The pattern of metastases in prostate cancer (PC) is evolving. Increased use of imaging, newer imaging techniques with higher sensitivity for disease detection and patients receiving multiple lines of novel therapies with increased life expectancy are likely to be contributory. Awareness of metastatic disease patterns improves early diagnosis, accurate staging, and initiation of appropriate therapy, and can inform prognostic information and anticipate potential disease complications. The aim of this review is to document the spectrum of metastases in PC including emerging and unusual patterns, and to highlight the role of novel imaging including prostate-specific membrane antigen (PSMA)-positron-emission tomography (PET) and whole-body magnetic resonance imaging (WB-MRI) to improve diagnostic and response assessment accuracy..

Advances in radiotherapy technology have increased precision of treatment delivery and in some tumour types, improved cure rates and decreased side effects. A new generation of radiotherapy machines, hybrids of an MRI scanner and a linear accelerator, has the potential to further transform the practice of radiation therapy in some cancers. Facilitating superior image quality and the ability to change the dose distribution online on a daily basis (termed "daily adaptive replanning"), MRI-guided radiotherapy machines allow for new possibilities including increasing dose, for hard to treat cancers, and more selective sparing of healthy tissues, where toxicity reduction is the key priority.These machines have already been used to treat most types of cancer, although experience is still in its infancy. This review summarises the potential and current evidence for MRI-guided radiotherapy, with a predominant focus on prostate cancer. Current advantages and disadvantages are discussed including a realistic appraisal of the likely potential to improve patient outcomes. In addition, horizon scanning for near-term possibilities for research and development will hopefully delineate the potential role for this technology over the next decade..

.

MRI can help to categorize tissues as malignant or non-malignant both anatomically and functionally, with a high level of spatial and temporal resolution. This non-invasive imaging modality has been integrated with radiotherapy in devices that can differentially target the most aggressive and resistant regions of tumours. The past decade has seen the clinical deployment of treatment devices that combine imaging with targeted irradiation, making the aspiration of integrated MRI-guided radiotherapy (MRIgRT) a reality. The two main clinical drivers for the adoption of MRIgRT are the ability to image anatomical changes that occur before and during treatment in order to adapt the treatment approach, and to image and target the biological features of each tumour. Using motion management and biological targeting, the radiation dose delivered to the tumour can be adjusted during treatment to improve the probability of tumour control, while simultaneously reducing the radiation delivered to non-malignant tissues, thereby reducing the risk of treatment-related toxicities. The benefits of this approach are expected to increase survival and quality of life. In this Review, we describe the current state of MRIgRT, and the opportunities and challenges of this new radiotherapy approach..

Aims

Materials and methods

Results

Conclusion

.

Purpose In 2009, the Radiation Therapy Oncology Group (RTOG) genitourinary members published a consensus atlas for contouring prostate pelvic nodal clinical target volumes (CTVs). Data have emerged further informing nodal recurrence patterns. The objective of this study is to provide an updated prostate pelvic nodal consensus atlas.Methods and materials A literature review was performed abstracting data on nodal recurrence patterns. Data were presented to a panel of international experts, including radiation oncologists, radiologists, and urologists. After data review, participants contoured nodal CTVs on 3 cases: postoperative, intact node positive, and intact node negative. Radiation oncologist contours were analyzed qualitatively using count maps, which provided a visual assessment of controversial regions, and quantitatively analyzed using Sorensen-Dice similarity coefficients and Hausdorff distances compared with the 2009 RTOG atlas. Diagnostic radiologists generated a reference table outlining considerations for determining clinical node positivity.Results Eighteen radiation oncologists' contours (54 CTVs) were included. Two urologists' volumes were examined in a separate analysis. The mean CTV for the postoperative case was 302 cm 3 , intact node positive case was 409 cm 3 , and intact node negative case was 342 cm 3 . Compared with the original RTOG consensus, the mean Sorensen-Dice similarity coefficient for the postoperative case was 0.63 (standard deviation [SD] 0.13), the intact node positive case was 0.68 (SD 0.13), and the intact node negative case was 0.66 (SD 0.18). The mean Hausdorff distance (in cm) for the postoperative case was 0.24 (SD 0.13), the intact node positive case was 0.23 (SD 0.09), and intact node negative case was 0.33 (SD 0.24). Four regions of CTV controversy were identified, and consensus for each of these areas was reached.Conclusions Discordance with the 2009 RTOG consensus atlas was seen in a group of experienced NRG Oncology and international genitourinary radiation oncologists. To address areas of variability and account for new data, an updated NRG Oncology consensus contour atlas was developed..

The drive towards hypofractionated prostate radiotherapy is motivated by a low alpha/beta ratio for prostate cancer (1 to 3 Gy) compared to surrounding organs at risk, implying an improved therapeutic ratio with increasing dose per fraction. Early evidence from studies of ultrahypofractionated (UHF) prostate HDR brachytherapy has shown good tolerability in terms of normal tissue toxicities and clinical outcomes similar to conventional fractionation schedules. MR-guided stereotactic body radiotherapy (SBRT) with online plan adaptation and real-time tumour imaging may enable UHF doses to be delivered to the prostate safely, without the invasiveness of brachytherapy. The feasibility of UHF prostate treatment planning for the Unity MR-Linac (MRL, Elekta AB, Stockholm) was investigated for target prescriptions and planning constraints derived from the HDR brachytherapy and SBRT literature. Monaco 5.40 (Elekta) was used to generate MRL step-and-shoot IMRT plans for three dose fractionation protocols (5, 2 and 1 fractions), for ten randomly selected previously treated prostate cancer patients. Of the ten plans per UHF scheme, all clinical goals were met in all cases for 5 fractions, and in six cases for both 2 and 1 fraction schemes. PTV D95% was compromised by up to 6.4% and 3.9% of the associated target dose for 2 and 1 fraction plans respectively. There were two cases of PTV D95% compromise greater than a 5% dose decrease for the 2 fraction plans. The study suggests feasibility of the UHF treatment planning approaches if combined with real-time motion mitigation strategies..

