Variation in target volume and centroid position due to breath holding during four-dimensional computed tomography scanning: A phantom study.

This study investigated the effects of respiratory motion, including unwanted breath holding, on the target volume and centroid position on four-dimensional computed tomography (4DCT) imaging. Cine 4DCT images were reconstructed based on a time-based sorting algorithm, and helical 4DCT images were reconstructed based on both the time-based sorting algorithm and an amplitude-based sorting algorithm. A spherical object 20 mm in diameter was moved according to several simulated respiratory motions, with a motion period of 4.0 s and maximum amplitude of 5 mm. The object was extracted automatically, and the target volume and centroid position in the craniocaudal direction were measured using a treatment planning system. When the respiratory motion included unwanted breath-holding times shorter than the breathing cycle, the root mean square errors (RSME) between the reference and imaged target volumes were 18.8%, 14.0%, and 5.5% in time-based images in cine mode, time-based images in helical mode, and amplitude-based images in helical mode, respectively. In helical mode, the RSME between the reference and imaged centroid position was reduced from 1.42 to 0.50 mm by changing the reconstruction method from time- to amplitude-based sorting. When the respiratory motion included unwanted breath-holding times equal to the breathing cycle, the RSME between the reference and imaged target volumes were 19.1%, 24.3%, and 15.6% in time-based images in cine mode, time-based images in helical mode, and amplitude-based images in helical mode, respectively. In helical mode, the RSME between the reference and imaged centroid position was reduced from 1.61 to 0.83 mm by changing the reconstruction method from time- to amplitude-based sorting. With respiratory motion including breath holding of shorter duration than the breathing cycle, the accuracies of the target volume and centroid position were improved by amplitude-based sorting, particularly in helical 4DCT.

Evaluation of Dynamic Tumor-tracking Intensity-modulated Radiotherapy for Locally Advanced Pancreatic Cancer.

Intensity-modulated radiotherapy (IMRT) is now regarded as an important treatment option for patients with locally advanced pancreatic cancer (LAPC). To reduce the underlying tumor motions and dosimetric errors during IMRT as well as the burden of respiratory management for patients, we started to apply a new treatment platform of the dynamic tumor dynamic tumor-tracking intensity-modulated radiotherapy (DTT-IMRT) using the gimbaled linac, which can swing IMRT toward the real-time tumor position under patients' voluntary breathing. Between June 2013 and March 2015, ten patients were treated, and the tumor-tracking accuracy and the practical benefits were evaluated. The mean PTV size in DTT-IMRT was 18% smaller than a conventional ITV-based PTV. The root-mean-squared errors between the predicted and the detected tumor positions were 1.3, 1.2, and 1.5 mm in left-right, anterior-posterior, and cranio-caudal directions, respectively. The mean in-room time was 24.5 min. This high-accuracy of tumor-tracking with reasonable treatment time are promising and beneficial to patients with LAPC.

Clinical results of dynamic tumor tracking intensity-modulated radiotherapy with real-time monitoring for pancreatic cancers using a gimbal mounted linac.

OBJECTIVES: We performed dynamic tumor-tracking IMRT (DTT-IMRT) in locally advanced pancreatic cancer (LAPC) patients using a gimbaled linac of Vero4DRT. The purpose of this study is to report the first clinical results. METHODS: From June 2013 to June 2015, eleven LAPC patients enrolled in this study and DTT-IMRT was successfully performed. The locoregional progression free survival (LRPFS), distant metastasis free survival (DMFS), overall survival (OS), hematologic and gastrointestinal (GI) toxicities were evaluated. Oncologic outcomes were estimated using Kaplan-Meier analysis, and toxicities using CTCAE v4.0. RESULTS: The median radiation dose was 48 Gy (range, 45-51) in 15 fractions. Concurrent chemoradiotherapy (CCRT) was performed using gemcitabine in 9 patients and S-1 in one, while one patient refused. With a median follow-up of 22.9 months, 1-year LRPFS, DMFS, and OS rates were 90.9%, 70.7%, and 100%, respectively. Median survival time was 23.6 months. Grade-3 leucopenia and neutropenia were observed in two (18%) and one patient (9%), respectively. Grade-2 acute GI toxicity occurred in 2 patients (18%) and late grade-3 in 1 patient (9%). CONCLUSIONS: Preliminarily application of DTT-IMRT using a gimbaled linac on CCRT in LAPC patients resulted in excellent locoregional control and OS without severe toxicity.

Development of a portable quality control application using a tablet-type electronic device.

