PURPOSE: Ultrahypofractionated radiation therapy (UHRT) is an effective treatment for localized prostate cancer with an acceptable toxicity profile; boosting the visible intraprostatic tumor has been shown to improve biochemical disease-free survival with no significant effect on genitourinary (GU) and gastrointestinal (GI) toxicity. METHODS AND MATERIALS: HERMES is a single-center noncomparative randomized phase 2 trial in men with intermediate or lower high risk prostate cancer. Patients were allocated (1:1) to 36.25 Gy in 5 fractions over 2 weeks or 24 Gy in 2 fractions over 8 days with an integrated boost to the magnetic resonance imaging (MRI) visible tumor of 27 Gy in 2 fractions. A minimization algorithm with a random element with risk group as a balancing factor was used for participant randomization. Treatment was delivered on the Unity MR-Linac (Elekta AB) with daily online adaption. The primary endpoint was acute GU Common Terminology Criteria for Adverse Events version 5.0 toxicity with the aim of excluding a doubling of the rate of acute grade 2+ GU toxicity seen in PACE. Analysis was by treatment received and included all participants who received at least 1 fraction of study treatment. This interim analysis was prespecified (stage 1 of a 2-stage Simon design) for when 10 participants in each treatment group had completed the acute toxicity monitoring period (12 weeks after radiation therapy). RESULTS: Acute grade 2 GU toxicity was reported in 1 (10%) patient in the 5-fraction group and 2 (20%) patients in the 2-fraction group. No grade 3+ GU toxicities were reported. CONCLUSIONS: At this interim analysis, the rate of GU toxicity in the 2-fraction and 5-fraction treatment groups was found to be below the prespecified threshold (5/10 grade 2+) and continuation of the study to complete recruitment of 23 participants per group was recommended..

BACKGROUND: Real-time dose estimation is a key-prerequisite to enable online intra-fraction treatment adaptation in magnetic resonance (MR)-guided radiotherapy (MRgRT). It is an essential component for the assessment of the dosimetric benefits and risks of online adaptive treatments, such as multi-leaf collimator (MLC)-tracking. PURPOSE: We present a proof-of-concept for a software workflow for real-time dose estimation of MR-guided adaptive radiotherapy based on real-time data-streams of the linac delivery parameters and target positions. METHODS: A software workflow, combining our in-house motion management software DynaTrack, a real-time dose calculation engine that connects to a research version of the treatment planning software (TPS) Monaco (v.6.09.00, Elekta AB, Stockholm, Sweden) was developed and evaluated. MR-guided treatment delivery on the Elekta Unity MR-linac was simulated with and without MLC-tracking for three prostate patients, previously treated on the Elekta Unity MR-linac (36.25 Gy/five fractions). Three motion scenarios were used: no motion, regular motion, and erratic prostate motion. Accumulated monitor units (MUs), centre of mass target position and MLC-leaf positions, were forwarded from DynaTrack at a rate of 25 Hz to a Monte Carlo (MC) based dose calculation engine which utilises the research GPUMCD-library (Elekta AB, Stockholm, Sweden). A rigid isocentre shift derived from the selected motion scenarios was applied to a bulk density-assigned session MR-image. The respective electron density used for treatment planning was accessed through the research Monaco TPS. The software workflow including the online dose reconstruction was validated against offline dose reconstructions. Our investigation showed that MC-based real-time dose calculations that account for all linac states (including MUs, MLC positions and target position) were infeasible, hence states were randomly sampled and used for calculation as follows; Once a new linac state was received, a dose calculation with 106 photons was started. Linac states that arrived during the time of the ongoing calculation were put into a queue. After completion of the ongoing calculation, one new linac state was randomly picked from the queue and assigned the MU accumulated from the previous state until the last sample in the queue. The queue was emptied, and the process repeated throughout treatment simulation. RESULTS: On average 27% (23%-30%) of received samples were used in the real-time calculation, corresponding to a calculation time for one linac state of 148 ms. Median gamma pass rate (2%/3 mm local) was 100.0% (99.9%-100%) within the PTV volume and 99.1% (90.1%-99.4.0%) with a 15% dose cut off. Differences in PTVDmean , CTVDmean , RectumD2% , and BladderD2% (offline-online, % of prescribed dose) were below 0.64%. Beam-by-beam comparisons showed deviations below 0.07 Gy. Repeated simulations resulted in standard deviations below 0.31% and 0.12 Gy for the investigated volume and dose criteria respectively. CONCLUSIONS: Real-time dose estimation was successfully performed using the developed software workflow for different prostate motion traces with and without MLC-tracking. Negligible dosimetric differences were seen when comparing online and offline reconstructed dose, enabling online intra-fraction treatment decisions based on estimates of the delivered dose..

Objective.Respiratory motion of lung tumours and adjacent structures is challenging for radiotherapy. Online MR-imaging cannot currently provide real-time volumetric information of the moving patient anatomy, therefore limiting precise dose delivery, delivered dose reconstruction, and downstream adaptation methods.Approach.We tailor a respiratory motion modelling framework towards an MR-Linac workflow to estimate the time-resolved 4D motion from real-time data. We develop a multi-slice acquisition scheme which acquires thick, overlapping 2D motion-slices in different locations and orientations, interleaved with 2D surrogate-slices from a fixed location. The framework fits a motion model directly to the input data without the need for sorting or binning to account for inter- and intra-cycle variation of the breathing motion. The framework alternates between model fitting and motion-compensated super-resolution image reconstruction to recover a high-quality motion-free image and a motion model. The fitted model can then estimate the 4D motion from 2D surrogate-slices. The framework is applied to four simulated anthropomorphic datasets and evaluated against known ground truth anatomy and motion. Clinical applicability is demonstrated by applying our framework to eight datasets acquired on an MR-Linac from four lung cancer patients.Main results.The framework accurately reconstructs high-quality motion-compensated 3D images with 2 mm3isotropic voxels. For the simulated case with the largest target motion, the motion model achieved a mean deformation field error of 1.13 mm. For the patient cases residual error registrations estimate the model error to be 1.07 mm (1.64 mm), 0.91 mm (1.32 mm), and 0.88 mm (1.33 mm) in superior-inferior, anterior-posterior, and left-right directions respectively for the building (application) data.Significance.The motion modelling framework estimates the patient motion with high accuracy and accurately reconstructs the anatomy. The image acquisition scheme can be flexibly integrated into an MR-Linac workflow whilst maintaining the capability of online motion-management strategies based on cine imaging such as target tracking and/or gating..

BACKGROUND: MR-Linac allows for daily online treatment adaptation to the observed geometry of tumor targets and organs at risk (OARs). Manual delineation for head and neck cancer (HNC) patients takes 45-75 minutes, making it unsuitable for online adaptive radiotherapy. This study aims to clinically and dosimetrically validate an in-house developed algorithm which automatically delineates the elective target volume and OARs for HNC patients in under a minute. METHODS: Auto-contours were generated by an in-house model with 2D U-Net architecture trained and tested on 52 MRI scans via leave-one-out cross-validation. A randomized selection of 684 automated and manual contours (split half-and-half) was presented to an oncologist to perform a blind test and determine the clinical acceptability. The dosimetric impact was investigated for 13 patients evaluating the differences in dosage for all structures. RESULTS: Automated contours were generated in 8 seconds per MRI scan. The blind test concluded that 114 (33%) of auto-contours required adjustments with 85 only minor and 15 (4.4%) of manual contours required adjustments with 12 only minor. Dosimetric analysis showed negligible dosimetric differences between clinically acceptable structures and structures requiring minor changes. The Dice Similarity coefficients for the auto-contours ranged from 0.66 ± 0.11 to 0.88 ± 0.06 across all structures. CONCLUSION: Majority of auto-contours were clinically acceptable and could be used without any adjustments. Majority of structures requiring minor adjustments did not lead to significant dosimetric differences, hence manual adjustments were needed only for structures requiring major changes, which takes no longer than 10 minutes per patient..

AIMS: Neoadjuvant chemoradiotherapy followed by surgery is the mainstay of treatment for patients with rectal cancer. Standard clinical target volume (CTV) to planning target volume (PTV) margins of 10 mm are used to accommodate inter- and intrafraction motion of target. Treating on magnetic resonance-integrated linear accelerators (MR-linacs) allows for online manual recontouring and adaptation (MRgART) enabling the reduction of PTV margins. The aim of this study was to investigate motion of the primary CTV (CTVA; gross tumour volume and macroscopic nodes with 10 mm expansion to cover microscopic disease) in order to develop a simultaneous integrated boost protocol for use on MR-linacs. MATERIALS AND METHODS: Patients suitable for neoadjuvant chemoradiotherapy were recruited for treatment on MR-linac using a two-phase technique; only the five phase 1 fractions on MR-linac were used for analysis. Intrafraction motion of CTVA was measured between pre-treatment and post-treatment MRI scans. In MRgART, isotropically expanded pre-treatment PTV margins from 1 to 10 mm were rigidly propagated to post-treatment MRI to determine overlap with 95% of CTVA. The PTV margin was considered acceptable if overlap was >95% in 90% of fractions. To understand the benefit of MRgART, the same methodology was repeated using a reference computed tomography planning scan for pre-treatment imaging. RESULTS: In total, nine patients were recruited between January 2018 and December 2020 with T3a-T4, N0-N2, M0 disease. Forty-five fractions were analysed in total. The median motion across all planes was 0 mm, demonstrating minimal intrafraction motion. A PTV margin of 3 and 5mm was found to be acceptable in 96 and 98% of fractions, respectively. When comparing to the computed tomography reference scan, the analysis found that PTV margins to 5 and 10 mm only acceptably covered 51 and 76% of fractions, respectively. CONCLUSION: PTV margins can be reduced to 3-5 mm in MRgART for rectal cancer treatment on MR-linac within an simultaneous integrated boost protocol..

The implementation of MRI-guided online adaptive radiotherapy has enabled extension of therapeutic radiographers' roles to include contouring. An offline interobserver variability study compared five radiographers' and five clinicians' contours on 10 MRIs acquired on a MR-Linac from 10 patients. All contours were compared to a "gold standard" created from an average of clinicians' contours. The median (range) DSC of radiographers' and clinicians' contours compared to the "gold standard" was 0.91 (0.86-0.96), and 0.93 (0.88-0.97) respectively illustrating non-inferiority of the radiographers' contours to the clinicians. There was no significant difference in HD, MDA or volume size between the groups..

BACKGROUND AND PURPOSE: The implementation of MRI-guided online adaptive radiotherapy has facilitated the extension of therapeutic radiographers' roles to include contouring, thus releasing the clinician from attending daily treatment. Following undergoing a specifically designed training programme, an online interobserver variability study was performed. MATERIALS AND METHODS: 117 images from six patients treated on a MR Linac were contoured online by either radiographer or clinician and the same images contoured offline by the alternate profession. Dice similarity coefficient (DSC), mean distance to agreement (MDA), Hausdorff distance (HD) and volume metrics were used to analyse contours. Additionally, the online radiographer contours and optimised plans (n = 59) were analysed using the offline clinician defined contours. After clinical implementation of radiographer contouring, target volume comparison and dose analysis was performed on 20 contours from five patients. RESULTS: Comparison of the radiographers' and clinicians' contours resulted in a median (range) DSC of 0.92 (0.86 - 0.99), median (range) MDA of 0.98 mm (0.2-1.7) and median (range) HD of 6.3 mm (2.5-11.5) for all 117 fractions. There was no significant difference in volume size between the two groups. Of the 59 plans created with radiographer online contours and overlaid with clinicians' offline contours, 39 met mandatory dose constraints and 12 were acceptable because 95 % of the high dose PTV was covered by 95 % dose, or the high dose PTV was within 3 % of online plan. A clinician blindly reviewed the eight remaining fractions and, using trial quality assurance metrics, deemed all to be acceptable. Following clinical implementation of radiographer contouring, the median (range) DSC of CTV was 0.93 (0.88-1.0), median (range) MDA was 0.8 mm (0.04-1.18) and HD was 5.15 mm (2.09-8.54) respectively. Of the 20 plans created using radiographer online contours overlaid with clinicians' offline contours, 18 met the dosimetric success criteria, the remaining 2 were deemed acceptable by a clinician. CONCLUSION: Radiographer and clinician prostate and seminal vesicle contours on MRI for an online adaptive workflow are comparable and produce clinically acceptable plans. Radiographer contouring for prostate treatment on a MR-linac can be effectively introduced with appropriate training and evaluation. A DSC threshold for target structures could be implemented to streamline future training..

OBJECTIVE: The goal of this consensus expert opinion was to define quality assurance (QA) tests for online magnetic resonance image (MRI) guided radiotherapy (oMRgRT) systems and to define the important medical physics aspects for installation and commissioning of an oMRgRT system. MATERIALS AND METHODS: Ten medical physicists and two radiation oncologists experienced in oMRgRT participated in the survey. In the first round of the consensus expert opinion, ideas on QA and commissioning were collected. Only tests and aspects different from commissioning of a CT guided radiotherapy (RT) system were considered. In the following two rounds all twelve participants voted on the importance of the QA tests, their recommended frequency and their suitability for the two oMRgRT systems approved for clinical use as well as on the importance of the aspects to consider during medical physics commissioning. RESULTS: Twenty-four QA tests were identified which are potentially important during commissioning and routine QA on oMRgRT systems compared to online CT guided RT systems. An additional eleven tasks and aspects related to construction, workflow development and training were collected. Consensus was found for most tests on their importance, their recommended frequency and their suitability for the two approved systems. In addition, eight aspects mostly related to the definition of workflows were also found to be important during commissioning. CONCLUSIONS: A program for QA and commissioning of oMRgRT systems was developed to support medical physicists to prepare for safe handling of such systems..

Hybrid systems that combine Magnetic Resonance Imaging (MRI) and linear accelerators are available clinically to guide and adapt radiotherapy. Vendor-approved MRI sequences are provided, however alternative sequences may offer advantages. The aim of this study was to develop a systematic approach for non-vendor sequence evaluation, to determine safety, accuracy and overall clinical application of two potential sequences for bladder cancer MRI guided radiotherapy. Non-vendor sequences underwent and passed clinical image qualitative review, phantom quality assurance, and radiotherapy planning assessments. Volunteer workflow tests showed the potential for one sequence to reduce workflow time by 27% compared to the standard vendor sequence..

INTRODUCTION: The Elekta Unity MR-Linac (MRL) has enabled adaptive radiotherapy (ART) for patients with head and neck cancers (HNC). Adapt-To-Shape-Lite (ATS-Lite) is a novel Adapt-to-Shape strategy that provides ART without requiring daily clinician presence to perform online target and organ at risk (OAR) delineation. In this study we compared the performance of our clinically-delivered ATS-Lite strategy against three Adapt-To-Position (ATP) variants: Adapt Segments (ATP-AS), Optimise Weights (ATP-OW), and Optimise Shapes (ATP-OS). METHODS: Two patients with HNC received radical-dose radiotherapy on the MRL. For each fraction, an ATS-Lite plan was generated online and delivered and additional plans were generated offline for each ATP variant. To assess the clinical acceptability of a plan for every fraction, twenty clinical goals for targets and OARs were assessed for all four plans. RESULTS: 53 fractions were analysed. ATS-Lite passed 99.9% of mandatory dose constraints. ATP-AS and ATP-OW each failed 7.6% of mandatory dose constraints. The Planning Target Volumes for 54 Gy (D95% and D98%) were the most frequently failing dose constraint targets for ATP. ATS-Lite median fraction times for Patient 1 and 2 were 40 mins 9 s (range 28 mins 16 s - 47 mins 20 s) and 32 mins 14 s (range 25 mins 33 s - 44 mins 27 s), respectively. CONCLUSIONS: Our early data show that the novel ATS-Lite strategy produced plans that fulfilled 99.9% of clinical dose constraints in a time frame that is tolerable for patients and comparable to ATP workflows. Therefore, ATS-Lite, which bridges the gap between ATP and full ATS, will be further utilised and developed within our institute and it is a workflow that should be considered for treating patients with HNC on the MRL..

AIMS: With interest in normal tissue sparing and dose-escalated radiotherapy in the treatment of inoperable locally advanced non-small cell lung cancer, this study investigated the impact of motion-managed moderate deep inspiration breath hold (mDIBH) on normal tissue sparing and dose-escalation potential and compared this to planning with a four-dimensional motion-encompassing internal target volume or motion-compensating mid-ventilation approach. MATERIALS AND METHODS: Twenty-one patients underwent four-dimensional and mDIBH planning computed tomography scans. Internal and mid-ventilation target volumes were generated on the four-dimensional scan, with mDIBH target volumes generated on the mDIBH scan. Isotoxic target dose-escalation guidelines were used to generate six plans per patient: three with a target dose cap and three without. Target dose-escalation potential, normal tissue complication probability and differences in pre-specified dose-volume metrics were evaluated for the three motion-management techniques. RESULTS: The mean total lung volume was significantly greater with mDIBH compared with four-dimensional scans. Lung dose (mean and V21 Gy) and mean heart dose were significantly reduced with mDIBH in comparison with four-dimensional-based approaches, and this translated to a significant reduction in heart and lung normal tissue complication probability with mDIBH. In 20/21 patients, the trial target prescription dose cap of 79.2 Gy was achievable with all motion-management techniques. CONCLUSION: mDIBH aids lung and heart dose sparing in isotoxic dose-escalated radiotherapy compared with four-dimensional planning techniques. Given concerns about lung and cardiac toxicity, particularly in an era of consolidation immunotherapy, reduced normal tissue doses may be advantageous for treatment tolerance and outcome..

Bladder tumour-focused magnetic resonance image-guided adaptive radiotherapy using a 1.5 Tesla MR-linac is feasible. A full online workflow adapting to anatomy at each fraction is achievable in approximately 30 min. Intra-fraction bladder filling did not compromise target coverage with the class solution employed..

PURPOSE: This study aims to develop and validate a simple geometric model of the accelerator head, from which a particle phase space can be calculated for application to fast Monte Carlo dose calculation in real-time adaptive photon radiotherapy. With this objective in view, the study investigates whether the phase space model can facilitate dose calculations which are compatible with those of a commercial treatment planning system, for convenient interoperability. MATERIALS AND METHODS: A dual-source model of the head of a Versa HD accelerator (Elekta AB, Stockholm, Sweden) was created. The model used parameters chosen to be compatible with those of 6-MV flattened and 6-MV flattening filter-free photon beams in the RayStation treatment planning system (RaySearch Laboratories, Stockholm, Sweden). The phase space model was used to calculate a photon phase space for several treatment plans, and the resulting phase space was applied to the Dose Planning Method (DPM) Monte Carlo dose calculation algorithm. Simple fields and intensity-modulated radiation therapy (IMRT) treatment plans for prostate and lung were calculated for benchmarking purposes and compared with the convolution-superposition dose calculation within RayStation. RESULTS: For simple square fields in a water phantom, the calculated dose distribution agrees to within ±2% with that from the commercial treatment planning system, except in the buildup region, where the DPM code does not model the electron contamination. For IMRT plans of prostate and lung, agreements of ±2% and ±6%, respectively, are found, with slightly larger differences in the high dose gradients. CONCLUSIONS: The phase space model presented allows convenient calculation of a phase space for application to Monte Carlo dose calculation, with straightforward translation of beam parameters from the RayStation beam model. This provides a basis on which to develop dose calculation in a real-time adaptive setting..

BACKGROUND: The prostate demonstrates inter- and intra- fractional changes and thus adaptive radiotherapy would be required to ensure optimal coverage. Daily adaptive radiotherapy for MRI-guided radiotherapy can be both time and resource intensive when structure delineation is completed manually. Contours can be auto-generated on the MR-Linac via a deformable image registration (DIR) based mapping process from the reference image. This study evaluates the performance of automatically generated target structure contours against manually delineated contours by radiation oncologists for prostate radiotherapy on the Elekta Unity MR-Linac. METHODS: Plans were generated from prostate contours propagated by DIR and rigid image registration (RIR) for forty fractions from ten patients. A two-dose level SIB (simultaneous integrated boost) IMRT plan is used to treat localised prostate cancer; 6000 cGy to the prostate and 4860 cGy to the seminal vesicles. The dose coverage of the PTV 6000 and PTV 4860 created from the manually drawn target structures was evaluated with each plan. If the dose objectives were met, the plan was considered successful in covering the gold standard (clinician-delineated) volume. RESULTS: The mandatory PTV 6000 dose objective (D98% > 5580 cGy) was met in 81 % of DIR plans and 45 % of RIR plans. The SV were mapped by DIR only and for all the plans, the PTV 4860 dose objective met the optimal target (D98% > 4617 cGy). The plans created by RIR led to under-coverage of the clinician-delineated prostate, predominantly at the apex or the bladder-prostate interface. CONCLUSION: Plans created from DIR propagation of prostate contours outperform those created from RIR propagation. In approximately 1 in 5 DIR plans, dosimetric coverage of the gold standard PTV was not clinically acceptable. Thus, at our institution, we use a combination of DIR propagation of contours alongside manual editing of contours where deemed necessary for online treatments..

A shift of the daily plan can mitigate target position changes that occur between daily MR acquisition and treatment for MR-linac radiotherapy, but increases the session time. We demonstrated that our workflow strategy and decision-making process, to determine whether a subsequent shift is necessary, is appropriate..

The drive towards hypofractionated prostate radiotherapy is motivated by a low alpha/beta ratio for prostate cancer (1 to 3 Gy) compared to surrounding organs at risk, implying an improved therapeutic ratio with increasing dose per fraction. Early evidence from studies of ultrahypofractionated (UHF) prostate HDR brachytherapy has shown good tolerability in terms of normal tissue toxicities and clinical outcomes similar to conventional fractionation schedules. MR-guided stereotactic body radiotherapy (SBRT) with online plan adaptation and real-time tumour imaging may enable UHF doses to be delivered to the prostate safely, without the invasiveness of brachytherapy. The feasibility of UHF prostate treatment planning for the Unity MR-Linac (MRL, Elekta AB, Stockholm) was investigated for target prescriptions and planning constraints derived from the HDR brachytherapy and SBRT literature. Monaco 5.40 (Elekta) was used to generate MRL step-and-shoot IMRT plans for three dose fractionation protocols (5, 2 and 1 fractions), for ten randomly selected previously treated prostate cancer patients. Of the ten plans per UHF scheme, all clinical goals were met in all cases for 5 fractions, and in six cases for both 2 and 1 fraction schemes. PTV D95% was compromised by up to 6.4% and 3.9% of the associated target dose for 2 and 1 fraction plans respectively. There were two cases of PTV D95% compromise greater than a 5% dose decrease for the 2 fraction plans. The study suggests feasibility of the UHF treatment planning approaches if combined with real-time motion mitigation strategies..

Over the last few years, magnetic resonance image-guided radiotherapy systems have been introduced into the clinic, allowing for daily online plan adaption. While quality assurance (QA) is similar to conventional radiotherapy systems, there is a need to introduce or modify measurement techniques. As yet, there is no consensus guidance on the QA equipment and test requirements for such systems. Therefore, this report provides an overview of QA equipment and techniques for mechanical, dosimetric, and imaging performance of such systems and recommendation of the QA procedures, particularly for a 1.5T MR-linac device. An overview of the system design and considerations for QA measurements, particularly the effect of the machine geometry and magnetic field on the radiation beam measurements is given. The effect of the magnetic field on measurement equipment and methods is reviewed to provide a foundation for interpreting measurement results and devising appropriate methods. And lastly, a consensus overview of recommended QA, appropriate methods, and tolerances is provided based on conventional QA protocols. The aim of this consensus work was to provide a foundation for QA protocols, comparative studies of system performance, and for future development of QA protocols and measurement methods..

