Cone beam computed tomography image guidance within a magnetic resonance imaging-only planning workflow.

Background and purpose: Magnetic Resonance Imaging (MRI)-only planning workflows offer many advantages but raises challenges regarding image guidance. The study aimed to assess the viability of MRI to Cone Beam Computed Tomography (CBCT) based image guidance for MRI-only planning treatment workflows. Materials and methods: An MRI matching training package was developed. Ten radiation therapists, with a range of clinical image guidance experience and experience with MRI, completed the training package prior to matching assessment. The matching assessment was performed on four match regions: prostate gold seed, prostate soft tissue, rectum/anal canal and gynaecological. Each match region consisted of five patients, with three CBCTs per patient, resulting in fifteen CBCTs for each match region. The ten radiation therapists performed the CBCT image matching to CT and to MRI for all regions and recorded the match values. Results: The median inter-observer variation for MRI-CBCT matching and CT-CBCT matching for all regions were within 2 mm and 1 degree. There was no statistically significant association in the inter-observer variation in mean match values and radiation therapist image guidance experience levels. There was no statistically significant association in inter-observer variation in mean match values for MRI experience levels for prostate soft tissue and gynaecological match regions, while there was a statistically significant difference for prostate gold seed and rectum match regions. Conclusion: The results of this study support the concept that with focussed training, an MRI to CBCT image guidance approach can be successfully implemented in a clinical planning workflow.

AAPM Task Group Report 307: Use of EPIDs for Patient-Specific IMRT and VMAT QA.

PURPOSE: Electronic portal imaging devices (EPIDs) have been widely utilized for patient-specific quality assurance (PSQA) and their use for transit dosimetry applications is emerging. Yet there are no specific guidelines on the potential uses, limitations, and correct utilization of EPIDs for these purposes. The American Association of Physicists in Medicine (AAPM) Task Group 307 (TG-307) provides a comprehensive review of the physics, modeling, algorithms and clinical experience with EPID-based pre-treatment and transit dosimetry techniques. This review also includes the limitations and challenges in the clinical implementation of EPIDs, including recommendations for commissioning, calibration and validation, routine QA, tolerance levels for gamma analysis and risk-based analysis. METHODS: Characteristics of the currently available EPID systems and EPID-based PSQA techniques are reviewed. The details of the physics, modeling, and algorithms for both pre-treatment and transit dosimetry methods are discussed, including clinical experience with different EPID dosimetry systems. Commissioning, calibration, and validation, tolerance levels and recommended tests, are reviewed, and analyzed. Risk-based analysis for EPID dosimetry is also addressed. RESULTS: Clinical experience, commissioning methods and tolerances for EPID-based PSQA system are described for pre-treatment and transit dosimetry applications. The sensitivity, specificity, and clinical results for EPID dosimetry techniques are presented as well as examples of patient-related and machine-related error detection by these dosimetry solutions. Limitations and challenges in clinical implementation of EPIDs for dosimetric purposes are discussed and acceptance and rejection criteria are outlined. Potential causes of and evaluations of pre-treatment and transit dosimetry failures are discussed. Guidelines and recommendations developed in this report are based on the extensive published data on EPID QA along with the clinical experience of the TG-307 members. CONCLUSION: TG-307 focused on the commercially available EPID-based dosimetric tools and provides guidance for medical physicists in the clinical implementation of EPID-based patient-specific pre-treatment and transit dosimetry QA solutions including intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) treatments.

Clinical validation of the Varian Truebeam intra-fraction motion review (IMR) system for prostate treatment guidance.

This study quantified the performance of Intra-fraction Motion Review (IMR) during prostate Stereotactic Body Radiotherapy (SBRT) treatments. IMR was evaluated using prostate motion data from patients treated in an SBRT clinical trial (PROMETHEUS, NCT00587990).IMR measured prostate displacements were compared to those of two 3D motion management methods: Kilovoltage Intra-fraction Motion management (KIM) and MV/kV triangulation. A planning study assessing the impact of a defined prostate motion (2-5 mm) on the PTV coverage with and without IMR was performed. A clinically relevant IMR search region for prostate cancer SBRT treatments was determined using a customised anthropomorphic pelvis phantom with implanted gold seeds and a motion platform. IMR showed submillimeter agreement with corresponding 2D projections from both KIM and MV/kV triangulation. However, IMR detected actual displacements consistently in considerably fewer frames than KIM (3D), with the actual numbers depending on the settings. The Default Search Region (DSR) method employing a circular search region proved superior to user-contoured structures in detecting clinically relevant prostate motion. Reducing the DSR search region radius can reduce the impact of the 2D nature of IMR and improve the detectability of actual motion (by 10% per 0.5 mm reduction) but must be balanced against increased beam interruptions from minor, clinically irrelevant motion. The use of IMR for SBRT prostate treatments has the potential to improve target dose coverage (minimum dose to 98% of the PTV, D98%) by > 20% compared to treatment without IMR. Calculated D98% of IMR monitored treatments with motion was within 1.5% of plans without motion.

