: Comparing incidental dose distributions (i.e. images) of patients with different outcomes is a straightforward way to explore dose-response hypotheses in radiotherapy. In this paper, we introduced ...a permutation test that compares images, such as dose distributions from radiotherapy, while tackling the multiple comparisons problem. A test statistic Tmax was proposed that summarizes the differences between the images into a single value and a permutation procedure was employed to compute the adjusted p-value. We demonstrated the method in two retrospective studies: a prostate study that relates 3D dose distributions to failure, and an esophagus study that relates 2D surface dose distributions of the esophagus to acute esophagus toxicity. As a result, we were able to identify suspicious regions that are significantly associated with failure (prostate study) or toxicity (esophagus study). Permutation testing allows direct comparison of images from different patient categories and is a useful tool for data mining in radiotherapy.
To quantify the localization accuracy and intrafraction stability of lung cancer patients treated with frameless, four-dimensional (4D) cone beam computed tomography (CBCT)-guided stereotactic body ...radiotherapy (SBRT) and to calculate and validate planning target volume (PTV) margins to account for the residual geometric uncertainties.
Sixty-five patients with small peripheral lung tumors were treated with SBRT without a body frame to 54 Gy in three fractions. For each fraction, three 4D-CBCT scans were acquired: before treatment to measure and correct the time-weighted mean tumor position, after correction to validate the correction applied, and after treatment to estimate the intrafraction stability. Patient-specific PTV margins were computed and subsequently validated using Monte Carlo error simulations.
Systematic tumor localization inaccuracies (1 SD) were 0.8, 0.8, and 0.9 mm for the left-right, craniocaudal, and anteroposterior direction, respectively. Random localization inaccuracies were 1.1, 1.1, and 1.4 mm. Baseline variations were 1.8, 2.9, and 3.0 mm (systematic) and 1.1, 1.5, and 2.0 mm (random), indicating the importance of image guidance. Intrafraction stability of the target was 1.2, 1.2, and 1.8 mm (systematic) and 1.3, 1.5, and 1.8 mm (random). Monte Carlo error simulations showed that patient-specific PTV margins (5.8-10.5 mm) were adequate for 94% of the evaluated cases (2-28 mm peak-to-peak breathing amplitude).
Frameless SBRT can be safely administered using 4D-CBCT guidance. Even with considerable breathing motion, the PTV margins can safely be kept small, allowing patients with larger tumors to benefit from the advantages of SBRT. In case bony anatomy would be used as a surrogate for tumor position, considerably larger PTV margins would be required.
Image-guided intensity modulated radiation therapy (IG-IMRT) allows significant dose reductions to organs at risk in prostate cancer patients. However, clinical data identifying the benefits of ...IG-IMRT in daily practice are scarce. The purpose of this study was to compare dose distributions to organs at risk and acute gastrointestinal (GI) and genitourinary (GU) toxicity levels of patients treated to 78 Gy with either IG-IMRT or 3D-CRT.
Patients treated with 3D-CRT (n=215) and IG-IMRT (n=260) receiving 78 Gy in 39 fractions within 2 randomized trials were selected. Dose surface histograms of anorectum, anal canal, and bladder were calculated. Identical toxicity questionnaires were distributed at baseline, prior to fraction 20 and 30 and at 90 days after treatment. Radiation Therapy Oncology Group (RTOG) grade ≥1, ≥2, and ≥3 endpoints were derived directly from questionnaires. Univariate and multivariate binary logistic regression analyses were applied.
The median volumes receiving 5 to 75 Gy were significantly lower (all P<.001) with IG-IMRT for anorectum, anal canal, and bladder. The mean dose to the anorectum was 34.4 Gy versus 47.3 Gy (P<.001), 23.6 Gy versus 44.6 Gy for the anal canal (P<.001), and 33.1 Gy versus 43.2 Gy for the bladder (P<.001). Significantly lower grade ≥2 toxicity was observed for proctitis, stool frequency ≥6/day, and urinary frequency ≥12/day. IG-IMRT resulted in significantly lower overall RTOG grade ≥2 GI toxicity (29% vs 49%, respectively, P=.002) and overall GU grade ≥2 toxicity (38% vs 48%, respectively, P=.009).
A clinically meaningful reduction in dose to organs at risk and acute toxicity levels was observed in IG-IMRT patients, as a result of improved technique and tighter margins. Therefore reduced late toxicity levels can be expected as well; additional research is needed to quantify such reductions.