AIMS: Target delineation uncertainty is arguably the largest source of geometric uncertainty in radiotherapy. Several factors can affect it, including the imaging modality used for delineation. It is accounted for by applying safety margins to the target to produce a planning target volume (PTV), to which treatments are designed. To determine the margin, the delineation uncertainty is measured as the delineation error, and then a margin recipe used. However, there is no published evidence of such analysis for recurrent gynaecological cancers (RGC). The aims of this study were first to quantify the delineation uncertainty for RGC gross tumour volumes (GTVs) and to calculate the associated PTV margins and then to quantify the difference in GTV, delineation uncertainty and PTV margin, between a computed tomography-magnetic resonance imaging (CT-MRI) and MRI workflow. MATERIALS AND METHODS: Seven clinicians delineated the GTV for 20 RGC tumours on co-registered CT and MRI datasets (CT-MRI) and on MRI alone. The delineation error, the standard deviation of distances from each clinician's outline to a reference, was measured and the required PTV margin determined. Differences between using CT-MRI and MRI alone were assessed. RESULTS: The overall delineation error and the resulting margin were 3.1 mm and 8.5 mm, respectively, for CT-MRI, reducing to 2.5 mm and 7.1 mm, respectively, for MRI alone. Delineation errors and therefore the theoretical margins, varied widely between patients. MRI tumour volumes were on average 15% smaller than CT-MRI tumour volumes. DISCUSSION: This study is the first to quantify delineation error for RGC tumours and to calculate the corresponding PTV margin. The determined margins were larger than those reported in the literature for similar patients, bringing into question both current margins and margin calculation methods. The wide variation in delineation error between these patients suggests that applying a single population-based margin may result in PTVs that are suboptimal for many. Finally, the reduced tumour volumes and safety margins suggest that patients with RGC may benefit from an MRI-only treatment workflow..

BACKGROUND AND PURPOSE: 4D and midposition MRI could inform plan adaptation in lung and abdominal MR-guided radiotherapy. We present deep learning-based solutions to overcome long 4D-MRI reconstruction times while maintaining high image quality and short scan times. METHODS: Two 3D U-net deep convolutional neural networks were trained to accelerate the 4D joint MoCo-HDTV reconstruction. For the first network, gridded and joint MoCo-HDTV-reconstructed 4D-MRI were used as input and target data, respectively, whereas the second network was trained to directly calculate the midposition image. For both networks, input and target data had dimensions of 256 × 256 voxels (2D) and 16 respiratory phases. Deep learning-based MRI were verified against joint MoCo-HDTV-reconstructed MRI using the structural similarity index (SSIM) and the naturalness image quality evaluator (NIQE). Moreover, two experienced observers contoured the gross tumour volume and scored the images in a blinded study. RESULTS: For 12 subjects, previously unseen by the networks, high-quality 4D and midposition MRI (1.25 × 1.25 × 3.3 mm3) were each reconstructed from gridded images in only 28 seconds per subject. Excellent agreement was found between deep-learning-based and joint MoCo-HDTV-reconstructed MRI (average SSIM ≥ 0.96, NIQE scores 7.94 and 5.66). Deep-learning-based 4D-MRI were clinically acceptable for target and organ-at-risk delineation. Tumour positions agreed within 0.7 mm on midposition images. CONCLUSION: Our results suggest that the joint MoCo-HDTV and midposition algorithms can each be approximated by a deep convolutional neural network. This rapid reconstruction of 4D and midposition MRI facilitates online treatment adaptation in thoracic or abdominal MR-guided radiotherapy..

Target volume delineation uncertainty (DU) is arguably one of the largest geometric uncertainties in radiotherapy that are accounted for using planning target volume (PTV) margins. Geometrical uncertainties are typically derived from a limited sample of patients. Consequently, the resultant margins are not tailored to individual patients. Furthermore, standard PTVs cannot account for arbitrary anisotropic extensions of the target volume originating from DU. We address these limitations by developing a method to measure DU for each patient by a single clinician. This information is then used to produce PTVs that account for each patient's unique DU, including any required anisotropic component. We do so using a two-step uncertainty evaluation strategy that does not rely on multiple samples of data to capture the DU of a patient's gross tumour volume (GTV) or clinical target volume. For simplicity, we will just refer to the GTV in the following. First, the clinician delineates two contour sets; one which bounds all voxels believed to have a probability of belonging to the GTV of 1, while the second includes all voxels with a probability greater than 0. Next, one specifies a probability density function for the true GTV boundary position within the boundaries of the two contours. Finally, a patient-specific PTV, designed to account for all systematic errors, is created using this information along with measurements of the other systematic errors. Clinical examples indicate that our margin strategy can produce significantly smaller PTVs than the van Herk margin recipe. Our new radiotherapy target delineation concept allows DUs to be quantified by the clinician for each patient, leading to PTV margins that are tailored to each unique patient, thus paving the way to a greater personalisation of radiotherapy..

BACKGROUND AND PURPOSE: Anatomical changes during external beam radiotherapy prevent the accurate delivery of the intended dose distribution. Resolving the delivered dose, which is currently unknown, is crucial to link radiotherapy doses to clinical outcomes and ultimately improve the standard of care. MATERIAL AND METHODS: In this study, we present a dose reconstruction workflow based on data routinely acquired during MR-guided radiotherapy. It employs 3D MR images, 2D cine MR images and treatment machine log files to calculate the delivered dose taking intrafractional motion into account. The developed pipeline was used to measure anatomical changes and assess their dosimetric impact in 89 prostate radiotherapy fractions delivered with a 1.5 T MR-linac at our institute. RESULTS: Over the course of radiation delivery, the CTV shifted 0.6 mm ± 2.1 mm posteriorly and 1.3 mm ± 1.5 mm inferiorly. When extrapolating the dose changes in each case to 20 fractions, the mean clinical target volume D98% and clinical target volume D50% dose-volume metrics decreased by 1.1 Gy ± 1.6 Gy and 0.1 Gy ± 0.2 Gy, respectively. Bladder D3% did not change (0.0 Gy ± 1.2 Gy), while rectum D3% decreased by 1.0 Gy ± 2.0 Gy. Although anatomical changes and their dosimetric impact were small in the majority of cases, large intrafractional motion caused the delivered dose to substantially deviate from the intended plan in some fractions. CONCLUSIONS: The presented end-to-end workflow is able to reliably, non-invasively and automatically reconstruct the delivered prostate radiotherapy dose by processing MR-linac treatment log files and online MR images. In the future, we envision this workflow to be adapted to other cancer sites and ultimately to enter widespread clinical use..

PURPOSE: Several studies have demonstrated potential improvements in treatment time through the use of dynamic arcs for delivery of stereotactic body radiation therapy (SBRT) on Cyberknife. However, the delivery system has a finite accuracy, so that potential exists for dosimetric uncertainties. This study estimates the expected dosimetric accuracy of dynamic delivery of SBRT, based on realistic estimates of the uncertainties in delivery parameters. METHODS: Five SBRT patient cases (prostate A - conventional, prostate B - brachytherapy-type, lung, liver, partial left breast) were retrospectively studied. Treatment plans were produced for a fixed arc trajectory using fluence optimization, segmentation, and direct aperture optimization. Dose rate uncertainty was modeled as a smoothly varying random fluctuation of ± 1.0%, ±2.0% or ± 5.0% over a time period of 10, 30 or 60 s. Multileaf collimator uncertainty was modeled as a lag in position of each leaf up to 0.25 or 0.5 mm. Robot pointing error was modeled as a shift of the target location, with the direction of the shift chosen as a random angle with respect to the multileaf collimator and with a random magnitude in the range 0.0-1.0 mm at the delivery nodes and with an additional random magnitude of 0.5-1.0 mm in between the delivery nodes. The impact of the errors was investigated using dose-volume histograms. RESULTS: Uncertainty in dose rate has the effect of varying the total monitor units delivered, which in turn produces a variation in mean dose to the planning target volume. The random sampling of dose rate error produces a distribution of mean doses with a standard deviation proportional to the magnitude of the dose rate uncertainty. A lag in multileaf collimator position of 0.25 or 0.5 mm produces a small impact on the delivered dose. In general, an increase in the PTV mean dose of around 1% is observed. An error in robot pointing of the order of 1 mm produces a small increase in dose inhomogeneity to the planning target volume, sometimes accompanied by an increase in mean dose by around 1%. CONCLUSIONS: Based upon the limited data available on the dose rate stability and geometric accuracy of the Cyberknife system, this study estimates that dynamic arc delivery can be accomplished with sufficient accuracy for clinical application. Dose rate variation produces a change in dose to the planning target volume according to the perturbation of total monitor units delivered, while multileaf collimator lag and robot pointing error typically increase the mean dose to the planning target volume by up to 1%..

Previous work has shown that PRESAGE® can be used successfully to perform 3D dosimetric measurements of complex radiotherapy treatments. However, measurements near the sample edges are known to be difficult to achieve. This is an issue when the doses at air-material interfaces are of interest, for example when investigating the electron return effect (ERE) present in treatments delivered by magnetic resonance (MR)-linac systems. To study this effect, a set of 3.5 cm-diameter cylindrical PRESAGE® samples was uniformly irradiated with multiple dose fractions, using either a conventional linac or an MR-linac. The samples were imaged between fractions using an optical-CT, to read out the corresponding accumulated doses. A calibration between TPS-predicted dose and optical-CT pixel value was determined for individual dosimeters as a function of radial distance from the axis of rotation. This data was used to develop a correction that was applied to four additional samples of PRESAGE® of the same formulation, irradiated with 3D-CRT and IMRT treatment plans, to recover significantly improved 3D measurements of dose. An alternative strategy was also tested, in which the outer surface of the sample was physically removed prior to irradiation. Results show that for the formulation studied here, PRESAGE® samples have a central region that responds uniformly and an edge region of 6-7 mm where there is gradual increase in dosimeter response, rising to an over-response of 24%-36% at the outer boundary. This non-uniform dose response increases in both extent and magnitude over time. Both mitigation strategies investigated were successful. In our four exemplar studies, we show how discrepancies at edges are reduced from 13%-37% of the maximum dose to between 2 and 8%. Quantitative analysis shows that the 3D gamma passing rates rise from 90.4, 69.3, 63.7 and 43.6% to 97.3, 99.9, 96.7 and 98.9% respectively..

Respiratory-gated radiotherapy treatments of lung tumors reduce the irradiated normal tissue volume and potentially lower the risk of side effects. However, in clinical routine, the gating signal is usually derived from external markers or other surrogate signals and may not always correlate well with the actual tumor position. This study uses the kV-imaging system of a LINAC in combination with a multiple template matching algorithm for markerless real-time detection of the tumor position in a dynamic anthropomorphic porcine lung phantom. The tumor was realized by a small container filled with polymer dosimetry gel, the so-called gel tumor. A full end-to-end test for a gated treatment was performed and the geometric and dosimetric accuracy was validated. The accuracy of the tumor detection algorithm in SI- direction was found to be [Formula: see text] mm and the gel tumor was automatically detected in 98 out of 100 images. The measured 3D dose distribution showed a uniform coverage of the gel tumor and comparison with the treatment plan revealed a high 3D [Formula: see text]-passing rate of [Formula: see text] ([Formula: see text]). The simulated treatment confirmed the employed margin sizes for residual motion within the gating window and serves as an end-to-end test for a gated treatment based on a markerless fluoroscopic real-time tumor detection..

INTRODUCTION: MR-guided adapted radiotherapy (MRgART) using a high field MR-linac has recently become available. We report the estimated delivered fractional dose of the first five prostate cancer patients treated at our centre using MRgART and compare this to C-Arm linac daily Image Guided Radiotherapy (IGRT). METHODS: Patients were treated using adapted treatment plans shaped to their daily anatomy. The treatments were recalculated on an MR image acquired immediately prior to treatment delivery in order to estimate the delivered fractional dose. C-arm linac non-adapted VMAT treatment plans were recalculated on the same MR images to estimate the fractional dose that would have been delivered using conventional radiotherapy techniques using a daily IGRT protocol. RESULTS: 95% and 93% of mandatory target coverage objectives and organ at risk dose constraints were achieved by MRgART and C-arm linac delivered dose estimates, respectively. Both delivery techniques were estimated to have achieved 98% of mandatory Organ At Risk (OAR) dose constraints whereas for the target clinical goals, 86% and 80% were achieved by MRgART and C-arm linac delivered dose estimates. CONCLUSIONS: Prostate MRgART can be delivered using the a high field MR-linac. Radiotherapy performed on a C-arm linac offers a good solution for prostate cancer patients who present with favourable anatomy at the time of reference imaging and demonstrate stable anatomy throughout the course of their treatment. For patients with critical OARs abutting target volumes on their reference image we have demonstrated the potential for a target dose coverage improvement for MRgART compared to C-arm linac treatment..

BACKGROUND AND PURPOSE: Combined photon intensity-modulated radiotherapy (IMRT) and sequential dose-escalated carbon ion beam therapy (IBT) is a technically advanced treatment option for head and neck malignancies. We proposed and evaluated an integrated planning strategy as opposed to an established and largely separated planning workflow. MATERIALS AND METHODS: Ten patients with representative malignancies of the head and neck region underwent combined carbon-photon radiotherapy (RT) in our facilities. Clinical plans were created according to the separated workflow with independent optimization stages for both modalities. Experimental plans incorporated the existing carbon IBT dose distribution into the optimization stage of a step-and-shoot photon IMRT (bias dose planning). RESULTS: Cumulative dose distributions showed statistically significant differences between the two planning strategies and were predominantly in favor of the integrated approach. As such, target irradiation was generally maintained or even improved in a subset of metrics, while normal tissue sparing was widely enhanced; for instance, in the ipsilateral temporal lobe with median Dmean of -16% (p < 0.001). Maximum doses D1% (with adjustment for different fractionation) fell below thresholds for toxicity risk in a minority of instances, where they were previously exceeded. Integral dose did not differ significantly. CONCLUSIONS: Our findings indicate that combination planning of carbon-photon RT for head and neck malignancies may benefit from a proposed bias dose method, yielding favorable dose distribution characteristics and a streamlined planning workflow with fewer plan revisions. Further research is necessary to validate these observations in terms of robustness and their potential for higher tumor control..

Whole bladder magnetic resonance image-guided radiotherapy using the 1.5 Telsa MR-linac is feasible. Full online adaptive planning workflow based on the anatomy seen at each fraction was performed. This was delivered within 45 min. Intra-fraction bladder filling did not compromise target coverage. Patients reported acceptable tolerance of treatment..

Breathing motion is challenging for radiotherapy planning and delivery. This requires advanced four-dimensional (4D) imaging and motion mitigation strategies and associated validation tools with known deformations. Numerical phantoms such as the XCAT provide reproducible and realistic data for simulation-based validation. However, the XCAT generates partially inconsistent and non-invertible deformations where tumours remain rigid and structures can move through each other. We address these limitations by post-processing the XCAT deformation vector fields (DVF) to generate a breathing phantom with realistic motion and quantifiable deformation. An open-source post-processing framework was developed that corrects and inverts the XCAT-DVFs while preserving sliding motion between organs. Those post-processed DVFs are used to warp the first XCAT-generated image to consecutive time points providing a 4D phantom with a tumour that moves consistently with the anatomy, the ability to scale lung density as well as consistent and invertible DVFs. For a regularly breathing case, the inverse consistency of the DVFs was verified and the tumour motion was compared to the original XCAT. The generated phantom and DVFs were used to validate a motion-including dose reconstruction (MIDR) method using isocenter shifts to emulate rigid motion. Differences between the reconstructed doses with and without lung density scaling were evaluated. The post-processing framework produced DVFs with a maximum [Formula: see text]-percentile inverse-consistency error of 0.02 mm. The generated phantom preserved the dominant sliding motion between the chest wall and inner organs. The tumour of the original XCAT phantom preserved its trajectory while deforming consistently with the underlying tissue. The MIDR was compared to the ground truth dose reconstruction illustrating its limitations. MIDR with and without lung density scaling resulted in small dose differences up to 1 Gy (prescription 54 Gy). The proposed open-source post-processing framework overcomes important limitations of the original XCAT phantom and makes it applicable to a wider range of validation applications within radiotherapy..

The Cyberknife system (Accuray Inc., Sunnyvale, CA) enables radiotherapy using stereotactic ablative body radiotherapy (SABR) with a large number of non-coplanar beam orientations. Recently, a multileaf collimator has also been available to allow flexibility in field shaping. This work aims to evaluate the quality of treatment plans obtainable with the multileaf collimator. Specifically, the aim is to find a subset of beam orientations from a predetermined set of candidate directions, such that the treatment quality is maintained but the treatment time is reduced. An evolutionary algorithm is used to successively refine a randomly selected starting set of beam orientations. By using an efficient computational framework, clinically useful solutions can be found in several hours. It is found that 15 beam orientations are able to provide treatment quality which approaches that of the candidate beam set of 110 beam orientations, but with approximately half of the estimated treatment time. Choice of an efficient subset of beam orientations offers the possibility to improve the patient experience and maximise the number of patients treated..

On-treatment imaging in radiotherapy has evolved over the last 60 years, bringing with it changes in the roles of radiographers, radiologists and oncologists. The ability to acquire and interpret high quality images (2D kilovoltage and megavoltage imaging and 3D CT and cone-beam CT) for radiotherapy planning and delivery requires therapy radiographers to have skills and knowledge that overlap with those of diagnostic radiographers. With the implementation of MRI-guided radiotherapy, treatment radiographers and clinical oncologists are exploring new territory, requiring truly collaborative working practices with their radiology partners. This short communication introduces the first images acquired using the hybrid MR Linac at our institution..

OBJECTIVES: To determine the potential for dose escalation to a biological equivalent dose BED10 ≅ 100 Gy in hypofractionated radiotherapy for locally advanced pancreatic cancer (LAPC). MATERIALS AND METHODS: Ten unselected LAPC patients were retrospectively included in the study. Two fractionation regimens were compared (5 and 15 fractions). The aim was to cover 95% of the Planning Target Volume (PTV) with a BED10 = 54 Gy (base dose = 33 Gy in 5 fractions, 42.5 Gy in 15 fractions) whilst respecting organs-at-risk (OAR) constraints. Once the highest PTV coverage was achieved dose escalation to a BED10 ≅ 100 Gy (escalated dose = 50 Gy in 5 fractions, 67.5 Gy in 15 fractions) was attempted, limiting the PTV maximum dose to 130% of the escalated dose. RESULTS: In 5 fractions, 95% PTV coverage by both base and escalated doses could be achieved for one patient with PTV more than 1 cm away from OAR. 95% and 90% PTV coverage by the base dose was achieved in one and two patients respectively. In all other patients, coverage even by the base dose had to be compromised to comply with OAR constraints. In 15 fractions, 95% PTV coverage by the base dose was feasible for all patients except one. Dose escalation allowed improvement in target coverage by the base dose in both fractionation regimen whilst covering a sub-volume of the PTV with a BED10 ≅ 100 Gy. Both fractionation schemes were equivalent in terms of dose escalation potential. CONCLUSION: LAPC patients with OAR close to the PTV are generally not eligible for hypofractionation with dose escalation. However, this planning study shows that it is possible to cover PTV sub-volumes with a BED10 ≅ 100 Gy in addition to delivering a BED10 = 54 Gy to 90-95% of the PTV as commonly prescribed to this population. Combined with an adaptive approach, this may maximize PTV coverage by a high BED on days with favourable anatomy..

CT-based radiotherapy workflow is limited by poor soft tissue definition in the pelvis and reliance on rigid registration methods. Current image-guided radiotherapy and adaptive radiotherapy models therefore have limited ability to improve clinical outcomes. The advent of MRI-guided radiotherapy solutions provides the opportunity to overcome these limitations with the potential to deliver online real-time MRI-based plan adaptation on a daily basis, a true "plan of the day." This review describes the application of MRI guided radiotherapy in two pelvic tumour sites likely to benefit from this approach..

PURPOSE: The use of dynamic arcs for delivery of stereotactic body radiation therapy (SBRT) on Cyberknife is investigated, with a view to improving treatment times. This study investigates the required modeling of robot and multileaf collimator (MLC) motion between control points in the trajectory and then uses this to develop an optimization method for treatment planning of a dynamic arc with Cyberknife. The resulting plans are compared in terms of dose-volume histograms and estimated treatment times with those produced by a conventional beam arrangement. METHODS: Five SBRT patient cases (prostate A - conventional, prostate B - brachytherapy-type, lung, liver, and partial left breast) were retrospectively studied. A suitable arc trajectory with control points spaced at 5° was proposed and treatment plans were produced for typical clinical protocols. The optimization consisted of a fluence optimization, segmentation, and direct aperture optimization using a gradient descent method. Dose delivered by the moving MLC was either taken to be the dose delivered discretely at the control points or modeled using effective fluence delivered between control points. The accuracy of calculated dose was assessed by recalculating after optimization using five interpolated beams and 100 interpolated apertures between each optimization control point. The resulting plans were compared using dose-volume histograms and estimated treatment times with those for a conventional Cyberknife beam arrangement. RESULTS: If optimization is performed based on discrete doses delivered at the arc control points, large differences of up to 40% of the prescribed dose are seen when recalculating with interpolation. When the effective fluence between control points is taken into account during optimization, dosimetric differences are <2% for most structures when the plans are recalculated using intermediate nodes, but there are differences of up to 15% peripherally. Treatment plan quality is comparable between the arc trajectory and conventional body path. All plans meet the relevant clinical goals, with the exception of specific structures which overlap with the planning target volume. Median estimated treatment time is 355 s (range 235-672 s) for arc delivery and 675 s (range 554-1025 s) for conventional delivery. CONCLUSIONS: The method of using effective fluence to model MLC motion between control points is sufficiently accurate to provide for accurate inverse planning of dynamic arcs with Cyberknife. The proposed arcing method produces treatment plans with comparable quality to the body path, with reduced estimated treatment delivery time..

OBJECTIVES: To systematically identify the preferred magnetic resonance imaging (MRI) sequences following volunteer imaging on a 1.5 Tesla (T) MR-Linear Accelerator (MR Linac) for future protocol development. METHODS: Non-patient volunteers were recruited to a Research and Ethics committee approved prospective MR-only imaging study on a 1.5T MR Linac system. Volunteers attended 1-3 imaging sessions that included a combination of mDixon, T1w, T2w sequences using 2-dimensional (2D) and 3-dimensional (3D) acquisitions. Each sequence was acquired over 2-7 minutes and reviewed by a panel of 3 observers to evaluate image quality using a visual grading analysis based on a 4-point Likert scale. Sequences were acquired and modified iteratively until deemed fit for purpose (online image matching or re-planning) and all observers agreed they were suitable in 3 volunteers. RESULTS: 26 volunteers underwent 31 imaging sessions of six general anatomical regions. Images were acquired in one or two of six general anatomical regions: male pelvis (n = 9), female pelvis (n = 4), chestwall/breast (n = 5), lung/oesophagus (n = 5), abdomen (n = 3) and head and neck (n = 5). Images were acquired using a pre-defined exam-card that on average, included six sequences (range 2-10), with a maximum scan time of approximately one hour. The majority of observers preferred T2-weighted sequences. The thorax teams were the only groups to prefer T1-weighted imaging. CONCLUSIONS: An iterative process identified sequence agreement in all anatomical regions. These sequences will now be evaluated in patient volunteers. ADVANCES IN KNOWLEDGE: This manuscript is the first publication sharing the results of the first systematic selection of MRI sequences for use in on-board MRI-guided radiotherapy by end-users (therapeutic radiographers and clinical oncologists) in healthy volunteers..