The dosimetric error due to uncorrected tumor rotation during real-time adaptive prostate stereotactic body radiation therapy.

BACKGROUND: During prostate stereotactic body radiation therapy (SBRT), prostate tumor translational motion may deteriorate the planned dose distribution. Most of the major advances in motion management to date have focused on correcting this one aspect of the tumor motion, translation. However, large prostate rotation up to 30° has been measured. As the technological innovation evolves toward delivering increasingly precise radiotherapy, it is important to quantify the clinical benefit of translational and rotational motion correction over translational motion correction alone. PURPOSE: The purpose of this work was to quantify the dosimetric impact of intrafractional dynamic rotation of the prostate measured with a six degrees-of-freedom tumor motion monitoring technology. METHODS: The delivered dose was reconstructed including (a) translational and rotational motion and (b) only translational motion of the tumor for 32 prostate cancer patients recruited on a 5-fraction prostate SBRT clinical trial. Patients on the trial received 7.25 Gy in a treatment fraction. A 5 mm clinical target volume (CTV) to planning target volume (PTV) margin was applied in all directions except the posterior direction where a 3 mm expansion was used. Prostate intrafractional translational motion was managed using a gating strategy, and any translation above the gating threshold was corrected by applying an equivalent couch shift. The residual translational motion is denoted as T r e s $T_{res}$ . Prostate intrafractional rotational motion R u n c o r r $R_{uncorr}$ was recorded but not corrected. The dose differences from the planned dose due to T r e s $T_{res}$ + R u n c o r r $R_{uncorr}$ , ΔD( T r e s $T_{res}$ + R u n c o r r $R_{uncorr}$ ) and due to T r e s $T_{res}$ alone, ΔD( T r e s $T_{res}$ ), were then determined for CTV D98, PTV D95, bladder V6Gy, and rectum V6Gy. The residual dose error due to uncorrected rotation, R u n c o r r $R_{uncorr}$ was then quantified: Δ D R e s i d u a l $\Delta D_{Residual}$ = ΔD( T r e s $T_{res}$ + R u n c o r r $R_{uncorr}$ ) - ΔD( T res ${T}_{\textit{res}}$ ). RESULTS: Fractional data analysis shows that the dose differences from the plan (both ΔD( T r e s $T_{res}$ + R u n c o r r $R_{uncorr}$ ) and ΔD( T r e s $T_{res}$ )) for CTV D98 was less than 5% in all treatment fractions. ΔD( T r e s $T_{res}$ + R u n c o r r $R_{uncorr}$ ) was larger than 5% in one fraction for PTV D95, in one fraction for bladder V6Gy, and in five fractions for rectum V6Gy. Uncorrected rotation, R u n c o r r $R_{uncorr}$ induced residual dose error, Δ D R e s i d u a l $\Delta D_{Residual}$ , resulted in less dose to CTV and PTV in 43% and 59% treatment fractions, respectively, and more dose to bladder and rectum in 51% and 53% treatment fractions, respectively. The cumulative dose over five fractions, ∑D( T r e s $T_{res}$ + R u n c o r r $R_{uncorr}$ ) and ∑D( T r e s $T_{res}$ ), was always within 5% of the planned dose for all four structures for every patient. CONCLUSIONS: The dosimetric impact of tumor rotation on a large prostate cancer patient cohort was quantified in this study. These results suggest that the standard 3-5 mm CTV-PTV margin was sufficient to account for the intrafraction prostate rotation observed for this cohort of patients, provided an appropriate gating threshold was applied to correct for translational motion. Residual dose errors due to uncorrected prostate rotation were small in magnitude, which may be corrected using different treatment adaptation strategies to further improve the dosimetric accuracy.

Verification of stereotactic radiosurgery plans for multiple brain metastases using a virtual phantom-based procedure.

