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Background and purpose: Accelerated partial breast irradiation (APBI) may benefit from the MR-Linac for target definition, patient setup, and motion monitoring. In this planning study, we investigated whether prone or supine position is dosimetrically beneficial for APBI on an MR-Linac and we evaluated patient comfort. Materials and methods: Twenty-patients (9 postoperative, 11 preoperative) with a DCIS or breast tumor

Background and purpose: In (ultra-)hypofractionation, the contribution of intrafraction motion to treatment accuracy becomes increasingly important. Our purpose was to evaluate intrafraction motion and resulting geometric uncertainties for breast tumor (bed) and individual axillary lymph nodes, and to compare prone and supine position for the breast tumor (bed). Materials and methods: During 1–3 min of free breathing, we acquired transverse/sagittal interleaved 1.5 T cine magnetic resonance imaging (MRI) of the breast tumor (bed) in prone and supine position and coronal/sagittal cine MRI of individual axillary lymph nodes in supine position. A total of 31 prone and 23 supine breast cine MRI (in 23 women) and 52 lymph node cine MRI (in 24 women) were included. Maximum displacement, breathing amplitude, and drift were analyzed using deformable image registration. Geometric uncertainties were calculated for all displacements and for breathing motion only. Results: Median maximum displacements (range over the three orthogonal orientations) were 1.1–1.5 mm for the breast tumor (bed) in prone and 1.8–3.0 mm in supine position, and 2.2–2.4 mm for lymph nodes. Maximum displacements were significantly smaller in prone than in supine position, mainly due to smaller breathing amplitude: 0.6–0.9 mm in prone vs. 0.9–1.4 mm in supine. Systematic and random uncertainties were 0.1–0.4 mm in prone position and 0.2–0.8 mm in supine position for the tumor (bed), and 0.4–0.6 mm for the lymph nodes. Conclusion: Intrafraction motion of breast tumor (bed) and individual lymph nodes was small. Motion of the tumor (bed) was smaller in prone than in supine position.

Contains fulltext : 251425.pdf (Publisher’s version ) (Open Access) PURPOSE: We aimed to evaluate changes in dynamic contrast-enhanced (DCE) and diffusion-weighted (DW) magnetic resonance imaging (MRI) scans acquired before and after single-dose ablative neoadjuvant partial breast irradiation (NA-PBI), and explore the relation between semiquantitative MRI parameters and radiologic and pathologic responses. METHODS AND MATERIALS: We analyzed 3.0T DCE and DW-MRI of 36 patients with low-risk breast cancer who were treated with single-dose NA-PBI, followed by breast-conserving surgery 6 or 8 months later. MRI was acquired before NA-PBI and 1 week, 2, 4, and 6 months after NA-PBI. Breast radiologists assessed the radiologic response and breast pathologists scored the pathologic response after surgery. Patients were grouped as either pathologic responders or nonresponders (

Contains fulltext : 219916.pdf (Publisher’s version ) (Closed access) PURPOSE: To assess the pathologic and radiologic response in patients with low-risk breast cancer treated with magnetic resonance (MR) guided neoadjuvant partial breast irradiation (NA-PBI) and to evaluate toxicity and patient-reported outcomes (PROs). METHODS AND MATERIALS: For this single-arm prospective trial, women with unifocal, non-lobular tumors with a maximum diameter of 20 mm (age, 50-70 years) or 30 mm (age, >/=70 years) and tumor-negative sentinel node(s) were eligible. Patients were treated with a single ablative dose of NA-PBI followed by breast-conserving surgery after an interval of 6 to 8 months. Target volumes were defined on radiation therapy planning computed tomography scan and additional magnetic resonance imaging. Prescribed doses to gross tumor volume and clinical target volume (gross tumor volume plus 20 mm margin) were 20 Gy and 15 Gy, respectively. Primary outcome was pathologic complete response (pCR). Secondary outcomes were radiologic response (on magnetic resonance imaging), toxicity (Common Terminology Criteria for Adverse Events), PROs (European Organisation for Research and Treatment of Cancer QLQ-BR23, Hospital Anxiety and Depression Scale), and cosmesis (assessed by patient, radiation oncologist, and BCCT.core software). RESULTS: Thirty-six patients were treated with NA-PBI, and pCR was reported in 15 patients (42%; 95% confidence interval, 26%-59%). Radiologic complete response was observed in 15 patients, 10 of whom had pCR (positive predictive value, 67%; 95% confidence interval, 39%-87%). After a median follow-up of 21 months (range, 12-41), all patients experienced grade 1 fibrosis in the treated breast volume. Transient grade 2 and 3 toxicity was observed in 31% and 3% of patients, respectively. Local recurrences were absent. No deterioration in PROs or cosmetic results was observed. CONCLUSIONS: NA-PBI has the potential to induce pCR in a substantial proportion of patients, with acceptable toxicity. This treatment seems a feasible alternative to standard postoperative irradiation and could even result in postponement or omission of surgery if pCR can be accurately predicted in selected low-risk patients.

