Comparison of stereotactic radiotherapy and protons for uveal melanoma patients.

Background and purpose: Uveal melanoma (UM) is the most common primary ocular malignancy. We compared fractionated stereotactic radiotherapy (SRT) with proton therapy, including toxicity risks for UM patients. Materials and methods: For a total of 66 UM patients from a single center, SRT dose distributions were compared to protons using the same planning CT. Fourteen dose-volume parameters were compared in 2-Gy equivalent dose per fraction (EQD2). Four toxicity profiles were evaluated: maculopathy, optic-neuropathy, visual acuity impairment (Profile I); neovascular glaucoma (Profile II); radiation-induced retinopathy (Profile III); and dry-eye syndrome (Profile IV). For Profile III, retina Mercator maps were generated to visualize the geographical location of dose differences. Results: In 9/66 cases, (14 %) proton plans were superior for all dose-volume parameters. Higher T stages benefited more from protons in Profile I, especially tumors located within 3 mm or less from the optic nerve. In Profile II, only 9/66 cases resulted in a better proton plan. In Profile III, better retina volume sparing was always achievable with protons, with a larger gain for T3 tumors. In Profile IV, protons always reduced the risk of toxicity with a median RBE-weighted EQD2 reduction of 15.3 Gy. Conclusions: This study reports the first side-by-side imaging-based planning comparison between protons and SRT for UM patients. Globally, while protons appear almost always better regarding the risk of optic-neuropathy, retinopathy and dry-eye syndrome, for other toxicity like neovascular glaucoma, a plan comparison is warranted. Choice would depend on the prioritization of risks.

Challenges and opportunities in the development and clinical implementation of artificial intelligence based synthetic computed tomography for magnetic resonance only radiotherapy.

Synthetic computed tomography (sCT) generated from magnetic resonance imaging (MRI) can serve as a substitute for planning CT in radiation therapy (RT), thereby removing registration uncertainties associated with multi-modality imaging pairing, reducing costs and patient radiation exposure. CE/FDA-approved sCT solutions are nowadays available for pelvis, brain, and head and neck, while more complex deep learning (DL) algorithms are under investigation for other anatomic sites. The main challenge in achieving a widespread clinical implementation of sCT lies in the absence of consensus on sCT commissioning and quality assurance (QA), resulting in variation of sCT approaches across different hospitals. To address this issue, a group of experts gathered at the ESTRO Physics Workshop 2022 to discuss the integration of sCT solutions into clinics and report the process and its outcomes. This position paper focuses on aspects of sCT development and commissioning, outlining key elements crucial for the safe implementation of an MRI-only RT workflow.

Explicitly encoding the cyclic nature of breathing signal allows for accurate breathing motion prediction in radiotherapy with minimal training data.

Background and purpose: Active breathing motion management in radiotherapy consists of motion monitoring, quantification and mitigation. It is impacted by associated latencies of a few 100 ms. Artificial neural networks can successfully predict breathing motion and eliminate latencies. However, they require usually a large dataset for training. The objective of this work was to demonstrate that explicitly encoding the cyclic nature of the breathing signal into the training data enables significant reduction of training datasets which can be obtained from healthy volunteers. Material and methods: Seventy surface scanner breathing signals from 25 healthy volunteers in anterior-posterior direction were used for training and validation (ratio 4:1) of long short-term memory models. The model performance was compared to a model using decomposition into phase, amplitude and a time-dependent baseline. Testing of the models was performed on 55 independent breathing signals in anterior-posterior direction from surface scanner (35 lung, 20 liver) of 30 patients with a mean breathing amplitude of (5.9 ± 6.7) mm. Results: Using the decomposed breathing signal allowed for a reduction of the absolute root-mean square error (RMSE) from 0.34 mm to 0.12 mm during validation. Testing using patient data yielded an average absolute RMSE of the breathing signal of (0.16 ± 0.11) mm with a prediction horizon of 500 ms. Conclusion: It was demonstrated that a motion prediction model can be trained with less than 100 datasets of healthy volunteers if breathing cycle parameters are considered. Applied to 55 patients, the model predicted breathing motion with a high accuracy.

Patterns of practice of image guided particle therapy for cranio-spinal irradiation: A site specific multi-institutional survey of European Particle Therapy Network.

