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Purpose: A biomechanical model was constructed to give insight into pelvic organ motion as a result of bladder filling changes. Methods: The authors used finite element(FE)modeling to simulate bladder wall deformation caused by urine inflow. For ten volunteers, a series of MRI scans of the pelvic area was recorded at regular intervals of 10 min over 1 h. For the series of scans, the bladder volume gradually increased while the rectal volume was constant. The MR image with the bladder volume closest to 250 ml was selected as the reference in each volunteer. All pelvic structures were defined from the reference image including bladder wall, small bowel, prostate (male), uterus (female), rectum, pelvic bone, and the rest of the body. These structures were translated to FE meshes. Using appropriate material properties for all organs, deformations of these organs as a response to changing bladder pressure were computed. Results: The computation results showed realistic anisotropic deformation of the bladder wall: The bladder became more elongated in the cranial and anterior directions with increasing bladder volume. After fitting the volume of the computed bladder to the actual bladder volume on the test images, the computed bladder shape agreed well with the real bladder shape (overlap from 0.79 to 0.93). The average mean bladder wall prediction errors of all the volunteers were 0.31 cm average and 0.29 cm SD. Conclusions: In conclusion, a FE based mechanical bladder model shows promise for the prediction of the short-term bladder shape change using only one pelvic scan and volume change of the bladder as input. The accuracy levels achieved with this method are likely mostly limited by inaccuracies in material properties and sliding tissue between organs, which has not been modeled. This model can potentially be used to improve image-guidedradiotherapy for bladder cancer patients, i.e., by prediction short-term bladder deformation.

Purpose Image based data mining (IBDM) is a novel technique in which dose response relationships are extracted from routine clinical data by relating the dose at each voxel in the planned dose to the eventual outcome for the patient. In IBDM many patients are registered to a reference patient to spatially normalise their dose distributions for analysis, eliminating the need for clinician contours and removing assumptions implicit in DVH based analyses. Recently, IBDM has been used to identify a dose sensitive region in the heart where patients receiving excess dose have poorer overall survival [1] . Methods In this work, a subset (n = 872) of the cohort of patients in [1] is used, but a more sophisticated IBDM technique is applied. A Cox regression, considering tumour size, age, performance status, dose and a dose-PS interaction is calculated in each voxel of the planned dose distribution. Performance status is binarised using a threshold of PS > = 1 to account for inaccuracy in its determination. This analysis leads to a map of hazard ratio across the reference patient anatomy. Statistical significance is assessed using a permutation test in which only survival labels are permuted. Results When performing the analysis with an interaction between performance status and dose present in the Cox model, a region is identified in the base of the heart where excess dose is detrimental to survival. This region overlaps with that found by other analyses, and suggests that patients with a performance status of 2 or greater suffer a more profound effect from dose in this region. In the present analysis statistical significance is not reached in any voxel for either the dose, PS or dose-PS interaction. Conclusions A region in the base of the heart is identified, consistent with other analyses, in which excess dose is related to poorer overall survival, particularly for those patients with poor performance. Statistical significance may be reached by including more data, or modifying the permutation technique.

Purpose Lung cancer patients treated with radiotherapy often present with multiple comorbidities which can interact with incidental dose to increase risk of death, as suggested by recent studies1. Although these comorbidities should be incorporated in survival analysis, such data is often missing from large datasets. We investigated whether calcifications, identified on the radiotherapy planning CT, can be used as a surrogate for general health. In particular, we investigated the interaction between calcifications, dose and survival. Methods Data from 846 unselected non-small cell lung cancer patients was used, all treated with 55 Gy in 20 fractions. Methodology was developed to automatically segment calcifications. The planning CT scan, acquired with a 3D protocol, and the lung and spinal cord delineations were processed using well-established image processing algorithms, e.g., convex hull, threshold, morphological operations, connected pixel analysis and flood filling to detect calcifications. A radiation oncologist manually identified calcifications in a small subset of 7 patients, and this group was used to estimate the success and error rate of the automatic segmentation. To reduce the impact of erroneous segmentations, an empirical threshold was used where patients showing more than 12 cm3 calcifications were excluded from analysis (n = 718 remaining). Finally, a multivariate Cox-regression analysis was performed for overall survival accounting for tumour size, total calcification volume and mean dose across all identified calcifications, including interaction between calcification volume and dose [1] . Results The success rate of the algorithm for identifying calcifications was 72.5%, its error rate was 23.2%. The Cox-regression analysis identified tumour size (continuous, p 0.0001) and the interaction of calcification volume and calcification dose (continuous, p = 0.023) as significant. The calcification volume (p = 0.172) or mean calcification dose alone (p = 0.535) were not found to be significant. Conclusions Multivariate analysis show a significant interaction between volume of the identified calcifications and radiotherapy dose predicting survival, which suggests that interaction rather than calcifications alone can be used as a factor in survival analysis. Further improvement and validation of our methodology is required, as well as linking our results with the established Agatston or Coronary Artery Calcium score. * EVO-FB share first authorship.

Modern precision radiotherapy allows small safety margins and dose escalation. Therefore, biological factors become much more important such as CTV delineation and thresholds for organ at risk tolerance. Our aim is to develop image based data mining for exploring voxel-based dose–response relationships in very large patient cohorts. Large numbers of planning CTs are deformably registered to a reference CT. Registration uncertainties are quantified using organ-at-risk contours, dose distributions are smoothed according to these uncertainties and mapped onto the reference. Next outcome measures are correlated voxel-by-voxel with the dose distributions. The resulting correlation maps are tested for significance using a test statistic, e.g. maximum t-value, using randomization to test for significance. We have applied this methodology in several tumour sites and a great strength of this technique is that it allows discovery of sensitive sub-structures of organs. For example, in lung cancer we demonstrated a relationship of dose to the base of the heart with early mortality (1100 patients); while in head and neck cancer, masseter dose correlated most with post treatment trismus. In prostate cancer, obturator dose relates to PSA control. To understand the results, it is important to study inherent correlations in voxel-wise dose distributions that are related to planning techniques that are often ignored in dose-volume based analyses. We conclude that voxel based dose response relationships can be discovered efficiently using deformable registration and novel statistical techniques and that these complement traditional dose–volume analyses, and are suitable for very large patient cohorts.

Purpose The development of 4DCT imaging allows clinicians to account for movement of both the target tumour and organs at risk, although the choice of method of image reconstruction can impact how accurately observers can contour nearby organs. Motion-compensated (MC) image reconstruction is a technique that reduces blurring compared to standard averaged reconstruction. This study aims to quantify the presence of sharper boundaries by taking the value of the image gradient at contour lines, and link this increase in tissue definition to lower inter-observer variation. Methods Eight patients with early stage non-small lung cancer were imaged with 4DCT, and these scans were reconstructed using both motion-compensated and averaged techniques. These two sets of scans were then each delineated by five clinicians, who contoured nearby organs at risk. The mean distance between observers’ contours was calculated and compared to the image gradient value at each point on the delineation. Results Drawing on results by McWilliam et al. [1] , the use of motion-compensated CT image reconstruction results in a reduction in inter-observer variation across all sites delineated. The use of MC increases definition of boundaries between organs, represented by an increase in the image gradient at the delineation boundary. This result was particularly pronounced around the trachea, where preliminary results show the use of motion-compensated reconstruction reduced delineation separation by 50%; across all patients, the heart saw very little improvement between imaging techniques. Conclusions The use of motion-compensated CT reconstruction produces images with more well-defined boundaries between tissue, and higher values of image gradient. When delineating organs at risk, the presence of large gradients is a statistically significant (p