A synthetic computed tomography (sCT) is required for daily plan optimization on an MRI-linac. Yet, only limited information is available on the accuracy of dose calculations on sCT for breast radiotherapy. This work aimed to (1) evaluate dosimetric accuracy of treatment plans for single-fraction neoadjuvant partial breast irradiation (PBI) on a 1.5 T MRI-linac calculated on a) bulk-density sCT mimicking the current MRI-linac workflow and b) deep learning-generated sCT, and (2) investigate the number of bulk-density levels required. For ten breast cancer patients we created three bulk-density sCTs of increasing complexity from the planning-CT, using bulk-density for: (1) body, lungs, and GTV (sCTBD1); (2) volumes for sCTBD1 plus chest wall and ipsilateral breast (sCTBD2); (3) volumes for sCTBD2 plus ribs (sCTBD3); and a deep learning-generated sCT (sCTDL) from a 1.5 T MRI in supine position. Single-fraction neoadjuvant PBI treatment plans for a 1.5 T MRI-linac were optimized on each sCT and recalculated on the planning-CT. Image evaluation was performed by assessing mean absolute error (MAE) and mean error (ME) in Hounsfield Units (HU) between the sCTs and the planning-CT. Dosimetric evaluation was performed by assessing dose differences, gamma pass rates, and dose-volume histogram (DVH) differences. The following results were obtained (median across patients for sCTBD1/sCTBD2/sCTBD3/sCTDL respectively): MAE inside the body contour was 106/104/104/75 HU and ME was 8/9/6/28 HU, mean dose difference in the PTVGTV was 0.15/0.00/0.00/−0.07 Gy, median gamma pass rate (2%/2 mm, 10% dose threshold) was 98.9/98.9/98.7/99.4%, and differences in DVH parameters were well below 2% for all structures except for the skin in the sCTDL. Accurate dose calculations for single-fraction neoadjuvant PBI on an MRI-linac could be performed on both bulk-density and deep learning sCT, facilitating further implementation of MRI-guided radiotherapy for breast cancer. Balancing simplicity and accuracy, sCTBD2 showed the optimal number of bulk-density levels for a bulk-density approach.

Highlights • A deep learning network facilitated dose calculation from CBCT. • 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. • Generation of synthetic-CT can be achieved within 10 s, facilitating online adaptive radiotherapy scenarios., 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 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.

Highlights • All MRI-linac plans met the coverage and predefined OAR constraints. • The prone approach appeared to be more favorable with respect to the chest wall, and ipsilateral lung dose compared to the supine position. • Overall, the MRI-linac and clinical plans were comparable, with minor absolute dosimetric differences., Background In selected patients with early-stage and low-risk breast cancer, an MRI-linac based treatment might enable a radiosurgical, non-invasive alternative for current standard breast conserving therapy. Aim To investigate whether single dose accelerated partial breast (APBI) to the intact tumor in both the prone and supine radiotherapy positions on the MRI-linac is dosimetrically feasible with respect to predefined coverage and organs at risk (OAR) constraints. Material & methods For 20 patients with cTis or low-risk cT1N0M0 non-lobular breast carcinoma, previously treated with single dose preoperative APBI in the supine (n = 10) or prone (n = 10) position, additional intensity modulated radiotherapy plans with 7 coplanar beams in the presence of a 1.5T magnetic field were generated. A 20 Gy and 15 Gy dose was prescribed to the gross tumor and clinical target volume, respectively. The percentage of plans achieving predefined organ at risk (OAR) constraints, currently used in clinical practice, was assessed. Dosimetry differences between the prone versus supine approach and the MRI-linac versus clinically delivered plans were evaluated. Results All MRI-linac plans met the coverage and predefined OAR constraints. The prone approach appeared to be more favorable with respect to the chest wall, and ipsilateral lung dose compared to the supine position. No dosimetric differences were observed for the ipsilateral breast. No treatment position was clearly more beneficial for the skin or heart, since dosimetry varied among parameters. Overall, the MRI-linac and clinical plans were comparable, with minor absolute dosimetric differences. Conclusion MRI-linac based single dose APBI to the intact tumor is a promising and a dosimetrically feasible strategy in patients with low-risk breast cancer. Preliminary OAR dosimetry favored the prone radiotherapy position.

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.

