Automated treatment planning of prostate stereotactic body radiotherapy with focal boosting on a fast-rotating O-ring linac: Plan quality comparison with C-arm linacs.

PURPOSE: The integration of auto-segmentation and automated treatment planning methods on a fast-rotating O-ring linac may improve the time efficiency of online adaptive radiotherapy workflows. This study investigates whether automated treatment planning of prostate SBRT with focal boosting on the O-ring linac could generate plans that are of similar quality as those obtained through manual planning on clinical C-arm linacs. METHODS: For 20 men with prostate cancer, reference treatment plans were generated on a TrueBeam STx C-arm linac with HD120 MLC and a TrueBeam C-arm linac with Millennium 120 MLC using 6 MV flattened dual arc VMAT. Manual planning on the Halcyon fast-rotating O-ring linac was performed using 6 MV FFF dual arc VMAT (HA2-DL10) and triple arc VMAT (HA3-DL10) to investigate the performance of the dual-layer MLC system. Automated planning was performed for triple arc VMAT on the Halcyon linac (ET3-DL10) using the automated planning algorithms of Ethos Treatment Planning. The prescribed dose was 35 Gy to the prostate and 30 Gy to the seminal vesicles in five fractions. The iso-toxic focal boost to the intraprostatic tumor nodule(s) was aimed to receive up to 50 Gy. Plan deliverability was verified using portal image dosimetry measurements. RESULTS: Compared to the C-arm linacs, ET3-DL10 shows increased seminal vesicles PTV coverage (D99% ) and reduced high-dose spillage to the bladder (V37Gy ) and urethra (D0.035cc ) but this came at the cost of increased high-dose spillage to the rectum (V38Gy ) and a higher intermediate dose spillage (D2cm). No statistically significant differences were found when benchmarking HA2-DL10 and HA3-DL10 with the C-arm linacs. All plans passed the patient-specific QA tolerance limit. CONCLUSIONS: Automated planning of prostate SBRT with focal boosting on the fast-rotating O-ring linac is feasible and achieves similar plan quality as those obtained on clinical C-arm linacs using manual planning.

Are offline ART decisions for NSCLC impacted by the type of dose calculation algorithm?

Introduction: Decisions for plan-adaptations may be impacted by a transitioning from one dose-calculation algorithm to another. This study examines the impact on dosimetric-triggered offline adaptation in LA-NSCLC in the context of a transition from superposition/convolution dose calculation algorithm (Type-B) to linear Boltzmann equation solver dose calculation algorithms (Type-C). Materials & Methods: Two dosimetric-triggered offline adaptive treatment workflows are compared in a retrospective planning study on 30 LA-NSCLC patients. One workflow uses a Type-B dose calculation algorithm and the other uses Type-C. Treatment plans were re-calculated on the anatomy of a mid-treatment synthetic-CT utilizing the same algorithm utilized for pre-treatment planning. Assessment for plan-adaptation was evaluated through a decision model based on target coverage and OAR constraint violation. The impact of algorithm during treatment planning was controlled for by recalculating the Type-B plan with Type-C. Results: In the Type-B approach, 13 patients required adaptation due to OAR-constraint violations, while 15 patients required adaptation in the Type-C approach. For 8 out of 30 cases, the decision to adapt was opposite in both approaches. None of the patients in our dataset encountered CTV-target underdosage that necessitated plan-adaptation. Upon recalculating the Type-B approach with the Type-C algorithm, it was shown that 10 of the original Type-B plans revealed clinically relevant dose reductions (≥3%) on the CTV in their original plans. This re-calculation identified 21 plans in total that required ART. Discussion: In our study, nearly one-third of the cases would have a different decision for plan-adaption when utilizing Type-C instead of Type-B. There was no substantial increase in the total number of plan-adaptations for LA-NSCLC. However, Type-C is more sensitive to altered anatomy during treatment compared to Type-B. Recalculating Type-B plans with the Type-C algorithm revealed an increase from 13 to 21 cases triggering ART.

New optically stimulated luminescence dosimetry film optimized for energy dependence guided by Monte Carlo simulations.

Optically stimulated luminescence (OSL) film dosimeters, based on BaFBr:Eu2+phosphor material, have major dosimetric advantages such as dose linearity, high spatial resolution, film re-usability, and immediate film readout. However, they exhibit an energy-dependent over-response at low photon energies because they are not made of tissue-equivalent materials. In this work, the OSL energy-dependent response was optimized by lowering the phosphor grain size and seeking an optimal choice of phosphor concentration and film thickness to achieve sufficient signal sensitivity. This optimization process combines measurement-based assessments of energy response in narrow x-ray beams with various energy response calculation methods applied to different film metrics. Theoretical approaches and MC dose simulations were used for homogeneous phosphor distributions and for isolated phosphor grains of different dimensions, where the dose in the phosphor grain was calculated. In total 8 OSL films were manufactured with different BaFBr:Eu2+median particle diameters (D50): 3.2µm, 1.5µm and 230 nm and different phosphor concentrations (1.6%, 5.3% and 21.3 %) and thicknesses (from 5.2 to 49µm). Films were irradiated in narrow x-ray spectra (N60, N80, N-150 and N-300) and the signal intensity relative to the nominal dose-to-water value was normalized to Co-60. Finally, we experimentally tested the response of several films in Varian 6MV TrueBeam STx linear accelerator using the following settings: 10 × 10 cm2field, 0deggantry angle, 90 cm SSD, 10 cm depth. The x-ray irradiation experiment reported a reduced energy response for the smallest grain size with an inverse correlation between response and grain size. The N-60 irradiation showed a 43% reduction in the energy over-response when going from 3µm to 230 nm grain size for the 5% phosphor concentration. Energy response calculation using a homogeneous dispersion of the phosphor underestimated the experimental response and was not able to obtain the experimental correlation between grain size and energy response. Isolated grain size modeling combined with MC dose simulations allowed to establish a good agreement with experimental data, and enabled steering the production of optimized OSL-films. The clinical 6 MV beam test confirmed a reduction in energy dependence, which is visible in small-grain films where a decrease in out-of-field over-response was observed.

