Online adaptive MR-guided radiotherapy: Conformity of contour adaptation for prostate cancer, rectal cancer and lymph node oligometastases among radiation therapists and radiation oncologists.

Background and purpose: Online adaptive MR-guided treatment planning workflows facilitate daily contour adaptation to the actual anatomy. Allocating contour adaptation to radiation therapists (RTTs) instead of radiation oncologists (ROs) might allow for increasing workflow efficiency. This study investigates conformity of adapted target contours provided by dedicated RTTs and ROs. Materials and methods: In a simulated online procedure, 6 RTTs and 6 ROs recontoured targets and organs at risk (OAR) in prostate cancer (n = 2), rectal cancer (n = 2) and lymph node-oligometastases (n = 2) cases. RTTs gained contouring competence beforehand by following a specific in-house training program. For all target contours and the reference delineations volumetric differences were determined and Dice similarity coefficient (DSC), conformity index (CI) and generalized CI were calculated. Delineation time and -confidence were registered for targets and OAR. Impact of contour adaptation on treatment plan quality was investigated. Results: Delineation conformity was generally high with DSC, CI and generalized CI values in the range of 0.81-0.94, 0.87-0.95 and 0.63-0.85 for prostate cancer, rectal cancer and LN-oligometastasis, respectively. Target volumes were comparable for both, RTTs and ROs. Time needed and confidence in contour adaptation was comparable as well. Treatment plans derived with adapted contours did not violate dose volume constrains as used in clinical routine. Conclusion: After tumor site specific training, daily contour adaptations as needed in adaptive online radiotherapy workflows can be accurately performed by RTTs. Conformity of the derived contours is high and comparable to contours as provided by ROs.

Comparison of Library of Plans with two daily adaptive strategies for whole bladder radiotherapy.

BACKGROUND AND PURPOSE: Whole bladder radiotherapy is challenging due to inter- and intrafraction size and shape changes. To account for these changes, currently a Library of Plans (LoP) technique is often applied, but daily adaptive radiotherapy is also increasingly becoming available. The aim of this study was to compare LoP with two magnetic resonance imaging guided radiotherapy (MRgRT) strategies by comparing target coverage and volume of healthy tissue inside the planning target volume (PTV) for whole bladder treatments. METHODS AND MATERIALS: Data from 25 MRgRT lymph node oligometastases treatments (125 fractions) were used, with three MRI scans acquired at each fraction at 0, 15 and 30 min. Bladders were delineated and used to evaluate three strategies: 1) LoP with two plans for a 15 min fraction, 2) MRgRT15min for a 15 min fraction and 3) MRgRT30min for a 30 min fraction. The volumes of healthy tissue inside and bladder outside the PTV were analyzed on the simulated post-treatment images. RESULTS: MRgRT30min had 120% and 121% more healthy tissue inside the PTV than LoP and MRgRT15min. For LoP slightly more target outside the PTV was found than for MRgRT30min and MRgRT15min, with median 0% (range 0-23%) compared to 0% (0-20%) and 0% (0-10%), respectively. CONCLUSIONS: Taking into account both target coverage and volume of healthy tissue inside the PTV, MRgRT15min performed better than LoP and MRgRT30min for whole bladder treatments. A 15 min daily adaptive radiotherapy workflow is needed to potentially benefit from replanning compared to LoP.

Inter-clinician delineation variation for a new highly-conformal flank target volume in children with renal tumors: A SIOP-Renal Tumor Study Group international multicenter exercise.

