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Background & Purpose: Deep learning (DL) based auto-segmentation has shown to be beneficial for online adaptive radiotherapy (OART). However, auto-segmentation of clinical target volumes (CTV) is complex, as clinical interpretations are crucial in their definition. The resulting variation between clinicians and institutes hampers the generalizability of DL networks. In OART the CTV is delineated during treatment preparation which makes the clinician intent explicitly available during treatment. We studied whether multicenter generalisability improves when using this prior clinical knowledge, the pre-treatment delineation, as a patient-specific prior for DL models for online auto-segmentation of the mesorectal CTV., Material & Methods: We included intermediate risk or locally advanced rectal cancer patients from three centers. Patient-specific weight maps were created by combining the patient-specific CTV delineation on the pre-treatment scan with population-based variation of likely inter-fraction mesorectal CTV deformations. We trained two models to auto-segment the mesorectal CTV on in-house data, one with (MRI + prior) and one without (MRI-only) priors. Both models were applied to two external datasets. An external baseline model was trained without priors from scratch for one external center. Performance was evaluated on the DSC, surface Dice, 95HD and MSD., Results: For both external centers, the MRI + prior model outperformed the MRI-only model significantly on the segmentation metrics (p-values < 0.01). There was no significant difference between the external baseline model and the MRI + prior model., Conclusion: Adding patient-specific weight maps makes the CTV segmentation model more robust to institutional preferences. Performance was comparable to a model trained locally from scratch. This makes this approach suitable for generalization to multiple centers., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Tomas Janssen reports financial support was provided by Elekta AB. Nicole Ferreira Silverio reports financial support was provided by Elekta AB. Wouter van den Wollenberg reports financial support was provided by Elekta AB. Anja Betgen reports financial support was provided by Elekta AB. Lisa Wiersema reports financial support was provided by Elekta AB. Femke Peters reports financial support was provided by Elekta AB. Corrie A. M. Marijnen reports was provided by Elekta AB. Uulke A. van der Heide reports financial support was provided by Elekta AB. Rita Simoes reports financial support was provided by Elekta AB. Martijn P. W. Intven reports financial support was provided by Elekta AB. Martijn P.W. Intven reports a relationship with Dutch Cancer Society that includes: funding grants. Martijn P. W. Intven reports a relationship with Elekta AB that includes: speaking and lecture fees. Martijn P. W. Intven reports a relationship with Dutch Society for Radiotherapy and Oncology that includes: board membership. co-author serves in an editorial capacity for the journal Radiation & Oncology − UAvdH If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper]., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: The focal radiation therapy (RT) boost technique was shown in a phase III randomized controlled trial (RCT) to improve prostate cancer outcomes without increasing toxicity. This technique relies on the accurate delineation of prostate tumors on MRI. A recent prospective study evaluated radiation oncologists' accuracy when asked to delineate prostate tumors on MRI and demonstrated high variability in tumor contours. We sought to evaluate the impact of contour variability and inaccuracy on predicted clinical outcomes. We hypothesized that radiation oncologists' contour inaccuracies would yield meaningfully worse clinical outcomes., Methods and Materials: Forty-five radiation oncologists and 2 expert radiologists contoured prostate tumors on 30 patient cases. Of these cases, those with CT simulation or diagnostic CT available were selected for analysis. A knowledge-based planning model was developed to generate focal RT boost plans for each contour per the RCT protocol. The probability of biochemical failure (BF) was determined using a model from the RCT. The primary metric evaluated was delta BF (DBF = Participant BF - Expert BF). An absolute increase in BF ≥5% was considered clinically meaningful., Results: Eight patient cases and 394 target volumes for focal RT boost planning were included in this analysis. In general, participant plans were associated with worse predicted clinical outcomes compared to the expert plan, with an average absolute increase in BF of 4.3%. Of participant plans, 37% were noted to have an absolute increase in BF of 5% or more., Conclusions: Radiation oncologists' attempts to contour tumor targets for focal RT boost are frequently inaccurate enough to yield meaningfully inferior clinical outcomes for patients., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: To provide a comprehensive review of the means by which to optimize target volume definition for the purposes of treatment planning for patients with intact prostate cancer with a specific emphasis on focal boost volume definition., Methods: Here we conduct a narrative review of the available literature summarizing the current state of knowledge on optimizing target volume definition for the treatment of localized prostate cancer., Results: Historically, the treatment of prostate cancer included a uniform prescription dose administered to the entire prostate with or without coverage of all or part of the seminal vesicles. The development of prostate magnetic resonance imaging (MRI) and positron emission tomography (PET) using prostate-specific radiotracers has ushered in an era in which radiation oncologists are able to localize and focally dose-escalate high-risk volumes in the prostate gland. Recent phase 3 data has