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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Due to the histological heterogeneity of the central gland, accurate detection of central gland prostate cancer remains a challenge.Purpose: To evaluate the efficacy of in vivo 3D 1 H MR spectroscopic imaging (3D 1 H MRSI) with a semi-localized adiabatic selective refocusing (sLASER) sequence and gradient-modulated offset-independent adiabatic (GOIA) pulses for detection of central gland prostate cancer. Additionally four risk models were developed to differentiate 1) normal vs. cancer, 2) low- vs. high-risk cancer, 3) low- vs. intermediate-risk cancer, and 4) intermediate- vs. high-risk cancer voxels.Study Type: Prospective.Subjects: Thirty-six patients with biopsy-proven central gland prostate cancer.Field Strength/sequence: 3T MRI / 3D 1 H MRSI using GOIA-sLASER.Assessment: Cancer and normal regions of interest (ROIs) were selected by an experienced radiologist and 1 H MRSI voxels were placed within the ROIs to calculate seven metabolite signal ratios. Voxels were split into two subsets, 80% for model training and 20% for testing.Statistical Tests: Four support vector machine (SVM) models were built using the training dataset. The accuracy, sensitivity, and specificity for each model were calculated for the testing dataset.Results: High-quality MR spectra were obtained for the whole central gland of the prostate. The normal vs. cancer diagnostic model achieved the highest predictive performance with an accuracy, sensitivity, and specificity of 96.2%, 95.8%, and 93.1%, respectively. The accuracy, sensitivity, and specificity of the low- vs. high-risk cancer and low- vs. intermediate-risk cancer models were 82.5%, 89.2%, 70.2%, and 73.0%, 84.7%, 60.8%, respectively. The intermediate- vs. high-risk cancer model yielded an accuracy, sensitivity, and specificity lower than 55%.Data Conclusion: The GOIA-sLASER sequence with an external phased-array coil allows for fast assessment of central gland prostate cancer. The classification offers a promising diagnostic tool for discriminating normal vs. cancer, low- vs. high-risk cancer, and low- vs. intermediate-risk cancer.Level Of Evidence: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:1926-1936. [ABSTRACT FROM AUTHOR]

Objectives: To report feasibility, early toxicity, and PSA kinetics following gantry-based, stereotactic radiotherapy (SBRT) boost within a prospective, phase 2, multicenter study (PROMETHEUS: ACTRN12615000223538). Methods: Patients were treated with gantry-based SBRT, 19–20 Gy in two fractions delivered 1 week apart, followed by conventionally fractionated IMRT (46 Gy in 23 fractions). The study mandated MRI fusion for RT planning, rectal displacement, and intrafraction image guidance. Toxicity was prospectively graded using the Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4). Results: Between March 2014 and July 2018, 135 patients (76% intermediate, 24% high-risk) with a median age of 70 years (range 53–81) were treated across five centers. Short course (≤6 months) androgen deprivation therapy (ADT) was used in 36% and long course in 18%. Rectal displacement method was SpaceOAR in 59% and Rectafix in 41%. Forty-two and ninety-three patients were treated at the 19 Gy and 20 Gy dose levels, respectively. Median follow-up was 24 months. Acute grade 2 gastrointestinal (GI) and urinary toxicity occurred in 4.4 and 26.6% with no acute grade 3 toxicity. At 6, 12, 18, 24, and 36 months post-treatment the prevalence of late grade ≥2 gastrointestinal toxicity was 1.6, 3.7, 2.2, 0, and 0%, respectively, and the prevalence of late grade ≥2 urinary toxicity was 0.8, 11, 12, 7.1, and 6.3%, respectively. Three patients experienced grade 3 late toxicity at 12 to 18 months which subsequently resolved to grade 2 or less. For patients not receiving ADT the median PSA value pre-treatment was 7.6 ug/L (1.1–20) and at 12, 24, and 36 months post-treatment was 0.86, 0.36, and 0.20 ug/L. Conclusions: Delivery of a gantry-based SBRT boost is feasible in a multicenter setting, is well-tolerated with low rates of early toxicity and is associated with promising PSA responses. A second transient peak in urinary toxicity was observed at 18 months which subsequently resolved. Follow-up is ongoing to document late toxicity, long-term patient reported outcomes, and tumor control with this approach. [ABSTRACT FROM AUTHOR]