BACKGROUND AND PURPOSE: Recently, the SIOP-RTSG developed a highly-conformal flank target volume definition for children with renal tumors. The aims of this study were to evaluate the inter-clinician delineation variation of this new target volume definition in an international multicenter setting and to explore the necessity of quality assurance. MATERIALS AND METHODS: Six pediatric renal cancer cases were transferred to ten radiation oncologists from seven European countries ('participants'). These participants delineated the pre- and postoperative Gross Tumor Volume (GTVpre/post), and Clinical Target Volume (CTV) during two test phases (case 1-2 and 3-4), followed by guideline refinement and a quality assurance phase (case 5-6). Reference target volumes (TVref) were established by three experienced radiation oncologists. The Dice Similarity Coefficient between the reference and participants (DSCref/part) was calculated per case. Delineations of case 5-6 were graded by four independent reviewers as 'per protocol' (0-4 mm), 'minor deviation' (5-9 mm) or 'major deviation' (≥10 mm) from the delineation guideline using 18 standardized criteria. Also, a major deviation resulting in underestimation of the CTVref was regarded as an unacceptable variation. RESULTS: A total of 57/60 delineation sets were completed. The median DSCref/part for the CTV was 0.55 without improvement after sequential cases (case 3-4 vs. case 5-6: p = 0.15). For case 5-6, a major deviation was found for 5/18, 12/17, 18/18 and 4/9 collected delineations of the GTVpre, GTVpost, CTV-T and CTV-N, respectively. An unacceptable variation from the CTVref was found for 7/9 participants for case 5 and 6/9 participants for case 6. CONCLUSION: This international multicenter delineation exercise demonstrates that the new consensus for highly-conformal postoperative flank target volume delineation leads to geometrical variation among participants. Moreover, standardized review showed an unacceptable delineation variation in the majority of the participants. These findings strongly suggest the need for additional training and centralized pre-treatment review when this target volume delineation approach is implemented on a larger scale.

Knowledge-Based Assessment of Focal Dose Escalation Treatment Plans in Prostate Cancer.

PURPOSE: In a randomized focal dose escalation radiation therapy trial for prostate cancer (FLAME), up to 95 Gy was prescribed to the tumor in the dose-escalated arm, with 77 Gy to the entire prostate in both arms. As dose constraints to organs at risk had priority over dose escalation and suboptimal planning could occur, we investigated how well the dose to the tumor was boosted. We developed an anatomy-based prediction model to identify plans with suboptimal tumor dose and performed replanning to validate our model. METHODS AND MATERIALS: We derived dose-volume parameters from planned dose distributions of 539 FLAME trial patients in 4 institutions and compared them between both arms. In the dose-escalated arm, we determined overlap volume histograms and derived features representing patient anatomy. We predicted tumor D98% with a linear regression on anatomic features and performed replanning on 21 plans. RESULTS: In the dose-escalated arm, the median tumor D50% and D98% were 93.0 and 84.7 Gy, and 99% of the tumors had a dose escalation greater than 82.4 Gy (107% of 77 Gy). In both arms organs at risk constraints were met. Five out of 73 anatomic features were found to be predictive for tumor D98%. Median predicted tumor D98% was 4.4 Gy higher than planned D98%. Upon replanning, median tumor D98% increased by 3.0 Gy. A strong correlation between predicted increase in D98% and realized increase upon replanning was found (ρ = 0.86). CONCLUSIONS: Focal dose escalation in prostate cancer was feasible with a dose escalation to 99% of the tumors. Replanning resulted in an increased tumor dose that correlated well with the prediction model. The model was able to identify tumors on which a higher boost dose could be planned. The model has potential as a quality assessment tool in focal dose escalated treatment plans.

Consensus on Contouring Primary Breast Tumors on MRI in the Setting of Neoadjuvant Partial Breast Irradiation in Trials.

PURPOSE: Our purpose was to present and evaluate expert consensus on contouring primary breast tumors on magnetic resonance imaging (MRI) in the setting of neoadjuvant partial breast irradiation in trials. METHODS AND MATERIALS: Expert consensus on contouring guidelines for target definition of primary breast tumors on contrast-enhanced MRI in trials was developed by an international team of experienced breast radiation oncologists and a dedicated breast radiologist during 3 meetings. At the first meeting, draft guidelines were developed through discussing and contouring 2 cases. At the second meeting 6 breast radiation oncologists delineated gross tumor volume (GTV) in 10 patients with early-stage breast cancer (cT1N0) according to draft guidelines. GTV was expanded isotropically (20 mm) to generate clinical target volume (CTV), excluding skin and chest wall. Delineations were reviewed for disagreement and guidelines were clarified accordingly. At the third meeting 5 radiation oncologists redelineated 6 cases using consensus-based guidelines. Interobserver variation of GTV and CTV was assessed using generalized conformity index (CI). CI was calculated as the sum of volumes each pair of observers agreed upon, divided by the sum of encompassing volumes for each pair of observers. RESULTS: For the 2 delineation sessions combined, mean GTV ranged between 0.19 and 2.44 cm3, CI for GTV ranged between 0.28 and 0.77, and CI for CTV between 0.77 and 0.94. The largest interobserver variation in GTV delineations was observed in cases with extended tumor spiculae, blood vessels near or markers within the tumor, or with increased enhancement of glandular breast tissue. Consensus-based guidelines stated to delineate all visible tumors on contrast enhanced-MRI scan 1 to 2 minutes after contrast injection and if a marker was inserted in the tumor to include this. CONCLUSIONS: Expert-based consensus on contouring primary breast tumors on MRI in trials has been reached. This resulted in low interobserver variation for CTV in the context of a uniform 20 mm GTV to CTV expansion margin.