demonstrated that incorporating focal dose escalation to high-risk subvolumes of the prostate improves biochemical control without significantly increasing toxicity. Still, several fundamental questions remain regarding the optimal target volume definition and prescription strategy to implement this technique. Given the remaining uncertainty, a knowledge of the pathological correlates of radiographic findings and the anatomic patterns of tumor spread may help inform clinical judgement for the definition of clinical target volumes., Conclusion: Advanced imaging has the ability to improve outcomes for patients with prostate cancer in multiple ways, including by enabling focal dose escalation to high-risk subvolumes. However, many questions remain regarding the optimal target volume definition and prescription strategy to implement this practice, and key knowledge gaps remain. A detailed understanding of the pathological correlates of radiographic findings and the patterns of local tumor spread may help inform clinical judgement for target volume definition given the current state of uncertainty., Competing Interests: Disclosures Uulke van der Heide has collaborative agreements with Elekta AB and Philips; received grants from the Dutch Cancer Society and travel funding from Elekta AB; and is a member of the ASTRO Scientific Council. Linda Kerkmeijer received honoraria from SIU (2021), VenVN (2021), and the Dutch guideline committee renal cell carcinoma by SKMS; received travel stipend from ESTRO (2022); is a board member of the Dutch Uro-Oncology study group. Baris Turkbey received royalties from the National Institutes of Health; has multiple patents in AI (details available on request); has cooperative research and development agreements with NVIDIA and Philips. William Hall received consulting fees from Aktis oncology; received honoraria from Elekta; received travel funding from Elekta; serves a position as the Vice Chair of the MR Linac Consortium Steering Committee. Provisional Patient 63/483,252 was filed by the institution on medical devices to assess radiation readiness. The other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Published by Elsevier Inc.)

Purpose: To quantify the difference in accuracy of adapt-to-position (ATP), adapt-to-rotation (ATR) and adapt-to-shape (ATS) workflows used in MRI-guided online adaptive radiotherapy for prostate carcinoma (PCa) by evaluating the margins required to accommodate intra-fraction motion of the clinical target volumes for prostate (CTVpros), prostate including seminal vesicles (CTVpros + sv) and gross tumor volume (GTV)., Materials and Methods: Clinical delineations of the CTVpros, CTVpros + sv and GTV of 24 patients with intermediate- and high-risk PCa, treated using ATS on a 1.5 T MR-Linac, were used for analysis. Delineations were available pre- and during beam-on. To simulate ATP and ATR workflows, we automatically generated the structures associated with these workflows using rigid transformations from the planning-MRI to the daily online MRIs. Clinical GTVs were analyzed as ATR GTVs and only ATP GTVs were simulated. Planning target volumes (PTVs) were generated with isotropic margins ranging 0.0-5.0 mm. The volumetric overlap was calculated between these PTVs and their corresponding clinical delineation on the MRI acquired during beam-on and averaged over all treatment fractions., Results: The PTV margin required to cover > 95% of the CTVpros was equal (2.5 mm) for all workflows. For the CTVpros + sv, this margin increased to 5.0, 4.0 and 3.5 mm in the ATP, ATR and ATS workflow, respectively. GTV coverage improved from ATP to ATR for margins up to 4.0 mm., Conclusion: ATP, ATR and ATS workflows ensure equal coverage of the CTVpros for the current clinical margins. For the CTVpros + sv, ATS showed optimal performance. GTV coverage improves by additional adaptations to prostate rotations., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objective. In online adaptive radiotherapy a new plan is generated every fraction based on the organ and clinical target volume (CTV) delineations of that fraction. This allows for a planning target volume margin that does not need to be constant over the whole course of treatment, as is the case in conventional radiotherapy. This work aims to introduce an approach to update the margins each fraction based on the per-patient treatment history and explore the potential benefits of such adaptive margins. Approach. We introduce a novel methodology to implement adaptive margins, isotropic and anisotropic, during a treatment course based on the accumulated dose to the CTV. We then simulate treatment histories for treatments delivered in up to 20 fractions using various choices for the standard deviations of the systematic and random errors and homogeneous and inhomogeneous dose distributions. The treatment-averaged adaptive margin was compared to standard constant margins. The change in the minimum dose delivered to the CTV was compared on a patient and a population level. All simulations were performed within the van Herk approach and its known limitations. Main results. The population mean treatment-averaged margins are down to 70% and 55% of the corresponding necessary constant margins for the isotropic and anisotropic approach. The reduction increases with longer fractionation schemes and an inhomogeneous target dose distribution. Most of the benefit can be attributed to the elimination of the effective systematic error over the course of treatment. Interpatient differences in treatment-averaged margins were largest for the isotropic margins. For the 10% of patients that would receive a lower than prescribed dose to the CTV this minimum dose to the CTV is increased using the adaptive margin approaches. Significance. Adaptive margins can allow to reduce margins in most patients without compromising patients with greater than average target motion., (Creative Commons Attribution license.)