Background and purpose: Local implementation of plan-specific quality assurance (QA) methods for intensity-modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) treatment plans may vary because of dissimilarities in procedures, equipment and software. The purpose of this work is detecting possible differences between local QA findings and those of an audit, using the same set of treatment plans. Methods: A pre-defined set of clinical plans was devised and imported in the participating institute’s treatment planning system for dose computation. The dose distribution was measured using an ionisation chamber, radiochromic film and an ionisation chamber array. The centres performed their own QA, which was compared to the audit findings. The agreement/disagreement between the audit and the institute QA results were assessed along with the differences between the dose distributions measured by the audit team and computed by the institute. Results: For the majority of the cases the results of the audit were in agreement with the institute QA findings: ionisation chamber: 92%, array: 88%, film: 76% of the total measurements. In only a few of these cases the evaluated measurements failed for both: ionisation chamber: 2%, array: 4%, film: 0% of the total measurements. Conclusion: Using predefined treatment plans, we found that in approximately 80% of the evaluated measurements the results of local QA of IMRT and VMAT plans were in line with the findings of the audit. However, the percentage of agreement/disagreement depended on the characteristics of the measurement equipment used and on the analysis metric. Keywords: Quality assurance, Dosimetry audit, IMRT, VMAT, QA devices

Pancreatic tumors show large interfractional position variation. In addition, changes in gastrointestinal gas volumes and body contour take place over the course of radiation therapy. We aimed to quantify the effect of these anatomical changes on target dose coverage, for the clinically used fiducial marker‐based patient position verification and, for comparison, also for simulated bony anatomy‐based position verification. Nine consecutive patients were included in this retrospective study. To enable fraction dose calculations on cone‐beam CT (CBCT), the planning CT was deformably registered to each CBCT (13–15 per patient); gas volumes visible on CBCT were copied to the deformed CT. Fraction doses were calculated for the clinically used 10 MV VMAT treatment plan (with for the planning target volume (PTV): D98% = 95%), according to fiducial marker‐based and bony anatomy‐based image registrations. Dose distributions were rigidly summed to yield the accumulated dose. To evaluate target dose coverage, we defined an iCTV +5 mm volume, i.e., the internal clinical target volume (iCTV) expanded with a 5 mm margin to account for remaining uncertainties including delineation uncertainties. We analyzed D98%, Dmean, and D2% for iCTV +5 mm and PTV (i.e., iCTV plus 10 mm margin). We found that for fiducial marker‐based registration, differences between fraction doses and planned dose were minimal. For bony anatomy‐based registration, fraction doses differed considerably, resulting in large differences between planned and accumulated dose for some patients, up to a decrease in D98% of the iCTV +5 mm from 95.9% to 85.8%. Our study shows that fractionated photon irradiation of pancreatic tumors is robust against variations in body contour and gastrointestinal gas, with dose coverage only mildly affected. However, as a result of interfractional tumor position variations, target dose coverage can severely decline when using bony anatomy for patient position verification. Therefore, the use of intratumoral fiducial marker‐based daily position verification is essential in pancreatic cancer patients.

To perform patient plan quality assurance (QA) on a newly installed MR-linac (MRL) it is necessary to have an MR-compatible QA device. An MR compatible device (MR-Delta4) has been developed together with Scandidos AB (Uppsala, Sweden). The basic characteristics of the detector response, such as short-term reproducibility, dose linearity, field size dependency, dose rate dependency, dose-per-pulse dependency and angular dependency, were investigated for the clinical Delta4-PT as well as for the MR compatible version. All tests were performed with both devices on a conventional linac and the MR compatible device was tested on the MRL as well. No statistically significant differences were found in the short-term reproducibility (

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.&#13.

Purpose: In radiation therapy of pancreatic cancer, tumor alignment prior to each treatment fraction is improved when intratumoral gold fiducial markers (from here onwards: markers), which are visible on computed tomography (CT) and cone beam CT, are used. Visibility of these markers on magnetic resonance imaging (MRI) might improve image registration between CT and magnetic resonance (MR) images for tumor delineation purposes. However, concomitant image artifacts induced by markers are undesirable. The extent of visibility and artifact size depend on MRI-sequence parameters. The authors’ goal was to determine for various markers their potential to be visible and to generate artifacts, using measures that are independent of the MRI-sequence parameters. Methods: The authors selected ten different markers suitable for endoscopic placement in the pancreas and placed them into a phantom. The markers varied in diameter (0.28–0.6 mm), shape, and iron content (0%–0.5%). For each marker, the authors calculated T 2 ∗-maps and ΔB 0-maps using MRI measurements. A decrease in relaxation time T 2 ∗ can cause signal voids, associated with visibility, while a change in the magnetic field B 0 can cause signal shifts, which are associated with artifacts. These shifts inhibit accurate tumor delineation. As a measure for potential visibility, the authors used the volume of low T 2 ∗, i.e., the volume for which T 2 ∗ differed from the background by >15 ms. As a measure for potential artifacts, the authors used the volume for which |ΔB 0| > 9.4 × 10−8 T (4 Hz). To test whether there is a correlation between visibility and artifact size, the authors calculated the Spearman’s correlation coefficient (Rs ) between the volume of low T 2 ∗ and the volume of high |ΔB 0|. The authors compared the maps with images obtained using a clinical MR-sequence. Finally, for the best visible marker as well as the marker that showed the smallest artifact, the authors compared the phantom data with in vivo MR-images in four pancreatic cancer patients. Results: The authors found a strong correlation (Rs = 1.00, p < 0.01) between the volume of low T 2 ∗ and the volume with high |ΔB 0|. Visibility in clinical MR-images increased with lower T 2 ∗. Signal shift artifacts became worse for markers with high |ΔB 0|. The marker that was best visible in the phantom, a folded marker with 0.5% iron content, was also visible in vivo, but showed artifacts on diffusion weighted images. The marker with the smallest artifact in the phantom, a small, stretched, ironless marker, was indiscernible on in vivo MR-images. Conclusions: Changes in T 2 ∗ and ΔB 0 are sequence-independent measures for potential visibility and artifact size, respectively. Improved visibility of markers correlates strongly to signal shift artifacts; therefore, marker choice will depend on the clinical purpose. When visibility of the markers is most important, markers that contain iron are optimal, preferably in a folded configuration. For artifact sensitive imaging, small ironless markers are best, preferably in a stretched configuration.