MR-guided radiotherapy treatment planning utilises the high soft-tissue contrast of MRI to reduce uncertainty in delineation of the target and organs at risk. Replacing 4D-CT with MRI-derived synthetic 4D-CT would support treatment plan adaptation on hybrid MR-guided radiotherapy systems for inter- and intrafractional differences in anatomy and respiration, whilst mitigating the risk of CT to MRI registration errors. Three methods were devised to calculate synthetic 4D and midposition (time-weighted mean position of the respiratory cycle) CT from 4D-T1w and Dixon MRI. The first approach employed intensity-based segmentation of Dixon MRI for bulk-density assignment (sCTD). The second step added spine density information using an atlas of CT and Dixon MRI (sCTDS). The third iteration used a polynomial function relating Hounsfield units and normalised T1w image intensity to account for variable lung density (sCTDSL). Motion information in 4D-T1w MRI was applied to generate synthetic CT in midposition and in twenty respiratory phases. For six lung cancer patients, synthetic 4D-CT was validated against 4D-CT in midposition by comparison of Hounsfield units and dose-volume metrics. Dosimetric differences found by comparing sCTD,DS,DSL and CT were evaluated using a Wilcoxon signed-rank test (p   =  0.05). Compared to sCTD and sCTDS, planning on sCTDSL significantly reduced absolute dosimetric differences in the planning target volume metrics to less than 98 cGy (1.7% of the prescribed dose) on average. When comparing sCTDSL and CT, average radiodensity differences were within 97 Hounsfield units and dosimetric differences were significant only for the planning target volume D99% metric. All methods produced clinically acceptable results for the organs at risk in accordance with the UK SABR consensus guidelines and the LungTech EORTC phase II trial. The overall good agreement between sCTDSL and CT demonstrates the feasibility of employing synthetic 4D-CT for plan adaptation on hybrid MR-guided radiotherapy systems..

Combined radiotherapy and hyperthermia offer great potential for the successful treatment of radio-resistant tumours through thermo-radiosensitization. Tumour response heterogeneity, due to intrinsic, or micro-environmentally induced factors, may greatly influence treatment outcome, but is difficult to account for using traditional treatment planning approaches. Systems oncology simulation, using mathematical models designed to predict tumour growth and treatment response, provides a powerful tool for analysis and optimization of combined treatments. We present a framework that simulates such combination treatments on a cellular level. This multiscale hybrid cellular automaton simulates large cell populations (up to 107 cells) in vitro, while allowing individual cell-cycle progression, and treatment response by modelling radiation-induced mitotic cell death, and immediate cell kill in response to heating. Based on a calibration using a number of experimental growth, cell cycle and survival datasets for HCT116 cells, model predictions agreed well (R2 > 0.95) with experimental data within the range of (thermal and radiation) doses tested (0-40 CEM43, 0-5 Gy). The proposed framework offers flexibility for modelling multimodality treatment combinations in different scenarios. It may therefore provide an important step towards the modelling of personalized therapies using a virtual patient tumour..

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..

Owing to its excellent soft-tissue contrast, magnetic resonance (MR) imaging has found an increased application in radiation therapy (RT). By harnessing these properties for treatment planning, automated segmentation methods can alleviate the manual workload burden to the clinical workflow. We investigated atlas-based segmentation methods of organs at risk (OARs) in the head and neck (H&N) region using one approach that selected the most similar atlas from a library of segmented images and two multi-atlas approaches. The latter were based on weighted majority voting and an iterative atlas-fusion approach called STEPS. We built the atlas library from pre-treatment T1-weighted MR images of 12 patients with manual contours of the parotids, spinal cord and mandible, delineated by a clinician. Following a leave-one-out cross-validation strategy, we measured the geometric accuracy by calculating Dice similarity coefficients (DSC), standard and 95% Hausdorff distances (HD and HD95), and the mean surface distance (MSD), whereby the manual contours served as the gold standard. To benchmark the algorithm, we determined the inter-observer variability (IOV) between three observers. To investigate the dosimetric effect of segmentation inaccuracies, we implemented an auto-planning strategy within the treatment planning system Monaco (Elekta AB, Stockholm, Sweden). For each set of auto-segmented OARs, we generated a plan for a 9-beam step and shoot intensity modulated RT treatment, designed according to our institution's clinical H&N protocol. Superimposing the dose distributions on the gold standard OARs, we calculated dose differences to OARs caused by delineation differences between auto-segmented and gold standard OARs. We investigated the correlations between geometric and dosimetric differences. The mean DSC was larger than 0.8 and the mean MSD smaller than 2 mm for the multi-atlas approaches, resulting in a geometric accuracy comparable to previously published results and within the range of the IOV. While dosimetric differences could be as large as 23% of the clinical goal, treatment plans fulfilled all imposed clinical goals for the gold standard OARs. Correlations between geometric and dosimetric measures were low with R2  <  0.5. The geometric accuracy and the ability to achieve clinically acceptable treatment plans indicate the suitability of using atlas-based contours for RT treatment planning purposes. The low correlations between geometric and dosimetric measures suggest that geometric measures alone are not sufficient to predict the dosimetric impact of segmentation inaccuracies on treatment planning for the data utilised in this study..

Adaptive radiotherapy (ART) strategies systematically monitor variations in target and neighbouring structures to inform treatment-plan modification during radiotherapy. This is necessary because a single plan designed before treatment is insufficient to capture the actual dose delivered to the target and adjacent critical structures during the course of radiotherapy. Magnetic resonance imaging (MRI) provides superior soft-tissue image contrast over current standard X-ray-based technologies without additional radiation exposure. With integrated MRI and radiotherapy platforms permitting motion monitoring during treatment delivery, it is possible that adaption can be informed by real-time anatomical imaging. This allows greater treatment accuracy in terms of dose delivered to target with smaller, individualised treatment margins. The use of functional MRI sequences would permit ART to be informed by imaging biomarkers, so allowing both personalised geometric and biological adaption. In this review, we discuss ART solutions enabled by MRI guidance and its potential gains for our patients across tumour types..

BACKGROUND AND PURPOSE: The superior soft-tissue contrast of 4D-T2w MRI motivates its use for delineation in radiotherapy treatment planning. We address current limitations of slice-selective implementations, including thick slices and artefacts originating from data incompleteness and variable breathing. MATERIALS AND METHODS: A method was developed to calculate midposition and 4D-T2w images of the whole thorax from continuously acquired axial and sagittal 2D-T2w MRI (1.5 × 1.5 × 5.0 mm3). The method employed image-derived respiratory surrogates, deformable image registration and super-resolution reconstruction. Volunteer imaging and a respiratory motion phantom were used for validation. The minimum number of dynamic acquisitions needed to calculate a representative midposition image was investigated by retrospectively subsampling the data (10-30 dynamic acquisitions). RESULTS: Super-resolution 4D-T2w MRI (1.0 × 1.0 × 1.0 mm3, 8 respiratory phases) did not suffer from data incompleteness and exhibited reduced stitching artefacts compared to sorted multi-slice MRI. Experiments using a respiratory motion phantom and colour-intensity projection images demonstrated a minor underestimation of the motion range. Midposition diaphragm differences in retrospectively subsampled acquisitions were <1.1 mm compared to the full dataset. 10 dynamic acquisitions were found sufficient to generate midposition MRI. CONCLUSIONS: A motion-modelling and super-resolution method was developed to calculate high quality 4D/midposition T2w MRI from orthogonal 2D-T2w MRI..

2D cine MR imaging may be utilized to monitor rapidly moving tumors and organs-at-risk for real-time adaptive radiotherapy. This study systematically investigates the impact of geometric imaging parameters on the ability of 2D cine MR imaging to guide template-matching-driven autocontouring of lung tumors and abdominal organs. Abdominal 4D MR images were acquired of six healthy volunteers and thoracic 4D MR images were obtained of eight lung cancer patients. At each breathing phase of the images, the left kidney and gallbladder or lung tumor, respectively, were outlined as volumes of interest. These images and contours were used to create artificial 2D cine MR images, while simultaneously serving as 3D ground truth. We explored the impact of five different imaging parameters (pixel size, slice thickness, imaging plane orientation, number and relative alignment of images as well as strategies to create training images). For each possible combination of imaging parameters, we generated artificial 2D cine MR images as training and test images. A template-matching algorithm used the training images to determine the tumor or organ position in the test images. Subsequently, a 3D base contour was shifted to the determined position and compared to the ground truth via centroid distance and Dice similarity coefficient. The median centroid distance between adapted and ground truth contours was 1.56 mm for the kidney, 3.81 mm for the gallbladder and 1.03 mm for the lung tumor (median Dice similarity coefficient: 0.95, 0.72 and 0.93). We observed that a decrease in image resolution led to a modest decrease in localization accuracy, especially for the small gallbladder. However, for all volumes of interest localization accuracy varied substantially more between subjects than due to the different imaging parameters. Automated tumor and organ localization using 2D cine MR imaging and template-matching-based autocontouring is robust against variation of geometric imaging parameters. Future work and optimization efforts of 2D cine MR imaging for real-time adaptive radiotherapy is needed to characterize the influence of sequence- and anatomical site-specific imaging contrast..

Dosimetric quality assurance (QA) of the new Elekta Unity (MR-linac) will differ from the QA performed of a conventional linac due to the constant magnetic field, which creates an electron return effect (ERE). In this work we aim to validate PRESAGE®dosimetry in a transverse magnetic field, and assess its use to validate the research version of the Monaco TPS of the MR-linac. Cylindrical samples of PRESAGE®3D dosimeter separated by an air gap were irradiated with a cobalt-60 unit, while placed between the poles of an electromagnet at 0.5 T and 1.5 T. This set-up was simulated in EGSnrc/Cavity Monte Carlo (MC) code and relative dose distributions were compared with measurements using 1D and 2D gamma criteria of 3% and 1.5 mm. The irradiation conditions were adapted for the MR-linac and compared with Monaco TPS simulations. Measured and EGSnrc/Cavity simulated profiles showed good agreement with a gamma passing rate of 99.9% for 0.5 T and 99.8% for 1.5 T. Measurements on the MR-linac also compared well with Monaco TPS simulations, with a gamma passing rate of 98.4% at 1.5 T. Results demonstrated that PRESAGE®can accurately measure dose and detect the ERE, encouraging its use as a QA tool to validate the Monaco TPS of the MR-linac for clinically relevant dose distributions at tissue-air boundaries..

Margins are employed in radiotherapy treatment planning to mitigate the dosimetric effects of geometric uncertainties for the clinical target volume (CTV). Unfortunately, whilst the use of margins can increase the probability that sufficient dose is delivered to the CTV, it can also result in delivering high dose of radiation to surrounding organs at risk (OARs). We expand on our previous work on beam-dependent margins and propose a novel adaptive margin concept, where margins are moulded away from selected OARs for better OAR-high-dose sparing, whilst maintaining similar dose coverage probability to the CTV. This, however, comes at a cost of a larger irradiation volume, and thus can negatively impact other structures. We investigate the impact of the adaptive margin concept when applied to prostate radiotherapy treatments, and compare treatment plans generated using our beam-dependent margins without adaptation, with adaption from the rectum and with adaptation from both the rectum and bladder. Five prostate patients were used in this planning study. All plans achieved similar dose coverage probability, and were able to ensure at least 90% population coverage with the target receiving at least 95% of the prescribed dose to [Formula: see text]. We observed overall better high-dose sparing to OARs that were considered when using the adapted beam-dependent PTVs, with the degree of sparing dependent on both the number of OARs under consideration as well as the relative position between the CTV and the OARs..

OBJECTIVE: Mimicking state-of-the-art patient radiotherapy with high-precision irradiators for small animals is expected to advance the understanding of dose-effect relationships and radiobiology in general. We work on the implementation of intensity-modulated radiotherapy-like irradiation schemes for small animals. As a first step, we present a fast analytical dose calculation algorithm for keV photon beams. METHODS: We follow a superposition-convolution approach adapted to kV X-rays, based on previous work for microbeam therapy. We assume local energy deposition at the photon interaction point due to the short electron ranges in tissue. This allows us to separate the dose calculation into locally absorbed primary dose and the scatter contribution, calculated in a point kernel approach. We validate our dose model against Geant4 Monte Carlo (MC) simulations and compare the results to Muriplan (XStrahl Ltd, Camberley, UK). RESULTS: For field sizes of (1 mm)(2) to (1 cm)(2) in water, the depth dose curves show a mean disagreement of 1.7% to MC simulations, with the largest deviations in the entrance region (4%) and at large depths (5% at 7 cm). Larger discrepancies are observed at water-to-bone boundaries, in bone and at the beam edges in slab phantoms and a mouse brain. Calculation times are in the order of 5 s for a single beam. CONCLUSION: The algorithm shows good agreement with MC simulations in an initial validation. It has the potential to become an alternative to full MC dose calculation. Advances in knowledge: The presented algorithm demonstrates the potential of kernel-based dose calculation for kV photon beams. It will be valuable in intensity-modulated radiotherapy and inverse treatment planning for high precision small-animal radiotherapy..

BACKGROUND AND PURPOSE: Computed tomography (CT) imaging is the current gold standard for radiotherapy treatment planning (RTP). The establishment of a magnetic resonance imaging (MRI) only RTP workflow requires the generation of a synthetic CT (sCT) for dose calculation. This study evaluates the feasibility of using a multi-atlas sCT synthesis approach (sCTa) for head and neck and prostate patients. MATERIAL AND METHODS: The multi-atlas method was based on pairs of non-rigidly aligned MR and CT images. The sCTa was obtained by registering the MRI atlases to the patient's MRI and by fusing the mapped atlases according to morphological similarity to the patient. For comparison, a bulk density assignment approach (sCTbda) was also evaluated. The sCTbda was obtained by assigning density values to MRI tissue classes (air, bone and soft-tissue). After evaluating the synthesis accuracy of the sCTs (mean absolute error), sCT-based delineations were geometrically compared to the CT-based delineations. Clinical plans were re-calculated on both sCTs and a dose-volume histogram and a gamma analysis was performed using the CT dose as ground truth. RESULTS: Results showed that both sCTs were suitable to perform clinical dose calculations with mean dose differences less than 1% for both the planning target volume and the organs at risk. However, only the sCTa provided an accurate and automatic delineation of bone. CONCLUSIONS: Combining MR delineations with our multi-atlas CT synthesis method could enable MRI-only treatment planning and thus improve the dosimetric and geometric accuracy of the treatment, and reduce the number of imaging procedures..

Combined radiotherapy (RT) and hyperthermia (HT) treatments may improve treatment outcome by heat induced radio-sensitisation. We propose an empirical cell survival model (AlphaR model) to describe this multimodality therapy. The model is motivated by the observation that heat induced radio-sensitisation may be explained by a reduction in the DNA damage repair capacity of heated cells. We assume that this repair is only possible up to a threshold level above which survival will decrease exponentially with dose. Experimental cell survival data from two cell lines (HCT116, Cal27) were considered along with that taken from the literature (baby hamster kidney [BHK] and Chinese hamster ovary cells [CHO]) for HT and combined RT-HT. The AlphaR model was used to study the dependence of clonogenic survival on treatment temperature, and thermal dose R(2) ≥ 0.95 for all fits). For HT survival curves (0-80 CEM43 at 43.5-57 °C), the number of free fit AlphaR model parameters could be reduced to two. Both parameters increased exponentially with temperature. We derived the relative biological effectiveness (RBE) or HT treatments at different temperatures, to provide an alternative description of thermal dose, based on our AlphaR model. For combined RT-HT, our analysis is restricted to the linear quadratic arm of the model. We show that, for the range used (20-80 CEM43, 0-12 Gy), thermal dose is a valid indicator of heat induced radio-sensitisation, and that the model parameters can be described as a function thereof. Overall, the proposed model provides a flexible framework for describing cell survival curves, and may contribute to better quantification of heat induced radio-sensitisation, and thermal dose in general..

In radiotherapy, abdominal and thoracic sites are candidates for performing motion tracking. With real-time control it is possible to adjust the multileaf collimator (MLC) position to the target position. However, positions are not perfectly matched and position errors arise from system delays and complicated response of the electromechanic MLC system. Although, it is possible to compensate parts of these errors by using predictors, residual errors remain and need to be compensated to retain target coverage. This work presents a method to statistically describe tracking errors and to automatically derive a patient-specific, per-segment margin to compensate the arising underdosage on-line, i.e. during plan delivery. The statistics of the geometric error between intended and actual machine position are derived using kernel density estimators. Subsequently a margin is calculated on-line according to a selected coverage parameter, which determines the amount of accepted underdosage. The margin is then applied onto the actual segment to accommodate the positioning errors in the enlarged segment. The proof-of-concept was tested in an on-line tracking experiment and showed the ability to recover underdosages for two test cases, increasing [Formula: see text] in the underdosed area about [Formula: see text] and [Formula: see text], respectively. The used dose model was able to predict the loss of dose due to tracking errors and could be used to infer the necessary margins. The implementation had a running time of 23 ms which is compatible with real-time requirements of MLC tracking systems. The auto-adaptivity to machine and patient characteristics makes the technique a generic yet intuitive candidate to avoid underdosages due to MLC tracking errors..

To tackle the problem of magnetic resonance imaging (MRI)-only radiotherapy treatment planning (RTP), we propose a multi-atlas information propagation scheme that jointly segments organs and generates pseudo x-ray computed tomography (CT) data from structural MR images (T1-weighted and T2-weighted). As the performance of the method strongly depends on the quality of the atlas database composed of multiple sets of aligned MR, CT and segmented images, we also propose a robust way of registering atlas MR and CT images, which combines structure-guided registration, and CT and MR image synthesis. We first evaluated the proposed framework in terms of segmentation and CT synthesis accuracy on 15 subjects with prostate cancer. The segmentations obtained with the proposed method were compared using the Dice score coefficient (DSC) to the manual segmentations. Mean DSCs of 0.73, 0.90, 0.77 and 0.90 were obtained for the prostate, bladder, rectum and femur heads, respectively. The mean absolute error (MAE) and the mean error (ME) were computed between the reference CTs (non-rigidly aligned to the MRs) and the pseudo CTs generated with the proposed method. The MAE was on average [Formula: see text] HU and the ME [Formula: see text] HU. We then performed a dosimetric evaluation by re-calculating plans on the pseudo CTs and comparing them to the plans optimised on the reference CTs. We compared the cumulative dose volume histograms (DVH) obtained for the pseudo CTs to the DVH obtained for the reference CTs in the planning target volume (PTV) located in the prostate, and in the organs at risk at different DVH points. We obtained average differences of [Formula: see text] in the PTV for [Formula: see text], and between [Formula: see text] and 0.05% in the PTV, bladder, rectum and femur heads for D mean and [Formula: see text]. Overall, we demonstrate that the proposed framework is able to automatically generate accurate pseudo CT images and segmentations in the pelvic region, potentially bypassing the need for CT scan for accurate RTP..

OBJECTIVES: The aim of this study was to develop and verify a method to obtain good temporal resolution T2-weighted 4-dimensional (4D-T2w) magnetic resonance imaging (MRI) by using motion information from T1-weighted 4D (4D-T1w) MRI, to support treatment planning in MR-guided radiotherapy. MATERIALS AND METHODS: Ten patients with primary non-small cell lung cancer were scanned at 1.5 T axially with a volumetric T2-weighted turbo spin echo sequence gated to exhalation and a volumetric T1-weighted stack-of-stars spoiled gradient echo sequence with golden angle spacing acquired in free breathing. From the latter, 20 respiratory phases were reconstructed using the recently developed 4D joint MoCo-HDTV algorithm based on the self-gating signal obtained from the k-space center. Motion vector fields describing the respiratory cycle were obtained by deformable image registration between the respiratory phases and projected onto the T2-weighted image volume. The resulting 4D-T2w volumes were verified against the 4D-T1w volumes: an edge-detection method was used to measure the diaphragm positions; the locations of anatomical landmarks delineated by a radiation oncologist were compared and normalized mutual information was calculated to evaluate volumetric image similarity. RESULTS: High-resolution 4D-T2w MRI was obtained. Respiratory motion was preserved on calculated 4D-T2w MRI, with median diaphragm positions being consistent with less than 6.6 mm (2 voxels) for all patients and less than 3.3 mm (1 voxel) for 9 of 10 patients. Geometrical positions were coherent between 4D-T1w and 4D-T2w MRI as Euclidean distances between all corresponding anatomical landmarks agreed to within 7.6 mm (Euclidean distance of 2 voxels) and were below 3.8 mm (Euclidean distance of 1 voxel) for 355 of 470 pairs of anatomical landmarks. Volumetric image similarity was commensurate between 4D-T1w and 4D-T2w MRI, as mean percentage differences in normalized mutual information (calculated over all respiratory phases and patients), between corresponding respiratory phases of 4D-T1w and 4D-T2w MRI and the tie-phase of 4D-T1w and 3-dimensional T2w MRI, were consistent to 0.41% ± 0.37%. Four-dimensional T2w MRI displayed tumor extent, structure, and position more clearly than corresponding 4D-T1w MRI, especially when mobile tumor sites were adjacent to organs at risk. CONCLUSIONS: A methodology to obtain 4D-T2w MRI that retrospectively applies the motion information from 4D-T1w MRI to 3-dimensional T2w MRI was developed and verified. Four-dimensional T2w MRI can assist clinicians in delineating mobile lesions that are difficult to define on 4D-T1w MRI, because of poor tumor-tissue contrast..

PURPOSE: Anchored electromagnetic transponders for tumor motion monitoring during lung radiotherapy were clinically evaluated. First, intrafractional motion patterns were analyzed as well as their interfractional variations. Second, intra- and interfractional changes of the geometric transponder positions were investigated. MATERIALS AND METHODS: Intrafractional motion data from 7 patients with an upper or middle lobe tumor and three implanted transponders each was used to calculate breathing amplitudes, overall motion amount and motion midlines in three mutual perpendicular directions and three-dimensionally (3D) for 162 fractions. For 6 patients intra- and interfractional variations in transponder distances and in the size of the triangle defined by the transponder locations over the treatment course were determined. RESULTS: Mean 3D values of all fractions were up to 4.0, 4.6 and 3.4 mm per patient for amplitude, overall motion amount and midline deviation, respectively. Intrafractional transponder distances varied with standard deviations up to 3.2 mm, while a maximal triangle shrinkage of 36.5% over 39 days was observed. CONCLUSIONS: Electromagnetic real-time motion monitoring was feasible for all patients. Detected respiratory motion was on average modest in this small cohort without lower lobe tumors, but changes in motion midline were of the same size as the amplitudes and greater midline motion can be observed in some fractions. Intra- and interfractional variations of the geometric transponder positions can be large, so for reliable motion management correlation between transponder and tumor motion needs to be evaluated per patient..

