http://repub.eur.nl/res/aut/167/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/31186/ 2011-08-01T00:00:00Z Purpose: To develop a delineation tool that refines physician-drawn contours of the gross tumor volume (GTV) in nasopharynx cancer, using combined pixel value information from x-ray computed tomography (CT) and magnetic resonance imaging (MRI) during delineation.Methods: Operator-guided delineation assisted by a so-called snake algorithm was applied on weighted CT-MRI registered images. The physician delineates a rough tumor contour that is continuously adjusted by the snake algorithm using the underlying image characteristics. The algorithm was evaluated on five nasopharyngeal cancer patients. Different linear weightings CT and MRI were tested as input for the snake algorithm and compared according to contrast and tumor to noise ratio (TNR). The semi-automatic delineation was compared with manual contouring by seven experienced radiation oncologists.Results: A good compromise for TNR and contrast was obtained by weighing CT twice as strong as MRI. The new algorithm did not notably reduce interobserver variability, it did however, reduce the average delineation time by 6 min per case.Conclusions: The authors developed a user-driven tool for delineation and correction based a snake algorithm and registered weighted CT image and MRI. The algorithm adds morphological information from CT during the delineation on MRI and accelerates the delineation task. http://repub.eur.nl/res/pub/31769/ 2011-01-01T00:00:00Z The aim of the present study is to determine and compare initial treatment costs of microsurgery, linear accelerator (LINAC) radiosurgery, and gamma knife radiosurgery in meningioma patients. Additionally, the follow-up costs in the first year after initial treatment were assessed. Cost analyses were performed at two neurosurgical departments in The Netherlands from the healthcare providers' perspective. A total of 59 patients were included, of whom 18 underwent microsurgery, 15 underwent LINAC radiosurgery, and 26 underwent gamma knife radiosurgery. A standardized microcosting methodology was employed to ensure that the identified cost differences would reflect only actual cost differences. Initial treatment costs, using equipment costs per fraction, were €12,288 for microsurgery, €1,547 for LINAC radiosurgery, and €2,412 for gamma knife radiosurgery. Higher initial treatment costs for microsurgery were predominantly due to inpatient stay (€5,321) and indirect costs (€4,350). LINAC and gamma knife radiosurgery were equally expensive when equipment was valued per treatment (€2,198 and €2,412, respectively). Follow-up costs were slightly, but not significantly, higher for microsurgery compared with LINAC and gamma knife radiosurgery. Even though initial treatment costs were over five times higher for microsurgery compared with both radiosurgical treatments, our study gives indications that the relative cost difference may decrease when follow-up costs occurring during the first year after initial treatment are incorporated. This reinforces the need to consider follow-up costs after initial treatment when examining the relative costs of alternative treatments. http://repub.eur.nl/res/pub/27980/ 2010-12-23T00:00:00Z Purpose: To compare pathology macroscopic tumor dimensions with magnetic resonance imaging (MRI) measurements and to establish the microscopic tumor extension of colorectal liver metastases. Methods and Materials: In a prospective pilot study we included patients with colorectal liver metastases planned for surgery and eligible for MRI. A liver MRI was performed within 48 hours before surgery. Directly after surgery, an MRI of the specimen was acquired to measure the degree of tumor shrinkage. The specimen was fixed in formalin for 48 hours, and another MRI was performed to assess the specimen/tumor shrinkage. All MRI sequences were imported into our radiotherapy treatment planning system, where the tumor and the specimen were delineated. For the macroscopic pathology analyses, photographs of the sliced specimens were used to delineate and reconstruct the tumor and the specimen volumes. Microscopic pathology analyses were conducted to assess the infiltration depth of tumor cell nests. Results: Between February 2009 and January 2010 we included 13 patients for analysis with 21 colorectal liver metastases. Specimen and tumor shrinkage after resection and fixation was negligible. The best tumor volume correlations between MRI and pathology