Calibration and time fading characterization of a new optically stimulated luminescence film dosimeter.

BACKGROUND: Optically stimulated luminescence (OSL) dosimeters produce a signal linear to the dose, which fades with time due to the spontaneous recombination of energetically unstable electron/hole traps. When used for radiotherapy (RT) applications, fading affects the signal-to-dose conversion and causes an error in the final dose measurement. Moreover, the signal fading depends to some extent on treatment-specific irradiation conditions such as irradiation times. PURPOSE: In this work, a dose calibration function for a novel OSL film dosimeter was derived accounting for signal fading. The proposed calibration allows to perform dosimetry evaluation for different RT treatment regimes. METHODS: A novel BaFBr:Eu2+ -based OSL film (Zeff , 6 MV  = 4.7) was irradiated on a TrueBeam STx using a 6 MV beam with setup: 0° gantry angle, 90 cm SSD, 10 cm depth, 10 × 10 cm2 field. A total of 86 measurements were acquired for dose-rates ( D ̇ $\dot{D}$ ) of 600, 300, and 200 MU/min for irradiation times (tir ) of 0.2, 1, 2, 4.5, 12, and 23 min and various readout times (tscan ) between 4 and 1440 min from the start of the exposure (beam-on time). The OSL signal, S ( D ̇ , t i r , t s c a n ) $S(\dot{D},{t}_{ir},{t}_{scan})$ , was modeled via robust nonlinear regression, and two different power-law fading models were tested, respectively, independent (linear model) and dependent on the specific t i r ${t}_{ir}$ (delivery-dependent model). RESULTS: After 1 day from the exposure, the error on the dose measurement can be as high as 48% if a fading correction is not considered. The fading contribution was characterized by two accurate models with adjusted-R2 of 0.99. The difference between the two models is <4.75% for all t i r ${t}_{ir}$ and t s c a n ${t}_{scan}$ . For different beam-on times, 3, 10.5, and 20 min, the optimum t s c a n ${t}_{scan}$ was calculated in order to achieve a signal-to-dose conversion with a model-related error <1%. In the case of a 3 min irradiation, this condition is already met when the OSL-film is scanned immediately after the end of the irradiation. For an irradiation of 10.5 and 20 min, the minimum scanning time to achieve this model-related error increases, respectively, to 30 and 90 min. Under these conditions, the linear model can be used for the signal-to-dose conversion as an approximation of the delivery-dependent model. The signal-to-dose function, D(Mi , j , t s c a n $\ {t}_{scan}$ ), has a residual mean error of 0.016, which gives a residual dose uncertainty of 0.5 mGy in the region of steep signal fading (i.e., t s c a n ${t}_{scan}\ $ = 4 min). The function of two variables is representable as a dose surface depending on the signal (Mi , j ) measured for each i,j-pixel and the time of scan ( t s c a n ${t}_{scan}$ ). CONCLUSIONS: The calibration of a novel OSL-film usable for dosimetry in different RT treatments was corrected for its signal fading with two different models. A linear calibration model independent from the treatment-specific irradiation condition results in a model-related error <1% if a proper scanning time is used for each irradiation length. This model is more practical than the delivery-dependent model because it does not need a pixel-to-pixel fading correction for different t i r ${t}_{ir}$ .

Treatment plan prediction for lung IMRT using deep learning based fluence map generation.

PURPOSE: Recently, it has been shown that automated treatment planning can be executed by direct fluence prediction from patient anatomy using convolutional neural networks. Proof of principle publications utilise a fixed dose prescription and fixed collimator (0°) and gantry angles. The goal of this work is to further develop these principles for the challenging lung cancer indication with variable dose prescriptions, collimator and gantry angles. First we investigate the impact of clinical applicable collimator angles and various input parameters. Then, the model is tested in a complete user independent planning workflow. METHODS: The dataset consists of 152 lung cancer patients, previously treated with IMRT. The patients are treated with either a left or a right beam setup and collimator angles and dose prescriptions adjusted to their tumour shape and stage. First we compare two CNNs with standard vs. personalised, clinical collimator angles. Next, four CNNs are trained with various combinations of CT and contour inputs. Finally, a complete user free treatment planning workflow is evaluated. RESULTS: The difference between the predicted and ground truth fluence maps for the fluence prediction CNN with all anatomical inputs in terms of the mean mean absolute error (MAE) is 4.17 × 10-4 for a fixed collimator angle and 5.46 × 10-4 for variable collimator angles. These differences vanish in terms of DVH metrics. Furthermore, the impact of anatomical inputs is small. The mean MAE is 5.88 × 10-4 if no anatomical information is given to the network. The DVH differences increase when a total user free planning workflow is examined. CONCLUSIONS: Fluence prediction with personalised collimator angles performs as good as fluence prediction with a standard collimator angle of zero degrees. The impact of anatomical inputs is small. The combination of a dose prediction and fluence prediction CNN deteriorates the fluence predictions. More investigation is required.