Purpose: For prostate cancer patients at risk for subclinical spread of the disease, we investigated whether incidental dose outside the target was associated with tumor control. Methods and Materials: We selected 352 intermediate-risk (mainly T2b-T3a) and high-risk (mainly T3b) patients treated in a randomized trial. Target volume was prostate (68-78 Gy) and seminal vesicles (50-78 Gy). Failure (clinical or biochemical) was evaluated at 4 years. To compare three-dimensional dose distributions, an automated mapping procedure was introduced. Between patients, these maps provide an approximate identification of corresponding anatomical locations. Maps of the dose difference between patients with and without failure were constructed. Univariate and multivariate analyses were performed including the dose in selected points. Results: Dose differences were mainly found in the obturatorial region for the high-risk patients, and in the presacral region for the intermediate risk group (>7 Gy, p

Lung cancer survival is poor, and radiation therapy patients often suffer serious treatment side effects. The esophagus is particularly sensitive leading to acute radiation-induced esophageal damage (ARIED). We investigated the feasibility of optical coherence tomography (OCT) for minimally invasive imaging of the esophagus with high resolution (10 μm) to detect ARIED in mice. Thirty mice underwent cone-beam computed tomography imaging for initial setup assessment and dose planning followed by a single-dose delivery of 4.0, 10.0, 16.0, and 20.0 Gy on 5.0-mm spots, spaced 10.0 mm apart in the esophagus. They were repeatedly imaged using OCT up to three months postirradiation. We compared OCT findings with histopathology obtained three months postirradiation qualitatively and quantitatively using the contrast-to-background-noise ratio (CNR). Histopathology mostly showed inflammatory infiltration and edema at higher doses; OCT findings were in agreement with most of the histopathological reports. We were able to identify the ARIED on OCT as a change in tissue scattering and layer thickness. Our statistical analysis showed significant difference between the CNR values of healthy tissue, edema, and inflammatory infiltration. Overall, the average CNR for inflammatory infiltration and edema damages was 1.6-fold higher and 1.6-fold lower than for the healthy esophageal wall, respectively. Our results showed the potential role of OCT to detect and monitor the ARIED in mice, which may translate to humans.

Purpose: To discuss the first clinical experience with a multiple region of interest (mROI) registration and correction method for high-precision radiotherapy of head-and-neck cancer patients.Materials and methods: 12-13 3D rectangular-shaped ROIs were automatically placed around bony structures on the planning CT scans (n = 50 patients) which were individually registered to subsequent CBCT scans. mROI registration was used to quantify global and local setup errors. The time required to perform the mROI registration was compared with that of a previously used single-ROI method. The number of scans with residual local setup error exceeding 5 mm/5 degrees (warnings) was scored together with the frequency ROIs exceeding these limits for three or more consecutive imaging fractions (systematic errors).Results: In 40% of the CBCT scans, one or more ROI-registrations exceeded the 5 mm/5 degrees. Most warnings were seen in ROI "hyoid", 31% of the rotation warnings and 14% of the translation warnings. Systematic errors lead to 52 consults of the treating physician. The preparation and registration time was similar for both registration methods.Conclusions: The mROI registration method is easy to use with little extra workload, provides additional information on local setup errors, and helps to select patients for re-planning. (C) 2009 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 94 (2010) 213-217

PURPOSE: To quantify and evaluate the accumulated prostate, rectum, and bladder dose for several strategies including rotational organ motion correction for intensity-modulated radiotherapy (IMRT) of prostate cancer using realistic organ motion data. METHODS AND MATERIALS: Repeat computed tomography (CT) scans of 19 prostate patients were used. Per patient, two IMRT plans with different uniform margins were created. To quantify prostate and seminal vesicle motion, repeat CT clinical target volumes (CTVs) were matched onto the planning CTV using deformable registration. Four different strategies, from online setup to full motion correction, were simulated. Rotations were corrected for using gantry and collimator angle adjustments. Prostate, rectum, and bladder doses were accumulated for each patient, plan, and strategy. Minimum CTV dose (D(min)), rectum equivalent uniform dose (EUD, n = 0.13), and bladder surface receiving >/=78 Gy (S78), were calculated. RESULTS: With online CTV translation correction, a 7-mm margin was sufficient (i.e., D(min) >/= 95% of the prescribed dose for all patients). A 4-mm margin required additional rotational correction. Margin reduction lowered the rectum EUD(n = 0.13) by approximately 2.6 Gy, and the bladder S78 by approximately 1.9%. CONCLUSIONS: With online correction of both translations and rotations, a 4-mm margin was sufficient for 15 of 19 patients, whereas the remaining four patients had an underdosed CTV volume

PURPOSE: To determine the effect of respiration-induced density variations on the estimated dose delivered to moving structures and, consequently, to evaluate the necessity of using full four-dimensional (4D) treatment plan optimization. METHODS AND MATERIALS: In 10 patients with large tumor motion (median, 1.9 cm; range, 1.1-3.6 cm), the clinical treatment plan, designed using the mid-ventilation ([MidV]; i.e., the 4D-CT frame closest to the time-averaged mean position) CT scan, was recalculated on all 4D-CT frames. The cumulative dose was determined by transforming the doses in all breathing phases to the MidV geometry using deformable registration and then averaging the results. To determine the effect of density variations, this cumulative dose was compared with the accumulated dose after similarly deforming the planned (3D) MidV-dose in each respiratory phase using the same transformation (i.e., "blurring the dose"). RESULTS: The accumulated tumor doses, including and excluding density variations, were almost identical. Relative differences in the minimum gross tumor volume (GTV) dose were less than 2% for all patients. The relative differences were even smaller in the mean lung dose and the V20 (

Treatment plans are usually designed, optimized, and evaluated based on the total 3D dose distribution, motivating a total 3D dose verification. The purpose of this study was to develop a 2D transmission-dosimetry method using an electronic portal imaging device (EPID) into a simple 3D method that provides 3D dose information. In the new method, the dose is reconstructed within the patient volume in multiple planes parallel to the EPID for each gantry angle. By summing the 3D dose grids of all beams, the 3D dose distribution for the total treatment fraction is obtained. The algorithm uses patient contours from the planning CT scan but does not include tissue inhomogeneity corrections. The 3D EPID dosimetry method was tested for IMRT fractions of a prostate, a rectum, and a head-and-neck cancer patient. Planned and in vivo-measured dose distributions were within 2% at the dose prescription point. Within the 50% isodose surface of the prescribed dose, at least 97% of points were in agreement, evaluated with a 3D gamma method with criteria of 3% of the prescribed dose and 0.3 cm. Full 3D dose reconstruction on a 0.1 x 0.1 x 0.1 cm3 grid and 3D gamma evaluation took less than 15 min for one fraction on a standard PC. The method allows in vivo determination of 3D dose-volume parameters that are common in clinical practice. The authors conclude that their EPID dosimetry method is an accurate and fast tool for in vivo dose verification of IMRT plans in 3D. Their approach is independent of the treatment planning system and provides a practical safety net for radiotherapy.

Purpose 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. Materials and Methods 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. Results 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). Conclusions 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.

Respiratory motion causes artifacts in cone-beam (CB) CT images acquired on slow rotating scanners integrated with linear accelerators. Respiration-correlated CBCT has been proposed to correct for the respiratory motion but only a subset of the CB projections is used to reconstruct each frame of the 4D CBCT image and, therefore, adequate image quality requires long acquisition times. In this article, the authors develop an on-the-fly solution to estimate and compensate for the respiratory motion in the reconstruction of a 3D CBCT image from all the CB projections. An a priori motion model of the patient respiratory cycle is estimated from the 4D planning CT. During the acquisition, the model is correlated with the respiration using a respiratory signal extracted from the CB projections. The estimated motion is next compensated for in an optimized reconstruction algorithm. The motion compensated for is forced to be null on average over the acquisition time to ensure that the compensation results in a CBCT image which describes the mean position of each organ, even if the a priori motion model is inaccurate. Results were assessed on simulated, phantom, and patient data. In all experiments, blur was visually reduced by motion-compensated CBCT. Simulations showed robustness to inaccuracies of the motion model observed on patient data such as amplitude variations, phase shifts, and setup errors, thus proving the efficiency of the compensation using an a priori motion model. Noise and view-aliasing artifacts were lower on motion-compensated CBCT images with 1 min scan than on respiration-correlated CBCT images with 4 min scan. Finally, on-the-fly motion estimation and motion-compensated reconstruction were within the acquisition time of the CB projections and the CBCT image available a few seconds after the end of the acquisition. In conclusion, the authors developed and implemented a method for correcting the respiratory motion during the treatment fractions which can replace respiration-correlated CBCT for improving image quality while decreasing acquisition time.