were found for T1-weighted (w) echo gradient sequence (rs= 0.99, slope = 1.06), and the T2-w fast spin echo (FSE) single-shot sequence (rs= 0.99, slope = 1.08), followed by the T2-w FSE fat saturation sequence (rs= 0.99, slope = 1.23), and the T1-w gadolinium-enhanced sequence (rs= 0.98, slope = 1.24). We observed 39 tumor cell nests beyond the tumor border in 12 metastases. Microscopic extension was found between 0.2 and 10 mm from the main tumor, with 90% of the cases within 6 mm. Conclusions: MRI tumor dimensions showed a good agreement with the macroscopic pathology suggesting that MRI can be used for accurate tumor delineation. However, microscopic extensions found beyond the tumor border indicate that caution is needed in selecting appropriate tumor margins. http://repub.eur.nl/res/pub/23963/ 2010-10-06T00:00:00Z Purpose: To validate and clinically evaluate autocontouring using atlas-based autosegmentation (ABAS) of computed tomography images. Methods and Materials: The data from 10 head-and-neck patients were selected as input for ABAS, and neck levels I-V and 20 organs at risk were manually contoured according to published guidelines. The total contouring times were recorded. Two different ABAS strategies, multiple and single subject, were evaluated, and the similarity of the autocontours with the atlas contours was assessed using Dice coefficients and the mean distances, using the leave-one-out method. For 12 clinically treated patients, 5 experienced observers edited the autosegmented contours. The editing times were recorded. The Dice coefficients and mean distances were calculated among the clinically used contours, autocontours, and edited autocontours. Finally, an expert panel scored all autocontours and the edited autocontours regarding their adequacy relative to the published atlas. Results: The time to autosegment all the structures using ABAS was 7 min/patient. No significant differences were observed in the autosegmentation accuracy for stage N0 and N+ patients. The multisubject atlas performed best, with a Dice coefficient and mean distance of 0.74 and 2 mm, 0.67 and 3 mm, 0.71 and 2 mm, 0.50 and 2 mm, and 0.78 and 2 mm for the salivary glands, neck levels, chewing muscles, swallowing muscles, and spinal cord-brainstem, respectively. The mean Dice coefficient and mean distance of the autocontours vs. the clinical contours was 0.8 and 2.4 mm for the neck levels and salivary glands, respectively. For the autocontours vs. the edited autocontours, the mean Dice coefficient and mean distance was 0.9 and 1.6 mm, respectively. The expert panel scored 100% of the autocontours as a "minor deviation, editable" or better. The expert panel scored 88% of the edited contours as good compared with 83% of the clinical contours. The total editing time was 66 min. Conclusion: Multiple-subject ABAS of computed tomography images proved to be a useful novel tool in the rapid delineation of target and normal tissues. Although editing of the autocontours is inevitable, a substantial time reduction was achieved using editing, instead of manual contouring (180 vs. 66 min). http://repub.eur.nl/res/pub/19657/ 2010-05-18T00:00:00Z Background/aims: To report the outcome of primary radiotherapy in patients with progressive optic nerve sheath meningioma (ONSM). Methods: The clinical records of all patients were reviewed in a retrospective, observational, multicentre study. Results: Thirty-four consecutive patients were included. Twenty-six women and eight men received conventional or stereotactic fractionated radiotherapy, and were followed for a median 58 (range 51-156) months. Fourteen eyes (41%) showed improved visual acuity of at least two lines on the Snellen chart. In 17 (50%) eyes, the vision stabilised, while deterioration was noted in three eyes (9%). The visual outcome was not associated with age at the time of radiotherapy (p=0.83), sex (p=0.43), visual acuity at the time of presentation (p=0.22) or type of radiotherapy (p=0.35). Optic disc swelling was associated with improved visual acuity (p<0.01) and 4/11 patients with optic atrophy also showed improvement. Long-term complications were dry eyes in five patients, cataracts in three, and mild radiation retinopathy in four. Conclusion: Primary radiotherapy for patients with ONSM is associated with long-term improvement of visual acuity and few adverse effects. http://repub.eur.nl/res/pub/28662/ 2010-03-15T00:00:00Z Purpose: To determine the variation in target delineation of nasopharyngeal carcinoma