Clinical applicability of setup margins in radiotherapy based on non-gaussian approach: A multiple-site comparison

Aim:In radiation therapy, accurate dose distribution in target volume requires accurate treatment setup. The set-up errors are unwanted and inherent in the treatment process. By achieving these errors, a set-up margin (SM) of clinical target volume (CTV) to planning target volume (PTV) can be determined. In the current study, systematic and random set-up errors that occurred during prostate cancer radiotherapy were measured by an electronic portal imaging device (EPID). The obtained values were used to propose the optimum CTV-to-PTV margin in prostate cancer radiotherapy.Materials and methods:A total of 21 patients with prostate cancer treated with external beam radiation therapy (EBRT) participated in this study. A total of 280 portal images were acquired during 12 months. Gross, population systematic (Σ) and random (σ) errors were obtained based on the portal images in Anterior–Posterior (AP), Medio-Lateral (ML) and Superior–Inferior (SI) directions. The SM of CTV to PTV were then calculated and compared by using the formulas presented by the International Commission on Radiation Units and Measurements (ICRU) 62, Stroom and Heijmen and Van Herk et al.Results:The findings showed that the population systematic errors during prostate cancer radiotherapy in AP, ML and SI directions were 1·40, 1·95 and 1·94 mm, respectively. The population random errors in AP, ML and SI directions were 2·09, 1·85 and 2·29 mm, respectively. The SM of CTV to PTV calculated in accordance with the formula of ICRU 62 in AP, ML and SI directions were 2·51, 2·68 and 3·00 mm, respectively. And according to Stroom and Heijmen, formula were 4·23, 5·19 and 5·48 mm, respectively. And Van Herk et al. formula were 4·96, 6·17 and 6·45 mm, respectively.Findings:The SM of CTV to PTV in all directions, based on the formulas of ICRU 62, Stroom and Heijmen and van Herk et al., were equal to 2·73, 4·98 and 5·86 mm, respectively; these values were obtained by averaging the margins in all directions.

BackgroundSet-up errors are an inherent part of radiation treatment process. Coverage of target volume is a direct function of set-up margins, which should be optimized to prevent inadvertent irradiation of adjacent normal tissues. The aim of this study was to evaluate three-dimensional (3D) set-up errors and propose optimum margins for target volume coverage in head and neck radiotherapy.MethodsThe dataset consisted of 93 pairs of orthogonal simulator and corresponding portal images on which 558 point positions were measured to calculate translational displacement in 25 patients undergoing conventional head and neck radiotherapy with antero-lateral wedge pair technique. Mean displacements, population systematic (Σ) and random (σ) errors and 3D vector of displacement was calculated. Set-up margins were calculated using published margin recipes.ResultsThe mean displacement in antero-posterior (AP), medio-lateral (ML) and supero-inferior (SI) direction was -0.25 mm (-6.50 to +7.70 mm), -0.48 mm (-5.50 to +7.80 mm) and +0.45 mm (-7.30 to +7.40 mm) respectively. Ninety three percent of the displacements were within 5 mm in all three cardinal directions. Population systematic (Σ) and random errors (σ) were 0.96, 0.98 and 1.20 mm and 1.94, 1.97 and 2.48 mm in AP, ML and SI direction respectively. The mean 3D vector of displacement was 3.84 cm. Using van Herk's formula, the clinical target volume to planning target volume margins were 3.76, 3.83 and 4.74 mm in AP, ML and SI direction respectively.ConclusionThe present study report compares well with published set-up error data relevant to head and neck radiotherapy practice. The set-up margins were <5 mm in all directions. Caution is warranted against adopting generic margin recipes as different margin generating recipes lead to a different probability of target volume coverage.

