overlapped by both fluoroscopic fields. Conclusions: We have proposed a new dosimetry method using Gafchromic XR‐SP2 films to measuresurface dose by fluoroscopyimaging. This phantom study has demonstrated that it may be feasible to assess surface dose to patients during dynamic tumor tracking irradiation in clinic with ease after further investigation. This research was supported by the Japan Society for the Promotion of Science (JSPS) through its Funding Program for World‐Leading Innovation R&D on Science and Technology (FIRST Program). Research sponsored in part by Mitsubishi Heavy Industries, Ltd.

We are developing an innovative dynamic tumor tracking irradiation technique using gold markers implanted around a tumor as a surrogate signal, a real‐time marker detection system, and a gimbaled X‐ray head in the Vero4DRT. The gold markers implanted in a normal organ will produce uncertainty in the dose calculation during treatment planning because the photon mass attenuation coefficient of a gold marker is much larger than that of normal tissue. The purpose of this study was to simulate the dose variation near the gold markers in a lung irradiated by a photon beam using the Monte Carlo method. First, the single‐beam and the opposing‐beam geometries were simulated using both water and lung phantoms. Subsequently, the relative dose profiles were calculated using a stereotactic body radiotherapy (SBRT) treatment plan for a lung cancer patient having gold markers along the anteriorposterior (AP) and right‐left (RL) directions. For the single beam, the dose at the gold marker‐phantom interface laterally along the perpendicular to the beam axis increased by a factor of 1.35 in the water phantom and 1.58 in the lung phantom, respectively. Furthermore, the entrance dose at the interface along the beam axis increased by a factor of 1.63 in the water phantom and 1.91 in the lung phantom, while the exit dose increased by a factor of 1.00 in the water phantom and 1.12 in the lung phantom, respectively. On the other hand, both dose escalations and dose de‐escalations were canceled by each beam for opposing portal beams with the same beam weight. For SBRT patient data, the dose at the gold marker edge located in the tumor increased by a factor of 1.30 in both AP and RL directions. In clinical cases, dose escalations were observed at the small area where the distance between a gold marker and the lung tumor was ≤ 5 mm, and it would be clinically negligible in multibeam treatments, although further investigation may be required. PACS number: 87.10.Rt

The present note addresses the development of a lung tumor position predictor to be used in dynamic tumor tracking radiotherapy, abbreviated as DTT-RT. As there exists 50-500 ms positioning lag in the control of the multi-leaf collimator (MLC) of commercial medical linear accelerators, prediction of future lung tumor position with sufficiently long prediction horizon is inevitable for the successful implementation of DTT-RT. The present article proposes a lung tumor position predictor, which is classified as a nonlinear autoregressive model with exogenous input (NARX). The proposed predictor was trained using seven lung tumor motion trajectories of patients who underwent respiratory gated radiotherapy at Yamaguchi University Hospital. We considered three different prediction horizons, 600 ms, 800 ms and 1 s, which were sufficiently long to compensate for the possible positioning control lag of the MLC. A patient-specific model corresponding to an intended prediction horizon was obtained by training it using the selected tumor motion trajectory with the specified horizon. Accordingly, we obtained three NARX predictors for a single patient. We calculated two performance metrics: the RMS prediction errors and the rate of coverage of the entire tumor trajectory defined by the number of samples of the measured tumor position which was inside the 4 mm cube centered at the corresponding predicted tumor position. The latter quantifies the feasibility of the predictors to generate future gating cubes in the implementation of DTT-RT. The [Formula: see text] (mean [Formula: see text] standard deviation) values of the rates of 600 ms, 800 ms and 1 s prediction horizon calculated using the proposed NARX predictors were [Formula: see text]%, [Formula: see text]% and [Formula: see text]%, respectively.

Purpose: Respiratory-gated radiation therapy (RT) using the real-time tumor-tracking radiotherapy (RTRT) system is an effective technique for managing tumor motion. High dosimetric and geometric accuracy is needed; however, quality assurance (QA) for respiratory-gated RT using the RTRT system has not been reported. The purpose of this study was to perform QA for respiratorygated RT using the RTRT system. Materials and Methods: The RTRT system detected the position of the fiducial marker and radiation delivery gated to the motion of the marker was performed. The dynamic anthropomorphic thorax phantom was positioned at the isocenter using the fiducial marker in the phantom. The phantom was irradiated only when the fiducial marker was within a three-dimensional gating window of ±2 mm from the planned position. First, the absolute doses were measured using anionization chamber inserted in the phantom under the stationary, gating and non-gating state for sinusoidal (nadir-to-peak amplitude [A]: 20 - 40 mm, breathing period [T]: 2 - 4 s) and the basic respiratory patterns. Second, the dose profiles were measured using Gafchromic films in the phantom under the same conditions. Differences between dose profiles were calculated to evaluate the dosimetric and geometric accuracy. Finally, differences between the actual and measured position of the fiducial marker were calculated to evaluate the tracking accuracy for sinusoidal and basic respiratory patterns. Results: For the sinusoidal patterns, the relative doses were 0.93 for non-gating and 0.99 for gating (A = 20 mm, T = 2 s), 0.94 for non-gating and 1.00 for gating (A = 20 mm, T = 4 s), 0.55 for non-gating and 1.00 for gating (A = 40 mm, T = 4 s), respectively. For the basic respiratory pattern, the relative doses were 1.00 for non-gating and 1.00 for gating, respectively. Compared to the stationary conditions, the differences in lateral distance between the 90% dose of dose profiles were 6.23 mm for non-gating and 0.36 mm for gating (A = 20 mm, T = 2 s), 8.79 mm for non-gating and 1.73 mm for gating (A = 20 mm, T = 4 s), 18.37 mm for non-gating and 0.67 mm for gating (A = 40 mm, T = 4 s), respectively. For the basic respiratory pattern, those were 5.23 mm for non-gating and 0.35 mm for gating. The root mean square (RMS) values of the tracking error were 0.18 mm (A = 20 mm, T = 2 s), 0.14 mm (A = 20 mm, T = 4 s), and 0.21 mm (A = 40 mm, T = 4 s) for sinusoidal and 0.79 mm for the basic respiratory pattern, respectively. Conclusion: We conducted QA for respiratory-gated RT using the RTRT system. The respiratory-gated RT using the RTRT system reduced the blurring effects on dose distribution with high dosimetric and geometric accuracy.