Purpose Changes in fraction size of external beam radiotherapy (EBRT) exert non-linear impacts on subsequent toxicity. Commonly described by the linear-quadratic model, fraction size sensitivity of normal tissues is expressed by the α/β ratio. Here we study individual α/β ratios for different late rectal side effects after prostate EBRT.Methods and materials The XXXXXXX trial (XX-REGISTRATION-NUMBER-XX) randomised men with non-metastatic prostate cancer 1:1:1 to 74Gy/37 fractions (Fr), 60Gy/20Fr or 57Gy/19Fr. Patients included had full dosimetric data and zero baseline toxicity. Toxicity scales were amalgamated to 6 bowel endpoints: bleeding, diarrhoea, pain, proctitis, sphincter control and stricture. Lyman-Kutcher-Burman models +/- equivalent dose in 2 Gy/fraction correction were log-likelihood fitted by endpoint, estimating α/β ratios. α/β ratio estimate sensitivity was assessed by sequential inclusion of dose modifying factors (DMFs): age, diabetes, hypertension, inflammatory bowel or diverticular disease (IBD/diverticular), and haemorrhoids. 95% confidence intervals (95% CIs) were bootstrapped. Likelihood ratio testing of 632 estimator log-likelihoods compared models.Results Late rectal α/β ratio estimates (without DMF) ranged from: bleeding G1+ α/β = 1.6 Gy (95% CI 0.9-2.5 Gy), up to sphincter control G1+ α/β = 3.1 Gy (1.4-9.1 Gy). Bowel pain modelled poorly (α/β 3.6 Gy, 95% CI 0.0 - 840 Gy). Inclusion of IBD/diverticular disease as a DMF significantly improved fits for stool frequency G2+ (p=0.00041) & proctitis G1+ (p=0.00046). However, the α/β ratios were similar in these no-DMF vs DMF models for both stool frequency G2+ (α/β 2.7 Gy vs 2.5 Gy) and proctitis G1+ (α/β 2.7 Gy vs 2.6 Gy). Frequency-weighted averaging of endpoint α/β ratios produced: G1+ α/β ratio=2.4 Gy; G2+ α/β ratio=2.3 Gy.Conclusions We estimated α/β ratios for several common late rectal radiotherapy side effects. When comparing dose-fractionation schedules we suggest using late rectal α/β ratio ≤ 3 Gy..

.

There has been growing interest in oligometastatic prostate cancer (OMPC) with a mounting body of evidence to suggest that it is a distinct disease state, both biologically and prognostically, when compared to polymetastatic prostate cancer. Three subgroups have been recognised; de novo synchronous, metachronous/oligorecurrent and oligoprogressive disease. The belief that patients with OMPC can be treated more aggressively to improve survival is transforming patient care. Identifying these patients poses the first challenge, and we explore the imaging modalities currently utilised and those that are promising. For patients with de novo synchronous OMPC, both early systemic treatment in addition to androgen deprivation therapy (ADT) and radiotherapy to the prostate increase overall survival (OS), and both are increasingly being integrated into routine clinical practice. Metastasis-directed therapy (MDT) has predominantly been delivered using stereotactic body radiotherapy (SBRT) in prostate cancer and studies have shown SBRT is well-tolerated, provides excellent local control and can be used to delay ADT in the metachronous setting. We discuss the current management strategies in OMPC, review the evidence supporting the use of SBRT and outline ongoing trials..

.

.

Online magnetic resonance-guided radiotherapy (oMRgRT) represents one of the most innovative applications of current image-guided radiation therapy (IGRT). The revolutionary concept of oMRgRT systems is the ability to acquire MR images for adaptive treatment planning and also online imaging during treatment delivery. The daily adaptive planning strategies allow to improve targeting accuracy while avoiding critical structures. This ESTRO-ACROP recommendation aims to provide an overview of available systems and guidance for best practice in the implementation phase of hybrid MR-linac systems. Unlike the implementation of other radiotherapy techniques, oMRgRT adds the MR environment to the daily practice of radiotherapy, which might be a new experience for many centers. New issues and challenges that need to be thoroughly explored before starting clinical treatments will be highlighted..

Purpose: MR-guided Radiation Therapy (MRgRT) allows for high-precision radiotherapy under real-time MR visualization. This enables margin reduction and subsequent dose escalation which may lead to higher tumor control and less toxicity. The Unity MR-linac (Elekta AB, Stockholm, Sweden) integrates a linear accelerator with a 1.5T diagnostic quality MRI and an online adaptive workflow. A prospective international registry was established to facilitate the evidence-based implementation of the Unity MR-linac into clinical practice, to systemically evaluate long-term outcomes, and to aid further technical development of MR-linac-based MRgRT. Methods and Results: In February 2019, the Multi-OutcoMe EvaluatioN of radiation Therapy Using the MR-linac study (MOMENTUM) started within the MR-linac Consortium. The MOMENTUM study is an international academic-industrial partnership between several hospitals and industry partner Elekta. All patients treated on the MR-linac are eligible for inclusion in MOMENTUM. For participants, we collect clinical patient data (e.g., patient, tumor, and treatment characteristics) and technical patient data which is defined as information generated on the MR-linac during treatment. The data are captured, pseudonymized, and stored in an international registry at set time intervals up to two years after treatment. Patients can choose to provide patient-reported outcomes and consent to additional MRI scans acquired on the MR-linac. This registry will serve as a data platform that supports multicenter research investigating the MR-linac. Rules and regulations on data sharing, data access, and intellectual property rights are summarized in an academic-industrial collaboration agreement. Data access rules ensure secure data handling and research integrity for investigators and institutions. Separate data access rules exist for academic and industry partners. This study is registered at ClinicalTrials.gov with ID: NCT04075305 (https://clinicaltrials.gov/ct2/show/NCT04075305). Conclusion: The multi-institutional MOMENTUM study has been set up to collect clinical and technical patient data to advance technical development, and facilitate evidenced-based implementation of MR-linac technology with the ultimate purpose to improve tumor control, survival, and quality of life of patients with cancer..