PURPOSE: This study investigates the feasibility and potential benefits of radiotherapy with a 1.5T MR-Linac for locally advanced non-small cell lung cancer (LA NSCLC) patients. MATERIAL AND METHODS: Ten patients with LA NSCLC were retrospectively re-planned six times: three treatment plans were created according to a protocol for conventionally fractionated radiotherapy and three treatment plans following guidelines for isotoxic target dose escalation. In each case, two plans were designed for the MR-Linac, either with standard (∼7mm) or reduced (∼3mm) planning target volume (PTV) margins, while one conventional linac plan was created with standard margins. Treatment plan quality was evaluated using dose-volume metrics or by quantifying dose escalation potential. RESULTS: All generated treatment plans fulfilled their respective planning constraints. For conventionally fractionated treatments, MR-Linac plans with standard margins had slightly increased skin dose when compared to conventional linac plans. Using reduced margins alleviated this issue and decreased exposure of several other organs-at-risk (OAR). Reduced margins also enabled increased isotoxic target dose escalation. CONCLUSION: It is feasible to generate treatment plans for LA NSCLC patients on a 1.5T MR-Linac. Margin reduction, facilitated by an envisioned MRI-guided workflow, enables increased OAR sparing and isotoxic target dose escalation for the respective treatment approaches..

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PURPOSE: Firstly, this study provides a real-time implementation of online dose reconstruction for tracked volumetric arc therapy (VMAT). Secondly, this study describes a novel offline quality assurance tool, based on commercial dose calculation algorithms. METHODS: Online dose reconstruction for VMAT is a computationally challenging task in terms of computer memory usage and calculation speed. To potentially reduce the amount of memory used, we analyzed the impact of beam angle sampling for dose calculation on the accuracy of the dose distribution. To establish the performance of the method, we planned two single-arc VMAT prostate stereotactic body radiation therapy cases for delivery with dynamic MLC tracking. For quality assurance of our online dose reconstruction method we have also developed a stand-alone offline dose reconstruction tool, which utilizes the RayStation treatment planning system to calculate dose. RESULTS: For the online reconstructed dose distributions of the tracked deliveries, we could establish strong resemblance for 72 and 36 beam co-planar equidistant beam samples with less than 1.2% deviation for the assessed dose-volume indicators (clinical target volume D98 and D2, and rectum D2). We could achieve average runtimes of 28-31 ms per reported MLC aperture for both dose computation and accumulation, meeting our real-time requirement. To cross-validate the offline tool we have compared the planned dose to the offline reconstructed dose for static deliveries and found excellent agreement (3%/3 mm global gamma passing rates of 99.8-100%). CONCLUSION: Being able to reconstruct dose during delivery enables online quality assurance and online replanning strategies for VMAT. The offline quality assurance tool provides the means to validate novel online dose reconstruction applications using a commercial dose calculation engine. This article is protected by copyright. All rights reserved..

Radiotherapy treatment planning for use with high-energy photon beams currently employs a binary approach in defining the planning target volume (PTV). We propose a margin concept that takes the beam directions into account, generating beam-dependent PTVs (bdPTVs) on a beam-by-beam basis. The resulting degree of overlaps between the bdPTVs are used within the optimisation process; the optimiser effectively considers the same voxel to be both target and organ at risk (OAR) with fractional contributions. We investigate the impact of this novel approach when applied to prostate radiotherapy treatments, and compare treatment plans generated using beam dependent margins to conventional margins. Five prostate patients were used in this planning study, and plans using beam dependent margins improved the sparing of high doses to target-surrounding OARs, though a trade-off in delivering additional low dose to the OARs can be observed. Plans using beam dependent margins are observed to have a slightly reduced target coverage. Nevertheless, all plans are able to satisfy 90% population coverage with the target receiving at least 95% of the prescribed dose to [Formula: see text]..

BACKGROUND AND PURPOSE: Adaptive radiotherapy (ART) using plan selection is being introduced clinically for bladder cancer, but the challenge of how to compensate for intra-fractional motion remains. The purpose of this study was to assess target coverage with respect to intra-fractional motion and the potential for normal tissue sparing in MRI-guided ART (MRIGART) using isotropic (MRIGARTiso), an-isotropic (MRIGARTanIso) and population-based margins (MRIGARTpop). MATERIALS AND METHODS: Nine bladder cancer patients treated in a phase II trial of plan selection underwent 6-7 weekly repeat MRI series, each with volumetric scans acquired over a 10 min period. Adaptive re-planning on the 0 min MRI scans was performed using density override, simulating a hypo-fractionated schedule. Target coverage was evaluated on the 10 min scan to quantify the impact of intra-fractional motion. RESULTS: MRIGARTanIso reduced the course-averaged PTV by median 304 cc compared to plan selection. Bladder shifts affected target coverage in individual fractions for all strategies. Two patients had a v95% of the bladder below 98% for MRIGARTiso. MRIGARTiso decreased the bowel V25 with 15-46 cc compared to MRIGARTpop. CONCLUSION: Online re-optimised ART has a considerable normal tissue sparing potential. MRIGART with online corrections for target shift during a treatment fraction should be considered in ART for bladder cancer..

PURPOSE: A study of real-time adaptive radiotherapy systems was performed to test the hypothesis that, across delivery systems and institutions, the dosimetric accuracy is improved with adaptive treatments over non-adaptive radiotherapy in the presence of patient-measured tumor motion. METHODS AND MATERIALS: Ten institutions with robotic(2), gimbaled(2), MLC(4) or couch tracking(2) used common materials including CT and structure sets, motion traces and planning protocols to create a lung and a prostate plan. For each motion trace, the plan was delivered twice to a moving dosimeter; with and without real-time adaptation. Each measurement was compared to a static measurement and the percentage of failed points for γ-tests recorded. RESULTS: For all lung traces all measurement sets show improved dose accuracy with a mean 2%/2mm γ-fail rate of 1.6% with adaptation and 15.2% without adaptation (p<0.001). For all prostate the mean 2%/2mm γ-fail rate was 1.4% with adaptation and 17.3% without adaptation (p<0.001). The difference between the four systems was small with an average 2%/2mm γ-fail rate of <3% for all systems with adaptation for lung and prostate. CONCLUSIONS: The investigated systems all accounted for realistic tumor motion accurately and performed to a similar high standard, with real-time adaptation significantly outperforming non-adaptive delivery methods..

BACKGROUND AND PURPOSE: There are concerns that radiotherapy doses delivered in a magnetic field might be distorted due to the Lorentz force deflecting secondary electrons. This study investigates this effect on lung stereotactic body radiotherapy (SBRT) treatments, conducted either with or without multileaf collimator (MLC) tumor tracking. MATERIAL AND METHODS: Lung SBRT treatments with an MR-linac were simulated for nine patients. Two different treatment techniques were compared: conventional, non-tracked deliveries and deliveries with real-time MLC tumor tracking, each conducted either with or without a 1.5T magnetic field. RESULTS: Slight dose distortions at air-tissue-interfaces were observed in the presence of the magnetic field. Most prominently, the dose to 2% of the skin increased by 1.4Gy on average. Regardless of the presence of the magnetic field, MLC tracking was able to spare healthy tissue, for example by decreasing the mean lung dose by 0.3Gy on average, while maintaining the target dose. CONCLUSIONS: Accounting for the magnetic field during treatment plan optimization allowed for design and delivery of clinically acceptable lung SBRT treatments with an MR-linac. Furthermore, the ability of MLC tumor tracking to decrease dose exposure of healthy tissue, was not inhibited by the magnetic field..

OBJECTIVE: To evaluate three image acquisition presets for four-dimensional cone beam CT (CBCT) to identify an optimal preset for lung tumour image quality while minimizing dose and acquisition time. METHODS: Nine patients undergoing radical conventionally fractionated radiotherapy for lung cancer had verification CBCTs acquired using three presets: Preset 1 on Day 1 (11 mGy dose, 240 s acquisition time), Preset 2 on Day 2 (9 mGy dose, 133 s acquisition time) and Preset 3 on Day 3 (9 mGy dose, 67 s acquisition time). The clarity of the tumour and other thoracic structures, and the acceptability of the match, were retrospectively graded by visual grading analysis (VGA). Logistic regression was used to identify the most appropriate preset and any factors that might influence the result. RESULTS: Presets 1 and 2 met a clinical requirement of 75% of structures to be rated "Clear" or above and 75% of matches to be rated "Acceptable" or above. Clarity is significantly affected by preset, patient, observer and structure. Match acceptability is significantly affected by preset. CONCLUSION: The application of VGA in this initial study enabled a provisional selection of an optimal preset (Preset 2) to be made. ADVANCES IN KNOWLEDGE: This was the first application of VGA to the investigation of presets for CBCT..

AIM: The aim of this study was to investigate potential advantages and disadvantages of three-dimensional conformal radiotherapy (3DCRT), multiple fixed-field intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) in terms of dose to the planning target volume (PTV), organs at risk (OARs) and normal tissue complication probability (NTCP) for delivering ipsilateral radiotherapy. MATERIALS AND METHODS: 3DCRT, IMRT and VMAT were compared in patients with well-lateralised primary tonsillar cancers who underwent primary radical ipsilateral radiotherapy. The following parameters were compared: conformity index (CI); homogeneity index (HI); dose-volume histograms (DVHs) of PTVs and OARs; NTCP, risk of radiation-induced cancer and dose accumulation during treatment. RESULTS: IMRT and VMAT were superior to 3DCRT in terms of CI, HI and dose to the target volumes, as well as mandible and dose accumulation robustness. The techniques were equivalent in terms of dose and NTCP for the contralateral oral cavity, contralateral submandibular gland and mandible, when specific dose constraint objectives were used on the oral cavity volume. Although the volume of normal tissue exposed to low-dose radiation was significantly higher with IMRT and VMAT, the risk of radiation-induced secondary malignancy was dependant on the mathematical model used. CONCLUSION: This study demonstrates the superiority of IMRT/VMAT techniques over 3DCRT in terms of dose homogeneity, conformity and consistent dose delivery to the PTV throughout the course of treatment in patients with lateralised oropharyngeal cancers. Dosimetry and NTCP calculations show that these techniques are equivalent to 3DCRT with regard to the risk of acute mucositis when specific dose constraint objectives were used on the contralateral oral cavity OAR..

PURPOSE: To quantify the performance of the Clarity ultrasound (US) imaging system (Elekta AB, Stockholm, Sweden) for real-time dynamic multileaf collimator (MLC) tracking. METHODS: The Clarity calibration and quality assurance phantom was mounted on a motion platform moving with a periodic sine wave trajectory. The detected position of a 30 mm hypoechogenic sphere within the phantom was continuously reported via Clarity's real-time streaming interface to an in-house tracking and delivery software and subsequently used to adapt the MLC aperture. A portal imager measured MV treatment field/MLC apertures and motion platform positions throughout each experiment to independently quantify system latency and geometric error. Based on the measured range of latency values, a prostate stereotactic body radiation therapy (SBRT) delivery was performed with three realistic motion trajectories. The dosimetric impact of system latency on MLC tracking was directly measured using a 3D dosimeter mounted on the motion platform. RESULTS: For 2D US imaging, the overall system latency, including all delay times from the imaging and delivery chain, ranged from 392 to 424 ms depending on the lateral sector size. For 3D US imaging, the latency ranged from 566 to 1031 ms depending on the elevational sweep. The latency-corrected geometric root-mean squared error was below 0.75 mm (2D US) and below 1.75 mm (3D US). For the prostate SBRT delivery, the impact of a range of system latencies (400-1000 ms) on the MLC tracking performance was minimal in terms of gamma failure rate. CONCLUSIONS: Real-time MLC tracking based on a noninvasive US input is technologically feasible. Current system latencies are higher than those for x-ray imaging systems, but US can provide full volumetric image data and the impact of system latency was measured to be small for a prostate SBRT case when using a US-like motion input..

PURPOSE: This study provides a proof of concept for real-time 4D dose reconstruction for lung stereotactic body radiation therapy (SBRT) with multileaf collimator (MLC) tracking and assesses the impact of tumor tracking on the size of target margins. METHODS: The authors have implemented real-time 4D dose reconstruction by connecting their tracking and delivery software to an Agility MLC at an Elekta Synergy linac and to their in-house treatment planning software (TPS). Actual MLC apertures and (simulated) target positions are reported to the TPS every 40 ms. The dose is calculated in real-time from 4DCT data directly after each reported aperture by utilization of precalculated dose-influence data based on a Monte Carlo algorithm. The dose is accumulated onto the peak-exhale (reference) phase using energy-mass transfer mapping. To investigate the impact of a potentially reducible safety margin, the authors have created and delivered treatment plans designed for a conventional internal target volume (ITV) + 5 mm, a midventilation approach, and three tracking scenarios for four lung SBRT patients. For the tracking plans, a moving target volume (MTV) was established by delineating the gross target volume (GTV) on every 4DCT phase. These were rigidly aligned to the reference phase, resulting in a unified maximum GTV to which a 1, 3, or 5 mm isotropic margin was added. All scenarios were planned for 9-beam step-and-shoot IMRT to meet the criteria of RTOG 1021 (3 × 18 Gy). The GTV 3D center-of-volume shift varied from 6 to 14 mm. RESULTS: Real-time dose reconstruction at 25 Hz could be realized on a single workstation due to the highly efficient implementation of dose calculation and dose accumulation. Decreased PTV margins resulted in inadequate target coverage during untracked deliveries for patients with substantial tumor motion. MLC tracking could ensure the GTV target dose for these patients. Organ-at-risk (OAR) doses were consistently reduced by decreased PTV margins. The tracked MTV + 1 mm deliveries resulted in the following OAR dose reductions: lung V20 up to 3.5%, spinal cord D2 up to 0.9 Gy/Fx, and proximal airways D2 up to 1.4 Gy/Fx. CONCLUSIONS: The authors could show that for patient data at clinical resolution and realistic motion conditions, the delivered dose could be reconstructed in 4D for the whole lung volume in real-time. The dose distributions show that reduced margins yield lower doses to healthy tissue, whilst target dose can be maintained using dynamic MLC tracking..

By adapting to the actual patient anatomy during treatment, tracked multi-leaf collimator (MLC) treatment deliveries offer an opportunity for margin reduction and healthy tissue sparing. This is assumed to be especially relevant for hypofractionated protocols in which intrafractional motion does not easily average out. In order to confidently deliver tracked treatments with potentially reduced margins, it is necessary to monitor not only the patient anatomy but also the actually delivered dose during irradiation. In this study, we present a novel real-time online dose reconstruction tool which calculates actually delivered dose based on pre-calculated dose influence data in less than 10 ms at a rate of 25 Hz. Using this tool we investigate the impact of clinical target volume (CTV) to planning target volume (PTV) margins on CTV coverage and organ-at-risk dose. On our research linear accelerator, a set of four different CTV-to-PTV margins were tested for three patient cases subject to four different motion conditions. Based on this data, we can conclude that tracking eliminates dose cold spots which can occur in the CTV during conventional deliveries even for the smallest CTV-to-PTV margin of 1 mm. Changes of organ-at-risk dose do occur frequently during MLC tracking and are not negligible in some cases. Intrafractional dose reconstruction is expected to become an important element in any attempt of re-planning the treatment plan during the delivery based on the observed anatomy of the day..

Volumetric modulated arc therapy (VMAT) has found widespread clinical application in recent years. A large number of treatment planning studies have evaluated the potential for VMAT for different disease sites based on the currently available commercial implementations of VMAT planning. In contrast, literature on the underlying mathematical optimization methods used in treatment planning is scarce. VMAT planning represents a challenging large scale optimization problem. In contrast to fluence map optimization in intensity-modulated radiotherapy planning for static beams, VMAT planning represents a nonconvex optimization problem. In this paper, the authors review the state-of-the-art in VMAT planning from an algorithmic perspective. Different approaches to VMAT optimization, including arc sequencing methods, extensions of direct aperture optimization, and direct optimization of leaf trajectories are reviewed. Their advantages and limitations are outlined and recommendations for improvements are discussed..

PURPOSE: To investigate the influence of interfractional changes on the delivered dose of intensity modulated proton (IMPT) and photon plans (IMXT). METHODS AND MATERIALS: Five postoperative head and neck cancer patients, previously treated with tomotherapy at our institute, were analyzed. The planning study is based on megavoltage (MV) control images. For each patient one IMPT plan and one IMXT plan were generated on the first MV-CT and recalculated on weekly control MV-CTs in the actual treatment position. Dose criteria for evaluation were coverage and conformity of the planning target volume (PTV), as well as mean dose to parotids and maximum dose to spinal cord. RESULTS: Considerable dosimetric changes were observed for IMPT and IMXT plans. Proton plans showed a more pronounced increase of maximum dose and decrease of minimum dose with local underdosage occurring even in the center of the PTV (worst IMPT vs. IMXT coverage: 66.7% vs. 85.0%). The doses to organs at risk (OARs) increased during the treatment period. However, the OAR doses of IMPT stayed below corresponding IMXT values at any time. For both modalities treatment plans did not necessarily worsen monotonically throughout the treatment. CONCLUSIONS: Although absolute differences between planned and reconstructed doses were larger in IMPT plans, doses to OARs were higher in IMXT plans. Tumor coverage was more stable in IMXT plans; IMPT dose distributions indicated a high risk for local underdosage during the treatment course..

PURPOSE: The authors investigated the potential of optimized noncoplanar irradiation trajectories for volumetric modulated arc therapy (VMAT) treatments of nasopharyngeal patients and studied the trade-off between treatment plan quality and delivery time in radiation therapy. METHODS: For three nasopharyngeal patients, the authors generated treatment plans for nine different delivery scenarios using dedicated optimization methods. They compared these scenarios according to dose characteristics, number of beam directions, and estimated delivery times. In particular, the authors generated the following treatment plans: (1) a 4π plan, which is a not sequenced, fluence optimized plan that uses beam directions from approximately 1400 noncoplanar directions and marks a theoretical upper limit of the treatment plan quality, (2) a coplanar 2π plan with 72 coplanar beam directions as pendant to the noncoplanar 4π plan, (3) a coplanar VMAT plan, (4) a coplanar step and shoot (SnS) plan, (5) a beam angle optimized (BAO) coplanar SnS IMRT plan, (6) a noncoplanar BAO SnS plan, (7) a VMAT plan with rotated treatment couch, (8) a noncoplanar VMAT plan with an optimized great circle around the patient, and (9) a noncoplanar BAO VMAT plan with an arbitrary trajectory around the patient. RESULTS: VMAT using optimized noncoplanar irradiation trajectories reduced the mean and maximum doses in organs at risk compared to coplanar VMAT plans by 19% on average while the target coverage remains constant. A coplanar BAO SnS plan was superior to coplanar SnS or VMAT; however, noncoplanar plans like a noncoplanar BAO SnS plan or noncoplanar VMAT yielded a better plan quality than the best coplanar 2π plan. The treatment plan quality of VMAT plans depended on the length of the trajectory. The delivery times of noncoplanar VMAT plans were estimated to be 6.5 min in average; 1.6 min longer than a coplanar plan but on average 2.8 min faster than a noncoplanar SnS plan with comparable treatment plan quality. CONCLUSIONS: The authors' study reconfirms the dosimetric benefits of noncoplanar irradiation of nasopharyngeal tumors. Both SnS using optimized noncoplanar beam ensembles and VMAT using an optimized, arbitrary, noncoplanar trajectory enabled dose reductions in organs at risk compared to coplanar SnS and VMAT. Using great circles or simple couch rotations to implement noncoplanar VMAT, however, was not sufficient to yield meaningful improvements in treatment plan quality. The authors estimate that noncoplanar VMAT using arbitrary optimized irradiation trajectories comes at an increased delivery time compared to coplanar VMAT yet at a decreased delivery time compared to noncoplanar SnS IMRT..

This study demonstrates the feasibility of automated marker tracking for the real-time detection of intrafractional target motion using noisy kilovoltage (kV) X-ray images degraded by the megavoltage (MV) treatment beam. The authors previously introduced the in-line imaging geometry, in which the flat-panel detector (FPD) is mounted directly underneath the treatment head of the linear accelerator. They found that the 121 kVp image quality was severely compromised by the 6 MV beam passing through the FPD at the same time. Specific MV-induced artefacts present a considerable challenge for automated marker detection algorithms. For this study, the authors developed a new imaging geometry by re-positioning the FPD and the X-ray tube. This improved the contrast-to-noise-ratio between 40% and 72% at the 1.2 mAs/image exposure setting. The increase in image quality clearly facilitates the quick and stable detection of motion with the aid of a template matching algorithm. The setup was tested with an anthropomorphic lung phantom (including an artificial lung tumour). In the tumour one or three Calypso beacons were embedded to achieve better contrast during MV radiation. For a single beacon, image acquisition and automated marker detection typically took around 76 ± 6 ms. The success rate was found to be highly dependent on imaging dose and gantry angle. To eliminate possible false detections, the authors implemented a training phase prior to treatment beam irradiation and also introduced speed limits for motion between subsequent images..

BACKGROUND AND PURPOSE: The latency of a multileaf collimator (MLC) tracking system used to overcome respiratory motion causes misalignment of the treatment beam with respect to the gross tumour volume, which may result in reduced target coverage. This study investigates the magnitude of this effect. MATERIAL AND METHODS: Simulated superior-inferior breathing motion was used to construct histograms of isocentre offset with respect to the gross tumour volume (GTV) for a variety of tracking latencies. Dose distributions for conformal volumetric modulated arc therapy (VMAT) arcs were then calculated at a range of offsets and summed according to these displacement histograms. The results were verified by delivering the plans to a Delta(4) phantom on a motion platform. RESULTS: In the absence of an internal target margin, a tracking latency of 150 ms reduces the GTV D95% by approximately 2%. With a margin of 2 mm, the same drop in dose occurs for a tracking latency of 450 ms. Lung V(13Gy) is unaffected by a range of latencies. These results are supported by the phantom measurements. CONCLUSIONS: Assuming that internal motion can be modelled by a rigid translation of the patient, MLC tracking of conformal VMAT can be effectively accomplished in the absence of an internal target margin for substantial breathing motion (4 s period and 20 mm peak-peak amplitude) so long as the system latency is less than 150 ms..

PURPOSE: The aim of this work was to compare and validate various computed tomography (CT) number calibration techniques with respect to cone beam CT (CBCT) dose calculation accuracy. METHODS: CBCT dose calculation accuracy was assessed for pelvic, lung, and head and neck (H&N) treatment sites for two approaches: (1) physics-based scatter correction methods (CBCTr); (2) density override approaches including assigning water density to the entire CBCT (W), assignment of either water or bone density (WB), and assignment of either water or lung density (WL). Methods for CBCT density assignment within a commercially available treatment planning system (RSauto), where CBCT voxels are binned into six density levels, were assessed and validated. Dose-difference maps and dose-volume statistics were used to compare the CBCT dose distributions with the ground truth of a planning CT acquired the same day as the CBCT. RESULTS: For pelvic cases, all CTN calibration methods resulted in average dose-volume deviations below 1.5 %. RSauto provided larger than average errors for pelvic treatments for patients with large amounts of adipose tissue. For H&N cases, all CTN calibration methods resulted in average dose-volume differences below 1.0 % with CBCTr (0.5 %) and RSauto (0.6 %) performing best. For lung cases, WL and RSauto methods generated dose distributions most similar to the ground truth. CONCLUSION: The RSauto density override approach is an attractive option for CTN adjustments for a variety of anatomical sites. RSauto methods were validated, resulting in dose calculations that were consistent with those calculated on diagnostic-quality CT images, for CBCT images acquired of the lung, for patients receiving pelvic RT in cases without excess adipose tissue, and for H&N cases..