A single neural network for cone-beam computed tomography-based radiotherapy of head-and-neck, lung and breast cancer.

Background and purpose Adaptive radiotherapy based on cone-beam computed tomography (CBCT) requires high CT number accuracy to ensure accurate dose calculations. Recently, deep learning has been proposed for fast CBCT artefact corrections on single anatomical sites. This study investigated the feasibility of applying a single convolutional network to facilitate dose calculation based on CBCT for head-and-neck, lung and breast cancer patients. Materials and Methods Ninety-nine patients diagnosed with head-and-neck, lung or breast cancer undergoing radiotherapy with CBCT-based position verification were included in this study. The CBCTs were registered to planning CT according to clinical procedures. Three cycle-consistent generative adversarial networks (cycle-GANs) were trained in an unpaired manner on 15 patients per anatomical site generating synthetic-CTs (sCTs). Another network was trained with all the anatomical sites together. Performances of all four networks were compared and evaluated for image similarity against rescan CT (rCT). Clinical plans were recalculated on rCT and sCT and analysed through voxel-based dose differences and γ -analysis. Results A sCT was generated in 10 s. Image similarity was comparable between models trained on different anatomical sites and a single model for all sites. Mean dose differences < 0.5 % were obtained in high-dose regions. Mean gamma (3%, 3 mm) pass-rates > 95 % were achieved for all sites. Conclusion Cycle-GAN reduced CBCT artefacts and increased similarity to CT, enabling sCT-based dose calculations. A single network achieved CBCT-based dose calculation generating synthetic CT for head-and-neck, lung, and breast cancer patients with similar performance to a network specifically trained for each anatomical site.

Gross Tumor Delineation in Esophageal Cancer on MRI Compared With 18F-FDG-PET/CT.

PURPOSE: Current delineation of the gross tumor volume (GTV) in esophageal cancer relies on computed tomography (CT) and combination with 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET). There is increasing interest in integrating magnetic resonance imaging (MRI) in radiation treatment, which can potentially obviate CT- or FDG-PET/CT-based delineation. The aim of this study is to evaluate the feasibility of target delineation on T2-weighted (T2W) MRI and T2W including diffusion-weighted MRI (T2W + DW-MRI) compared with current-practice FDG-PET/CT. METHODS: Ten observers delineated primary esophageal tumor GTVs of 6 patients on FDG-PET/CT, T2W-MRI, and T2W + DW-MRI. GTVs, generalized conformity indices, in-slice delineation variation (root mean square), and standard deviations in the position of the most cranial and caudal delineated slice were calculated. RESULTS: Delineations on MRI showed smaller GTVs compared with FDG-PET/CT-based delineations. The main variation was seen at the cranial and caudal border. No differences were observed in conformity indices (FDG-PET/CT, 0.68; T2W-MRI, 0.66; T2W + DW-MRI, 0.68) and in-slice variation (root mean square, 0.13 cm on FDG-PET/CT; 0.10 cm on T2W-MRI; 0.14 cm on T2W + DW-MRI). In the 2 tumors involving the gastroesophageal junction, addition of DW-MRI to T2W-MRI significantly decreased caudal border variation. CONCLUSIONS: MRI-based target delineation of the esophageal tumor is feasible with interobserver variability comparable to that with FDG-PET/CT, despite limited experience with delineation on MRI. Most variation was seen at cranial-caudal borders, and addition of DW-MRI to T2W-MRI may reduce caudal delineation variation of gastroesophageal junction tumors.

Contouring of prostate tumors on multiparametric MRI: Evaluation of clinical delineations in a multicenter radiotherapy trial.