Background Kilovoltage Intrafraction Monitoring ( KIM) is a method which determines the three-dimensional position of the prostate from two-dimensional kilovoltage ( kV) projections taken during linac based radiotherapy treatment with real-time feedback. Rectal displacement devices ( RDDs) allow for improved rectal dosimetry during prostate cancer treatment. This study used KIM to perform a preliminary investigation of prostate intrafraction motion observed in patients with an RDD in place. Methods Ten patients with intermediate to high-risk prostate cancer were treated with a Rectafix RDD in place during two boost fractions of 9.5-10 Gy delivered using volumetric modulated arc therapy ( VMAT) on Clinac iX and Truebeam linacs. Two-dimensional kV projections were acquired during treatment. KIM software was used following treatment to determine the displacement of the prostate over time. The displacement results were analyzed to determine the percentage of treatment time the prostate spent within 1 mm, between 1 and 2 mm, between 2 and 3 mm and greater than 3 mm from its initial position. Results KIM successfully measured displacement for 19 prostate stereotactic boost fractions. The prostate was within 1 mm of its initial position for 84.8%, 1-2 mm for 14%, 2-3 mm 1.2% and ≥3 mm only 0.4% of the treatment time. Conclusions In this preliminary study using KIM, KIM was successfully used to measure prostate intrafraction motion, which was found to be small in the presence of a rectal displacement device. Trial registration The Hunter New England Human Research Ethics Committee reference number is 14/08/20/3.01. [ABSTRACT FROM AUTHOR]

Background: This paper describes the multi-institutional prospective phase II clinical trial, SPARK: Stereotactic Prostate Adaptive Radiotherapy utilizing Kilovoltage Intrafraction Monitoring (KIM). KIM is a real-time image guided radiotherapy technology being developed and clinically pioneered for prostate cancer treatment in Australia. It has potential for widespread use for target radiotherapy treatment of cancers of the pelvis, thorax and abdomen.Methods: In the SPARK trial we will measure the cancer targeting accuracy and patient outcomes for 48 prostate cancer patients who will be treated in five treatment sessions as opposed to the conventional 40 sessions. The reduced number of treatment sessions is enabled by the KIM's increased cancer targeting accuracy.Discussion: Real-time imaging in radiotherapy has the potential to decrease the time taken during cancer treatment and reduce the imaging dose required. With the imaging being acquired during the treatment, and the analysis being automated, there is potential for improved throughput. The SPARK trial will be conducted under the auspices of the Trans-Tasman Radiation Oncology Group (TROG).Trial Registration: This trial was registered on ClinicalTrials.gov on 09 March 2015. The identifier is: NCT02397317. [ABSTRACT FROM AUTHOR]

Background: MOSFET dosimetry is a method that has been used to measure in-vivo doses during brachytherapy treatments and during linac based radiotherapy treatment. Rectal displacement devices (RDDs) allow for safe dose escalation for prostate cancer treatment. This study used dual MOSkin detectors to assess real-time in vivo rectal wall dose in patients with an RDD in place during a high dose prostate stereotactic body radiation therapy (SBRT) boost trial.Methods: The PROMETHEUS study commenced in 2014 and provides a prostate SBRT boost dose with a RDD in place. Twelve patients received two boost fractions of 9.5-10 Gy each delivered to the prostate with a dual arc volumetric modulated arc therapy (VMAT) technique. Two MOSkins in a face-to-face arrangement (dual MOSkin) were used to decrease angular dependence. A dual MOSkin was attached to the anterior surface of the Rectafix and read out at 1 Hz during each treatment. The planned dose at each measurement point was exported from the planning system and compared with the measured dose. The root mean square error normalised to the total planned dose was calculated for each measurement point and treatment arc for the entire course of treatment.Results: The average difference between the measured and planned doses over the whole course of treatment for all arcs measured was 9.7% with a standard deviation of 3.6%. The cumulative MOSkin reading was lower than the total planned dose for 64% of the arcs measured. The average difference between the final measured and final planned doses for all arcs measured was 3.4% of the final planned dose, with a standard deviation of 10.3%.Conclusions: MOSkin detectors were an effective tool for measuring dose delivered to the anterior rectal wall in real time during prostate SBRT boost treatments for the purpose of both ensuring the rectal doses remain within acceptable limits during the treatment and for the verification of final rectal doses. [ABSTRACT FROM AUTHOR]