Purpose To quantify local geometrical uncertainties in anatomical sub-regions during radiotherapy for head-and-neck cancer patients. Methods and Materials 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). Results 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. Conclusion 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.

A technique was developed for bladder tumour demarcation with lipiodol injection through a flexible cystoscope. The technique proved to be simple and useful for image-guided radiotherapy in bladder cancer as well as a helpful aid in the tumour delineation process.

Purpose To discuss planning target volumes (PTVs) based on internal target volume (PTV ITV ), exhale-gated radiotherapy (PTV Gating ), and a new proposed midposition (PTV MidP ; time-weighted mean tumor position) and compare them with the conventional free-breathing CT scan PTV (PTV Conv ). Methods and Materials Respiratory motion induces systematic and random geometric uncertainties. Their contribution to the clinical target volume (CTV)-to-PTV margins differs for each PTV approach. The uncertainty margins were calculated using a dose–probability-based margin recipe (based on patient statistics). Tumor motion in four-dimensional CT scans was determined using a local rigid registration of the tumor. Geometric uncertainties for interfractional setup errors and tumor baseline variation were included. For PTV Gating , the residual motion within a 30% gating (time) window was determined. The concepts were evaluated in terms of required CTV-to-PTV margin and PTV volume for 45 patients. Results Over the patient group, the PTV ITV was on average larger (+6%) and the PTV Gating and PTV MidP smaller (−10%) than the PTV Conv using an off-line (bony anatomy) setup correction protocol. With an on-line (soft tissue) protocol the differences in PTV compared with PTV Conv were +33%, −4%, and 0, respectively. Conclusions The internal target volume method resulted in a significantly larger PTV than conventional CT scanning. The exhale-gated and mid-position approaches were comparable in terms of PTV. However, mid-position (or mid-ventilation) is easier to use in the clinic because it only affects the planning part of treatment and not the delivery.

Purpose To quantify the interfractional variability in lung tumor trajectory and mean position during the course of radiation therapy. Methods and Materials 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. Results 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. Conclusions 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.

Purpose: To derive guidelines for the need to use positron emission tomography (PET) for delineation of the primary tumor (PT) according to its anatomical location in the lung. Methods and Materials: In 22 patients with non-small-cell lung cancer, thoracic X-ray computed tomography (CT) and PET were performed. Eleven radiation oncologists delineated the PT on the CT and on the CT-PET registered scans. The PTs were classified into two groups. In Group I patients, the PT was surrounded by lung or visceral pleura, without venous invasion, without extension to chest wall or the mediastinum over more than one quarter of its surface. In Group II patients, the PT invaded the hilar region, heart, great vessels, pericardium, mediastinum over more than one quarter of its surface and/or associated with atelectasis. A comparison of interobserver variability for each group was performed and expressed as a local standard deviation. Results: The comparison of delineations showed a good reproducibility for Group I, with an average SD of 0.4 cm on CT and an average SD of 0.3 cm on CT-PET (p = 0.1628). There was also a significant improvement with CT-PET for Group II, with an average SD of 1.3 cm on CT and SD of 0.4 cm on CT-PET (p = 0.0003). The improvement was mainly located at the atelectasis/tumor interface. At the tumor/lung and tumor/hilum interfaces, the observer variation was similar with both modalities. Conclusions: Using PET for PT delineation is mandatory to decrease interobserver variability in the hilar region, heart, great vessels, pericardium, mediastinum, and/or the region associated with atelectasis; however it is not essential for delineation of PT surrounded by lung or visceral pleura, without venous invasion or extension to the chest wall.

As radiotherapy becomes more complicated, dose and geometry verification become more necessary. The aim of this study was to use back-projected EPID-based 3D in vivo dosimetry and cone-beam CT (CBCT) to obtain a complete account of the entire treatment for a select patient group. Nine hypo-fractionated rectum IMRT patient plans were investigated. The absolute dose was reconstructed at multiple planes using patient contours and EPID images acquired for all fields during treatment. The meso-rectal fat (m-R) was re-delineated on daily CBCT scans, acquired prior to each fraction. The total accumulated dose was determined by mapping the m-R surface of each fraction to the planned m-R surface. Average planned and measured isocentre dose ratios were 0.98 (+/-0.01SD). 3D gamma analysis (3% maximum dose and 3mm) revealed mean gamma, gamma(mean)=0.35 (+/-0.03 SD), maximum 1% of gamma points, gamma(max1%)=1.02 (+/-0.14SD) and the percentage of points with gamma < or = 1, P(gamma < or = 1)=99% (range [96%, 100%]), averaged over all patients. CBCT m-R volumes varied by up to 20% of planned volumes, but remained in the high dose region. Over-dosage of up to 4.5% in one fraction was measured in the presence of gas pockets. By combining EPID dosimetry with CBCT geometry information, the total dose can be verified in 3D in vivo and compared with the planned dose distribution. This method can provide a safety net for advanced treatments involving dose escalation, as well as a full account of the delivered dose to specific volumes, allowing adaptation of the treatment from the original plan if necessary.

PURPOSE: To evaluate the influence of a dietary protocol on cone beam computed tomography (CBCT) image quality, which is an indirect indicator for short-term (intrafraction) prostate motion, and on interfraction motion. Image quality is affected by motion (e.g., moving gas) during imaging and influences the performance of automatic prostate localization on CBCT scans. METHODS AND MATERIALS: Twenty-six patients (336 CBCT scans) followed the dietary protocol and 23 patients (240 CBCT scans) did not. Prostates were automatically localized by using three dimensional (3D) gray-value registration (GR). Feces and (moving) gas occurrence in the CBCT scans, the success rate of 3D-GR, and the statistics of prostate motion data were assessed. RESULTS: Feces, gas, and moving gas significantly decreased from 55%, 61%, and 43% of scans in the nondiet group to 31%, 47%, and 28% in the diet group (all p < 0.001). Since there is a known relation between gas and short-term prostate motion, intrafraction prostate motion probably also decreased. The success rate of 3D-GR improved from 83% to 94% (p < 0.001). A decrease in random interfraction prostate motion also was found, which was not significant after Bonferroni's correction. Significant deviations from planning CT position for rotations around the left-right axis were found in both groups. CONCLUSIONS: The dietary protocol significantly decreased the incidence of feces and (moving) gas. As a result, CBCT image quality and the success rate of 3D-GR significantly increased. A trend exists that random interfraction prostate motion decreases. Using a dietary protocol therefore is advisable, also without CBCT-based image guidance