Background and purpose: Structure -based deformable image registration (DIR) can be used to calculate accumulated brachytherapy (BT) and external -beam radiation therapy (EBRT) dose-volume histogram (DVH) parameters in cervical cancer. Since direct parameter addition does not take dose non uniformity into account, the added value of DIR over addition methods was investigated for bladder and rectum.Materials and methods: For twelve patients (EBRT: 46 Gy, EBRT + BT: D-90 85-90 Gy(EQD2) in equivalent dose in 2 Gy fractions) the EBRT planning CT and BT planning MRI were registered using DIR. Affected lymph nodes, located far from the BT boost region, received an EBRT boost (9.2 Gy) not contributing to the BT boost dose. Cumulative bladder/rectum D-2cm3/D-1cm3 were calculated and compared to direct addition methods, assuming uniform EBRT doses (UD), or overlapping high dose volumes (OHD).Results: Between the three methods, the maximum differences in the cumulative DVH parameters were 3.2 GY(EQD2) (bladder) and 3.3 GY(EQD2) (rectum). The difference between DIR and UD was

Purpose: To quantify magnetic resonance imaging (MRI)distortions on a plastic intracavitary/interstitial applicator with plastic needles at a field strength of 3 T and to determine the dosimetric impact, using patient data.Methods and Materials: For 11 cervical cancer patients, our clinical MRI protocol was extended with 3 scans. From the first scan, a multi-echo acquisition, a map of the magnetic field (B-0) was calculated and used to quantify the field inhomogeneity. The expected displacements of the applicator were quantified for the clinical sequence using the measured field inhomogeneity and the clinical sequence's bandwidth. The second and third scan were our routine clinical sequence (duration

Radiotherapy using charged particles is characterized by a low dose to the surrounding healthy organs, while delivering a high dose to the tumor. However, interfractional anatomical changes can greatly affect the robustness of particle therapy. Therefore, we compared the dosimetric impact of interfractional anatomical changes (i.e. body contour differences and gastrointestinal gas volume changes) in photon, proton and carbon ion therapy for pancreatic cancer patients. In this retrospective planning study, photon, proton and carbon ion treatment plans were created for 9 patients. Fraction dose calculations were performed using daily cone-beam CT (CBCT) images. To this end, the planning CT was deformably registered to each CBCT; gastrointestinal gas volumes were delineated on the CBCTs and copied to the deformed CT. Fraction doses were accumulated rigidly. To compare planned and accumulated dose, dose-volume histogram (DVH) parameters of the planned and accumulated dose of the different radiotherapy modalities were determined for the internal gross tumor volume, internal clinical target volume (iCTV) and organs-at-risk (OARs; duodenum, stomach, kidneys, liver and spinal cord). Photon plans were highly robust against interfractional anatomical changes. The difference between the planned and accumulated DVH parameters for the photon plans was less than 0.5% for the target and OARs. In both proton and carbon ion therapy, however, coverage of the iCTV was considerably reduced for the accumulated dose compared with the planned dose. The near-minimum dose ([Formula: see text]) of the iCTV reduced with 8% for proton therapy and with 10% for carbon ion therapy. The DVH parameters of the OARs differed less than 3% for both particle modalities. Fractionated radiotherapy using photons is highly robust against interfractional anatomical changes. In proton and carbon ion therapy, such changes can severely reduce the dose coverage of the target.

Purpose The purpose of this study was to investigate if FDG-PET and DWI identify the same or different targets for dose escalation in the GTV of HN cancer patients. Additionally, the dose coverage of DWI-targets in an FDG-PET-based dose painting plan was analyzed. Materials and methods Eighteen HN cancer patients underwent FDG-PET and DWI exams, which were converted to standardized uptake value (SUV)- and apparent diffusion coefficient (ADC)-maps. The correspondence between the two imaging modalities was determined on a voxel-level using Spearman's correlation coefficient ( ρ ). Dose painting plans were optimized based on the 50% isocontour of the maximum SUV ( SUV 50%max ). Dose coverage was analyzed in three different SUV- and three different ADC-targets using the mean dose and the near-minimum and near-maximum doses. Results The average maximum SUV was 13.9 and the mean ADC was 1.17·10 −3 mm 2 /s. The average ρ between SUV and ADC was −0.2 (range: −0.6 to 0.4). The ADC-targets were only partly overlapping the SUV 50%max -target and the dose parameters were significantly smaller in the ADC-targets compared to the SUV 50%max -target. Conclusions FDG-PET and DWI contain different information, resulting in different targets. Further information about failure patterns and dose relations can be obtained by adding DWI to currently ongoing dose painting trials.