Purpose: The feasibility of radiation therapy treatment planning using substitute computed tomography (sCT) generated from magnetic resonance images (MRIs) has been demonstrated by a number of research groups. One challenge with an MRI-alone workflow is the accurate identification of intraprostatic gold fiducial markers, which are frequently used for prostate localization prior to each dose delivery fraction. This paper investigates a template-matching approach for the detection of these seeds in MRI. Methods: Two different gradient echo T1 and T2* weighted MRI sequences were acquired from fifteen prostate cancer patients and evaluated for seed detection. For training, seed templates from manual contours were selected in a spectral clustering manifold learning framework. This aids in clustering "similar" gold fiducial markers together. The marker with the minimum distance to a cluster centroid was selected as the representative template of that cluster during training. During testing, Gaussian mixture modeling followed by a Markovian model was used in automatic detection of the probable candidates. The probable candidates were rigidly registered to the templates identified from spectral clustering, and a similarity metric is computed for ranking and detection. Results: A fiducial detection accuracy of 95% was obtained compared to manual observations. Expert radiation therapist observers were able to correctly identify all three implanted seeds on 11 of the 15 scans (the proposed method correctly identified all seeds on 10 of the 15). Conclusions: An novel automatic framework for gold fiducial marker detection in MRI is proposed and evaluated with detection accuracies comparable to manual detection. When radiation therapists are unable to determine the seed location in MRI, they refer back to the planning CT (only available in the existing clinical framework); similarly, an automatic quality control is built into the automatic software to ensure that all gold seeds are either correctly detected or a warning is raised for further manual intervention. [ABSTRACT FROM AUTHOR]

Purpose: To estimate the prevalence of rectal and urinary dysfunctional symptoms using image guided radiation therapy (IGRT) with fiducials and magnetic resonance planning for prostate cancer. Methods and Materials: During the implementation stages of IGRT between September 2008 and March 2010, 367 consecutive patients were treated with prostatic irradiation using 3-dimensional conformal radiation therapy with and without IGRT (non-IGRT). In November 2010, these men were asked to report their bowel and bladder symptoms using a postal questionnaire. The proportions of patients with moderate to severe symptoms in these groups were compared using logistic regression models adjusted for tumor and treatment characteristic variables. Results: Of the 282 respondents, the 154 selected for IGRT had higher stage tumors, received higher prescribed doses, and had larger volumes of rectum receiving high dosage than did the 128 selected for non-IGRT. The follow-up duration was 8 to 26 months. Compared with the non-IGRT group, improvement was noted in all dysfunctional rectal symptoms using IGRT. In multivariable analyses, IGRT improved rectal pain (odds ratio [OR] 0.07 [0.009-0.7], P=.02), urgency (OR 0.27 [0.11-0.63], P=<.01), diarrhea (OR 0.009 [0.02-0.35], P<.01), and change in bowel habits (OR 0.18 [0.06-0.52], P<.010). No correlation was observed between rectal symptom levels and dose-volume histogram data. Urinary dysfunctional symptoms were similar in both treatment groups. Conclusions: In comparison with men selected for non-IGRT, a significant reduction of bowel dysfunctional symptoms was confirmed in men selected for IGRT, even though they had larger volumes of rectum treated to higher doses. [Copyright &y& Elsevier]