PURPOSE: The purpose of this study was to determine the value of (99m)Tc Hynic-rh-Annexin-V-Scintigraphy (TAVS), a non-invasive in vivo technique to demonstrate apoptosis in patients with head and neck squamous cell carcinoma. METHODS: TAVS were performed before and within 48 h after the first course of cisplatin-based chemoradiation. Radiation dose given to the tumour at the time of post-treatment TAVS was 6-8 Gy. Single-photon emission tomography data were co-registered to planning CT scan. Complete sets of these data were available for 13 patients. The radiation dose at post-treatment TAVS was calculated for several regions of interest (ROI): primary tumour, involved lymph nodes and salivary glands. Annexin uptake was determined in each ROI, and the difference between post-treatment and baseline TAVS represented the absolute Annexin uptake: Delta uptake (DeltaU). RESULTS: In 24 of 26 parotid glands, treatment-induced Annexin uptake was observed. Mean DeltaU was significantly correlated with the mean radiation dose given to the parotid glands (r = 0.59, p = 0.002): Glands that received higher doses showed more Annexin uptake. DeltaU in primary tumour and pathological lymph nodes showed large inter-patient differences. A high correlation was observed on an inter-patient level (r = 0.71, p = 0.006) between the maximum DeltaU in primary tumour and in the lymph nodes. CONCLUSIONS: Within the dose range of 0-8 Gy, Annexin-V-scintigraphy showed a radiation-dose-dependent uptake in parotid glands, indicative of early apoptosis during treatment. The inter-individual spread in Annexin uptake in primary tumours could not be related to differences in dose or tumour volume, but the Annexin uptake in tumour and lymph nodes were closely correlated. This effect might represent a tumour-specific apoptotic response

The purpose of this work was the development of a probabilistic planning method with biological cost functions that does not require the definition of margins. Geometrical uncertainties were integrated in tumor control probability (TCP) and normal tissue complication probability (NTCP) objective functions for inverse planning. For efficiency reasons random errors were included by blurring the dose distribution and systematic errors by shifting structures with respect to the dose. Treatment plans were made for 19 prostate patients following four inverse strategies: Conformal with homogeneous dose to the planning target volume (PTV), a simultaneous integrated boost using a second PTV, optimization using TCP and NTCP functions together with a PTV, and probabilistic TCP and NTCP optimization for the clinical target volume without PTV. The resulting plans were evaluated by independent Monte Carlo simulation of many possible treatment histories including geometrical uncertainties. The results showed that the probabilistic optimization technique reduced the rectal wall volume receiving high dose, while at the same time increasing the dose to the clinical target volume. Without sacrificing the expected local control rate, the expected rectum toxicity could be reduced by 50% relative to the boost technique. The improvement over the conformal technique was larger yet. The margin based biological technique led to toxicity in between the boost and probabilistic techniques, but its control rates were very variable and relatively low. During evaluations, the sensitivity of the local control probability to variations in biological parameters appeared similar for all four strategies. The sensitivity to variations of the geometrical error distributions was strongest for the probabilistic technique. It is concluded that probabilistic optimization based on tumor control probability and normal tissue complication probability is feasible. It results in robust prostate treatment plans with an improved balance between local control and rectum toxicity, compared to conventional techniques.

The gamma-evaluation method is a tool by which dose distributions can be compared in a quantitative manner combining dose-difference and distance-to-agreement criteria. Since its introduction, the gamma evaluation has been used in many studies and is on the verge of becoming the preferred dose distribution comparison method, particularly for intensity-modulated radiation therapy (IMRT) verification. One major disadvantage, however, is its long computation time, which especially applies to the comparison of three-dimensional (3D) dose distributions. We present a fast algorithm for a full 3D gamma evaluation at high resolution. Both the reference and evaluated dose distributions are first resampled on the same grid. For each point of the reference dose distribution, the algorithm searches for the best point of agreement according to the gamma method in the evaluated dose distribution, which can be done at a subvoxel resolution. Speed, computer memory efficiency, and high spatial resolution are achieved by searching around each reference point with increasing distance in a sphere, which has a radius of a chosen maximum search distance and is interpolated "on-the-fly" at a chosen sample step size. The smaller the sample step size and the larger the differences between the dose distributions, the longer the gamma evaluation takes. With decreasing sample step size, statistical measures of the 3D gamma distribution converge. Two clinical examples were investigated using 3% of the prescribed dose as dose-difference and 0.3 cm as distance-to-agreement criteria. For 0.2 cm grid spacing, the change in gamma indices was negligible below a sample step size of 0.02 cm. Comparing the full 3D gamma evaluation and slice-by-slice 2D gamma evaluations ("2.5D") for these clinical examples, the gamma indices improved by searching in full 3D space, with the average gamma index decreasing by at least 8%.

PURPOSE: Kilovoltage cone-beam computed tomography (CBCT) has been developed to provide accurate soft-tissue and bony setup information. We evaluated clinical CBCT setup data and compared CBCT measurements with electronic portal imaging device (EPID) images for lung cancer patients. METHODS AND MATERIALS: The setup error for CBCT scans at the treatment unit relative to the planning CT was measured for 62 patients (524 scans). For 19 of these patients (172 scans) portal images were also made. The mean, systematic setup error (Sigma), and random setup error (sigma) were calculated for the CBCT and the EPID. The differences between CBCT and EPID and the rotational setup error derived from the CBCT were also evaluated. An offline shrinking action level correction protocol, based on the CBCT measurements, was used to reduce systematic setup errors and the impact of this protocol was evaluated. RESULTS: The CBCT setup errors were significantly larger than the EPID setup errors for the cranial-caudal and anterior-posterior directions (p < 0.05). The mean overall setup errors after correction measured with the CBCT were 0.2 mm (Sigma = 1.6 mm, sigma = 2.9 mm) in the left-right, -0.8 mm (Sigma = 1.7 mm, sigma = 4.0 mm) in cranial-caudal and 0.0 mm (Sigma = 1.5 mm, sigma = 2.0 mm) in the anterior-posterior direction. Using our correction protocol only 2 patients had mean setup errors larger than 5 mm, without this correction protocol 51% of the patients would have had a setup error larger than 5 mm. CONCLUSION: Use of CBCT scans provided more accurate information concerning the setup of lung cancer patients than did portal imaging

PURPOSE: The short-term displacement and reproducibility of the breast or chest wall, and the internal mammary (IM), infraclavicular (ICV), and supraclavicular (SCV) nodal regions have been assessed as a function of breath-hold state using an active breathing control (ABC) device for patients receiving loco-regional breast radiation therapy. METHODS AND MATERIALS: Ten patients underwent computed tomographic scanning using an ABC device at breath-hold states of end-exhale and 20%, 40%, 60%, and 80% of vital capacity (VC). Patients underwent scanning before treatment and at one third and two thirds of the way through treatment. A regional registration was performed for each target using a rigid-body transformation with mutual information as a metric. RESULTS: Between exhale and 40% of VC, the mean displacement was 0.27/0.34, 0.24/0.31, 0.22/0.19, and 0.13/0.19 cm anterior/superior for the breast or chest wall, and IM, ICV, and SCV nodes, respectively. At 80% of VC, the mean displacement from exhale was 0.84/.88, 0.76/.79, 0.70/0.79, and 0.54/0.56 cm anterior/superior for the breast or chest wall, and IM, ICV, and SCV nodes, respectively. The short-term reproducibility (standard deviation) was

PURPOSE: To determine the planning target volume (PTV) margin for an adaptive radiotherapy procedure that uses five computed tomography (CT) scans to calculate an average prostate position and rectum shape. To evaluate alternative methods to determine an average rectum based on a single delineation. METHODS AND MATERIALS: Repeat CT scans (8-13) of 19 patients were used. The contoured prostates of the first four scans were matched on the planning CT (pCT) prostate contours. With the resulting translations and rotations the average prostate position was determined. An average rectum was obtained by either averaging the coordinates of corresponding points on the rectal walls or by selecting the "best" rectum or transforming the pCT rectum. Dose distributions were calculated for various expanded average prostates. The remaining CT scans were used to determine the dose received by prostate and rectum during treatment. RESULTS: For the prostate of the pCT scan and a 10-mm margin, all patients received more than 95% of the prescribed dose to 95% of the prostate. For the average prostate, a margin of 7 mm was needed to obtain a similar result (average PTV reduction 30%). The average rectum overestimated the mean dose to the rectum by 0.4 +/- 1.6 Gy, which was better than the pCT rectum (2.1 +/- 3.0 Gy) and the alternative average rectums (1.0 +/- 2.6 Gy and 1.4 +/- 3.2 Gy). CONCLUSIONS: Our adaptive procedure allows for reduction of the PTV margin to 7 mm without decreasing prostate coverage during treatment. For accurate estimation of the rectum dose, rectums need to be delineated and averaged over multiple scans