Experimental investigation of dynamic real-time rotation-including dose reconstruction during prostate tracking radiotherapy.

BACKGROUND: Hypofractionation in prostate radiotherapy is of increasing interest. Steep dose gradients and a large weight on each individual fraction emphasize the need for motion management. Real-time motion management techniques such as multileaf collimator (MLC) tracking or couch tracking typically adjust for translational motion while rotations remain uncompensated with unknown dosimetric impact. PURPOSE: The purpose of this study is to demonstrate and validate dynamic real-time rotation-including dose reconstruction during radiotherapy experiments with and without MLC and couch tracking. METHODS: Real-time dose reconstruction was performed using the in-house developed software DoseTracker. DoseTracker receives streamed target positions and accelerator parameters during treatment delivery and uses a pencil beam algorithm with water density assumption to reconstruct the dose in a moving target. DoseTracker's ability to reconstruct motion-induced dose errors in a dynamically rotating and translating target was investigated during three different scenarios: (1) no motion compensation and translational motion correction with (2) MLC tracking and (3) couch tracking. In each scenario, dose reconstruction was performed online and in real time during delivery of two dual-arc volumetric-modulated arc therapy prostate plans with a prescribed fraction dose of 7 Gy to the prostate and simultaneous intraprostatic lesion boosts with doses of at least 8 Gy, but up to 10 Gy as long as the organs at risk dose constraints were fulfilled. The plans were delivered to a pelvis phantom that replicated three patient-measured motion traces using a rotational insert with 21 layers of EBT3 film spaced 2.5 mm apart. DoseTracker repeatedly calculated the actual motion-including dose increment and the planned static dose increment since the last calculation in 84 500 points in the film stack. The experiments were performed with a TrueBeam accelerator with MLC and couch tracking based on electromagnetic transponders embedded in the film stack. The motion-induced dose error was quantified as the difference between the final cumulative dose with motion and without motion using the 2D 2%/2 mm γ-failure rate and the difference in dose to 95% of the clinical target volume (CTV ΔD95% ) and the gross target volume (GTV ΔD95% ) as well as the difference in dose to 0.1 cm3 of the urethra, bladder, and rectum (ΔD0.1CC ). The motion-induced errors were compared between dose reconstructions and film measurements. RESULTS: The dose was reconstructed in all calculation points at a mean frequency of 4.7 Hz. The root-mean-square difference between real-time reconstructed and film-measured motion-induced errors was 3.1%-points (γ-failure rate), 0.13 Gy (CTV ΔD95% ), 0.23 Gy (GTV ΔD95% ), 0.19 Gy (urethra ΔD0.1CC ), 0.09 Gy (bladder ΔD0.1CC ), and 0.07 Gy (rectum ΔD0.1CC ). CONCLUSIONS: In a series of phantom experiments, online real-time rotation-including dose reconstruction was performed for the first time. The calculated motion-induced errors agreed well with film measurements. The dose reconstruction provides a valuable tool for monitoring dose delivery and investigating the efficacy of advanced motion-compensation techniques in the presence of translational and rotational motion.

Companding technique for high dynamic range measurements using Gafchromic films.

PURPOSE: To introduce a methodology to perform dose measurements using Gafchromic films which can span several decades of dose levels. METHODS: The technique is based on a rescaling approach using different films irradiated at different dose levels. This is combined with a registration protocol correcting positioning and scaling factors for each film. The methodology is validated using TLD's for out-of-field doses. Furthermore, two examples are provided using the technique to characterize small sized radiosurgery cones and compared with measurements made with a pinpoint chamber. RESULTS: Excellent agreement with TLD, planning systems and measurement was found. The superior resolution of the film technique was apparent. CONCLUSIONS: The authors have introduced a new technique allowing users to quantify very low doses in conjunction with commissioning measurements. The use of film also provides 2D information on beam characteristics in high resolution measurements.

Six degrees of freedom dynamic motion-including dose reconstruction in a commercial treatment planning system.