Abstract: Background and purpose: Dose planning requires a CT scan which provides the electron density distribution for dose calculation. MR provides superior soft tissue contrast compared to CT and the use of MR-alone for prostate planning would provide further benefits such as lower cost to the patient. This study compares the accuracy of MR-alone based dose calculations with bulk electron density assignment to CT-based dose calculations for prostate radiotherapy. Materials and methods: CT and whole pelvis MR images were contoured for 39 prostate patients. Plans with uniform density and plans with bulk density values assigned to bone and tissue were compared to the patient’s gold standard full density CT plan. The optimal bulk density for bone was calculated using effective depth measurements. The plans were evaluated using ICRU point doses, dose volume histograms, and Chi comparisons. Differences in spatial uniformity were investigated for the CT and MR scans. Results: The calculated dose for CT bulk bone and tissue density plans was 0.1±0.6% (mean±1 SD) higher than the corresponding full density CT plan. MR bulk bone and tissue density plans were 1.3±0.8% lower than the full density CT plan. CT uniform density plans and MR uniform density plans were 1.4±0.9% and 2.6±0.9% lower, respectively. Paired t-tests performed on specific points on the DVH graphs showed that points on DVHs for all bulk electron density plans were equivalent with two exceptions. There was no significant difference between doses calculated on Pinnacle and Eclipse. The dose distributions of six patients produced Chi values outside the acceptable range of values when MR-based plans were compared to the full density plan. Conclusions: MR-alone bulk density planning is feasible provided bone is assigned a density, however, manual segmentation of bone on MR images will have to be replaced with automatic methods. The major dose differences for MR bulk density plans are due to differences in patient external contours introduced by the MR couch-top and pelvic coil. [Copyright &y& Elsevier]

Dose planning for prostate radiation therapy is performed using computed tomography (CT) scans that provide the electron density information needed for individual patients' radiation dose calculations.For visualising the prostate and determining the target volume for radiation treatment, magnetic resonance imaging (MRI) gives vastly superior soft‐tissue contrast. However, currently, MRI scans cannot be used for dose planning, as they do not provide the electron density information.We aimed to develop an alternative and efficient MRI‐only image‐based workflow, enabling both organ delineation and dose planning to be performed using MRI, with "pseudo‐CT scans" generated from MRI scans supplying the information for dose planning.The feasibility of implementing MRI‐based prostate radiation therapy planning is being investigated through collaboration between the clinical and medical physics group at the Calvary Mater Newcastle Hospital/University of Newcastle and the biomedical imaging processing group at the CSIRO (Commonwealth Scientific and Industrial Research Organisation) Australian e‐Health Research Centre.Results comparing Hounsfield units calculated from CT scans and from MRI‐based pseudo‐CT scans for 39 patients showed very similar average values for the prostate, bladder, bones and rectum, confirming that pseudo‐CT scans can replace CT scans for accurate radiation dose calculations.MRI‐based radiotherapy planning can also be used for tumours in other locations, such as head and neck, and breast cancers. [ABSTRACT FROM AUTHOR]

Abstract: The purpose of this study was to develop an evidence-based off-line setup correction protocol for systematic errors in prostate radiation therapy. Daily orthogonal electronic portal images were acquired from 30 patients. Field displacements were measured in the medial-lateral (ML), superior-inferior (SI), and anterior-posterior (AP) directions for each treatment fraction. The off-line protocol corrects the mean field displacement found from n consecutive images, starting at a particular fraction of treatment, with a fixed tolerance level. Simulations were performed with the measured data to determine (1) how many images (n) should be averaged to determine the systematic error; (2) on which treatment fraction should the protocol be initiated; and (3) what tolerance level should be applied to determine whether the patient position should be corrected. Uncorrected systematic errors in the ML, SI, and AP directions were (mean position ± 1 standard deviation [SD]): −0.7 ± 2.2 mm, −1.5 ± 1.3 mm, and 1.4 ± 2.6 mm, respectively. Random errors (1 SD and range) were 1.9 mm (1.3–3.3), 1.5 mm (0.–4.1), and 1.8 mm (1.0–2.6), respectively. A correction based on a single image taken on the first fraction actually increased the systematic errors in the ML and SI directions compared with no correction. More accurate correction of systematic errors was achieved with increasing number of images averaged, with only small benefit after 5 images. With fewer images averaged, delaying the start of the protocol resulted in more accurate correction because of the influence of unrepresentative positions at early fractions. The number of corrections made on patients with small (&#60;2 mm) systematic errors was minimized for tolerance values of 2 mm and n ≥ 5 images averaged. The optimal off-line setup correction protocol would be to shift the patient by the mean displacement of the first 5 portal images of a radical course of radiation therapy. A small tolerance level should be utilized with 2 mm giving good accuracy with minimal unnecessary shifts. [Copyright &y& Elsevier]