PURPOSE: Real-time, markerless localization of lung tumors with kV imaging is often inhibited by ribs obscuring the tumor and poor soft-tissue contrast. This study investigates the use of dual-energy imaging, which can generate radiographs with reduced bone visibility, to enhance automated lung tumor tracking for real-time adaptive radiotherapy. METHODS: kV images of an anthropomorphic breathing chest phantom were experimentally acquired and radiographs of actual lung cancer patients were Monte-Carlo-simulated at three imaging settings: low-energy (70 kVp, 1.5 mAs), high-energy (140 kVp, 2.5 mAs, 1 mm additional tin filtration), and clinical (120 kVp, 0.25 mAs). Regular dual-energy images were calculated by weighted logarithmic subtraction of high- and low-energy images and filter-free dual-energy images were generated from clinical and low-energy radiographs. The weighting factor to calculate the dual-energy images was determined by means of a novel objective score. The usefulness of dual-energy imaging for real-time tracking with an automated template matching algorithm was investigated. RESULTS: Regular dual-energy imaging was able to increase tracking accuracy in left-right images of the anthropomorphic phantom as well as in 7 out of 24 investigated patient cases. Tracking accuracy remained comparable in three cases and decreased in five cases. Filter-free dual-energy imaging was only able to increase accuracy in 2 out of 24 cases. In four cases no change in accuracy was observed and tracking accuracy worsened in nine cases. In 9 out of 24 cases, it was not possible to define a tracking template due to poor soft-tissue contrast regardless of input images. The mean localization errors using clinical, regular dual-energy, and filter-free dual-energy radiographs were 3.85, 3.32, and 5.24 mm, respectively. Tracking success was dependent on tumor position, tumor size, imaging beam angle, and patient size. CONCLUSIONS: This study has highlighted the influence of patient anatomy on the success rate of real-time markerless tumor tracking using dual-energy imaging. Additionally, the importance of the spectral separation of the imaging beams used to generate the dual-energy images has been shown..

BACKGROUND: With the development of more conformal and precise radiation techniques such as Intensity-Modulated Radiotherapy (IMRT), Stereotactic Body Radiotherapy (SBRT) and Image-Guided Radiotherapy (IGRT), patients with hepatic tumors could be treated with high local doses by sparing normal liver tissue. However, frequently occurring large HCC tumors are still a dosimetric challenge in spite of modern high sophisticated RT modalities. This interventional clinical study has been set up to evaluate the value of different fiducial markers, and to use the modern imaging methods for further treatment optimization using physical and informatics approaches. METHODS AND DESIGN: Surgically implanted radioopaque or electromagnetic markers are used to detect tumor local-ization during radiotherapy. The required markers for targeting and observation during RT can be implanted in a previously defined optimal position during the oncologically indicated operation. If there is no indication for a surgical resection or open biopsy, markers may be inserted into the liver or tumor tissue by using ultrasound-guidance. Primary study aim is the detection of the patients' anatomy at the time of RT by observation of the marker position during the indicated irradiation (IGRT). Secondary study aims comprise detection and recording of 3D liver and tumor motion during RT. Furthermore, the study will help to develop technical strategies and mechanisms based on the recorded information on organ motion to avoid inaccurate dose application resulting from fast organ motion and deformation. DISCUSSION: This is an open monocentric non-randomized, prospective study for the evaluation of organ motion using interstitial markers or implantable radiotransmitter. The trial will evaluate the full potential of different fiducial markers to further optimize treatment of moving targets, with a special focus on liver lesions..

PURPOSE: The dosimetric verification of treatment plans in helical tomotherapy usually is carried out via verification measurements. In this study, a method for independent dose calculation of tomotherapy treatment plans is presented, that uses a conventional treatment planning system with a pencil kernel dose calculation algorithm for generation of verification dose distributions based on patient CT data. METHODS: A pencil beam algorithm that directly uses measured beam data was configured for dose calculation for a tomotherapy machine. Tomotherapy treatment plans were converted into a format readable by an in-house treatment planning system by assigning each projection to one static treatment field and shifting the calculation isocenter for each field in order to account for the couch movement. The modulation of the fluence for each projection is read out of the delivery sinogram, and with the kernel-based dose calculation, this information can directly be used for dose calculation without the need for decomposition of the sinogram. The sinogram values are only corrected for leaf output and leaf latency. Using the converted treatment plans, dose was recalculated with the independent treatment planning system. Multiple treatment plans ranging from simple static fields to real patient treatment plans were calculated using the new approach and either compared to actual measurements or the 3D dose distribution calculated by the tomotherapy treatment planning system. In addition, dose-volume histograms were calculated for the patient plans. RESULTS: Except for minor deviations at the maximum field size, the pencil beam dose calculation for static beams agreed with measurements in a water tank within 2%/2 mm. A mean deviation to point dose measurements in the cheese phantom of 0.89% ± 0.81% was found for unmodulated helical plans. A mean voxel-based deviation of -0.67% ± 1.11% for all voxels in the respective high dose region (dose values >80%), and a mean local voxel-based deviation of -2.41% ± 0.75% for all voxels with dose values >20% were found for 11 modulated plans in the cheese phantom. Averaged over nine patient plans, the deviations amounted to -0.14% ± 1.97% (voxels >80%) and -0.95% ± 2.27% (>20%, local deviations). For a lung case, mean voxel-based deviations of more than 4% were found, while for all other patient plans, all mean voxel-based deviations were within ± 2.4%. CONCLUSIONS: The presented method is suitable for independent dose calculation for helical tomotherapy within the known limitations of the pencil beam algorithm. It can serve as verification of the primary dose calculation and thereby reduce the need for time-consuming measurements. By using the patient anatomy and generating full 3D dose data, and combined with measurements of additional machine parameters, it can substantially contribute to overall patient safety..

PURPOSE: To evaluate the performance of the Elekta Agility multileaf collimator (MLC) for dynamic real-time tumor tracking. METHODS: The authors have developed a new control software which interfaces to the Agility MLC to dynamically program the movement of individual leaves, the dynamic leaf guides (DLGs), and the Y collimators ("jaws") based on the actual target trajectory. A motion platform was used to perform dynamic tracking experiments with sinusoidal trajectories. The actual target positions reported by the motion platform at 20, 30, or 40 Hz were used as shift vectors for the MLC in beams-eye-view. The system latency of the MLC (i.e., the average latency comprising target device reporting latencies and MLC adjustment latency) and the geometric tracking accuracy were extracted from a sequence of MV portal images acquired during irradiation for the following treatment scenarios: leaf-only motion, jaw + leaf motion, and DLG + leaf motion. RESULTS: The portal imager measurements indicated a clear dependence of the system latency on the target position reporting frequency. Deducting the effect of the target frequency, the leaf adjustment latency was measured to be 38 ± 3 ms for a maximum target speed v of 13 mm/s. The jaw + leaf adjustment latency was 53 ± 3 at a similar speed. The system latency at a target position frequency of 30 Hz was in the range of 56-61 ms for the leaves (v ≤ 31 mm/s), 71-78 ms for the jaw + leaf motion (v ≤ 25 mm/s), and 58-72 ms for the DLG + leaf motion (v ≤ 59 mm/s). The tracking accuracy showed a similar dependency on the target position frequency and the maximum target speed. For the leaves, the root-mean-squared error (RMSE) was between 0.6-1.5 mm depending on the maximum target speed. For the jaw + leaf (DLG + leaf) motion, the RMSE was between 0.7-1.5 mm (1.9-3.4 mm). CONCLUSIONS: The authors have measured the latency and geometric accuracy of the Agility MLC, facilitating its future use for clinical tracking applications..

This report, compiled by experts on the treatment of mobile targets with advanced radiotherapy, summarizes the main conclusions and innovations achieved during the 4D treatment planning workshop 2013. This annual workshop focuses on research aiming to advance 4D radiotherapy treatments, including all critical aspects of time resolved delivery, such as in-room imaging, motion detection, motion managing, beam application, and quality assurance techniques. The report aims to revise achievements in the field and to discuss remaining challenges and potential solutions. As main achievements advances in the development of a standardized 4D phantom and in the area of 4D-treatment plan optimization were identified. Furthermore, it was noticed that MR imaging gains importance and high interest for sequential 4DCT/MR data sets was expressed, which represents a general trend of the field towards data covering a longer time period of motion. A new point of attention was work related to dose reconstructions, which may play a major role in verification of 4D treatment deliveries. The experimental validation of results achieved by 4D treatment planning and the systematic evaluation of different deformable image registration methods especially for inter-modality fusions were identified as major remaining challenges. A challenge that was also suggested as focus for future 4D workshops was the adaptation of image guidance approaches from conventional radiotherapy into particle therapy. Besides summarizing the last workshop, the authors also want to point out new evolving demands and give an outlook on the focus of the next workshop..

We report on recent progress in the field of mobile tumor treatment with scanned particle beams, as discussed in the latest editions of the 4D treatment planning workshop. The workshop series started in 2009, with about 20 people from 4 research institutes involved, all actively working on particle therapy delivery and development. The first workshop resulted in a summary of recommendations for the treatment of mobile targets, along with a list of requirements to apply these guidelines clinically. The increased interest in the treatment of mobile tumors led to a continuously growing number of attendees: the 2012 edition counted more than 60 participants from 20 institutions and commercial vendors. The focus of research discussions among workshop participants progressively moved from 4D treatment planning to complete 4D treatments, aiming at effective and safe treatment delivery. Current research perspectives on 4D treatments include all critical aspects of time resolved delivery, such as in-room imaging, motion detection, beam application, and quality assurance techniques. This was motivated by the start of first clinical treatments of hepato cellular tumors with a scanned particle beam, relying on gating or abdominal compression for motion mitigation. Up to date research activities emphasize significant efforts in investigating advanced motion mitigation techniques, with a specific interest in the development of dedicated tools for experimental validation. Potential improvements will be made possible in the near future through 4D optimized treatment plans that require upgrades of the currently established therapy control systems for time resolved delivery. But since also these novel optimization techniques rely on the validity of the 4DCT, research focusing on alternative 4D imaging technique, such as MRI based 4DCT generation will continue..

Electromagnetic (EM) tracking allows localization of small EM sensors in a magnetic field of known geometry without line-of-sight. However, this technique requires a cable connection to the tracked object. A wireless alternative based on magnetic fields, referred to as transponder tracking, has been proposed by several authors. Although most of the transponder tracking systems are still in an early stage of development and not ready for clinical use yet, Varian Medical Systems Inc. (Palo Alto, California, USA) presented the Calypso system for tumor tracking in radiation therapy which includes transponder technology. But it has not been used for computer-assisted interventions (CAI) in general or been assessed for accuracy in a standardized manner, so far. In this study, we apply a standardized assessment protocol presented by Hummel et al (2005 Med. Phys. 32 2371-9) to the Calypso system for the first time. The results show that transponder tracking with the Calypso system provides a precision and accuracy below 1 mm in ideal clinical environments, which is comparable with other EM tracking systems. Similar to other systems the tracking accuracy was affected by metallic distortion, which led to errors of up to 3.2 mm. The potential of the wireless transponder tracking technology for use in many future CAI applications can be regarded as extremely high..

PURPOSE: 4d cone-beam computed tomography (CBCT) scans are usually reconstructed by extracting the motion information from the 2d projections or an external surrogate signal, and binning the individual projections into multiple respiratory phases. In this "after-the-fact" binning approach, however, projections are unevenly distributed over respiratory phases resulting in inefficient utilization of imaging dose. To avoid excess dose in certain respiratory phases, and poor image quality due to a lack of projections in others, the authors have developed a novel 4d CBCT acquisition framework which actively triggers 2d projections based on the forward-predicted position of the tumor. METHODS: The forward-prediction of the tumor position was independently established using either (i) an electromagnetic (EM) tracking system based on implanted EM-transponders which act as a surrogate for the tumor position, or (ii) an external motion sensor measuring the chest-wall displacement and correlating this external motion to the phase-shifted diaphragm motion derived from the acquired images. In order to avoid EM-induced artifacts in the imaging detector, the authors devised a simple but effective "Faraday" shielding cage. The authors demonstrated the feasibility of their acquisition strategy by scanning an anthropomorphic lung phantom moving on 1d or 2d sinusoidal trajectories. RESULTS: With both tumor position devices, the authors were able to acquire 4d CBCTs free of motion blurring. For scans based on the EM tracking system, reconstruction artifacts stemming from the presence of the EM-array and the EM-transponders were greatly reduced using newly developed correction algorithms. By tuning the imaging frequency independently for each respiratory phase prior to acquisition, it was possible to harmonize the number of projections over respiratory phases. Depending on the breathing period (3.5 or 5 s) and the gantry rotation time (4 or 5 min), between ∼90 and 145 projections were acquired per respiratory phase resulting in a dose of ∼1.7-2.6 mGy per respiratory phase. Further dose savings and decreases in the scanning time are possible by acquiring only a subset of all respiratory phases, for example, peak-exhale and peak-inhale only scans. CONCLUSIONS: This study is the first experimental demonstration of a new 4d CBCT acquisition paradigm in which imaging dose is efficiently utilized by actively triggering only those projections that are desired for the reconstruction process..

PURPOSE: The authors have developed a system that monitors intrafractional target motion perpendicular to the treatment beam with the aid of radioopaque markers by means of separating kV image and megavoltage (MV) treatment field on a single flat-panel detector. METHODS: They equipped a research Siemens Artiste linear accelerator (linac) with a 41 × 41 cm(2) a-Si flat-panel detector underneath the treatment head. The in-line geometry allows kV (imaging) and MV (treatment) beams to share closely aligned beam axes. The kV source, usually mounted directly across from the flat-panel imager, was retracted toward the gantry by 13 cm to intentionally misalign kV and MV beams, resulting in a geometric separation of MV treatment field and kV image on the detector. Two consecutive images acquired within 140 ms (the first with MV-only and the second with kV and MV signal) were subtracted to generate a kV-only image. The images were then analyzed "online" with an automated threshold-based marker detection algorithm. They employed a 3D and a 4D phantom equipped with either a single radioopaque marker or three Calypso beacons to mimic respiratory motion. Measured room positions were either cross-referenced with a phantom voltage signal (single marker) or the Calypso system. The accuracy of the back-projection (from detected marker positions into room coordinates) was verified by a simulation study. RESULTS: A phantom study has demonstrated that the imaging framework is capable of automatically detecting marker positions and sending this information to the tracking tool at an update rate of 7.14 Hz. The system latency is 86.9 ± 1.0 ms for single marker detection in the absence of MV radiation. In the presence of a circular MV field of 5 cm diameter, the latency is 87.1 ± 0.9 ms. The total RMS position detection accuracy is 0.20 mm (without MV radiation) and 0.23 mm (with MV). CONCLUSIONS: Based on the evaluated motion patterns and MV field size, the positional accuracy and system latency indicate that this system is suitable for real-time adaptive applications..

PURPOSE: To present an approach to fast, interfractional adaptive RT in intensity-modulated radiation therapy (IMRT) of head and neck tumors in clinical routine. Ensuring adequate patient position throughout treatment proves challenging in high-precision RT despite elaborate immobilization. Because of weight loss, treatment plans must be adapted to account for requiring supportive therapy incl. feeding tube or parenteral nutrition without treatment breaks. METHODS AND MATERIALS: In-room CT position checks are used to create adapted IMRT treatment plans by stereotactic correlation to the initial setup, and volumes are adapted to the new geometry. New IMRT treatment plans are prospectively created on the basis of position control scans using the initial optimization parameters in KonRad without requiring complete reoptimization and thus facilitating quick replanning in daily routine. Patients treated for squamous cell head and neck cancer (SCCHN) in 2006-2007 were evaluated as to necessity/number of replannings, weight loss, dose, and plan parameters. RESULTS: Seventy-two patients with SCCHN received IMRT to the primary site and lymph nodes (median dose 70.4 Gy). All patients received concomitant chemotherapy requiring supportive therapy by feeding tube or parenteral nutrition. Median weight loss was 7.8 kg, median volume loss was approximately 7%. Fifteen of 72 patients required adaptation of their treatment plans at least once. Target coverage was improved by up to 10.7% (median dose). The increase of dose to spared parotid without replanning was 11.7%. Replanning including outlining and optimization was feasible within 2 hours for each patient, and treatment could be continued without any interruptions. CONCLUSION: To preserve high-quality dose application, treatment plans must be adapted to anatomical changes. Replanning based on position control scans therefore presents a practical approach in clinical routine. In the absence of clinically usable online correction methods, this approach allows significant improvement of target volume coverage and continuous parotid sparing without treatment delays..

PURPOSE: The goal of this work was to compare different methods of incorporating the additional dose of mega-voltage cone-beam CT (MV-CBCT) for image-guided intensity modulated radiotherapy (IMRT) of different tumor entities. MATERIAL AND METHODS: The absolute dose delivered by the MV-CBCT was calculated and considered by creating a scaled IMRT plan (scIMRT) by renormalizing the clinically approved plan (orgIMRT) so that the sum with the MV-CBCT dose yields the same prescribed dose. In the other case, a newly optimized plan (optIMRT) was generated by including the dose distribution of the MV-CBCT as pre-irradiation. Both plans were compared with the orgIMRT plan and a plan where the last fraction was skipped. RESULTS: No significant changes were observed regarding the 95% conformity index of the target volume. The mean dose of the organs at risk (OAR) increased by approx. 7% for the scIMRT plan and 5% for the optIMRT plan. A significant increase of the mean dose to the outline contour was observed, ranging from 3.1 ± 1.3% (optIMRT) to 13.0 ± 6.1% (scIMRT) for both methods over all entities. If the dose of daily MV-CBCT would have been ignored, the additional dose accumulated to nearly a whole treatment fraction with a general increase of approx. 10% to the OARs and approx. 4% to the target volume. CONCLUSION: Both methods of incorporating the additional MV-CBCT dose into the treatment plan are suitable for clinical practice. The dose distribution of the target volume could be achieved as conformal as with the orgIMRT plan, while only a moderate increase of mean dose to OAR was observed..

We present a novel technical concept of a two-dimensional binary multileaf collimator (2D-bMLC) especially designed for fast dose delivery in rotational IMRT. The 2D-bMLC consists of individually controlled absorber channels, which are arranged side by side forming a 2D collimator aperture. In each channel three separate tungsten modules are arranged behind each other. To open and close an element, the central module is shifted between two positions. The purpose of this work is the presentation of the 2D-bMLC concept and its dosimetric evaluation. To determine the dosimetric properties, we designed a Monte Carlo model of an exemplary 2D-bMLC, consisting of 30 × 30 elements. A virtual source model of a flattening filter-free 7 MV linac was used to characterize the linac phase space. A primary radiation efficiency factor of 43% was calculated for the open 2D-bMLC by dividing the integral dose scored for a 2D-bMLC field by the integral dose scored for an open field with the same dimensions. The leakage calculated for the closed collimator was below 0.5%. Following the primary photon fluence distribution, the bixel intensity decreases with the distance of the element to the central axis of the treatment machine. From the collimator field's center toward its borders, the geometric bixel widths increase in a symmetric and predictable manner by up to 4%. The increase is explained by the specific design of the 2D-bMLC. Abutting element beams exhibit a slight tongue-and-groove effect if opened sequentially. This effect as well as the primary radiation efficiency is basically affected by the source size and the dimensions of the collimator elements. We successfully established and evaluated a dosimetric model of the 2D-bMLC. The results are promising, and we will therefore investigate on real patient plans, if the concept could be advantageous for fast rotational IMRT treatments..

In this work, the image quality of a novel megavoltage cone-beam-computed tomography (CBCT) scanner is compared to three other image-guided radiation therapy devices by analysing images of different-sized quality assurance phantoms. The following devices are compared in terms of image uniformity, signal-to-noise ratio, contrast-to-noise ratio (CNR), electron density to HU conversion, presampling modulation transfer function (MTF(pre)) and combined spatial resolution and noise (Q-factor): (i) the Siemens Artiste kilovoltage (kV) (121 kV) CBCT device, (ii) the Artiste treatment beam line (TBL), 6 MV, (iii) the Tomotherapy (3.5 MV) fan-beam CT and (iv) Siemens' novel approach using a carbon target for a dedicated imaging beam line (IBL), 4.2 MV. Machine settings were selected to produce the same imaging dose for all devices. For a head phantom, IBL scans display CNR values 2.6 ± 0.3 times higher than for the TBL at the same dose level (for a CT-number range of -200 to -60 HU). kV CBCT, on the other hand, displays CNR values 7.9 ± 0.3 times higher than the IBL. There was no significant deviation in spatial resolution between IBL, TBL and Tomotherapy in terms of 50% and 10% MTF(pre). For kV CBCT, the MTF(pre) was significantly higher than those for other devices. In our Q-factor analysis, the IBL (14.6) scores higher than the TBL (7.9) and Tomotherapy (9.7) due to its lower noise level. The linearity of electron density to HU conversion is demonstrated for different-sized phantoms. Employing the IBL instead of the TBL significantly reduces the imaging dose by up to a factor of 5 at a constant image quality level, providing an immediate benefit for the patient..

BACKGROUND: To evaluate the impact of image-guided radiation therapy (IGRT) versus non-image-guided radiation therapy (non-IGRT) on the dose to the clinical target volume (CTV) and the cervical spinal cord during fractionated intensity-modulated radiation therapy (IMRT) for head-and-neck cancer (HNC) patients. MATERIAL AND METHODS: For detailed investigation, 4 exemplary patients with daily control-CT scans (total 118 CT scans) were analyzed. For the IGRT approach a target point correction (TPC) derived from a rigid registration focused to the high-dose region was used. In the non-IGRT setting, instead of a TPC, an additional cohort-based safety margin was applied. The dose distributions of the CTV and spinal cord were calculated on each control-CT and the resulting dose volume histograms (DVHs) were compared with the planned ones fraction by fraction. The D50 and D98 values for the CTV and the D5 values of the spinal cord were additionally reported. RESULTS: In general, the D50 and D98 histograms show no remarkable difference between both strategies. Yet, our detailed analysis also reveals differences in individual dose coverage worth inspection. Using IGRT, the D5 histograms show that the spinal cord less frequently receives a higher dose than planned compared to the non-IGRT setting. This effect is even more pronounced when looking at the curve progressions of the respective DVHs. CONCLUSIONS: Both approaches are equally effective in maintaining CTV coverage. However, IGRT is beneficial in spinal cord sparing. The use of an additional margin in the non-IGRT approach frequently results in a higher dose to the spinal cord than originally planned. This implies that a margin reduction combined with an IGRT correction helps to maintain spinal cord dose sparing best as possible. Yet, a detailed analysis of the dosimetric consequences dependent on the used strategy is required, to detect single fractions with unacceptable dosimetric deviations..

Pencil beam algorithms are still considered as standard photon dose calculation methods in Radiotherapy treatment planning for many clinical applications. Despite their established role in radiotherapy planning their performance and clinical applicability has to be continuously adapted to evolving complex treatment techniques such as adaptive radiation therapy (ART). We herewith report on a new highly efficient version of a well-established pencil beam convolution algorithm which relies purely on measured input data. A method was developed that improves raytracing efficiency by exploiting the capability of modern CPU architecture for a runtime reduction. Since most of the current desktop computers provide more than one calculation unit we used symmetric multiprocessing extensively to parallelize the workload and thus decreasing the algorithmic runtime. To maximize the advantage of code parallelization, we present two implementation strategies - one for the dose calculation in inverse planning software, and one for traditional forward planning. As a result, we could achieve on a 16-core personal computer with AMD processors a superlinear speedup factor of approx. 18 for calculating the dose distribution of typical forward IMRT treatment plans..

