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Background and Purpose: Automatic delineations are often used as a starting point in the radiotherapy contouring workflow, after which they are manually reviewed and adapted. The purpose of this work was to quantify the geometric differences between automatic and manually edited breast clinical target volume (CTV) contours and evaluate the dosimetric impact of such differences., Materials and Methods: Eighty-seven automatically generated and manually edited contours of the left breast were retrieved from our clinical database. The automatic contours were obtained with a commercial auto-segmentation toolbox. The geometrical comparison was performed both locally and globally using the Dice score and the 95% Hausdorff distance (HD). Two treatment plans were generated for each patient and the obtained dosimetric differences were quantified using dose-volume histogram (DVH) parameters in the lungs, heart and planning target volume (PTV). An inter-observer variability study with four observers was performed on a subset of ten patients., Results: A median Dice score of 0.95 and a median 95% HD of 9.7 mm were obtained. Larger breasts were consistently under-contoured. Cranial under-contouring resulted in more than 5% relative decrease in PTV coverage in 15% of the patients while lateroposterior over-contouring increased the lung V 20Gy by a maximum of 2%. The inter-observer variability of the PTV coverage was smaller than the difference between PTV coverage achieved by the automatic and the consensus contours., Conclusions: Cranial under-contouring resulted in under-treatment, while lateroposterior over-contouring resulted in an increased lung dosage that is clinically irrelevant, showing the need to consider dose distributions to assess the clinical impact of local geometrical differences., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2019 The Authors.)

Background and Purpose: The scatter induced image quality degradation of cone-beam computed tomography (CBCT) prevents more advanced applications in radiotherapy. We evaluated the dose calculation accuracy on CBCT of various disease sites using different scatter mitigation strategies., Materials and Methods: CBCT scans of two patient cohorts (C1, C2) were reconstructed using a uniform (USC) and an iterative scatter correction (ISC) method, combined with an anti-scatter grid (ASG). Head and neck (H&N), lung, pelvic region, and prostate patients were included. To achieve a high accuracy Hounsfield unit and physical density calibrations were performed. The dose distributions of the original treatment plans were analyzed with the γ evaluation method using criteria of 1%/2 mm using the planning CT as the reference. The investigated parameters were the mean γ (γ mean ), the points in agreement (P γ≤1 ) and the 99th percentile (γ 1% )., Results: Significant differences between USC and ISC in C1 were found for the lung and prostate, where the latter using the ISC produced the best results with medians of 0.38, 98%, and 1.1 for γ mean , P γ≤1 and γ 1% , respectively. For C2 the ISC with ASG showed an improvement for all imaging sites. The lung demonstrated the largest relative increase in accuracy with improvements between 48% and 54% for the medians of γ mean , P γ≤1 and γ 1% ., Conclusions: The introduced method demonstrated high dosimetric accuracy for H&N, prostate and pelvic region if an ASG is applied. A significantly lower accuracy was seen for lung. The ISC yielded a higher robustness against scatter variations than the USC., (© 2019 The Authors.)

Purpose: Many authors suggest that extremity soft tissue sarcomas (ESTS) do not change significantly in size during preoperative radiation therapy (RT). This cone beam computed tomography study investigates the justification to deliver the entire course with 1 initial RT plan by observing anatomic changes during RT., Methods and Materials: Between 2015 and 2017, 99 patients with ESTS were treated with either curative (n = 80) or palliative intent (n = 19) with a regimen of at least 6 fractions. The clinical target volume to planning target volume margin was 1 cm. Action levels were assigned by radiation technicians. An extremity contour change of >1 cm and/or tumor size change >0.5 cm required a physician's action before the next fraction., Results: A total of 982 cone beam computed tomography logfiles were studied. In 41 of 99 patients, the dose coverage of the initial treatment plan was fully satisfactory throughout the RT course. However, action levels were observed in 58 patients (59%). In 41 of these 58 patients, a contour increase of 5 to 23 mm was noted (29 tumor size increase only, 3 extremity contour increase, and 9 both). In 21 of 58 patients, a decrease of 5 to 33 mm was observed (20 tumor size decrease only and 1 tumor size decrease and extremity contour decrease). In 4 cases, contours initially increased and subsequently decreased. In 33 of 41 patients with increasing contours, the dose distribution adequately covered gross tumor volume because of the 1 cm planning target volume margin applied. For the remaining 8 patients (8%), the plan needed to be adapted., Conclusions: ESTS volumes may change substantially during RT in 59% of all patients, leading to plan adaptations resulting from increased volumes in 8%. Daily critical observation of these patients is mandatory to avoid geographic misses because of increases in size and overdosing of normal tissues when masses shrink., (Copyright © 2018 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: In recent decades, outcomes of patients with head and neck cancer (HNC) have improved as a result of implementing several strategies, such as chemoradiation. However, these improvements were achieved at the cost of increased toxicity. One way to reduce radiation-related toxicity is by reducing the margins., Materials and Methods: Between 2013 and 2016, 206 consecutive patients were treated with CTV-PTV margin of 5 mm and subsequently 208 patients with 3 mm margin. This study evaluates the impact of reducing clinical target volume (CTV) to planning target volume (PTV) margin on outcome and toxicity., Results: All patients were treated with volumetric modulated arc therapy (VMAT) with daily-image guidance using cone-beam CT (CBCT). Overall acute grade 3 toxicity was significantly lower in 3 mm-group, compared to 5 mm-group (53.8% vs. 65%, respectively, p = 0.032). The same was true for acute grade 3 mucositis (30.8% vs. 42.2%, p = 0.008) and for acute grade 3 dysphagia (feeding tube-dependence) (22.1% vs. 33.5%, p = 0.026). The incidence of ongoing feeding tube-dependence after 3 months of radiotherapy was 11.1% and 20.4%, respectively (p = 0.012). The 2-year incidence of late grade ≥2 xerostomia was 15.8% and 19.4% (p = 0.8). The 2-year loco-regional control rates of patients treated in 3 mm and 5 mm-groups were 79.9% and 79.2% (p = 1.0). The figures for disease-free survival were 71.5% and 72.7 (p = 0.6) and for overall survival were 75.2% and 75.1% (p = 0.9)., Conclusion: Reducing the CTV-PTV margin from 5 to 3 mm combined with daily CBCT-guided VMAT reduced the severity, frequency, and duration of radiation-related toxicity without jeopardizing outcome., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Purpose: Day-to-day shape variation in the rectum CTV results in considerable geometric uncertainties during rectal cancer radiotherapy. To ensure coverage a large CTV-to-PTV margin is required. The purpose of this study was to increase the accuracy of treatment delivery by building a population based library of planning CTVs for rectal cancer patients and to evaluate its potential for rectum PTV margin and PTV volume reduction., Methods: Analysis was done retrospectively on 33 early-stage rectal cancer patients with daily repeat CTs who received short-course pre-operative radiotherapy in 5 fractions of 5 Gy. We created signed distance maps from the planning rectum CTV to each of the repeat CTVs, from which we calculated the group mean, systematic and random error. The correlation between different regions of the rectum CTV was analyzed and used in combination with the distance maps to create the library of nine planning CTVs. For each of the repeat CTVs the best fitting CTV structure in the library was automatically selected defined by the plan that minimized the mean absolute distance between the repeat and library CTV. Residual distance maps were calculated from which a new PTV margin was constructed. Bootstrapping was performed on the margin difference to assess its significance., Results: Residual errors were found to decrease with the number of plans in the library, but adding more than five plans yields negligible further error reduction. Margin reduction of up to 50% was achieved at the upper-anterior site of the mesorectum. The average PTV volume decreased by 15.5% when a library is introduced., Conclusions: A library of plans strategy for rectal cancer based on population statistics is feasible and results in a considerably reduced average rectum PTV volume compared to conventional radiotherapy., (© 2018 American Association of Physicists in Medicine.)

