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.

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.

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.

Impact of magnetic resonance-guided versus conventional radiotherapy workflows on organ at risk doses in stereotactic body radiotherapy for lymph node oligometastases.

Background and purpose: Magnetic resonance (MR)-linac delivery is expected to improve organ at risk (OAR) sparing. In this study, OAR doses were compared for online adaptive MR-linac treatments and conventional cone beam computed tomography (CBCT)-linac radiotherapy, taking into account differences in clinical workflows, especially longer session times for MR-linac delivery. Materials and methods: For 25 patients with pelvic/abdominal lymph node oligometastases, OAR doses were calculated for clinical pre-treatment and daily optimized 1.5 T MR-linac treatment plans (5 × 7 Gy) and compared with simulated CBCT-linac plans for the pre-treatment and online anatomical situation. Bowelbag and duodenum were re-contoured on MR-imaging acquired before, during and after each treatment session. OAR hard constraint violations, D0.5cc and D10cc values were evaluated, focusing on bowelbag and duodenum. Results: Overall, hard constraints for all OAR were violated less often in daily online MR-linac treatment plans compared with CBCT-linac: in 5% versus 22% of fractions, respectively. D0.5cc and D10cc values did not differ significantly. When taking treatment duration and intrafraction motion into account, estimated delivered doses to bowelbag and duodenum were lower with CBCT-linac if identical planning target volume (PTV) margins were used for both modalities. When reduced PTV margins were achievable with MR-linac treatment, bowelbag doses were lower compared with CBCT-linac. Conclusions: Compared with CBCT-linac treatments, the online adaptive MR-linac approach resulted in fewer hard planning constraint violations compared with single-plan CBCT-linac delivery. With respect to other bowelbag/duodenum dose-volume parameters, the longer duration of MR-linac treatment sessions negatively impacts the potential dosimetric benefit of daily adaptive treatment planning.

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.

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.

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.

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.

Clinical implementation of MRI-based organs-at-risk auto-segmentation with convolutional networks for prostate radiotherapy.

BACKGROUND: Structure delineation is a necessary, yet time-consuming manual procedure in radiotherapy. Recently, convolutional neural networks have been proposed to speed-up and automatise this procedure, obtaining promising results. With the advent of magnetic resonance imaging (MRI)-guided radiotherapy, MR-based segmentation is becoming increasingly relevant. However, the majority of the studies investigated automatic contouring based on computed tomography (CT). PURPOSE: In this study, we investigate the feasibility of clinical use of deep learning-based automatic OARs delineation on MRI. MATERIALS AND METHODS: We included 150 patients diagnosed with prostate cancer who underwent MR-only radiotherapy. A three-dimensional (3D) T1-weighted dual spoiled gradient-recalled echo sequence was acquired with 3T MRI for the generation of the synthetic-CT. The first 48 patients were included in a feasibility study training two 3D convolutional networks called DeepMedic and dense V-net (dV-net) to segment bladder, rectum and femurs. A research version of an atlas-based software was considered for comparison. Dice similarity coefficient, 95% Hausdorff distances (HD95), and mean distances were calculated against clinical delineations. For eight patients, an expert RTT scored the quality of the contouring for all the three methods. A choice among the three approaches was made, and the chosen approach was retrained on 97 patients and implemented for automatic use in the clinical workflow. For the successive 53 patients, Dice, HD95 and mean distances were calculated against the clinically used delineations. RESULTS: DeepMedic, dV-net and the atlas-based software generated contours in 60 s, 4 s and 10-15 min, respectively. Performances were higher for both the networks compared to the atlas-based software. The qualitative analysis demonstrated that delineation from DeepMedic required fewer adaptations, followed by dV-net and the atlas-based software. DeepMedic was clinically implemented. After retraining DeepMedic and testing on the successive patients, the performances slightly improved. CONCLUSION: High conformality for OARs delineation was achieved with two in-house trained networks, obtaining a significant speed-up of the delineation procedure. Comparison of different approaches has been performed leading to the succesful adoption of one of the neural networks, DeepMedic, in the clinical workflow. DeepMedic maintained in a clinical setting the accuracy obtained in the feasibility study.

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.

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.

Influence of daily setup measurements and corrections on the estimated delivered dose during IMRT treatment of prostate cancer patients.

PURPOSE: To evaluate the impact of marker-based position verification, using daily imaging and an off-line correction protocol, by calculating the delivered dose to prostate, rectum and bladder. METHODS: Prostate cancer patients (n=217) were treated with IMRT, receiving 35 daily fractions. Plans with five beams were optimized taking target coverage (CTV, boost) and organs-at-risk (rectum and bladder) into account. PTV margins were 8mm. Prostate position was verified daily using implanted fiducial gold markers by imaging the first segment of all the five beams on an EPID. Setup deviations were corrected off-line using an adapted shrinking-action-level protocol. The estimated delivered dose, including daily organ movements, was calculated using a version of PLATO's dose engine, enabling batch processing of large numbers of patients. The dose was calculated +/- inclusion of setup corrections, and was evaluated relative to the original static plan. The marker-based measurements were considered representative for all organs. RESULTS: Daily organ movements would result in an underdosage of 2-3Gy to CTV and boost volume relative to the original plan, which was prevented by daily setup corrections. The dose to rectum and bladder was on average unchanged, but a large spread was introduced by organ movements, which was reduced by including setup corrections. CONCLUSIONS: Without position verification and setup corrections, margins of 8mm would be insufficient to account for position uncertainties during IMRT of prostate cancer. With the daily off-line correction protocol, the remaining variations are accommodated adequately.