PURPOSE: To investigate the current practice patterns in image-guided particle therapy (IGPT) for cranio-spinal irradiation (CSI). METHODS: A multi-institutional survey was distributed to European particle therapy centres to analyse all aspects of IGPT. Based on the survey results, a Delphi consensus analysis was developed to define minimum requirements and optimal workflow for clinical practice. The centres participating in the institutional survey were invited to join the Delphi process. RESULTS: Eleven centres participated in the survey. Imaging for treatment planning was rather similar among the centres with Computed Tomography (CT) being the main modality. For positioning verification, 2D IGPT was more commonly used than 3D IGPT. Two centres performed routinely imaging for plan adaptation, by the rest ad hoc. Eight centres participated in the Delphi consensus analysis. The full consensus was reached on the use of CT imaging without contrast for treatment planning and the role of magnetic resonance imaging (MRI) in target and organs-at-risk delineation. There was an agreement on the necessity to perform patient position verification and correction before each isocentre. The most important outcome was the clear need for standardization and harmonization of the workflow. CONCLUSION: There were differences in CSI IGPT clinical practice among the European particle therapy centres. Moreover, the optimal workflow as identified by experts was not yet reached. There is a strong need for consensus guidelines. The state-of-the-art imaging technology and protocols need to be implemented into clinical practice to improve the quality of IGPT for CSI.

A generalized model for monitor units determination in ocular proton therapy using machine learning: A proof-of-concept study.

Objective.Determining and verifying the number of monitor units is crucial to achieving the desired dose distribution in radiotherapy and maintaining treatment efficacy. However, current commercial treatment planning system(s) dedicated to ocular passive eyelines in proton therapy do not provide the number of monitor units for patient-specific plan delivery. Performing specific pre-treatment field measurements, which is time and resource consuming, is usually gold-standard practice. This proof-of-concept study reports on the development of a multi-institutional-based generalized model for monitor units determination in proton therapy for eye melanoma treatments.Approach.To cope with the small number of patients being treated in proton centers, three European institutes participated in this study. Measurements data were collected to address output factor differences across the institutes, especially as function of field size, spread-out Bragg peak modulation width, residual range, and air gap. A generic model for monitor units prediction using a large number of 3748 patients and broad diversity in tumor patterns, was evaluated using six popular machine learning algorithms: (i) decision tree; (ii) random forest, (iii) extra trees, (iv) K-nearest neighbors, (v) gradient boosting, and (vi) the support vector regression. Features used as inputs into each machine learning pipeline were: Spread-out Bragg peak width, range, air gap, fraction and calibration doses. Performance measure was scored using the mean absolute error, which was the difference between predicted and real monitor units, as collected from institutional gold-standard methods.Main results.Predictions across algorithms were accurate within 3% uncertainty for up to 85.2% of the plans and within 10% uncertainty for up to 98.6% of the plans with the extra trees algorithm.Significance.A proof-of-concept of using machine learning-based generic monitor units determination in ocular proton therapy has been demonstrated. This could trigger the development of an independent monitor units calculation tool for clinical use.

Clinical Implementation and Evaluation of Auto-Segmentation Tools for Multi-Site Contouring in Radiotherapy.

Background and purpose: Tools for auto-segmentation in radiotherapy are widely available, but guidelines for clinical implementation are missing. The goal was to develop a workflow for performance evaluation of three commercial auto-segmentation tools to select one candidate for clinical implementation. Materials and Methods: One hundred patients with six treatment sites (brain, head-and-neck, thorax, abdomen, and pelvis) were included. Three sets of AI-based contours for organs-at-risk (OAR) generated by three software tools and manually drawn expert contours were blindly rated for contouring accuracy. The dice similarity coefficient (DSC), the Hausdorff distance, and a dose/volume evaluation based on the recalculation of the original treatment plan were assessed. Statistically significant differences were tested using the Kruskal-Wallis test and the post-hoc Dunn Test with Bonferroni correction. Results: The mean DSC scores compared to expert contours for all OARs combined were 0.80 ± 0.10, 0.75 ± 0.10, and 0.74 ± 0.11 for the three software tools. Physicians' rating identified equivalent or superior performance of some AI-based contours in head (eye, lens, optic nerve, brain, chiasm), thorax (e.g., heart and lungs), and pelvis and abdomen (e.g., kidney, femoral head) compared to manual contours. For some OARs, the AI models provided results requiring only minor corrections. Bowel-bag and stomach were not fit for direct use. During the interdisciplinary discussion, the physicians' rating was considered the most relevant. Conclusion: A comprehensive method for evaluation and clinical implementation of commercially available auto-segmentation software was developed. The in-depth analysis yielded clear instructions for clinical use within the radiotherapy department.