PURPOSE: To date no guidelines are available for contouring prostate cancer inside the gland, as visible on multiparametric (mp-) MRI. We assessed inter-institutional differences in interpretation of mp-MRI in the multicenter phase III FLAME trial. METHODS: We analyzed clinical delineations on mp-MRI and clinical characteristics from 260 patients across three institutes. We performed a logistic regression analysis to examine each institute's weighting of T2w, ADC and Ktrans intensity maps in the delineation of the cancer. As reviewing of all delineations by an expert panel is not feasible, we made a selection based on discrepancies between a published tumor probability (TP) model and each institute's clinical delineations using Areas Under the ROC Curve (AUC) analysis. RESULTS: Regression coefficients for the three institutes were -0.07, -0.27 and -0.11 for T2w, -1.96, -0.53 and -0.65 for ADC and 0.15, 0.20 and 0.62 for Ktrans, with significant differences between institutes for ADC and Ktrans. AUC analysis showed median AUC values of 0.92, 0.80 and 0.79. Five patients with lowest AUC values were reviewed by a uroradiologist. CONCLUSION: Regression coefficients revealed considerably different interpretations of mp-MRI in tumor contouring between institutes and demonstrated the need for contouring guidelines. Based on AUC values outlying delineations could efficiently be identified for review.

Non-rigid CT/CBCT to CBCT registration for online external beam radiotherapy guidance.

Image-guided external beam radiotherapy (EBRT) allows radiation dose deposition with a high degree of accuracy and precision. Guidance is usually achieved by estimating the displacements, via image registration, between cone beam computed tomography (CBCT) and computed tomography (CT) images acquired at different stages of the therapy. The resulting displacements are then used to reposition the patient such that the location of the tumor at the time of treatment matches its position during planning. Moreover, ongoing research aims to use CBCT-CT image registration for online plan adaptation. However, CBCT images are usually acquired using a small number of x-ray projections and/or low beam intensities. This often leads to the images being subject to low contrast, low signal-to-noise ratio and artifacts, which ends-up hampering the image registration process. Previous studies addressed this by integrating additional image processing steps into the registration procedure. However, these steps are usually designed for particular image acquisition schemes, therefore limiting their use on a case-by-case basis. In the current study we address CT to CBCT and CBCT to CBCT registration by the means of the recently proposed EVolution registration algorithm. Contrary to previous approaches, EVolution does not require the integration of additional image processing steps in the registration scheme. Moreover, the algorithm requires a low number of input parameters, is easily parallelizable and provides an elastic deformation on a point-by-point basis. Results have shown that relative to a pure CT-based registration, the intrinsic artifacts present in typical CBCT images only have a sub-millimeter impact on the accuracy and precision of the estimated deformation. In addition, the algorithm has low computational requirements, which are compatible with online image-based guidance of EBRT treatments.

Superior target delineation for stereotactic body radiotherapy of bone metastases from renal cell carcinoma on MRI compared to CT.

BACKGROUND: In metastatic renal cell carcinoma (mRCC) there has been a treatment shift towards targeted therapy, which has resulted in improved overall survival. Therefore, there is a need for better local control of the tumor and its metastases. Image-guided stereotactic body radiotherapy (SBRT) in bone metastases provides improved symptom palliation and local control. With the use of SBRT there is a need for accurate target delineation. The hypothesis is that MRI allows for better visualization of the extend of bone metastases in mRCC and will optimize the accuracy of tumor delineation for stereotactic radiotherapy purposes, compared with CT only. METHODS: From 2013 to 2016, patients who underwent SBRT for RCC bone metastases were included. A planning CT and MRI were performed in radiotherapy treatment position. Gross tumor volumes (GTV) in both CT and MRI were delineated. Contouring was performed by a radiation oncologist specialized in bone metastases and verified by a radiologist, based on local consensus contouring guidelines. In both CT and MRI, the GTV volumes, conformity index (CI) and distance between the centers of mass (dCOM) were compared. RESULTS: Nine patients with 11 RCC bone metastases were included. The GTV volume as defined on MRI was in all cases larger or at least as large as the GTV volume on CT. The median GTV volume on MRI was 33.4 mL (range 0.2-247.6 mL), compared to 18.1 mL on CT (range 0.1-195.9) (P=0.013). CONCLUSIONS: Contouring of RCC bone metastases on MRI resulted in clinically relevant and statistically significant larger lesions (mean increase 41%) compared with CT. MRI seems to represent the extend of the GTV in RCC bone metastases more accurately. Contouring based on CT-only could result in an underestimation of the actual tumor volume, which may cause underdosage of the GTV in SBRT treatment plans.