Purpose: High-field magnetic resonance-linear accelerators (MR-Linacs), linear accelerators combined with a diagnostic magnetic resonance imaging (MRI) scanner and online adaptive workflow, potentially give rise to novel online anatomic and response adaptive radiation therapy paradigms. The first high-field (1.5T) MR-Linac received regulatory approval in late 2018, and little is known about clinical use, patient tolerability of daily high-field MRI, and toxicity of treatments. Herein we report the initial experience within the MOMENTUM Study (NCT04075305), a prospective international registry of the MR-Linac Consortium., Methods and Materials: Patients were included between February 2019 and October 2020 at 7 institutions in 4 countries. We used descriptive statistics to describe the patterns of care, tolerability (the percentage of patients discontinuing their course early), and safety (grade 3-5 Common Terminology Criteria for Adverse Events v.5 acute toxicity within 3 months after the end of treatment)., Results: A total 943 patients participated in the MOMENTUM Study, 702 of whom had complete baseline data at the time of this analysis. Patients were primarily male (79%) with a median age of 68 years (range, 22-93) and were treated for 39 different indications. The most frequent indications were prostate (40%), oligometastatic lymph node (17%), brain (12%), and rectal (10%) cancers. The median number of fractions was 5 (range, 1-35). Six patients discontinued MR-Linac treatments, but none due to an inability to tolerate repeated high-field MRI. Of the 415 patients with complete data on acute toxicity at 3-month follow-up, 18 (4%) patients experienced grade 3 acute toxicity related to radiation. No grade 4 or 5 acute toxicity related to radiation was observed., Conclusions: In the first 21 months of our study, patterns of care were diverse with respect to clinical utilization, body sites, and radiation prescriptions. No patient discontinued treatment due to inability to tolerate daily high-field MRI scans, and the acute radiation toxicity experience was encouraging., (Copyright © 2021. Published by Elsevier Inc.)

Purpose and Background: 3D dosimetric verification of online adaptive workflows is essential as their complexity is unprecedented in radiation oncology. The aim of this work is to demonstrate the feasibility of back-projection portal dosimetry for 3D dosimetric verification of Unity MR-linac treatments., Material and Methods: An earlier presented 2D back-projection algorithm for the Unity MR-linac geometry was extended for 3D dose reconstruction and comparison against planned dose distributions. 'In-air' as well as in-vivo portal EPID images can be used as input. The method was validated using data from treatments of 5 patients (2 rectal, 2 prostate cancer and one oligo metastasis). 3D pre-treatment verification of the reference plan using 'in-air' EPID images was performed and compared against measured (with the Octavius 4D system) and planned (in the planning CT) dose distributions. In-vivo EPID dose distributions were compared to the TPS for the first three adaptations of all treatments. For all comparisons, dose difference values at the reference point and γ-parameters were reported., Results: The comparison against the OCTAVIUS 4D system (3%, 2 mm, local) showed y-mean = 0.52 ± 0.10 and y-passrate = 91.9%, 95% CI [85.4, 98.4], and ΔD RP  = -0.1 ± 1.1%. Pre-treatment verification against TPS data (3%, 2 mm, global) showed y-mean = 0.52 ± 0.04, y-passrate = 93.5%, 95% CI [92.4, 94.6] and ΔD RP  = -0.9 ± 1.5%. The averaged y-results for the in-vivo 3D verification were y-mean = 0.52 ± 0.05, y-passrate = 92.5%, 95% CI [90.2, 94.8] and ΔD RP  = 0.8 ± 2.1%., Conclusion: 3D dosimetric verification of Unity MR-linac treatments using portal dosimetry is feasible, pre-treatment as well as in-vivo., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: The STAR-TReC trial is an international multi-center, randomized, phase II