Although radiation dose escalation improves prostate cancer disease control, it can cause increased toxicity. Genitourinary (GU) symptoms after prostate radiation therapy affect patient health-related quality of life (QoL). We compared patient-reported GU QoL outcomes following 2 alternative urethral sparing stereotactic body radiation therapy regimens. Expanded Prostate Cancer Index Composite (EPIC)–26 GU scores were compared between 2 urethral sparing stereotactic body radiation therapy trials. The SPARK trial prescribed a "Monotherapy" dose of 36.25 Gy in 5 fractions to the prostate. The PROMETHEUS trial prescribed 2 phases: a 19- to 21-Gy in 2 fractions "Boost" to the prostate, followed by 46 Gy in 23 fractions or 36 Gy in 12 fractions. The biological effective dose (BED) for urethral toxicity was 123.9 Gy for Monotherapy and 155.8 to 171.2 Gy for Boost. Mixed effects logistic regression models were utilized to estimate the difference in the odds of a minimal clinically important change from baseline EPIC-26 GU score between regimens at each follow-up. 46 Monotherapy and 149 Boost patients completed baseline EPIC-26 scoring. Mean EPIC-26 GU scores revealed statistically superior urinary incontinence outcomes for Monotherapy at 12 months (mean difference, 6.9; 95% confidence interval [CI], 1.6-12.1; P =.01) and 36 months (mean difference, 9.6; 95% CI, 4.1-15.1; P <.01). Monotherapy also revealed superior mean urinary irritative/obstructive outcomes at 12 months (mean difference, 6.9; 95% CI, 2.0-12.9; P <.01) and 36 months (mean difference, 6.3; 95% CI, 1.9-10.8; P <.01). For both domains and at all time points, the absolute differences were <10%. There were no significant differences in the odds of reporting a minimal clinically important change between regimens at any time point. Even in the presence of urethral sparing, the higher BED delivered in the Boost schedule may have a small adverse effect on GU QoL compared with Monotherapy. However, this did not translate to statistically significant differences in minimal clinically important changes. Whether the higher BED of the boost arm offers an efficacy advantage is being investigated in the Trans Tasman Radiation Oncology Group 18.01 NINJA randomized trial. [ABSTRACT FROM AUTHOR]

Background: CT–MR registration is a critical component of many radiation oncology protocols. In prostate external beam radiation therapy, it allows the propagation of MR-derived contours to reference CT images at the planning stage, and it enables dose mapping during dosimetry studies. The use of carefully registered CT–MR atlases allows the estimation of patient specific electron density maps from MRI scans, enabling MRI-alone radiation therapy planning and treatment adaptation. In all cases, the precision and accuracy achieved by registration influences the quality of the entire process. Problem: Most current registration algorithms do not robustly generalize and lack inverse-consistency, increasing the risk of human error and acting as a source of bias in studies where information is propagated in a particular direction, e.g. CT to MR or vice versa. In MRI-based treatment planning where both CT and MR scans serve as spatial references, inverse-consistency is critical, if under-acknowledged. Purpose: A robust, inverse-consistent, rigid/affine registration algorithm that is well suited to CT–MR alignment in prostate radiation therapy is presented. Method: The presented method is based on a robust block-matching optimization process that utilises a half-way space definition to maintain inverse-consistency. Inverse-consistency substantially reduces the influence of the order of input images, simplifying analysis, and increasing robustness. An open source implementation is available online at http://aehrc.github.io/Mirorr/ . Results: Experimental results on a challenging 35 CT–MR pelvis dataset demonstrate that the proposed method is more accurate than other popular registration packages and is at least as accurate as the state of the art, while being more robust and having an order of magnitude higher inverse-consistency than competing approaches. Conclusion: The presented results demonstrate that the proposed registration algorithm is readily applicable to prostate radiation therapy planning. [ABSTRACT FROM AUTHOR]

