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Purpose: A new system for software-controlled, highly automated correction of intrafraction prostate motion,' intrafraction stereographic targeting' (iSGT), is described and evaluated. Methods: At our institute, daily prostate positioning is routinely performed at the start of treatment beam using stereographic targeting (SGT). iSGT was implemented by extension of the SGT software to facilitate fast and accurate intrafraction motion corrections with minimal user interaction. iSGT entails megavoltage (MV) image acquisitions with the first segment of selected IMRT beams, automatic registration of implanted markers, followed by remote couch repositioning to correct for intrafraction motion above a predefined threshold, prior to delivery of the remaining segments. For a group of 120 patients, iSGT with corrections for two nearly lateral beams was evaluated in terms of workload and impact on effective intrafraction displacements in the sagittal plane. Results: SDs of systematic (Σ) and random (σ) displacements relative to the planning CT measured directly after initial SGT setup correction were <0.5 and <0.8 mm, respectively. Without iSGT corrections, effective Σ and σ for the 11-min treatments would increase to Σeff < 1.1 mm and σeff < 1.2 mm. With the iSGT procedure with an action level of 4 mm, effective positioning errors were reduced to Σeff < 0.8 mm and σeff < 1.0 mm, with 23.1% of all fractions requiring a correction. Computer simulations demonstrated that with an action level of 2 mm, the errors would have been reduced to Σeff < 0.6 mm and σeff < 0.7 mm, requiring corrections in 82.4% of the fractions. Because iSGT is highly automated, the extra time added by iSGT is <30 s if a correction is required. Conclusions: Without increasing imaging dose, iSGT successfully reduces intrafraction prostate motion with minimal workload and increase in fraction time. An action level of 2 mm is recommended. [ABSTRACT FROM AUTHOR]

A high dosimetric accuracy is required for radiotherapy treatments where IMRT in combination with narrow treatment margins is applied to achieve optimally conformal dose distributions. In order to routinely verify the in vivo fluence delivery (i.e., during the actual patient treatment), our method for predicting portal dose images with a patient in the beam was validated. A unique feature of this method is that it is fully based on calibration measurements with an EPID. The portal dose image (PDI) behind a patient is dependent on the transmission of primary radiation through the patient and a contribution of scattered radiation from the patient. To derive both components, the patient geometry as observed in the planning CT scan is converted into an equivalent homogeneous phantom. A limited set of EPID measurements is required to derive the input parameters of this model. The accuracy of the in vivo PDI prediction was verified using measurements behind phantoms and four prostate cancer patients treated with IMRT. Behind homogeneous slab phantoms, the local differences between measured and predicted PDIs were within 2% inside the field, while behind a lung and a pelvic phantom, the agreement was within 3% or within 3 mm in regions with steep gradients. Outside the fields, the PDIs agreed within 2% of the global dose maximum. Evaluation of the in vivo PDI measurements behind patients showed that, on average, 87% of the pixels inside the field fulfilled the 3% local dose and 3 mm distance-to-agreement criteria. For half of the failing pixels the differences occurred due to changes in patient geometry with respect to the planning CT or due to beam attenuation by the treatment couch that was not accounted for. A fully EPID-based method for predicting portal dose images using the planning CT scan has been implemented and validated for phantoms and clinical patients. [ABSTRACT FROM AUTHOR]

Purpose: A fully automated, fast, on-line prostate repositioning scheme using implanted markers, kilovoltage/megavoltage imaging, and remote couch movements has been developed and clinically applied. The initial clinical results of this stereographic targeting (SGT) method, as well as phantom evaluations, are presented. Methods and Materials: Using the SGT method, portal megavoltage images are acquired with the first two to six monitor units of a treatment beam, immediately followed by acquisition of an orthogonal kilovoltage image without gantry motion. The image pair is automatically analyzed to obtain the marker positions and three-dimensional prostate displacement and rotation. Remote control couch shifts are applied to correct for the displacement. The SGT performance was measured using both phantom images and images from 10 prostate cancer patients treated using SGT. Results: With phantom measurements, the accuracy of SGT was 0.5, 0.2, and 0.3 mm (standard deviation [SD]) for the left–right, craniocaudal, and anteroposterior directions, respectively, for translations and 0.5° (SD) for the rotations around all axes. Clinically, the success rate for automatic marker detection was 99.5%, and the accuracy was 0.3, 0.5 and 0.8 mm (SD) in the left–right, craniocaudal, and anteroposterior axes. The SDs of the systematic center-of-mass positioning errors (Σ) were reduced from 4.0 mm to <0.5 mm for all axes. The corresponding SD of the random (σ) errors was reduced from 3.0 to <0.8 mm. These small residual errors were achieved with a treatment time extension of <1 min. Conclusion: Stereographic targeting yields systematic and random prostate positioning errors of <1 mm with <1 min of added treatment time. [Copyright &y& Elsevier]