Background: The purpose of this study was to describe the use of the VIPER software for patient-specific quality assurance (PSQA) of single-isocenter multitarget (SIMT) stereotactic radiosurgery (SRS) plans. Materials and methods: Twenty clinical of intensity-modulated (IMRT) SIMT SRS plans were reviewed. A total of 88 brain metastases were included. Number of lesions per plan and their individual volumes ranged from 2 to 35 and from 0.03 to 32.8 cm3, respectively. Plans were designed with the Eclipse system, and delivered using a Varian CLINAC linac. SRS technique consisted of non-coplanar static-field sliding-window IMRT. Each plan was mapped onto a virtual cylindrical water phantom (VCP) in the Eclipse to calculate a 3D dose distribution (verification plan). The VIPER software reconstructed the 3D dose distribution inside the VCP from the acquired in-air electronic portal image device (EPID) images of the treatment fields. A 3D gamma analysis was used to compare the reconstructed doses to the Eclipse planned doses on the VCP. Gamma passing rates (GPRs) were calculated using 3% global/2 mm criteria and dose thresholds ranged from 10% to 90% of the maximum dose. Results: The averages (± 1 SD) of the 3D GPRs over the 20 SRS plans were: 99.9 ± 0.2%, 99.7 ± 0.3%, 99.6 ± 0.5%, 99.3 ± 0.9%,99.1 ± 1.6%, 99.0 ± 1.6%, and 98.5 ± 3.3%, for dose thresholds of 10%, 20%, 30%, 50%, 70%, 80% and 90% respectively. Conclusions: This work shows the feasibility of the VIPER software for PSQA of SIMT SRS plans, being a reliable alternative to commercially available 2D detector arrays.

Quality assurance for MRI-only radiation therapy: A voxel-wise population-based methodology for image and dose assessment of synthetic CT generation methods.

The quality assurance of synthetic CT (sCT) is crucial for safe clinical transfer to an MRI-only radiotherapy planning workflow. The aim of this work is to propose a population-based process assessing local errors in the generation of sCTs and their impact on dose distribution. For the analysis to be anatomically meaningful, a customized interpatient registration method brought the population data to the same coordinate system. Then, the voxel-based process was applied on two sCT generation methods: a bulk-density method and a generative adversarial network. The CT and MRI pairs of 39 patients treated by radiotherapy for prostate cancer were used for sCT generation, and 26 of them with delineated structures were selected for analysis. Voxel-wise errors in sCT compared to CT were assessed for image intensities and dose calculation, and a population-based statistical test was applied to identify the regions where discrepancies were significant. The cumulative histograms of the mean absolute dose error per volume of tissue were computed to give a quantitative indication of the error for each generation method. Accurate interpatient registration was achieved, with mean Dice scores higher than 0.91 for all organs. The proposed method produces three-dimensional maps that precisely show the location of the major discrepancies for both sCT generation methods, highlighting the heterogeneity of image and dose errors for sCT generation methods from MRI across the pelvic anatomy. Hence, this method provides additional information that will assist with both sCT development and quality control for MRI-based planning radiotherapy.

CAN3D: Fast 3D medical image segmentation via compact context aggregation.

Direct automatic segmentation of objects in 3D medical imaging, such as magnetic resonance (MR) imaging, is challenging as it often involves accurately identifying multiple individual structures with complex geometries within a large volume under investigation. Most deep learning approaches address these challenges by enhancing their learning capability through a substantial increase in trainable parameters within their models. An increased model complexity will incur high computational costs and large memory requirements unsuitable for real-time implementation on standard clinical workstations, as clinical imaging systems typically have low-end computer hardware with limited memory and CPU resources only. This paper presents a compact convolutional neural network (CAN3D) designed specifically for clinical workstations and allows the segmentation of large 3D Magnetic Resonance (MR) images in real-time. The proposed CAN3D has a shallow memory footprint to reduce the number of model parameters and computer memory required for state-of-the-art performance and maintain data integrity by directly processing large full-size 3D image input volumes with no patches required. The proposed architecture significantly reduces computational costs, especially for inference using the CPU. We also develop a novel loss function with extra shape constraints to improve segmentation accuracy for imbalanced classes in 3D MR images. Compared to state-of-the-art approaches (U-Net3D, improved U-Net3D and V-Net), CAN3D reduced the number of parameters up to two orders of magnitude and achieved much faster inference, up to 5 times when predicting with a standard commercial CPU (instead of GPU). For the open-access OAI-ZIB knee MR dataset, in comparison with manual segmentation, CAN3D achieved Dice coefficient values of (mean = 0.87 ± 0.02 and 0.85 ± 0.04) with mean surface distance errors (mean = 0.36 ± 0.32 mm and 0.29 ± 0.10 mm) for imbalanced classes such as (femoral and tibial) cartilage volumes respectively when training volume-wise under only 12G video memory. Similarly, CAN3D demonstrated high accuracy and efficiency on a pelvis 3D MR imaging dataset for prostate cancer consisting of 211 examinations with expert manual semantic labels (bladder, body, bone, rectum, prostate) now released publicly for scientific use as part of this work.

SEAFARER - A new concept for validating radiotherapy patient specific QA for clinical trials and clinical practice.