Purpose: Kilovoltage intrafraction monitoring (KIM) is a novel software platform implemented on standard radiation therapy systems and enabling real-time image guided radiation therapy (IGRT). In a multi-institutional prospective trial, we investigated whether real-time IGRT improved the accuracy of the dose patients with prostate cancer received during radiation therapy.Methods and Materials: Forty-eight patients with prostate cancer were treated with KIM-guided SABR with 36.25 Gy in 5 fractions. During KIM-guided treatment, the prostate motion was corrected for by either beam gating with couch shifts or multileaf collimator tracking. A dose reconstruction method was used to evaluate the dose delivered to the target and organs at risk with and without real-time IGRT. Primary outcome was the effect of real-time IGRT on dose distributions. Secondary outcomes included patient-reported outcomes and toxicity.Results: Motion correction occurred in ≥1 treatment for 88% of patients (42 of 48) and 51% of treatments (121 of 235). With real-time IGRT, no treatments had prostate clinical target volume (CTV) D98% dose 5% less than planned. Without real-time IGRT, 13 treatments (5.5%) had prostate CTV D98% doses 5% less than planned. The prostate CTV D98% dose with real-time IGRT was closer to the plan by an average of 1.0% (range, -2.8% to 20.3%). Patient outcomes showed no change in the 12-month patient-reported outcomes compared with baseline and no grade ≥3 genitourinary or gastrointestinal toxicities.Conclusions: Real-time IGRT is clinically effective for prostate cancer SABR. [ABSTRACT FROM AUTHOR]

Prostate cancer is the most common solid organ cancer in men, and the second most common cause of male cancer-related mortality. It has few effective therapies, and is difficult to diagnose accurately. Prostate-specific antigen (PSA), which is currently the most effective diagnostic tool available, cannot reliably discriminate between different pathologies, and in fact only around 30% of patients found to have elevated levels of PSA are subsequently confirmed to actually have prostate cancer. As such, there is a desperate need for more reliable diagnostic tools that will allow the early detection of prostate cancer so that the appropriate interventions can be applied. Nuclear magnetic resonance (NMR) spectroscopy and magnetic resonance spectroscopy (MRS) are 2 high throughput, noninvasive analytical procedures that have the potential to enable differentiation of prostate cancer from other pathologies using metabolomics, by focusing specifically on certain metabolites which are associated with the development of prostate cancer cells and its progression. The value that this type of approach has for the early detection, diagnosis, prognosis, and personalized treatment of prostate cancer is becoming increasingly apparent. Recent years have seen many promising developments in the fields of NMR spectroscopy and MRS, with improvements having been made to hardware as well as to techniques associated with the acquisition, processing, and analysis of related data. This review focuses firstly on proton NMR spectroscopy of blood serum, urine, and expressed prostatic secretions in vitro, and then on 1- and 2-dimensional proton MRS of the prostate in vivo. Major advances in these fields and methodological principles of data collection, acquisition, processing, and analysis are described along with some discussion of related challenges, before prospects that proton MRS has for future improvements to the clinical management of prostate cancer are considered. [ABSTRACT FROM AUTHOR]

Purpose: Methods have been recently developed to generate pseudo-computed tomography (pCT) for dose calculation in magnetic resonance imaging (MRI)-only radiation therapy. This study aimed to propose an original nonlocal mean patch-based method (PBM) and to compare this PBM to an atlas-based method (ABM) and to a bulk density method (BDM) for prostate MRI-only radiation therapy.Materials and Methods: Thirty-nine patients received a volumetric modulated arc therapy for prostate cancer. In addition to the planning computed tomography (CT) scans, T2-weighted MRI scans were acquired. pCTs were generated from MRIs using 3 methods: an original nonlocal mean PBM, ABM, and BDM. The PBM was performed using feature extraction and approximate nearest neighbor search in a training cohort. The PBM accuracy was evaluated in a validation cohort by using imaging and dosimetric endpoints. Imaging endpoints included mean absolute error and mean error between Hounsfield units of the pCT and the reference CT (CTref). Dosimetric endpoints were based on dose-volume histograms calculated from the CTref and the pCTs for various volumes of interest and on 3-dimensional gamma analyses. The PBM uncertainties were compared with those of the ABM and BDM.Results: The mean absolute error and mean error obtained from the PBM were 41.1 and -1.1 Hounsfield units. The PBM dose-volume histogram differences were 0.7% for prostate planning target volume V95%, 0.5% for rectum V70Gy, and 0.2% for bladder V50Gy. Compared with ABM and BDM, PBM provided significantly lower dose uncertainties for the prostate planning target volume (70-78 Gy), the rectum (8.5-29 Gy, 40-48 Gy, and 61-73 Gy), and the bladder (12-78 Gy). The PBM mean gamma pass rate (99.5%) was significantly higher than that of ABM (94.9%) or BDM (96.1%).Conclusions: The proposed PBM provides low uncertainties with dose planned on CTref. These uncertainties were smaller than those of ABM and BDM and are unlikely to be clinically significant. [ABSTRACT FROM AUTHOR]