To quantify the interfractional variability in lung tumor trajectory and mean position during the course of radiation therapy.
Repeat four-dimensional (4D) cone-beam computed tomography (CBCT) scans ...(median, nine scans/patient) routinely acquired during the course of treatment were analyzed for 56 patients with lung cancer. Tumor motion was assessed by using local rigid registration of a region of interest in the 3D planning CT to each phase in the 4D CBCT. Displacements of the mean tumor position relative to the planned position (baseline variations) were obtained by using time-weighted averaging of the motion curve.
The tumor trajectory shape was found to be stable interfractionally, with mean variability not exceeding 1 mm (1 SD) in each direction for the inhale and exhale phases. Interfractional baseline variations, however, were large, with 1.6- (left-right), 3.9- (cranial-caudal), and 2.8-mm (anterior-posterior) systematic variations (1 SD) and 1.2- (left-right), 2.4- (cranial-caudal) and 2.2-mm (anterior-posterior) random variations. Eliminating baseline variations by using soft-tissue guidance decreases planning target volume margins by approximately 50% compared with bony anatomy-driven protocols for conventional fractionation schemes.
Systematic and random baseline variations constitute a substantial portion of the geometric variability present in the treatment of patients with lung cancer and require generous safety margins when relying on accurate setup/immobilization or bony anatomy-driven correction strategies. The 4D-CBCT has the ability to accurately monitor tumor trajectory shape and baseline variations and drive image-guided correction strategies that allows safe margin reduction.
To quantify local geometrical uncertainties in anatomical sub-regions during radiotherapy for head-and-neck cancer patients.
Local setup accuracy was analyzed for 38 patients, who had received ...intensity-modulated radiotherapy and were regularly scanned during treatment with cone beam computed tomography (CBCT) for offline patient setup correction. In addition to the clinically used large region of interest (ROI), we defined eight ROIs in the planning CT that contained rigid bony structures: the mandible, larynx, jugular notch, occiput bone, vertebrae C1-C3, C3-C5, and C5-C7, and the vertebrae caudal of C7. By local rigid registration to successive CBCT scans, the local setup accuracy of each ROI was determined and compared with the overall setup error assessed with the large ROI. Deformations were distinguished from rigid body movements by expressing movement relative to a reference ROI (vertebrae C1-C3).
The offline patient setup correction protocol using the large ROI resulted in residual systematic errors (1 SD) within 1.2 mm and random errors within 1.5 mm for each direction. Local setup errors were larger, ranging from 1.1 to 3.4 mm (systematic) and 1.3 to 2.5 mm (random). Systematic deformations ranged from 0.4 mm near the reference C1-C3 to 3.8 mm for the larynx. Random deformations ranged from 0.5 to 3.6 mm.
Head-and-neck cancer patients show considerable local setup variations, exceeding residual global patient setup uncertainty in an offline correction protocol. Current planning target volume margins may be inadequate to account for these uncertainties. We propose registration of multiple ROIs to drive correction protocols and adaptive radiotherapy to reduce the impact of local setup variations.
Respiratory correlated cone beam CT Sonke, Jan-Jakob; Zijp, Lambert; Remeijer, Peter ...
Medical physics (Lancaster),
April 2005, Letnik:
32, Številka:
4
Journal Article
Recenzirano
A cone beam computed tomography (CBCT) scanner integrated with a linear accelerator is a powerful tool for image guided radiotherapy. Respiratory motion, however, induces artifacts in CBCT, while the ...respiratory correlated procedures, developed to reduce motion artifacts in axial and helical CT are not suitable for such CBCT scanners. We have developed an alternative respiratory correlated procedure for CBCT and evaluated its performance. This respiratory correlated CBCT procedure consists of retrospective sorting in projection space, yielding subsets of projections that each corresponds to a certain breathing phase. Subsequently, these subsets are reconstructed into a four-dimensional (4D) CBCT dataset. The breathing signal, required for respiratory correlation, was directly extracted from the 2D projection data, removing the need for an additional respiratory monitor system. Due to the reduced number of projections per phase, the contrast-to-noise ratio in a 4D scan reduced by a factor 2.6–3.7 compared to a 3D scan based on all projections. Projection data of a spherical phantom moving with a 3 and 5 s period with and without simulated breathing irregularities were acquired and reconstructed into 3D and 4D CBCT datasets. The positional deviations of the phantoms center of gravity between 4D CBCT and fluoroscopy were small:
0.13
±
0.09
mm
for the regular motion and
0.39
±
0.24
mm
for the irregular motion. Motion artifacts, clearly present in the 3D CBCT datasets, were substantially reduced in the 4D datasets, even in the presence of breathing irregularities, such that the shape of the moving structures could be identified more accurately. Moreover, the 4D CBCT dataset provided information on the 3D trajectory of the moving structures, absent in the 3D data. Considerable breathing irregularities, however, substantially reduces the image quality. Data presented for three different lung cancer patients were in line with the results obtained from the phantom study. In conclusion, we have successfully implemented a respiratory correlated CBCT procedure yielding a 4D dataset. With respiratory correlated CBCT on a linear accelerator, the mean position, trajectory, and shape of a moving tumor can be verified just prior to treatment. Such verification reduces respiration induced geometrical uncertainties, enabling safe delivery of 4D radiotherapy such as gated radiotherapy with small margins.