Background and Purpose: The clinical target volume (CTV) in radiotherapy of rectal cancer is subject to large deformations. With a plan library strategy, the treatment may be adapted to these deformations. The purpose of this study was to determine feasibility and consistency in plan selection for a plan library strategy in radiotherapy of rectal cancer., Material and Methods: Thirty rectal cancer patients were included in this retrospective study with in total 150 CBCT scans. A library of CTVs was constructed with in-house built software using population statistics on daily rectal deformations. The library consisted of five plans based on: the original CTV, two larger, and two smaller CTVs. An inter-observer study (study-I) was performed to test the consistency in plan choices between four observers (all RTTs). After five months the observers were asked to re-evaluate (study-II) the same set of scans based on refined guidelines., Results: In study-I the observers reached accordance with the majority choice in 69% of cases. This improved to 87% in study-II. The consensus meeting revealed that inconsistency in choices mainly arose from inadequate instructions, which were later clarified and formulated more accurately., Conclusion: Plan selection based on daily CBCT scans for rectal cancer patients is feasible, and can be performed consistently by well-trained RTTs., (© 2018 The Authors.)

Background & Purpose: With the introduction of more conformal techniques for breast cancer radiation therapy (RT), motion management is becoming increasingly important. We studied the breast-shape variability during RT after breast-conserving surgery (BCS)., Materials & Methods: Planning computed tomography (CT) and follow-up cone-beam CT (CBCT) scans were available for 71 fractions of 17 patients undergoing RT after BCS. First, the CT and the CBCT scans were registered on bones. Subsequently, breast-contour data were generated. The CBCT contours were analyzed in 3D in terms of deviations (mean and standard deviation) relative to the contour of the CT scan for the upper medial, lower medial, upper lateral, and lower lateral breast quadrants, and the axilla., Results: Regional systematic and random standard deviations of the breast quadrants varied between 1.5 and 2.1 mm and 1.0-1.6 mm, respectively, and were larger for the axilla (3.0 mm). An absolute average shape change of  ≥4.0 mm in at least one region was present in 21/71 fractions (30%), predominantly in breast volumes > 800 cc ( p  = <0.01). Furthermore, seroma was associated with larger shape changes ( p  = 0.04)., Conclusions: Breast-shape variability varies between anatomic locations. Changes in the order of 4 mm are frequently observed during RT, especially for large breasts. This should be taken into account in the development of protocols for partial breast irradiation and boost treatment., (© 2018 The Authors.)

Background: Plan adaptation during the course of (chemo)radiotherapy of H&N cancer requires repeat CT scanning to capture anatomy changes such as parotid gland shrinkage. Hydration, applied to prevent nephrotoxicity from cisplatin, could temporarily alter the hydrogen balance and hence the captured anatomy. The aim of this study was to determine geometric changes of parotid glands as function of hydration during chemoradiotherapy compared to a control group treated with radiotherapy only., Methods: This study included an experimental group (n = 19) receiving chemoradiotherapy, and a control group (n = 19) receiving radiotherapy only. Chemoradiotherapy patients received cisplatin with 9 l of saline solution during hydration in the first, fourth and seventh week. The delineations of the parotid glands on the planning CT scan were automatically propagated to Cone Beam CT scans using deformable image registration. Relative volume and position of the parotid glands were determined at the second chemotherapy cycle (week four) and at fraction 35., Results: When saline solution was administrated, the volume temporarily increased on the first day (7.2 %, p < 0.001), second day (10.8 %, p < 0.001) and third day (7.0 %, p = 0.016). The gland positions shifted lateral, the distance between glands increased on the first day with 1.5 mm (p < 0.001), on the second day 2.2 mm (p < 0.001). At fraction 35, with both groups the mean shrinkage was 24 % ± 11 % (1SD) and the mean medial distance between the parotid glands decreased by 0.47 cm ± 0.27 cm., Conclusions: Hydration significantly modulates parotid gland geometry. Unless, in the context of adaptive RT, a repeat CT scan is timed during a chemotherapy cycle, these effects are of minor clinical relevance.