PURPOSE: One limitation of accurate dose delivery in radiotherapy is intrafractional movement of the tumor or the entire patient which may lead to an underdosage of the target tissue or an overdosage of adjacent organs at risk. In order to compensate for this movement, different techniques have been developed. In this study the tracking performances of a multileaf collimator (MLC) tracking system and a robotic treatment couch tracking system were compared under equal conditions. METHODS: MLC tracking was performed using a tracking system based on the Siemens 160 MLC. A HexaPOD robotic treatment couch tracking system was also installed at the same linac. A programmable 4D motion stage was used to reproduce motion trajectories with different target phantoms. Motion localization of the target was provided by the 4D tracking system of Calypso Medical Inc. The gained positional data served as input signal for the control systems of the MLC and HexaPOD tracking systems attempting to compensate for the target motion. The geometric and dosimetric accuracy for the tracking of eight different respiratory motion trajectories was investigated for both systems. The dosimetric accuracy of both systems was also evaluated for the tracking of five prostate motion trajectories. RESULTS: For the respiratory motion the average root mean square error of all trajectories in y direction was reduced from 4.1 to 2.0 mm for MLC tracking and to 2.2 mm for HexaPOD tracking. In x direction it was reduced from 1.9 to 0.9 mm (MLC) and to 1.0 mm (HexaPOD). The average 2%/2 mm gamma pass rate for the respiratory motion trajectories was increased from 76.4% for no tracking to 89.8% and 95.3% for the MLC and the HexaPOD tracking systems, respectively. For the prostate motion trajectories the average 2%/2 mm gamma pass rate was 60.1% when no tracking was applied and was improved to 85.0% for MLC tracking and 95.3% for the HexaPOD tracking system. CONCLUSIONS: Both systems clearly increased the geometric and dosimetric accuracy during tracking of respiratory motion trajectories. Thereby, the geometric accuracy was increased almost equally by both systems, whereas the dosimetric accuracy of the HexaPOD tracking system was slightly better for all considered respiratory motion trajectories. Substantial improvement of the dosimetric accuracy was also observed during tracking of prostate motion trajectories during an intensity-modulated radiotherapy plan. Thereby, the HexaPOD tracking system showed better results than the MLC tracking..

We have previously developed a tumour tracking system, which adapts the aperture of a Siemens 160 MLC to electromagnetically monitored target motion. In this study, we exploit the use of a novel linac-mounted kilovoltage x-ray imaging system for MLC tracking. The unique in-line geometry of the imaging system allows the detection of target motion perpendicular to the treatment beam (i.e. the directions usually featuring steep dose gradients). We utilized the imaging system either alone or in combination with an external surrogate monitoring system. We equipped a Siemens ARTISTE linac with two flat panel detectors, one directly underneath the linac head for motion monitoring and the other underneath the patient couch for geometric tracking accuracy assessments. A programmable phantom with an embedded metal marker reproduced three patient breathing traces. For MLC tracking based on x-ray imaging alone, marker position was detected at a frame rate of 7.1 Hz. For the combined external and internal motion monitoring system, a total of only 85 x-ray images were acquired prior to or in between the delivery of ten segments of an IMRT beam. External motion was monitored with a potentiometer. A correlation model between external and internal motion was established. The real-time component of the MLC tracking procedure then relied solely on the correlation model estimations of internal motion based on the external signal. Geometric tracking accuracies were 0.6 mm (1.1 mm) and 1.8 mm (1.6 mm) in directions perpendicular and parallel to the leaf travel direction for the x-ray-only (the combined external and internal) motion monitoring system in spite of a total system latency of ~0.62 s (~0.51 s). Dosimetric accuracy for a highly modulated IMRT beam--assessed through radiographic film dosimetry--improved substantially when tracking was applied, but depended strongly on the respective geometric tracking accuracy. In conclusion, we have for the first time integrated MLC tracking with x-ray imaging in the in-line geometry and demonstrated highly accurate respiratory motion tracking..

PURPOSE: Dynamic multileaf collimator tracking represents a promising method for high-precision radiotherapy to moving tumors. In the present study, we report on the integration of electromagnetic real-time tumor position monitoring into a multileaf collimator-based tracking system. METHODS AND MATERIALS: The integrated system was characterized in terms of its geometric and radiologic accuracy. The former was assessed from portal images acquired during radiation delivery to a phantom in tracking mode. The tracking errors were calculated from the positions of the tracking field and of the phantom as extracted from the portal images. Radiologic accuracy was evaluated from film dosimetry performed for conformal and intensity-modulated radiotherapy applied to different phantoms moving on sinusoidal trajectories. A static radiation delivery to the nonmoving target served as a reference for the delivery to the moving phantom with and without tracking applied. RESULTS: Submillimeter tracking accuracy was observed for two-dimensional target motion despite the relatively large system latency of 500 ms. Film dosimetry yielded almost complete recovery of a circular dose distribution with tracking in two dimensions applied: 2%/2 mm gamma-failure rates could be reduced from 59.7% to 3.3%. For single-beam intensity-modulated radiotherapy delivery, accuracy was limited by the finite leaf width. A 2%/2 mm gamma-failure rate of 15.6% remained with tracking applied. CONCLUSION: The integrated system we have presented marks a major step toward the clinical implementation of high-precision dynamic multileaf collimator tracking. However, several challenges such as irregular motion traces or a thorough quality assurance still need to be addressed..

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INTRODUCTION: Despite enormous efforts to improve therapeutic strategies for patients with advanced ovarian carcinoma, outcome remains poor even with the advent cisplatinum-based chemotherapy regimen or taxanes with over 70% of patients developing local failure. Several trials were able to establish the potential benefit of adjuvant whole abdominal RT (WAI) though at the cost of sometimes marked side-effects. New technologies like IMRT have the potential of sparing normal tissues thus also potentially limiting treatment-related toxicity, hence a phase I trial was initiated to evaluate potential clinical benefit of WAI with IMRT. We intended to demonstrate that whole-abdominal IMRT is feasible and can be used in a routine clinical setting. METHODS: A water-equivalent phantom containing OARs was created simulating organ shape of the upper abdomen to investigate the necessary number of beams for the upper abdominal target irrespective of the number of segments and hence treatment times. We prescribed a total dose of 30 Gy in 1.5 Gy fractions to the median of the target. IMRT treatment plans for three patients with advanced ovarian cancer were created using 2 isocentres and between 12 and 14 beams while restricting the number of segments so as to restrict treatment times to less than 45 min. Dose to OARs such as kidneys and liver was strictly limited even below established maxima. RESULTS: In the phantom plans, no clear indication as to the optimum number of beams could be shown though there seems to be a slight trend toward a higher number of beams yielding better results. Examples demonstrating clinically inacceptable dose distributions for plans using only 9 beams. Acceptable treatment plans for real patients could be achieved using 12-14 beams and 2 isocentres. Treatment plans consisted of 264-286 segments resulting in an overall treatment time of approximately 37-45 min. Mean doses to the kidneys could be limited to 29.3% [23.1-33.2%] (right), and 26.8% [21-30.4%] (left). 50% of the liver received less than 72.4% [61-83%]. CONCLUSION: IMRT for whole abdominal irradiation in patients with advanced ovarian carcinoma is applicable and feasible though treatment planning is complex and time-consuming. There is a significant reduction of dose to critical organs by using IMRT while maintaining target volume coverage..

Prediction of respiratory motion is essential for real-time tracking of lung or liver tumours in radiotherapy to compensate for system latencies. This study compares the performance of respiratory motion prediction based on linear regression (LR), neural networks (NN), kernel density estimation (KDE) and support vector regression (SVR) for various sampling rates and system latencies ranging from 0.2 to 0.6 s. Root-mean-squared prediction errors are evaluated on 12 3D lung tumour motion traces acquired at 30 Hz during radiotherapy treatments. The effect of stationary predictor training versus continuous predictor retraining as well as full 3D motion processing versus independent coordinate-wise motion processing is investigated. Model parameter optimization is performed through a grid search in the model parameter space for each predictor and all considered latencies, sampling rates, training schemes and 3D data-processing modes. Comparison of the predictors is performed in the clinically applicable setting of patient-independent model parameters. The considered predictors roughly halve the prediction errors compared to using no prediction. When averaging over all sampling rates and latencies, prediction errors normalized to errors of using no prediction of 0.44, 0.46, 0.49 and 0.55 for NN, SVR, LR and KDE are observed. The small differences between the predictors emphasize the relative importance of adequate model parameter optimization compared to the actual prediction model selection. Thorough model parameter tuning is therefore essential for fair predictor comparisons..

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PURPOSE: Normal tissue changes (NTC) of the normal lung parenchyma are commonly seen after stereotactic single-dose radiotherapy (radiosurgery) of lung tumors. The aim of this study was to investigate the extent and dynamics of NTCs after radiosurgery. METHODS AND MATERIALS: Fifty lung tumors in 49 patients were treated with radiosurgery. Follow-up CTs were anatomically matched to the treatment planning CTs, incorporating the treatment plan and enabling spatial correlation of initial radiation dose distribution and subsequent NTCs of the lung. Lung parenchyma was divided into nine areas of different radiation dose exposures (range, 6-35 Gy). Areas were investigated and compared at different time points according to the development of NTCs. RESULTS: Twenty-six patients developed NTCs during follow-up. The evaluation of the dependency of the extent of NTCs on the amount of radiation dose lead to a linear model for the fixed effects: Fraction of reacting volume =Intercept(T) +0.0208 * Dose ("Dose" should be given in Gy). Dose had a slope of 0.0208 (fraction of normal tissue reaction/Gy) (SE 0.000804, p < 0.0001), implying a significant correlation between dose level and the extent of NTC. CONCLUSION: For radiosurgery of lung tumors, a significant correlation of radiation dose and the extent of NTCs could be demonstrated. Using the introduced formula, a preview on the extent of NTCs to develop in normal lung parenchyma according to the dose level can be performed..

PURPOSE: Advanced high quality radiation therapy techniques such as IMRT require an accurate delivery of precisely modulated radiation fields to the target volume. Interfractional and intrafractional motion of the patient's anatomy, however, may considerably deteriorate the accuracy of the delivered dose to the planned dose distributions. In order to compensate for these potential errors, a dynamic real-time capable MLC control system was designed. METHODS: The newly developed adaptive MLC control system contains specialized algorithms which are capable of continuous optimization and correction of the aperture of the MLC according to the motion of the target volume during the dose delivery. The algorithms calculate the new leaf positions based on target information provided online to the system. The algorithms were implemented in a dynamic target tracking control system designed for a Siemens 160 MLC. To assess the quality of the new target tracking system in terms of dosimetric accuracy, experiments with various types of motion patterns using different phantom setups were performed. The phantoms were equipped with radiochromic films placed between solid water slabs. Dosimetric results of exemplary deliveries to moving targets with and without dynamic MLC tracking applied were compared in terms of the gamma criterion to the reference dose delivered to a static phantom. RESULTS: Our measurements indicated that dose errors for clinically relevant two-dimensional target motion can be compensated by the new control system during the dose delivery of open fields. For a clinical IMRT dose distribution, the gamma success rate was increased from 19% to 77% using the new tracking system. Similar improvements were achieved for the delivery of a complete IMRT treatment fraction to a moving lung phantom. However, dosimetric accuracy was limited by the system's latency of 400 ms and the finite leaf width of 5 mm in the isocenter plane. CONCLUSIONS: Different experimental setups representing different target tracking scenarios proved that the tracking concept, the new algorithms and the dynamic control system make it possible to effectively compensate for dose errors due to target motion in real-time. These early results indicate that the method is suited to increasing the accuracy and the quality of the treatment delivery for the irradiation of moving tumors..

PURPOSE: To investigate whether a new multileaf collimator with a leaf width of 5 mm (MLC-5) over the entire field size of 40 x 40 cm(2) improves plan quality compared to a leaf width of 10 mm (MLC-10) in intensity-modulated radiotherapy (IMRT) with integrated boost for head and neck cancer. PATIENTS AND METHODS: A plan comparison was performed for ten patients with head and neck cancer. For each patient, seven plans were calculated: one plan with MLC-10 and nine beams, four plans with MLC-5 and nine beams (with different intensity levels and two-dimensional median filter sizes [2D-MFS]), and one seven-beam plan with MLC-5 and MLC-10, respectively. Isocenter, beam angles and planning constraints were not changed. Mean values of common plan parameters over all ten patients were estimated, and plan groups of MLC-5 and MLC-10 with nine and seven beams were compared. RESULTS: The use of MLC-5 led to a significantly higher conformity index and an improvement of the 90% coverage of PTV1 (planning target volume) and PTV2 compared with MLC-10. This was noted in the nine- and seven-beam plans. Within the nine-beam group with MLC-5, a reduction of the segment number by up to 25% at reduced intensity levels and for increased 2D-MFS did not markedly worsen plan quality. Interestingly, a seven-beam IMRT with MLC-5 was inferior to a nine-beam IMRT with MLC-5, but superior to a nine-beam IMRT with MLC-10. CONCLUSION: The use of an MLC-5 has significant advantages over an MLC-10 with respect to target coverage and protection of normal tissues in step-and-shoot IMRT of head and neck cancer..

This article reports on a 4D-treatment planning workshop (4DTPW), held on 7-8 December 2009 at the Paul Scherrer Institut (PSI) in Villigen, Switzerland. The participants were all members of institutions actively involved in particle therapy delivery and research. The purpose of the 4DTPW was to discuss current approaches, challenges, and future research directions in 4D-treatment planning in the context of actively scanned particle radiotherapy. Key aspects were addressed in plenary sessions, in which leaders of the field summarized the state-of-the-art. Each plenary session was followed by an extensive discussion. As a result, this article presents a summary of recommendations for the treatment of mobile targets (intrafractional changes) with actively scanned particles and a list of requirements to elaborate and apply these guidelines clinically..

PURPOSE: Four-dimensional (4D) imaging is a key to motion-adapted radiotherapy of lung tumors. We evaluated in a ventilated ex vivo system how size and displacement of artificial pulmonary nodules are reproduced with helical 4D-CT, 4D-MRI, and linac-integrated cone beam CT (CBCT). METHODS AND MATERIALS: Four porcine lungs with 18 agarose nodules (mean diameters 1.3-1.9 cm), were ventilated inside a chest phantom at 8/min and subject to 4D-CT (collimation 24 x 1.2 mm, pitch 0.1, slice/increment 24 x 10(2)/1.5/0.8 mm, pitch 0.1, temporal resolution 0.5 s), 4D-MRI (echo-shared dynamic three-dimensional-flash; repetition/echo time 2.13/0.72 ms, voxel size 2.7 x 2.7 x 4.0 mm, temporal resolution 1.4 s) and linac-integrated 4D-CBCT (720 projections, 3-min rotation, temporal resolution approximately 1 s). Static CT without respiration served as control. Three observers recorded lesion size (RECIST-diameters x/y/z) and axial displacement. Interobserver- and interphase-variation coefficients (IO/IP VC) of measurements indicated reproducibility. RESULTS: Mean x/y/z lesion diameters in cm were equal on static and dynamic CT (1.88/1.87; 1.30/1.39; 1.71/1.73; p > 0.05), but appeared larger on MRI and CBCT (2.06/1.95 [p < 0.05 vs. CT]; 1.47/1.28 [MRI vs. CT/CBCT p < 0.05]; 1.86/1.83 [CT vs. CBCT p < 0.05]). Interobserver-VC for lesion sizes were 2.54-4.47% (CT), 2.29-4.48% (4D-CT); 5.44-6.22% (MRI) and 4.86-6.97% (CBCT). Interphase-VC for lesion sizes ranged from 2.28% (4D-CT) to 10.0% (CBCT). Mean displacement in cm decreased from static CT (1.65) to 4D-CT (1.40), CBCT (1.23) and MRI (1.16). CONCLUSIONS: Lesion sizes are exactly reproduced with 4D-CT but overestimated on 4D-MRI and CBCT with a larger variability due to limited temporal and spatial resolution. All 4D-modalities underestimate lesion displacement..

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PURPOSE: Arc-modulated cone beam therapy (AMCBT) is a fast treatment technique deliverable in a single rotation with a conventional C-arm shaped linac. In this planning study, the authors assess the dosimetric properties of single-arc therapy in comparison to helical tomotherapy for three different tumor types. METHODS: Treatment plans for three patients with prostate carcinoma, three patients with anal cancer, and three patients with head and neck cancer were optimized for helical tomotherapy and AMCBT. The dosimetric comparison of the two techniques is based on physical quantities derived from dose-volume histograms. RESULTS: For prostate cancer, the quality of dose distributions calculated for AMCBT was of equal quality as that generated for tomotherapy with the additional benefits of a faster delivery and a lower integral dose. For highly complex geometries, the plan quality achievable with helical tomotherapy could not be achieved with arc-modulated cone beam therapy. CONCLUSIONS: Rotation therapy with a conventional linac in a single arc is capable to deliver a high and homogeneous dose to the target and spare organs at risk. Advantages of this technique are a fast treatment time and a lower integral dose in comparison to helical tomotherapy. For highly complex cases, e.g., with several target regions, the dose shaping capabilities of AMCBT are inferior to those of tomotherapy. However, treatment plans for AMCBT were also clinically acceptable..

BACKGROUND: While IMRT is widely used in treating complex oncological cases in adults, it is not commonly used in pediatric radiation oncology for a variety of reasons. This report evaluates our 9 year experience using stereotactic-guided, inverse planned intensity-modulated radiotherapy (IMRT) in children and adolescents in the context of the current literature. METHODS: Between 1999 and 2008 thirty-one children and adolescents with a mean age of 14.2 years (1.5 - 20.5) were treated with IMRT in our department. This heterogeneous group of patients consisted of 20 different tumor entities, with Ewing's sarcoma being the largest (5 patients), followed by juvenile nasopharyngeal fibroma, esthesioneuroblastoma and rhabdomyosarcoma (3 patients each). In addition a review of the available literature reporting on technology, quality, toxicity, outcome and concerns of IMRT was performed. RESULTS: With IMRT individualized dose distributions and excellent sparing of organs at risk were obtained in the most challenging cases. This was achieved at the cost of an increased volume of normal tissue receiving low radiation doses. Local control was achieved in 21 patients. 5 patients died due to progressive distant metastases. No severe acute or chronic toxicity was observed. CONCLUSION: IMRT in the treatment of children and adolescents is feasible and was applied safely within the last 9 years at our institution. Several reports in literature show the excellent possibilities of IMRT in selective sparing of organs at risk and achieving local control. In selected cases the quality of IMRT plans increases the therapeutic ratio and outweighs the risk of potentially increased rates of secondary malignancies by the augmented low dose exposure..

The problem of the enormous amount of scattered radiation in kV CBCT (kilo voltage cone beam computer tomography) is addressed. Scatter causes undesirable streak- and cup-artifacts and results in a quantitative inaccuracy of reconstructed CT numbers, so that an accurate dose calculation might be impossible. Image contrast is also significantly reduced. Therefore we checked whether an appropriate implementation of the fast iterative scatter correction algorithm we have developed for MV (mega voltage) CBCT reduces the scatter contribution in a kV CBCT as well. This scatter correction method is based on a superposition of pre-calculated Monte Carlo generated pencil beam scatter kernels. The algorithm requires only a system calibration by measuring homogeneous slab phantoms with known water-equivalent thicknesses. In this study we compare scatter corrected CBCT images of several phantoms to the fan beam CT images acquired with a reduced cone angle (a slice-thickness of 14 mm in the isocenter) at the same system. Additional measurements at a different CBCT system were made (different energy spectrum and phantom-to-detector distance) and a first order approach of a fast beam hardening correction will be introduced. The observed image quality of the scatter corrected CBCT images is comparable concerning resolution, noise and contrast-to-noise ratio to the images acquired in fan beam geometry. Compared to the CBCT without any corrections the contrast of the contrast-and-resolution phantom with scatter correction and additional beam hardening correction is improved by a factor of about 1.5. The reconstructed attenuation coefficients and the CT numbers of the scatter corrected CBCT images are close to the values of the images acquired in fan beam geometry for the most pronounced tissue types. Only for extreme dense tissue types like cortical bone we see a difference in CT numbers of 5.2%, which can be improved to 4.4% with the additional beam hardening correction. Cupping is reduced from 20% to 4% with scatter correction and 3% with an additional beam hardening correction. After 3 iterations (small phantoms) and 6 to 7 iterations (large phantoms) the algorithm converges. Therefore the algorithm is very fast, that means 1.3 seconds per projection for 3 iterations on a standard PC..

PURPOSE: A study to quantitatively compare the image quality of four different image guided radiotherapy (IGRT) devices based on phantom measurements with respect to the additional dose delivered to the patient. METHODS: Images of three different head-sized phantoms (diameter 16-18 cm) were acquired with the following four IGRT-CT solutions: (i) the Siemens Primatom single slice fan beam computed tomography (CT) scanner with an acceleration voltage of 130 kV, (ii) a Tomotherapy HI-ART II unit using a fan beam scanner with an energy of 3.5 MeV and (iii) the Siemens Artíste prototype, providing the possibility to perform kV (121 kV) and MV (6 MV) cone beam (CB) CTs. For each device three scan protocols (named low, normal, high) were selected to yield the same weighted computed tomography dose index (CTDI(w)). Based on the individual inserts of the different phantoms the image quality achieved with each device at a certain dose level was characterized in terms of homogeneity, spatial resolution, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and electron density-to-CT-number conversion. RESULTS: Based on the current findings for head-sized phantoms all devices show an electron density-to-CT-number conversion almost independent of the imaging parameters and hence can be suited for treatment planning purposes. The evaluation of the image quality, however, points out clear differences due to the different energies and geometries. The Primatom standard CT scanner shows throughout the best performance, especially for soft tissue contrast and spatial resolution with low imaging doses. Reasonable soft tissue contrast can be obtained with slightly higher doses compared to the CT scanner with the kVCB and the Tomotherapy unit. In order to get similar results with the MVCB system a much higher dose needs to be applied to the patient. CONCLUSION: Considering the entire investigations, especially in terms of contrast and spatial resolution, a rough tendency for decreasing image quality can be given: Primatom, Artíste prototype kVCB, Tomotherapy, Artíste prototype MVCB..

New technical developments constantly aim at improving the outcome of radiation therapy. With the use of a computer-controlled multileaf collimator (MLC), the quality of the treatment and the efficiency in patient throughput is significantly increased. New MLC designs aim to further enhance the advantages. In this article, we present the first detailed experimental investigation of the new 160 MLC, Siemens Medical Solutions. The assessment included the experimental investigation of typical MLC characteristics such as leakage, tongue-and-groove effect, penumbra, leaf speed, and leaf positioning accuracy with a 6 MV treatment beam. The leakage is remarkably low with an average of 0.37% due to a new design principle of slightly tilted leaves instead of the common tongue-and-groove design. But due to the tilt, the triangular tongue-and-groove effect occurs. Its magnitude of approximately 19% is similar to the dose defect measured for MLCs with the common tongue-and-groove design. The average longitudinal penumbra measured at depth d(max) = 15 mm with standard 100 x 100 mm2 fields is 4.1 +/- 0.5 mm for the central range and increases to 4.9 +/- 1.3 mm for the entire field range of 400 x 400 mm2. The increase is partly due to the single-focusing design and the large distance between the MLC and the isocenter enabling a large patient clearance. Regarding the leaf speed, different velocity tests were performed. The positions of the moving leaves were continuously recorded with the kilovoltage-imaging panel. The maximum leaf velocities measured were 42.9 +/- 0.6 mm/s. In addition, several typical intensity-modulated radiation therapy treatments were performed and the delivery times compared to the Siemens OPTIFOCUS MLC. An average decrease of 11% in delivery time was observed. The experimental results presented in this article indicate that the dosimetric characteristics of the 160 MLC are capable of improving the quality of dose delivery with respect to precision and dose conformity..