Evidence is accumulating for seven and less fractions in localised prostate cancer, including one large randomised trial. However, there is much more evidence yet to come and changing practice in advance of this may be premature. We review the reasons to persist with moderate hypofractionation for prostate cancer radiotherapy, until the results of further phase III studies are known..

Purpose To report a planned analysis of the efficacy and toxicity of dose escalation to the intraprostatic dominant nodule identified on multiparametric magnetic resonance imaging using standard and hypofractionated external beam radiation therapy.Methods and materials DELINEATE is a single centre prospective phase 2 multicohort study including standard (cohort A: 74 Gy in 37 fractions) and moderately hypofractionated (cohort B: 60 Gy in 20 fractions) prostate image guided intensity modulated radiation therapy in patients with National Comprehensive Cancer Network intermediate- and high-risk disease. Patients received an integrated boost of 82 Gy (cohort A) and 67 Gy (cohort B) to lesions visible on multiparametric magnetic resonance imaging. Fifty-five patients were treated in cohort A, and 158 patients were treated in cohort B; the first 50 sequentially treated patients in cohort B were included in this planned analysis. The primary endpoint was late Radiation Therapy Oncology Group rectal toxicity at 1 year. Secondary endpoints included acute and late toxicity measured with clinician- and patient-reported outcomes at other time points and biochemical relapse-free survival for cohort A. Median follow-up was 74.5 months for cohort A and 52.0 months for cohort B.Results In cohorts A and B, 27% and 40% of patients, respectively, were classified as having National Comprehensive Cancer Network high-risk disease. The cumulative 1-year incidence of Radiation Therapy Oncology Group grade 2 or worse rectal and urinary toxicity was 3.6% and 0% in cohort A and 8% and 10% in cohort B, respectively. There was no reported late grade 3 rectal toxicity in either cohort. Within cohort A, 4 of 55 (7%) patients had biochemical relapse.Conclusions Delivery of a simultaneous integrated boost to intraprostatic dominant nodules is feasible in prostate radiation therapy using standard and moderately hypofractionated regimens, with rectal and genitourinary toxicity comparable to contemporary series without an intraprostatic boost..

The MR-Linac (MRL) provides a novel treatment modality that enables online adaptive treatments, but also creates new challenges for patient positioning in a laser-free environment. The accuracy and duration of prostate patient set-up on the MRL using two different methods for patient alignment was determined to establish standard of practice on the MRL. Differences in set-up accuracy were significant in the longitudinal direction and are accounted for in online plan adaption. Both methods recorded similar set-up times. The vendor recommended alignment method involves less manipulation of the patient and will be adopted as the standard positioning method for prostate and other pelvic patients on the MRL in future..

Introduction:MR-guided adapted radiotherapy (MRgART) using a high field MR-linac has recently become available. We report the estimated delivered fractional dose of the first five prostate cancer patients treated at our centre using MRgART and compare this to C-Arm linac daily Image Guided Radiotherapy (IGRT). Methods:Patients were treated using adapted treatment plans shaped to their daily anatomy. The treatments were recalculated on an MR image acquired immediately prior to treatment delivery in order to estimate the delivered fractional dose. C-arm linac non-adapted VMAT treatment plans were recalculated on the same MR images to estimate the fractional dose that would have been delivered using conventional radiotherapy techniques using a daily IGRT protocol. Results:95% and 93% of mandatory target coverage objectives and organ at risk dose constraints were achieved by MRgART and C-arm linac delivered dose estimates, respectively. Both delivery techniques were estimated to have achieved 98% of mandatory Organ At Risk (OAR) dose constraints whereas for the target clinical goals, 86% and 80% were achieved by MRgART and C-arm linac delivered dose estimates. Conclusions:Prostate MRgART can be delivered using the a high field MR-linac. Radiotherapy performed on a C-arm linac offers a good solution for prostate cancer patients who present with favourable anatomy at the time of reference imaging and demonstrate stable anatomy throughout the course of their treatment. For patients with critical OARs abutting target volumes on their reference image we have demonstrated the potential for a target dose coverage improvement for MRgART compared to C-arm linac treatment..

Background and purpose Daily image guidance is standard care for prostate radiotherapy. Innovations which improve the accuracy and efficiency of ultrasound guidance are needed, particularly with respect to reducing interobserver variation. This study explores automation tools for this purpose, demonstrated on the Elekta Clarity Autoscan®. The study was conducted as part of the Clarity-Pro trial (NCT02388308). Materials and methods Ultrasound scan volumes were collected from 32 patients. Prostate matches were performed using two proposed workflows and the results compared with Clarity's proprietary software. Gold standard matches derived from manually localised landmarks provided a reference. The two workflows incorporated a custom 3D image registration algorithm, which was benchmarked against a third-party application (Elastix). Results Significant reductions in match errors were reported from both workflows compared to standard protocol. Median (IQR) absolute errors in the left-right, anteroposterior and craniocaudal axes were lowest for the Manually Initiated workflow: 0.7(1.0) mm, 0.7(0.9) mm, 0.6(0.9) mm compared to 1.0(1.7) mm, 0.9(1.4) mm, 0.9(1.2) mm for Clarity. Median interobserver variation was ≪0.01 mm in all axes for both workflows compared to 2.2 mm, 1.7 mm, 1.5 mm for Clarity in left-right, anteroposterior and craniocaudal axes. Mean matching times was also reduced to 43 s from 152 s for Clarity. Inexperienced users of the proposed workflows attained better match precision than experienced users on Clarity. Conclusion Automated image registration with effective input and verification steps should increase the efficacy of interfraction ultrasound guidance compared to the current commercially available tools..

