Mean Tumor Motion Research Articles

Evaluation of Lung Tumor Target Volume in a Large Sample: Target and Clinical Factors Influencing the Volume Derived From Four-Dimensional CT and Cone Beam CT.

Background and PurposeThis study aimed to systematically evaluate the influence of target-related and clinical factors on volume differences and the similarity of targets derived from four-dimensional computed tomography (4DCT) and cone beam computed tomography (CBCT) images in lung stereotactic body radiation therapy (SBRT).Materials and Methods4DCT and CBCT image data of 210 tumors from 195 patients were analyzed. The internal gross target volume (IGTV) derived from the maximum intensity projection (MIP) of 4DCT (IGTV-MIP) and the IGTV from CBCT (IGTV-CBCT) were compared with the reference IGTV from 10 phases of 4DCT (IGTV-10). The target size, tumor motion, and the similarity between IGTVs were measured. The influence of target-related and clinical factors on the adequacy of IGTVs derived from 4DCT MIP and CBCT images was evaluated.ResultsThe mean tumor motion amplitude in the 3D direction was 6.5 ± 5 mm. The mean size ratio of IGTV-CBCT and IGTV-MIP compared to IGTV-10 in all patients was 0.71 ± 0.21 and 0.8 ± 0.14, respectively. Female sex, greater BSA, and larger target size were protective factors, while the Karnofsky Performance Status, body mass index, and motion were risk factors for the similarity between IGTV-MIP and IGTV-10. Older age and larger target size were protective factors, while adhesion to the heart, coexistence with cardiopathy, and tumor motion were risk factors for the similarity between IGTV-CBCT and IGTV-10.ConclusionClinical factors should be considered when using MIP images for defining ITV, and when using CBCT images for verifying treatment targets.

Lung Cancer Radiotherapy: Can Breathing Movement Evaluation be Improved By More Than One 4D-CT?

A recent national survey showed that a significant number of radiation oncologists resorted to more than one 4D-CT scans before lung cancer treatment planning. To our best knowledge, only two studies investigated whether only one 4D-CT was sufficient to evaluate breathing-induced motion of pulmonary tumors. However, the results were limited by the number of patients (10 to 26), and the old-generation scan machines. The present study was carried out to update the available data. The aim of the study was to assess the benefit of processing more than one 4D-CT in lung cancer patients as well as the immediate impact on patient’s quality of life. Data about all consecutive patients undergoing a curative radiotherapy for lung tumor (primary or metastases) were prospectively collected between April and July 2017. Patients had several 4D-CTs within a maximum of seven days but not on the same day. The ITV was contoured on each 4D-CT. The center of mass (used as a surrogate of the tumor position) was defined as the position of the barycenter of the tumor and was collected on each phase along with its standard deviation. The peak to peak tumor motion (distance between extreme tumor positions within one breathing cycle) and the three-dimensional tumor motion (left-right, supero-inferior and antero-posterior direction) were assessed. Patient’s self-reported quality of life was collected. 24 patients had two 4D-CT and were included. Mean age was 63 (range: 18-83). Contrast agent infusion was performed in 5 patients (20.8%). Abdominal compression was applied to 10 patients (41.7%) The mean volume of ITV was 125 cm3 (SD± 71,9 cm3). Between the repeated 4D-CTs, the ITV volume did not significantly vary (mean ITV variation: 8% i.e. 9 cm3, p=0.06). A variation of the ITV≥10% was observed in 9 patients (37.5%). The maximum variation of ITV volume between repeated 4D-CTs was 24.6%. The maximal mean peak to peak tumor motion in the prominent direction (i.e. possibly combining motions in the three different directions) was 1,79 ± 1,09 cm. Between 4D-CT, a relevant variation (≥2mm) was observed only in three patients. No variation reached 3mm, whatever the considered direction. The position of the center of mass did not significantly vary between repeated 4D-CTs (p=0.06). The mean three-dimensional tumor motion was 2,36 ± 1,33 cm (range : -3,04 cm to +1,92 cm). The mean tumor motion was higher at the first 4D-CT than at the second (p=0.035). Between repeated 4D-CTs, 4 patients (16%) had a mean tumor motion>5mm, with a 9mm motion in 2 patients (8%). Repeated 4D-CTs had no impact on patient’s quality of life. The repetition of 4D-CT did not highlight variations in tumor movement for most patients. However in 16% of patients, the second 4D-CT revealed an extra tumor motion that exceeded the standard additional margins used in SBRT. Although a second 4D-CT does not seem useful in normo-fractionnated radiotherapy given the usual margins, it seems essential for an accurate definition of ITV in SBRT.