An optimal plan in modern treatment planning tools is found through the use of an iterative optimization algorithm, which deals with a high amount of patient-related data and number of treatment parameters to be optimized. Thus, calculating a good plan is a very time-consuming process which limits the application for patients in clinics and for research activities aiming for more accuracy. A common technique to handle the vast amount of radiation dose data is the concept of the influence matrix (DIJ), which stores the dose contribution of each bixel to the patient in the main memory of the computer. This study revealed that a bottleneck for the optimization time arises from the data transfer of the dose data between the memory and the CPU. In this note, we introduce a new method which speeds up the data transportation from stored dose data to the CPU. As an example we used the DIJ approach as is implemented in our treatment planning tool KonRad, developed at the German Cancer Research Center (DKFZ) in Heidelberg. A data cycle reordering method is proposed to take the advantage of modern memory hardware. This induces a minimal eviction policy which results in a memory behaviour exhibiting a 2.6 times faster algorithm compared to the naive implementation. Although our method is described for the DIJ approach implemented in KonRad, we believe that any other planning tool which uses a similar approach to store the dose data will also benefit from the described methods..

BACKGROUND: To determine whether proton radiotherapy has clinical advantages over photon radiotherapy, we modeled the dose characteristics of both to critical normal tissue volumes using data from patients with four types of childhood brain tumors. PROCEDURES: Three-dimensional imaging and treatment planning data, including targeted tumor and normal tissues contours, were acquired for 40 patients, 10 each with optic pathway glioma (OPG), craniopharyngioma (CR), infratentorial ependymoma (EP), or medulloblastoma (MB). Dose-volume data were collected for the entire brain, temporal lobes, cochlea, and hypothalamus from each patient. The data were averaged and compared based on treatment modality (protons vs. photons) using dose-cognitive effects models. Outcomes were estimated over 5 years. RESULTS: Relatively small critical normal tissue volumes such as the cochlea and hypothalamus may be spared from radiation exposure when not adjacent to the primary tumor volume. Larger normal tissue volumes such as the supratentorial brain or temporal lobes receive less of the low and intermediate doses. When applied to longitudinal models of radiation dose-cognitive effects, these differences resulted in clinically significant higher IQ scores for patients with MB and CR and academic reading scores in patients with OPG. Extreme differences between proton and photon dose distributions precluded meaningful comparison of protons and photons for patients with EP. CONCLUSIONS: Differences in the overall dose distributions, as indicated by modeling changes in cognitive function, showed that a reduction in the lower-dose volumes or mean dose would have long-term, clinical advantages for children with MB, CR, and OPG..

Intrafractional organ motion remains a source of error in conformal radiotherapy of dynamic targets such as tumours of the lung or of the prostate. The purpose of this work was to devise a method for the continuous and routine measurement of intrafractional organ motion. The method consists of a combination of an electromagnetic (EM), internal marker-based tracking system with the on-board kilovoltage x-ray imaging system of a modern treatment machine. The EM system continuously tracks the target, while x-ray images can be acquired simultaneously if demand arises. An image processing algorithm has been developed to automatically localize and track the EM markers in the x-ray images. We have demonstrated simultaneous target tracking using the EM system and x-ray imaging of a mobile target inside a programmable thorax phantom. The target motion was very well reproduced by both systems. The comparability of the target locations reported by both systems was established (better than 0.25 mm up to target velocities of 3 cm s(-1)). One immediate use of the synchronized system was shown: the generation of a 4D cone beam computed tomography data set using the EM system for the measurement of motion. In conclusion, we have developed a system for the routine measurement of intrafractional motion that continuously provides the 3D position of the target with the ability to acquire images of the treatment field only when needed, thereby eliminating avoidable imaging dose to the patient..

Respiratory motion limits the potential of modern high-precision radiotherapy techniques such as IMRT and particle therapy. Due to the uncertainty of tumour localization, the ability of achieving dose conformation often cannot be exploited sufficiently, especially in the case of lung tumours. Various methods have been proposed to track the position of tumours using external signals, e.g. with the help of a respiratory belt or by observing external markers. Retrospectively gated time-resolved x-ray computed tomography (4D CT) studies prior to therapy can be used to register the external signals with the tumour motion. However, during treatment the actual motion of internal structures may be different. Direct control of tissue motion by online imaging during treatment promises more precise information. On the other hand, it is more complex, since a larger amount of data must be processed in order to determine the motion. Three major questions arise from this issue. Firstly, can the motion that has occurred be precisely determined in the images? Secondly, how large must, respectively how small can, the observed region be chosen to get a reliable signal? Finally, is it possible to predict the proximate tumour location within sufficiently short acquisition times to make this information available for gating irradiation? Based on multiple studies on a porcine lung phantom, we have tried to examine these questions carefully. We found a basic characteristic of the breathing cycle in images using the image similarity method normalized mutual information. Moreover, we examined the performance of the calculations and proposed an image-based gating technique. In this paper, we present the results and validation performed with a real patient data set. This allows for the conclusion that it is possible to build up a gating system based on image data, solely, or (at least in avoidance of an exceeding exposure dose) to verify gates proposed by the various external systems..

BACKGROUND: The aim of this treatment planning study was to investigate the potential advantages of intensity-modulated (IM) proton therapy (IMPT) compared with IM photon therapy (IMRT) in nasopharyngeal carcinoma (NPC). METHODS: Eight NPC patients were chosen. The dose prescriptions in cobalt Gray equivalent (GyE) for gross tumor volumes of the primary tumor (GTV-T), planning target volumes of GTV-T and metastatic (PTV-TN) and elective (PTV-N) lymph node stations were 72.6 GyE, 66 GyE, and 52.8 GyE, respectively. For each patient, nine coplanar fields IMRT with step-and-shoot technique and 3D spot-scanned three coplanar fields IMPT plans were prepared. Both modalities were planned in 33 fractions to be delivered with a simultaneous integrated boost technique. All plans were prepared and optimized by using the research version of the inverse treatment planning system KonRad (DKFZ, Heidelberg). RESULTS: Both treatment techniques were equal in terms of averaged mean dose to target volumes. IMPT plans significantly improved the tumor coverage and conformation (P < 0.05) and they reduced the averaged mean dose to several organs at risk (OARs) by a factor of 2-3. The low-to-medium dose volumes (0.33-13.2 GyE) were more than doubled by IMRT plans. CONCLUSION: In radiotherapy of NPC patients, three-field IMPT has greater potential than nine-field IMRT with respect to tumor coverage and reduction of the integral dose to OARs and non-specific normal tissues. The practicality of IMPT in NPC deserves further exploration when this technique becomes available on wider clinical scale..

In intensity modulated treatment techniques, the modulation of each treatment field is obtained using an optimization algorithm. Multiple optimization algorithms have been proposed in the literature, e.g. steepest descent, conjugate gradient, quasi-Newton methods to name a few. The standard optimization algorithm in our in-house inverse planning tool KonRad is a quasi-Newton algorithm. Although this algorithm yields good results, it also has some drawbacks. Thus we implemented an improved optimization algorithm based on the limited-memory Broyden-Fletcher-Goldfarb-Shanno (L-BFGS) routine. In this paper the improved optimization algorithm is described. To compare the two algorithms, several treatment plans are optimized using both algorithms. This included photon (IMRT) as well as proton (IMPT) intensity modulated therapy treatment plans. To present the results in a larger context the widely used conjugate gradient algorithm was also included into this comparison. On average, the improved optimization algorithm was six times faster to reach the same objective function value. However, it resulted not only in an acceleration of the optimization. Due to the faster convergence, the improved optimization algorithm usually terminates the optimization process at a lower objective function value. The average of the observed improvement in the objective function value was 37%. This improvement is clearly visible in the corresponding dose-volume-histograms. The benefit of the improved optimization algorithm is particularly pronounced in proton therapy plans. The conjugate gradient algorithm ranked in between the other two algorithms with an average speedup factor of two and an average improvement of the objective function value of 30%..

Advanced radiotherapeutical techniques like intensity-modulated radiation therapy (IMRT) are based on an accurate knowledge of the location of the radiation target. An accurate dose delivery, therefore, requires a method to account for the inter- and intrafractional target motion and the target deformation occurring during the course of treatment. A method to compensate in real time for changes in the position and shape of the target is the use of a dynamic multileaf collimator (MLC) technique which can be devised to automatically arrange the treatment field according to real-time image information. So far, various approaches proposed for leaf sequencers have had to rely on a priori known target motion data and have aimed to optimize the overall treatment time. Since for a real-time dose delivery the target motion is not known a priori, the velocity range of the leading leaves is restricted by a safety margin to c x v(max) while the following leaves can travel with an additional maximum speed to compensate for the respective target movements. Another aspect to be considered is the tongue and groove effect. A uniform radiation field can only be achieved if the leaf movements are synchronized. The method presented in this note is the first to combine a synchronizing sequencer and real-time tracking with a dynamic MLC. The newly developed algorithm is capable of online optimizing the leaf velocities by minimizing the overall treatment time while at the same time it synchronizes the leaf trajectories in order to avoid the tongue and groove effect. The simultaneous synchronization is performed with the help of an online-calculated mid-time leaf trajectory which is common for all leaf pairs and which takes into account the real-time target motion and deformation information..

In this paper, we propose an optimization concept for a rotation therapy technique which is referred to as arc-modulated cone beam therapy (AMCBT). The aim is a reduction of the treatment time while achieving a treatment plan quality equal to or better than that of IMRT. Therefore, the complete dose is delivered in one single gantry rotation and the beam is modulated by a multileaf collimator. The degrees of freedom are the field shapes and weights for a predefined number of beam directions. In the new optimization loop, the beam weights are determined by a gradient algorithm and the field shapes by a tabu search algorithm. We present treatment plans for AMCBT for two clinical cases. In comparison to step-and-shoot IMRT treatment plans, it was possible by AMCBT to achieve dose distributions with a better dose conformity to the target and a lower mean dose for the most relevant organ at risk. Furthermore, the number of applied monitor units was reduced for AMCBT in comparison to IMRT treatment plans..

BACKGROUND: Presenting the initial clinical results in the treatment of complex shaped adenoid cystic carcinomas (ACC) of the head and neck region by inverse planned stereotactic IMRT. MATERIALS: 25 patients with huge ACC in different areas of the head and neck were treated. At the time of radiotherapy two patients already suffered from distant metastases. A complete resection of the tumor was possible in only 4 patients. The remaining patients were incompletely resected (R2: 20; R1: 1). 21 patients received an integrated boost IMRT (IBRT), which allow the use of different single doses for different target volumes in one fraction. All patients were treated after inverse treatment planning and stereotactic target point localization. RESULTS: The mean follow-up was 22.8 months (91-1490 days). According to Kaplan Meier the three year overall survival rate was 72%. 4 patients died caused by a systemic progression of the disease. The three-year recurrence free survival was according to Kaplan Meier in this group of patients 38%. 3 patients developed an in-field recurrence and 3 patient showed a metastasis in an adjacent lymph node of the head and neck region. One patient with an in-field recurrence and a patient with the lymph node recurrence could be re-treated by radiotherapy. Both patients are now controlled. Acute side effects >Grade II did only appear so far in a small number of patients. CONCLUSION: The inverse planned stereotactic IMRT is feasible in the treatment of ACC. By using IMRT, high control rates and low side effects could by achieved. Further evaluation concerning the long term follow-up is needed. Due to the technical advantage of IMRT this treatment modality should be used if a particle therapy is not available..

A new online imaging approach, linac-integrated cone beam CT (CBCT), has been developed over the past few years. It has the advantage that a patient can be examined in their treatment position directly before or during a radiotherapy treatment. Unfortunately, respiratory organ motion, one of the largest intrafractional organ motions, often leads to artefacts in the reconstructed 3D images. One way to take this into account is to register the breathing phase during image acquisition for a phase-correlated image reconstruction. Therefore, the main focus of this work is to present a system which has the potential to investigate the correlation between internal (movement of the diaphragm) and external (data of a respiratory gating system) information about breathing phase and amplitude using an inline CBCT scanner. This also includes a feasibility study about using the acquired information for a respiratory-correlated 4D CBCT reconstruction. First, a moving lung phantom was used to develop and to specify the required methods which are based on an image reconstruction using only projections belonging to a certain moving phase. For that purpose, the corresponding phase has to be detected for each projection. In the case of the phantom, an electrical signal allows one to track the movement in real time. The number of projections available for the image reconstruction depends on the breathing phase and the size of the position range from which projections should be used for the reconstruction. The narrower this range is, the better the inner structures can be located, but also the noise of the images increases due to the limited number of projections. This correlation has also been analysed. In a second step, the methods were clinically applied using data sets of patients with lung tumours. In this case, the breathing phase was detected by an external gating system (AZ-733V, Anzai Medical Co.) based on a pressure sensor attached to the patient's abdominal region with a fixation belt. The comparison of the reconstructed 4D CBCT images and the corresponding 4D CT images used for the treatment planning provides the required information for the calculation of possible setup errors. So, a repositioning of the patient is feasible even though the patient moves due to respiration. In addition to the external signal, the position of the diaphragm in the cranial-caudal direction could be extracted from each projection. Both independent sources of information show a very good agreement of the phase and even the amplitude of the movement and the external signal respectively. This suggests the usability of such a system for a gated dose delivery approach. However, more studies involving patients with different incidences have to be carried out to confirm these first results..

BACKGROUND: Even today, treatment of Stage III NSCLC still poses a serious challenge. So far, surgical resection is the treatment of choice. Patients whose tumour is not resectable or who are unfit to undergo surgery are usually referred to a combined radio-chemotherapy. However, combined radio-chemotherapeutic treatment is also associated with sometimes marked side effects but has been shown to be more efficient than radiation therapy alone. Nevertheless, there is a significant subset of patients whose overall condition does not permit administration of chemotherapy in a combined-modality treatment. It could be demonstrated though, that NSCLCs often exhibit over-expression of EGF-receptors hence providing an excellent target for the monoclonal EGFR-antagonist cetuximab (Erbitux) which has already been shown to be effective in colorectal as well as head-and-neck tumours with comparatively mild side-effects. METHODS/DESIGN: The NEAR trial is a prospective phase II feasibility study combining a monoclonal EGF-receptor antibody with loco-regional irradiation in patients with stage III NSCLC. This trial aims at testing the combination's efficacy and rate of development of distant metastases with an accrual of 30 patients. Patients receive weekly infusions of cetuximab (Erbitux) plus loco-regional radiation therapy as intensity-modulated radiation therapy. After conclusion of radiation treatment patients continue to receive weekly cetuximab for 13 more cycles. DISCUSSION: The primary objective of the NEAR trial is to evaluate toxicities and feasibility of the combined treatment with cetuximab (Erbitux) and IMRT loco-regional irradiation. Secondary objectives are remission rates, 3-year-survival and local/systemic progression-free survival..

For intensity modulated radiotherapy (IMRT) of deep-seated tumours, dosimetric variations of the original static dose profiles due to breathing motion can be primarily considered as blurring effects known from conventional radiotherapy. The purpose of this dosimetric study was to clarify whether these results are transferable to superficial targets and to quantify the additional effect of fractionation. A solid polystyrene phantom and an anthropomorphic phantom were used for film and ion chamber dose measurements. The phantoms were installed on an electric driven device and moved with a frequency of 6 or 12 cycles per minute and an amplitude of 4 mm or 10 mm. A split beam geometry of two adjacent asymmetric fields and an IMRT treatment plan with 12 fields for irradiation of the breast were investigated. For the split beam geometry the dose modifications due to unintended superposition of partial fields were reduced by fractionation and completely smoothed out after 20 fractions. IMRT applied to the moving phantom led to a more homogeneous dose distribution compared to the static phantom. The standard deviation of the target dose which is a measure of the dose homogeneity was 10.3 cGy for the static phantom and 7.7 cGy for a 10 mm amplitude. The absolute dose values, measured with ionization chambers, remained unaffected. Irradiation of superficial targets by IMRT in the step-and-shoot technique did not result in unexpected dose perturbations due to breathing motion. We conclude that regular breathing motion does not jeopardize IMRT of superficial target volumes..

BACKGROUND: The purpose of the study was the clinical implementation of a kV cone beam CT (CBCT) for setup correction in radiotherapy. PATIENTS AND METHODS: For evaluation of the setup correction workflow, six tumor patients (lung cancer, sacral chordoma, head-and-neck and paraspinal tumor, and two prostate cancer patients) were selected. All patients were treated with fractionated stereotactic radiotherapy, five of them with intensity modulated radiotherapy (IMRT). For patient fixation, a scotch cast body frame or a vacuum pillow, each in combination with a scotch cast head mask, were used. The imaging equipment, consisting of an x-ray tube and a flat panel imager (FPI), was attached to a Siemens linear accelerator according to the in-line approach, i.e. with the imaging beam mounted opposite to the treatment beam sharing the same isocenter. For dose delivery, the treatment beam has to traverse the FPI which is mounted in the accessory tray below the multi-leaf collimator. For each patient, a predefined number of imaging projections over a range of at least 200 degrees were acquired. The fast reconstruction of the 3D-CBCT dataset was done with an implementation of the Feldkamp-David-Kress (FDK) algorithm. For the registration of the treatment planning CT with the acquired CBCT, an automatic mutual information matcher and manual matching was used. RESULTS AND DISCUSSION: Bony landmarks were easily detected and the table shifts for correction of setup deviations could be automatically calculated in all cases. The image quality was sufficient for a visual comparison of the desired target point with the isocenter visible on the CBCT. Soft tissue contrast was problematic for the prostate of an obese patient, but good in the lung tumor case. The detected maximum setup deviation was 3 mm for patients fixated with the body frame, and 6 mm for patients positioned in the vacuum pillow. Using an action level of 2 mm translational error, a target point correction was carried out in 4 cases. The additional workload of the described workflow compared to a normal treatment fraction led to an extra time of about 10-12 minutes, which can be further reduced by streamlining the different steps. CONCLUSION: The cone beam CT attached to a LINAC allows the acquisition of a CT scan of the patient in treatment position directly before treatment. Its image quality is sufficient for determining target point correction vectors. With the presented workflow, a target point correction within a clinically reasonable time frame is possible. This increases the treatment precision, and potentially the complex patient fixation techniques will become dispensable..

One of the most prominent imaging techniques in image-guided radiotherapy (IGRT) is the acquisition of cone beam computed tomographies (CBCTs) at the linac with the patient in treatment position. CBCTs provide accurate 3-dimensional (3D) knowledge about the patient's anatomy for every treatment fraction and are therefore well suited for all adaptive corrections of errors related to interfractional uncertainties of the treatment process. In this paper, we first describe the technical development and implementation of this new imaging technique at our linac, i.e., the hardware components and their operating parameters are discussed in detail for a standard image acquisition of CBCTs. Then, an extension of this approach for the acquisition of complete images for extended field of views--the "shifted detector" technique--is presented followed by a first investigation of how CBCTs can be reliably used for adaptive dose calculations. Finally, a first clinical application, the process of automatic patient positioning based on CBCT images, is discussed. From our investigations, we conclude that the technical development of linac-integrated CBCTs bears an enormous potential for the correction of interfractional treatment errors. However, image quality and reconstruction speed of the images leave room for improvement. The development of clinical strategies for the optimal application of this new image modality in a clinical environment is one the major tasks for the future..

PURPOSE: A planning study to analyze the impact of different leaf widths on the achievable dose distributions with intensity modulated radiation therapy (IMRT). METHODS: Five patients (3 intra- and 2 extra-cranial) with projected planning target volume (PTV) sizes smaller than 10 cm by 10 cm were re-planned with four different multileaf collimators (MLC). Two internal collimators with an isocentric leaf width of 4 and 10 mm and two add-on collimators with an isocentric leaf width of 2.75 and were evaluated. The inverse treatment planning system KonRad (Siemens Medical Solutions) was used to create IMRT 'step & shoot' plans. For each patient the same arrangement of beams and the same parameters for the optimization were used for all MLCs. The beamlet size for all treatment plans was chosen to coincide with the leaf width of the respective MLC. To evaluate the treatment plans 3D dose distributions and dose volume histograms were analyzed. As indicators for the quality of the PTV dose distribution the minimum dose, maximum dose and the standard deviation were used. For the organs at risk (OAR) the equivalent uniform dose (EUD) was calculated. To measure the dose coverage of the PTV the volume (V(90)) that received doses higher than 90% of the prescribed dose was calculated where for the conformity the dose conformity index given by Baltas et al. was determined. RESULTS: The MLC with the smallest leaf width yields the best mean value of all five patients for the PTV coverage and for the conformity. For the MLCs with the same leaf width, the add-on MLC leads to superior treatment plans than the internal MLC. This is due to the sharper penumbra of the add-on MLC. The number of IMRT field segments to deliver increased by approximately a factor of two if 2. MLC leafs are used instead of the standard 10 mm leafs. In case of the para-spinal patients the EUD value for the spinal cord is only reduced slightly by using MLCs with leaf widths smaller than 5 mm. For the intra-cranial the EUD value for some organs improved with reduced leaf widths while for some organs the 10 mm MLC leafs give comparable values. CONCLUSION: As expected the MLC with the smallest leaf width always yields the best PTV coverage. Reducing the leaf width from 4 to 2.75 mm results in a slight enhancement of the PTV coverage. With the selected organ parameters no significant improvement for most OAR was found. The disadvantage of the reduction of the leaf width is the increasing number of segments due to the more complex fluence patterns and therefore an increased delivery time..

One aim of adaptive radiotherapy (ART) is the observation of organ motion followed by a subsequent adaptation of the treatment plan. One way of achieving this goal is a kV x-ray source mounted at a linear accelerator in combination with a flat-panel imager. Two imaging hardware configurations were evaluated for their potential for online tracking and the subsequent correction of organ motion by using fluoroscopic images: x-ray tube positioned with (A) 90 degrees and (B) 180 degrees offset to the MV beam. For one lung case two IMRT plans with five coplanar beams and the table positioned at 0 degrees were optimized for two multileaf collimators (MLCs) with 10 mm and 2.75 mm leaf width. Respiratory motion, modelled by rigid transformation in the lungs, was investigated for different amplitudes. The 3D dose distributions for different cases (no movement, uncorrected movement, correction for the movement perpendicular to the respective kV beam) were evaluated with the help of dose volume histograms (DVHs) and a modified conformity (Baltas et al 1998 Int. J. Radiat. Oncol. Biol. Phys. 40 515-24) and coverage index using the 90% isodose. For the corrected treatment plans the influence of the observed displacement vector caused by organ movement was accounted for by a respective displacement of the target point. For the simulated movement with a small amplitude (3 mm) in the anterior-posterior (AP) direction the dose distributions resulting from the correction of the displacement vector using imaging system A or B showed similar results for both systems and were in good agreement with the dose distribution of the static (not moving) patient. Increasing the amplitude in the AP direction to 6 mm or even 9 mm leads for both amplitudes and both MLCs to almost the same conformity and coverage index as the static dose distribution if imaging system B is used for the online correction. For the dose distribution obtained with correction based on imaging system A the deviation between the optimal and the corrected dose distribution is increasing with increasing amplitude. For the MLC with the smaller leaf width the difference between the optimal and the corrected dose distributions is always significantly larger than for the less conformal dose distributions created by the MLC with the 10 mm leaves. These results can be explained by the fact that system A cannot observe movement in the AP-LR plane perpendicular to the MV beam and therefore cannot correct for these movements whereas system B only fails to observe the motion in the beam direction which for photon irradiation has less impact on the dose distribution..