and the impact of measures to minimize this variation.Materials and methods: For ten nasopharyngeal cancer patients, ten observers each delineated the Clinical Target Volume (CTV) and the CTV elective. After 3D analysis of the delineated volumes, a second delineation was performed. This implied improved delineation instructions, a combined delineation on CT and co-registered MRI, forced use of sagittal reconstructions, and an on-line anatomical atlas.Results: Both for the CTV and the CTV elective delineations, the 3D SD decreased from Phase 1 to Phase 2, from 4.4 to 3.3 mm for the CTV and from 5.9 to 4.9 mm for the elective. There was an increase agreement, where the observers intended to delineate the same structure, from 36 to 64 surface % (p = 0.003) for the CTV and from 17 to 59% (p = 0.004) for the elective. The largest variations were at the caudal border of the delineations but these were smaller when an observer utilized the sagittal window. Hence, the use of sagittal side windows was enforced in the second phase and resulted in a decreased standard deviation for this area from 7.7 to 3.3 mm (p = 0.001) for the CTV and 7.9 to 5.6 mm (p = 0.03) for the CTV elective.Discussion: Attempts to decrease the variation need to be tailored to the specific causes of the variation. Use of delineation instructions multimodality imaging, the use of sagittal windows and an on-line atlas result in a higher agreement on the intended target. http://repub.eur.nl/res/pub/24395/ 2009-11-15T00:00:00Z Purpose: To assess day-to-day differences between planned and delivered target volume (TV) and organ-at-risk (OAR) dose distributions in liver stereotactic body radiation therapy (SBRT), and to investigate the dosimetric impact of setup corrections. Methods and Materials: For 14 patients previously treated with SBRT, the planning CT scan and three treatment scans (one for each fraction) were included in this study. For each treatment scan, two dose distributions were calculated: one using the planned setup for the body frame (no correction), and one using the clinically applied (corrected) setup derived from measured tumor displacements. Per scan, the two dose distributions were mutually compared, and the clinically delivered distribution was compared with planning. Doses were recalculated in equivalent 2-Gy fraction doses. Statistical analysis was performed with the linear mixed model. Results: With setup corrections, the mean loss in TV coverage relative to planning was 1.7%, compared with 6.8% without corrections. For calculated equivalent uniform doses, these figures were 2.3% and 15.5%, respectively. As for the TV, mean deviations of delivered OAR doses from planning were small (between -0.4 and +0.3 Gy), but the spread was much larger for the OARs. In contrast to the TV, the mean impact of setup corrections on realized OAR doses was close to zero, with large positive and negative exceptions. Conclusions: Daily correction of the treatment setup is required to obtain adequate TV coverage. Because of day-to-day patient anatomy changes, large deviations in OAR doses from planning did occur. On average, setup corrections had no impact on these doses. Development of new procedures for image guidance and adaptive protocols is warranted. http://repub.eur.nl/res/pub/24393/ 2009-06-01T00:00:00Z Purpose: To find a dose-volume effect for inhomogeneous irradiated lacrimal glands. Methods and Materials: Between 1999 and 2006, 72 patients (42 men and 30 women) were treated with fractionated stereotactic radiotherapy in a prospective, nonrandomized clinical trial (median follow-up, 32 months). A total dose of 50 Gy was given on 5 consecutive days. The mean of all Schirmer test results obtained ≥6 months after treatment was correlated with the radiation dose delivered to the lacrimal gland. Also, the appearance of dry eye syndrome (DES) was related to the lacrimal gland dose distribution. Results: Of the 72 patients, 17 developed a late Schirmer value <10 mm; 9 patients developed DES. A statistically significant relationship was found between the received median dose in the lacrimal gland vs. reduced tear production (p = 0.000) and vs. the appearance of DES (p = 0.003), respectively. A median dose of 7 Gy/fraction to the lacrimal gland caused a 50% risk of low Schirmer results. A median dose of 10 Gy resulted in a 50% probability of DES. Conclusion: We found a clear dose-volume relationship for irradiated lacrimal glands with regard to reduced tear production and the appearance of