Individually optimized contrast-enhanced 4D-CT for radiotherapy simulation in pancreatic ductal adenocarcinoma.

To develop an individually optimized contrast-enhanced (CE) 4D-computed tomography (CT) for radiotherapy simulation in pancreatic ductal adenocarcinomas (PDA). Ten PDA patients were enrolled. Each underwent three CT scans: a 4D-CT immediately following a CE 3D-CT and an individually optimized CE 4D-CT using test injection. Three physicians contoured the tumor and pancreatic tissues. Image quality scores, tumor volume, motion, tumor-to-pancreas contrast, and contrast-to-noise ratio (CNR) were compared in the three CTs. Interobserver variations were also evaluated in contouring the tumor using simultaneous truth and performance level estimation. Average image quality scores for CE 3D-CT and CE 4D-CT were comparable (4.0 and 3.8, respectively; P = 0.082), and both were significantly better than that for 4D-CT (2.6, P < 0.001). Tumor-to-pancreas contrast results were comparable in CE 3D-CT and CE 4D-CT (15.5 and 16.7 Hounsfield units (HU), respectively; P = 0.21), and the latter was significantly higher than in 4D-CT (9.2 HU, P = 0.001). Image noise in CE 3D-CT (12.5 HU) was significantly lower than in CE 4D-CT (22.1 HU, P = 0.013) and 4D-CT (19.4 HU, P = 0.009). CNRs were comparable in CE 3D-CT and CE 4D-CT (1.4 and 0.8, respectively; P = 0.42), and both were significantly better in 4D-CT (0.6, P = 0.008 and 0.014). Mean tumor volumes were significantly smaller in CE 3D-CT (29.8 cm3, P = 0.03) and CE 4D-CT (22.8 cm3, P = 0.01) than in 4D-CT (42.0 cm3). Mean tumor motion was comparable in 4D-CT and CE 4D-CT (7.2 and 6.2 mm, P = 0.17). Interobserver variations were comparable in CE 3D-CT and CE 4D-CT (Jaccard index 66.0% and 61.9%, respectively) and were worse for 4D-CT (55.6%) than CE 3D-CT. CE 4D-CT demonstrated characteristics comparable to CE 3D-CT, with high potential for simultaneously delineating the tumor and quantifying tumor motion with a single scan.

TH‐EF‐BRA‐04: Individually Optimized Contrast‐Enhanced 4D‐CT for Radiotherapy Simulation in Pancreatic Ductal Adenocarcinoma

Purpose:To develop an individually optimized contrast‐enhanced (CE) 4D‐CT for radiotherapy simulation in pancreatic ductal adenocarcinomas (PDA).Methods:Ten PDA patients were enrolled. Each underwent 3 CT scans: a 4D‐CT immediately following a CE 3D‐CT and an individually optimized CE 4D‐CT using test injection. Three physicians contoured the tumor and pancreatic tissues. We compared image quality scores, tumor volume, motion, tumor‐to‐pancreas contrast, and contrast‐to‐noise ratio (CNR) in the 3 CTs. We also evaluated interobserver variations in contouring the tumor using simultaneous truth and performance level estimation (STAPLE).Results:Average image quality scores for CE 3DCT and CE 4D‐CT were comparable (4.0 and 3.8, respectively; P=0.47), and both were significantly better than that for 4D‐CT (2.6, P&lt;0.001). Tumor‐to‐pancreas contrast results were comparable in CE 3D‐CT and CE 4D‐CT (15.5 and 16.7 HU, respectively; P=0.71), and the latter was significantly higher than in 4D‐CT (9.2 HU, P=0.03). Image noise in CE 3D‐CT (12.5 HU) was significantly lower than in CE 4D‐CT (22.1 HU, P&lt;0.001) and 4D‐CT (19.4 HU, P=0.005). CNRs were comparable in CE 3D‐CT and CE 4DCT (1.4 and 0.8, respectively; P=0.23), and the former was significantly better than in 4D‐CT (0.6, P = 0.04). Mean tumor volumes were smaller in CE 3D‐CT (29.8 cm3) and CE 4D‐CT (22.8 cm3) than in 4D‐CT (42.0 cm3), although these differences were not statistically significant. Mean tumor motion was comparable in 4D‐CT and CE 4D‐CT (7.2 and 6.2 mm, P=0.23). Interobserver variations were comparable in CE 3D‐CT and CE 4D‐CT (Jaccard index 66.0% and 61.9%, respectively) and were worse for 4D‐CT (55.6%) than CE 3D‐CT.Conclusion:CE 4D‐CT demonstrated characteristics comparable to CE 3D‐CT, with high potential for simultaneously delineating the tumor and quantifying tumor motion with a single scan.Supported in part by Philips Healthcare.