Probabilistic treatment planning for pancreatic cancer treatment: prospective incorporation of respiratory motion shows only limited dosimetric benefit.

BACKGROUND: We introduced a probabilistic treatment planning approach that prospectively incorporates respiratory-induced motion in the treatment plan optimization. The aim of this study was to determine the potential dosimetric benefit by comparing this approach to the use of an internal target volume (ITV). MATERIAL AND METHOD: We retrospectively compared the probabilistic respiratory motion-incorporated (RMI) approach to the ITV approach for 18 pancreatic cancer patients, for seven simulated respiratory amplitudes from 5 to 50 mm in the superior-inferior (SI) direction. For each plan, we assessed the target coverage (required: D98%≥95% of 50 Gy prescribed dose). For the RMI plans, we investigated whether target coverage was robust against daily variations in respiratory amplitude. We determined the distance between the clinical target volume and the 30 Gy isodose line (i.e. dose gradient steepness) in the SI direction. To investigate the clinical benefit of the RMI approach, we created for each patient an ITV and RMI treatment plan for the three-dimensional (3D) respiratory amplitudes observed on their pretreatment 4D computed tomography (4DCT). We determined Dmean, V30Gy, V40Gy and V50Gy for the duodenum. RESULTS: All treatment plans yielded good target coverage. The RMI plans were robust against respiratory amplitude variations up to 10 mm, as D98% remained ≥95%. We observed steeper dose gradients compared to the ITV approach, with a mean decrease from 25.9 to 19.2 mm for a motion amplitude of 50 mm. For the 4DCT motion amplitudes, the RMI approach resulted in a mean decrease of 0.43 Gy, 1.1 cm3, 1.4 cm3 and 0.9 cm3 for the Dmean, V30Gy, V40Gy and V50Gy of the duodenum, respectively. CONCLUSION: The probabilistic treatment planning approach yielded significantly steeper dose gradients and therefore significantly lower dose to surrounding healthy tissues than the ITV approach. However, the observed dosimetric gain for clinically observed respiratory motion amplitudes for this patient group was limited.

Post-lumpectomy CT-guided tumor bed delineation for breast boost and partial breast irradiation: Can additional pre- and postoperative imaging reduce interobserver variability?

For breast boost radiotherapy or accelerated partial breast irradiation, the tumor bed (TB) is delineated by the radiation oncologist on a planning computed tomography (CT) scan. The aim of the present study was to investigate whether the interobserver variability (IOV) of the TB delineation is reduced by providing the radiation oncologist with additional magnetic resonance imaging (MRI) or CT scans. A total of 14 T1-T2 breast cancer patients underwent a standard planning CT in the supine treatment position following lumpectomy, as well as additional pre- and postoperative imaging in the same position. Post-lumpectomy TBs were independently delineated by four breast radiation oncologists on standard postoperative CT and on CT registered to an additional imaging modality. The additional imaging modalities used were postoperative MRI, preoperative contrast-enhanced (CE)-CT and preoperative CE-MRI. A cavity visualization score (CVS) was assigned to each standard postoperative CT by each observer. In addition, the conformity index (CI), volume and distance between centers of mass (dCOM) of the TB delineations were calculated. On CT, the median CI was 0.57, with a median volume of 22 cm3 and dCOM of 5.1 mm. The addition of postoperative MRI increased the median TB volume significantly to 28 cm3 (P<0.001), while the CI (P=0.176) and dCOM (P=0.110) were not affected. The addition of preoperative CT or MRI increased the TB volume to 26 and 25 cm3, respectively (both P<0.001), while the CI increased to 0.58 and 0.59 (both P<0.001) and the dCOM decreased to 4.7 mm (P=0.004) and 4.6 mm (P=0.001), respectively. In patients with CVS≤3, the median CI was 0.40 on CT, which was significantly increased by all additional imaging modalities, up to 0.52, and was accompanied by a median volume increase up to 6 cm3. In conclusion, the addition of postoperative MRI, preoperative CE-CT or preoperative CE-MRI did not result in a considerable reduction in the IOV in postoperative CT-guided TB delineation, while target volumes marginally increased. The value of additional imaging may be dependent on CVS.

Full-thickness closure in breast-conserving surgery: the impact on radiotherapy target definition for boost and partial breast irradiation. A multimodality image evaluation.