Purpose Four-dimensional positron emission tomography (4D PET) imaging of the thorax produces sharper images with reduced motion artifacts. Current radiation therapy planning systems, however, do not facilitate 4D plan optimization. When images are acquired in a 2-minute time slot, the signal-to-noise ratio of each 4D frame is low, compromising image quality. The purpose of this study was to implement and evaluate the construction of mid-position 3D PET scans, with motion compensated using a 4D computed tomography (CT)-derived motion model. Methods and Materials All voxels of 4D PET were registered to the time-averaged position by using a motion model derived from the 4D CT frames. After the registration the scans were summed, resulting in a motion-compensated 3D mid-position PET scan. The method was tested with a phantom dataset as well as data from 27 lung cancer patients. Results PET motion compensation using a CT-based motion model improved image quality of both phantoms and patients in terms of increased maximum SUV (SUV max ) values and decreased apparent volumes. In homogenous phantom data, a strong relationship was found between the amplitude-to-diameter ratio and the effects of the method. In heterogeneous patient data, the effect correlated better with the motion amplitude. In case of large amplitudes, motion compensation may increase SUV max up to 25% and reduce the diameter of the 50% SUV max volume by 10%. Conclusions 4D CT-based motion-compensated mid-position PET scans provide improved quantitative data in terms of uptake values and volumes at the time-averaged position, thereby facilitating more accurate radiation therapy treatment planning of pulmonary lesions.

Modern radiation therapy techniques are exceptionally flexible in the deposition of radiation dose in a target volume. Complex distributions of dose can be delivered reliably, so that the tumor is exposed to a high dose, whereas nearby healthy structures can be avoided. As a result, an increase in curative dose is no longer invariably associated with an increased level of toxicity. This modern technology can be exploited further by modulating the required dose in space so as to match the variation in radiation sensitivity in the tumor. This approach is called dose painting. For dose painting to be effective, functional imaging techniques are essential to identify regions in a tumor that require a higher dose. Several techniques are available in nuclear medicine and radiology. In recent years, there has been a considerable research effort concerning the integration of magnetic resonance imaging (MRI) into the external radiotherapy workflow motivated by the superior soft tissue contrast as compared to computed tomography. In MRI, diffusion-weighted MRI reflects the cell density of tissue and thus may indicate regions with a higher tumor load. Dynamic contrast-enhanced MRI reflects permeability of the microvasculature and blood flow, correlated to the oxygenation of the tumor. These properties have impact on its radiation sensitivity. New questions must be addressed when these techniques are applied in radiation therapy: scanning in treatment position requires alternative solutions to the standard patient setup in the choice of receive coils compared to a diagnostic department. This standard positioning also facilitates repeated imaging. The geometrical accuracy of MR images is critical for high-precision radiotherapy. In particular, when multiparametric functional data are used for dose painting, quantification of functional parameters at a high spatial resolution becomes important. In this review, we will address these issues and describe clinical developments in MRI-guided dose painting.

Background and purpose: We evaluated the robustness of carbon ion therapy for pancreatic cancer patients by investigating the impact of interfractional anatomical changes on the accumulated dose when using bony anatomy- and fiducial marker-based position verification.Material and methods: Carbon ion treatment plans were created for 9 patients in this retrospective planning study. The planning CT was deformably registered to each daily cone-beam CT (CBCT). The gastrointestinal gas volume visible on each CBCT was copied to these deformed CT images. Subsequently, the fraction doses were calculated by aligning the treatment plan according to a bony anatomy- and a fiducial marker-based registration.We compared the accumulated fraction doses with the planned dose using dose-volume histograms (DVHs) of the internal gross tumour volume (iGTV), internal clinical target volume (iCTV), duodenum, stomach, liver, spinal cord and kidneys.Results: iCTV coverage (D-98%) was on average reduced from 98.6% as planned to 81.9% and 88.6% for the bony anatomy- and marker-based registrations, respectively. DVHs of the duodenum showed large differences between the planned and accumulated dose.Conclusions: Severe reductions in dose coverage of the target due to interfractional anatomical changes were observed in both position verification methods. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

At the UMC Utrecht, a linear accelerator with integrated magnetic resonance imaging (MRI) has been developed, the MR-linac. Patient-specific quality assurance (QA) of treatment plans for MRI-based image guided radiotherapy requires QA equipment compatible with this 1.5 T magnetic field. The purpose of this study was to examine the performance characteristics of the ArcCHECK-MR in a transverse 1.5 T magnetic field. To this end, the short-term reproducibility, dose linearity, dose rate dependence, field size dependence, dose per pulse dependence and inter-diode dose response variation of the ArcCHECK-MR diode array were evaluated on a conventional linac and on the MR-linac. The ArcCHECK-MR diode array performed well for all tests on both linacs, no significant differences in performance characteristics were observed. Differences in the maximum dose deviations between both linacs were less than 1.5%. Therefore, we conclude that the ArcCHECK-MR can be used in a transverse 1.5 T magnetic field.