Various applications of head-tilting techniques in whole-brain radiotherapy (WBRT) have been introduced. However, a study on the setup uncertainties and margins in head-tilting techniques has not been reported. This study evaluated the setup uncertainties and determined the appropriate planning target volume (PTV) margins for patients treated in the head-tilted supine (ht-SP) and conventional supine position (c-SP) in WBRT. Thirty patients who received WBRT at our institution between October 2020 and May 2021 in the c-SP and ht-SP were investigated. The DUON head mask (60124, Orfit Industries, Wijnegem, Belgium) was used in the c-SP, and a thermoplastic U-Frame Mask (R420U, Klarity Medical & Equipment Co. Ltd., Lan Yu, China) was used in the ht-SP. Daily setup verification using planning computed tomography (CT) and cone-beam CT was corrected for translational (lateral, longitudinal, and vertical) and rotational (yaw) errors. In the c-SP, the means of systematic errors were -0.80, 0.79, and 0.37 mm and random errors were 0.27, 0.54, and 0.39 mm in the lateral, longitudinal, and vertical translational dimensions, respectively. Whereas, for the ht-SP, the means of systematic errors were -0.07, 0.73, and -0.63 mm, and random errors were 0.75, 1.39, 1.02 mm in the lateral, longitudinal, and vertical translational dimensions, respectively. The PTV margins were calculated using Stroom et al.’s [2Σ+0.7σ] and van Herk et al.’s recipe [2.5Σ+0.7σ]. Appropriate PTV margins with van Herk et al.’s recipe in WBRT were <2 mm and 1.5° in the c-SP and <3 mm and 2° in the ht-SP in the translational and rotational directions, respectively. Although the head tilt in the supine position requires more margin, it can be applied as a sufficiently stable and effective position in radiotherapy.

Objective To determine the planning target volume margins of head and neck cancers treated by image guided radiotherapy (IGRT).Methods 464 sets cone beam computed tomography (CBCT) images before setup correction and 126 sets CBCT images after correction were obtained from 51 head and neck cancer patients treated by IGRT in our department.The systematic and random errors were evaluated by either online or offline correction through registering the CBCT images to the planning CT.The data was divided into 3 groups according to the online correction times.Results The isocenter shift were 0.37 mm±2.37 mm, -0.43 mm±2.30 mm and 0.47 mm±2.65 mm in right-left (RL), anterior-posterior (AP) and superior-inferior (SI) directions respectively before correction, and it reduced to 0.08 mm±0.68 mm, -0.03 mm±0.74 mm and 0.03 mm±0.80 mm when evaluated by 126 sets corrected CBCT images.The planning target volume (PTV) margin from clinical target volume (CTV) before correction were:6.41 mm,6.15 mm and 7.10 mm based on two parameter model, and it reduced to 1.78 mm,1.80 mm and 1.97 mm after correction.The PTV margins were 3.8 mm,3.8 mm,4.0 mm;4.0 mm,4.0 mm,5.0 mm and 5.4 mm,5.2 mm,6.1 mm in RL, AP and SI respectively when online-correction times were more than 15 times, 11-15 times,5-10 times.Conclusions CBCT-based on online correction reduce the PTV margin for head and neck cancers treated by IGRT and ensure more precise dose delivery and less normal tissue complications. Key words: Intensity modulated radiotherapy; Image guided radiotherapy; Setup error; Treatment margin

Objective To investigate how much the patient setup accuracy for irradiation of head and neck cancer can be improved by online setup verification and offline setup verification using cone-beam computed tomography(CBCT), and the feasibility of image-guided adaptive correction procedure to reduce the PIN margin.Methods 16 patients of head-and-neck cancer treated with three-dimensional conformal radiotherapy (3D-CRT)or intensity modulated radiotherapy(IMRT)were investigated. The first online kV CBCT scan, rigid image registration, setup correction were performed before radiotherapy. The second kV CBCT scan were acquired immediately after treatment and analysis was performed as above. CBCT scans were acquired at two or three fractions weekly during the entire course of radiotherapy and CBCT online-guided correction data were recorded. The data was used to calculate the population-based CTV-PTV margins under the condition of non-correction, correction every fraction and compensation of the systematic setup error respectively. The number of initial images required to predict systematic setup error was evaluated with the permission of 0.5 mm residue error. Results Total of 320 sets of CBCT images were analyzed for 16 patients. Under the condition of non-correction, the margins required to account for total error are 5.7 mm,5.6 mm,and 7.3 mm in the left-right(X axis),cranio-eaudal(Y axis), and anterior-posterior (Z axis)directions respectively, when the tumor was corrected every fraction, the margins required to account for intrafraetion error are 1.7 mm,1.7 mm,and 2.3 mm in X, Y,and Z axis.To correct the systematic setup error,8 sets of CBCT images are adequate. After compensation for the effect of the systematic setup error, 2.7 mm,2.5 mm, and 3.6 mm PTV margins are necessary in X, Y, and Z axis respectively. Conclusions There exists some extent of setup error in head and neck 3D-CRT or IMRT.The on-line CBCT correction and the approach based on off-line adaptive correction both can be used to reduce the impact of setup error obviously, the required margins for the PTV was reduced accordingly. Key words: Head and neck cancer; Planning target volume; Adaptive radiotherapy; Image-guided radiotherapy ; Cone-beam CT