study assessing the feasibility of short-course radiotherapy or long-course chemoradiotherapy as an alternative to total mesorectal excision surgery. A new target volume is used for both (chemo)radiotherapy arms which includes only the mesorectum. The treatment planning QA revealed substantial variation in dose to organs at risk (OAR) between centers. Therefore, the aim of this study was to determine the treatment plan variability in terms of dose to OAR and assess the effect of a national study group meeting on the quality and variability of treatment plans for mesorectum-only planning for rectal cancer., Methods: Eight centers produced 25 × 2 Gy treatment plans for five cases. The OAR were the bowel cavity, bladder and femoral heads. A study group meeting for the participating centers was organized to discuss the planning results. At the meeting, the values of the treatment plan DVH parameters were distributed among centers so that results could be compared. Subsequently, the centers were invited to perform replanning if they considered this to be necessary., Results: All treatment plans, both initial planning and replanning, fulfilled the target constraints. Dose to OAR varied considerably for the initial planning, especially for dose levels below 20 Gy, indicating that there was room for trade-offs between the defined OAR. Five centers performed replanning for all cases. One center did not perform replanning at all and two centers performed replanning on two and three cases, respectively. On average, replanning reduced the bowel cavity V20Gy by 12.6%, bowel cavity V10Gy by 22.0%, bladder V35Gy by 14.7% and bladder V10Gy by 10.8%. In 26/30 replanned cases the V10Gy of both the bowel cavity and bladder was lower, indicating an overall lower dose to these OAR instead of a different trade-off. In addition, the bowel cavity V10Gy and V20Gy showed more similarity between centers., Conclusions: Dose to OAR varied considerably between centers, especially for dose levels below 20 Gy. The study group meeting and the distribution of the initial planning results among centers resulted in lower dose to the defined OAR and reduced variability between centers after replanning., Trial Registration: The STAR-TReC trial, ClinicalTrials.gov Identifier: NCT02945566. Registered 26 October 2016, https://clinicaltrials.gov/ct2/show/NCT02945566).

Background and Purpose: A GTV boost is suggested to result in higher complete response rates in rectal cancer patients, which is attractive for organ preservation. Fiducials may offer GTV position verification on (CB)CT, if the fiducial-GTV spatial relationship can be accurately defined on MRI. The study aim was to evaluate the MRI visibility of fiducials inserted in the rectum., Materials and Methods: We tested four fiducial types (two Visicoil types, Cook and Gold Anchor), inserted in five patients each. Four observers identified fiducial locations on two MRI exams per patient in two scenarios: without (scenario A) and with (scenario B) (CB)CT available. A fiducial was defined to be consistently identified if 3 out of 4 observers labeled that fiducial at the same position on MRI. Fiducial visibility was scored on an axial and sagittal T2-TSE sequence and a T1 3D GRE sequence., Results: Fiducial identification was poor in scenario A for all fiducial types. The Visicoil 0.75 and Gold Anchor were the most consistently identified fiducials in scenario B with 7 out of 9 and 8 out of 11 consistently identified fiducials in the first MRI exam and 2 out of 7 and 5 out of 10 in the second MRI exam, respectively. The consistently identified Visicoil 0.75 and Gold Anchor fiducials were best visible on the T1 3D GRE sequence., Conclusion: The Visicoil 0.75 and Gold Anchor fiducials were the most visible fiducials on MRI as they were most consistently identified. The use of a registered (CB)CT and a T1 3D GRE MRI sequence is recommended., (Copyright © 2018 The Author(s). Published by Elsevier B.V. All rights reserved.)