PURPOSE: To quantify distortions on MR images of the Utrecht interstitial CT/MR applicator at a field strength of 3T using an MRI-only method.MATERIALS AND METHODS: An MR-compatible phantom suspending the applicator in water was built and imaged on a Philips Ingenia 3T MRI scanner. A map of the magnetic field (B-0) was calculated from multiecho images and used to quantify the field inhomogeneity. The expected displacements of the applicator could be quantified using the measured field inhomogeneity and sequence bandwidth. Additionally, two scans were acquired using opposing readout gradients. These scans were rigidly matched and their displacement was compared with the expected displacements from the B-0 map.These same methods were applied in 4 patients. By rigid matching of the scans acquired with opposing readout direction the applicator displacement due to image distortion from B-0 inhomogeneity as well as patient movement and organ deformation was determined.RESULTS: According to the B-0 map, the displacement on the intrauterine device of the plastic brachytherapy applicator was

Purpose: The dose response relationship of the parotid gland has been described most frequently using the Lyman-Kutcher-Burman model. However, various other normal tissue complication probability (NTCP) models exist. We evaluated in a large group of patients the value of six NTCP models that describe the parotid gland dose response 1 year after radiotherapy.Methods and Materials: A total of 347 patients with head-and-neck tumors were included in this prospective parotid gland dose response study. The patients were treated with either conventional radiotherapy or intensitymodulated radiotherapy. Dose volume histograms for the parotid glands were derived from three-dimensional dose calculations using computed tomography scans. Stimulated salivary flow rates were measured before and 1 year after radiotherapy. A threshold of 25% of the pretreatment flow rate was used to define a complication. The evaluated models included the Lyman-Kutcher-Burman model, the mean dose model, the relative seriality model, the critical volume model, the parallel functional subunit model, and the dose threshold model. The goodness of fit (GOF) was determined by the deviance and a Monte Carlo hypothesis test. Ranking of the models was based on Akaike's information criterion (AIC).Results: None of the models was rejected based on the evaluation of the GOF. The mean dose model was ranked as the best model based on the AIC. The TD50 in these models was approximately 39 Gy.Conclusions: The mean dose model was preferred for describing the dose response relationship of the parotid gland. (C) 2010 Elsevier Inc.

In radiation therapy of pancreatic cancer, tumor alignment prior to each treatment fraction is improved when intratumoral gold fiducial markers (from here onwards: markers), which are visible on computed tomography (CT) and cone beam CT, are used. Visibility of these markers on magnetic resonance imaging (MRI) might improve image registration between CT and magnetic resonance (MR) images for tumor delineation purposes. However, concomitant image artifacts induced by markers are undesirable. The extent of visibility and artifact size depend on MRI-sequence parameters. The authors' goal was to determine for various markers their potential to be visible and to generate artifacts, using measures that are independent of the MRI-sequence parameters.The authors selected ten different markers suitable for endoscopic placement in the pancreas and placed them into a phantom. The markers varied in diameter (0.28-0.6 mm), shape, and iron content (0%-0.5%). For each marker, the authors calculated T2 (∗)-maps and ΔB0-maps using MRI measurements. A decrease in relaxation time T2 (∗) can cause signal voids, associated with visibility, while a change in the magnetic field B0 can cause signal shifts, which are associated with artifacts. These shifts inhibit accurate tumor delineation. As a measure for potential visibility, the authors used the volume of low T2 (∗), i.e., the volume for which T2 (∗) differed from the background by15 ms. As a measure for potential artifacts, the authors used the volume for which |ΔB0|9.4 × 10(-8) T (4 Hz). To test whether there is a correlation between visibility and artifact size, the authors calculated the Spearman's correlation coefficient (Rs) between the volume of low T2 (∗) and the volume of high |ΔB0|. The authors compared the maps with images obtained using a clinical MR-sequence. Finally, for the best visible marker as well as the marker that showed the smallest artifact, the authors compared the phantom data with in vivo MR-images in four pancreatic cancer patients.The authors found a strong correlation (Rs = 1.00, p0.01) between the volume of low T2 (∗) and the volume with high |ΔB0|. Visibility in clinical MR-images increased with lower T2 (∗). Signal shift artifacts became worse for markers with high |ΔB0|. The marker that was best visible in the phantom, a folded marker with 0.5% iron content, was also visible in vivo, but showed artifacts on diffusion weighted images. The marker with the smallest artifact in the phantom, a small, stretched, ironless marker, was indiscernible on in vivo MR-images.Changes in T2 (∗) and ΔB0 are sequence-independent measures for potential visibility and artifact size, respectively. Improved visibility of markers correlates strongly to signal shift artifacts; therefore, marker choice will depend on the clinical purpose. When visibility of the markers is most important, markers that contain iron are optimal, preferably in a folded configuration. For artifact sensitive imaging, small ironless markers are best, preferably in a stretched configuration.