A single reference measurement can predict liver tumor motion during respiration

AimTo evaluate liver tumor motion and how well reference measurement predicts motion during treatment. Material and methodsThis retrospective study included 20 patients with colorectal cancer that had metastasized to the liver who were treated with stereotactic ablative radiotherapy. An online respiratory tumor tracking system was used. Tumor motion amplitudes in the superior-inferior (SI), latero-lateral (LL), and anterior-posterior (AP) directions were collected to generate patient-specific margins. Reference margins were generated as the mean motion and 95th percentile of motion from measurements recorded for different lengths of time (1, 3, and 5min). We analyzed the predictability of tumor motion in each axis, based on the reference measurement and intra-/interfraction motions. ResultsAbout 96,000 amplitudes were analyzed. The mean tumor motions were 9.9±4.2mm, 2.6±0.8mm, and 4.5±1.8mm in the SI, LL, and AP directions, respectively. The intrafraction variations were 3.5±1.8mm, 0.63±0.35mm, and 1.4±0.65mm for the SI, LL, and AP directions, respectively. The interfraction motion variations were 1.32±0.79mm, 0.31±0.23mm, and 0.68±0.62mm for the SI, LL, and AP directions, respectively. The Pearson's correlation coefficients for margins based on the reference measurement (mean motion or 95th percentile) and margins covering 95% of the motion during the whole treatment were 0.8–0.91, 0.57–0.7, and 0.77–0.82 in the SI, LL, and AP directions, respectively. ConclusionLiver tumor motion in the SI direction can be adequately represented by the mean tumor motion amplitude generated from a single 1min reference measurement. Longer reference measurements did not improve results for patients who were well-educated about the importance of regular breathing. Although the study was based on tumor tracking data, the results are useful for ITV delineation when tumor tracking is not available.

SU‐E‐J‐182: Reproducibility of Tumor Motion Probability Distribution Function in Stereotactic Body Radiation Therapy of Lung Using Real‐Time Tumor‐Tracking Radiotherapy System

Purpose:We aim to achieve new four‐dimensional radiotherapy (4DRT) using the next generation real‐time tumor‐tracking (RTRT) system and flattening‐filter‐free techniques. To achieve new 4DRT, it is necessary to understand the respiratory motion of tumor. The purposes of this study were: 1.To develop the respiratory motion analysis tool using log files. 2.To evaluate the reproducibility of tumor motion probability distribution function (PDF) during stereotactic body RT (SBRT) of lung tumor.Methods:Seven patients having fiducial markers closely implanted to the lung tumor were enrolled in this study. The positions of fiducial markers were measured using the RTRT system (Mitsubishi Electronics Co., JP) and recorded as two types of log files during the course of SBRT. For each patients, tumor motion range and tumor motion PDFs in left‐right (LR), anterior‐posterior (AP) and superior‐inferior (SI) directions were calculated using log files of all beams per fraction (PDFn). Fractional PDF reproducibility (Rn) was calculated as Kullback‐Leibler (KL) divergence between PDF1 and PDFn of tumor motion. The mean of Rn (Rm) was calculated for each patient and correlated to the patient's mean tumor motion range (Am). The change of Rm during the course of SBRT was also evluated. These analyses were performed using in‐house developed software.Results:The Rm were 0.19 (0.07–0.30), 0.14 (0.07–0.32) and 0.16 (0.09–0.28) in LR, AP and SI directions, respectively. The Am were 5.11 mm (2.58–9.99 mm), 7.81 mm (2.87–15.57 mm) and 11.26 mm (3.80–21.27 mm) in LR, AP and SI directions, respectively. The PDF reproducibility decreased as the tumor motion range increased in AP and SI direction. That decreased slightly through the course of RT in SI direction.Conclusion:We developed the respiratory motion analysis tool for 4DRT using log files and quantified the range and reproducibility of respiratory motion for lung tumors.