Purpose: Mobility of the seminal vesicles relative to the prostate challenges adequate dose coverage. The aim of this study was to assess the impact of tumour invasion on SV mobility., Methods and Materials: Three groups of 30 prostate cancer patients with (1) no invasion on MR, (2) minimal invasion (<5mm), and (3) extensive invasion (>5mm) were studied. Translations and rotations of the SV were measured with CBCT and compared between the three groups., Results: In the extensive group the random SV translations were significantly lower in comparison with the no invasion group in the LR: 0.15 vs 0.16 cm (p=0.015), CC: 0.17 vs 0.23 cm (p=0.004) and AP direction: 0.19 vs 0.26 cm (p=0.002). Also the random SV rotation on the LR axis was significantly lower: 5.2 vs 6.3° (p=0.035). In comparison with the minimal invasion group the random SV translations were significantly lower in the extensive group in the CC: 0.17 vs 0.24 cm (p=0.001) and AP direction 0.19 vs 0.31 cm (p=0.007) and for the rotation on the LR axis: 5.2 vs 6.5° (p=0.043)., Conclusion: Increasing tumour invasion in the SV reduces the mobility of the SV, however the mobility remains considerable., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background and Purpose: Conebeam-CT (CBCT) guidance is often used for setup verification of lung cancer patients treated with radiotherapy. The purpose of this study was to quantify intra-thoracic anatomical changes (ITACs) during the radiotherapy treatment and to hand over a decision support system to guide the radiation therapy technologist and radiation oncologist in prioritizing these changes., Materials and Methods: 1793 CBCT-scans of 177 lung cancer patients treated in 2010 in our institute with radical radiotherapy were evaluated. Our decision support system: "the Traffic Light Protocol", was retrospectively applied to these CBCT-scans. The protocol has four levels: red (immediate action before treatment), orange (action before next fraction), yellow (no action required) and green (no change)., Results: In 128 patients (72%), 210 ITACs were observed with a maximum level of red, orange and yellow in 12%, 36% and 24% respectively. Types of observed ITACs were, tumor regression (35%), tumor baseline shift (27%), changes in atelectasis (19%), tumor progression (10%), pleural effusion (6%) and infiltrative changes (3%)., Conclusions: ITACs have been observed in 72% of all lung cancer patients during the course of radical radiotherapy. The clinical relevance of the proposed ITAC classification in lung radiotherapy needs to be validated in a prospective analysis., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Purpose: To establish the reproducibility of the MRI-defined spinal cord position within the spinal canal., Materials and Methods: We acquired T1- and T2-weighted MRI scans of 15 volunteers on spine levels C7, T8 or L2. The scan protocol was repeated several times for different postures and time intervals. We determined the spinal cord shift (LR, AP, CC) using a rigid, grey value, vertebral body registration, followed by a spinal cord registration. We tested the sensitivity of our method, introducing artificial spinal cord shifts by varying the size and direction of the water-fat-shift (WFS) of the MR sequences., Results: The spinal cord position on MRI is reproducible within approximately 0.2mm SD (LR, AP) and 0.7mm SD (CC) when reproducing the posture on the same day, as well as several weeks later. However, when comparing different postures, shifts of ∼1.5mm were found. Varying the WFS difference between scans (0.6-3.0mm) induced equivalent virtual spinal cord shifts (0.5-2.5mm)., Conclusions: Displacement of the spinal cord inside the spinal canal may occur as a result of posture change. Considering the total geometric accuracy of spine SBRT, MRI-defined spinal cord position is sufficiently reproducible and requires no addition to the typical setup-and-intrafraction motion PRV margin if posture is identical throughout the RT process., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Purpose: To compare inter- and intra-fraction bladder volume variations and bladder wall motion during radiotherapy (RT) for bladder cancer with full and empty bladder protocols., Materials and Methods: Bladder volumes, filling rates and bladder wall movement were retrospectively analyzed for 24 patients with at least 4 sets of delineable pre and post treatment cone beam CT (CBCT)-scans. Eight patients were treated with an 'empty bladder' (EB) protocol and sixteen patients with a 'full bladder' (FB) protocol., Results: 24 planning CT-scans and 356 CBCT-scans (178 sets) were analyzed. The average time between pre and post irradiation CBCT was 8min (range 6-18min). Median filling rate was 1.94ml/min and did not differ between EB and FB. Random variation in bladder volume and inter-fraction wall movement was slightly but not significantly larger for FB, whereas intra-fraction bladder wall movement was slightly but not significantly smaller for FB. The largest inter- and intra-fraction bladder wall movement was found in the cranial anterior direction., Conclusion: Empty and full bladder protocols show similar inter- and intra-fraction wall motion, and therefore treatment choices could be purely based on organ at risk criteria., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Purpose: To investigate the heart position variability in deep-inspiration breath-hold (DIBH) radiation therapy (RT) for breast cancer when 3D surface imaging would be used for monitoring the BH depth during treatment delivery. For this purpose, surface setup data were compared with heart setup data., Materials and Methods: Twenty patients treated with DIBH-RT after breast-conserving surgery were included. Retrospectively, heart registrations were performed for cone-beam computed tomography (CBCT) to planning CT. Further, breast-surface registrations were performed for a surface, captured concurrently with CBCT, to planning CT. The resulting setup errors were compared with linear regression analysis. Furthermore, geometric uncertainties of the heart (systematic [Σ] and random [σ]) were estimated relative to the surface registration. Based on these uncertainties planning organ at risk volume (PRV) margins for the heart were calculated: 1.3Σ-0.5σ., Results: Moderate correlation between surface and heart setup errors was found: R(2)=0.64, 0.37, 0.53 in left-right (LR), cranio-caudal (CC), and in anterior-posterior (AP) direction, respectively. When surface imaging would be used for monitoring, the geometric uncertainties of the heart (cm) are [Σ=0.14, σ=0.14]; [Σ=0.66, σ=0.38]; [Σ=0.27, σ=0.19] in LR; CC; AP. This results in PRV margins of 0.11; 0.67; 0.25 cm in LR; CC; AP., Conclusion: When DIBH-RT after breast-conserving surgery is guided by the breast-surface position then PRV margins should be used to take into account the heart-position variability relative to the breast-surface., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Purpose: Bladder tumor delineation and localization during treatment are challenging problems in radiotherapy for bladder cancer. The purpose of this study is to investigate improvement of tumor delineation by the fusion of cystoscopy images with the planning CT-scan using lipiodol markers injected around the visible tumor during cystoscopy., Methods: A registration method was developed for the fusion of cystoscopy images with a planning CT-scan and was tested on a phantom and retrospectively on the imaging data of four bladder cancer patients. For the patients, small deposits of lipiodol were injected at the visible margin of the tumor or previous transurethral resection site during cystoscopy. These deposits were clearly visible on the planning CT-scan and served as markers for both tumor delineation and image guidance of the radiotherapy treatment. Here, the markers were used for the registration of cystoscopy images with the planning CT-scan. The registration procedure works as follows: First, coarse registrations were made to orient the cystoscopy image correctly, using the center of gravity of the markers, the center of the CT bladder, and one of N markers as fiducial points in a point matching procedure. Starting from these N orientations, full registrations are performed taking lens deformation into account. Since a cystoscopy image is 2D, each pixel corresponds to a line-of-sight. The distances between the CT markers and the lines-of-sight of the cystoscopy markers were minimized. The final cost function (the root mean square distance between corresponding CT markers and lines-of-sight) was used to quantify the quality of the registration. The registration with the lowest final cost was considered to represent the correct orientation. The CT-based tumor delineation was finally backprojected onto the cystoscopy image., Results: The fusion of cystoscopy images with a planning CT-scan succeeded for the phantom and three out of four patients. The fiducial registration error (FRE) for the phantom image registration based on five markers was 1.1 mm, while the target registration error was 1.2-1.7 mm. The FREs for the patient images were 0.1-3.6 mm. The registration procedure failed for one patient, since it was not possible to indicate unambiguously the corresponding lipiodol marker locations in the cystoscopy image and the planning CT-scan. The difference between the CT and cystoscopy defined tumor outlines clearly exceeded the registration accuracy., Conclusions: Registration of cystoscopy images and planning CT-scan is feasible and allows for improvement of tumor delineation. However, the lipiodol injection protocol needs to be improved to facilitate identification of markers on both cystoscopy images and planning CT-scans.