Purpose: The first clinical MR-linac will soon become operational, therefore patient plan QA procedures and equipment have to become MRcompatible. Reference dosimetry is affected by the magnetic field, however, relative dosimetry using patient QA systems haven’t been investigated extensively. The purpose of this study was to examine the performance characteristics of the MR-compatible ArcCHECK and Delta4 systems in a transverse 1.5 T magnetic field. Methods: Recently MR-compatible versions of both ArcCheck (Sun Nuclear) and Delta4 (Scandidos) have been developed. To examine the performance characteristics within the magnetic field, the reproducibility, dose linearity, dose rate dependence, field size and angular dependence were evaluated on the MR-linac (8 MV FFF beam, SAD of 142 cm) and a conventional linac (Elekta, 6MV). To allow comparison of the measurements with and without magnetic field, the measurement setup for the conventional linac is adapted to mimic the setup at the MR-linac if possible (e.g. SAD, dose rate). The results from the MR-linac were benchmarked to the results from the conventional linac as being the clinical reference. Results: At the moment of writing, measurements for the Delta4 are still running. Therefore, only the results of the ArcCheck are presented in this abstract. No significant difference was observed in the reproducibility of the ArcCheck (

Conclusions: During this feasibility study of a TRUS/CT treatment planning workflow for cervix cancer BT a full treatment could be simulated for one patient, resulting in a clinically acceptable dose distribution. A need for improved applicator localisation in TRUS volumes has been identified. Image registration accuracy could be improved by automatic applicator tracking during US acquisition, thus minimizing reconstruction uncertainties due to insufficient depiction of the whole applicator on US images.

Purpose We investigated radiation-induced changes in the salivary glands, 6weeks after RT, using MRI. Materials and methods Eighteen oropharyngeal cancer patients were treated with salivary gland sparing IMRT. All patients received a 3T MRI exam before and 6weeks after the end of RT, including a T 1 -weighted (T 1 w), a T 2 -weighted (T 2 w), and a dynamic contrast-enhanced (DCE) MRI. For both time points separately, the parotid and submandibular glands were delineated on the MR images. Differences in median signal intensity and signal variation within the glands were tested for significance. Correlations were studied between the MR changes and the planned RT dose. Results The volume of the glands reduced significantly by 25%. The T 1 w signal decreased by 10% and the T 2 w signal increased by 23%. The k ep value decreased, while the v e increased. A correlation of the changes in T 2 w signal with the mean dose was found in both glands. Conclusions Overall radiation-induced changes and volume loss were observed in the parotid and submandibular gland using MR. The observed differences indicated an increased water content such as found in oedema. The overall changes could be related to the mean dose, with a slightly greater impact in the high dose area.

Purpose Besides sparing the parotid gland, sparing the submandibular gland is considered to be important in preventing xerostomia in head-and-neck cancer patients. Delineation of the submandibular gland at CT, and even on T 1 - and T 2 -weighted MR images, is difficult, due to low contrast with the surrounding tissues. MR sialography might be used for delineation. Methods and materials Sixteen oropharyngeal cancer patients received a CT and MRI exam as part of the standard treatment imaging protocol. Patients were scanned in their five-point RT immobilization mask. The MRI exam included T 1 - and T 2 -weighted MRI scans and an MR sialography scan. Thirty submandibular glands were delineated on only CT, on the combined CT and T 1 - and T 2 -weighted MRI scans and on all MR images. A Wilcoxon signed-rank test was performed to test if the delineated volumes were significantly different. Results The delineated volume of the submandibular gland was 7.3mL in the CT-delineation, 7.1mL in the CT/MRI-delineation and 8.1mL in the MRI-delineation. The MRI-delineation was significantly larger than the other delineations ( p Conclusion The delineation of the submandibular gland was improved in the cranial direction by using T 1 - and T 2 -weighted MRI and MR sialography, compared to the other delineations.

To analyze the combined and updated results from the University of Michigan and University Medical Center Utrecht on normal tissue complication probability (NTCP) of the parotid gland 1 year after radiotherapy (RT) for head-and-neck (HN) cancer.A total of 222 prospectively analyzed patients with various HN malignancies were treated with conventional and intensity-modulated RT. Stimulated individual parotid gland flow rates were measured before RT and 1 year after RT using Lashley cups at both centers. A flow ratio25% of pretreatment was defined as a complication. The data were fitted to the Lyman-Kutcher-Burman model.A total of 384 parotid glands (Michigan: 157; Utrecht: 227 glands) was available for analysis 1 year after RT. Combined NTCP analysis based on mean dose resulted in a TD(50) (uniform dose leading to 50% complication probability) of 39.9 Gy and m (steepness of the curve) of 0.40. The resulting NTCP curve had good qualitative agreement with the combined clinical data. Mean doses of 25-30 Gy were associated with 17-26% NTCP.A definite NTCP curve for parotid gland function 1 year after RT is presented, based on mean dose. No threshold dose was observed, and TD(50) was equal to 40 Gy.