BACKGROUND: During breast-conserving surgery (BCS), surgeons increasingly perform full-thickness closure (FTC) to prevent seroma formation. This could potentially impair precision of target definition for boost and accelerated partial breast irradiation (APBI). The purpose of this study was to investigate the precision of target volume definition following BCS with FTC among radiation oncologists, using various imaging modalities. METHODS: Twenty clinical T1-2N0 patients, scheduled for BCS involving clip placement and FTC, were included in the study. Seven experienced breast radiation oncologists contoured the tumor bed on computed tomography (CT), magnetic resonance imaging (MRI) and fused CT-MRI datasets. A total of 361 observer pairs per image modality were analyzed. A pairwise conformity among the generated contours of the observers and the distance between their centers of mass (dCOM) were calculated. RESULTS: On CT, median conformity was 44 % [interquartile range (IQR) 28-58 %] and median dCOM was 6 mm (IQR 3-9 mm). None of the outcome measures improved when MRI or fused CT-MRI were used. In two patients, superficial closure was performed instead of FTC. In these 14 image sets and 42 observer pairs, median conformity increased to 70 %. CONCLUSIONS: Localization of the radiotherapy target after FTC is imprecise, on both CT and MRI. This could potentially lead to a geographical miss in patients at increased risk of local recurrence receiving a radiation boost, or for those receiving APBI. These findings highlight the importance for breast surgeons to clearly demarcate the tumor bed when performing FTC.

Effect of magnesium oxide on interfraction prostate motion and rectal filling in prostate cancer radiotherapy: analysis of a randomized clinical trial.

PURPOSE: To investigate whether magnesium oxide reduces the interfraction motion of the prostate and the amount of rectal filling and rectal gas, which influences prostate position during radiotherapy for prostate cancer. PATIENTS AND METHODS: From December 2008 to February 2010, 92 prostate cancer patients scheduled for intensity-modulated radiotherapy (77 Gy in 35 fractions) using fiducial marker-based position verification were randomly assigned to receive magnesium oxide (500 mg twice a day) or placebo during radiotherapy. In a previous study, we investigated the effect on intrafraction motion and did not find a difference between the treatment arms. Here, we compared the interfraction prostate motion between the two treatment arms as well as the amount of rectal filling and rectal air pockets using pretreatment planning computed tomography and magnetic resonance imagingscans. RESULTS: There was no statistically significant difference between the treatment arms in translation and rotation of the prostate between treatment fractions, except for the rotation around the cranial caudal axis. However, the difference was less than 1° and therefore considered not clinically relevant. There was no significant difference in the amount of rectal filling and rectal air pockets between the treatment arms. CONCLUSION: Magnesium oxide is not effective in reducing the interfraction prostate motion or the amount of rectal filling and rectal gas during external-beam radiotherapy. Therefore, magnesium oxide is not recommended in clinical practice for these purposes.

MRI and CT imaging for preoperative target volume delineation in breast-conserving therapy.

BACKGROUND: Accurate tumor bed delineation after breast-conserving surgery is important. However, consistency among observers on standard postoperative radiotherapy planning CT is low and volumes can be large due to seroma formation. A preoperative delineation of the tumor might be more consistent. Therefore, the purpose of this study was to determine the consistency of preoperative target volume delineation on CT and MRI for breast-conserving radiotherapy. METHODS: Tumors were delineated on preoperative contrast-enhanced (CE) CT and newly developed 3D CE-MR images, by four breast radiation oncologists. Clinical target volumes (CTVs) were created by addition of a 1.5 cm margin around the tumor, excluding skin and chest wall. Consistency in target volume delineation was expressed by the interobserver variability. Therefore, the conformity index (CI), center of mass distance (dCOM) and volumes were calculated. Tumor characteristics on CT and MRI were scored by an experienced breast radiologist. RESULTS: Preoperative tumor delineation resulted in a high interobserver agreement with a high median CI for the CTV, for both CT (0.80) and MRI (0.84). The tumor was missed on CT in 2/14 patients (14%). Leaving these 2 patients out of the analysis, CI was higher on MRI compared to CT for the GTV (p<0.001) while not for the CTV (CT (0.82) versus MRI (0.84), p=0.123). The dCOM did not differ between CT and MRI. The median CTV was 48 cm3 (range 28-137 cm3) on CT and 59 cm3 (range 30-153 cm3) on MRI (p<0.001). Tumor shapes and margins were rated as more irregular and spiculated on CE-MRI. CONCLUSIONS: This study showed that preoperative target volume delineation resulted in small target volumes with a high consistency among observers. MRI appeared to be necessary for tumor detection and the visualization of irregularities and spiculations. Regarding the tumor delineation itself, no clinically relevant differences in interobserver variability were observed. These results will be used to study the potential for future MRI-guided and neoadjuvant radiotherapy. TRIAL REGISTRATION: International Clinical Trials Registry Platform NTR3198.