BACKGROUND AND PURPOSE:Anatomical changes during external beam radiotherapy prevent the accurate delivery of the intended dose distribution. Resolving the delivered dose, which is currently unknown, is crucial to link radiotherapy doses to clinical outcomes and ultimately improve the standard of care. MATERIAL AND METHODS:In this study, we present a dose reconstruction workflow based on data routinely acquired during MR-guided radiotherapy. It employs 3D MR images, 2D cine MR images and treatment machine log files to calculate the delivered dose taking intrafractional motion into account. The developed pipeline was used to measure anatomical changes and assess their dosimetric impact in 89 prostate radiotherapy fractions delivered with a 1.5 T MR-linac at our institute. RESULTS:Over the course of radiation delivery, the CTV shifted 0.6 mm ± 2.1 mm posteriorly and 1.3 mm ± 1.5 mm inferiorly. When extrapolating the dose changes in each case to 20 fractions, the mean clinical target volume D98% and clinical target volume D50% dose-volume metrics decreased by 1.1 Gy ± 1.6 Gy and 0.1 Gy ± 0.2 Gy, respectively. Bladder D3% did not change (0.0 Gy ± 1.2 Gy), while rectum D3% decreased by 1.0 Gy ± 2.0 Gy. Although anatomical changes and their dosimetric impact were small in the majority of cases, large intrafractional motion caused the delivered dose to substantially deviate from the intended plan in some fractions. CONCLUSIONS:The presented end-to-end workflow is able to reliably, non-invasively and automatically reconstruct the delivered prostate radiotherapy dose by processing MR-linac treatment log files and online MR images. In the future, we envision this workflow to be adapted to other cancer sites and ultimately to enter widespread clinical use..

•PIVOTALboost evaluates benefits/toxicity of pelvic node RT and focal boost dose escalation.•Unfavourable intermediate/high risk and bulky local disease are most likely to benefit.•Functional MRI imaging is used to select patients for different types of dose escalation.•HDR brachytherapy or focal dose escalation with IMRT are used as options.•Training and support is provided to reduce variations of contouring and radiotherapy planning.•The trial is recruiting patients in 38 radiotherapy centres through the UK..

PURPOSE OF REVIEW:This review summarizes the prospective clinical evidence regarding local therapy in metastatic prostate cancer. RECENT FINDINGS:The phase 3 STAMPEDE trial showed that prostate radiotherapy confers a survival benefit for newly diagnosed patients with low volume metastatic hormone-sensitive prostate cancer (HSPC). No survival benefit was noted for those with high volume disease. A subsequent meta-analysis combining the data of the STAMPEDE trial with that of the HORRAD trial corroborated these findings. The phase 2 randomized STOMP trial investigated local treatment of metastases in patients with oligometastatic HSPC, and showed an improvement in hormone therapy-free survival. Local prostate radiotherapy should be offered to patients with newly diagnosed low volume metastatic HSPC. Early clinical evidence suggests that local treatment to metastatic disease might be beneficial for patients with oligometastatic HSPC, but larger trials are awaited..

Objective To present the long-term adjuvant radiotherapy outcomes of patients with pN3 squamous cell carcinoma of the penis (SCCp) treated at two UK centres.Patients and methods We conducted a retrospective audit of all pN3 SCCp patients, deemed suitable for adjuvant therapy by a specialist multidisciplinary team at St George's and Leeds Hospitals, who received adjuvant radiotherapy. Primary outcomes were recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS). Secondary outcomes were time to adjuvant treatment, frequency of in-field recurrence, site and side of recurrence, and dose and schedule of radiotherapy.Results A total of 146 patients were included: 121 completed radiotherapy, 4 did not complete radiotherapy and 21 did not start it. The median (interquartile range [IQR]) age was 59 (54-70)years. The 5-year RFS was 51%, CSS was 51% and OS was 44%. Adjuvant radiotherapy was started at a median (IQR) of 75 (48-106) days. A dose of 45 Gy in 20 fractions was most commonly used. Of the 125 patients who started adjuvant treatment, 55 relapsed. Of these relapses, 30 occurred in an inguinal or pelvic nodal station and 26 of the 30 were in a radiation field. Relapses in 18 of the 55 cases were in visceral sites only and seven were in both nodal (non-irradiated sites) and visceral sites. Doses of <50 Gy were used more commonly before 2013 and higher doses (>50 Gy) were more commonly used after 2013.Conclusions Application of a standard radiotherapy protocol within a centralized supra-network setting has achieved survival outcomes that would appear better than those previously documented for either radiotherapy or chemotherapy in a cohort with solely pN3 disease. The addition of adjuvant chemotherapy may improve these outcomes further. These data suggest that adjuvant radiotherapy has a role to play in the management of men with pN3 SCCp..