BACKGROUND: The quality of radiotherapy delivery has been shown to significantly impact clinical outcomes including patient survival. To identify errors, institutions perform Patient Specific Quality Assurance (PSQA) assessing each individual radiotherapy plan prior to starting patient treatments. Externally administered Dosimetry Audits have found problems despite institutions passing their own PSQA. Hence a new audit concept which assesses the institution's ability to detect errors with their routine PSQA is needed. METHODS: Purposefully introduced edits which simulated treatment delivery errors were embedded into radiation treatment plans of participating institutions. These were designed to produce clinically significant changes yet were mostly within treatment delivery specifications. Actual impact was centrally assessed for each plan. Institutions performed PSQA on each plan, without knowing which contained errors. RESULTS: Seventeen institutions using six radiation treatment planning systems and two delivery systems performed PSQA on twelve plans each. Seventeen erroneous plans (across seven institutions) passed PSQA despite causing >5% increase in spinal cord dose relative to the original plans. Six plans (from four institutions) passed despite a >10% increase. CONCLUSIONS: This novel audit concept evolves beyond testing an institution's ability to deliver a single test case, to increasing the number of errors caught by institutions themselves, thus increasing quality of radiation therapy and impacting every patient treated. Administered remotely this audit also provides advantages in cost, environmental impact, and logistics.

Validation of an MRI-only planning workflow for definitive pelvic radiotherapy.

PURPOSE: Previous work on Magnetic Resonance Imaging (MRI) only planning has been applied to limited treatment regions with a focus on male anatomy. This research aimed to validate the use of a hybrid multi-atlas synthetic computed tomography (sCT) generation technique from a MRI, using a female and male atlas, for MRI only radiation therapy treatment planning of rectum, anal canal, cervix and endometrial malignancies. PATIENTS AND METHODS: Forty patients receiving radiation treatment for a range of pelvic malignancies, were separated into male (n = 20) and female (n = 20) cohorts for the creation of gender specific atlases. A multi-atlas local weighted voting method was used to generate a sCT from a T1-weighted VIBE DIXON MRI sequence. The original treatment plans were copied from the CT scan to the corresponding sCT for dosimetric validation. RESULTS: The median percentage dose difference between the treatment plan on the CT and sCT at the ICRU reference point for the male cohort was - 0.4% (IQR of 0 to - 0.6), and - 0.3% (IQR of 0 to - 0.6) for the female cohort. The mean gamma agreement for both cohorts was > 99% for criteria of 3%/2 mm and 2%/2 mm. With dose criteria of 1%/1 mm, the pass rate was higher for the male cohort at 96.3% than the female cohort at 93.4%. MRI to sCT anatomical agreement for bone and body delineated contours was assessed, with a resulting Dice score of 0.91 ± 0.2 (mean ± 1 SD) and 0.97 ± 0.0 for the male cohort respectively; and 0.96 ± 0.0 and 0.98 ± 0.0 for the female cohort respectively. The mean absolute error in Hounsfield units (HUs) within the entire body for the male and female cohorts was 59.1 HU ± 7.2 HU and 53.3 HU ± 8.9 HU respectively. CONCLUSIONS: A multi-atlas based method for sCT generation can be applied to a standard T1-weighted MRI sequence for male and female pelvic patients. The implications of this study support MRI only planning being applied more broadly for both male and female pelvic sites. Trial registration This trial was registered in the Australian New Zealand Clinical Trials Registry (ANZCTR) ( www.anzctr.org.au ) on 04/10/2017. Trial identifier ACTRN12617001406392.

Comparison of Synthetic Computed Tomography Generation Methods, Incorporating Male and Female Anatomical Differences, for Magnetic Resonance Imaging-Only Definitive Pelvic Radiotherapy.

PURPOSE: There are several means of synthetic computed tomography (sCT) generation for magnetic resonance imaging (MRI)-only planning; however, much of the research omits large pelvic treatment regions and female anatomical specific methods. This research aimed to apply four of the most popular methods of sCT creation to facilitate MRI-only radiotherapy treatment planning for male and female anorectal and gynecological neoplasms. sCT methods were validated against conventional computed tomography (CT), with regard to Hounsfield unit (HU) estimation and plan dosimetry. METHODS AND MATERIALS: Paired MRI and CT scans of 40 patients were used for sCT generation and validation. Bulk density assignment, tissue class density assignment, hybrid atlas, and deep learning sCT generation methods were applied to all 40 patients. Dosimetric accuracy was assessed by dose difference at reference point, dose volume histogram (DVH) parameters, and 3D gamma dose comparison. HU estimation was assessed by mean error and mean absolute error in HU value between each sCT and CT. RESULTS: The median percentage dose difference between the CT and sCT was <1.0% for all sCT methods. The deep learning method resulted in the lowest median percentage dose difference to CT at -0.03% (IQR 0.13, -0.31) and bulk density assignment resulted in the greatest difference at -0.73% (IQR -0.10, -1.01). The mean 3D gamma dose agreement at 3%/2 mm among all sCT methods was 99.8%. The highest agreement at 1%/1 mm was 97.3% for the deep learning method and the lowest was 93.6% for the bulk density method. Deep learning and hybrid atlas techniques gave the lowest difference to CT in mean error and mean absolute error in HU estimation. CONCLUSIONS: All methods of sCT generation used in this study resulted in similarly high dosimetric agreement for MRI-only planning of male and female cancer pelvic regions. The choice of the sCT generation technique can be guided by department resources available and image guidance considerations, with minimal impact on dosimetric accuracy.