The aim of this study is to calculate setup margin based on six-dimensional (6D) corrected residual positional errors from kV cone beam computed tomography (CBCT) and from intrafraction projection kV imaging in coplanar and in noncoplanar couch positions in stereotactic radiotherapy. Six dimensional positional corrections were carried out before patient treatments, using a robotic couch and CBCT matching. A CBCT and stereoscopic ExacTrac image were acquired post-table position correction. Further, a series of intrafraction ExacTrac images were obtained for the variable couch position. Translational and rotational errors were identified as lateral (X), longitudinal (Y), vertical (Z); roll (Ɵ°), pitch (Φ°) and yaw (Ψ°). A total of 699 intrafraction image sets (361 coplanar and 338 noncoplanar) for 51 SRS/SRT patients were analysed. Rotational errors were corrected in terms of translational coordinates. Residual set-up margins were calculated from CBCT shifts. ExacTrac shifts give residual+intrafraction setup margins as a function of coplanar and noncoplanar couchpositions. The average residual positional error obtained from CBCT in X, Y, Z, Ɵ, Φ, Ψ were 0.1±0.4mm, 0.0±0.6mm,0.0±0.5mm, 0.2±0.8°, 0.1±0.6° and -0.1±0.7° respectively. For ExacTrac, the shits were -0.5±0.9mm, -0.0±1mm, -0.6±1.0mm, 0.4±0.9°, -0.2±0.6°, and -0.0±0.8°. CBCT calculated linear setup margins in X, Y, Z direction were 0.5, 1.2, and 1mm respectively. ExacTrac yielded coplanar and noncoplanar linear setup margins were 1.2, 1.3, 1.5, 1.4, 1.5, and 2.1mm respectively. CBCT-based gross residual set-up margin is equal to 1mm. ExacTrac calculated residual plus intrafraction setup margin falls within a 2mm range; attributed to intrafraction patient movement, table position inaccuracies, and poor image fusion in noncoplanar geometry. There could be variations in the required additional margin between centers and between machines, which require further studies.

Objective To study the more safe and accurate guidance scheme of cone beam computed tomography (CBCT) in nasopharyngeal carcinoma. Methods CBCT was regularly performed on 87 patients with nasopharyngeal carcinoma in Meizhou People's Hospital from November 2014 to August 2015. For each patient, 10 times CBCT scans were obtained pre-treatment. All the setup errors were obtained and analysed on the orientation X (left and right), Y (head and foot) and Z (vertical) axis. Results With the increase of the number of CBCT scans, there was no statistically significant difference among the mean setup errors of the 10 times scans in X (left and right) and Y (head and foot) directions (all P > 0.05). And there was no statistically significant difference among the mean setup errors of 6 times scans in Z (vertical) direction, but from the beginning of the 7th, the systematic error in Z direction was increasing, the system error of the 7th, 8th, 9th, 10th time was 0.140, 0.292, 0.461, and 0.640 mm. Moreover, the difference of the mean systematic errors among the first 7 times was statistically significant (H = 15.232, P = 0.019), and the differences of the mean systematic errors among the first 8, 9 and 10 times were statistically significant (all P < 0.05). Conclusions Non-consecutive scans of CBCT could reduce the systematic and random errors. The appropriate frequency of application of CBCT based on the change law of setup errors is an ideal CBCT guidance scheme for nasopharyngeal carcinoma. Key words: Nasopharyngeal neoplasms; Imaging guided radiation therapy; Cone beam computed tomography; Setup errors