A survey of practice patterns for real-time intrafractional motion-management in particle therapy.

Background and purpose: Organ motion compromises accurate particle therapy delivery. This study reports on the practice patterns for real-time intrafractional motion-management in particle therapy to evaluate current clinical practice and wishes and barriers to implementation. Materials and methods: An institutional questionnaire was distributed to particle therapy centres worldwide (7/2020-6/2021) asking which type(s) of real-time respiratory motion management (RRMM) methods were used, for which treatment sites, and what were the wishes and barriers to implementation. This was followed by a three-round DELPHI consensus analysis (10/2022) to define recommendations on required actions and future vision. With 70 responses from 17 countries, response rate was 100% for Europe (23/23 centres), 96% for Japan (22/23) and 53% for USA (20/38). Results: Of the 68 clinically operational centres, 85% used RRMM, with 41% using both rescanning and active methods. Sixty-four percent used active-RRMM for at least one treatment site, mostly with gating guided by an external marker. Forty-eight percent of active-RRMM users wished to expand or change their RRMM technique. The main barriers were technical limitations and limited resources. From the DELPHI analysis, optimisation of rescanning parameters, improvement of motion models, and pre-treatment 4D evaluation were unanimously considered clinically important future focus. 4D dose calculation was identified as the top requirement for future commercial treatment planning software. Conclusion:  A majority of particle therapy centres have implemented RRMM. Still, further development and clinical integration were desired by most centres. Joint industry, clinical and research efforts are needed to translate innovation into efficient workflows for broad-scale implementation.

A survey of practice patterns for adaptive particle therapy for interfractional changes.

Background and purpose: Anatomical changes may compromise the planned target coverage and organs-at-risk dose in particle therapy. This study reports on the practice patterns for adaptive particle therapy (APT) to evaluate current clinical practice and wishes and barriers to further implementation. Materials and methods: An institutional questionnaire was distributed to PT centres worldwide (7/2020-6/2021) asking which type of APT was used, details of the workflow, and what the wishes and barriers to implementation were. Seventy centres from 17 countries participated. A three-round Delphi consensus analysis (10/2022) among the authors followed to define recommendations on required actions and future vision. Results: Out of the 68 clinically operational centres, 84% were users of APT for at least one treatment site with head and neck being most common. APT was mostly performed offline with only two online APT users (plan-library). No centre used online daily re-planning. Daily 3D imaging was used for APT by 19% of users. Sixty-eight percent of users had plans to increase their use or change their technique for APT. The main barrier was "lack of integrated and efficient workflows". Automation and speed, reliable dose deformation for dose accumulation and higher quality of in-room volumetric imaging were identified as the most urgent task for clinical implementation of online daily APT. Conclusion: Offline APT was implemented by the majority of PT centres. Joint efforts between industry research and clinics are needed to translate innovations into efficient and clinically feasible workflows for broad-scale implementation of online APT.

Tools for large-scale data analytics of an international multi-center study in radiation oncology for cervical cancer.

PURPOSE: To develop and implement a software that enables centers, treating patients with state-of-the-art radiation oncology, to compare their patient, treatment, and outcome data to a reference cohort, and to assess the quality of their treatment approach. MATERIALS AND METHODS: A comprehensive data dashboard was designed, which al- lowed holistic assessment of institutional treatment approaches. The software was tested in the ongoing EMBRACE-II study for locally advanced cervical cancer. The tool created individualized dashboards and automatic analysis scripts, verified pro- tocol compliance and checked data for inconsistencies. Identified quality assurance (QA) events were analysed. A survey among users was conducted to assess usability. RESULTS: The survey indicated favourable feedback to the prototype and highlighted its value for internal monitoring. Overall, 2302 QA events were identified (0.4% of all collected data). 54% were due to missing or incomplete data, and 46% originated from other causes. At least one QA event was found in 519/1001 (52%) of patients. QA events related to primary study endpoints were found in 16% of patients. Sta- tistical methods demonstrated good performance in detecting anomalies, with precisions ranging from 71% to 100%. Most frequent QA event categories were Treatment Technique (27%), Patient Characteristics (22%), Dose Reporting (17%), Outcome 156 (15%), Outliers (12%), and RT Structures (8%). CONCLUSION: A software tool was developed and tested within a clinical trial in radia- tion oncology. It enabled the quantitative and qualitative comparison of institutional patient and treatment parameters with a large multi-center reference cohort. We demonstrated the value of using statistical methods to automatically detect implau- sible data points and highlighted common pitfalls and uncertainties in radiotherapy for cervical cancer.