PURPOSE: Our aim was to develop a portable quality control (QC) application using a thermometer, a barometer, an angle gauge, and a range finder implemented in a tablet-type consumer electronic device (CED) and to assess the accuracies of the measurements made. METHODS: The QC application was programmed using Java and OpenCV libraries. First, temperature and atmospheric pressure were measured over 30 days using the temperature and pressure sensors of the CED and compared with those measured by a double-tube thermometer and a digital barometer. Second, the angle gauge was developed using the accelerometer of the CED. The roll and pitch angles of the CED were measured from 0 to 90° at intervals of 10° in the clockwise (CW) and counterclockwise (CCW) directions. The values were compared with those measured by a digital angle gauge. Third, a range finder was developed using the tablet's built-in camera and image-processing capacities. Surrogate markers were detected by the camera and their positions converted to actual positions using a homographic transformation method. Fiducial markers were placed on a treatment couch and moved 100 mm in 10-mm steps in both the lateral and longitudinal directions. The values were compared with those measured by the digital output of the treatment couch. The differences between CED values and those of other devices were compared by calculating means ± standard deviations (SDs). RESULTS: The means ± SDs of differences in temperature and atmospheric pressure were -0.07 ± 0.25°C and 0.05 ± 0.10 hPa, respectively. The means ± SDs of the difference in angle was -0.17 ± 0.87° (0.15 ± 0.23° degrees excluding the 90° angle). The means ± SDs of distances were 0.01 ± 0.07 mm in both the lateral and longitudinal directions. CONCLUSIONS: Our portable QC application was accurate and may be used instead of standard measuring devices. Our portable CED is efficient and simple when used in the field of medical physics.

Geometric and dosimetric accuracy of dynamic tumor tracking during volumetric-modulated arc therapy using a gimbal mounted linac.

PURPOSE: The aim was to examine the feasibility of a dynamic tumor-tracking volumetric modulated arc therapy (DTT-VMAT) technique using a gimbal-mounted linac and assess its positional, mechanical and dosimetric accuracy. MATERIALS AND METHODS: DTT-VMAT was performed using a surrogated signal-based technique. The positional tracking accuracy was evaluated as the difference between the predicted and detected target positions for various wave patterns. Mechanical accuracy measurements included gantry, multileaf collimator (MLC) and gimbal positions. The differences between the command and the measured positions were evaluated for various wave patterns. Dosimetric verification was performed using Gafchromic EBT3 films in the benchmark phantom and two clinical cases. RESULTS: The root mean square error (RMSE) of the positional accuracy was within 0.31 mm. The RMSE of mechanical accuracy was within 0.14° for the gantry, 0.11 ±â€¯0.02 mm for the MLC and 0.13 mm for the gimbal positions. The passing rate of the 3%/3 mm gamma index was greater than 83.3% and 91.2% for the benchmark phantom and two clinical cases, respectively. CONCLUSIONS: The positional, mechanical and dosimetric accuracy of DTT-VMAT were evaluated. DTT-VMAT with a gimbal-mounted linac had sufficient accuracy and presents a new strategy for treatment of several tumors with respiratory motion.

Use of a second-dose calculation algorithm to check dosimetric parameters for the dose distribution of a first-dose calculation algorithm for lung SBRT plans.

PURPOSE: To verify lung stereotactic body radiotherapy (SBRT) plans using a secondary treatment planning system (TPS) as an independent method of verification and to define tolerance levels (TLs) in lung SBRT between the primary and secondary TPSs. METHODS: A total of 147 lung SBRT plans calculated using X-ray voxel Monte Carlo (XVMC) were exported from iPlan to Eclipse in DICOM format. Dose distributions were recalculated using the Acuros XB (AXB) and the anisotropic analytical algorithm (AAA), while maintaining monitor units (MUs) and the beam arrangement. Dose to isocenter and dose-volumetric parameters, such as D2, D50, D95 and D98, were evaluated for each patient. The TLs of all parameters between XVMC and AXB (TLAXB) and between XVMC and AAA (TLAAA) were calculated as the mean±1.96 standard deviations. RESULTS: AXB values agreed with XVMC values within 3.5% for all dosimetric parameters in all patients. By contrast, AAA sometimes calculated a 10% higher dose in PTV D95 and D98 than XVMC. The TLAXB and TLAAA of the dose to isocenter were -0.3±1.4% and 0.6±2.9%, respectively. Those of D95 were 1.3±1.8% and 1.7±3.6%, respectively. CONCLUSIONS: This study quantitatively demonstrated that the dosimetric performance of AXB is almost equal to that of XVMC, compared with that of AAA. Therefore, AXB is a more appropriate algorithm for an independent verification method for XVMC.

Inter- and Intrafractional Variation in the 3-Dimensional Positions of Pancreatic Tumors Due to Respiration Under Real-Time Monitoring.