The use of prostate MR imaging in radiotherapy continues to evolve. This article describes its current application in the selection of treatment regimens, integration in treatment planning or simulation, and assessment of response. An expert consensus statement from the annual MR in RT symposium is presented, as a list of 21 key quality indicators for the practice of MR imaging simulation in prostate cancer. Although imaging requirements generally follow PIRADSv2 guidelines, additional requirements specific to radiotherapy planning are described. MR imaging-only workflows and MR imaging-guided treatment systems are expected to replace conventional computed tomography-based practice, further adding specific requirements for MR imaging in radiotherapy., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Radiation therapy to the prostate involves increasingly sophisticated delivery techniques and changing fractionation schedules. With a low estimated α/β ratio, a larger dose per fraction would be beneficial, with moderate fractionation schedules rapidly becoming a standard of care. The integration of a magnetic resonance imaging (MRI) scanner and linear accelerator allows for accurate soft tissue tracking with the capacity to replan for the anatomy of the day. Extreme hypofractionation schedules become a possibility using the potentially automated steps of autosegmentation, MRI-only workflow, and real-time adaptive planning. The present report reviews the steps involved in hypofractionated adaptive MRI-guided prostate radiation therapy and addresses the challenges for implementation., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: In this planning study, we investigated the dosimetric benefit of repeat CT-based treatment planning at each fraction vs. the use of a single CT-based treatment plan for all fractions for high-dose-rate endorectal brachytherapy (HDREBT) for rectal cancer., Methods and Materials: We included 11 patients that received a CT scan with applicator in situ for all three fractions. The treatment plan of the first fraction was projected on the repeat CT scans to simulate the use of a single treatment plan. In addition, replanning was performed on the repeat CT scans, and these were compared to the corresponding projected treatment plans., Results: Repeat CT-based treatment planning resulted on average in a 21% higher (p = 0.01) conformity index compared to single CT-based treatment planning. Projecting the initial treatment plan to the repeat CT scans of fraction two and three, 12/22 fractions reached a CTV D98 of 85% of the prescribed dose of 7 Gy, which increased to 14/22 using replanning. For the remaining fractions, median CTV D98 was 4.2 Gy, and an intervention would be necessary to correct applicator balloon setup or to remove remaining air and/or feces between the CTV and the applicator., Conclusions: Using a single CT-based treatment plan for all fractions may result in a suboptimal treatment at later fractions. Therefore, repeat CT imaging should be the minimal standard practice in HDREBT for rectal cancer to determine whether an intervention would be necessary. Replanning based on repeat CT imaging resulted in more conformal treatment plans and is therefore recommended., (Copyright © 2017 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Dose painting by numbers (DPBN) refers to a voxel-wise prescription of radiation dose modelled from functional image characteristics, in contrast to dose painting by contours which requires delineations to define the target for dose escalation. The direct relation between functional imaging characteristics and DPBN implies that random variations in images may propagate into the dose distribution. The stability of MR-only prostate cancer treatment planning based on DPBN with respect to these variations is as yet unknown. We conducted a test-retest study to investigate the stability of DPBN for prostate cancer in a semi-automated MR-only treatment planning workflow. Twelve patients received a multiparametric MRI on two separate days prior to prostatectomy. The tumor probability (TP) within the prostate was derived from image features with a logistic regression model. Dose mapping functions were applied to acquire a DPBN prescription map that served to generate an intensity modulated radiation therapy (IMRT) treatment plan. Dose calculations were done on a pseudo-CT derived from the MRI. The TP and DPBN map and the IMRT dose distribution were compared between both MRI sessions, using the intraclass correlation coefficient (ICC) to quantify repeatability of the planning pipeline. The quality of each treatment plan was measured with a quality factor (QF). Median ICC values for the TP and DPBN map and the IMRT dose distribution were 0.82, 0.82 and 0.88, respectively, for linear dose mapping and 0.82, 0.84 and 0.94 for square root dose mapping. A median QF of 3.4% was found among all treatment plans. We demonstrated the stability of DPBN radiotherapy treatment planning in prostate cancer, with excellent overall repeatability and acceptable treatment plan quality. Using validated tumor probability modelling and simple dose mapping techniques it was shown that despite day-to-day variations in imaging data still consistent treatment plans were obtained.