Assessment of tumor motion reproducibility with audio‐visual coaching through successive 4D CT sessions

This study aimed to compare combined audio‐visual coaching with audio coaching alone and assess their respective impact on the reproducibility of external breathing motion and, one step further, on the internal lung tumor motion itself, through successive sessions. Thirteen patients with NSCLC were enrolled in this study. The tumor motion was assessed by three to four successive 4D CT sessions, while the breathing signal was measured from magnetic sensors positioned on the epigastric region. For all sessions, the breathing was regularized with either audio coaching alone (AC, n=5) or combined with a real‐time visual feedback (A/VC, n=8) when tolerated by the patients. Peak‐to‐peak amplitude, period and signal shape of both breathing and tumor motions were first measured. Then, the correlation between the respiratory signal and internal tumor motion over time was evaluated, as well as the residual tumor motion for a gated strategy. Although breathing and tumor motions were comparable between AC and AV/C groups, A/VC approach achieved better reproducibility through sessions than AC alone (mean tumor motion of 7.2 mm±1 vs. 8.6 mm±1.8 mm, and mean breathing motion of 14.9 mm±1.2 mm vs. 13.3 mm±3.7 mm, respectively). High internal/external correlation reproducibility was achieved in the superior‐inferior tumor motion direction for all patients. For the anterior‐posterior tumor motion direction, better correlation reproducibility has been observed when visual feedback has been used. For a displacement‐based gating approach, A/VC might also be recommended, since it led to smaller residual tumor motion within clinically relevant duty cycles. This study suggests that combining real‐time visual feedback with audio coaching might improve the reproducibility of key characteristics of the breathing pattern, and might thus be considered in the implementation of lung tumor radiotherapy.PACS number: 87

Reproducibility of Tumor Motion Probability Distribution Function in Stereotactic Body Radiation Therapy of Lung Cancer

To evaluate the reproducibility of tumor motion probability distribution function (PDF) in stereotactic body radiation therapy (SBRT) of lung cancer using cine megavoltage (MV) images. Cine MV images of 20 patients acquired during three-dimensional conformal (6-11 beams) SBRT treatments were retrospectively analyzed to extract tumor motion trajectories. For each patient, tumor motion PDFs were generated per fraction (PDF(n)) using three selected "usable" beams. Patients without at least three usable beams were excluded from the study. Fractional PDF reproducibility (R(n)) was calculated as the Dice similarity coefficient between PDF(n) to a "ground-truth" PDF (PDF(g)), which was generated using the selected beams of all fractions. The mean of R(n), labeled as R(m), was calculated for each patient and correlated to the patient's mean tumor motion rang (A(m)). Change of R(m) during the course of SBRT treatments was also evaluated. Intra- and intersubject coefficient of variation (CV) of R(m) and A(m) were determined. Thirteen patients had at least three usable beams and were analyzed. The mean of R(m) was 0.87 (range, 0.84-0.95). The mean of A(m) was 3.18 mm (range, 0.46-7.80 mm). R(m) was found to decrease as A(m) increases following an equation of R(m) = 0.17e(-0.9Am) + 0.84. R(m) also decreased slightly throughout the course of treatments. Intersubject CV of R(m) (0.05) was comparable to intrasubject CV of R(m) (range, 0.02-0.09); intersubject CV of A(m) (0.73) was significantly greater than intrasubject CV of A(m) (range, 0.09-0.24). Tumor motion PDF can be determined using cine MV images acquired during the treatments. The reproducibility of lung tumor motion PDF decreased exponentially as the tumor motion range increased and decreased slightly throughout the course of the treatments.