Objective: With increasing incorporation of MRI in radiotherapy, we investigate two MRI sequences for prostate delineation in radiographer-led image guidance.Methods: Five therapeutic radiographers contoured the prostate individually on CT, T 2 weighted (T 2 W) and T 2 * weighted (T 2 *W) imaging for 10 patients. Contours were analysed with Monaco ADMIRE (research v. 2.0) to assess interobserver variability and accuracy by comparison with a gold standard clinician contour. Observers recorded time taken for contouring and scored image quality and confidence in contouring.Results: There is good agreement when comparing radiographer contours to the gold-standard for all three imaging types with Dice similarity co-efficient 0.91-0.94, Cohen's κ 0.85-0.91, Hausdorff distance 4.6-7.6 mm and mean distance between contours 0.9-1.2 mm. In addition, there is good concordance between radiographers across all imaging modalities. Both T 2 W and T 2 *W MRI show reduced interobserver variability and improved accuracy compared to CT, this was statistically significant for T 2 *W imaging compared to CT across all four comparison metrics. Comparing MRI sequences reveals significantly reduced interobserver variability and significantly improved accuracy on T 2 *W compared to T 2 W MRI for DSC and Cohen's κ. Both MRI sequences scored significantly higher compared to CT for image quality and confidence in contouring, particularly T 2 *W. This was also reflected in the shorter time for contouring, measuring 15.4, 9.6 and 9.8 min for CT, T 2 W and T 2 *W MRI respectively. Conclusion: Therapeutic radiographer prostate contours are more accurate, show less interobserver variability and are more confidently and quickly outlined on MRI compared to CT, particularly using T 2 *W MRI. Advances in knowledge: Our work is relevant for MRI sequence choice and development of the roles of the interprofessional team in the advancement of MRI-guided radiotherapy..

Background and purpose Intraprostatic fiducial markers (FM) improve the accuracy of radiotherapy (RT) delivery. Here we assess geometric integrity and contouring consistency using a T2*-weighted (T2*W) sequence alone, which allows visualization of the FM.Material and methods Ten patients scanned within the Prostate Advances in Comparative Evidence (PACE) trial (NCT01584258) had prostate images acquired with computed tomography (CT) and Magnetic Resonance (MR) Imaging: T2-weighted (T2W) and T2*W sequences. The prostate was contoured independently on each imaging dataset by three clinicians. Interobserver variability was assessed using comparison indices with Monaco ADMIRE (research version 2.0, Elekta AB) and examined for statistical differences between imaging sets. CT and MR images of two test objects were acquired to assess geometric distortion and accuracy of marker positioning. The first was a linear test object comprising straight tubes in three orthogonal directions, the second was a smaller test object with markers suspended in gel.Results Interobserver variability for prostate contouring was lower for both T2W and T2*W compared to CT, this was statistically significant when comparing CT and T2*W images. All markers are visible in T2*W images with 29/30 correctly identified, only 3/30 are visible in T2W images. Assessment of geometric distortion revealed in-plane displacements were under 0.375 mm in MRI, and through plane displacements could not be detected. The signal loss in the MR images is symmetric in relation to the true marker position shown in CT images.Conclusion Prostate T2*W images are geometrically accurate, and yield consistent prostate contours. This single sequence can be used to identify FM and for prostate delineation in a mixed MR-CT workflow..

Purpose With the availability of ultra-sensitive PSA assays, early biochemical relapse (eBCR) of prostate cancer is increasingly being detected at values much lower than the conventional threshold of 0.2 ng/ml. Accurate localisation of disease in this setting may allow treatment modification and improved outcomes, especially in patients with pelvis-confined or extra-pelvic oligometastasis (defined as up to three pelvic nodal or distant sites). We aimed to measure the detection rate of [68]Ga-PSMA-HBNED-CC (PSMA)-PET/CT and its influence on patient management in eBCR of prostate cancer following radical prostatectomy (RP).Methods We retrospectively identified 28 patients who underwent PSMA-PET/CT for post-RP eBCR (PSA < 0.5 ng/ml) at our tertiary care cancer centre. Two nuclear medicine physicians independently recorded the sites of PSMA-PET/CT positivity. Multidisciplinary meeting records were accessed to determine changes in management decisions following PSMA-PET/CT scans.Results The mean age of patients was 65.6 years (range: 50-76.2 years); median PSA was 0.22 ng/ml (interquartile range: 0.15 ng/ml to 0.34 ng/ml). Thirteen patients (46.4%) had received radiotherapy in the past. PSMA-PET/CT was positive in 17 patients (60.7%). Only one patient had polymetastasis (> 3 sites); the remainder either had prostatectomy bed recurrence (n = 2), pelvic oligometastasis (n = 10), or extra-pelvic oligometastasis (n = 4). PSMA-PET/CT resulted in management change in 12 patients (42.8%), involving stereotactic body radiotherapy (n = 6), salvage radiotherapy (n = 4), and systemic treatment (n = 2).Conclusions Our findings show that PSMA-PET/CT has a high detection rate in the eBCR setting following RP, with a large proportion of patients found to have fewer than three lesions. PSMA-PET/CT may be of value in patients with early PSA failure, and impact on the choice of potentially curative salvage treatments..

We have developed a method to determine intrafraction motion of the prostate through automatic fiducial marker (FM) tracking on 3D cine-magnetic resonance (MR) images with high spatial and temporal resolution. Twenty-nine patients undergoing prostate stereotactic body radiotherapy (SBRT), with four implanted cylindrical gold FMs, had cine-MR imaging sessions after each of five weekly fractions. Each cine-MR examination consisted of 55 sequentially obtained 3D datasets ('dynamics'), acquired over a 11 s period, covering a total of 10 min. FM locations in the first dynamic were manually identified by a clinician, FM centers in subsequent dynamics were automatically determined. Center of mass (COM) translations and rotations were determined by calculating the rigid transformations between the FM template of the first and subsequent dynamics. The algorithm was applied to 7315 dynamics over 133 scans of 29 patients and the obtained results were validated by comparing the COM locations recorded by the clinician at the halfway-dynamic (after 5 min) and end dynamic (after 10 min). The mean COM translations at 10 min were X: 0.0 [Formula: see text] 0.8 mm, Y: 1.0 [Formula: see text] 1.9 mm and Z: 0.9 [Formula: see text] 2.0 mm. The mean rotation results at 10 min were X: 0.1 [Formula: see text] 3.9°, Y: 0.0 [Formula: see text] 1.3° and Z: 0.1 [Formula: see text] 1.2°. The tracking success rate was 97.7% with a mean 3D COM error of 1.1 mm. We have developed a robust, fast and accurate FM tracking algorithm for cine-MR data, which allows for continuous monitoring of prostate motion during MR-guided radiotherapy (MRgRT). These results will be used to validate automatic prostate tracking based on soft-tissue contrast..