The key goal and main challenge of radiation therapy is the elimination of tumors without any concurring damages of the surrounding healthy tissues and organs. Radiation doses required to achieve ...sufficient cancer‐cell kill exceed in most clinical situations the dose that can be tolerated by the healthy tissues, especially when large parts of the affected organ are irradiated. High‐precision radiation oncology aims at optimizing tumor coverage, while sparing normal tissues. Medical imaging during the preparation phase, as well as in the treatment room for localization of the tumor and directing the beam, referred to as image‐guided radiotherapy (IGRT), is the cornerstone of precision radiation oncology. Sophisticated high‐resolution real‐time IGRT using X‐rays, computer tomography, magnetic resonance imaging, or ultrasound, enables delivery of high radiation doses to tumors without significant damage of healthy organs. IGRT is the most convincing success story of radiation oncology over the last decades, and it remains a major driving force of innovation, contributing to the development of personalized oncology, for example, through the use of real‐time imaging biomarkers for individualized dose delivery.
Sophisticated, high‐resolution, real‐time image‐guided radiotherapy (IGRT) using X‐rays, computer tomography, magnetic resonance imaging, or ultrasound, enables delivery of high radiation doses to tumors without significant damage of healthy organs. Here, we review IGRT research and applications and discuss how they contribute to the development of personalized oncology, for example, through the use of real‐time imaging biomarkers for individualized dose delivery.
Purpose
Cone beam computed tomography (CBCT) has been widely adopted in clinical practice for image‐guided radiotherapy. Soft tissue contrast and Hounsfield units are impaired to the presence of ...scattered radiation. In our previous work, we proposed a high selectivity anti‐scatter grid (ASG) as a possible solution to the problem. An alternative approach is the application of iterative scatter correction using deconvolution with scatter point spread function (PSF). The purpose of this work was to compare the performance of ASGs with different selectivity with and without the iterative and uniform scatter corrections in terms of CBCT image quality. A secondary objective of this study was to develop a novel measurement approach to measure the scatter point spread functions.
Methods
The scatter PSF was modeled as a sum of two bivariate Gaussian functions. The PSF parameters were estimated from a series of transmission measurements through polystyrene slabs of varying thickness with lead partial beam‐blocker for three different ASG designs ranging from low (5.6), medium (9), and high (11) selectivity. The scatter correction scheme is based on iterative convolution of the current estimate of the primary with the scatter PSF until the root mean square deviation (RMSD) of the measured projection and the sum of the estimate of primary and scatter falls below a predefined threshold. The image quality was evaluated with the CIRS CBCT Image Quality and Electron Density phantom in a head and neck and pelvis configuration and the CIRS Virtual Male Human Patient. The image quality was quantified by the contrast‐to‐noise ratio (CNR) relative to the uncorrected scans and the root mean square deviation of the average gray values for different regions with respect to the nominal Hounsfield units and the mean difference of the reconstructed HU between the planning CT and CBCTs of the virtual human phantom.
Results
For the head and neck phantom, the CNR increased with more advanced scatter correction algorithm and the ASG selectivity, reaching 3.9, 3.7, 3.5, and 3.1 for the high, medium, light, and with no grid configuration, respectively, combined with the iterative software correction. The same is true for the pelvis phantom with CNR improvement reaching 1.5 for the heavy and medium grid, 1.3 for the light grid, and 1.1 on its own. The HU RMSD for the head and neck phantom was 22 HU, 13 HU, 12 HU, and 6 HU for iterative correction without the grid, with the light grid, medium grid and the heavy grid, respectively. For same correction strategies, the values for the pelvis phantom where 170, 120, 34, and 27 HU. The average difference with the PCT of the virtual human phantom was 59 ± 48 HU and 63 ± 59 HU with scans reconstructed with the iterative correction and two higher selectivity grids. Visual inspection revealed similar trends for a head‐and‐neck and prostate cancer patient.