Cone-beam CT in an offline image guidance strategy: Margin and efficiency gains

The evaluation of treatment-associated errors is important in the radiotherapy process, particularly those resulting related to patient setup. This research aimed to assess the interfractional setup errors and determine the Clinical Target Volume to Planning Target Volume (CTV to PTV) margin in patients undergoing 3-Dimensional Conformal Radiation Therapy (3DCRT) for head and neck cancer by means of electronic portal imaging device. In this analytical study, 300 portal images were acquired from 50 patients undergoing 3DCRT for head and neck cancer. Using the portal images of Lateral (LAT) and Antero-Posterior (AP) fields, population systematic (∑) and random (σ) errors were obtained in the lateral, longitudinal, and vertical directions. Finally, based on the International Commission on Radiation Units and Measurements (ICRU) Report 62's, Stroom's and Van Herk's methods, Planning target volume margins were determined. The translational shift ranges were 0-8.1 mm in the ML, 0-9 mm in the SI (AP), 0-8.8 mm in the SI (LAT), and 0-10 mm in the AP directions. The population systematic and random errors were respectively 3.230, 2.753, and 2.997 mm, and 1.476, 1.853, and 1.715 mm in X, Y, and Z directions. The calculated PTV margins using the ICRU-62, Stroom's, and Van Herk's formulae were ranging from 3.236-3.551, 6.605-7.493, and 7.932-9.108 mm, respectively. A PTV margin of 7.5-9.5 mm seems safe for ensuring adequate treatment volume coverage. In addition, the EPID is an effective equipment for verifying patient positioning and reducing treatment setup errors.

Evaluation of set-up errors in head and neck radiotherapy using electronic portal imaging

In this study, the egs_cbct code's ability to replicate an electronic portal imaging device (EPID) is explored. We have investigated head and neck (H&N) setup verification on an Elekta Precise linear accelerator. It is equipped with an electronic portal imaging device (EPID) that can capture a set of projection images over different gantry angles. Cone-beam computed tomography (CBCT) images were reconstructed from projection images of two different setup scenarios. Projections of an Anthropomorphic Rando head phantom were also simulated by using the egs_cbct Monte Carlo code for comparison with the measured projections.Afterwards, CBCT images were reconstructed from this data. Image quality was evaluated against a metric defined as the image acquisition interval (IAI). It determines the number of projection images to be used for CBCT image reconstruction. From this results it was established that phantom shifts could be determined within 2 mm and rotations within one degree accuracy using only 20 projection images (IAI = 10 degrees). Similar results were obtained with the simulated data. In this study it is demonstrated that a head and neck setup can be verified using substantially fewer projection images. Bony landmarks and air cavities could still be observed in the reconstructed Rando head phantom. The egs_cbct code can be used as a tool to investigate setup errors without tedious measurements with an EPID system.

Objective To compare set-up error and the positioning and error correction time between the infrared markers automatic positioning+ ExacTrac (A) and the manual positioning+ cone-beam computed tomography (CBCT) image-guided radiotherapy (IGRT)(B) in intensity-modulated radiotherapy (IMRT) for lung cancer. Methods A total of 20 patients with lung cancer were randomly divided into Group A and Group B. In Group A, after automatic positioning, a group of orthogonal X-rays images were taken using kV X-rays, which matched digitally reconstructed radiographs to obtain errors before correction. In group B, after manual positioning, images were taken using CBCT, which matched reference computed tomography images to obtain errors before correction. The positioning and error correction time was recorded in both groups. After error correction, errors after correction were obtained in each group using IGRT. Between-group comparison was made using the paired t test. Results The errors in lateral, longitudinal, vertical, and spinning vertical directions were significantly reduced after correction in both Group A and B (A: 1.8±1.3 vs. 0.4±0.1, P=0.000; 2.7±1.9 vs. 0.5±0.1, P=0.000; 2.8±1.7 vs. 0.4±0.1, P=0.000; 1.6±1.0 vs. 0.3±0.9, P=0.000; B: 2.6±1.9 vs. 0.5±0.5, P=0.000; 3.1±2.5 vs. 0.6±0.6, P=0.000; 2.1±1.8 vs. 0.5±0.5, P=0.000; 0.9±0.7 vs. 0.3±0.1, P=0.000). There were no significant differences in errors after correction between Group A and Group B (0.4±0.1 vs. 0.5±0.5, P=0.204; 0.5±0.1 vs. 0.6±0.6, P=0.257; 0.4±0.1 vs. 0.5±0.5, P=0.518; 0.3±0.9 vs. 0.3±0.1, P=0.755). However, the positioning and error correction time in Group A was significantly shorter than that in Group B (199.1±16.2 vs. 315.2±13.7, P=0.000). Conclusions The application of ExacTrac or CBCT IGRT can substantially reduce set-up errors and improve set-up accuracy in IMRT. In addition, the application of the ExacTrac system can substantially shorten the positioning and error correction time. Key words: Lung neoplasms/intensity-modulated radiotherapy; ExacTrac; CBCT; Set-up errors; Positioning and error correction time