PURPOSE: To quantify the 3-dimensional pancreatic tumor motion during the overall treatment course using real-time orthogonal kilovoltage X-ray imaging. METHODS AND MATERIALS: This study included 10 patients with pancreatic cancer who underwent 6-port static intensity modulated radiation therapy with real-time tumor tracking in 15 fractions, except for 1 patient (5 fractions). The tumor and abdominal wall positions were acquired simultaneously during the overall treatment course. Then the tumor motion amplitude and reference positions were determined. RESULTS: The mean tumor amplitudes were 4.9, 6.5, and 13.4 mm in the left-right (LR), anterior-posterior (AP), and superior-inferior (SI) directions, respectively. The intrafractional variations of the reference tumor position were up to 5.4, 10.2, and 10.7 mm in the LR, AP, and SI directions, and those of the reference abdominal position were up to 10.5 mm. The reference tumor position drifted significantly in the AP and SI directions after 10 minutes, and that of abdominal wall motion drifted during the first 15 minutes (P<.05). The interfractional variation of the reference tumor position after setup correction, based on bony structures, was up to 8.9, 9.8, and 11.0 mm in the LR, AP, and SI directions, respectively. CONCLUSIONS: Appropriate respiratory motion management techniques should be applied for the accurate localization of pancreatic tumors.

Impact of sampling interval in training data acquisition on intrafractional predictive accuracy of indirect dynamic tumor-tracking radiotherapy.

PURPOSE: To explore the effect of sampling interval of training data acquisition on the intrafractional prediction error of surrogate signal-based dynamic tumor-tracking using a gimbal-mounted linac. MATERIALS AND METHODS: Twenty pairs of respiratory motions were acquired from 20 patients (ten lung, five liver, and five pancreatic cancer patients) who underwent dynamic tumor-tracking with the Vero4DRT. First, respiratory motions were acquired as training data for an initial construction of the prediction model before the irradiation. Next, additional respiratory motions were acquired for an update of the prediction model due to the change of the respiratory pattern during the irradiation. The time elapsed prior to the second acquisition of the respiratory motion was 12.6 ± 3.1 min. A four-axis moving phantom reproduced patients' three dimensional (3D) target motions and one dimensional surrogate motions. To predict the future internal target motion from the external surrogate motion, prediction models were constructed by minimizing residual prediction errors for training data acquired at 80 and 320 ms sampling intervals for 20 s, and at 500, 1,000, and 2,000 ms sampling intervals for 60 s using orthogonal kV x-ray imaging systems. The accuracies of prediction models trained with various sampling intervals were estimated based on training data with each sampling interval during the training process. The intrafractional prediction errors for various prediction models were then calculated on intrafractional monitoring images taken for 30 s at the constant sampling interval of a 500 ms fairly to evaluate the prediction accuracy for the same motion pattern. In addition, the first respiratory motion was used for the training and the second respiratory motion was used for the evaluation of the intrafractional prediction errors for the changed respiratory motion to evaluate the robustness of the prediction models. RESULTS: The training error of the prediction model was 1.7 ± 0.7 mm in 3D for all sampling intervals. The intrafractional prediction error for the same motion pattern was 1.9 ± 0.7 mm in 3D for an 80 ms sampling interval, which increased larger than 1 mm in 10.0% of prediction models trained at a 2,000 ms sampling interval with a significant difference (P < 0.01) and up to 2.5% for the other sampling intervals without a significant difference (P > 0.05). The intrafractional prediction error for the changed respiratory motion pattern increased to 5.1 ± 2.4 mm in 3D for an 80 ms sampling interval; however, there was not a significant difference in the robustness of the prediction model between the 80 ms sampling interval and other sampling intervals (P > 0.05). CONCLUSIONS: Although the training error of the prediction model was consistent for the all sampling intervals, the prediction model using the larger sampling interval of the 2,000 ms increased the intrafractional prediction error for the same motion pattern. The realistic accuracy of the prediction model was difficult to estimate using the larger sampling interval during the training process. It is recommended to construct the prediction model at sampling interval ≤ 1,000 ms and to reconstruct the model during treatment.

Development of a four-axis moving phantom for patient-specific QA of surrogate signal-based tracking IMRT.