A novel bone suppression algorithm in intensity-based 2D/3D image registration for real-time tumor motion monitoring: Development and phantom-based validation.

BACKGROUND: Real-time tumor motion monitoring (TMM) is a crucial process for intra-fractional respiration management in lung cancer radiotherapy. Since the tumor can be partly or fully located behind the ribs, the TMM is challenging. PURPOSE: The aim of this work was to develop a bone suppression (BS) algorithm designed for real-time 2D/3D marker-less TMM to increase the visibility of the tumor when overlapping with bony structures and consequently to improve the accuracy of TMM. METHOD: A BS method was implemented in the in-house developed software for ultrafast intensity-based 2D/3D tumor registration (Fast Image-based Registration [FIRE]). The method operates on both, digitally reconstructed radiograph (DRR) and intra-fractional X-ray images. The bony structures are derived from computed tomography data by thresholding during ray-casting, and the resulting bone DRR is subtracted from intra-fractional X-ray images to obtain a soft-tissue-only image for subsequent tumor registration. The accuracy of TMM utilizing BS was evaluated within a retrospective phantom study with nine different 3D-printed tumor phantoms placed in the in-house developed Advanced Radiation DOSimetry (ARDOS) breathing phantom. A 24 mm craniocaudal tumor motion, including rib eclipses, was simulated, and X-ray images were acquired on the Elekta Versa HD Linac in the lateral and posterior-anterior directions. An error assessment for BS images was evaluated with respect to the ground truth tumor position. RESULTS: A total error (root mean square error) of 0.87 ± 0.23 mm and 1.03 ± 0.26 mm was found for posterior-anterior and lateral imaging; the mean time for BS was 8.03 ± 1.54 ms. Without utilizing BS, TMM failed in all X-ray images since the registration algorithm focused on the rib position due to the predominant intensity of this tissue within DRR and X-ray images. CONCLUSION: The BS algorithm developed and implemented improved the accuracy, robustness, and stability of real-time TMM in lung cancer in a phantom study, even in the case of rib interlude where normal tumor registration fails.

Improving organs-at-risk sparing for choroidal melanoma patients: A CT-based two-beam strategy in ocular proton therapy with a dedicated eyeline.

PURPOSE: To investigate the potential clinical benefit of a two-beam arrangement technique using three-dimensional (3D) imaging of uveal melanoma (UM) patients treated with proton therapy and a dedicated eyeline. MATERIAL/METHODS: Retrospective CT-based treatment plans of 39 UM patients performed using a single beam (SB) were compared to plans with two beams (TB) optimized for better trade-offs in organs-at-risk sparing. The RBE-weighted prescribed dose was 60 Gy (DRBE, GTV = 60 Gy) in four fractions, assuming an RBE of 1.1. Dosimetric findings were analyzed for three patient groups based on tumor-optic nerve distance and UM staging (group GrA: ≤3 mm, T1 T2 UM; GrB: ≤3 mm, T3 UM; GrC: >3 mm, T1 T2 T3 UM). Finally, two schedules were compared on biologically effective dose (BED): both beams being delivered either the same day (TB), or on alternate days (TBalter). RESULTS: All strategies resulted in dosimetrically acceptable plans. A dose reduction to the anterior structures was achieved in 23/39 cases with the two-beam plans. D25% was significantly lowered compared to SB plans by 12.4 and 15.4 Gy RBE-weighted median dose in GrA and GrB, respectively. D2% was reduced by 18.6 and 6.0 Gy RBE-weighted median dose in GrA and GrB, respectively. A cost to the optic nerve was observed with a median difference up to 3.8 Gy RBE-weighted dose in GrB. BED differences were statistically significant for all considered parameters in favor of two beams delivered the same day. CONCLUSION: A two-beam strategy appears beneficial for posterior tumors abutting the optic nerve. This strategy might have a positive impact on the risk of ocular complications.