Background Localised prostate cancer is commonly treated with external-beam radiotherapy. Moderate hypofractionation has been shown to be non-inferior to conventional fractionation. Ultra-hypofractionated stereotactic body radiotherapy would allow shorter treatment courses but could increase acute toxicity compared with conventionally fractionated or moderately hypofractionated radiotherapy. We report the acute toxicity findings from a randomised trial of standard-of-care conventionally fractionated or moderately hypofractionated radiotherapy versus five-fraction stereotactic body radiotherapy for low-risk to intermediate-risk localised prostate cancer.Methods PACE is an international, phase 3, open-label, randomised, non-inferiority trial. In PACE-B, eligible men aged 18 years and older, with WHO performance status 0-2, low-risk or intermediate-risk prostate adenocarcinoma (Gleason 4 + 3 excluded), and scheduled to receive radiotherapy were recruited from 37 centres in three countries (UK, Ireland, and Canada). Participants were randomly allocated (1:1) by computerised central randomisation with permuted blocks (size four and six), stratified by centre and risk group, to conventionally fractionated or moderately hypofractionated radiotherapy (78 Gy in 39 fractions over 7·8 weeks or 62 Gy in 20 fractions over 4 weeks, respectively) or stereotactic body radiotherapy (36·25 Gy in five fractions over 1-2 weeks). Neither participants nor investigators were masked to allocation. Androgen deprivation was not permitted. The primary endpoint of PACE-B is freedom from biochemical or clinical failure. The coprimary outcomes for this acute toxicity substudy were worst grade 2 or more severe Radiation Therapy Oncology Group (RTOG) gastrointestinal or genitourinary toxic effects score up to 12 weeks after radiotherapy. Analysis was per protocol. This study is registered with ClinicalTrials.gov, NCT01584258. PACE-B recruitment is complete and follow-up is ongoing.Findings Between Aug 7, 2012, and Jan 4, 2018, we randomly assigned 874 men to conventionally fractionated or moderately hypofractionated radiotherapy (n=441) or stereotactic body radiotherapy (n=433). 432 (98%) of 441 patients allocated to conventionally fractionated or moderately hypofractionated radiotherapy and 415 (96%) of 433 patients allocated to stereotactic body radiotherapy received at least one fraction of allocated treatment. Worst acute RTOG gastrointestinal toxic effect proportions were as follows: grade 2 or more severe toxic events in 53 (12%) of 432 patients in the conventionally fractionated or moderately hypofractionated radiotherapy group versus 43 (10%) of 415 patients in the stereotactic body radiotherapy group (difference -1·9 percentage points, 95% CI -6·2 to 2·4; p=0·38). Worst acute RTOG genitourinary toxicity proportions were as follows: grade 2 or worse toxicity in 118 (27%) of 432 patients in the conventionally fractionated or moderately hypofractionated radiotherapy group versus 96 (23%) of 415 patients in the stereotactic body radiotherapy group (difference -4·2 percentage points, 95% CI -10·0 to 1·7; p=0·16). No treatment-related deaths occurred.Interpretation Previous evidence (from the HYPO-RT-PC trial) suggested higher patient-reported toxicity with ultrahypofractionation. By contrast, our results suggest that substantially shortening treatment courses with stereotactic body radiotherapy does not increase either gastrointestinal or genitourinary acute toxicity.Funding Accuray and National Institute of Health Research..

Oligoprogressive disease is a relatively new clinical concept describing progression at only a few sites of metastasis in patients with otherwise controlled widespread disease. In the era of well-tolerated targeted treatments, resistance inevitably occurs and overcoming this is a challenge. Local ablative therapy for oligoprogressive disease may allow the continuation of systemic treatments by overcoming the few sub-clones that have developed resistance. Stereotactic body radiotherapy is now frequently used in treating oligometastatic disease using ablative doses with minimally invasive techniques and acceptable toxicity. We discuss the current retrospective clinical evidence base supporting the use of local ablative therapy for oligoprogression in metastatic patients on targeted treatments within multiple tumour sites. As there is currently a lack of published prospective data available, the best management for these patients remains unclear. We discuss current trials in recruitment and the potential advancements in treating this group of patients with stereotactic radiotherapy..

Background Stereotactic body radiotherapy (SBRT) and elective nodal radiotherapy (ENRT) are being investigated as metastasis-directed treatments in oligorecurrent prostate cancer (PC); however, comparative data are still lacking.Objective To compare outcome and toxicity between both treatments. Primary endpoint was metastasis-free survival, adjusted for selected variables (aMFS).Design, setting, and participants This was a multi-institutional, retrospective analysis of 506 (SBRT: 309, ENRT: 197) patients with hormone-sensitive nodal oligorecurrent PC (five or fewer lymph nodes (LNs; N1/M1a), treated between 2004 and 2017. Median follow-up was 36 mo (interquartile range 23-56).Intervention SBRT was defined as a minimum of 5 Gy per fraction to each lesion with a maximum of 10 fractions. ENRT was defined as a minimum dose of 45 Gy in up to 25 fractions to the elective nodes, with or without a simultaneous boost to the suspicious node(s). The choice of radiotherapy (RT) was at the discretion of the treating physician, with treatments being unbalanced over the centers.Outcome measurements and statistical analysis In total, 506 patients from 15 different treatment centers were included. Primary treatment was radical prostatectomy, RT, or their combination. Nodal recurrences were detected by positron emission tomography/computer tomography (97%) or conventional imaging (3%). Descriptive statistics was used to summarize patient characteristics.Results and limitations ENRT was associated with fewer nodal recurrences compared with SBRT (p < 0.001). In a multivariable analysis, patients with one LN at recurrence had longer aMFS after ENRT (hazard ratio: 0.50, 95% confidence interval 0.30-0.85, p = 0.009). Late toxicity was higher after ENRT compared with that after SBRT (16% vs. 5%, p < 0.01). Limitations include higher use of hormone therapy in the ENRT cohort and nonstandardized follow-up.Conclusions ENRT reduces the number of nodal recurrences as compared with SBRT, however at higher toxicity. Our findings hypothesize that ENRT should be preferred to SBRT in the treatment of nodal oligorecurrences. This hypothesis needs to be evaluated in a randomized trial.Patient summary This study investigated the difference between stereotactic and elective nodal radiotherapy in treating limited nodal metastatic prostate cancer. Nodal relapse was less frequent following elective nodal radiotherapy than following stereotactic body radiotherapy, and thus elective nodal radiotherapy might be the preferred treatment..