PURPOSE: The purposes of this study were two-fold: first, to develop a four-axis moving phantom for patient-specific quality assurance (QA) in surrogate signal-based dynamic tumor-tracking intensity-modulated radiotherapy (DTT-IMRT), and second, to evaluate the accuracy of the moving phantom and perform patient-specific dosimetric QA of the surrogate signal-based DTT-IMRT. METHODS: The four-axis moving phantom comprised three orthogonal linear actuators for target motion and a fourth one for surrogate motion. The positional accuracy was verified using four laser displacement gauges under static conditions (±40 mm displacements along each axis) and moving conditions [eight regular sinusoidal and fourth-power-of-sinusoidal patterns with peak-to-peak motion ranges (H) of 10-80 mm and a breathing period (T) of 4 s, and three irregular respiratory patterns with H of 1.4-2.5 mm in the left-right, 7.7-11.6 mm in the superior-inferior, and 3.1-4.2 mm in the anterior-posterior directions for the target motion, and 4.8-14.5 mm in the anterior-posterior direction for the surrogate motion, and T of 3.9-4.9 s]. Furthermore, perpendicularity, defined as the vector angle between any two axes, was measured using an optical measurement system. The reproducibility of the uncertainties in DTT-IMRT was then evaluated. Respiratory motions from 20 patients acquired in advance were reproduced and compared three-dimensionally with the originals. Furthermore, patient-specific dosimetric QAs of DTT-IMRT were performed for ten pancreatic cancer patients. The doses delivered to Gafchromic films under tracking and moving conditions were compared with those delivered under static conditions without dose normalization. RESULTS: Positional errors of the moving phantom under static and moving conditions were within 0.05 mm. The perpendicularity of the moving phantom was within 0.2° of 90°. The differences in prediction errors between the original and reproduced respiratory motions were -0.1 ± 0.1 mm for the lateral direction, -0.1 ± 0.2 mm for the superior-inferior direction, and -0.1 ± 0.1 mm for the anterior-posterior direction. The dosimetric accuracy showed significant improvements, of 92.9% ± 4.0% with tracking versus 69.8% ± 7.4% without tracking, in the passing rates of γ with the criterion of 3%/1 mm (p < 0.001). Although the dosimetric accuracy of IMRT without tracking showed a significant negative correlation with the 3D motion range of the target (r = - 0.59, p < 0.05), there was no significant correlation for DTT-IMRT (r = 0.03, p = 0.464). CONCLUSIONS: The developed four-axis moving phantom had sufficient accuracy to reproduce patient respiratory motions, allowing patient-specific QA of the surrogate signal-based DTT-IMRT under realistic conditions. Although IMRT without tracking decreased the dosimetric accuracy as the target motion increased, the DTT-IMRT achieved high dosimetric accuracy.

Multivariate analysis for the estimation of target localization errors in fiducial marker-based radiotherapy.

PURPOSE: To assess the target localization error (TLE) in terms of the distance between the target and the localization point estimated from the surrogates (|TMD|), the average of respiratory motion for the surrogates and the target (|aRM|), and the number of fiducial markers used for estimating the target (n). METHODS: This study enrolled 17 lung cancer patients who subsequently underwent four fractions of real-time tumor tracking irradiation. Four or five fiducial markers were implanted around the lung tumor. The three-dimensional (3D) distance between the tumor and markers was at maximum 58.7 mm. One of the markers was used as the target (Pt), and those markers with a 3D |TMDn| ≤ 58.7 mm at end-exhalation were then selected. The estimated target position (Pe) was calculated from a localization point consisting of one to three markers except Pt. Respiratory motion for Pt and Pe was defined as the root mean square of each displacement, and |aRM| was calculated from the mean value. TLE was defined as the root mean square of each difference between Pt and Pe during the monitoring of each fraction. These procedures were performed repeatedly using the remaining markers. To provide the best guidance on the answer with n and |TMD|, fiducial markers with a 3D |aRM ≥ 10 mm were selected. Finally, a total of 205, 282, and 76 TLEs that fulfilled the 3D |TMD| and 3D |aRM| criteria were obtained for n = 1, 2, and 3, respectively. Multiple regression analysis (MRA) was used to evaluate TLE as a function of |TMD| and |aRM| in each n. RESULTS: |TMD| for n = 1 was larger than that for n = 3. Moreover, |aRM| was almost constant for all n, indicating a similar scale for the marker's motion near the lung tumor. MRA showed that |aRM| in the left-right direction was the major cause of TLE; however, the contribution made little difference to the 3D TLE because of the small amount of motion in the left-right direction. The TLE calculated from the MRA ((MRA)TLE) increased as |TMD| and |aRM| increased and adversely decreased with each increment of n. The median 3D (MRA)TLE was 2.0 mm (range, 0.6-4.3 mm) for n = 1, 1.8 mm (range, 0.4-4.0 mm) for n = 2, and 1.6 mm (range, 0.3-3.7 mm) for n = 3. Although statistical significance between n = 1 and n = 3 was observed in all directions, the absolute average difference and the standard deviation of the (MRA)TLE between n = 1 and n = 3 were 0.5 and 0.2 mm, respectively. CONCLUSIONS: A large |TMD| and |aRM| increased the differences in TLE between each n; however, the difference in 3D (MRA)TLEs was, at most, 0.6 mm. Thus, the authors conclude that it is acceptable to continue fiducial marker-based radiotherapy as long as |TMD| is maintained at ≤58.7 mm for a 3D |aRM| ≥ 10 mm.