Clinical necessity of multi-image based (4DMIB) optimization for targets affected by respiratory motion and treated with scanned particle therapy - A comprehensive review.

4D multi-image-based (4DMIB) optimization is a form of robust optimization where different uncertainty scenarios, due to anatomy variations, are considered via multiple image sets (e.g., 4DCT). In this review, we focused on providing an overview of different 4DMIB optimization implementations, introduced various frameworks to evaluate the robustness of scanned particle therapy affected by breathing motion and summarized the existing evidence on the necessity of using 4DMIB optimization clinically. Expected potential benefits of 4DMIB optimization include more robust and/or interplay-effect-resistant doses for the target volume and organs-at-risk for indications affected by anatomical variations (e.g., breathing, peristalsis, etc.). Although considerable literature is available on the research and technical aspects of 4DMIB, clinical studies are rare and often contain methodological limitations, such as, limited patient number, motion amplitude, motion and delivery time structure considerations, number of repeat CTs, etc. Therefore, the data are not conclusive. In addition, multiple studies have found that robust 3D optimized plans result in dose distributions within the set clinical tolerances and, therefore, are suitable for a treatment of moving targets with scanned particle therapy. We, therefore, consider the clinical necessity of 4DMIB optimization, when treating moving targets with scanned particle therapy, as still to be demonstrated.

Characterization of the HollandPTC proton therapy beamline dedicated to uveal melanoma treatment and an interinstitutional comparison.

PURPOSE: Eye-dedicated proton therapy (PT) facilities are used to treat malignant intraocular lesions, especially uveal melanoma (UM). The first commercial ocular PT beamline from Varian was installed in the Netherlands. In this work, the conceptual design of the new eyeline is presented. In addition, a comprehensive comparison against five PT centers with dedicated ocular beamlines is performed, and the clinical impact of the identified differences is analyzed. MATERIAL/METHODS: The HollandPTC eyeline was characterized. Four centers in Europe and one in the United States joined the study. All centers use a cyclotron for proton beam generation and an eye-dedicated nozzle. Differences among the chosen ocular beamlines were in the design of the nozzle, nominal energy, and energy spectrum. The following parameters were collected for all centers: technical characteristics and a set of distal, proximal, and lateral region measurements. The measurements were performed with detectors available in-house at each institution. The institutions followed the International Atomic Energy Agency (IAEA) Technical Report Series (TRS)-398 Code of Practice for absolute dose measurement, and the IAEA TRS-398 Code of Practice, its modified version or International Commission on Radiation Units and Measurements Report No. 78 for spread-out Bragg peak normalization. Energy spreads of the pristine Bragg peaks were obtained with Monte Carlo simulations using Geant4. Seven tumor-specific case scenarios were simulated to evaluate the clinical impact among centers: small, medium, and large UM, located either anteriorly, at the equator, or posteriorly within the eye. Differences in the depth dose distributions were calculated. RESULTS: A pristine Bragg peak of HollandPTC eyeline corresponded to the constant energy of 75 MeV (maximal range 3.97 g/cm2 in water) with an energy spread of 1.10 MeV. The pristine Bragg peaks for the five participating centers varied from 62.50 to 104.50 MeV with an energy spread variation between 0.10 and 0.70 MeV. Differences in the average distal fall-offs and lateral penumbrae (LPs) (over the complete set of clinically available beam modulations) among all centers were up to 0.25 g/cm2 , and 0.80 mm, respectively. Average distal fall-offs of the HollandPTC eyeline were 0.20 g/cm2 , and LPs were between 1.50 and 2.15 mm from proximal to distal regions, respectively. Treatment time, around 60 s, was comparable among all centers. The virtual source-to-axis distance of 120 cm at HollandPTC was shorter than for the five participating centers (range: 165-350 cm). Simulated depth dose distributions demonstrated the impact of the different beamline characteristics among institutions. The largest difference was observed for a small UM located at the posterior pole, where a proximal dose between two extreme centers was up to 20%. CONCLUSIONS: HollandPTC eyeline specifications are in accordance with five other ocular PT beamlines. Similar clinical concepts can be applied to expect the same high local tumor control. Dosimetrical properties among the six institutions induce most likely differences in ocular radiation-related toxicities. This interinstitutional comparison could support further research on ocular post-PT complications. Finally, the findings reported in this study could be used to define dosimetrical guidelines for ocular PT to unify the concepts among institutions.