Background and purpose Prostate bed radiotherapy is a standard treatment after radical prostatectomy. Recent evidence suggests that, for patients with a PSA > 0.34 ng/ml, the radiotherapy treatment volume should include not only the prostate bed but also the pelvic lymph nodes. We describe the patterns of failure after prostate bed radiotherapy, focussing on the proportion of patients with radiologically confirmed pelvic nodal failure only, in the absence of distant disease.Materials and methods Patients included were men receiving prostate bed radiotherapy at the Royal Marsden Hospital between 1997 and 2013. The key outcome of interest was the pattern of radiologic failure after prostate bed radiotherapy. Baseline characteristics of patients experiencing pelvic nodal failure without distant disease were compared versus all other relapse patterns. Comparisons were by Chi-square test, with multiple testing adjusted p < 0.005 significant.Results 140 of 322 patients developed biochemical failure after salvage RT. Radiologic failure occurred in 89 patients. 35 of the 89 patients (39%) with radiologic failure had pelvic nodal failure without distant disease, with no significant differences in baseline characteristics when compared to all other patients. The rate of pelvic nodal failure was the same for patients with PSA above or below 0.34 ng/ml (16/149, 95% CI = 6-17% vs 19/171, 95% CI = 7-17%).Conclusions Pelvic lymph node disease, without more distant disease, is a common site of failure in men receiving radiotherapy to the prostate bed, including those with PSA < 0.34 ng/ml. This observation informs the case for including the pelvic lymph nodes in the radiotherapy treatment volume..

.

Six UK studies investigating stereotactic ablative radiotherapy (SABR) are currently open. Many of these involve the treatment of oligometastatic disease at different locations in the body. Members of all the trial management groups collaborated to generate a consensus document on appropriate organ at risk dose constraints. Values from existing but older reviews were updated using data from current studies. It is hoped that this unified approach will facilitate standardised implementation of SABR across the UK and will allow meaningful toxicity comparisons between SABR studies and internationally..

Radiation therapy to the prostate involves increasingly sophisticated delivery techniques and changing fractionation schedules. With a low estimated α/β ratio, a larger dose per fraction would be beneficial, with moderate fractionation schedules rapidly becoming a standard of care. The integration of a magnetic resonance imaging (MRI) scanner and linear accelerator allows for accurate soft tissue tracking with the capacity to replan for the anatomy of the day. Extreme hypofractionation schedules become a possibility using the potentially automated steps of autosegmentation, MRI-only workflow, and real-time adaptive planning. The present report reviews the steps involved in hypofractionated adaptive MRI-guided prostate radiation therapy and addresses the challenges for implementation..

Background: Magnetic resonance (MR)-fusion contouring is the standard of care in prostate stereotactic body radiotherapy (SBRT) for target volume localisation. However, the planning computerised tomography (CT) scan continues to be used for dose calculation and treatment planning and verification. Discrepancies between the planning MR and CT scans may negate the benefits of MR-fusion contouring and it adds a significant resource burden. We aimed to determine whether CT-only contouring resulted in a dosimetric detriment compared with MR-fusion contouring in prostate SBRT planning. Methods: We retrospectively compared target volumes and SBRT plans for 20 patients treated clinically with MR-fusion contouring (standard of care) with those produced by re-contouring using CT data only. Dose was 36.25 Gy in 5 fractions. CT-only contouring was done on two occasions blind to MR data and reviewed by a separate observer. Primary outcome was the difference in rectal volume receiving 36 Gy or above. Results: Absolute target volumes were similar: 63.5 cc (SD ± 27.9) versus 63.2 (SD ± 26.5), Dice coefficient 0.86 (SD ± 0.04). Mean difference in apex superior-inferior position was 1.1 (SD ± 3.5; CI: −0.4–2.6). Small dosimetric differences in favour of CT-only contours were seen, with the mean rectal V36 Gy 0.3 cc (95% CI: 0.1–0.5) lower for CT-only contouring. Conclusions: Prostate SBRT can be successfully planned without MR-fusion contouring. Consideration can be given to omitting MR-fusion from the prostate SBRT workflow, provided reference to diagnostic MR imaging is available. Development of MR-only work flow is a key research priority to gain access to the anatomical fidelity of MR imaging..