PURPOSE: To evaluate the image quality of retrospectively attenuation corrected Positron Emission Tomography (PET) scans used for gross tumor volume (GTV) delineation in lung cancer patients. MATERIALS AND METHODS: Data of 13 lymph node positive lung cancer patients were acquired on separate CT and PET scanners under free breathing conditions (for radiotherapy planning). First we determined a protocol for CT/PET registration. Second, we compared the image quality of attenuation-corrected PET images using positron transmission images and CT images, in terms of signal-to-noise ratio (SNR) and lesion-to-background ratio (contrast). RESULTS: The largest differences between manual and automatic CT/PET registration were found in the anterior-posterior direction with a mean of 1.8 mm (SD 1.0 mm). Differences in rotations were always smaller than 1.0 degrees . The attenuation-corrected images using CT showed a larger SNR (mean 30%, SD 17%) and larger contrast (mean 14.0%, SD 8.5%) compared to attenuation-corrected images using positron transmission. For lymph nodes, the mean contrast was 16% (SD 6.4%) larger. CONCLUSIONS: This study demonstrated that attenuation correction based on CT provides a better image quality for GTV delineation than when using positron transmission for attenuation correction. Retrospective attenuation correction of PET scans based on registered CT is a good alternative for a dedicated PET/CT scanner if a free-breathing CT is available, e.g., for radiotherapy planning, and allows the use of CT with diagnostic quality for attenuation correction

Purpose: The objective of this project was to define consensus guidelines for delineating organs at risk (OARS) for head and neck radiotherapy for routine daily, practice and for research purposes.Methods: Consensus guidelines were formulated based on in-depth discussions of a panel of European, North American, Asian and Australian radiation oncologists.Results: Twenty-five OARS in the head and neck region were defined with a concise description of their main anatomic boundaries. The Supplemental material provides an atlas of the consensus guidelines, projected on 1 mm axial slices. The atlas can also be obtained in DICOM-RT format on request.Conclusion: Consensus guidelines for head and neck OAR delineation were defined, aiming to decrease interobserver variability among clinicians and radiotherapy centers. (C) 2015 The Authors. Published by Elsevier Ireland Ltd.

The aims of this work were to evaluate the performance of several deformable image registration (DIR) algorithms implemented in our in-house software (NiftyReg) and the uncertainties inherent to using different algorithms for dose warping.The authors describe a DIR based adaptive radiotherapy workflow, using CT and cone-beam CT (CBCT) imaging. The transformations that mapped the anatomy between the two time points were obtained using four different DIR approaches available in NiftyReg. These included a standard unidirectional algorithm and more sophisticated bidirectional ones that encourage or ensure inverse consistency. The forward (CT-to-CBCT) deformation vector fields (DVFs) were used to propagate the CT Hounsfield units and structures to the daily geometry for "dose of the day" calculations, while the backward (CBCT-to-CT) DVFs were used to remap the dose of the day onto the planning CT (pCT). Data from five head and neck patients were used to evaluate the performance of each implementation based on geometrical matching, physical properties of the DVFs, and similarity between warped dose distributions. Geometrical matching was verified in terms of dice similarity coefficient (DSC), distance transform, false positives, and false negatives. The physical properties of the DVFs were assessed calculating the harmonic energy, determinant of the Jacobian, and inverse consistency error of the transformations. Dose distributions were displayed on the pCT dose space and compared using dose difference (DD), distance to dose difference, and dose volume histograms.All the DIR algorithms gave similar results in terms of geometrical matching, with an average DSC of 0.85 ± 0.08, but the underlying properties of the DVFs varied in terms of smoothness and inverse consistency. When comparing the doses warped by different algorithms, we found a root mean square DD of 1.9% ± 0.8% of the prescribed dose (pD) and that an average of 9% ± 4% of voxels within the treated volume failed a 2%pD DD-test (DD2%-pp). Larger DD2%-pp was found within the high dose gradient (21% ± 6%) and regions where the CBCT quality was poorer (28% ± 9%). The differences when estimating the mean and maximum dose delivered to organs-at-risk were up to 2.0%pD and 2.8%pD, respectively.The authors evaluated several DIR algorithms for CT-to-CBCT registrations. In spite of all methods resulting in comparable geometrical matching, the choice of DIR implementation leads to uncertainties in dose warped, particularly in regions of high gradient and/or poor imaging quality.

Background and purpose: Target dose verification for VMAT treatments of head-and-neck (H&N) cancer using 3D in vivo EPID dosimetry is expected to be affected by daily anatomical changes. By including these anatomical changes through cone-beam CT (CBCT) information, the magnitude of this effect is investigated. Materials and methods: For 20 VMAT-treated H&N cancer patients, all plan-CTs (pCTs), 633 CBCTs and 1266 EPID movies were used to compare four dose distributions per fraction: treatment planning system (TPS) calculated dose and EPID reconstructed in vivo dose, both determined using the pCT and using the CBCT. D2, D50 and D98 of the planning target volume (PTV) were determined per dose distribution. Results: When including daily anatomical information, D2, D50 and D98 of the PTV change on average by 0.0 +/- 0.4% according to TPS calculations; the standard deviation of the difference between EPID and TPS target dose changes from 2.5% (pCT) to 2.1% (CBCT). Small time trends are seen for both TPS and EPID dose distributions when using the pCT, which disappear when including CBCT information. Conclusions: Daily anatomical changes hardly influence the target dose distribution for H&N VMAT treatments according to TPS recalculations. Including CBCT information in EPID dose reconstructions slightly improves the agreement with TPS calculations. (C) 2015 Elsevier Ireland Ltd. All rights reserved

The use of gradient information is well-known to be highly useful in single-objective optimization-based image registration methods. However, its usefulness has not yet been investigated for deformable image registration from a multi-objective optimization perspective. To this end, within a previously introduced multi-objective optimization framework, we use a smooth B-spline-based dual-dynamic transformation model that allows us to derive gradient information analytically, while still being able to account for large deformations. Within the multi-objective framework, we previously employed a powerful evolutionary algorithm (EA) that computes and advances multiple outcomes at once, resulting in a set of solutions (a so-called Pareto front) that represents efficient trade-offs between the objectives. With the addition of the B-spline-based transformation model, we studied the usefulness of gradient information in multiobjective deformable image registration using three different optimization algorithms: the (gradient-less) EA, a gradientonly algorithm, and a hybridization of these two. We evaluated the algorithms to register highly deformed images: 2D MRI slices of the breast in prone and supine positions. Results demonstrate that gradient-based multi-objective optimization significantly speeds up optimization in the initial stages of optimization. However, allowing sufficient computational resources, better results could still be obtained with the EA. Ultimately, the hybrid EA found the best overall approximation of the optimal Pareto front, further indicating that adding gradient-based optimization for multiobjective optimization-based deformable image registration can indeed be beneficial.