Multiatlas-based segmentation with preregistration atlas selection.

PURPOSE: Automatic, atlas-based segmentation of medical images benefits from using multiple atlases, mainly in terms of robustness. However, a large disadvantage of using multiple atlases is the large computation time that is involved in registering atlas images to the target image. This paper aims to reduce the computation load of multiatlas-based segmentation by heuristically selecting atlases before registration. METHODS: To be able to select atlases, pairwise registrations are performed for all atlas combinations. Based on the results of these registrations, atlases are clustered, such that each cluster contains atlas that registers well to each other. This can all be done in a preprocessing step. Then, the representatives of each cluster are registered to the target image. The quality of the result of this registration is estimated for each of the representatives and used to decide which clusters to fully register to the target image. Finally, the segmentations of the registered images are combined into a single segmentation in a label fusion procedure. RESULTS: The authors perform multiatlas segmentation once with postregistration atlas selection and once with the proposed preregistration method, using a set of 182 segmented atlases of prostate cancer patients. The authors performed the full set of 182 leave-one-out experiments and in each experiment compared the result of the atlas-based segmentation procedure to the known segmentation of the atlas that was chosen as a target image. The results show that preregistration atlas selection is slightly less accurate than postregistration atlas selection, but this is not statistically significant. CONCLUSIONS: Based on the results the authors conclude that the proposed method is able to reduce the number of atlases that have to be registered to the target image with 80% on average, without compromising segmentation accuracy.

Radiofrequency heating induced by 7T head MRI: thermal assessment using discrete vasculature or Pennes' bioheat equation.

PURPOSE: To evaluate and compare the maximum temperature (T(max) ) in the head after exposure to a 300 MHz radiofrequency (RF) field induced by a magnetic resonance imaging (MRI) coil using two thermal simulation methods: Pennes' bioheat equation (PBHE) and discrete vasculature (DIVA). MATERIALS AND METHODS: The electromagnetic field induced in the head by a 7T birdcage coil was simulated using finite-difference time-domain (FDTD) and validated by MRI. The specific absorption rate (SAR) distributions normalized to the 10-gram maximum or the whole-head average were used for PBHE and DIVA simulations. RESULTS: For all cases, the T(max) in PBHE was slightly higher than in DIVA. The T(max) was 37.9-38.4°C, depending on the simulation method or perfusion rate. CONCLUSION: In some situations, RF exposure limited to SAR(max,10g) led to a T(max) higher than allowed by International Electrotechnical Commission (IEC) regulations. Therefore, it is advisable to use thermal simulations to evaluate RF safety of MRI. The simulation method used only slightly influenced the observed maximum temperature; the observed temperature with PBHE was higher in all situations. So PBHE is an appropriate method for RF safety assessment of MRI in the head. Using DIVA simulations, it was found unlikely that the body temperature increases significantly due to energy deposited by a head coil under normal circumstances.

A double-blind placebo-controlled randomized clinical trial with magnesium oxide to reduce intrafraction prostate motion for prostate cancer radiotherapy.

PURPOSE: To investigate whether magnesium oxide during external-beam radiotherapy for prostate cancer reduces intrafraction prostate motion in a double-blind, placebo-controlled randomized trial. METHODS AND MATERIALS: At the Department of Radiotherapy, prostate cancer patients scheduled for intensity-modulated radiotherapy (77 Gy in 35 fractions) using fiducial marker-based position verification were randomly assigned to receive magnesium oxide (500 mg twice a day) or placebo during radiotherapy. The primary outcome was the proportion of patients with clinically relevant intrafraction prostate motion, defined as the proportion of patients who demonstrated in ≥ 50% of the fractions an intrafraction motion outside a range of 2 mm. Secondary outcome measures included quality of life and acute toxicity. RESULTS: In total, 46 patients per treatment arm were enrolled. The primary endpoint did not show a statistically significant difference between the treatment arms with a percentage of patients with clinically relevant intrafraction motion of 83% in the magnesium oxide arm as compared with 80% in the placebo arm (p = 1.00). Concerning the secondary endpoints, exploratory analyses demonstrated a trend towards worsened quality of life and slightly more toxicity in the magnesium oxide arm than in the placebo arm; however, these differences were not statistically significant. CONCLUSIONS: Magnesium oxide is not effective in reducing the intrafraction prostate motion during external-beam radiotherapy, and therefore there is no indication to use it in clinical practice for this purpose.