• A clinical target volume delineation quality assurance (QA) framework for MRI-guided prostate radiotherapy was proposed. • The framework adopted a deep learning network with Monte Carlo dropout for uncertainty estimation. • Spatial correlation between the manual delineation and the area of uncertainty generated by the network was incorporated in the QA criteria. • The framework was evaluated on a multicentre MRI-only prostate radiotherapy trial dataset and achieved promising performance in QA classification. Previous studies on automatic delineation quality assurance (QA) have mostly focused on CT-based planning. As MRI-guided radiotherapy is increasingly utilized in prostate cancer treatment, there is a need for more research on MRI-specific automatic QA. This work proposes a clinical target volume (CTV) delineation QA framework based on deep learning (DL) for MRI-guided prostate radiotherapy. The proposed workflow utilized a 3D dropblock ResUnet++ (DB-ResUnet++) to generate multiple segmentation predictions via Monte Carlo dropout which were used to compute an average delineation and area of uncertainty. A logistic regression (LR) classifier was employed to classify the manual delineation as pass or discrepancy based on the spatial association between the manual delineation and the network's outputs. This approach was evaluated on a multicentre MRI-only prostate radiotherapy dataset and compared with our previously published QA framework based on AN-AG Unet. The proposed framework achieved an area under the receiver operating curve (AUROC) of 0.92, a true positive rate (TPR) of 0.92 and a false positive rate of 0.09 with an average processing time per delineation of 1.3 min. Compared with our previous work using AN-AG Unet, this method generated fewer false positive detections at the same TPR with a much faster processing speed. To the best of our knowledge, this is the first study to propose an automatic delineation QA tool using DL with uncertainty estimation for MRI-guided prostate radiotherapy, which can potentially be used for reviewing prostate CTV delineation in multicentre clinical trials. [ABSTRACT FROM AUTHOR]

Purpose: Gantry-mounted megavoltage electronic portal imaging devices (EPIDs) have become ubiquitous on linear accelerators. WatchDog is a novel application of EPIDs, in which the image frames acquired during treatment are used to monitor treatment delivery in real time. We report on the preliminary use of WatchDog in a prospective study of cancer patients undergoing intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) and identify the challenges of clinical adoption.Methods and Materials: At the time of submission, 28 cancer patients (head and neck, pelvis, and prostate) undergoing fractionated external beam radiation therapy (24 IMRT, 4 VMAT) had ≥1 treatment fraction verified in real time (131 fractions or 881 fields). EPID images acquired continuously during treatment were synchronized and compared with model-generated transit EPID images within a frame time (∼0.1 s). A χ comparison was performed to cumulative frames to gauge the overall delivery quality, and the resulting pass rates were reported graphically during treatment delivery. Every frame acquired (500-1500 per fraction) was saved for postprocessing and analysis.Results: The system reported the mean ± standard deviation in real time χ 91.1% ± 11.5% (83.6% ± 13.2%) for cumulative frame χ analysis with 4%, 4 mm (3%, 3 mm) criteria, global over the integrated image.Conclusions: A real-time EPID-based radiation delivery verification system for IMRT and VMAT has been demonstrated that aims to prevent major mistreatments in radiation therapy. [ABSTRACT FROM AUTHOR]