PURPOSE: Intrafractional motion during radiotherapy delivery can deteriorate the delivered dose. Dynamic rotational motion of up to 38 degrees has been reported during prostate cancer radiotherapy, but methods to determine the dosimetric consequences of such rotations are lacking. Here, we create and experimentally validate a dose reconstruction method that accounts for dynamic rotations and translations in a commercial treatment planning system (TPS). Interplay effects are quantified by comparing dose reconstructions with dynamic and constant rotations. METHODS: The dose reconstruction accumulates the dose in points of interest while the points are moved in six degrees of freedom (6DoF) in a precalculated time-resolved four-dimensional (4D) dose matrix to emulate dynamic motion in a patient. The required 4D dose matrix was generated by splitting the original treatment plan into multiple sub-beams, each representing 0.4 s dose delivery, and recalculating the dose of the split plan in the TPS (Eclipse). The dose accumulation was performed via TPS scripting by querying the dose of each sub-beam in dynamically moving points, allowing dose reconstruction with any dynamic motion. The dose reconstruction was validated with film dosimetry for two prostate dual arc VMAT plans with intra-prostatic lesion boosts. The plans were delivered to a pelvis phantom with internal dynamic rotational motion of a film stack (21 films with 2.5 mm separation). Each plan was delivered without motion and with three prostate motion traces. Motion-including dose reconstruction was performed for each motion experiment using the actual dynamic rotation as well as a constant rotation equal to the mean rotation during the experiment. For each experiment, the 3%/2 mm γ failure rate of the TPS dose reconstruction was calculated with the film measurement being the reference. For each motion experiment, the motion-induced 3%/2 mm γ failure rate was calculated using the static delivery as the reference and compared between film measurements and TPS dose reconstruction. DVH metrics for RT structures fully contained in the film volume were also compared between film and TPS. RESULTS: The mean γ failure rate of the TPS dose reconstructions when compared to film doses was 0.8% (two static experiments) and 1.7% (six dynamic experiments). The mean (range) of the motion-induced γ failure rate in film measurements was 35.4% (21.3-59.2%). The TPS dose reconstruction agreed with these experimental γ failure rates with root-mean-square errors of 2.1% (dynamic rotation dose reconstruction) and 17.1% (dose reconstruction assuming constant rotation). By DVH metrics, the mean (range) difference between dose reconstructions with dynamic and constant rotation was 4.3% (-0.3-10.6%) (urethra D 2 % ), -0.6% (-5.6%-2.5%) (urethra D 99 % ), 1.1% (-7.1-7.7%) (GTV D 2 % ), -1.4% (-17.4-7.1%) (GTV D 95 % ), -1.2% (-17.1-5.7%) (GTV D 99 % ), and -0.1% (-3.2-7.6%) (GTV mean dose). Dose reconstructions with dynamic motion revealed large interplay effects (cold and hot spots). CONCLUSIONS: A method to perform dose reconstructions for dynamic 6DoF motion in a TPS was developed and experimentally validated. It revealed large differences in dose distribution between dynamic and constant rotations not identifiable through dose reconstructions with constant rotation.

Dosimetric impact of intrafraction prostate rotation and accuracy of gating, multi-leaf collimator tracking and couch tracking to manage rotation: An end-to-end validation using volumetric film measurements.

BACKGROUND AND PURPOSE: Both gating and tracking can mitigate the deteriorating dosimetric impact of intrafraction translation during prostate stereotactic body radiotherapy (SBRT). However, their ability to manage intrafraction rotation has not yet been thoroughly investigated. The dosimetric accuracy of gating, MLC tracking and couch tracking to manage intrafraction prostate rotation was investigated. MATERIALS AND METHODS: Treatment plans for end-to-end tests of prostate SBRT with focal boosting were generated for a dynamic anthropomorphic pelvis phantom. The phantom applied internal lateral rotation (up to 25°) and coupled vertical and longitudinal translation of a radiochromic film stack that was used for dose measurements. Dose was delivered for each plan while the phantom applied motion according to three typical prostate motion traces without compensation (i), with gating (ii), with MLC tracking (iii) or with couch tracking (iv). Measured doses for the four motion compensation strategies were compared with the planned dose in terms of γ-index analysis, target coverage and organs at risk (OAR) sparing. RESULTS: Intrafraction rotation reduced the 3%(global)/2mm γ-index passing rate (γPR) for the prostate target volume by median (range) -33.2% (-68.6%, -4.1%) when no motion compensation was applied. The use of motion compensation improved the γPR by 13.2% (-0.4%, 32.9%) for gating, by 6.0% (-0.8%, 27.7%) for MLC tracking and by 11.1% (1.2%, 22.9%) for couch tracking. The three compensation techniques improved the target coverage in most cases. Gating showed better OAR sparing than MLC tracking or couch tracking. CONCLUSIONS: Compensation of intrafraction prostate rotation with gating, MLC tracking and couch tracking was investigated experimentally for the first time. All three techniques improved the dosimetric accuracy, but residual motion-related dose errors remained due to the lack of rotation correction.

Modulating ultrasound contrast generation from injectable nanodroplets for proton range verification by varying the degree of superheat.