Contains fulltext : 152592.pdf (Publisher’s version ) (Open Access) Portal dosimetry using electronic portal imaging devices (EPIDs) is often applied to verify high-energy photon beam treatments. Due to the change in photon energy spectrum, the resulting dose values are, however, not very accurate in the case of wedged beams if the pixel-to-dose conversion for the situation without wedge is used. A possible solution would be to consider a wedged beam as another photon beam quality requiring separate beam modeling of the dose calculation algorithm. The aim of this study was to investigate a more practical solution: to make aSi EPID-based dosimetry models also applicable for wedged beams without an extra commissioning effort of the parameters of the model. For this purpose two energy-dependent wedge multiplication factors have been introduced to be applied for portal images taken with and without a patient/phantom in the beam. These wedge multiplication factors were derived from EPID and ionization chamber measurements at the EPID level for wedged and nonwedged beams, both with and without a polystyrene slab phantom in the beam. This method was verified for an EPID dosimetry model used for wedged beams at three photon beam energies (6, 10, and 18 MV) by comparing dose values reconstructed in a phantom with data provided by a treatment planning system (TPS), as a function of field size, depth, and off-axis distance. Generally good agreement, within 2%, was observed for depths between dose maximum and 15 cm. Applying the new model to EPID dose measurements performed during ten breast cancer patient treatments with wedged 6 MV photon beams showed that the average isocenter underdosage of 5.3% was reduced to 0.4%. Gamma-evaluation (global 3%/3 mm) of these in vivo data showed an increase in percentage of points with gamma

Background In contemporary positron emission tomography (PET)/computed tomography (CT) scanners, PET attenuation correction is performed by means of a CT-based attenuation map. Respiratory motion can however induce offsets between the PET and CT data. Studies have demonstrated that these offsets can cause errors in quantitative PET measures. The purpose of this study is to quantify the effects of respiration-induced CT differences on the attenuation correction of pulmonary 18-fluordeoxyglucose (FDG) 3D PET/CT in a patient population and to investigate contributing factors. Methods For 32 lung cancer patients, 3D-CT, 4D-PET and 4D-CT data were acquired. The 4D FDG PET data were attenuation corrected (AC) using a free-breathing 3D-CT (3D-AC), the end-inspiration CT (EI-AC), the end-expiration CT (EE-AC) or phase-by-phase (P-AC). After reconstruction and AC, the 4D-PET data were averaged. In the 4Davg data, we measured maximum tumour standardised uptake value (SUV)max in the tumour, SUVmean in a lung volume of interest (VOI) and average SUV (SUVmean) in a muscle VOI. On the 4D-CT, we measured the lung volume differences and CT number changes between inhale and exhale in the lung VOI. Results Compared to P-AC, we found −2.3% (range −9.7% to 1.2%) lower tumour SUVmax in EI-AC and 2.0% (range −0.9% to 9.5%) higher SUVmax in EE-AC. No differences in the muscle SUV were found. The use of 3D-AC led to respiration-induced SUVmax differences up to 20% compared to the use of P-AC. SUVmean differences in the lung VOI between EI-AC and EE-AC correlated to average CT differences in this region (ρ = 0.83). SUVmax differences in the tumour correlated to the volume changes of the lungs (ρ = −0.55) and the motion amplitude of the tumour (ρ = 0.53), both as measured on the 4D-CT. Conclusions Respiration-induced CT variations in clinical data can in extreme cases lead to SUV effects larger than 10% on PET attenuation correction. These differences were case specific and correlated to differences in CT number in the lungs.

Purpose To assess the usefulness of electronic portal imaging device (EPID)-based 3-dimensional (3D) transit dosimetry in a radiation therapy department by analyzing a large set of dose verification results. Methods and materials In our institution, routine in vivo dose verification of all treatments is performed by means of 3D transit dosimetry using amorphous silicon EPIDs. The total 3D dose distribution is reconstructed using a back-projection algorithm and compared with the planned dose distribution using 3D gamma evaluation. Dose reconstruction and gamma evaluation software runs automatically in our clinic, and analysis results are (almost) immediately available. If a deviation exceeds our alert criteria, manual inspection is required. If necessary, additional phantom measurements are performed to separate patient-related errors from planning or delivery errors. Three-dimensional transit dosimetry results were analyzed per treatment site between 2012 and 2014 and the origin of the deviations was assessed. Results In total, 4689 of 15,076 plans (31%) exceeded the alert criteria between 2012 and 2014. These alerts were patient-related and attributable to limitations of our back-projection and dose calculation algorithm or to external sources. Clinically relevant deviations were detected for approximately 1 of 430 patient treatments. Most of these errors were because of anatomical changes or deviations from the routine clinical procedure and would not have been detected by pretreatment verification. Although cone beam computed tomography scans yielded information about anatomical changes, their effect on the dose delivery was assessed quantitatively by means of 3D in vivo dosimetry. Conclusions EPID-based transit dosimetry is a fast and efficient dose verification technique. It provides more useful information and is less time-consuming than pretreatment verification measurements of intensity modulated radiation therapy and volumetric modulated arc therapy. Large-scale implementation of 3D transit dosimetry is therefore a powerful method to guarantee safe dose delivery during radiation therapy.

This document is the report of a task group of the AAPM and has been prepared primarily to advise medical physicists involved in the external-beam radiation therapy of patients with thoracic, abdominal, and pelvic tumors affected by respiratory motion. This report describes the magnitude of respiratory motion, discusses radiotherapy specific problems caused by respiratory motion, explains techniques that explicitly manage respiratory motion during radiotherapy and gives recommendations in the application of these techniques for patient care, including quality assurance (QA) guidelines for these devices and their use with conformal and intensity modulated radiotherapy. The technologies covered by this report are motion-encompassing methods, respiratory gated techniques, breath-hold techniques, forced shallow-breathing methods, and respiration-synchronized techniques. The main outcome of this report is a clinical process guide for managing respiratory motion. Included in this guide is the recommendation that tumor motion should be measured (when possible) for each patient for whom respiratory motion is a concern. If target motion is greater than 5 mm, a method of respiratory motion management is available, and if the patient can tolerate the procedure, respiratory motion management technology is appropriate. Respiratory motion management is also appropriate when the procedure will increase normal tissue sparing. Respiratory motion management involves further resources, education and the development of and adherence to QA procedures.

The use of electronic portal imaging devices (EPIDs) is a promising method for the dosimetric verification of external beam, megavoltage radiation therapy-both pretreatment and in vivo. In this study, a previously developed EPID back-projection algorithm was modified for IMRT techniques and applied to an amorphous silicon EPID. By using this back-projection algorithm, two-dimensional dose distributions inside a phantom or patient are reconstructed from portal images. The model requires the primary dose component at the position of the EPID. A parametrized description of the lateral scatter within the imager was obtained from measurements with an ionization chamber in a miniphantom. In addition to point dose measurements on the central axis of square fields of different size, we also used dose profiles of those fields as reference input data for our model. This yielded a better description of the lateral scatter within the EPID, which resulted in a higher accuracy in the back-projected, two-dimensional dose distributions. The accuracy of our approach was tested for pretreatment verification of a five-field IMRT plan for the treatment of prostate cancer. Each field had between six and eight segments and was evaluated by comparing the back-projected, two-dimensional EPID dose distribution with a film measurement inside a homogeneous slab phantom. For this purpose, the y-evaluation method was used with a dose-difference criterion of 2% of dose maximum and a distance-to-agreement criterion of 2 mm. Excellent agreement was found between EPID and film measurements for each field, both in the central part of the beam and in the penumbra and low-dose regions. It can be concluded that our modified algorithm is able to accurately predict the dose in the midplane of a homogeneous slab phantom. For pretreatment IMRT plan verification, EPID dosimetry is a reliable and potentially fast tool to check the absolute dose in two dimensions inside a phantom for individual IMRT fields. Film measurements inside a phantom can therefore be replaced by EPID measurements.