Purpose: To evaluate the efficacy of the No Action Level (NAL) off-line correction protocol in the reduction of systematic prostate displacements as determined from electronic portal images (EPI) using implanted markers. Methods and Materials: Four platinum markers, two near the apex and two near the base of the prostate, were implanted for localization purposes in patients who received fractionated high dose rate brachytherapy. During the following course of 25 fractions of external beam radiotherapy, the position of each marker relative to the corresponding position in digitally reconstructed radiographs (DRRs) was measured in EPI in 15 patients for on average 17 fractions per patient. These marker positions yield the composite displacements due to both setup error and internal prostate motion, relative to the planning computed tomography scan. As the NAL protocol is highly effective in reducing systematic errors (recurring each fraction) due to setup inaccuracy alone, we investigated its efficacy in reducing systematic composite displacements. The analysis was performed for the center of mass (COM) of the four markers, as well as for the cranial and caudal markers separately. Furthermore, the impact of prostate rotation on the achieved positioning accuracy was determined. Results: In case of no setup corrections, the standard deviations of the systematic composite displacements of the COM were 3-4 mm in the craniocaudal and anterior-posterior directions, and 2 mm in the left-right direction. The corresponding SDs of the random displacements (interfraction fluctuations) were 2-3 mm in each direction. When applying a NAL protocol based on three initial treatment fractions, the SDs of the systematic COM displacements were reduced to 1-2 mm. Displacements at the cranial end of the prostate were slightly larger than at the caudal end, and quantitative analysis showed this originates from left-right axis rotations about the prostate apex. Further analysis revealed that significant time trends are present in these prostate rotations. No significant trends were observed for the prostate translations. Conclusions: The NAL protocol based on marker positions in EPI halved the composite systematic displacements using only three imaged fractions per patient, and thus allowed for a significant reduction of planning margins. Although large rotations of the prostate, and time trends therein, were observed, the net impact on the measured displacements and on the accuracy obtained with NAL was small. [ABSTRACT FROM AUTHOR]

Purpose: In a recent study, large systematic setup errors were detected in patients with lung cancer when a conventional simulation procedure was used to define and mark the treatment isocenter. In the present study, we describe a procedure to omit the session at a conventional simulator to remove simulation errors entirely. Isocenter definition and verification was performed at a computed tomography (CT) simulator, and digitally reconstructed radiographs (DRRs) were used for setup verification and correction at the treatment unit.Methods and Materials: A CT simulation protocol was developed, in which radiopaque markers were used to verify the coincidence of the isocenter marked on the patients’ skin with the isocenter defined in the planning CT scan. This protocol was evaluated for 20 patients. Subsequently, electronic portal images were acquired at the treatment unit. The three-dimensional setup error was established from a template match of the appropriate anatomy visible in two orthogonal beams with the corresponding anatomy in DRRs. An offline setup correction protocol was applied to reduce systematic setup errors.Results: For all patients, the skin marks defined the planning CT scan isocenter to within ± 1.5 mm in each of the three main directions. Random setup errors at the treatment unit were 1.8, 2.0, and 1.9 mm (1 SD) for the lateral (x), the superior-inferior (y), and the anterior-posterior (z) directions, respectively. With the use of the correction protocol, the systematic errors for x, y, and z were 1.5, 1.5, and 1.3 mm (1 SD).Conclusions: Because the distributions of treatment setup errors measured against DRRs obtained in our CT simulation were equal to previously obtained distributions measured against simulator films, conventional simulation can be omitted and DRRs are well-suited for setup verification. By adopting our CT simulation procedure, the large systematic simulation setup errors, which remain hidden if a conventional simulation is performed, can be avoided. [Copyright &y& Elsevier]