MRI is increasingly being used in radiotherapy of the liver. The purpose of this study was to develop and validate a strategy to acquire MR images for treatment planning and image guidance in the presence of respiratory motion. By interleaving two navigator triggered MRI sequences, a fast but low-resolution image in mid-ventilation (midV) and a high-resolution image in exhale were acquired efficiently. Deformable registration was applied to map the exhale image to the midV anatomy. Cine-MRI scans were acquired for motion quantification. The method was validated with a motion phantom, 10 volunteers and 1 patient with a liver tumor. The time-weighted mean position of a local structure in a cine-scan was defined as the midV-position ground truth and used to determine the accuracy of the midV-triggering method. Deformable registration accuracy was validated using the SIFT algorithm. Acquisition time of the midV/exhale-scan was 3-5min. The accuracy of the midV-position was ⩽0.5±0.5mm for phantom motion and ⩽0.9±1.2mm for the volunteers. Mean residuals after deformable registration were ⩽0.2±1.8mm. The accuracy and reproducibility of the method are within inter- and intra-fraction liver position variability (Case et al., 2009) and could in the future be incorporated in a conventional liver radiotherapy or MR-linac workflow., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Aim: To determine the levels at which consensus could be reached regarding general and site-specific principles of MRI simulation for offline MRI-aided external beam radiation treatment planning., Methods: A process inspired by the Delphi method was employed to determine levels of consensus using a series of questionnaires interspersed with controlled opinion feedback., Results: In general, full consensus was reached regarding general principles of MRI simulation. However, the level of consensus decreased when site-specific principles of MRI simulation were considered., Conclusions: These results indicate variability in MRI simulation approaches that are largely explained by the use of MRI in combination with CT., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background and Purpose: To evaluate volume changes and position shifts and their contribution to treatment margins of pelvic and para-aortic lymph nodes during Intensity Modulated Radiation Therapy (IMRT) for advanced cervical cancer., Materials and Methods: Seventeen patients with visible nodes on MR images underwent T2-weighted MR scans before and weekly during the course of IMRT. Thirty-nine pelvic and para-aortic nodes were delineated on all scans. Margins accommodating for volume and position changes were taken from the boundaries of the nodal volumes in the six main directions., Results: Nodal volume regression from the pre-treatment situation to week 4 was 58% on average (range: 11.7% increase to 100% decrease). Nodal volumes partly increased between the pre-treatment scans and the scans in weeks 1-3, but in week 4 all nodes except one had regressed. Around the nodal volumes manually derived ITV margins accounting for volume changes and position shifts of 7.0, 4.0, 7.0, 8.0, 7.0 and 9.0mm to the medial, lateral, anterior, posterior, superior and inferior directions were needed to cover 95% of all nodes., Conclusions: We used weekly MR scans to derive inhomogeneous margins that accommodate for nodal volume and position changes during treatment. These margins should be taken into consideration when planning external beam radiotherapy (EBRT) boosts, especially for highly conformal boosting techniques., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

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., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Purpose: For focal boost strategies in the prostate, the robustness of magnetic resonance imaging-based tumor delineations needs to be improved. To this end we developed a statistical model that predicts tumor presence on a voxel level (2.5×2.5×2.5 mm3) inside the peripheral zone. Furthermore, we show how this model can be used to derive a valuable input for radiotherapy treatment planning., Methods and Materials: The model was created on 87 radiotherapy patients. For the validation of the voxelwise performance of the model, an independent group of 12 prostatectomy patients was used. After model validation, the model was stratified to create three different risk levels for tumor presence: gross tumor volume (GTV), high-risk clinical target volume (CTV), and low-risk CTV., Results: The model gave an area under the receiver operating characteristic curve of 0.70 for the prediction of tumor presence in the prostatectomy group. When the registration error between magnetic resonance images and pathologic delineation was taken into account, the area under the curve further improved to 0.89. We propose that model outcome values with a high positive predictive value can be used to define the GTV. Model outcome values with a high negative predictive value can be used to define low-risk CTV regions. The intermediate outcome values can be used to define a high-risk CTV., Conclusions: We developed a logistic regression with a high diagnostic performance for voxelwise prediction of tumor presence. The model output can be used to define different risk levels for tumor presence, which in turn could serve as an input for dose planning. In this way the robustness of tumor delineations for focal boost therapy can be greatly improved., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background and Purpose: This study presents an overview of the experience with transrectal and transperineal implantations of fiducial markers for position verification in prostate radiotherapy, regarding the practical feasibility, procedure-related toxicity and influence on quality of life (QoL)., Material and Methods: Since 2001, 914 patients scheduled for intensity-modulated radiotherapy (IMRT) have received gold markers in the prostate. The incidence of severe toxicity, defined by the CTCAE v3.0, was evaluated retrospectively. The influence on QoL was measured prospectively in 36 patients using a combination of three validated questionnaires: the Rand-36, the EORTC QLQ-C30(+3) and the prostate cancer-specific EORTC QLQ-PR25. Next, the incidence of marker migration was assessed., Results: From 2001 to 2005, 402 patients received markers via the transrectal route. Two of these patients developed urosepsis (grade 3 toxicity). Since 2005, 512 patients received markers via the transperineal route. No grade 3 or 4 toxicity occurred in this group. No significant and clinically relevant differences were found in QoL between pre- and post-implant measures. In 5 patients marker migration led to discontinuation of the marker-based IMRT., Conclusions: Clinical use of transperineal-implanted fiducial gold markers for position verification in external beam radiotherapy for prostate cancer is a feasible and safe procedure without influencing patients' QoL., (Copyright 2010 Elsevier Ireland Ltd. All rights reserved.)