Assessing the impact of magnetic resonance treatment simulation (MRSIM) on target volume delineation and dose to organs at risk for oropharyngeal radiotherapy.

INTRODUCTION: Assessing the use of a radiation therapy (RT) planning MRI performed in the treatment position (pMRI) on target volume delineation and effect on organ at risk dose for oropharyngeal cancer patients planned with diagnostic MRI (dMRI) and CT scan. METHODS: Diagnostic MRI scans were acquired for 26 patients in a neutral patient position using a 3T scanner (dMRI). Subsequent pMRI scans were acquired on the same scanner with a flat couch top and the patient in their immobilisation mask. Each series was rigidly registered to the patients planning CT scan and volumes were first completed with the CT/dMRI. The pMRI was then made available for volume modification. For the group with revised volumes, two IMRT plans were developed to demonstrate the impact of the modification. Image and registration quality was also evaluated. RESULTS: The pMRI registration led to the modification of target volumes for 19 of 26 participants. The pMRI target volumes were larger in absolute volume resulting in reduced capacity for organ sparing. Predominantly, modifications occurred for the primary gross tumour volume (GTVp) with a mean Dice Similarity Coefficient (DSC) of 0.7 and the resulting high risk planning target volume, a mean DSC of 0.89. Both MRIs scored similarly for image quality, with the pMRI demonstrating improved registration quality and efficiency. CONCLUSIONS: A pMRI provides improvement in registration efficiency, quality and a higher degree of oncologist confidence in target delineation. These results have led to a practice change within our department, where a pMRI is acquired for all eligible oropharyngeal cancer patients.

Diagnosis of transition zone prostate cancer by multiparametric MRI: added value of MR spectroscopic imaging with sLASER volume selection.

BACKGROUND: Current multiparametric MRI (mp-MRI) in routine clinical practice has poor-to-moderate diagnostic performance for transition zone prostate cancer. The aim of this study was to evaluate the potential diagnostic performance of novel 1H magnetic resonance spectroscopic imaging (MRSI) using a semi-localized adiabatic selective refocusing (sLASER) sequence with gradient offset independent adiabaticity (GOIA) pulses in addition to the routine mp-MRI, including T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI) and quantitative dynamic contrast enhancement (DCE) for transition zone prostate cancer detection, localization and grading. METHODS: Forty-one transition zone prostate cancer patients underwent mp-MRI with an external phased-array coil. Normal and cancer regions were delineated by two radiologists and divided into low-risk, intermediate-risk, and high-risk categories based on TRUS guided biopsy results. Support vector machine models were built using different clinically applicable combinations of T2WI, DWI, DCE, and MRSI. The diagnostic performance of each model in cancer detection was evaluated using the area under curve (AUC) of the receiver operating characteristic diagram. Then accuracy, sensitivity and specificity of each model were calculated. Furthermore, the correlation of mp-MRI parameters with low-risk, intermediate-risk and high-risk cancers were calculated using the Spearman correlation coefficient. RESULTS: The addition of MRSI to T2WI + DWI and T2WI + DWI + DCE improved the accuracy, sensitivity and specificity for cancer detection. The best performance was achieved with T2WI + DWI + MRSI where the addition of MRSI improved the AUC, accuracy, sensitivity and specificity from 0.86 to 0.99, 0.83 to 0.96, 0.80 to 0.95, and 0.85 to 0.97 respectively. The (choline + spermine + creatine)/citrate ratio of MRSI showed the highest correlation with cancer risk groups (r = 0.64, p < 0.01). CONCLUSION: The inclusion of GOIA-sLASER MRSI into conventional mp-MRI significantly improves the diagnostic accuracy of the detection and aggressiveness assessment of transition zone prostate cancer.

Validation of virtual water phantom software for pre-treatment verification of single-isocenter multiple-target stereotactic radiosurgery.