PURPOSE: To quantify the effect of set-up errors and respiratory motion on dose distributions for non-small cell lung cancer (NSCLC) treatment. METHODS AND MATERIALS: Irradiations of 5 NSCLC patients were planned with 3 techniques, two (conformal radiation therapy (CRT) and intensity modulated radiation therapy (IMRT1)) with a homogeneous dose in the planning target volume (PTV) and a third (IMRT2) with dose heterogeneity. Set-up errors were simulated for gross target volume (GTV) and organs at risk (OARs). For the GTV, the respiration was also simulated with a periodical motion around a varying average. Two configurations were studied for the breathing motion, to describe the situations of free-breathing (FB) and respiration-correlated (RC) CT scans, each with 2 amplitudes (5 and 10 mm), thus resulting in 4 scenarios (FB_5, FB_10, RC_5 and RC_10). Five thousand treatment courses were simulated, producing probability distributions for the dosimetric parameters. RESULTS: For CRT and IMRT1, RC_5, RC_10 and FB_5 were associated with a small degradation of the GTV coverage. IMRT2 with FB_10 showed the largest deterioration of the GTV dosimetric indices, reaching 7% for Dmin at the 95% probability level. Removing the systematic error due to the periodic breathing motion was advantageous for a 10 mm respiration amplitude. The estimated probability of radiation pneumonitis and acute complication for the esophagus showed limited sensitivity to geometrical uncertainties. Dmax in the spinal cord and the parameters predicting the risk of late esophageal toxicity were associated to a probability up to 50% of violating the dose tolerances. CONCLUSIONS: Simulating the effect of geometrical uncertainties on the individual patient plan should become part of the standard pre-treatment verification procedure.

Purpose: Four-dimensional (4D) respiration-correlated imaging techniques can be used to obtain (respiration) artifact-free computed tomography (CT) images of the thorax. Current radiotherapy planning systems, however, do not accommodate 4D-CT data. The purpose of this study was to develop a simple, new concept to incorporate patient-specific motion information, using 4D-CT scans, in the radiotherapy planning process of lung cancer patients to enable smaller error margins. Methods and Materials: A single CT scan was selected from the 4D-CT data set. This scan represented the tumor in its time-averaged position over the respiratory cycle (the mid-ventilation CT scan). To select the appropriate CT scan, two methods were used. First, the three-dimensional tumor motion was analyzed semiautomatically to calculate the mean tumor position and the corresponding respiration phase. An alternative automated method was developed to select the correct CT scan using the diaphragm motion. Results: Owing to hysteresis, mid-ventilation selection using the three-dimensional tumor motion had a tumor position accuracy (with respect to the mean tumor position) better than 1.1 ± 1.1 mm for all three directions (inhalation and exhalation). The accuracy in the diaphragm motion method was better than 1.1 ± 1.1 mm. Conventional free-breathing CT scanning had an accuracy better than 0 ± 3.9 mm. The mid-ventilation concept can result in an average irradiated volume reduction of 20% for tumors with a diameter of 40 mm. Conclusion: Tumor motion and the diaphragm motion method can be used to select the (artifact-free) mid-ventilation CT scan, enabling a significant reduction of the irradiated volume.

Background and purpose Localisation images normally acquired to verify patient positioning also contain information about the patient's internal anatomy. The aim of this study was to investigate the anatomical changes observed in localisation images and examples of dosimetric consequences. Patients and methods Localisation images were obtained weekly prior to radiotherapy with an electronic portal imaging device (EPID). A series of ‘difference images' was created by subtracting the first localisation image from that of subsequent fractions. Images from 81 lung, 40 head and neck and 34 prostate cancer patients were classified according to the changes observed. Changes were considered relevant if the average pixel value over an area of at least 1cm 2 differed by more than 5%, to allow for variations in linac output and EPID signal. Two patients were selected to illustrate the dosimetric effects of relevant changes. Their plans were re-calculated with repeat CT scans acquired after 4 weeks of treatment and compared with the difference images of the corresponding days. Results Progressive changes were detected for 57% of lung and 37% of head and neck cancer patients studied. Random changes were observed in 37% of lung, 28% of head and neck and 82% of prostate cancer patients. For a lung case, an increase of 10.0% in EPID dose due to tumour shrinkage corresponded to an increase of 9.8% in mean lung dose. Gas pockets in the rectum region of the prostate case increased the EPID dose by 6.3%, and resulted in a decrease of the minimum dose to the planning target volume of 26.4%. Conclusions Difference images are an efficient means of qualitatively detecting anatomical changes for various treatment sites in clinical practice. They can be used to identify changes for a particular patient, to indicate if the dose delivered to the patient would differ from planning and to detect if there is a need for re-planning.

The feasibility of high precision radiotherapy to the bladder region is limited by bladder motion and volume changes. In the near future, we plan to begin treatment delivery of bladder cancer patients with the acquisition of a cone beam CT image on which the complete bladder will be semi-automatically localized. Subsequently, a bladder shape model that was developed in a previous study will be used for bladder localization and for the prediction of shape changes in the time interval between acquisition and beam delivery. For such predictions, knowledge about urinary inflow rate is required. Therefore, a series of MR images was acquired over 1 h with time intervals of 10 min for 18 healthy volunteers. To gain insight in the reproducibility of the bladder shape over longer periods of time, two additional MRI series were recorded for 10 of the volunteers. To a good approximation, the bladder volume increased linearly in time for all individuals. Despite receiving drinking instructions, we found a large variation in the inflow rate between individuals, ranging from 2.1 to 15 cc/min (mean value: 9 +/- 3 cc/min). In contrast, the intravolunteer variation was much smaller, with a mean standard deviation (SD) of 0.4 cc/min. The inflow rate was linearly correlated with age (negative slope). To study the reproducibility of the bladder shape, we compared bladder shapes of equal volume. For all individuals, the caudal part of the bladder was the most reproducible (variations

To study dose-effect relations of prostate implants with I-125 seeds, accurate knowledge of the dose distribution in the prostate is essential. Commonly, a post-implant computed tomography (CT) scan is used to determine the geometry of the implant and to delineate the contours of the prostate. However, the delineation of the prostate on CT slices is very cumbersome due to poor contrast between the prostate capsule and surrounding tissues. Transrectal Ultrasound (TRUS) on the other hand offers good visualization of the prostate but poor visualization of the implanted seeds. The purpose of this study was to investigate the applicability of combining CT with 3D TRUS by means of image fusion. The advantage of fused TRUS-CT imaging is that both prostate contours and implanted seeds will be well visible. In our clinic, post-implant imaging was realized by simultaneously acquiring a TRUS scan and a CT scan. The TRUS transducer was inserted while the patient was on the CT couch and the CT scan was made directly after the TRUS scan, with the probe still in situ. With the TRUS transducer being visible on both TRUS and CT images, the geometrical relationship between both image sets could be defined by registration on the transducer. Having proven the applicability of simultaneous imaging, the accuracy of this registration method was investigated by additional registration on visible seeds, after preregistration on the transducer. In 4 out of 23 investigated cases an automatic grey value registration on seeds failed for each of the investigated cost functions, and in 2 cases for both cost functions, due to poor visibility of the seeds on the TRUS scan. The average deviations of the seed registration with respect to the transducer registration were negligible. However, in a few individual cases the deviations were significant and probably due to movement of the patient between TRUS and CT scan. In case of a registration on the transducer it is important to avoid patient movement in-between the TRUS and CT scan and to keep the time in-between the scans as short as possible. It can be concluded that fusion of a CT scan and a simultaneously made TRUS scan by means of a three-dimensional (3D) transducer is feasible and accurate when performing a registration on the transducer, if necessary, fine-tuned by a registration on seeds. These fused images are likely to be of great value for post-implant dose distribution evaluations.

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.