Single blind randomized phase III trial to investigate the benefit of a focal lesion ablative microboost in prostate cancer (FLAME-trial): study protocol for a randomized controlled trial.

BACKGROUND: The treatment results of external beam radiotherapy for intermediate and high risk prostate cancer patients are insufficient with five-year biochemical relapse rates of approximately 35%. Several randomized trials have shown that dose escalation to the entire prostate improves biochemical disease free survival. However, further dose escalation to the whole gland is limited due to an unacceptable high risk of acute and late toxicity. Moreover, local recurrences often originate at the location of the macroscopic tumor, so boosting the radiation dose at the macroscopic tumor within the prostate might increase local control. A reduction of distant metastases and improved survival can be expected by reducing local failure. The aim of this study is to investigate the benefit of an ablative microboost to the macroscopic tumor within the prostate in patients treated with external beam radiotherapy for prostate cancer. METHODS/DESIGN: The FLAME-trial (Focal Lesion Ablative Microboost in prostatE cancer) is a single blind randomized controlled phase III trial. We aim to include 566 patients (283 per treatment arm) with intermediate or high risk adenocarcinoma of the prostate who are scheduled for external beam radiotherapy using fiducial markers for position verification. With this number of patients, the expected increase in five-year freedom from biochemical failure rate of 10% can be detected with a power of 80%. Patients allocated to the standard arm receive a dose of 77 Gy in 35 fractions to the entire prostate and patients in the experimental arm receive 77 Gy to the entire prostate and an additional integrated microboost to the macroscopic tumor of 95 Gy in 35 fractions. The secondary outcome measures include treatment-related toxicity, quality of life and disease-specific survival. Furthermore, by localizing the recurrent tumors within the prostate during follow-up and correlating this with the delivered dose, we can obtain accurate dose-effect information for both the macroscopic tumor and subclinical disease in prostate cancer. The rationale, study design and the first 50 patients included are described. TRIAL REGISTRATION: This study is registered at ClinicalTrials.gov: NCT01168479.

Influence of antiflatulent dietary advice on intrafraction motion for prostate cancer radiotherapy.

PURPOSE: To evaluate the effect of an antiflatulent dietary advice on the intrafraction prostate motion in patients treated with intensity-modulated radiotherapy (IMRT) for prostate cancer. METHODS AND MATERIALS: Between February 2002 and December 2009, 977 patients received five-beam IMRT for prostate cancer to a dose of 76 Gy in 35 fractions combined with fiducial markers for position verification. In July 2008, the diet, consisting of dietary guidelines to obtain regular bowel movements and to reduce intestinal gas by avoiding certain foods and air swallowing, was introduced to reduce the prostate motion. The intrafraction prostate movement was determined from the portal images of the first segment of all five beams. Clinically relevant intrafraction motion was defined as ≥50% of the fractions with an intrafraction motion outside a range of 3 mm. RESULTS: A total of 739 patients were treated without the diet and 105 patients were treated with radiotherapy after introduction of the diet. The median and interquartile range of the average intrafraction motion per patient was 2.53 mm (interquartile range, 2.2-3.0) without the diet and 3.00 mm (interquartile range, 2.4-3.5) with the diet (p < .0001). The percentage of patients with clinically relevant intrafraction motion increased statistically significant from 19.1% without diet to 42.9% with a diet (odds ratio, 3.18; 95% confidence interval, 2.07-4.88; p < .0001). CONCLUSIONS: The results of the present study suggest that antiflatulent dietary advice for patients undergoing IMRT for prostate cancer does not reduce the intrafraction movement of the prostate. Therefore, antiflatulent dietary advice is not recommended in clinical practice for this purpose.