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.

Feasibility of stereotactic radiotherapy using a 1.5 T MR-linac: Multi-fraction treatment of pelvic lymph node oligometastases.

Online adaptive radiotherapy using the 1.5 Tesla MR-linac is feasible for SBRT (5 × 7 Gy) of pelvic lymph node oligometastases. The workflow allows full online planning based on daily anatomy. Session duration is less than 60 min. Quality assurance tests, including independent 3D dose calculations and film measurements were passed.

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.

Pancreatic gross tumor volume contouring on computed tomography (CT) compared with magnetic resonance imaging (MRI): Results of an international contouring conference.

PURPOSE: Accurate identification of the gross tumor volume (GTV) in pancreatic adenocarcinoma is challenging. We sought to understand differences in GTV delineation using pancreatic computed tomography (CT) compared with magnetic resonance imaging (MRI). METHODS AND MATERIALS: Twelve attending radiation oncologists were convened for an international contouring symposium. All participants had a clinical and research interest in pancreatic adenocarcinoma. CT and MRI scans from 3 pancreatic cases were used for contouring. CT and MRI GTVs were analyzed and compared. Interobserver variability was compared using Dice's similarity coefficient (DSC), Hausdorff distances, and Jaccard indices. Mann-Whitney tests were used to check for significant differences. Consensus contours on CT and MRI scans and constructed count maps were used to visualize the agreement. Agreement regarding the optimal method to determine GTV definition using MRI was reached. RESULTS: Six contour sets (3 from CT and 3 from MRI) were obtained and compared for each observer, totaling 72 contour sets. The mean volume of contours on CT was significantly larger at 57.48 mL compared with a mean of 45.76 mL on MRI, P = .011. The standard deviation obtained from the CT contours was significantly larger than the standard deviation from the MRI contours (P = .027). The mean DSC was 0.73 for the CT and 0.72 for the MRI (P = .889). The conformity index measurement was similar for CT and MRI (P = .58). Count maps were created to highlight differences in the contours from CT and MRI. CONCLUSIONS: Using MRI as a primary image set to define a pancreatic adenocarcinoma GTV resulted in smaller contours compared with CT. No differences in DSC or the conformity index were seen between MRI and CT. A stepwise method is recommended as an approach to contour a pancreatic GTV using MRI.

Intrafraction motion of the prostate during external-beam radiation therapy: analysis of 427 patients with implanted fiducial markers.

PURPOSE: To analyze the intrafraction motion of the prostate during external-beam radiation therapy of patients with prostate cancer. METHODS AND MATERIALS: Between August 2001-December 2005, 427 patients with Stage T3Nx/0Mx/0 prostate carcinoma received intensity-modulated radiation therapy treatment combined with position verification with fiducial gold markers. For a total of 11,426 treatment fractions (average, 27 per patient), portal images were taken of the first segment of all five beams. The irradiation time of the technique varied between 5-7 min. From these data, the location of gold markers could be established within every treatment beam under the assumption of minimal marker movement. RESULTS: In 66% of treatment fractions, a motion outside a range of 2 mm was observed, with 28% outside a range of 3 mm. The intrafraction marker movements showed that motion directions were often reversed. However, the effect was small. Even with perfect online position-correction at the start of irradiation, intrafraction motion caused position uncertainty, but systematic errors (Sigma) were limited to <0.6 mm, and random errors (sigma) to <0.9 mm. This would result in a lower limit of 2 mm for margins, in the absence of any other uncertainties. CONCLUSIONS: Intrafraction motion of the prostate occurs frequently during external-beam irradiation on a time scale of 5-7 min. Margins of 2 mm account for these intrafraction motions. However, larger margins are required in practice to accommodate other uncertainties in the treatment.

Analysis of fiducial marker-based position verification in the external beam radiotherapy of patients with prostate cancer.

PURPOSE: Evaluate the fiducial marker-based position verification in the external-beam radiotherapy of patients with prostate cancer. METHODS: Four hundred and fifty-three patients with prostate cancer received an IMRT treatment combined with fiducial marker-based position verification. Portal images were taken in all 35 treatment fractions. This database was used to study the accuracy of detecting the prostate position as well as the presence of time trends and the effectiveness of commonly used off-line correction protocols. RESULTS: The variation in inter-marker distance shows that the prostate position can be detected with an accuracy better than 0.6 mm. Significant time trends in prostate position occurred in 35%, 18% and 48% of the patients in the vertical, lateral and longitudinal directions, respectively, with 34%, 9% and 35% deviating more than 3 mm over the course of the treatment. Off-line correction protocols that estimate a deviation only in the first fractions of the treatment (shrinking action level (SAL), no action level (NAL)) are not effective in following these trends. With daily off-line position correction using an adapted SAL protocol we reduced systematic positioning errors in clinical practice to less than 0.8 mm in all directions. CONCLUSION: Fiducial markers are a reliable tool for prostate position verification. Time trends occur frequently. Correction procedures must take such trends into account.

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.