The aim of this study was to benchmark the accuracy of the VIrtual Phantom Epid dose Reconstruction (VIPER) software for pre-treatment dosimetric verification of multiple-target stereotactic radiosurgery (SRS). VIPER is an EPID-based method to reconstruct a 3D dose distribution in a virtual phantom from in-air portal images. Validation of the VIPER dose calculation was assessed using several MLC-defined fields for a 6 MV photon beam. Central axis percent depth doses (PDDs) and output factors were measured with an ionization chamber in a water tank, while dose planes at a depth of 10 cm in a solid flat phantom were acquired with radiochromic films. The accuracy of VIPER for multiple-target SRS plan verification was benchmarked against Monte Carlo simulations. Eighteen multiple-target SRS plans designed with the Eclipse treatment planning system were mapped to a cylindrical water phantom. For each plan, the 3D dose distribution reconstructed by VIPER within the phantom was compared with the Monte Carlo simulation, using a 3D gamma analysis. Dose differences (VIPER vs. measurements) generally within 2% were found for the MLC-defined fields, while film dosimetry revealed gamma passing rates (GPRs) ≥95% for a 3%/1 mm criteria. For the 18 multiple-target SRS plans, average 3D GPRs greater than 93% and 98% for the 3%/2 mm and 5%/2 mm criteria, respectively. Our results validate the use of VIPER as a dosimetric verification tool for pre-treatment QA of single-isocenter multiple-target SRS plans. The method requires no setup time on the linac and results in an accurate 3D characterization of the delivered dose.

A novel quality assurance procedure for trajectory log validation using phantom-less real-time latency corrected EPID images.

The use of trajectory log files for routine patient quality assurance is gaining acceptance. Such use requires the validation of the trajectory log itself. However, the accurate localization of a multileaf collimator (MLC) leaf while it is in motion remains a challenging task. We propose an efficient phantom-less technique using the EPID to verify the dynamic MLC positions with high accuracy. Measurements were made on four Varian TrueBeams equipped with M120 MLCs. Two machines were equipped with the S1000 EPID; two were equipped with the S1200 EPID. All EPIDs were geometrically corrected prior to measurements. Dosimetry mode EPID measurements were captured by a frame grabber card directly linked to the linac. All leaf position measurements were corrected both temporally and geometrically. The readout latency of each panel, as a function of pixel row, was determined using a 40 × 1.0 cm2 sliding window (SW) field moving at 2.5 cm/s orthogonal to the row readout direction. The latency of each panel type was determined by averaging the results of two panels of the same type. Geometric correction was achieved by computing leaf positions with respect to the projected isocenter position as a function of gantry angle. This was determined by averaging the central axis position of fields at two collimator positions of 90° and 270°. The radiological to physical leaf end position was determined by comparison of the measured gap with that determined using a feeler gauge. The radiological to physical leaf position difference was found to be 0.1 mm. With geometric and latency correction, the proposed method was found to be improve the ability to detect dynamic MLC positions from 1.0 to 0.2 mm for all leaves. Latency and panel residual geometric error correction improve EPID-based MLC position measurement. These improvements provide for the first time a trajectory log QA procedure.

Toward real-time verification for MLC tracking treatments using time-resolved EPID imaging.

PURPOSE: In multileaf collimator (MLC) tracking, the MLC positions from the original treatment plan are continuously modified to account for intrafraction tumor motion. As the treatment is adapted in real time, there is additional risk of delivery errors which cannot be detected using traditional pretreatment dose verification. The purpose of this work is to develop a system for real-time geometric verification of MLC tracking treatments using an electronic portal imaging device (EPID). METHODS: MLC tracking was utilized during volumetric modulated arc therapy (VMAT). During these deliveries, treatment beam images were taken at 9.57 frames per second using an EPID and frame grabber computer. MLC positions were extracted from each image frame and used to assess delivery accuracy using three geometric measures: the location, size, and shape of the radiation field. The EPID-measured field location was compared to the tumor motion measured by implanted electromagnetic markers. The size and shape of the beam were compared to the size and shape from the original treatment plan, respectively. This technique was validated by simulating errors in phantom test deliveries and by comparison between EPID measurements and treatment log files. The method was applied offline to images acquired during the LIGHT Stereotactic Ablative Body Radiotherapy (SABR) clinical trial, where MLC tracking was performed for 17 lung cancer patients. The EPID-based verification results were subsequently compared to post-treatment dose reconstruction. RESULTS: Simulated field location errors were detected during phantom validation tests with an uncertainty of 0.28 mm (parallel to MLC motion) and 0.38 mm (perpendicular), expressed as a root-mean-square error (RMSError ). For simulated field size errors, the RMSError was 0.47 cm2 and field shape changes were detected for random errors with standard deviation ≥ 2.5 mm. For clinical lung SABR deliveries, field location errors of 1.6 mm (parallel MLC motion) and 4.9 mm (perpendicular) were measured (expressed as a full-width-half-maximum). The mean and standard deviation of the errors in field size and shape were 0.0 ± 0.3 cm2 and 0.3 ± 0.1 (expressed as a translation-invariant normalized RMS). No correlation was observed between geometric errors during each treatment fraction and dosimetric errors in the reconstructed dose to the target volume for this cohort of patients. CONCLUSION: A system for real-time delivery verification has been developed for MLC tracking using time-resolved EPID imaging. The technique has been tested offline in phantom-based deliveries and clinical patient deliveries and was used to independently verify the geometric accuracy of the MLC during MLC tracking radiotherapy.

