"Scan-(pre)Plan-Treat" Workflow for Bone Metastases Using the Ethos Therapy System: A Single-Center, In Silico Experience.

Purpose: To report on the accuracy of automated delineation, treatment plan quality, and duration of an in-silico "scan-(pre)plan-treat" (SPT) workflow for vertebral bone metastases using a 1 × 8 Gy regimen. Method and Materials: The cloud-based emulator system of the Ethos therapy system was used to adapt an organ-at-risk-sparing preplan created on the diagnostic CT to the anatomy-of-the-day using the cone beam CT made before treatment. Results: SPT using the Ethos emulator system resulted in relatively good coverage of the PTV and acceptable dose to the OAR. Delivery time and plan homogeneity was the best for 7-field IMRT plan template. Conclusions: A SPT workflow formula results in a highly conformal treatment delivery while maintaining an acceptable timeframe for the patient on the treatment couch.

From once-weekly to semi-weekly whole prostate gland stereotactic radiotherapy with focal boosting: Primary endpoint analysis of the multicenter phase II hypo-FLAME 2.0 trial.

BACKGROUND AND PURPOSE: The hypo-FLAME trial showed that once-weekly (QW) focal boosted prostate stereotactic body radiotherapy (SBRT) is associated with acceptable acute genitourinary (GU) and gastrointestinal (GI) toxicity. Currently, we investigated the safety of reducing the overall treatment time (OTT) of focal boosted prostate SBRT from 29 to 15 days. MATERIAL AND METHODS: Patients with intermediate- and high-risk prostate cancer were treated with SBRT delivering 35 Gy in 5 fractions to the whole prostate gland with an iso-toxic boost up to 50 Gy to the intraprostatic lesion(s) in a semi-weekly (BIW) schedule. The primary endpoint was radiation-induced acute toxicity (CTCAE v5.0). Changes in quality of life (QoL) were examined in terms of proportions achieving a minimal clinically important change (MCIC). Finally, acute toxicity and QoL scores of the BIW schedule were compared with the results of the prior QW hypo-FLAME schedule (n = 100). RESULTS: Between August 2020 and February 2022, 124 patients were enrolled and treated BIW. No grade ≥3 GU or GI toxicity was observed. The 90-days cumulative incidence of grade 2 GU and GI toxicity rates were 47.5% and 7.4%, respectively. Patients treated QW scored significant less grade 2 GU toxicity (34.0%, p = 0.01). No significant differences in acute GI toxicity were observed. Furthermore, patients treated QW had a superior acute bowel and urinary QoL. CONCLUSION: Semi-weekly prostate SBRT with iso-toxic focal boosting is associated with acceptable acute GU and GI toxicity. Based on the comparison between the QW and BIW schedule, patients should be counselled regarding the short-term advantages of a more protracted schedule. Registration number ClinicalTrials.gov: NCT04045717.

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 ${t}_{ir}$ .

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.

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.

68Ga-PSMA-11 PET, 18F-PSMA-1007 PET, and MRI for Gross Tumor Volume Delineation in Primary Prostate Cancer: Intermodality and Intertracer Variability.

PURPOSE: To assess the intermodality and intertracer variability of gallium-68 (68Ga)- or fluorine-18 (18F)-labeled prostate-specific membrane antigen (PSMA) positron emission tomography (PET) and biparametric magnetic resonance imaging (bpMRI)-based gross tumor volume (GTV) delineation for focal boosting in primary prostate cancer. METHODS: Nineteen prospectively enrolled patients with prostate cancer underwent a PSMA PET/MRI scan, divided into a 1:1 ratio between 68Ga-PSMA-11 and 18F-PSMA-1007, before radical prostatectomy (IWT140193). Four delineation teams performed manual contouring of the GTV based on bpMRI and PSMA PET imaging, separately. Index lesion coverage (overlap%) and interobserver variability were assessed. Furthermore, the distribution of the voxelwise normalized standardized uptake values (SUV%) was determined for the majority-voted (>50%) GTV (GTVmajority) and whole prostate gland to investigate intertracer variability. The median patientwise SUV% contrast ratio (SUV%-CR, calculated as median GTVmajority SUV% / median prostate gland without GTVmajority SUV%) was calculated according to the tracer used. RESULTS: A significant difference in overlap% favoring PSMA PET compared with bpMRI was found in the 18F subgroup (median, 63.0% vs 53.1%; P = .004) but was not present in the 68Ga subgroup (32.5% vs 50.6%; P = .100). Regarding interobserver variability, measured Sørensen-Dice coefficients (0.58 vs 0.72) and calculated mean distances to agreement (2.44 mm vs 1.22 mm) were statistically significantly lower and higher, respectively, for the 18F cohort compared with the 68Ga cohort. For the bpMRI-based delineations, the median Sørensen-Dice coefficient and mean distance to agreement were 0.63 and 1.76 mm, respectively. Median patientwise SUV%-CRs of 1.8 (interquartile range [IQR], 1.6-2.7) for 18F-PSMA and 3.3 (IQR, 2.7-5.9) for 68Ga-PSMA PET images were found. CONCLUSIONS: Both MRI and PSMA PET provided consistent intraprostatic GTV lesion detection. However, the PSMA tracer seems to have a major influence on the contour characteristics, owing to an apparent difference in SUV% distribution in the prostate gland.