Purpose: We sought to determine whether short-term neoadjuvant androgen deprivation (STAD) duration influences the optimal time point from which Phoenix fail (time to biochemical failure; TTBF) should be measured. Methods and Materials: In the Trans-Tasman Radiation Oncology Group 96.01 trial, men with locally advanced prostate cancer were randomized to 3 or 6 months STAD before and during prostatic irradiation (XRT) or to XRT alone. The prognostic value of TTBF measured from the end of radiation (ERT) and randomization were compared using Cox models. Results: Between 1996 and 2000, 802 eligible patients were randomized. In 436 men with Phoenix failure, TTBF measured from randomization was a powerful predictor of prostate cancer–specific survival and marginally more accurate than TTBF measured from ERT in Cox models. Insufficient data were available to confirm that TTBF measured from testosterone recovery may also be a suitable option. Conclusions: TTBF measured from randomization (commencement of therapy) performed well in this trial dataset and will be a convenient option if this finding holds in other datasets that include long-term androgen deprivation data. [Copyright &y& Elsevier]

Purpose: We studied prostate-specific antigen (PSA) changes after radiation with or without neoadjuvant androgen deprivation to determine posttreatment PSA scenarios in which false-positive biochemical failures (FPBF) are most likely to occur. Methods and Materials: In the Trans-Tasman Radiation Oncology 96.01 Group trial, patients with T2b, 2c, 3, 4 N0 prostate cancer were randomized to 3 or 6 months goserelin and flutamide (STAD) before and during 66 Gy to the prostate and seminal vesicles (XRT) or to XRT alone. Piecewise longitudinal changes in PSA before relapse were characterized and quantified to determine which might cause FPBF calls. Results: Between 1996 and 2000, 802 eligible patients were randomized. Of these, 492 met the criteria for American Society for Therapeutic Radiology and Oncology (ASTRO) failure and 467 for Phoenix failure. Seventy-seven ASTRO fails and 39 Phoenix fails were deemed false positives (FPs). The majority of FPBFs were associated with the “plateauing” in PSA values that follow posttreatment nadir. FPBFs were particularly common in men treated with STAD, in whom small, consecutive PSA rises before or during this phenomenon triggered 56 FP ASTRO fail calls. In these men, the Phoenix fail criteria triggered only 15 FPBF calls. However, the Phoenix criteria were more vulnerable than ASTRO to short-term isolated PSA rises during plateau, which resulted in 15 Phoenix fail calls but only 3 FP ASTRO fails. Conclusions: The Phoenix definition avoided 50% of FPBF calls that occurred with the ASTRO definition. Failures should be confirmed by further PSA rises before investigation and treatment is considered. [Copyright &y& Elsevier]

Purpose: Prostate radiation therapy dose planning directly on magnetic resonance imaging (MRI) scans would reduce costs and uncertainties due to multimodality image registration. Adaptive planning using a combined MRI-linear accelerator approach will also require dose calculations to be performed using MRI data. The aim of this work was to develop an atlas-based method to map realistic electron densities to MRI scans for dose calculations and digitally reconstructed radiograph (DRR) generation. Methods and Materials: Whole-pelvis MRI and CT scan data were collected from 39 prostate patients. Scans from 2 patients showed significantly different anatomy from that of the remaining patient population, and these patients were excluded. A whole-pelvis MRI atlas was generated based on the manually delineated MRI scans. In addition, a conjugate electron-density atlas was generated from the coregistered computed tomography (CT)-MRI scans. Pseudo-CT scans for each patient were automatically generated by global and nonrigid registration of the MRI atlas to the patient MRI scan, followed by application of the same transformations to the electron-density atlas. Comparisons were made between organ segmentations by using the Dice similarity coefficient (DSC) and point dose calculations for 26 patients on planning CT and pseudo-CT scans. Results: The agreement between pseudo-CT and planning CT was quantified by differences in the point dose at isocenter and distance to agreement in corresponding voxels. Dose differences were found to be less than 2%. Chi-squared values indicated that the planning CT and pseudo-CT dose distributions were equivalent. No significant differences (p > 0.9) were found between CT and pseudo-CT Hounsfield units for organs of interest. Mean ± standard deviation DSC scores for the atlas-based segmentation of the pelvic bones were 0.79 ± 0.12, 0.70 ± 0.14 for the prostate, 0.64 ± 0.16 for the bladder, and 0.63 ± 0.16 for the rectum. Conclusions: The electron-density atlas method provides the ability to automatically define organs and map realistic electron densities to MRI scans for radiotherapy dose planning and DRR generation. This method provides the necessary tools for MRI-alone treatment planning and adaptive MRI-based prostate radiation therapy. [Copyright &y& Elsevier]