PURPOSE: Despite the physical benefits of protons over conventional photon radiation in cancer treatment, range uncertainties impede the ability to harness the full potential of proton therapy. While monitoring the proton range in vivo could reduce the currently adopted safety margins, a routinely applicable range verification technique is still lacking. Recently, phase-change nanodroplets were proposed for proton range verification, demonstrating a reproducible relationship between the proton range and generated ultrasound contrast after radiation-induced vaporization at 25°C. In this study, previous findings are extended with proton irradiations at different temperatures, including the physiological temperature of 37°C, for a novel nanodroplet formulation. Moreover, the potential to modulate the linear energy transfer (LET) threshold for vaporization by varying the degree of superheat is investigated, where the aim is to demonstrate vaporization of nanodroplets directly by primary protons. METHODS: Perfluorobutane nanodroplets with a shell made of polyvinyl alcohol (PVA-PFB) or 10,12-pentacosadyinoic acid (PCDA-PFB) were dispersed in polyacrylamide hydrogels and irradiated with 62 MeV passively scattered protons at temperatures of 37°C and 50°C. Nanodroplet transition into echogenic microbubbles was assessed using ultrasound imaging (gray value and attenuation analysis) and optical images. The proton range was measured independently and compared to the generated contrast. RESULTS: Nanodroplet design proved crucial to ensure thermal stability, as PVA-shelled nanodroplets dramatically outperformed their PCDA-shelled counterpart. At body temperature, a uniform radiation response proximal to the Bragg peak is attributed to nuclear reaction products interacting with PVA-PFB nanodroplets, with the 50% drop in ultrasound contrast being 0.17 mm ± 0.20 mm (mean ± standard deviation) in front of the proton range. Also at 50°C, highly reproducible ultrasound contrast profiles were obtained with shifts of -0.74 mm ± 0.09 mm (gray value analysis), -0.86 mm ± 0.04 mm (attenuation analysis) and -0.64 mm ± 0.29 mm (optical analysis). Moreover, a strong contrast enhancement was observed near the Bragg peak, suggesting that nanodroplets were sensitive to primary protons. CONCLUSIONS: By varying the degree of superheat of the nanodroplets' core, one can modulate the intensity of the generated ultrasound contrast. Moreover, a submillimeter reproducible relationship between the ultrasound contrast and the proton range was obtained, either indirectly via the visualization of secondary reaction products or directly through the detection of primary protons, depending on the degree of superheat. The potential of PVA-PFB nanodroplets for in vivo proton range verification was confirmed by observing a reproducible radiation response at physiological temperature, and further studies aim to assess the nanodroplets' performance in a physiological environment. Ultimately, cost-effective online or offline ultrasound imaging of radiation-induced nanodroplet vaporization could facilitate the reduction of safety margins in treatment planning and enable adaptive proton therapy.

Overview of artificial intelligence-based applications in radiotherapy: Recommendations for implementation and quality assurance.

Artificial Intelligence (AI) is currently being introduced into different domains, including medicine. Specifically in radiation oncology, machine learning models allow automation and optimization of the workflow. A lack of knowledge and interpretation of these AI models can hold back wide-spread and full deployment into clinical practice. To facilitate the integration of AI models in the radiotherapy workflow, generally applicable recommendations on implementation and quality assurance (QA) of AI models are presented. For commonly used applications in radiotherapy such as auto-segmentation, automated treatment planning and synthetic computed tomography (sCT) the basic concepts are discussed in depth. Emphasis is put on the commissioning, implementation and case-specific and routine QA of AI models needed for a methodical introduction in clinical practice.

Radiotherapy Treatment plannINg study Guidelines (RATING): A framework for setting up and reporting on scientific treatment planning studies.

Radiotherapy treatment planning studies contribute significantly  to advances and improvements in radiation treatment of cancer patients. They are a pivotal step to support and facilitate the introduction of novel techniques into clinical practice, or as a first step before clinical trials can be carried out. There have been numerous examples published in the literature that demonstrated the feasibility of such techniques as IMRT, VMAT, IMPT, or that compared different treatment methods (e.g. non-coplanar vs coplanar treatment), or investigated planning approaches (e.g. automated planning). However, for a planning study to generate trustworthy new knowledge and give confidence in applying its findings, then its design, execution and reporting all need to meet high scientific standards. This paper provides a 'quality framework' of recommendations and guidelines that can contribute to the quality of planning studies and resulting publications. Throughout the text, questions are posed and, if applicable to a specific study and if met, they can be answered positively in the provided 'RATING' score sheet. A normalised weighted-sum score can then be calculated from the answers as a quality indicator. The score sheet can also be used to suggest how the quality might be improved, e.g. by focussing on questions with high weight, or by encouraging consideration of aspects given insufficient attention. Whilst the overall aim of this framework and scoring system is to improve the scientific quality of treatment planning studies and papers, it might also be used by reviewers and journal editors to help to evaluate scientific manuscripts reporting planning studies.

Machine learning applications in radiation oncology: Current use and needs to support clinical implementation.

BACKGROUND AND PURPOSE: The use of artificial intelligence (AI)/ machine learning (ML) applications in radiation oncology is emerging, however no clear guidelines on commissioning of ML-based applications exist. The purpose of this study was therefore to investigate the current use and needs to support implementation of ML-based applications in routine clinical practice. MATERIALS AND METHODS: A survey was conducted among medical physicists in radiation oncology, consisting of four parts: clinical applications (1), model training, acceptance and commissioning (2), quality assurance (QA) in clinical practice and General Data Protection Regulation (GDPR) (3), and need for education and guidelines (4). Survey answers of medical physicists of the same radiation oncology centre were treated as a separate unique responder in case reporting on different AI applications. RESULTS: In total, 213 medical physicists from 202 radiation oncology centres were included in the analysis. Sixty-nine percent (1 4 7) was using (37%) or preparing (32%) to use ML in clinic, mostly for contouring and treatment planning. In 86%, human observers were still involved in daily clinical use for quality check of the output of the ML algorithm. Knowledge on ethics, legislation and data sharing was limited and scattered among responders. Besides the need for (implementation) guidelines, training of medical physicists and larger databases containing multicentre data was found to be the top priority to accommodate the further introduction of ML in clinical practice. CONCLUSION: The results of this survey indicated the need for education and guidelines on the implementation and quality assurance of ML-based applications to benefit clinical introduction.