MO-D-BRB-03: Investigation of the Reproducibility of Probability Distribution function (PDF) of Tumor Motion in Lung Stereotactic Body Radiation Therapy (SBRT)

Purpose: To investigate the reproducibility of probability distribution function (PDF) of lungtumor motion using cine‐MV images from lungSBRTtreatments. Findings of the study will provide valuable information for probability‐based treatment planning. Methods: Ten lungcancer patients who underwent SBRTtreatment were included in this study. All treatment plans were created using 3D‐conformal technique with 8 to 11 beams and wedges. Cine‐MV images were acquired during treatment for each beam at a rate of 1 frame/sec. Tumor motion tracking was achieved using an cross‐correlation algorithm. Tumor motion trajectories were extracted for all beams in all fractions of all patients. Inaccurate tracking results (based on visual inspection) were removed from further study. Only 3 beams with the best tracking results from each fraction were used to calculate the tumor motion PDF, which is defined as the probability of finding the tumor at different positions. For each patient the tumor motion PDF was generated for each fraction (PDFn) using the 3 selected beams and a mean PDF (PDFm) was generated as the mean of all fractional PDFs. Inter‐fractional PDF reproducibility (Rn) was calculated by comparing PDFn to PDFm. Mean tumor motion range (Dm) was determined for each patient and correlated to the mean PDF reproducibility (Rm). Results: Inter‐fractional PDF reproducibility of lungtumor motion ranged from 0.750 to 0.986 among all patients. Mean PDF reproducibility of the patient (Rm) ranged from 0.840 to 0.954, with an average of 0.89± 0.05. Mean PDF reproducibility decreased exponentially as a function of the mean tumor motion range: Rm=0.15exp(−0.45Dm)+0.85. Conclusions: Tumor motion PDF for lungSBRT patients can be determined using cine‐MV images. PDF reproducibility varied between patients and decreased exponentially as tumor motion range increased.

Comparison of Liver Tumor Motion With and Without Abdominal Compression Using Cine-Magnetic Resonance Imaging

Abdominal compression (AC) can be used to reduce respiratory liver motion in patients undergoing liver stereotactic body radiotherapy. The purpose of the present study was to measure the changes in three-dimensional liver tumor motion with and without compression using cine-magnetic resonance imaging. A total of 60 patients treated as a part of an institutional research ethics board-approved liver stereotactic body radiotherapy protocol underwent cine T2-weighted magnetic resonance imaging through the tumor centroid in the coronal and sagittal planes. A total of 240 cine-magnetic resonance imaging sequences acquired at one to three images each second for 30-60 s were evaluated using an in-house-developed template matching tool (based on the coefficient correlation) to measure the magnitude of the tumor motion. The average tumor edge displacements were used to determine the magnitude of changes in the caudal-cranial (CC) and anteroposterior (AP) directions, with and without AC. The mean tumor motion without AC of 11.7 mm (range, 4.8-23.3) in the CC direction was reduced to 9.4 mm (range, 1.6-23.4) with AC. The tumor motion was reduced in both directions (CC and AP) in 52% of the patients and in a single direction (CC or AP) in 90% of the patients. The mean decrease in tumor motion with AC was 2.3 and 0.6 mm in the CC and AP direction, respectively. Increased motion occurred in one or more directions in 28% of patients. Clinically significant (>3 mm) decreases were observed in 40% and increases in <2% of patients in the CC direction. AC can significantly reduce three-dimensional liver tumor motion in most patients, although the magnitude of the reduction was smaller than previously reported.

Determination of Respiratory Motion for Distal Esophagus Cancer Using Four-Dimensional Computed Tomography

To investigate the motion characteristics of distal esophagus cancer primary tumors using four-dimensional computed tomography (4D CT). Thirty-one consecutive patients treated for esophagus cancer who received respiratory-gated 4D CT imaging for treatment planning were selected. Deformable image registration was used to map the full expiratory motion gross tumor volume (GTV) to the full-inspiratory CT image, allowing quantitative assessment of each voxel's displacement. These displacements were correlated with patient tumor and respiratory characteristics. The mean (SE) tidal volume was 608 (73) mL. The mean GTV volume was 64.3 (10.7) mL on expiration and 64.1 (10.7) mL on inspiration (no significant difference). The mean tumor motion in the x-direction was 0.13 (0.006) cm (average of absolute values), in the y-direction 0.23 (0.01) cm (anteriorly), and in the z-direction 0.71 (0.02) cm (inferiorly). Tumor motion correlated with tidal volume. Comparison of tumor motion above vs. below the diaphragm was significant for the average net displacement (p = 0.014), motion below the diaphragm was greater than above. From the cumulative distribution 95% of the tumors moved less than 0.80 cm radially and 1.75 cm inferiorly. Primary esophagus tumor motion was evaluated with 4D CT. According to the results of this study, when 4D CT is not available, a radial margin of 0.8 cm and axial margin of +/-1.8 cm would provide tumor motion coverage for 95% of the cases in our study population.