AAPM Task Group 264: The safe clinical implementation of MLC tracking in radiotherapy.

The era of real-time radiotherapy is upon us. Robotic and gimbaled linac tracking are clinically established technologies with the clinical realization of couch tracking in development. Multileaf collimators (MLCs) are a standard equipment for most cancer radiotherapy systems, and therefore MLC tracking is a potentially widely available technology. MLC tracking has been the subject of theoretical and experimental research for decades and was first implemented for patient treatments in 2013. The AAPM Task Group 264 Safe Clinical Implementation of MLC Tracking in Radiotherapy Report was charged to proactively provide the broader radiation oncology community with (a) clinical implementation guidelines including hardware, software, and clinical indications for use, (b) commissioning and quality assurance recommendations based on early user experience, as well as guidelines on Failure Mode and Effects Analysis, and (c) a discussion of potential future developments. The deliverables from this report include: an explanation of MLC tracking and its historical development; terms and definitions relevant to MLC tracking; the clinical benefit of, clinical experience with and clinical implementation guidelines for MLC tracking; quality assurance guidelines, including example quality assurance worksheets; a clinical decision pathway, future outlook and overall recommendations.

Increased Dose to Organs in Urinary Tract Associates With Measures of Genitourinary Toxicity in Pooled Voxel-Based Analysis of 3 Randomized Phase III Trials.

Purpose: Dose information from organ sub-regions has been shown to be more predictive of genitourinary toxicity than whole organ dose volume histogram information. This study aimed to identify anatomically-localized regions where 3D dose is associated with genitourinary toxicities in healthy tissues throughout the pelvic anatomy. Methods and Materials: Dose distributions for up to 656 patients of the Trans-Tasman Radiation Oncology Group 03.04 RADAR trial were deformably registered onto a single exemplar CT dataset. Voxel- based multiple comparison permutation dose difference testing, Cox regression modeling and LASSO feature selection were used to identify regions where 3D dose-increase was associated with late grade ≥ 2 genitourinary dysuria, incontinence and frequency, and late grade ≥ 1 haematuria. This was externally validated by registering dose distributions from the RT01 (up to n = 388) and CHHiP (up to n = 247) trials onto the same exemplar and repeating the voxel-based tests on each of these data sets. All three datasets were then combined, and the tests repeated. Results: Voxel-based Cox regression and multiple comparison permutation dose difference testing revealed regions where increased dose was correlated with genitourinary toxicity. Increased dose in the vicinity of the membranous and spongy urethra was associated with dysuria for all datasets. Haematuria was similarly correlated with increased dose at the membranous and spongy urethra, for the RADAR, CHHiP, and combined datasets. Some evidence was found for the association between incontinence and increased dose at the internal and external urethral sphincter for RADAR and the internal sphincter alone for the combined dataset. Incontinence was also strongly correlated with dose from posterior oblique beams. Patients with fields extending inferiorly and posteriorly to the CTV, adjacent to the membranous and spongy urethra, were found to experience increased frequency. Conclusions: Anatomically-localized dose-toxicity relationships were determined for late genitourinary symptoms in the urethra and urinary sphincters. Low-intermediate doses to the extraprostatic urethra were associated with risk of late dysuria and haematuria, while dose to the urinary sphincters was associated with incontinence.

Reduced Dose Posterior to Prostate Correlates With Increased PSA Progression in Voxel-Based Analysis of 3 Randomized Phase 3 Trials.