Background: The use of intraprostatic gold fiducial markers (FMs) ensures highly accurate and precise image-guided radiation therapy for patients diagnosed with prostate cancer thanks to the ease of localising FMs on photon-based imaging, like Computed Tomography (CT) images. Recently, Magnetic Resonance (MR)-only radiotherapy has been proposed to simplify the workflow and reduce possible systematic uncertainties. A critical, determining factor in the accuracy of such an MR-only simulation will be accurate FM localisation using solely MR images.Purpose: The aim of this study is to evaluate the performances of manual MR-based FM localisation within a clinical environment.Methods: We designed a study in which 5 clinically involved radiation therapy technicians (RTTs) independently localised the gold FMs implanted in 16 prostate cancer patients in two scenarios: employing a single MR sequence or a combination of sequences. Inter-observer precision and accuracy were assessed for the two scenarios for localisation in terms of 95% limit of agreement on single FMs (LoA)/ centre of mass (LoA CM) and inter-marker distances (IDs), respectively.Results: The number of precisely located FMs (LoA <2 mm) increased from 38/48 to 45/48 FMs when localisation was performed using multiple sequences instead of single one. When performing localisation on multiple sequences, imprecise localisation of the FMs (3/48 FMs) occurred for 1/3 implanted FMs in three different patients. In terms of precision, we obtained LoA CM within 0.25 mm in all directions over the precisely located FMs. In terms of accuracy, IDs difference of manual MR-based localisation versus CT-based localisation was on average (±1 STD) 0.6 ±0.6 mm.Conclusions: For both the investigated scenarios, the results indicate that when FM classification was correct, the precision and accuracy are high and comparable to CT-based FM localisation. We found that use of multiple sequences led to better localisation performances compared with the use of single sequence. However, we observed that, due to the presence of calcification and motion, the risk of mislocated patient positioning is still too high to allow the sole use of manual FM localisation. Finally, strategies to possibly overcome the current challenges were proposed. [ABSTRACT FROM AUTHOR]

Abstract: Background and purpose: In our clinic a QA program for IMRT verification, fully based on dosimetric measurements with electronic portal imaging devices (EPID), has been running for over 3 years. The program includes a pre-treatment dosimetric check of all IMRT fields. During a complete treatment simulation at the linac, a portal dose image (PDI) is acquired with the EPID for each patient field and compared with a predicted PDI. In this paper, the results of this pre-treatment procedure are analysed, and intercepted errors are reported. An automated image analysis procedure is proposed to limit the number of fields that need human intervention in PDI comparison. Materials and methods: Most of our analyses are performed using the γ index with 3% local dose difference and 3mm distance to agreement as reference values. Scalar parameters are derived from the γ values to summarize the agreement between measured and predicted 2D PDIs. Areas with all pixels having γ values larger than one are evaluated, making decisions based on clinically relevant criteria more straightforward. Results: In 270 patients, the pre-treatment checks revealed four clinically relevant errors. Calculation of statistics for a group of 75 patients showed that the patient-averaged mean γ value inside the field was 0.43±0.13 (1SD) and only 6.1±6.8% of pixels had a γ value larger than one. With the proposed automated image analysis scheme, visual inspection of images can be avoided in 2/3 of the cases. Conclusion: EPIDs may be used for high accuracy and high resolution routine verification of IMRT fields to intercept clinically relevant dosimetric errors prior to the start of treatment. For the majority of fields, PDI comparison can fully rely on an automated procedure, avoiding excessive workload. [Copyright &y& Elsevier]

• Focal intraprostatic lesion SBRT boosting is associated with low acute toxicity. • No acute grade ≥3 toxicity was reported in the phase II hypo-FLAME trial. • SBRT for PCa is attractive to both patients and radiation oncology departments. 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. 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. 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. Simultaneous focal boosting to the macroscopic tumour(s) in addition to whole gland prostate SBRT is associated with acceptable acute GU and GI toxicity. [ABSTRACT FROM AUTHOR]

• SBRT represents a valid treatment option for men with low/intermediate risk PCa. • Adding a focal boost to the intraprostatic tumor may improve disease control. • A focal boost might have favourable toxicity compared to whole-gland dose-escalation. • Currently, SBRT with a focal boost for PCa should be restricted to clinical trials. 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). [ABSTRACT FROM AUTHOR]