A procedure is described using diagnostic CT and/or MRI scans to simulate treatment fields for painful vertebral metastases. Cone beam CT guidance subsequently corrects patient setup. Our first 100 patients are analyzed and compared to another 100 patients after conventional simulation. This procedure proved to be quick and patient friendly., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Purpose: To investigate the applicability of 3-dimensional (3D) surface imaging for image guidance in deep-inspiration breath-hold radiation therapy (DIBH-RT) for patients with left-sided breast cancer. For this purpose, setup data based on captured 3D surfaces was compared with setup data based on cone beam computed tomography (CBCT)., Methods and Materials: Twenty patients treated with DIBH-RT after breast-conserving surgery (BCS) were included. Before the start of treatment, each patient underwent a breath-hold CT scan for planning purposes. During treatment, dose delivery was preceded by setup verification using CBCT of the left breast. 3D surfaces were captured by a surface imaging system concurrently with the CBCT scan. Retrospectively, surface registrations were performed for CBCT to CT and for a captured 3D surface to CT. The resulting setup errors were compared with linear regression analysis. For the differences between setup errors, group mean, systematic error, random error, and 95% limits of agreement were calculated. Furthermore, receiver operating characteristic (ROC) analysis was performed., Results: Good correlation between setup errors was found: R(2)=0.70, 0.90, 0.82 in left-right, craniocaudal, and anterior-posterior directions, respectively. Systematic errors were ≤0.17 cm in all directions. Random errors were ≤0.15 cm. The limits of agreement were -0.34-0.48, -0.42-0.39, and -0.52-0.23 cm in left-right, craniocaudal, and anterior-posterior directions, respectively. ROC analysis showed that a threshold between 0.4 and 0.8 cm corresponds to promising true positive rates (0.78-0.95) and false positive rates (0.12-0.28)., Conclusions: The results support the application of 3D surface imaging for image guidance in DIBH-RT after BCS., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: To quantify set-up uncertainties during voluntary deep inspiration breath hold (DIBH) radiotherapy using 3D-surface imaging in patients with left sided breast cancer., Material and Methods: Nineteen patients were included. Cone-beam CT-scan (CBCT) was used for online set-up correction while patients were instructed to perform a voluntary DIBH. The reproducibility of the DIBH during treatment was monitored with 2D-fluoroscopy and portal imaging. Simultaneously, a surface imaging system was used to capture 3D-surfaces throughout CBCT acquisition and delivery of treatment beams. Retrospectively, all captured surfaces were registered to the planning-CT surface. Interfraction, intra-fraction and intra-beam set-up variability were quantified in left-right, cranio-caudal and anterior-posterior direction., Results: Inter-fraction systematic (Σ) and random (σ) translational errors (1SD) before and after set-up correction were between 0.20-0.50 cm and 0.09-0.22 cm, respectively, whereas rotational Σ and σ errors were between 0.08 and 1.56°. The intra-fraction Σ and σ errors were ≤ 0.14 cm and ≤ 0.47°. The intra-beam SD variability was ≤ 0.08 cm and ≤ 0.28° in all directions., Conclusion: Quantification of 3D set-up variability in DIBH RT showed that patients are able to perform a very stable and reproducible DIBH within a treatment fraction. However, relatively large inter-fraction variability requires online image guided set-up corrections., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Purpose: To investigate the accuracy of surface imaging for monitoring intrafraction motion purposes in frameless stereotactic body radiotherapy (SBRT) of lung cancer by comparison with cone-beam computed tomography (CBCT)., Materials and Methods: Thirty-six patients (18 males, 18 females) were included. During each fraction, three CBCT scans were acquired; CBCT1: before treatment, CBCT2: after correction for tumor misalignment, and CBCT3: after treatment. Intrafraction motion was derived by registering CBCT2 and CBCT3 to the mid-ventilation planning CT scan. Surfaces were captured concurrently with CBCT acquisitions. Retrospectively, for each set of surfaces, an average surface was created: Surface1, Surface2, and Surface3. Subsequently, Surface3 was registered to Surface2 to assess intrafraction motion. For the differences between CBCT- and surface-imaging-derived 3D intrafraction motions, group mean, systematic error, random error and limits of agreement (LOA) were calculated., Results: Group mean, systematic and random errors were smaller for females than for males: 0.4 vs. 1.3, 1.3 vs. 3.1, and 1.7 vs. 3.3 mm respectively. For female patients deviations between CBCT-tumor- and 3D-surface-imaging-derived intrafraction motions were between -3.3 and 4.3 mm (95% LOA). For male patients these were substantially larger: -5.9-9.5mm., Conclusion: Surface imaging is a promising technology for monitoring intrafraction motion purposes in SBRT for female patients., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Purpose: To determine the use of surgical clips as a surrogate for localization of the excision cavity and to quantify the stability of the clips' positions during the course of external beam radiotherapy for breast cancer patients, using cone beam computed tomography (CBCT) scans., Methods and Materials: Twenty-one breast cancer patients with surgical clips placed in the breast excision cavity were treated in a supine position with 28 daily fractions. CBCT scans were regularly acquired for a setup correction protocol. Retrospectively, the CBCT scans were registered to the planning CT scans, using gray-value registration of the excision cavity region and chamfer matching of the clips. Subsequently, residual setup errors (systematic [Σ] and random [σ]) of the excision cavity were estimated relative to the clips' registration. Finally, the stability of the clips' positions were quantified as the movement of each separate clip according to the center of gravity of the excision cavity., Results: When clips were used for online setup corrections, the residual errors of the excision cavity were Σ(left-right) = 1.2, σ(left-right) = 1.0; Σ(cranial-caudal)  = 1.3, σ(cranial-caudal) = 1.2; and Σ(anterior-posterior)  = 0.7, σ(anterior-posterior) = 0.9 mm. Furthermore, the average distance (over all patients) between the clips and centers of gravity of the excision cavities was 18.8 mm (on the planning CT) and was reduced to 17.4 mm (measured on the last CBCT scan)., Conclusion: Clips move in the direction of the center of gravity of the excision cavity, on average, 1.4 mm. The clips are good surrogates for locating the excision cavity and providing small residual errors., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Purpose: Three boost radiotherapy (RT) techniques were compared to evaluate the dosimetric effect of seroma reduction during RT after breast-conserving surgery (BCS)., Materials and Methods: Twenty-one patients who developed seroma after BCS were included. Each patient underwent three CT scans: one week before RT (CT(-1)), in the third (CT(3)) and fifth (CT(5)) week of RT. For each patient, three plans were generated. (1) SEQ: whole breast irradiation planned on CT(-1,) sequential boost planned on CT(5), (2) SIB: simultaneous integrated boost planned on CT(-1), (3) SIB adaptive radiation therapy (SIB-ART): planned on CT(-1) and re-planned on CT(3). Irradiated volumes, mean lung (MLD) and maximum heart dose (HD(max)) were projected and compared on CT(5)., Results: On average 62% seroma reduction during RT was observed. Volumes receiving ≥ 107% of prescribed whole breast dose were significantly smaller with SIB-ART compared to SEQ and SIB. The undesired volume receiving ≥ 95% of prescribed total dose was also significantly smaller with SIB-ART. For SEQ, SIB-ART and SIB, respectively, small but significant differences were found in MLD (4.2 vs. 4.6 vs. 4.7 Gy) and in HD(max) for patients with left-sided breast cancer (39.9 vs. 35.8 vs. 36.9 Gy)., Conclusions: This study demonstrates a dosimetric advantage for patients with seroma when simultaneous integrated boost is used with re-planning halfway through treatment., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

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-guided radiotherapy for bladder cancer patients, i.e., by prediction short-term bladder deformation.