Conclusions
The best scatter mitigation strategy was found to be a combination of a grid with selectivity larger than 9, combined with iterative scatter estimation. None of the investigated grids required increasing the imaging dose. The PSF determined using proposed method leads to image quality improvements results for all but one of the investigated scenarios.
To compare deformable image registration (DIR) accuracy and precision for normal and tumor tissues in head and neck cancer patients during the course of radiation therapy (RT).
Thirteen patients with ...oropharyngeal tumors, who underwent submucosal implantation of small gold markers (average 6, range 4-10) around the tumor and were treated with RT were retrospectively selected. Two observers identified 15 anatomical features (landmarks) representative of normal tissues in the planning computed tomography (pCT) scan and in weekly cone beam CTs (CBCTs). Gold markers were digitally removed after semiautomatic identification in pCTs and CBCTs. Subsequently, landmarks and gold markers on pCT were propagated to CBCTs, using a b-spline-based DIR and, for comparison, rigid registration (RR). To account for observer variability, the pair-wise difference analysis of variance method was applied. DIR accuracy (systematic error) and precision (random error) for landmarks and gold markers were quantified. Time trend of the precisions for RR and DIR over the weekly CBCTs were evaluated.
DIR accuracies were submillimeter and similar for normal and tumor tissue. DIR precision (1 SD) on the other hand was significantly different (P<.01), with 2.2 mm vector length in normal tissue versus 3.3 mm in tumor tissue. No significant time trend in DIR precision was found for normal tissue, whereas in tumor, DIR precision was significantly (P<.009) degraded during the course of treatment by 0.21 mm/week.
DIR for tumor registration proved to be less precise than that for normal tissues due to limited contrast and complex non-elastic tumor response. Caution should therefore be exercised when applying DIR for tumor changes in adaptive procedures.
We set out to investigate loss of target coverage from anatomy changes in head and neck cancer patients as a function of applied safety margins and to verify a cone beam computed tomography ...(CBCT)-based adaptive strategy with an average patient anatomy to overcome possible target underdosage.
For 19 oropharyngeal cancer patients, volumetric modulated arc therapy treatment plans (2 arcs; simultaneous integrated boost, 70 and 54.25 Gy; 35 fractions) were automatically optimized with uniform clinical target volume (CTV)-to-planning target volume margins of 5, 3, and 0 mm. We applied b-spline CBCT-to-computed tomography (CT) deformable registration to allow recalculation of the dose on modified CT scans (planning CT deformed to daily CBCT following online positioning) and dose accumulation in the planning CT scan. Patients with deviations in primary or elective CTV coverage >2 Gy were identified as candidates for adaptive replanning. For these patients, a single adaptive intervention was simulated with an average anatomy from the first 10 fractions.
Margin reduction from 5 mm to 3 mm to 0 mm generally led to an organ-at-risk (OAR) mean dose (Dmean) sparing of approximately 1 Gy/mm. CTV shrinkage was mainly seen in the elective volumes (up to 10%), likely related to weight loss. Despite online repositioning, substantial systematic errors were present (>3 mm) in lymph node CTV, the parotid glands, and the larynx. Nevertheless, the average increase in OAR dose was small: maximum of 1.2 Gy (parotid glands, Dmean) for all applied margins. Loss of CTV coverage >2 Gy was found in 1, 3, and 7 of 73 CTVs, respectively. Adaptive intervention in 0-mm plans substantially improved coverage: in 5 of 7 CTVs (in 6 patients) to <2 Gy of initially planned.
Volumetric modulated arc therapy head and neck cancer treatment plans with 5-mm margins are robust for anatomy changes and show a modest increase in OAR dose. Margin reduction improves OAR sparing with approximately 1 Gy/mm at the expense of target coverage in a subgroup of patients. Patients at risk of CTV underdosage >2 Gy in 0-mm plans may be identified early in treatment using dose accumulation. A single intervention with an average anatomy derived from CBCT effectively mitigates discrepancies.
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