Extended field radiotherapy measurements in a single shot using a BaFBr-based OSL-film.

This work evaluated the use of a class solution specific calibration for an extra-large BaFBr-based optically stimulated luminescence film (OSL; 43 × 35 cm2; Z eff = 4.55). The clinical need for such large dosimeters follows from the increased use of extended-field radiation therapy (EFRT). E.g. for prostate cancer EFRT is currently used in the first prospective trial investigating the benefit of adding elective irradiation of the para-aortic lymph nodes in pN1 prostate cancer. The full extent of these EFRT dose distributions is not covered by the well-established standard sized radiochromic film or 2D detector arrays. Here we investigate an OSL calibration methodology, that tackles BaFBr-based OSL's inherent energy dependence by a class solution specific calibration. 10 EFRT treatment plans used in the PART trial were investigated. One plan was used to build a class solution specific bilinear calibration model, that distinguishes between in-field and penumbra dose contributions. The effect of this calibration was evaluated with respect to a standard linear calibration, using standard IMRT patterns, the nine remaining patient plans, and to smaller prostate treatment plans. A single OSL-dosimeter could be reused for all measurements. The dosimeter captured the full extent of the dose distributions (maximum EFRT field size = 33.5 cm). The bilinear correction reduced the residual dose differences from above 10% to an average of 0.7% (max 3.6%) in comparison with a Monte Carlo simulation. Consequently global gamma agreement scores (3%-3 mm) of 95.5% ± 2.7% were reached. A more strict local evaluation resulted in an average gamma-agreement score of 93.3% ± 3.2%. The BaFBr-based OSL film, with reduced Z eff requires a class-solution specific correction. The current work shows that such a correction can be as simple as a bilinear residual dose correction driven by the measured signal. As far as we know this is the first 2D dosimeter combining reusability, a sub-mm resolution, and a size covering the typical EFRT treatment plans.

Validation and IMRT/VMAT delivery quality of a preconfigured fast-rotating O-ring linac system.

PURPOSE: A fast-rotating O-ring dedicated intensity modulated radiotherapy (IMRT)/volumetric modulated arc therapy (VMAT) delivery system, the Halcyon, is delivered by default with a fully preconfigured photon beam model in the treatment planning system (TPS). This work reports on the validation and achieved IMRT/VMAT delivery quality on the system. METHODS: Acceptance testing followed the vendor's installation product acceptance and was supplemented with mechanical QA. The dosimetric calibration was performed according to the IAEA TRS-398 code-of-practice, delivering 600 cGy/min at 10 cm depth, a 90 cm source-surface distance, and a 10 × 10 cm² field size. The output factors, multileaf collimator (MLC) transmission and dosimetric leaf gap (DLG) were validated by comparing measurements with the modeled values in the TPS. Validation of IMRT/VMAT was conducted following AAPM reports (MPPG 5.a, TG-119). Next, dose measurements were performed for end-to-end (E2E) checks in heterogeneous anthropomorphic phantoms using radiochromic film in multiple planes and using ionization chambers (IC) point measurements. E2E checks were performed for VMAT (cranial, rectum, spine, and head and neck) and IMRT (lung). Additionally, IROC Houston mailed dosimetry audits were performed for the beam calibration and E2E measurements using a thorax phantom (IMRT) and a head and neck phantom (VMAT). Lastly, extensive patient-specific QA was performed for the first patients of each new indication, 26 in total (nrectum = 2, nspine = 5, nlung = 5, nesophagus = 2, nhead and neck = 7, ncranial = 5), treated on the fast-rotating O-ring linac. The patient-specific QA followed the AAPM TG-218 guidelines and comprised of portal dosimetry, ArcCHECK diode array, radiochromic film dosimetry in a MultiCube phantom, and IC point measurements. RESULTS: The measured output factors showed an agreement <1% for fields ≥3 × 3 cm². Field sizes ≤2 × 2 cm² had a difference of <2%. The measured single-layer MLC transmission was 0.42 ± 0.01% and the measured DLG was 0.27 ± 0.22 mm. The AAPM MPPG 5.a measurements were fully compliant with the guideline criteria. Dose differences larger than 2% were found for the PDD at large depths (>25 cm). TG-119's confidence limits were achieved for the VMAT point dose measurements and for both the IMRT and VMAT radiochromic film measurements. The TG-119 confidence limits were not achieved for IMRT point dose measurements in both the target (5.9%) and the avoidance structure (6.4%). All E2E tests had point differences below 2.3% and gamma agreement scores above 90.6%. The IROC beam calibration audit showed agreement of <1%. The IROC lung IMRT audit and head and neck VMAT audit had results compliant with the IROC Houston's credentialing criteria. All IMRT and VMAT plans selected for patient-specific QA were within the action limits suggested by TG-218. CONCLUSIONS: The fast-rotating O-ring linac and its preconfigured TPS are compliant with the international commissioning criteria of AAPM MPPG 5.a and AAPM TG-119. E2E measurements on heterogeneous anthropomorphic phantoms were within clinically acceptable tolerances. IROC Houston's audits satisfied the credentialing criteria. This work comprises the first extensive dataset reporting on the preconfigured fast-rotating O-ring linac.