Purpose: To investigate in a three-dimensional framework the effectiveness and reproducibility of reducing the respiratory motion of liver tumors using abdominal compression in a stereotactic body frame. Methods and Materials: A total of 12 patients with liver tumors, who were treated with stereotactic body radiotherapy, were included in this study. These patients had three gold fiducial markers implanted in the healthy liver tissue surrounding the tumor. Fluoroscopic videos were acquired on the planning day and before each treatment fraction to visualize the motion of the fiducial markers during free breathing and varying levels of abdominal compression. Software was developed to track the fiducial markers and measure their excursions. Results: Abdominal compression reduced the patient group median excursion by 62% in the craniocaudal and 38% in the anteroposterior direction with respect to the median free-breathing excursions. In the left–right direction, the median excursion increased 15% (maximal increase 1.6 mm). The median residual excursion was 4.1 mm in the craniocaudal, 2.4 mm in the anteroposterior, and 1.8 mm in the left–right direction. The mean excursions were reduced by compression to <5 mm in all patients and all directions, with two exceptions (craniocaudal excursion reduction of 20.5 mm to 7.4 mm and of 21.1 mm to 5.9 mm). The residual excursions reproduced well during the treatment course, and the craniocaudal excursions measured on the treatment days were never significantly (α = 0.05) greater than on the planning days. Fine tuning the compression did not considerably change the excursion on the treatment days. Conclusions: Abdominal compression effectively reduced liver tumor motion, yielding small and reproducible excursions in three dimensions. The compression level established at planning could have been safely used on the treatment days. [Copyright &y& Elsevier]

Purpose: To determine the effect of image-guided procedures (with computed tomography [CT] and electronic portal images before each treatment fraction) on target coverage in stereotactic body radiotherapy for liver patients using a stereotactic body frame (SBF) and abdominal compression. CT guidance was used to correct for day-to-day variations in the tumor's mean position in the SBF. Methods and Materials: By retrospectively evaluating 57 treatment sessions, tumor coverage, as obtained with the clinically applied CT-guided protocol, was compared with that of alternative procedures. The internal target volume-plus (ITV(+)) was introduced to explicitly include uncertainties in tumor delineations resulting from CT-imaging artifacts caused by residual respiratory motion. Tumor coverage was defined as the volume overlap of the ITV(+), derived from a tumor delineated in a treatment CT scan, and the planning target volume. Patient stability in the SBF, after acquisition of the treatment CT scan, was evaluated by measuring the displacement of the bony anatomy in the electronic portal images relative to CT. Results: Application of our clinical protocol (with setup corrections following from manual measurements of the distances between the contours of the planning target volume and the daily clinical target volume in three orthogonal planes, multiple two-dimensional) increased the frequency of nearly full (> or = 99%) ITV(+) coverage to 77% compared with 63% without setup correction. An automated three-dimensional method further improved the frequency to 96%. Patient displacements in the SBF were generally small (< or = 2 mm, 1 standard deviation), but large craniocaudal displacements (maximal 7.2 mm) were occasionally observed. Conclusion: Daily, CT-assisted patient setup may substantially improve tumor coverage, especially with the automated three-dimensional procedure. In the present treatment design, patient stability in the SBF should be verified with portal imaging. [ABSTRACT FROM AUTHOR]

Radiotherapy patients are increasingly treated with intensity-modulated radiotherapy (IMRT) and high tumor doses. As part of our quality control program to ensure accurate dose delivery, a new method was investigated that enables the verification of the IMRT fluence delivered during patient treatment using an electronic portal imaging device (EPID), irrespective of changes in patient geometry.Each IMRT treatment field is split into a static field and a modulated field, which are delivered in sequence. Images are acquired for both fields using an EPID. The portal dose image obtained for the static field is used to determine changes in patient geometry between the planning CT scan and the time of treatment delivery. With knowledge of these changes, the delivered IMRT fluence can be verified using the portal dose image of the modulated field. This method, called split IMRT field technique (SIFT), was validated first for several phantom geometries, followed by clinical implementation for a number of patients treated with IMRT.The split IMRT field technique allows for an accurate verification of the delivered IMRT fluence (generally within 1% [standard deviation]), even if large interfraction changes in patient geometry occur. For interfraction radiological path length changes of 10 cm, deliberately introduced errors in the delivered fluence could still be detected to within 1% accuracy. Application of SIFT requires only a minor increase in treatment time relative to the standard IMRT delivery.A new technique to verify the delivered IMRT fluence from EPID images, which is independent of changes in the patient geometry, has been developed. SIFT has been clinically implemented for daily verification of IMRT treatment delivery. [Copyright &y& Elsevier]