Results of an independent dosimetry audit for scanned proton beam therapy facilities.

PURPOSE: An independent dosimetry audit based on end-to-end testing of the entire chain of radiation therapy delivery is highly recommended to ensure consistent treatments among proton therapy centers. This study presents an auditing methodology developed by the MedAustron Ion Beam Therapy Center (Austria) in collaboration with the National Physical Laboratory (UK) and audit results for five scanned proton beam therapy facilities in Europe. METHODS: The audit procedure used a homogeneous and an anthropomorphic head phantom. The phantoms were loaded either with an ionization chamber or with alanine pellets and radiochromic films. Homogeneously planned doses of 10Gy were delivered to a box-like target volume in the homogeneous phantom and to two clinical scenarios with increasing complexity in the head phantom. RESULTS: For all tests the mean of the local differences of the absolute dose to water determined with the alanine pellets compared to the predicted dose from the treatment planning system installed at the audited institution was determined. The mean value taken over all tests performed was -0.1±1.0%. The measurements carried out with the ionization chamber were consistent with the dose determined by the alanine pellets with a mean deviation of -0.5±0.6%. CONCLUSION: The developed dosimetry audit method was successfully applied at five proton centers including various "turn-key" Cyclotron solutions by IBA, Varian and Mevion. This independent audit with extension to other tumour sites and use of the correspondent anthropomorphic phantoms may be proposed as part of a credentialing procedure for future clinical trials in proton beam therapy.

Dosimetric Impact of Intrafraction Motion in Online-Adaptive Intensity Modulated Proton Therapy for Cervical Cancer.

PURPOSE: A method was recently developed for online-adaptive intensity modulated proton therapy (IMPT) in patients with cervical cancer. The advantage of this approach, relying on the use of tight margins, is challenged by the intrafraction target motion. The purpose of this study was to evaluate the dosimetric effect of intrafraction motion on the target owing to changes in bladder filling in patients with cervical cancer treated with online-adaptive IMPT. METHODS AND MATERIALS: In 10 patients selected to have large uterus motion induced by bladder filling, the intrafraction anatomic changes were simulated for several prefraction durations for online (automated) contouring and planning. For each scenario, the coverage of the primary target was evaluated with margins of 2.5 and 5 mm. RESULTS: Using a 5- mm planning target volume margin, median accumulated D98% was greater than 42.75 GyRBE1.1 (95% of the prescribed dose) in the case of a prefraction duration of 5 and 10 minutes. For a prefraction duration of 15 minutes, this parameter deteriorated to 42.6 GyRBE1.1. When margins were reduced to 2.5 mm, only a 5-minute duration resulted in median target D98% above 42.75 GyRBE1.1. In addition, smaller bladders were found to be associated with larger dose degradations compared with larger bladders. CONCLUSIONS: This study indicates that intrafraction anatomic changes can have a substantial dosimetric effect on target coverage in an online-adaptive IMPT scenario for patients subject to large uterus motion. A margin of 5 mm was sufficient to compensate for the intrafraction motion due to bladder filling for up to 10 minutes of prefraction time. However, compensation for the uncertainties that were disregarded in this study, by using margins or robust optimization, is also required. Furthermore, a large bladder volume restrains intrafraction target motion and is recommended for treating patients in this scenario. Assuming that online-adaptive IMPT remains beneficial as long as narrow margins are used (5 mm or below), this study demonstrates its feasibility with regard to intrafraction motion.

Gradient corrections for reference dosimetry using Farmer-type ionization chambers in single-layer scanned proton fields.