Volumetric modulated arc therapy of head-and-neck cancer on a fast-rotating O-ring linac: Plan quality and delivery time comparison with a C-arm linac.

BACKGROUND AND PURPOSE: Linac improvements in gantry speed, leaf speed and dose rate may increase the time-efficiency of volumetric modulated arc therapy (VMAT) delivery. The plan quality achievable with faster VMAT however remains to be investigated. In this study, a fast-rotating O-ring linac with fast-moving leaves is compared with a C-arm linac in terms of plan quality and delivery time for VMAT of head-and-neck cancer (HNC). MATERIAL AND METHODS: For 30 patients with HNC, treatment planning was performed using dual-arc (HA2) and triple-arc (HA3) VMAT on a Halcyon fast-rotating O-ring linac and using dual-arc VMAT on a TrueBeam C-arm linac (TB2). Target coverage metrics and complication probabilities were compared. Plan delivery was verified using 3%/3 mm gamma-index analysis of helical diode array measurements. Volumetric image acquisition and plan delivery times were compared. RESULTS: All studied VMAT-techniques fulfilled the target coverage objectives. D2% to the boost volume was higher for HA2 (median 103.7%, 1st-3rd quartile [103.5%;104.0%]) and HA3 (103.2% [103.0%;103.7%)] than for TB2 (102.6% [102.3%;103.0%)], resulting in an increased boost target dose heterogeneity for HA2 and HA3. Complication probabilities were comparable between HA2 and TB2, while HA3 showed a xerostomia probability reduction (0.8% [0.2%;1.8%]) and dysphagia probability reduction (1.0% [0.2%;1.8%]) compared with TB2. Gamma-index agreement scores were never below 93.0% for HA2, HA3 and TB2. Volumetric imaging and plan delivery time was shorter for HA2 (1 m 24 s ±â€¯1 s) and HA3 (1 m 54 s ±â€¯1 s) than for TB2 (2 m 47 s ±â€¯1 s). CONCLUSION: For VMAT of HNC, the fast-rotating O-ring linac at least maintains the plan quality of two arcs on a C-arm linac while reducing the image acquisition and plan delivery time.

Characterization of a novel liquid fiducial marker for multimodal image guidance in stereotactic body radiotherapy of prostate cancer.

PURPOSE: Liquid fiducial markers have shown to be a promising alternative to solid gold markers in terms of imaging artifact reduction, patient comfort, and compatibility with different imaging modalities. This study aims to investigate the performance of the novel BioXmark® liquid marker for state-of-the-art multimodal imaging used in prostate cancer (PCa) radiotherapy, encompassing kV CT/CBCT, multiparametric MRI, and kV x-ray imaging. In addition, automatic detection of the liquid markers in x-ray imaging for prostate motion monitoring during treatment was investigated. METHODS: A total of eight BioXmark® liquid markers with varying volumes (range 5-300 µL) were casted on a square grid into a gelatin phantom insert. A cylindrical gold marker (QLRAD, length = 7 mm, Ø = 1 mm) was inserted for reference. Liquid marker visibility and streaking artifacts in CT/CBCT imaging were evaluated by placing the gelatin phantom into a CIRS anthropomorphic phantom. Relevant MRI characteristics such as the T2 and T1 relaxation times, the ADC value, and the relative proton density (ρH) were quantified by placing the gelatin phantom insert next to a T1MES mapping phantom and a water-filled syringe for reference. Ex vivo multiparametric MRI images were acquired by placing the gelatin phantom next to a resected prostate specimen. Anterior-posterior x-ray projection images were obtained by placing the gelatin phantom insert on top of an anthropomorphic pelvic phantom with internal pelvic bony structures and were acquired for five positions relative to the bony anatomy and 24 clinically relevant x-ray exposure settings. To quantify individual automatic marker detection, single markers were artificially isolated in the x-ray images using postprocessing. RESULTS: Markers of all sizes were clearly visible on CT and CBCT images with only the largest marker volumes (100-300 µL) displaying artifacts similar in size to the gold fiducial marker. Artifact size increased with increasing liquid marker volume. Liquid markers displayed good contrast in ex vivo T1-weighted and ρH-weighted images. The markers were not visible in the ex vivo T2-weighted image. The liquid markers induced a chemical shift artifact in the obtained ADC-map. Automated detection in x-ray imaging was feasible with high detection success (four of five positions) for marker volumes in the range of 25-200 µL. None of the liquid markers were detected successfully when superimposed on a bony edge, independent of their size. CONCLUSIONS: This study is the first to show the compatibility of BioXmark® liquid markers with multimodal image-guided radiotherapy for PCa. Compared to a solid gold marker, they had favorable results in both visibility and induced imaging artifacts. Liquid marker visibility in MRI imaging of the prostate does not solely depend on the low ρH value (not visible on T2-weighted image) but is also influenced by its relaxation times. Automated marker detection in x-ray images was feasible but better adapted marker detection algorithms are necessary for marker localization in the presence of bony edges. Hence, the liquid marker provides a minimally invasive (fine needles) and highly applicable alternative to current solid gold markers for multimodal image-guided prostate radiotherapy treatments.