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.

Optimal 68Ga-PSMA and 18F-PSMA PET window levelling for gross tumour volume delineation in primary prostate cancer.

PURPOSE: This study proposes optimal tracer-specific threshold-based window levels for PSMA PET-based intraprostatic gross tumour volume (GTV) contouring to reduce interobserver delineation variability. METHODS: Nine 68Ga-PSMA-11 and nine 18F-PSMA-1007 PET scans including GTV delineations of four expert teams (GTVmanual) and a majority-voted GTV (GTVmajority) were assessed with respect to a registered histopathological GTV (GTVhisto) as the gold standard reference. The standard uptake values (SUVs) per voxel were converted to a percentage (SUV%) relative to the SUVmax. The statistically optimised SUV% threshold (SOST) was defined as those that maximises accuracy for threshold-based contouring. A leave-one-out cross-validation receiver operating characteristic (ROC) curve analysis was performed to determine the SOST for each tracer. The SOST analysis was performed twice, first using the GTVhisto contour as training structure (GTVSOST-H) and second using the GTVmajority contour as training structure (GTVSOST-MA) to correct for any limited misregistration. The accuracy of both GTVSOST-H and GTVSOST-MA was calculated relative to GTVhisto in the 'leave-one-out' patient of each fold and compared with the accuracy of GTVmanual. RESULTS: ROC curve analysis for 68Ga-PSMA-11 PET revealed a median threshold of 25 SUV% (range, 22-27 SUV%) and 41 SUV% (40-43 SUV%) for GTVSOST-H and GTVSOST-MA, respectively. For 18F-PSMA-1007 PET, a median threshold of 42 SUV% (39-45 SUV%) for GTVSOST-H and 44 SUV% (42-45 SUV%) for GTVSOST-MA was found. A significant pairwise difference was observed when comparing the accuracy of the GTVSOST-H contours with the median accuracy of the GTVmanual contours (median, - 2.5%; IQR, - 26.5-0.2%; p = 0.020), whereas no significant pairwise difference was found for the GTVSOST-MA contours (median, - 0.3%; IQR, - 4.4-0.6%; p = 0.199). CONCLUSIONS: Threshold-based contouring using GTVmajority-trained SOSTs achieves an accuracy comparable with manual contours in delineating GTVhisto. The median SOSTs of 41 SUV% for 68Ga-PSMA-11 PET and 44 SUV% for 18F-PSMA-1007 PET form a base for tracer-specific window levelling. TRIAL REGISTRATION: Clinicaltrials.gov ; NCT03327675; 31-10-2017.

The use of tumour markers in oesophageal cancer to quantify setup errors and baseline shifts during treatment.

PURPOSE: To prospectively evaluate the feasibility of solid gold marker placement in oesophageal cancer patients and to quantify inter-fractional and intra-fractional (baseline shift) marker motion during radiation treatment. Radiotherapy target margins and matching strategies were investigated. MATERIALS/METHODS: Thirty-four markers were implanted by echo-endoscopy in 10 patients. Patients received a planning 4D CT, daily pre-treatment cone-beam CT (CBCT) and a post-treatment CBCT for at least five fractions. For fractions with both pre- and post-treatment CBCT, marker displacement between planning CT and pre-treatment CBCT (inter-fractional) and between pre-treatment and post-treatment CBCT (intra-fractional; only for fractions without rotational treatment couch correction) were calculated in left-right (LR), cranio-caudal (CC) and anterior-posterior (AP) direction after bony-anatomy and soft-tissue matching. Systematic/random setup errors were estimated; treatment margins were calculated. RESULTS: No serious adverse events occurred. Twenty-three (67.6%) markers were visible during radiotherapy (n = 3 middle oesophagus, n = 16 distal oesophagus, n = 4 proximal stomach). Margins for inter-fractional displacement after bony-anatomy match depended on the localisation of the primary tumour and were 11.2 mm (LR), 16.4 mm (CC) and 8.2 mm (AP) for distal markers. Soft-tissue matching reduced the CC margin for these markers (16.4 mm to 10.5 mm). The mean intra-fractional shift of 12 distal markers was 0.4 mm (LR), 2.3 mm (CC) and 0.7 mm (AP). Inclusion of this shift resulted in treatment margins for distal markers of 12.8 mm (LR), 17.3 mm (CC) and 10.4 mm (AP) after bony-anatomy matching and 12.4 mm (LR), 11.4 mm (CC) and 9.7 mm (AP) after soft-tissue matching. CONCLUSION: This study demonstrated that the implantation of gold markers was safe, albeit less stable compared to other marker types. Inter-fractional motion was largest cranio-caudally for markers in the distal oesophagus, which was reduced after soft-tissue compared to bony-anatomy matching. The impact of intra-fractional baseline shifts on margin calculation was rather small.