BACKGROUND AND PURPOSE: The goal of this work is to develop and evaluate strategies to reduce the uncertainty in the prostate position and rectum shape that arises in the preparation stage of the radiation treatment of prostate cancer. PATIENTS AND METHODS: Nineteen prostate cancer patients, who were treated with 3-dimensional conformal radiotherapy, received each a planning CT scan and 8-13 repeat CT scans during the treatment period. We quantified prostate motion relative to the pelvic bone by first matching the repeat CT scans on the planning CT scan using the bony anatomy. Subsequently, each contoured prostate, including seminal vesicles, was matched on the prostate in the planning CT scan to obtain the translations and rotations. The variation in prostate position was determined in terms of the systematic, random and group mean error. We tested the performance of two correction strategies to reduce the systematic error due to prostate motion. The first strategy, the pre-treatment strategy, used only the initial rectum volume in the planning CT scan to adjust the angle of the prostate with respect to the left-right (LR) axis and the shape and position of the rectum. The second strategy, the adaptive strategy, used the data of repeat CT scans to improve the estimate of the prostate position and rectum shape during the treatment. RESULTS: The largest component of prostate motion was a rotation around the LR axis. The systematic error (1 SD) was 5.1 degrees and the random error was 3.6 degrees (1 SD). The average LR-axis rotation between the planning and the repeat CT scans correlated significantly with the rectum volume in the planning CT scan (r=0.86, P

Contains fulltext : 49013.pdf (Publisher’s version ) (Closed access) BACKGROUND AND PURPOSE: To evaluate the process of target volume delineation in lung cancer for optimization of imaging, delineation protocol and delineation software. PATIENTS AND METHODS: Eleven radiation oncologists (observers) from five different institutions delineated the Gross Tumor Volume (GTV) including positive lymph nodes of 22 lung cancer patients (stages I-IIIB) on CT only. All radiation oncologist-computer interactions were recorded with a tool called 'Big Brother'. For each radiation oncologist and patient the following issues were analyzed: delineation time, number of delineated points and corrections, zoom levels, level and window (L/W) settings, CT slice changes, use of side windows (coronal and sagittal) and software button use. RESULTS: The mean delineation time per GTV was 16 min (SD 10 min). The mean delineation time for lymph node positive patients was on average 3 min larger (P = 0.02) than for lymph node negative patients. Many corrections (55%) were due to L/W change (e.g. delineating in mediastinum L/W and then correcting in lung L/W). For the lymph node region, a relatively large number of corrections was found (3.7 corr/cm2), indicating that it was difficult to delineate lymph nodes. For the tumor-atelectasis region, a relative small number of corrections was found (1.0 corr/cm2), indicating that including or excluding atelectasis into the GTV was a clinical decision. Inappropriate use of L/W settings was frequently found (e.g. 46% of all delineated points in the tumor-lung region were delineated in mediastinum L/W settings). Despite a large observer variation in cranial and caudal direction of 0.72 cm (1 SD), the coronal and sagittal side windows were not used in 45 and 60% of the cases, respectively. For the more difficult cases, observer variation was smaller when the coronal and sagittal side windows were used. CONCLUSIONS: With the 'Big Brother' tool a method was developed to trace the delineation process. The differences between observers concerning the delineation style were large. This study led to recommendations on how to improve delineation accuracy by adapting the delineation protocol (guidelines for L/W use) and delineation software (double window with lung and mediastinum L/W settings at the same time, enforced use of coronal and sagittal views) and including FDG-PET information (lymph nodes and atelectasis).

Purpose: Previously, we developed an automatic three-dimensional gray-value registration (GR) method for fast prostate localization that could be used during online or offline image-guided radiotherapy. The method was tested on conventional computed tomography (CT) scans. In this study, the performance of the algorithm to localize the prostate on cone-beam CT (CBCT) scans acquired on the treatment machine was evaluated. Methods and Materials: Five to 17 CBCT scans of 32 prostate cancer patients (332 scans in total) were used. For 18 patients (190 CBCT scans), the CBCT scans were acquired with a collimated field of view (FOV) (craniocaudal). This procedure improved the image quality considerably. The prostate (i.e., prostate plus seminal vesicles) in each CBCT scan was registered to the prostate in the planning CT scan by automatic 3D gray-value registration (normal GR) starting from a registration on the bony anatomy. When these failed, registrations were repeated with a fixed rotation point locked at the prostate apex (fixed apex GR). Registrations were visually assessed in 3D by one observer with the help of an expansion (by 3.6 mm) of the delineated prostate contours of the planning CT scan. The percentage of successfully registered cases was determined from the combined normal and fixed apex GR assessment results. The error in gray-value registration for both registration methods was determined from the position of one clearly defined calcification in the prostate gland (9 patients, 71 successful registrations). Results: The percentage of successfully registered CBCT scans that were acquired with a collimated FOV was about 10% higher than for CBCT scans that were acquired with an uncollimated FOV. For CBCT scans that were acquired with a collimated FOV, the percentage of successfully registered cases improved from 65%, when only normal GR was applied, to 83% when the results of normal and fixed apex GR were combined. Gray-value registration mainly failed (or registrations were difficult to assess) because of streaks in the CBCT scans caused by moving gas pockets in the rectum during CBCT image acquisition (i.e., intrafraction motion). The error in gray-value registration along the left-right, craniocaudal, and anteroposterior axes was 1.0, 2.4, and 2.3 mm (1 SD) for normal GR, and 1.0, 2.0, and 1.7 mm (1 SD) for fixed apex GR. The systematic and random components of these SDs contributed approximately equally to these SDs, for both registration methods. Conclusions: The feasibility of automatic prostate localization on CBCT scans acquired on the treatment machine using an adaptation of the previously developed three-dimensional gray-value registration algorithm, has been validated in this study. Collimating the FOV during CBCT image acquisition improved the CBCT image quality considerably. Artifacts in the CBCT images caused by large moving gas pockets during CBCT image acquisition were the main cause for unsuccessful registration. From this study, we can conclude that CBCT scans are suitable for online and offline position verification of the prostate, as long as the amount of nonstationary gas is limited.

Target definition is a major source of errors in both prostate and head and neck external-beam radiation treatment. Delineation errors remain constant during the course of radiation and therefore have a large impact on the dose to the tumor. Major sources of delineation variation are visibility of the target including its extensions, disagreement on the target extension, and interpretation or lack of delineation protocols. The visibility of the target can be greatly improved with the use of multimodality imaging. Both in the head and neck and the prostate, computed tomography (CT)-magnetic resonance imaging coregistration decreases the target volume and its variability. CT-positron emission tomography delineation is promising for delineation in head and neck cancer. Despite the better visibility, a different interpretation of the target extension remains a major source of error. The use of coregistration of CT with a second modality, together with improved guidelines for delineation and an online anatomical atlas, increases agreement between observers in prostate, lung, and nasopharynx tumors. Delineation errors should not be treated differently from other geometrical errors. Similar margin recipes for the correction of setup errors and organ motion should be adapted to incorporate the effect of delineation errors. A calculation of a 3-dimensional clinical target volume-planning target volume margin incorporating delineation errors for the head and neck is around 6.1 to 9.7 mm. Given the good local control of IMRT with smaller margins and smaller pathological specimens, it is likely that the delineated CTV frequently overestimates the actual volume.

The minimum margins required to compensate for random geometric uncertainties in the delivery of radiotherapy treatment were determined for a spherical Clinical Target Volume, using an analytic model for the cumulative dose. Margins were calculated such that the minimum dose in the target would be no less than 95% of the prescribed dose for 90% of the patients. The dose distribution model incorporated two Gaussians, and could accurately represent realistic dose profiles for various target sizes in lung and water. It was found that variations in target size and tissue density lead to significant changes in the minimum margin required for random errors. The random error margin increased with tissue density, and decreased with target size. The required margins were similar for dose distributions of spherical and cylindrical symmetry. Significant dose outside the spherical high dose region, as could result from multiple incident beams, lead to an increased margin for the larger targets. We could confirm that the previously proposed margin of 0.7 times the standard deviation of the random errors is safe for standard deviations up to 5 mm, except for very small targets in dense material.