Purpose: To evaluate the feasibility, cardiac dose reduction, and the influence of the setup error on the delivered dose for fluoroscopy-guided deep inspiration breath hold (DIBH) irradiation using a cone-beam CT for irradiation of left-sided breast cancer patients., Methods and Materials: Nineteen patients treated according to the DIBH protocol were evaluated regarding dose to the ipsilateral breast (or thoracic wall), heart, (left ventricle [LV] and left anterior descending artery [LAD]), and lung. The DIBH treatment plan was compared to the free-breathing (FB) treatment planning and to the dose data in which setup error was taken into account (i.e., actual delivered dose)., Results: The largest setup variability was observed in the direction perpendicular to the RT field (μ = -0.8 mm, Σ = 2.9 mm, σ = 2.0 mm). The mean (D(mean)) and maximum (D(max)) doses of the DIBH treatment plan was significantly lower compared with the FB treatment plan for the heart (34% and 25%, p < 0.001), LV (71% and 28%, p < 0.001), and LAD (52% and 39.8%, p < 0.001). For some patients, large differences were observed between the heart D(max) according to the DIBH treatment plan and the actual delivered dose (up to 71%), although D(max) was always smaller than the planned FB dose (mean group reduction = 29%, p < 0.001)., Conclusion: The image-guided DIBH treatment protocol is a feasible irradiation method with small setup variability that significantly reduces the dose to the heart, LV, and LAD., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Purpose: To quantify the differences in setup errors measured with the cone-beam computed tomography (CBCT) and electronic portal image devices (EPID) in breast cancer patients., Methods and Materials: Repeat CBCT scan were acquired for routine offline setup verification in 20 breast cancer patients. During the CBCT imaging fractions, EPID images of the treatment beams were recorded. Registrations of the bony anatomy for CBCT to planning CT and EPID to digitally reconstructed-radiographs (DRRs) were compared. In addition, similar measurements of an anthropomorphic thorax phantom were acquired. Bland-Altman and linear regression analysis were performed for clinical and phantom registrations. Systematic and random setup errors were quantified for CBCT and EPID-driven correction protocols in the EPID coordinate system (U, V), with V parallel to the cranial-caudal axis and U perpendicular to V and the central beam axis., Results: Bland-Altman analysis of clinical EPID and CBCT registrations yielded 4 to 6-mm limits of agreement, indicating that both methods were not compatible. The EPID-based setup errors were smaller than the CBCT-based setup errors. Phantom measurements showed that CBCT accurately measures setup error whereas EPID underestimates setup errors in the cranial-caudal direction. In the clinical measurements, the residual bony anatomy setup errors after offline CBCT-based corrections were Σ(U) = 1.4 mm, Σ(V) = 1.7 mm, and σ(U) = 2.6 mm, σ(V) = 3.1 mm. Residual setup errors of EPID driven corrections corrected for underestimation were estimated at Σ(U) = 2.2mm, Σ(V) = 3.3 mm, and σ(U) = 2.9 mm, σ(V) = 2.9 mm., Conclusion: EPID registration underestimated the actual bony anatomy setup error in breast cancer patients by 20% to 50%. Using CBCT decreased setup uncertainties significantly., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Purpose: To investigate the stability of a novel type of markers used in partial bladder tumor irradiation and tumor deformation as indicated by the markers., Materials and Methods: In 15 patients with solitary bladder cancer, lipiodol was injected in the bladder wall during flexible cystoscopy to identify the tumor. A planning CT scan was made, followed by daily cone-beam CT (CBCT) scans during treatment. To study the accuracy of using these markers for image guidance, uncertainties U1 and U2 were calculated, which were defined as the difference between submask registration (covering single marker) and the average of all submask registrations and the difference between the submask registration and the general mask registration (including all markers), respectively. Finally, to study tumor deformation, the relative movement of each marker pair was correlated with the relative bladder volume (RBV)., Results: The analyzed patients had 2.3 marker injections on average. The lipiodol spot size was 0.72 +/- 1.1 cm(3). The intensity of spots in both CT and CBCT was significantly higher than the surrounding bladder tissue. The uncertainties U1 and U2 were comparable, and the uncertainties in left-right direction (0.14-0.19 cm) were smaller than those in cranial-caudal and anterior-posterior directions (0.19-0.32 cm). The relative marker movement of within-zone marker pairs was much smaller (and has less dependence on the RBV) than across-zones marker pairs., Conclusions: Lipiodol markers are a feasible method to track bladder tumor by using online CBCT. Tumor deformation is observed, especially for tumors that cross the defined bladder zones.

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 5mm/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 5mm/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., (Copyright 2009 Elsevier Ireland Ltd. All rights reserved.)

Background and Purpose: To demonstrate the feasibility of back-projection portal dosimetry for accurate 3D dosimetric verification of volumetric-modulated arc therapy (VMAT), pre-treatment as well as in vivo., Materials and Methods: Several modifications to our existing approach were implemented to make the method applicable to VMAT: (i) gantry angle-resolved data acquisition, (ii) calculation of the patient transmission, (iii) compensation for detector 'flex' and (iv) 3D dose reconstruction and evaluation., Results: Planned and EPID-(Electronic Portal Image Detector)-reconstructed dose distributions show good agreement for pre-treatment verification of two prostate, a stereotactic lung and a head-and-neck VMAT plan and for in vivo verification of VMAT treatments of prostate and lung cancer. Averaged over pre-treatment verifications, planned and measured isocentre dose ratios were -1.2% (range [-4.7%,1.8%]). 3D gamma analysis (3% maximum dose, 3mm) revealed mean gamma gamma(mean)=0.37 [0.34,0.39], maximum 1% gamma gamma(1%)=0.72 [0.66,0.81] and percentage of points with gamma1 P(gamma)(1)=99% [97%,100%]. For in vivo verification, the average isocentre dose ratio was -1.2% [-0.8%,-1.7%], gamma(mean)=0.52 [0.40,0.64], gamma(1%)=0.92 [0.76,1.08] and P(gamma)(1)=96% [93%,100%]., Conclusions: Our portal dosimetry method was successfully adapted for verification of VMAT treatments, pre-treatment as well as in vivo., (Copyright 2010 Elsevier Ireland Ltd. All rights reserved.)