Intensity modulated radiation therapy (IMRT) is a new promising treatment technique, which allows a more conformal application of the dose to the tumor volume, as compared to conventional radio-oncological approaches, while protecting the surrounding normal tissue more accurately. This manuscript presents the final results of IMRT in the treatment of unresectable pleural mesothelioma in Heidelberg..

BACKGROUND: Pancreatic cancer is the fourth commonest cause of death from cancer in men and women. Advantages in surgical techniques, radiation therapy techniques, chemotherapeutic regimes, and different combined-modality approaches have yielded only a modest impact on the prognosis of patients with pancreatic cancer. Thus there is clearly a need for additional strategies. One approach involves using the identification of a number of molecular targets that may be responsible for the resistance of cancer cells to radiation or to other cytotoxic agents. As such, these molecular determinants may serve as targets for augmentation of the radiotherapy or chemotherapy response. Of these, the epidermal growth factor receptor (EGFR) has been a molecular target of considerable interest and investigation, and there has been a tremendous surge of interest in pursuing targeted therapy of cancers via inhibition of the EGFR. METHODS/DESIGN: The PARC study is designed as an open, controlled, prospective, randomized phase II trial. Patients in study arm A will be treated with chemoradiation using intensity modulated radiation therapy (IMRT) combined with gemcitabine and simultaneous cetuximab infusions. After chemoradiation the patients receive gemcitabine infusions weekly over 4 weeks. Patients in study arm B will be treated with chemoradiation using intensity modulated radiation therapy (IMRT) combined with gemcitabine and simultaneous cetuximab infusions. After chemoradiation the patients receive gemcitabine weekly over 4 weeks and cetuximab infusions over 12 weeks. A total of 66 patients with locally advanced adenocarcinoma of the pancreas will be enrolled. An interim analysis for patient safety reasons will be done one year after start of recruitment. Evaluation of the primary endpoint will be performed two years after the last patient's enrollment. DISCUSSION: The primary objective of this study is to evaluate the feasibility and the toxicity profile of trimodal therapy in pancreatic adenocarcinoma with chemoradiation therapy with gemcitabine and intensity modulated radiation therapy (IMRT) and EGFR-targeted therapy using cetuximab and to compare between two different methods of cetuximab treatment schedules (concomitant versus concomitant and sequential cetuximab treatment). Secondary objectives are to determine the role and the mechanism of cetuximab in patient's chemoradiation regimen, the response rate, the potential of this combined modality treatment to concert locally advanced lesions to potentially resectable lesions, the time to progression interval and the quality of life..

Respiratory organ motion is known to be one of the largest intrafractional organ motions. Therefore, it is important to investigate the potential benefit of gated dose delivery approaches which aim to account for the respective dose uncertainties. In this study respiration is simulated by a moving lung phantom; the movement is not restricted to a normal sinusoidal progression and simulates the one of the embedded lung tumour in the cranial-caudal direction. An IMRT plan with a total of 29 beam segments was designed for the treatment of this tumour. It was irradiated in its resting position-which is the position at exhalation-and during movement. Furthermore the irradiation was triggered using different amplitude thresholds, which means that the irradiation only proceeded if the deviation of the tumour's position from its resting position is smaller than the given threshold. We determined the gating-related increase of the treatment time for various gating procedures. We also measured the resulting dose distribution in specific slices of the phantom perpendicular to the direction of the movement using film dosimetry and compared it to the dose distribution of the static case. Since these film measurements cannot be done inside the whole tumour, additionally the movement and gating was simulated using the planning software to calculate the 3D dose distribution inside the tumour and to generate dose volume histograms for different treatment modalities. The total treatment time was observed to increase by 20%-100% depending on the individual gating threshold and can be calculated easily. The analysis of the films showed that irradiation without gating leads to significant underdosages up to 33%, especially at the edge of the tumour. With gating it is possible to considerably reduce this underdosage down to 9% depending on the trigger threshold. The calculation of the dose volume histograms makes it possible to find a reasonable compromise between the improvement of the dose distribution and the increase of the treatment time..

The aim of this treatment planning comparison study was to explore different spinal irradiation techniques with respect to the risk of late side-effects, particularly radiation-induced cancer. The radiotherapy techniques compared were conventional photon therapy, intensity modulated x-ray therapy (IMXT), conventional electron therapy, intensity/energy modulated electron therapy (IMET) and proton therapy (IMPT).CT images for radiotherapy use from five children, median age 8 and diagnosed with medulloblastoma, were selected for this study. Target volumes and organs at risk were defined in 3-D. Treatment plans using conventional photon therapy, IMXT, conventional electron therapy, IMET and IMPT were set up. The probability of normal tissue complication (NTCP) and the risk of cancer induction were calculated using models with parameters-sets taken from published data for the general population; dose data were taken from dose volume histograms (DVH). Similar dose distributions in the targets were achieved with all techniques but the absorbed doses in the organs-at-risk varied significantly between the different techniques. The NTCP models based on available data predicted very low probabilities for side-effects in all cases. However, the effective mean doses outside the target volumes, and thus the predicted risk of cancer induction, varied significantly between the techniques. The highest lifetime risk of secondary cancers was estimated for IMXT (30%). The lowest risk was found with IMPT (4%). The risks associated with conventional photon therapy, electron therapy and IMET were 20%, 21% and 15%, respectively. This model study shows that spinal irradiation of young children with photon and electron techniques results in a substantial risk of radiation-induced secondary cancers. Multiple beam IMXT seems to be associated with a particularly high risk of secondary cancer induction. To minimise this risk, IMPT should be the treatment of choice. If proton therapy is not available, advanced electron therapy may provide a better alternative..

A neutron radiation area monitoring system has been developed for proton accelerator facilities dedicated to cancer therapy. The system comprises commercial measurement equipment, computer hardware and a suite of software applications that were developed specifically for use in a medical accelerator environment. The system is designed to record and display the neutron dose-equivalent readings from 16 to 24 locations (depending on the size of the proton therapy centre) throughout the facility. Additional software applications provide for convenient data analysis, plotting, radiation protection reporting, and system maintenance and administration tasks. The system performs with a mean time between failures of >6 months. Required data storage capabilities and application execution times are met with inexpensive off-the-shelf computer hardware..

PURPOSE: To evaluate salivary gland function after inversely planned stereotactic intensity-modulated radiotherapy (IMRT) for tumors of the head-and-neck region using quantitative pertechnetate scintigraphy. METHODS AND MATERIALS: Since January 2000, 18 patients undergoing IMRT for cancer of the head and neck underwent pre- and posttherapeutic scintigraphy to examine salivary gland function. The mean dose to the primary planning target volume was 61.5 Gy (range 50.4-73.2), and the median follow-up was 23 months. In all cases, the parotid glands were directly adjacent to the planning target volume. The treatment planning goal was for at least one parotid gland to receive a mean dose of <26 Gy. Two quantitative parameters (change in maximal uptake and change in the relative excretion rate before and after IMRT) characterizing the change in salivary gland function after radiotherapy were determined. These parameters were compared with respect to the dose thresholds of 26 and 30 Gy for the mean dose. In addition, dose-response curves were calculated. RESULTS: Using IMRT, it was possible in 16 patients to reduce the dose for at least one parotid gland to < or =26 Gy. In 7 patients, protection of both parotid glands was possible. No recurrent disease adjacent to the protected parotid glands was observed. Using the Radiation Therapy Oncology Group/European Organization for the Research and Treatment of Cancer scoring system, only 3 patients had Grade 2 xerostomia. No greater toxicity was seen for the salivary glands. The change in the relative excretion rate was significantly greater, if the parotid glands received a mean dose of > or =26 Gy or > or =30 Gy. For the change in maximal uptake, a statistically significant difference was seen only for the parotid glands and a dose threshold of 30 Gy. For the end point of a reduction in the parotid excretion rate of >50% and 75%, the dose-response curves yielded a dose at 50% complication probability of 34.8 +/- 3.6 and 40.8 +/- 5.3 Gy, respectively. CONCLUSION: Using IMRT, it is possible to protect the parotid glands and reduce the incidence and severity of xerostomia in patients. Doses <26-30 Gy significantly preserve salivary gland function. The results support the hypothesis that application of IMRT does not lead to increased local failure rates..

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BACKGROUND AND PURPOSE: In recent years photon intensity modulated radiation therapy (IMRT) has gained attention due to its ability to improve conformity of dose distributions. A potential advantage of electron-IMRT is that the dose fall off in the depth dose curve makes it possible to modulate the dose distribution in the direction of the beam by selecting different electron energies. This paper examines the use of a computer based energy selection in combination with the IMRT technique to optimise the electron dose distribution. MATERIALS AND METHODS: One centimetre square electron beamlets ranging from 2.5 to 50 MeV were pre-calculated in water using Monte Carlo methods. A modified IMRT optimisation tool was then used to find an optimum mix of electron energies and intensities. The main principles used are illustrated in some simple geometries and tested on two clinical cases of post-operated ca. mam. RESULTS: It is clearly illustrated that the energy optimisation procedure lowers the dose to lung and heart and makes the dose in the target more homogeneous. Increasing the energy at steep gradients compensates for lack of target coverage at beam edges and steep gradients. Comparison with a clinically acceptable four segment plan indicates the advantage of the used electron IMRT technique. CONCLUSIONS: Using an intensity optimised mix of computer selected electron energies has the potential to improve electron treatments for mastectomy patients with good target coverage and reduced dose to normal tissue such as lung and heart..

A common requirement of radiation therapy is that treatment planning for different radiation modalities is devised on the basis of the same treatment planning system (TPS). The present study presents a novel multi-modal TPS with separate modules for the dose calculation, the optimization engine and the graphical user interface, which allows to integrate different treatment modalities. For heavy-charged particles, both most promising techniques, the distal edge tracking (DET) and the 3-dimensional scanning (3D) technique can be optimized. As a first application, the quality of optimized intensity-modulated treatment plans for photons (IMXT) and protons (IMPT) was analyzed in one clinical case on the basis of the achieved physical dose distributions. A comparison of the proton plans with the photon plans showed no significant improvement in terms of target volume dose, however there was an improvement in terms of organs at risk as well as a clear reduction of the total integral dose. For the DET technique, it is possible to create a treatment plan with almost the same quality of the 3D technique, however with a clearly reduced number (factor of 5) of beam spots as well as a reduced optimization time. Due to its modular design, the system can be easily expanded to more sophisticated dose-calculation algorithms or to modeling of biological effects..

PURPOSE/OBJECTIVE: The aim of this analysis is to evaluate the feasibility of inverse treatment planning and intensity modulated radiation therapy (IMRT) for head and neck cancer in daily clinical routine. A step and shoot IMRT approach was developed which allows the treatment of large target volumes without the need to use a split beam technique. By using the IMRT approach better protection of different organs at risk in the head and neck region may be achieved and an escalation of the dose in the tumor should be possible. We evaluated the feasibility of the treatment technique and the patient tolerance to the treatment. First clinical results are reported. MATERIALS AND METHODS: Between 1999 and 2002, 48 patients with a carcinoma of the head and neck region were treated with curative intention. All patients were treated in a patient-specific Scotch-Cast mask. Patients who required treatment of the lymph node levels I-VI, were additionally positioned by a vacuum pillow in order to immobilize the upper part of the thorax. For inverse treatment planning, the software module KonRad was used which was integrated into the VIRTUOS planning system. Each treatment plan was verified using quantitative film dosimetry in a head and neck phantom. The step and shoot IMRT technique with a multileaf collimator integrated in a Primus (Siemens) accelerator was used for treatment. For all target volumes the whole target including the lymph nodes were covered completely by the IMRT treatment. RESULTS: The mean total dose for the target volumes of macroscopic disease ranged between 63.0 and 64.1 Gy. The mean total dose of microscopic disease ranged between 55.2 and 60.1 Gy. The mean percentage of planning target volume receiving <90% of the prescribed dose ranged between 3.0 and 11.5%. For the treatment, the median number of beams was seven (range: five to nine). The time to deliver the treatment ranged between 9 and 18 min. The results of the verification revealed a mean deviation between measured and calculated absolute doses for the 48 patients of 0.1+/-1.4%. Including the phantom verification the IMRT treatment of the patients could be started approximately after five working days. The treatment was well tolerated by all patients. The 2-year actuarial overall survival was 92% and the 2-year actuarial local control rate was 93%. According to the Radiation Therapy Oncology Group (RTOG), no higher acute toxicity than Grade 3 was seen. Observation of the late effects revealed only one transient Grade 4 toxicity of the bone and only four patients had a xerostomia higher than Grade 1. CONCLUSION: The use of an inversely-planned and intensity-modulated step and shoot approach is feasible in clinical routine for head and neck tumors. Treatment could be applied as planned and no increased toxicity was found. Compared to other IMRT approaches for the head and neck region the used technique allows the treatment of the primary tumor and the lymph nodes level I-VI with only one intensity modulated treatment volume. The presented technique avoids to match conventional radiotherapy fields and IMRT fields, and therefore, reduce the risk of overdosage or underdosage at the matching line. Compared to conventional treatment techniques IMRT shows advantages in tumor dose and dose at the organs at risk..

To investigate the role of sophisticated dose calculation methods for treatment planning, we compared conventional pencil beam optimized 6 and 15 MV intensity-modulated treatment plans with optimizations based on the superposition technique. Five lung and five head and neck IMRT cases with spatial resolutions of bixels and dose voxels usually employed in clinical practice were considered for tumor volumes between 15 and 500 cm3. We investigated the systematic error of the pencil beam algorithm and the pencil beam induced error to the optimal solution of bixel weights. For the lung cases, the pencil beam overestimated the mean dose deposited inside the planning target volume (PTV) by about 8%, for small lung tumors even up to 20.6%. In the head and neck cases only a slight overestimation in mean PTV dose of 1.5% was observed. The optimization with the superposition method substantially improved the dose coverage of the considered radiation targets. Additionally, for the head and neck cases, the brainstem was significantly spared by about 4% mean PTV dose through the use of the superposition technique. Our studies showed that, in target regions with intricate tissue inhomogeneities, superposition or Monte Carlo techniques have to be used for the optimization and the final dose calculation of intensity-modulated treatment plans..

Optimization algorithms in inverse radiotherapy planning need information about the desired dose distribution. Usually the planner defines physical dose constraints for each structure of the treatment plan, either in form of minimum and maximum doses or as dose-volume constraints. The concept of equivalent uniform dose (EUD) was designed to describe dose distributions with a higher clinical relevance. In this paper, we present a method to consider the EUD as an optimization constraint by using the method of projections onto convex sets (POCS). In each iteration of the optimization loop, for the actual dose distribution of an organ that violates an EUD constraint a new dose distribution is calculated that satisfies the EUD constraint, leading to voxel-based physical dose constraints. The new dose distribution is found by projecting the current one onto the convex set of all dose distributions fulfilling the EUD constraint. The algorithm is easy to integrate into existing inverse planning systems, and it allows the planner to choose between physical and EUD constraints separately for each structure. A clinical case of a head and neck tumor is optimized using three different sets of constraints: physical constraints for all structures, physical constraints for the target and EUD constraints for the organs at risk, and EUD constraints for all structures. The results show that the POCS method converges stable and given EUD constraints are reached closely..

Background and Purpose: Complex-shaped malignant pleural mesotheliomas (MPMs) with challenging volumes are extremely difficult to treat by conventional radiotherapy due to tolerance doses of the surrounding normal tissue. In a feasibility study, we evaluated if inversely planned stereotactic intensity-modulated radiation therapy (IMRT) could be applied in the treatment of MPM. Patients and Methods: Eight patients with unresectable lesions were treated after failure of chemotherapy. All patients were positioned using noninvasive patient fixation techniques which can be attached to the applied extracranial stereotactic system. Due to craniocaudal extension of the tumor, it was necessary to develop a special software attached to the inverse planning program KonRad, which can connect two inverse treatment plans and consider the applied dose of the first treatment plan in the area of the matchline of the second treatment plan. Results: Except for one patient, in whom radiotherapy was canceled due to abdominal metastasis, treatment could be completed in all patients and was well tolerated. Median survival after diagnosis was 20 months and after IMRT 6.5 months. Therefore, both the 1-year actuarial overall survival from the start of radiotherapy and the 2-year actuarial overall survival since diagnosis were 28%. IMRT did not result in clinically significant acute side effects. By using the described inverse planning software, over- or underdosage in the region of the field matchline could be prevented. Pure treatment time ranged between 10 and 21 min. Conclusion: This study showed that IMRT is feasible in advanced unresectable MPM. The presented possibilities of stereotactic IMRT in the treatment of MPM will justify the evaluation of IMRT in early-stage pleural mesothelioma combined with chemotherapy in a study protocol, in order to improve the outcome of these patients. Furthermore, dose escalation should be possible by using IMRT..

In order to provide automatic IMRT dose delivery with an add-on MMLC a technical integration of a MMLC system with a linear accelerator was realized. The principle of this integration and the changes and enhancements of the existing hard- and software are briefly described. The system was tested by the automatic delivery of an IMRT plan designed for a head and neck phantom. A verification of dose delivery was performed with film dosimetry. The plan consisting of 78 "step and shoot" segments could be delivered within 17 minutes. A high spatial accuracy of the fluence pattern at the isocentre was reached by a resolution of 2.75x2.75 mm(2). The measured dose profiles were within 3% of the maximum dose of the calculated profiles..

In inverse planning for intensity-modulated radiotherapy, the dose calculation is a crucial element limiting both the maximum achievable plan quality and the speed of the optimization process. One way to integrate accurate dose calculation algorithms into inverse planning is to precalculate the dose contribution of each beam element to each voxel for unit fluence. These precalculated values are stored in a big dose calculation matrix. Then the dose calculation during the iterative optimization process consists merely of matrix look-up and multiplication with the actual fluence values. However, because the dose calculation matrix can become very large, this ansatz requires a lot of computer memory and is still very time consuming, making it not practical for clinical routine without further modifications. In this work we present a new method to significantly reduce the number of entries in the dose calculation matrix. The method utilizes the fact that a photon pencil beam has a rapid radial dose falloff, and has very small dose values for the most part. In this low-dose part of the pencil beam, the dose contribution to a voxel is only integrated into the dose calculation matrix with a certain probability. Normalization with the reciprocal of this probability preserves the total energy, even though many matrix elements are omitted. Three probability distributions were tested to find the most accurate one for a given memory size. The sampling method is compared with the use of a fully filled matrix and with the well-known method of just cutting off the pencil beam at a certain lateral distance. A clinical example of a head and neck case is presented. It turns out that a sampled dose calculation matrix with only 1/3 of the entries of the fully filled matrix does not sacrifice the quality of the resulting plans, whereby the cutoff method results in a suboptimal treatment plan..

PURPOSE: Inverse treatment planning and intensity-modulated radiation therapy (IMRT) promise advantages in the treatment of tumors of the head and neck region. Currently published studies use IMRT only in the treatment of the primary tumor. In these studies, the lymph nodes of the neck were treated using conventional techniques. The feasibility of an IMRT technique which allows treatment of the complete target volume, including the primary tumor and lymph nodes, without a beam split is described. PATIENT AND METHOD: For inverse treatment planning, the KonRad planning system was used. The primary as well as the secondary PTV (bilateral lymph node levels) were treated with one intensity-modulated primary plan. To increase the dose in the primary PTV and suspicious lymph nodes, an intensity-modulated boost plan was performed. The "step and shoot" IMRT technique was used. A plan comparison between the described IMRT approach and an IMRT approach using a split-beam technique was performed focusing on the treatment time. A patient with a carcinoma of the nasopharynx was treated with curative intent by a combined radiochemotherapy. RESULTS: The median total dose to the primary PTV was 70 Gy, to suspicious lymph nodes > or = 66.0 Gy, and to the secondary PTV 52 Gy. The defined maximum doses to the organs at risk were not exceeded, and the median dose to the protected parotid gland amounted to 21 Gy. Comparison of the treatment time between both IMRT approaches revealed only a slightly shorter treatment time (1-3 min) for the split-beam IMRT technique without considering the remaining conventional treatment parts of the split-beam IMRT technique. The patient achieved a complete response, and 18 months after treatment no signs of recurrent disease are visible. CONCLUSIONS: IMRT allows the treatment of the target volumes with high doses combined with an excellent sparing of the organs at risk. The IMRT approach presented here makes the treatment of the whole target volume with a single-beam arrangement feasible and does not increase the treatment time compared to a split-beam IMRT technique. Treatment time was comparable to a conventional three-field technique combined with electrons. This IMRT technique can prevent over- or underdosage at field matchlines in the head and neck region and, moreover, is able to spare parotid glands and therefore better avoid xerostomia compared to conventional techniques..

Current methods for intensity-modulated radiotherapy (IMRT) in breast cancer use forward planning based on equivalent radiological path length to design intensity modulated tangential beams. Compared to conventional tangential techniques, dose reduction of organs at risk is limited using these techniques. We developed a method for intensity modulation of multiple beams for adjuvant radiotherapy of breast cancer by application of a virtual bolus defined on CT for inverse optimization. This method enables multibeam IMRT, which provides improved sparing of lung and heart tissue. In this paper, we present the general aspects of this approach and an evaluation of the optimum beam configuration for IMRT based on inverse treatment planning. We compared this method to conventional techniques. Different clinical examples illustrate the possible indications and feasibility of this new approach. This method is superior to conventional techniques because of the reduction of high-dose area of a substantial cardiac volume in those cases where the parasternal lymph nodes are part of the target volume..

UNLABELLED: The following question is investigated: How narrow do the leaves of a multileaf collimator have to be such that further reduction of the leaf width does not lead to physical improvements of the dose distribution. Because of the physical principles of interaction between radiation and matter, dose distributions in radiotherapy are generally relatively smooth. According to the theory of sampling, the dose distribution can therefore be represented by a set of evenly spaced samples. The distance between the samples is identified with the distance between the leaf centers of a multileaf collimator. The optimum sampling distance is derived from the 20% to 80% field edge penumbra through the concept of the dose deposition kernel, which is approximated by a Gaussian. The leaf width of the multileaf collimator is considered to be independent from the sampling distance. Two cases are studied in detail: (i) the leaf width equals the sampling distance, which is the regular case, and (ii) the leaf width is twice the sampling distance. The practical delivery of the latter treatment geometry requires a couch movement or a collimator rotation. The optimum sampling distance equals the 20%-80% penumbra divided by 1.7 and is on the order of 1.5-2 mm for a typical 6 MV beam in soft tissue. The optimum leaf width equals this sampling distance in the regular case. A relatively small deterioration results if the leaf width is doubled, while the sampling distance remains the same. The deterioration can be corrected for by deconvolving the fluence profile with an inverse filter. CONCLUSIONS: With the help of the sampling theory and, more generally, the theory of linear systems, one can find a general answer to the question about the optimum leaf width of a multileaf collimator from a physical point of view. It is important to distinguish between the sampling distance and the leaf width. The sampling distance is more critical than the leaf width. The leaf width can be up to twice as large as the sampling width. Furthermore, the derived sampling distance can be used to select the optimum resolution of both the fluence and the dose grid in dose calculation and inverse planning algorithms..

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