PURPOSE: The local depth dose gradient and the displacement correction factor for Farmer-type ionization chambers are quantified for reference dosimetry at shallow depth in single-layer scanned proton fields. METHOD: Integrated radial profiles as a function of depth (IRPDs) measured at three proton therapy centers were smoothed by polynomial fits. The local relative depth dose gradient at measurement depths from 1 to 5 cm were derived from the derivatives of those fits. To calculate displacement correction factors, the best estimate of the effective point of measurement was derived from reviewing experimental and theoretical determinations reported in the literature. Displacement correction factors for the use of Farmer-type ionization chambers with their reference point (at the center of the cavity volume) positioned at the measurement depth were derived as a ratio of IRPD values at the measurement depth and at the effective point of measurement. RESULTS: Depth dose gradients are as low as 0.1-0.4% per mm at measurement depths from 1 to 5 cm in the highest clinical proton energies (with residual ranges higher than 15 cm) and increase to 1% per mm at a residual range of 4 cm and become larger than 3% per mm for residual ranges lower than 2 cm. The literature review shows that the effective point of measurement of Farmer-type ionization chambers is, similarly as for carbon ion beams, located 0.75 times the cavity radius closer to the beam origin as the center of the cavity. If a maximum displacement correction of 2% is deemed acceptable to be included in calculated beam quality correction factors, Farmer-type ICs can be used at measurements depths from 1 to 5 cm for which the residual range is 4 cm or larger. If one wants to use the same beam quality correction factors as applicable to the conventional measurement point for scattered beams, located at the center of the SOBP, the relative standard uncertainty on the assumption that the displacement correction factor is unity can be kept below 0.5% for measurement depths of at least 2 cm and for residual ranges of 15 cm or higher. CONCLUSION: The literature review confirmed that for proton beams the effective point of measurement of Farmer-type ionization chambers is located 0.75 times the cavity radius closer to the beam origin as the center of the cavity. Based on the findings in this work, three options can be recommended for reference dosimetry of scanned proton beams using Farmer-type ionization chambers: (a) positioning the effective point of measurement at the measurement depth, (b) positioning the reference point at the measurement depth and applying a displacement correction factor, and (c) positioning the reference point at the measurement depth without applying a displacement correction factor. Based on limiting the acceptable uncertainty on the gradient correction factor to 0.5% and the maximum deviation of the displacement perturbation correction factor from unity to 2%, the first two options can be allowed for residual ranges of at least 4 cm while the third option only for residual ranges of at least 15 cm.

Clinical implementations of 4D pencil beam scanned particle therapy: Report on the 4D treatment planning workshop 2016 and 2017.

In 2016 and 2017, the 8th and 9th 4D treatment planning workshop took place in Groningen (the Netherlands) and Vienna (Austria), respectively. This annual workshop brings together international experts to discuss research, advances in clinical implementation as well as problems and challenges in 4D treatment planning, mainly in spot scanned proton therapy. In the last two years several aspects like treatment planning, beam delivery, Monte Carlo simulations, motion modeling and monitoring, QA phantoms as well as 4D imaging were thoroughly discussed. This report provides an overview of discussed topics, recent findings and literature review from the last two years. Its main focus is to highlight translation of 4D research into clinical practice and to discuss remaining challenges and pitfalls that still need to be addressed and to be overcome.

Improved source path localisation in ring applicators and the clinical impact for gynecological brachytherapy.

PURPOSE: The path of subsequent dwell positions of an afterloader source being moved through a ring applicator for cervix cancer brachytherapy deviates from an ideal circle and the position of marker wires. This can lead to deviations of several millimetres between real and assumed dwell positions for treatment planning with simplified source path models. The aim of this study was to test video- and autoradiography-based methods for source path determination, and to study the influence of dwell position accuracy on dose-volume histogram (DVH)-parameters. MATERIAL AND METHODS: Videos of the exact motion of the source wire through three different (r = 26, 30, 34 mm) computed tomography/magnetic resonance (CT/MR) compatible plastic ring applicators were recorded. Observed dwell positions covering the whole length of each applicators channel were used to adjust the circular source path model. The agreement of the true source positions derived from video analysis with those of the corrected circular source path was verified using autoradiography. The impact of an accurate source path definition on dose planning was analysed by simulating clinically relevant uncertainties in 10 clinical treatment plans. RESULTS: Depending on the ring size, source path diameters had to be increased by 0.5-1.0 mm in order to achieve acceptable maximum differences between observed and corrected dwell positions (1.3-2.0 mm). Autoradiography analysis showed a positional accuracy within ± 3 mm (extended standard deviation k = 2). For shifts of ± 2.5 mm for even all dwell positions, the systematic and random variation of the D2cm(3) for bladder, rectum, and sigmoid was within 3%, while the impact on DVH uncertainties was much smaller for clinical target volume (CTV)HR and gross tumour volume (GTV). CONCLUSIONS: It is strongly advised to verify the real source path for ring applicators during acceptance testing in order to assure accurate source path definition and dose planning. Autoradiography can be used for source path verification with acceptable accuracy for treatment planning and dose reporting.