PURPOSE: Reducing margins during treatment planning to decrease dose to healthy organs surrounding the prostate can risk inadequate treatment of subclinical disease. This study aimed to investigate whether lack of dose to subclinical disease is associated with increased disease progression by using high-quality prostate radiation therapy clinical trial data to identify anatomically localized regions where dose variation is associated with prostate-specific antigen progression (PSAP). METHODS AND MATERIALS: Planned dose distributions for 683 patients of the Trans-Tasman Radiation Oncology Group 03.04 Randomized Androgen Deprivation and Radiotherapy (RADAR) trial were deformably registered onto a single exemplar computed tomography data set. These were divided into high-risk and intermediate-risk subgroups for analysis. Three independent voxel-based statistical tests, using permutation testing, Cox regression modeling, and least absolute shrinkage selection operator feature selection, were applied to identify regions where dose variation was associated with PSAP. Results from the intermediate-risk RADAR subgroup were externally validated by registering dose distributions from the RT01 (n = 388) and Conventional or Hypofractionated High Dose Intensity Modulated Radiotherapy for Prostate Cancer Trial (CHHiP) (n = 253) trials onto the same exemplar and repeating the tests on each of these data sets. RESULTS: Voxel-based Cox regression revealed regions where reduced dose was correlated with increased prostate-specific androgen progression. Reduced dose in regions associated with coverage at the posterior prostate, in the immediate periphery of the posterior prostate, and in regions corresponding to the posterior oblique beams or posterior lateral beam boundary, was associated with increased PSAP for RADAR and RT01 patients, but not for CHHiP patients. Reduced dose to the seminal vesicle region was also associated with increased PSAP for RADAR intermediate-risk patients. CONCLUSIONS: Ensuring adequate dose coverage at the posterior prostate and immediately surrounding posterior region (including the seminal vesicles), where aggressive cancer spread may be occurring, may improve tumor control. It is recommended that particular care be taken when defining margins at the prostate posterior, acknowledging the trade-off between quality of life due to rectal dose and the preferences of clinicians and patients.

Voxel-based supervised machine learning of peripheral zone prostate cancer using noncontrast multiparametric MRI.

PURPOSE: The aim of this study was to develop and assess the performance of supervised machine learning technique to classify magnetic resonance imaging (MRI) voxels as cancerous or noncancerous using noncontrast multiparametric MRI (mp-MRI), comprised of T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), and advanced diffusion tensor imaging (DTI) parameters. MATERIALS AND METHODS: In this work, 191 radiomic features were extracted from mp-MRI from prostate cancer patients. A comprehensive set of support vector machine (SVM) models for T2WI and mp-MRI (T2WI + DWI, T2WI + DTI, and T2WI + DWI + DTI) were developed based on novel Bayesian parameters optimization method and validated using leave-one-patient-out approach to eliminate any possible overfitting. The diagnostic performance of each model was evaluated using the area under the receiver operating characteristic curve (AUROC). The average sensitivity, specificity, and accuracy of the models were evaluated using the test data set and the corresponding binary maps generated. Finally, the SVM plus sigmoid function of the models with the highest performance were used to produce cancer probability maps. RESULTS: The T2WI + DWI + DTI models using the optimal feature subset achieved the best performance in prostate cancer detection, with the average AUROC , sensitivity, specificity, and accuracy of 0.93 ± 0.03, 0.85 ± 0.05, 0.82 ± 0.07, and 0.83 ± 0.04, respectively. The average diagnostic performance of T2WI + DTI models was slightly higher than T2WI + DWI models (+3.52%) using the optimal radiomic features. CONCLUSIONS: Combination of noncontrast mp-MRI (T2WI, DWI, and DTI) features with the framework of a supervised classification technique and Bayesian optimization method are able to differentiate cancer from noncancer voxels with high accuracy and without administration of contrast agent. The addition of cancer probability maps provides additional functionality for image interpretation, lesion heterogeneity evaluation, and treatment management.

Relationships between rectal and perirectal doses and rectal bleeding or tenesmus in pooled voxel-based analysis of 3 randomised phase III trials.

BACKGROUND AND PURPOSE: This study aimed to identify anatomically-localised regions where planned radiotherapy dose is associated with gastrointestinal toxicities in healthy tissues throughout the pelvic anatomy. MATERIALS AND METHODS: Planned dose distributions for up to 657 patients of the Trans Tasman Radiation Oncology Group 03.04 RADAR trial were deformably registered onto a single exemplar computed tomography dataset. Voxel-based multiple comparison permutation dose difference testing, Cox regression modelling and LASSO feature selection were used to identify regions where dose-increase was associated with grade ≥2 rectal bleeding (RB) or tenesmus, according to the LENT/SOMA scale. This was externally validated by registering dose distributions from the RT01 (n = 388) and CHHiP (n = 241) trials onto the same exemplar and repeating the tests on each of these data sets, and on all three datasets combined. RESULTS: Voxel-based Cox regression and permutation dose difference testing revealed regions where increased dose was correlated with gastrointestinal toxicity. Grade ≥2 RB was associated with posteriorly extended lateral beams that manifested high doses (>55 Gy) in a small rectal volume adjacent to the clinical target volume. A correlation was found between grade ≥2 tenesmus and increased low-intermediate dose (∼25 Gy) at the posterior beam region, including the posterior rectum and perirectal fat space (PRFS). CONCLUSIONS: The serial response of the rectum with respect to RB has been demonstrated in patients with posteriorly extended lateral beams. Similarly, the parallel response of the PRFS with respect to tenesmus has been demonstrated in patients treated with the posterior beam.