DES. http://repub.eur.nl/res/pub/29686/ 2008-04-01T00:00:00Z 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. http://repub.eur.nl/res/pub/29715/ 2008-04-01T00:00:00Z Purpose: Stereotactic body radiation therapy (SBRT) provides a high local control rate for primary and metastatic liver tumors. The aim of this study is to assess the impact of this treatment on the patient's quality of life. This is the first report of quality of life associated with liver SBRT. Methods and Materials: From October 2002 to March 2007, a total of 28 patients not suitable for other local treatments and with Karnofsky performance status of at least 80% were entered in a Phase I-II study of SBRT for liver tumors. Quality of life was a secondary end point. Two generic quality of life instruments were investigated, EuroQol-5D (EQ-5D) and EuroQoL-Visual Analogue Scale (EQ-5D VAS), in addition to a disease-specific questionnaire, the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ C-30). Points of measurement were directly before and 1, 3, and 6 months after treatment. Mean scores and SDs were calculated. Statistical analysis was performed using paired-samples t-test and Student t-test. Results: The calculated EQ-5D index, EQ-5D VAS and QLQ C-30 global health status showed that mean quality of life of the patient group was not significantly influenced by treatment with SBRT; if anything, a tendency toward improvement was found. Conclusions: Stereotactic body radiation therapy combines a high local control rate, by delivering a high dose per fraction, with no significant change in quality of life. Multicenter studies including larger numbers of patients are recommended and under development. http://repub.eur.nl/res/pub/35825/ 2007-04-01T00:00:00Z 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°. 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. http://repub.eur.nl/res/pub/4695/ 2004-01-01T00:00:00Z PURPOSE: High-precision external beam radiotherapy (EBRT) has been suggested as a potential alternative to endovascular brachytherapy for the treatment of coronary artery in-stent restenosis. The purpose of our study was to investigate and compare different options to define a smallest feasible target volume. METHODS AND MATERIALS: The cardiac motion of 17 coronary artery stents in 17 patients was studied by use of biplane conventional angiography, recorded during breath-hold. Each stent was reconstructed in three dimensions by use of biplane sets of frames covering an entire cardiac cycle. The volume traversed by the stent during the entire or part of the cardiac cycle was determined. Four options to define the stent-traversed volume (STV) as a target for high-precision EBRT were investigated. RESULTS: The mean STV during the entire cardiac cycle was 3.5 cm3; the STV represented less than 1% of the heart volume in all patients. The STV during the diastolic and systolic phase resulted in a mean reduction of 26.6% and 29.1%, respectively, compared with the STV during the entire cardiac cycle. The smallest STV, measured during a 160-ms interval within the cardiac cycle, resulted in a mean maximal reduction of 75.9% compared with the STV during the entire cardiac cycle. CONCLUSIONS: The STV during the entire cardiac cycle represents a small potential target volume for high-precision EBRT. A significant reduction of this target volume is possible in case of definition during a selected interval within the cardiac cycle. http://repub.eur.nl/res/pub/4793/ 2002-06-24T00:00:00Z Three-dimensional reconstructions of 19 coronary artery stents from biplane angiograms were used for measurement of the volume through which the stents traversed during the cardiac cycle. This volume, less than 0.8% of the whole heart volume in all patients, represents a target volume for high-precision radiotherapy to treat coronary artery in-stent restenosis. http://repub.eur.nl/res/pub/4800/ 2002-02-01T00:00:00Z PURPOSE: To measure the effect of cardiac motion on coronary artery stent position during the cardiac cycle as a first step toward exploring the feasibility of stereotactic external beam radiation therapy targeted at restenotic stented coronary arteries. METHODS AND MATERIALS: The three-dimensional (3D) position of eight coronary artery stents in 8 patients immobilized in a stereotactic body frame was studied noninvasively by single-breathhold ECG-gated multislice spiral computed tomography (MSCT) during 10 retrospectively selected phases, equally distributed throughout the R-R interval of consecutive