Dose-painting intensity-modulated proton therapy for intermediate- and high-risk meningioma.

BACKGROUND: Newly diagnosed WHO grade II-III or any WHO grade recurrent meningioma exhibit an aggressive behavior and thus are considered as high- or intermediate risk tumors. Given the unsatisfactory rates of disease control and survival after primary or adjuvant radiation therapy, optimization of treatment strategies is needed. We investigated the potential of dose-painting intensity-modulated proton beam-therapy (IMPT) for intermediate- and high-risk meningioma. MATERIAL AND METHODS: Imaging data from five patients undergoing proton beam-therapy were used. The dose-painting target was defined using [68]Ga-[1,4,7,10-tetraazacyclododecane tetraacetic acid]- d-Phe(1),Tyr(3)-octreotate ([68]Ga-DOTATATE)-positron emission tomography (PET) in target delineation. IMPT and photon intensity-modulated radiation therapy (IMRT) treatment plans were generated for each patient using an in-house developed treatment planning system (TPS) supporting spot-scanning technology and a commercial TPS, respectively. Doses of 66 Gy (2.2 Gy/fraction) and 54 Gy (1.8 Gy/fraction) were prescribed to the PET-based planning target volume (PTVPET) and the union of PET- and anatomical imaging-based PTV, respectively, in 30 fractions, using simultaneous integrated boost. RESULTS: Dose coverage of the PTVsPET was equally good or slightly better in IMPT plans: dose inhomogeneity was 10 ± 3% in the IMPT plans vs. 13 ± 1% in the IMRT plans (p = 0.33). The brain Dmean and brainstem D50 were small in the IMPT plans: 26.5 ± 1.5 Gy(RBE) and 0.002 ± 0.0 Gy(RBE), respectively, vs. 29.5 ± 1.5 Gy (p = 0.001) and 7.5 ± 11.1 Gy (p = 0.02) for the IMRT plans, respectively. The doses delivered to the optic structures were also decreased with IMPT. CONCLUSIONS: Dose-painting IMPT is technically feasible using currently available planning tools and resulted in dose conformity of the dose-painted target comparable to IMRT with a significant reduction of radiation dose delivered to the brain, brainstem and optic apparatus. Dose escalation with IMPT may improve tumor control and decrease radiation-induced toxicity.

Imaging dose assessment for IGRT in particle beam therapy.

INTRODUCTION: Image-guided advanced photon and particle beam treatments are promising options for improving lung treatments. Extensive use of imaging increases the overall patient dose. The aim of this study was to determine the imaging dose for different IGRT solutions used in photon and particle beam therapy. MATERIAL AND METHODS: Measurements were performed in an Alderson phantom with TLDs. Clinically applied protocols for orthogonal planar kV imaging, stereoscopic imaging, CT scout views, fluoroscopy, CT, 4D-CT and CBCT were investigated at five ion beam centers and one conventional radiotherapy department. The overall imaging dose was determined for a patient undergoing a lung tumor irradiation with institute specific protocols. RESULTS: OAR doses depended on imaging modality and OAR position. Dose values were in the order of 1 mGy for planar and stereoscopic imaging and 10-50 mGy for volumetric imaging, except for one CBCT device leading to lower doses. The highest dose per exam (up to 150 mGy to the skin) was recorded for a 3-min fluoroscopy. DISCUSSION: Modalities like planar kV or stereoscopic imaging result in very low doses (≈ 1 mGy) to the patient. Imaging a moving target during irradiation, low-dose protocols and protocol optimization can reduce the imaging dose to the patient substantially.