Background and Purpose: The use of dynamic contrast-enhanced (DCE) imaging for delineation of prostate tumors requires that decisions are made on a voxel wise basis about the presence of tumor. While the sensitivity and specificity of this technique is high, we propose a probabilistic approach to deal with the intrinsic imaging uncertainty., Material and Methods: Twenty-nine patients with biopsy-proven prostate cancer underwent a DCE-CT exam prior to radiotherapy. From a logistic regression on K(trans) values from healthy and diseased appearing prostate regions we obtained a probability function for the presence of tumor. K(trans) parameter maps were converted into probability maps and a stratification was applied at the 5% and 95% probability level, to identify low-, intermediate-, and high-risk areas for the presence of tumor., Results: In all patients, regions with high-, intermediate-, and low-risk were identified, with median volume percentages of 7.6%, 40.0%, and 52.1%, respectively. The contiguous areas that resulted from the voxel wise stratification can be interpreted as GTV, high-risk CTV, and CTV., Conclusions: K(trans) parameter maps from a DCE-CT exam can be converted into probability maps for the presence of tumor. In this way, the intrinsic uncertainty that a voxel contains tumor can be incorporated into the treatment planning process., (Copyright 2009 Elsevier Ireland Ltd. All rights reserved.)

Background and Purpose: During radiation delivery, target volumes change their position and shape due to intrafraction motion. The extent of these changes and the capability to correct for them will contribute to the benefit of an MRI-accelerator in terms of PTV margin reduction. Therefore, we investigated the primary CTV motion within a typical IMRT delivery time for cervical cancer patients for various correction techniques: no registration, rigid bony anatomy registration, and rigid soft tissue registration., Materials and Methods: Twenty-two patients underwent 2-3 offline MRI exams before and during their radiation treatment. Each MRI exam included four sagittal and four axial MRI scans alternately within 16min. We addressed the CTV motion by comparing subsequent midsagittal CTV delineations and investigated the correlation with intrafraction bladder filling., Results: The maximum (residual) motions within 16min for all points on the CTV contour for 90% of the MRI exams without registration, with rigid bony anatomy registration, and with rigid soft tissue registration were 10.6, 9.9, and 4.0mm. A significant but weak correlation was found between intrafraction bladder filling and CTV motion., Conclusions: Considerable intrafraction CTV motion is observed in cervical cancer patients. Intrafraction MRI-guided soft tissue registration using an MRI-accelerator will correct for this motion.

Purpose: To investigate the influence of translational and rotational errors on prostate intensity-modulated radiotherapy (IMRT) with an integrated boost to the tumor and to evaluate the effect of the use of an on-line correction protocol., Methods and Materials: For 19 patients, who had been treated with prostate IMRT and fiducial marker-based position verification, highly inhomogeneous IMRT plans, including an integrated tumor boost, were made using varying margins (2, 4, 6, and 8 mm). The measured translational and rotational errors were used to calculate the dose using two positioning strategies: an off-line and an on-line protocol to correct the translational shifts. The estimated dose to the targets and the organs at risk was compared with the intended dose., Results: Residual deviations after off-line correction led to statistically significant, but very small, reductions in dose coverage. Even when a 2-mm margin was used, the average reduction in dose to 99% of the volume was 1.4 +/- 1.9 Gy for the tumor, 1.5 +/- 1.5 Gy for the prostate without seminal vesicles (boost volume), and 4.3 +/- 4.6 Gy, including the seminal vesicles (clinical target volume). Patients with large systematic rotational errors demonstrated a substantial decrease in dose, especially for the clinical target volume. If an on-line correction protocol was used, the average mean dose and dose to 99% of the volume of the targets improved. However, the extensive dose reduction for patients with large rotational errors barely recovered with on-line correction., Conclusion: For complex prostate IMRT with an integrated tumor boost, the use of an on-line correction protocol yields little improvement without the correction of rotational errors.