Objective To evaluate the effect of setup errors upon the target area and the organs at risk (OAR) during radiotherapy for prostate cancer. Methods Twelve prostate cancer patients receiving treatment in the recent 1 year were randomly recruited in this study. The position of each patient was verified by using cone beam CT (CBCT) for 6-10 times during the treatment. In treatment planning system (TPS), the isocenter position was moved along the setup errors with averaging error value (Plan_A) and each CBCT value (Plan_F). The dose distribution was recalculated without changing the beam setting, weight factors and monitor units (MUs). The dose difference was statistically compared between the simulation and original plans (Plan_O). Results For clinical target volume (CTV) D95, there was a significant difference between Plan_A and Plan_O (P=0.008), whereas no significant difference was observed between Plan_F and Plan_O. There were significant differences between Plan_F and Plan_O, Plan_A and Plan_O (P=0.004, and 0.041) for the planned target volume (PTV) D95.For OAR, rectal V60, Dmax, left femoral V20, Dmax and right femoral Dmax significantly differed between Plan_F and Plan_O (P=0.026, 0.015, 0.041, 0.049, 0.003). However, only left femoral Dmax significantly differed between Plan_A and Plan_O (P=0.045). The movement in the superior-inferior (SI) direction was significantly correlated with the changes in the rectal V40, V50 and V60 and PTV D95(r=-0.785, -0.887, -0.833, 0.682). The movement in the anterior-posterior (AP) direction was significantly associated with the variations in the bladder V20, V30, V40, V50 and V60(r=-0.945, -0.823, -0.853, -0.818, -0.774). The evaluation indexes of all normal tissues in the re-plan could meet the clinical requirements. However, the volume of target prescription volume had different levels of deficit, and the deficit of Plan_F was greater than that of Plan_A. Conclusions The simulation results of averaging into the TPS underestimates the effect of daily setup errors on the dose distribution. The effect of setup errors on the dose distribution in target area is greater than that of normal tissues. Y-direction errors are more likely to cause the variations of the rectal and PTV dose, and the errors in the z-direction are inclined to cause the changes in the bladder dose. Key words: Prostate neoplasm/radiotherapy; Setup error; Dose distribution

Set-Up Errors, Organ Motion, Tumour Regression and its Implications on Internal Target Volume–Planning Target Volume During Cervical Cancer Radiotherapy: Results From a Prospective Study

Objective To study the real-time correction of setup error in intensity modulated radia-tion therapy (IMRT) for nasopharyngeal carcinoma (NPC) using an electronic portal imaging device (EP-ID), and to reduce systematic and random setup errors. Methods Thirty NPC patients treated by IMRT were enrolled into this study. During irradiation, three metal markers which embedded in the occlusal splint were used to monitor the setup error. Anterior and lateral isocentric electronic portal images were acquired before radiation and compared to digitally reconstructed radiographs. If the setup error in x-axis (right-left direction ) , y-axis ( superior-inferior direction) or z-axis ( anterior-posterior direction) exceeded 2 mm, real-time correction was performed before radiation and then the setup error after the correction were recorded. Results Before correction, 88.3% of all translational setup errors were less than 3 mm, and 99.1% less than 5 mm. Real-time correction was given to 16 patients who had translational setup errors more than 2 mm in one or two directions. The standard deviation of overall systematic and random setup errors after correction were obviously lower than those before correction. The M PTV value before correction was about 3 mm in the three directions and was only about 1.5 mm after correction. Conclusions In IMRT for NPC, Real-time correction of setup error using EPID and oeclusal splint method can improve the setup accuracy by reducing the systematic and random setup errors, and reduce the margin from CTV to PTV. Key words: Nasopharyngeal neoplasms/intensity modulation radiotherapy; Electronic portal ima-ging device; Setup error; Correction method