cardiac cycles. The volume encompassing all measured 3D positions of the stent was measured. RESULTS: Stent volumes measured by MSCT closely agreed with measurements by quantitative coronary angiography (r > 0.99). The mean of the maximum 3D stent center of mass displacement between any two phases during the cardiac cycle for all eight coronary arteries was 7.5 mm (range 3.3-20.5 mm) in the lateral direction, 8.6 mm (range 2.7-21.6 mm) in the ventrodorsal direction, and 8.2 mm (range 2.5-19.7 mm) in the craniocaudal direction. As was anticipated, the volume encompassing all measured 3D positions of the stent represented only a fraction of the whole heart volume in all patients, i.e., less than 0.6%. CONCLUSIONS: ECG-gated MSCT allowed the measurement of the volume encompassing multiphase 3D positions of coronary artery stents during the cardiac cycle. This volume, a measure of the cardiac motion effect on coronary artery stent position during the cardiac cycle, represents a moving gross target for stereotactic external beam radiation therapy. http://repub.eur.nl/res/pub/4816/ 2001-12-01T00:00:00Z Purpose: Different methods have been described to define a target volume for the treatment of restenotic (stented) coronary arteries by external beam radiation therapy (EBRT). The purpose of this study was to explore two methods to define a target for such therapy, and to compare these with previously investigated methods. Materials and methods: The 3-D position of a stent throughout the cardiac cycle in the three major epicardial coronary arteries was measured in three patients by single-breathhold multislice spiral CT and breathhold biplane conventional X-ray angiography, both indexed in time with the ECG. The volume through which the stent traversed (STV) during the cardiac cycle was determined by use of displacement measurements. Results: For multislice CT and biplane angiography, respectively, the mean STV was 1.23 cm3 (range 0.65-2.22 cm3) and 2.81 cm3 (range 1.60-4.99 cm3). The STV represented only a fraction of the whole heart volume in all patients, that is, equal to or less than 0.4%. Conclusions: Multislice CT and biplane angiography allowed the measurement of a relatively small potential target, that is the STV, for EBRT of restenotic stented coronary arteries. Both studied imaging modalities are instrumental for targeting the STV by highly conformal radiation therapy in case of restenotic stented coronary arteries. http://repub.eur.nl/res/pub/20367/ 1997-12-03T00:00:00Z When no lymph node metastases are detected clinically in patients with head and neck cancer, the neck is staged as NO. The elective treatment of the NO neck, by either surgery or radiotherapy, results in excellent local control rates. This thesis specifically deals with the use of radiotherapy as a single modality treatment for the clinically negative neck. Given the risk of radiation-induced side effects, elective neck irradiation is advocated in many institutions only if the probability of subclinical disease is considered to be more than 10-20%. The major side effects of the elective irradiation of the neck are the dry mouth syndrome (xerostomia) and dental caries due to damage to the major and minor salivary glands. A major advance in radiotherapy in the last decade has been the development and clinical implementation of conformal radiotherapy. With the introduction of three-dimensional CT-based radiotherapy planning systems, it has become feasible to conform the high dose region to the target volume. In case of elective neck irradiation for example, high doses of radiation can be delivered to the neck with sparing of the salivary glands and other normal tissues such as the spinal cord. The main objective of this thesis is to provide a three-dimensional CT definition of the target of the NO neck which will indeed allow the design of conformal radiotherapy techniques for elective neck irradiation. It is defined and presented in such a way that it can be studied and verified interactively on CD-i. The second goal of this thesis is the development of conformal radiotherapy treatment plans and subsequently, to demonstrate the potential for reducing the side effects of elective neck irradiation by using such conformal techniques. The coverage of the three-dimensional NO neck target and the amount of sparing of the parotid (and submandibular) salivary glands can subsequently be studied interactively with a CD-i, using all CT-, MRI- and anatomical slices obtained from a human cadaver.