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 quantify the day-to-day target volume shape variation in rectal-cancer patients treated with preoperative 5x5Gy radiotherapy., Materials and Methods: For 27 patients a prone position plan-CT (pCT) and five daily pre-treatment cone-beam-CT (CBCT) scans were acquired. A sub-region of the CTV (MesoRect, anus up to the cranial end of the mesorectal-fascia) was delineated on all scans. The MesoRect deformation was quantified by the distance between pCT- and CBCT-delineations and was stored in surface-maps. Finally, the influence of bladder and rectum filling on MesoRect deformation was evaluated. Data were analyzed for male and female patients separately., Results: A large range of systematic and random deformations, 1-7mm (1SD), on different areas of the MesoRect were found. The maximum deformations were located at the upper-anterior-side of the MesoRect. For females the errors were up to 3mm larger than for males. Small correlations, r(2)0.4, were found with changes in bladder volume. Larger correlations, r(2)0.7, were found for rectal volume in a distinctive area in the upper-half of the MesoRect., Conclusions: Substantial and heterogeneous deformations of the MesoRect were found. Therefore different PTV margins in positions along the cranio-caudal axis, in the anterior-posterior direction. Margins should also be larger for female patients compared to male patients.

Purpose: To quantify the interfraction position variability of the excision cavity (EC) and to compare the rib and breast surface as surrogates for the cavity. Additionally, we sought to determine the required margin for on-line, off-line and no correction protocols in external beam radiotherapy., Methods and Materials: A total of 20 patients were studied who had been treated in the supine position for 28 daily fractions. Cone-beam computed tomography scans were regularly acquired according to a shrinking action level setup correction protocol based on bony anatomy registration of the ribs and sternum. The position of the excision area was retrospectively analyzed by gray value cone-beam computed tomography-to-computed tomography registration. Subsequently, three setup correction strategies (on-line, off-line, and no corrections) were applied, according to the rib and breast surface registrations, to estimate the residual setup errors (systematic [Sigma] and random [sigma]) of the excision area. The required margins were calculated using a margin recipe., Results: The image quality of the cone-beam computed tomography scans was sufficient for localization of the EC. The margins required for the investigated setup correction protocols and the setup errors for the left-right, craniocaudal and anteroposterior directions were 8.3 mm (Sigma = 3.0, sigma = 2.6), 10.6 mm (Sigma = 3.8, sigma = 3.2), and 7.7 mm (Sigma = 2.7, sigma = 2.9) for the no correction strategy; 5.6 mm (Sigma = 2.0, Sigma = 1.8), 6.5 mm (Sigma = 2.3, sigma = 2.3), and 4.5 mm (Sigma = 1.5, sigma = 1.9) for the on-line rib strategy; and 5.1 mm (Sigma = 1.8, sigma = 1.7), 4.8 mm (Sigma = 1.7, sigma = 1.6), and 3.3 mm (Sigma = 1.1, sigma = 1.6) for the on-line surface strategy, respectively., Conclusion: Considerable geometric uncertainties in the position of the EC relative to the bony anatomy and breast surface have been observed. By using registration of the breast surface, instead of the rib, the uncertainties in the position of the EC area were reduced.

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: 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: First, to quantify bladder-tumor motion in 3 dimensions during a 4-week to 5-week course of external radiotherapy. Second, to relate the motion to the tumor location on the bladder wall. Third, to extensively evaluate gross tumor volume (GTV) shape and volume changes during the course of the treatment., Methods and Materials: Multiple repeat computed tomography (CT) images were obtained for 21 bladder cancer patients. These scans were matched to the rigid bony anatomy. For each patient, the main direction and magnitude of the tumor movement was determined by use of principle-component analysis. To study GTV shape changes, all GTVs were registered to the GTV in the planning CT scan, and the residual shape errors were determined by measurement of edge variations perpendicular to the median surface., Results: Gross tumor volume translations were largest in cranial-caudal and anterior-posterior direction (SD, 0.1 to approximately 0.9 cm). The translations were strongly correlated with the tumor location on the bladder wall. The average value of the local standard deviations of the GTV shape ranged from 0.1 to approximately 0.35 cm., Conclusions: Despite large differences in bladder filling, variations in GTV shape were small compared with variations in GTV position. Geometric uncertainties in the GTV position depended strongly on the tumor location on the bladder wall.

Purpose: To evaluate the feasibility of adaptive radiotherapy (ART) in combination with a partial bladder irradiation., Methods and Materials: Twenty-one patients with solitary T1-T4 N0M0 bladder cancer were treated to the bladder tumor + 2 cm margin planning target volume (PTV(CONV)). During the first treatment week, five daily computed tomography (CT) scans were made immediately before or after treatment. In the second week, a volume was constructed encompassing the gross tumor volumes (GTVs) on the planning scan and the five CT scans (GTV(ART)). The GTV(ART) was expanded with a 1 cm margin for the construction of a PTV(ART). Starting in the third week, patients were treated to PTV(ART). Repeat CT scans were used to evaluate treatment accuracy., Results: On 5 of 91 repeat CT scans (5%), the GTV was not adequately covered by the PTV(ART). On treatment planning, there was only one scan in which the GTV was not adequately covered by the 95% isodose. On average, the treatment volumes were reduced by 40% when comparing PTV(ART) with PTV(CONV) (p < 0.0001)., Conclusion: The adaptive strategy for bladder cancer is an effective way to deal with treatment errors caused by variations in bladder tumor position and leads to a substantial reduction in treatment volumes.

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<0.3 cm in all cases). The cranial and posterior parts of the bladder was much less reproducible, with local SD values up to approximately 1.2 cm for bladders with a volume of 200 cc. These large long-term variations were primarily caused by changes in position and filling of the small bowel and rectum. However, for short time intervals, the rectal filling was (nearly) constant. Therefore, the reproducibility of urinary inflow, combined with the previously developed shape model gives us an excellent tool to predict short-term shape changes. We intend to use this tool for further improvement of image-guided radiotherapy for bladder cancer patients.

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.