Patient-specific bolus for range shifter air gap reduction in intensity-modulated proton therapy of head-and-neck cancer studied with Monte Carlo based plan optimization.

BACKGROUND & PURPOSE: Intensity-modulated proton therapy (IMPT) of superficial lesions requires pre-absorbing range shifter (RS) to deliver the more shallow spots. RS air gap minimization is important to avoid spot size degradation, but remains challenging in complex geometries such as in head-and-neck cancer (HNC). In this study, clinical endpoints were investigated for patient-specific bolus and for conventional RS solutions, making use of a Monte Carlo (MC) dose engine for IMPT optimization. METHODS AND MATERIALS: For 5 oropharyngeal cancer patients, IMPT spot maps were generated using beamlets calculated with MC. The plans were optimized for three different RS configurations: 3D printed on-skin bolus, snout- and nozzle-mounted RS. Organ-at-risk (OAR) doses and late toxicity probabilities were compared between all configuration-specific optimized plans. RESULTS: The use of bolus reduced the mean dose to all OARs compared to snout and nozzle-mounted RS. The contralateral parotid gland and supraglottic larynx received on average 2.9Gy and 4.2Gy less dose compared to the snout RS. Bolus reduced the average probability for xerostomia by 3.0%. For dysphagia, bolus reduced the probability by 2.7%. CONCLUSIONS: Quantification of the dosimetric advantage of patient-specific bolus shows significant reductions compared to conventional RS solutions for xerostomia and dysphagia probability. These results motivate the development of a patient-specific bolus solution in IMPT for HNC.

Benefits of Elective Para-Aortic Radiotherapy for pN1 Prostate Cancer Using Arc Therapy (Intensity-Modulated or Volumetric Modulated Arc Therapy): Protocol for a Nonrandomized Phase II Trial.

BACKGROUND: In patients with prostate cancer (PCa) with histopathologically proven pelvic lymph node (LN) metastasis (pN1) after extended pelvic lymph node dissection (ePLND), multimodality treatment consisting of treatment of the primary tumor and whole pelvic radiotherapy (WPRT) combined with androgen deprivation therapy (ADT) offers promising results, leading to better cause-specific survival rates compared with ADT alone. However, in case more than one pelvic LN is invaded by the tumor, approximately 40% of the patients relapse biochemically and clinically. Clinical relapse is present in the para-aortic LNs (M1a disease) in up to 77% of the relapsing cases. OBJECTIVE: We hypothesize that, based on the evidence that positive LNs represent the door to hematogenous dissemination, elective para-aortic irradiation will reduce the development of both retroperitoneal nodal (M1a) and distant metastasis (M1b or M1c disease), postpone the need for palliative ADT, and prolong the time to castration-refractory disease. METHODS: To test this hypothesis, we will conduct a prospective, nonrandomized phase II trial to study the efficacy of additional elective para-aortic radiotherapy (PART) in pN1 patients compared with those who were historically treated with adjuvant WPRT alone. We aim to include 137 patients with PCa and presence of pN1 disease after ePLND. With this number of patients, an improvement of 15% in the 5-year clinical relapse-free survival can be detected with a power of 80%. RESULTS: Recruitment of patients for this trial started in 2017 and will be completed approximately by March 2020. CONCLUSIONS: This is the first phase II trial to investigate the benefits of an elective PART in patients with PCa. The results of this trial will potentially serve as a sound base for a later randomized phase III trial. All participants are given a PART information sheet and required to give written informed consent. Results are expected to be published in a peer-reviewed journal. TRIAL REGISTRATION: ClinicalTrials.gov NCT03079323; https://clinicaltrials.gov/ct2/show/NCT03079323 (Archived by WebCite at http://www.webcitation.org/73ELimv1d). INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/11256.

Regional variability in radiation-induced lung damage can be predicted by baseline CT numbers.

BACKGROUND AND PURPOSE: Lung volumes are functionally heterogeneous but typically considered uniformly during radiotherapy planning. The present study aims to predict regional differences in radiation-induced lung damage based on pre-treatment CT information. MATERIALS AND METHODS: For 42 lung cancer patients (including 15 from an external validation set), two 200cc lung subvolumes (low-density (LD) and high-density (HD)) were auto-segmented in the ipsilateral lung of the planning CT0. After non-rigid registration of 3month follow-up CT scans, sigmoidal dose-density change (ΔHU=HU3M-HU0) response curves were determined for all subvolumes. Predictive factors for the sigmoidal response parameters D50 and saturation level ΔHUmax were analyzed. RESULTS: The baseline density difference between LD (mostly in the upper lobe) and HD (mostly in the lower lobe) was on average 102HU. The saturation level ΔHUmax,LD was significantly smaller than ΔHUmax,HD (p=0.03). Expressed as mass density increase relative to the baseline density, saturation levels were 20.7% on average irrespective of baseline density, and they could be predicted in LD and HD subvolumes (AUC=0.70-0.78). Intra-lung differences in D50 were significantly smaller than inter-patient differences. CONCLUSIONS: Limited amount of damage was observed in LD subvolumes, while the relative density increase of all subvolumes was well predictable. This could allow dose redistribution preferentially targeting low-density lung regions.