Background and purpose The submandibular glands are proposed to be important in preventing xerostomia in head-and-neck cancer patients. We investigated the feasibility of sparing the contralateral submandibular gland (cSMG) by reducing the dose to the contralateral planning target volume (PTV) and by reducing the clinical target volume (CTV)-to-PTV margin. Materials and methods Ten oropharyngeal cancer patients with a contralateral elective PTV were included in this planning study, using intensity modulated radiotherapy (IMRT). The effect on the mean dose to the cSMG of reducing the dose coverage to the contralateral elective PTV from 95 to 90% of the prescribed dose (54Gy in 1.8Gy daily fractions) was determined. The influence of reducing the margin for position uncertainty from 5 to 2mm was investigated. Results The mean dose to the cSMG was reduced from 54Gy to approximately 40Gy if the dose coverage to the contralateral PTV was reduced to 90% of the prescribed dose. The estimated normal tissue complication probability (NTCP) was reduced below 50%. Reducing the margin from 5 to 2mm resulted in a decrease in the mean dose to the cSMG of approximately 6Gy. Conclusions Reducing the mean dose to the cSMG below 40Gy is possible with a reasonable dose coverage of the contralateral elective PTV.

Purpose: MRI is increasingly used as a single imaging modality for brachytherapy treatment planning. The presence of a brachytherapy applicator may cause distortions in the images, especially at higher field strengths. Our aim is to develop a procedure to quantify these distortions theoretically for any MR-sequence and to verify the estimated deformations for clinical sequences. Methods: Image distortions due to perturbation of the B0-field are proportional to the ratio of the induced frequency shift and the read-out bandwidth of the applied sequence. By reconstructing a frequency-shift map from the phase data from a multi-echo sequence, distortions can be calculated for any MR-sequence. Verification of this method for estimating distortions was performed by acquiring images with opposing read-out directions and consequently opposing distortions. The applicator shift can be determined by rigidly matching these images. Clinically, T2W-TSE-images are used for this purpose. For pre-clinical tests, EPI-sequences with narrow read-out bandwidth (19.5–47.5Hz), consequently large distortions, were added to the set of clinical MRsequences. To quantify deformations of the Utrecht Interstitial CT/MR applicator (Elekta Brachytherapy) on a Philips Ingenia 3T MRI, pre-clinical tests were performed in a phantom with the applicator in water, followed by clinical validation. Results: Deformations observed in the narrow bandwidth EPI-images were well predicted using the frequency-shift, the latter giving an overestimation up to 30%/up to 1 voxel. For clinically applied MR-sequences distortions were well below the voxel size. In patient setup distortions determined from the frequency-shift map were at sub-voxel level (

Purpose: Pancreatic tumors show large interfractional position variations. In addition, changes in gastrointestinal air volume and body contour take place during treatment. We aim to investigate the robustness of the clinical treatment plans by quantifying the dosimetric effects of these anatomical changes. Methods: Calculations were performed for up to now 3 pancreatic cancer patients who had intratumoral fiducials for daily CBCT-based positioning during their 3-week treatment. For each patient, deformable image registration of the planning CT was used to assign Hounsfield Units to each of the 13—15 CBCTs; air volumes and body contour were copied from CBCT. The clinical treatment plan was used (CTV-PTV margin = 10 mm; 36Gy; 10MV; 1 arc VMAT). Fraction dose distributions were calculated and accumulated. The V95% of the clinical target volume (CTV) and planning target volume (PTV) were analyzed, as well as the dose to stomach, duodenum and liver. Dose accumulation was done for patient positioning based on the fiducials (as clinically used) as well as for positioning based on bony anatomy. Results: For all three patients, the V95% of the CTV remained 100%, for both fiducial- and bony anatomy-based positioning. For fiducial-based positioning, dose to duodenum en stomach showed no discernable differences withmore » planned dose. For bony anatomy-based positioning, the PTV V95% of the patient with the largest systematic difference in tumor position (patient 1) decreased to 85%; the liver Dmax increased from 33.5Gy (planned) to 35.5Gy. Conclusion: When using intratumoral fiducials, CTV dose coverage was only mildly affected by the daily anatomical changes. When using bony anatomy for patient positioning, we found a decline in PTV dose coverage due to the interfractional tumor position variations. Photon irradiation treatment plans for pancreatic tumors are robust to variations in body contour and gastrointestinal gas, but the use of fiducial-based daily position verification is imperative. This work was supported by the foundation Bergh in het Zadel through the Dutch Cancer Society (KWF Kankerbestrijding) project No. UVA 2011-5271.« less