Purpose: To evaluate the impact of different tabletops with or without a knee support on the position of the rectum, prostate, and bulb of the penis; and to evaluate the effect of these patient-positioning devices on treatment planning., Methods and Materials: For 10 male volunteers, five MRI scans were made in four different positions: on a flat tabletop with knee support, on a flat tabletop without knee support, on a rounded tabletop with knee support, and on a rounded tabletop without knee support. The fifth scan was in the same position as the first. With image registration, the position differences of the rectum, prostate, and bulb of the penis were measured at several points in a sagittal plane through the central axis of the prostate. A planning target volume was generated from the delineated prostates with a margin of 10 mm in three dimensions. A three-field treatment plan with a prescribed dose of 78 Gy to the International Commission on Radiation Units and Measurements point was automatically generated from each planning target volume. Dose-volume histograms were calculated for all rectal walls., Results: The shape of the tabletop did not affect the rectum and prostate position. Addition of a knee support shifted the anterior and posterior rectal walls dorsally. For the anterior rectal wall, the maximum dorsal shift was 9.9 mm (standard error of the mean [SEM] 1.7 mm) at the top of the prostate. For the posterior rectal wall, the maximum dorsal shift was 10.2 mm (SEM 1.5 mm) at the middle of the prostate. Therefore, the rectal filling was pushed caudally when a knee support was added. The knee support caused a rotation of the prostate around the left-right axis at the apex (i.e., a dorsal rotation) by 5.6 degrees (SEM 0.8 degrees ) and shifts in the caudal and dorsal directions of 2.6 mm (SEM 0.4 cm) and 1.4 mm (SEM 0.6 mm), respectively. The position of the bulb of the penis was not influenced by the use of a knee support or rounded tabletop. The volume of the rectal wall receiving the same dose range (e.g., 40-75 Gy) was reduced by 3.5% (SEM 0.9%) when a knee support was added. No significant differences were observed between the first and fifth scan (flat tabletop with knee support) for all measured points, thereby excluding time trends., Conclusions: The rectum and prostate were significantly shifted dorsally by the use of a knee support. The rectum shifted more than the prostate, resulting in a dose benefit compared with irradiation without knee support. The shape of the tabletop did not influence the rectum or prostate position.

The purpose of this study is to develop a model that quantifies in three dimensions changes in bladder shape due to changes in bladder and/or rectal volume. The new technique enables us to predict changes in bladder shape over a short period of time, based on known urinary inflow. Shortly prior to the treatment, the patient will be scanned using a cone beam CT scanner (x-ray volume imager) that is integrated with the linear accelerator. After (automated) delineation of the bladder, the model will be used to predict the short-term shape changes of the bladder for the time interval between image acquisition and dose delivery. The model was developed using multiple daily CT scans of the pelvic area of 19 patients. For each patient, the rigid bony structure in follow-up scans was matched to that of the planning CT scan, and the outer bladder and rectal wall were delineated. Each bladder wall was subdivided in 2500 domains. A fixed reference point inside the bladder was used to calculate for each bladder structure a "Mercator-like" 2D scalar map (similar to a height map of the globe), containing the distances from this reference point to each domain on the bladder wall. Subsequently, for all bladder shapes of a patient and for all domains on the wall individually, the distance to the reference point was fitted by a linear function of both bladder and rectal volume. The model uses an existing bladder structure to create a new structure via expansion (or contraction), until the expressed volume is reached. To evaluate the predictive power of the model, the jack-knife method was used. The errors in the fitting procedure depended on the part of the bladder and range from 0 to 0.5 cm (0.2 cm on average). It was found that a volume increase of 150 cc can lead to a displacement up to about 2.5 cm of the cranial part of the bladder. With the model, the uncertainty in the position of the bladder wall can be reduced down to a maximum value of about 0.5 cm in case the bladder volume increase is known. Furthermore, it was found that a change in rectal filling causes a shift of the bladder, while its shape is hardly influenced. In conclusion, we developed a model that describes the bladder shape and position as a function of the bladder volume and the rectal filling. The model accurately describes the complex shape of the bladder as it works on each domain of the bladder separately.

To assess the benefit of beam fringe (50%-90% dose level) sharpening for lung tumors, we performed a numerical simulation in which all geometrical errors (breathing motion, random and systematic errors) are included. A 50 mm diameter lung tumor, located centrally in a lung-equivalent phantom was modeled. Treatment plans were designed with varying number and direction of beams, both with and without the use of intensity modulation to sharpen the beam fringe. Field size and prescribed dose were varied under the constraint of a constant mean lung dose of 20 Gy, which yields a predicted complication probability of about 10%. After numerical simulation of the effect of setup errors and breathing, the resulting dose distribution was evaluated using the minimum dose and the equivalent uniform dose (EUD) in the moving clinical target volume (CTV). When the dose in the CTV was constrained between 95% and 107% of the prescribed dose, the maximum attainable EUD was 71 Gy for a four-field noncoplanar technique with simple conformal beams. When penumbra sharpening was applied using a single beam segment at the edge of the open field, this EUD could be raised to 87 Gy. For a hypothetical infinitely steep penumbra, further escalation to an EUD of 104 Gy was possible. When the dose in the CTV was not constrained, a large escalation of the EUD was possible compared to the constrained case. In this case, the maximum attainable EUD for open fields was 115 Gy, using the four-field noncoplanar technique. The benefit of penumbra sharpening was only modest, with no increase of the EUD for the single-segment technique and a small increase to 125 Gy for the infinitely steep penumbra. From these results we conclude that beam fringe sharpening in combination with field-size reduction leads to a large increase in EUD when a homogeneous target dose is pursued. Further escalation of the EUD is possible when the homogeneity constrained is relaxed, but the relative benefit of beam-fringe sharpening then decreases.

Purpose: To quantify in three dimensions the geometric uncertainties of bladder irradiation (i.e., uncertainties in target delineation, organ motion, and patient setup)., Methods and Materials: Pelvic CT images were obtained for 10 male bladder cancer patients. Apart from the initial planning CT scan, three follow-up scans were made for each of the patients. The bladder volumes in the planning CT scan were outlined by seven radiation oncologists. One observer also delineated the bladder volumes in the follow-up scans. Two-dimensional scalar maps of the interobserver variation and organ motion of the bladder surfaces were constructed. The setup errors were derived from the portal imaging results of the pooled group of bladder and prostate patients., Results: All bladder volumes were consistently outlined by all observers. Generally small variations occurred (1.5-3 mm, 1 SD), although in 50% of the patients, larger discrepancies were observed in discriminating the bladder from the base of the prostate. Analysis of the portal imaging data showed setup errors of up to 3 mm (1 SD). Organ motion is the predominant geometric uncertainty in the radiotherapy process (5 mm, 1 SD, at the cranial side of the bladder), although 9 of 10 patients were able to preserve a fairly reproducible bladder volume during the complete treatment course., Conclusion: Anisotropic margins between the clinical target volume and planning target volume are needed in conformal radiotherapy of the bladder. Especially at the cranial side of the bladder, larger margins are needed because of the impact of bladder shape variation.