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.

Knowledge-Based Assessment of Focal Dose Escalation Treatment Plans in Prostate Cancer.

PURPOSE: In a randomized focal dose escalation radiation therapy trial for prostate cancer (FLAME), up to 95 Gy was prescribed to the tumor in the dose-escalated arm, with 77 Gy to the entire prostate in both arms. As dose constraints to organs at risk had priority over dose escalation and suboptimal planning could occur, we investigated how well the dose to the tumor was boosted. We developed an anatomy-based prediction model to identify plans with suboptimal tumor dose and performed replanning to validate our model. METHODS AND MATERIALS: We derived dose-volume parameters from planned dose distributions of 539 FLAME trial patients in 4 institutions and compared them between both arms. In the dose-escalated arm, we determined overlap volume histograms and derived features representing patient anatomy. We predicted tumor D98% with a linear regression on anatomic features and performed replanning on 21 plans. RESULTS: In the dose-escalated arm, the median tumor D50% and D98% were 93.0 and 84.7 Gy, and 99% of the tumors had a dose escalation greater than 82.4 Gy (107% of 77 Gy). In both arms organs at risk constraints were met. Five out of 73 anatomic features were found to be predictive for tumor D98%. Median predicted tumor D98% was 4.4 Gy higher than planned D98%. Upon replanning, median tumor D98% increased by 3.0 Gy. A strong correlation between predicted increase in D98% and realized increase upon replanning was found (ρ = 0.86). CONCLUSIONS: Focal dose escalation in prostate cancer was feasible with a dose escalation to 99% of the tumors. Replanning resulted in an increased tumor dose that correlated well with the prediction model. The model was able to identify tumors on which a higher boost dose could be planned. The model has potential as a quality assessment tool in focal dose escalated treatment plans.

Primary endpoint analysis of the multicentre phase II hypo-FLAME trial for intermediate and high risk prostate cancer.

BACKGROUND AND PURPOSE: Local recurrences after radiotherapy for prostate cancer (PCa) often originate at the location of the macroscopic tumour(s). Since PCa cells are known to be sensitive to high fraction doses, hypofractionated whole gland stereotactic body radiotherapy (SBRT) in conjunction with a simultaneous ablative microboost to the macroscopic tumour(s) within the prostate could be a way to reduce the risk of local failure. We investigated the safety of this treatment strategy. MATERIALS AND METHODS: Patients with intermediate or high risk PCa were enrolled in a prospective phase II trial, called hypo-FLAME. All patients were treated with extreme hypofractionated doses of 35 Gy in 5 weekly fractions to the whole prostate gland with an integrated boost up to 50 Gy to the multiparametric (mp) MRI-defined tumour(s). Treatment-related toxicity was measured using the CTCAE v4.0. The primary endpoint of the trial was treatment-related acute toxicity. RESULTS: Between April 2016 and December 2018, 100 men were treated in 4 academic centres. All patients were followed up for a minimum of 6 months. The median mean dose delivered to the visible tumour nodule(s) on mpMRI was 44.7 Gy in this trial. No grade ≥3 acute genitourinary (GU) or gastrointestinal (GI) toxicity was observed. Furthermore, 90 days after start of treatment, the cumulative acute grade 2 GU and GI toxicity rates were 34.0% and 5.0%, respectively. CONCLUSION: Simultaneous focal boosting to the macroscopic tumour(s) in addition to whole gland prostate SBRT is associated with acceptable acute GU and GI toxicity.

Stereotactic body radiation therapy with optional focal lesion ablative microboost in prostate cancer: Topical review and multicenter consensus.

Stereotactic body radiotherapy (SBRT) for prostate cancer (PCa) is gaining interest by the recent publication of the first phase III trials on prostate SBRT and the promising results of many other phase II trials. Before long term results became available, the major concern for implementing SBRT in PCa in daily clinical practice was the potential risk of late genitourinary (GU) and gastrointestinal (GI) toxicity. A number of recently published trials, including late outcome and toxicity data, contributed to the growing evidence for implementation of SBRT for PCa in daily clinical practice. However, there exists substantial variability in delivering SBRT for PCa. The aim of this topical review is to present a number of prospective trials and retrospective analyses of SBRT in the treatment of PCa. We focus on the treatment strategies and techniques used in these trials. In addition, recent literature on a simultaneous integrated boost to the tumor lesion, which could create an additional value in the SBRT treatment of PCa, was described. Furthermore, we discuss the multicenter consensus of the FLAME consortium on SBRT for PCa with a focal boost to the macroscopic intraprostatic tumor nodule(s).

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.