MO‐E‐M100F‐06: Intra‐Fraction and Inter‐Fraction Real‐Time Tumor Motion Prediction Using Multiple External Surrogates

Purpose: To determine the feasibility of predicting real‐time tumor positions using multiple external surrogates and Partial‐Least‐Squares (PLS) regression. Methods: Nine patients with lung tumors underwent extracranial stereotactic radiosurgery comprising 3 fractions with the Cyberknife Synchrony™ system. Three LED markers were placed on the patient's abdomen and in close contact with the skin. Synchronous LED marker and tumor marker coordinates were measured periodically using an LED camera and stereoscopic x‐ray images, respectively. PLS performs regression on a small number of latent variables (LVs), which represent the underlying factors responsible for the variation in the output response. They are linear combinations of the original independent variables. The number of LVs in the PLS model was determined by performing a cross‐validation using a training data set and minimizing the error. The LV coefficients were then extracted from the cross‐correlation of input and output variables. Tumor position prediction errors were evaluated for the following scenarios: (1) tumor/external surrogate relationship for a given fraction, (2) predictive model developed in one fraction and applied to other fractions. Prediction errors were compared with standard multiple linear regression (MLR). Results: The mean tumor motion displacement was 7.3 mm for the patient data investigated. The average error for intra‐fraction tumor position prediction based on external markers was 1.47±0.90 mm for PLS and 3.07±1.67 mm for MLR when data from a single fraction was used. When the predictive model from one fraction was applied to the remaining two fractions, the average real‐time inter‐fraction error was 1.48±0.57 mm for PLS and 6.69±3.58 mm for MLR. Conclusion: PLS can predict the tumor position using external surrogates with errors of &lt; 2mm and with superior accuracy compared with MLR. Intra‐ and inter‐fraction prediction errors were statistically similar.

SU‐FF‐J‐05: A Four‐Dimensional Planning and Monte‐Carlo Dose Calculation Framework for Real‐Time Tumor Motion Compensation

Purpose: To perform 4D dose calculations using a feedback‐controlled treatment couch in 15 lung and abdominal patients Methods: Fifteen patients undergoing 4D CT were considered in this work. The GTV was delineated on ten 3D CT data sets by independent experts, with a planning margin added corresponding to the 2σ deviation from the mean center‐of‐mass. Tumor trajectories were derived from 4D CT data and fitted to a Fourier series expansion. Intra‐ and inter‐fraction statistical variations in amplitude and period were applied by considering literature estimates of the standard deviations. The couch feedback control system was simulated using second‐order couch dynamics and a first‐order controller. The residual tumor trajectory was calculated by inputting the tumor trajectory to the control system. A 7‐beam IMRT plan was generated on the end‐exhale CT with a prescription dose of 66 Gy. The resulting 4D dose distribution was calculated by sampling the isocenter position along the continuous tumor trajectory before and after motion compensation using a previously published Monte Carlo algorithm. Results: The mean tumor motion amplitude was 11.4±3.4 (SD) mm. After compensation the amplitude was 0.42±0.23 mm. Degradation of the tumor dose up to 35% was observed. After compensation, an average of 18.8 ± 4.7% improvement in the 100% dose coverage was seen for end inhale, and 13.4 ± 4.7% for the 90% coverage. For the combined 4D dose, GTV dose coverage was 94.7±4.7% (for 100% coverage) after compensation, but degraded to 87.3±4.5% without compensation. Conclusion: We have developed a framework for performing 4D dose calculations using real‐time tumor trajectories. For IMRT plans, the average improvement in the dose coverage to the PTV for mobile tumors with a feedback‐controlled couch was X% Conflict of Interest: Supported by 3DLine Medical Systems.