Background and Purpose: During cervical cancer treatment, target volumes change position and shape due to organ motion and tumour regression. An MRI-accelerator will provide information on these changes by online magnetic resonance imaging (MRI) guidance throughout each treatment fraction. The purpose of this intensity-modulated radiation therapy (IMRT) planning study is to assess the benefit of online MRI guidance in healthy tissue sparing., Materials and Methods: Weekly MRI scans of 11 cervical cancer patients were used. We created four IMRT plans per patient, based on these weekly MRI scans, to simulate an online-IMRT approach. We applied a primary and nodal planning target volume (PTV) margin of 4 mm. As reference, we created an IMRT plan based on the pre-treatment MRI scan (pre-IMRT) using a primary and nodal PTV margin of 15 and 10 mm. The weekly defined bladder, rectum, bowel, and sigmoid contours were evaluated on the online-IMRT and pre-IMRT dose distributions at six dose levels (V10(Gy), V20(Gy), V30(Gy), V40(Gy), V42.8(Gy), and V45(Gy))., Results: Online-IMRT compared to pre-IMRT significantly reduced the volume of healthy tissue irradiated to all dose levels, except V10(Gy)., Conclusions: Online MRI guidance reduces healthy tissue involvement in patients with cervical cancer.

We evaluated the acute and late toxicity after high-dose intensity-modulated radiotherapy (IMRT) with fiducial marker-based position verification for prostate cancer. Between 2001 and 2004, 331 patients with prostate cancer received 76 Gy in 35 fractions using IMRT combined with fiducial marker-based position verification. The symptoms before treatment (pre-treatment) and weekly during treatment (acute toxicity) were scored using the Common Toxicity Criteria (CTC). The goal was to score late toxicity according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC) scale with a follow-up time of at least three years. Twenty-two percent of the patients experienced pre-treatment grade > or = 2 genitourinary (GU) complaints and 2% experienced grade 2 gastrointestinal (GI) complaints. Acute grade 2 GU and GI toxicity occurred in 47% and 30%, respectively. Only 3% of the patients developed acute grade 3 GU and no grade > or = 3 GI toxicity occurred. After a mean follow-up time of 47 months with a minimum of 31 months for all patients, the incidence of late grade 2 GU and GI toxicity was 21% and 9%, respectively. Grade > or = 3 GU and GI toxicity rates were 4% and 1%, respectively, including one patient with a rectal fistula and one patient with a severe hemorrhagic cystitis (both grade 4). In conclusion, high-dose intensity-modulated radiotherapy with fiducial marker-based position verification is well tolerated. The low grade > or = 3 toxicity allows further dose escalation if the same dose constraints for the organs at risk will be used.

Purpose/objectives: In radiotherapy the healthy tissue involvement still poses serious dose limitations. This results in sub-optimal tumour dose and complications. Daily image guided radiotherapy (IGRT) is the key development in radiation oncology to solve this problem. MRI yields superb soft-tissue visualization and provides several imaging modalities for identification of movements, function and physiology. Integrating MRI functionality with an accelerator can make these capacities available for high precision, real time IGRT., Design and Results: The system being built at the University Medical Center Utrecht is a 1.5T MRI scanner, with diagnostic imaging functionality and quality, integrated with a 6MV radiotherapy accelerator. The realization of a prototype of this hybrid system is a joint effort between the Radiotherapy Department of the University of Utrecht, the Netherlands, Elekta, Crawley, U.K., and Philips Research, Hamburg, Germany. Basically, the design is a 1.5 T Philips Achieva MRI scanner with a Magnex closed bore magnet surrounded by a single energy (6 MV) Elekta accelerator. Monte Carlo simulations are used to investigate the radiation beam properties of the hybrid system, dosimetry equipment and for the construction of patient specific dose deposition kernels in the presence of a magnetic field. The latter are used to evaluate the IMRT capability of the integrated MRI linac., Conclusions: A prototype hybrid MRI/linac for on-line MRI guidance of radiotherapy (MRIgRT) is under construction. The aim of the system is to deliver the radiation dose with mm precision based on diagnostic quality MR images.

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.