Purpose: To define margins for systematic rotations and translations, based on known statistical distributions of these deviations., Methods and Materials: The confidence interval-based expansion method for translations, known as the "rolling ball algorithm," was extended to include rotations. This new method, which we call the Rotational and Translational Confidence Limit (RTCL) method, is exact for a point with arbitrary rotations and translations or for a finite shape with rotations only. The method was compared with two existing expansion methods: a rolling ball algorithm without rotations, and a convolution (blurring) method which included rotations. On the basis of these methods, planning target volumes (PTVs, expanded clinical target volumes [CTVs]) were constructed for a number of shapes (a sphere, a sphere with an extension, and three prostate cases), and evaluated in several ways by means of a Monte Carlo method. The accuracy of each method was measured by determining the probability of finding the CTV completely inside the PTV (P(CTVinPTV)), using parameters that yield a 90% probability for a sphere-shaped CTV without rotations. Furthermore, with the expansion parameters adjusted to give an equal P(CTVinPTV) for all methods, PTV volumes were compared., Results: With the expansion algorithm parameters chosen to yield P(CTVinPTV) = 90% for a sphere, an average P(CTVinPTV) of 84%, 57%, and 46% was obtained for the other shapes, using the RTCL method, coverage probability, and rolling ball, respectively. With the parameters adjusted to yield an equal P(CTVinPTV) for all methods, the PTV volume was on average 8% larger for the coverage probability method and 15% larger for the rolling ball algorithm compared to the RTCL method., Conclusion: The RTCL method provides an accurate way to include the effects of systematic rotations in the margin. Compared to other algorithms, the method is less sensitive to the shape of the CTV, and, given a fixed probability of finding the CTV inside the PTV, a smaller PTV volume can be obtained.

Purpose: To correctly evaluate realistic treatment plans in terms of absorbed dose to the clinical target volume (CTV), equivalent uniform dose (EUD), and tumor control probability (TCP) in the presence of execution (random) and preparation (systematic) geometric errors., Materials and Methods: The dose matrix is blurred with all execution errors to estimate the total dose distribution of all fractions. To include preparation errors, the CTV is randomly displaced (and optionally rotated) many times with respect to its planned position while computing the dose, EUD, and TCP for the CTV using the blurred dose matrix. Probability distributions of these parameters are computed by combining the results with the probability of each particular preparation error. We verified the method by comparing it with an analytic solution. Next, idealized and realistic prostate plans were tested with varying margins and varying execution and preparation error levels., Results: Probability levels for the minimum dose, computed with the new method, are within 1% of the analytic solution. The impact of rotations depends strongly on the CTV shape. A margin of 10 mm between the CTV and planning target volume is adequate for three-field prostate treatments given the accuracy level in our department; i.e., the TCP in a population of patients, TCP(pop), is reduced by less than 1% due to geometric errors. When reducing the margin to 6 mm, the dose must be increased from 80 to 87 Gy to maintain the same TCP(pop). Only in regions with a high-dose gradient does such a margin reduction lead to a decrease in normal tissue dose for the same TCP(pop). Based on a rough correspondence of 84% minimum dose with 98% EUD, a margin recipe was defined. To give 90% of patients at least 98% EUD, the planning target volume margin must be approximately 2.5 Sigma + 0.7 sigma - 3 mm, where Sigma and sigma are the combined standard deviations of the preparation and execution errors. This recipe corresponds accurately with 1% TCP(pop) loss for prostate plans with clinically reasonable values of Sigma and sigma., Conclusion: The new method computes in a few minutes the influence of geometric errors on the statistics of target dose and TCP(pop) in clinical treatment plans. Too small margins lead to a significant loss of TCP(pop) that is difficult to compensate for by dose escalation.

Purpose: To provide an analytical description of the effect of random and systematic geometrical deviations on the target dose in radiotherapy and to derive margin rules., Methods and Materials: The cumulative dose distribution delivered to the clinical target volume (CTV) is expressed analytically. Geometrical deviations are separated into treatment execution (random) and treatment preparation (systematic) variations. The analysis relates each possible preparation (systematic) error to the dose distribution over the CTV and allows computation of the probability distribution of, for instance, the minimum dose delivered to the CTV., Results: The probability distributions of the cumulative dose over a population of patients are called dose-population histograms in short. Large execution (random) variations lead to CTV underdosage for a large number of patients, while the same level of preparation (systematic) errors leads to a much larger underdosage for some of the patients. A single point on the histogram gives a simple "margin recipe." For example, to ensure a minimum dose to the CTV of 95% for 90% of the patients, a margin between CTV and planning target volume (PTV) is required of 2.5 times the total standard deviation (SD) of preparation (systematic) errors (Sigma) plus 1.64 times the total SD of execution (random) errors (sigma') combined with the penumbra width, minus 1.64 times the SD describing the penumbra width (sigma(p)). For a sigma(p) of 3.2 mm, this recipe can be simplified to 2.5 Sigma + 0.7 sigma'. Because this margin excludes rotational errors and shape deviations, it must be considered as a lower limit for safe radiotherapy., Conclusion: Dose-population histograms provide insight into the effects of geometrical deviations on a population of patients. Using a dose-probability based approach, simple algorithms for choosing margins were derived.

A generic method for three-dimensional (3-D) evaluation of target volume delineation in multiple imaging modalities is presented. The evaluation includes geometrical and statistical methods to estimate observer differences and variability in defining the Gross Tumor Volume (GTV) in relation to the diagnostic CT and MRI modalities. The geometrical method is based on mapping the 3-D shape of the target volume to a scalar representation, thus enabling a one-dimensional statistical analysis. The statistical method distinguishes observer and modality related uncertainties, which are expressed in terms of three error components: random observer deviations, systematic observer differences, and systematic modality differences. Monte Carlo simulations demonstrate that the standard errors of each of the three model parameters are inversely proportional to the square root of the product of the patient group size and the number of observers and proportional to the intraobserver variation. For 18 patients and 3 observers the standard errors of the estimated systematic modality and observer differences are 19% and 14% of the intraobserver standard deviation, respectively. A scalar representation of the shape of the prostate, delineated by 3 observers for 18 patients, was obtained by sampling the distance between the average center of gravity of the prostate in CT and the prostate surface for a large number of directions (2500), using polar coordinates. Observer variability and differences were obtained by applying the statistical method to the samples independently. The intraobserver variation for CT was largest in regions near the seminal vesicles (s.d: 3 mm) and the apex (s.d: 3 mm). The systematic observer variation in CT was largest in a region near the plexus Santorini, at the caudal-anterior side of the prostate (s.d.: 2 mm). The sensitivity for the choice of origin was tested by using the average center of gravity from axial MRI instead of CT. The results were almost identical. The polar map measures distances in the scanning directions. A correction procedure to get the variability in directions perpendicular to the surface of the prostate yielded variations that were a factor of 0.85 smaller for all directions. It is concluded that by separating the shape evaluation in a geometrical and a statistical part, the complexity of the analysis of 3-D shape differences can be significantly reduced. The method was successfully applied to a group of prostate patients, where we demonstrated that delineation variability is nonhomogeneous, with the largest variations occurring near the seminal vesicles and the apex.