There is currently significant interest in the potential benefits of combining radiation and immune checkpoint blockade (ICB) to stimulate both regional and distant abscopal immune responses. In melanoma and lung cancer, patients who have received radiation therapy during ICB appear to have prolonged survival. The PLUMMB trial (Pembrolizumab in Muscle-invasive/Metastatic Bladder cancer) (NCT02560636) is a phase I study to test the tolerability of a combination of weekly radiation therapy with pembrolizumab in patients with metastatic or locally advanced urothelial cancer of the bladder. In the first dose-cohort, patients received pembrolizumab 100 mg 3-weekly, starting 2 weeks before commencing weekly adaptive bladder radiation therapy to a dose of 36 Gy in 6 fractions. The first dose-cohort was stopped after 5 patients, having met the predefined definition of dose-limiting toxicity. Three patients experienced grade 3 urinary toxicities, 2 of which were attributable to therapy. One patient experienced a grade 4 rectal perforation. In view of these findings, the trial has been paused and the protocol will be amended to reduce radiation therapy dose per fraction. The authors advise caution to those combining radiation therapy and ICB, particularly when radiation therapy is given at high dose per fraction for pelvic tumours. The PLUMMB trial met the protocol-defined definition of dose-limiting toxicity and will be amended to reduce radiation therapy dose..

AIMS:There are limited data on dosimetric correlates of toxicity in stereotactic body radiotherapy (SBRT) for prostate cancer. We aimed to identify potential relationships between dose and toxicity using conventional dose-volume histograms (DVHs) and dose-surface maps (DSMs). MATERIALS AND METHODS:Urinary bladder trigone and rectum DSMs were produced for a single-institution service evaluation cohort of 50 patients receiving SBRT for localised prostate cancer, together with conventional DVHs for bladder and rectum. Patients had been prospectively recruited to this cohort and treated according to a pre-defined protocol to a dose of 36.25 Gy in five fractions. Radiation Therapy Oncology Group (RTOG) and International Prostate Symptom Score (IPSS) toxicity data were recorded prospectively. Logistic regression was used to identify dosimetric predictors of acute IPSS+10 (rise of 10 points or more above baseline) and grade 2+ RTOG toxicity. RESULTS:On univariate analysis, trigone area receiving 40 Gy and trigone Dmax were associated with IPSS+10 (odds ratio 1.06 [1.02-1.11], P = 0.007 and odds ratio 1.54 [1.06-2.25], P = 0.024, respectively). These two variables were highly correlated. In a multivariate model, including all baseline variables, trigone Dmax remained associated with IPSS+10 (odds ratio 1.91 [1.13-3.22], P = 0.016). These findings were not significant with Holm-Bonferroni correction for multiple testing (corrected P value threshold 0.006). No associations were seen between rectal toxicity and DVH or DSM parameters. CONCLUSIONS:Our study suggests a potential relationship between high doses to the urinary bladder trigone and patient-reported urinary toxicity in prostate SBRT, and is consistent with previous studies in conventionally fractionated radiotherapy, justifying further evaluation in larger cohorts..

PURPOSE:Our purpose was to perform an in vivo validation of ultrasound imaging for intrafraction motion estimation using the Elekta Clarity Autoscan system during prostate radiation therapy. The study was conducted as part of the Clarity-Pro trial (NCT02388308). METHODS AND MATERIALS:Initial locations of intraprostatic fiducial markers were identified from cone beam computed tomography scans. Marker positions were translated according to Clarity intrafraction 3-dimensional prostate motion estimates. The updated locations were projected onto the 2-dimensional electronic portal imager plane. These Clarity-based estimates were compared with the actual portal-imaged 2-dimensional marker positions. Images from 16 patients encompassing 80 fractions were analyzed. To investigate the influence of intraprostatic markers and image quality on ultrasound motion estimation, 3 observers rated image quality, and the marker visibility on ultrasound images was assessed. RESULTS:The median difference between Clarity-defined intrafraction marker locations and portal-imaged marker locations was 0.6 mm (with 95% limit of agreement at 2.5 mm). Markers were identified on ultrasound in only 3 of a possible 240 instances. No linear relationship between image quality and Clarity motion estimation confidence was identified. The difference between Clarity-based motion estimates and electronic portal-imaged marker location was also independent of image quality. Clarity estimation confidence was degraded in a single fraction owing to poor probe placement. CONCLUSIONS:The accuracy of Clarity intrafraction prostate motion estimation is comparable with that of other motion-monitoring systems in radiation therapy. The effect of fiducial markers in the study was deemed negligible as they were rarely visible on ultrasound images compared with intrinsic anatomic features. Clarity motion estimation confidence was robust to variations in image quality and the number of ultrasound-imaged anatomic features; however, it was degraded as a result of poor probe placement..

.

PURPOSE OF REVIEW: It is now accepted that prostate cancer has a low alpha/beta ratio, establishing a strong basis for hypofractionation of prostate radiotherapy. This review focuses on the rationale for hypofractionation and presents the evidence base for establishing moderate hypofractionation for localised disease as the new standard of care. The emerging evidence for extreme hypofractionation in managing localized and oligometastatic prostate cancer is reviewed. RECENT FINDINGS: The 5-year efficacy and toxicity outcomes from four phase III studies have been published within the last 12 months. These studies randomizing over 6000 patients to conventional fractionation (1.8-2.0 Gy per fraction) or moderate hypofractionation (3.0-3.4 Gy per fraction). They demonstrate hypofractionation to be non-inferior to conventional fractionation. Moderate hypofractionation for localized prostate cancer is safe and effective. There is a growing body of evidence in support of extreme hypofractionation for localized prostate cancer. Extreme hypofractionation may have a role in managing prostate oligometastases, but further studies are needed..

Background The optimal management of the primary tumor in metastatic at diagnosis (M1) prostate cancer (PCa) patients is not yet established. We retrospectively evaluated the effect of locoregional treatment (LRT) on overall survival (OS) hypothesizing that this could improve outcome through better local disease control and the induction of an antitumor immune response (abscopal effect).Patients and methods M1 at diagnosis PCa patients referred to the Prostate Targeted Therapy Group at the Royal Marsden between June 2003 and December 2013 were identified. LRT was defined as either surgery, radiotherapy (RT) or transurethral prostatectomy (TURP) administered to the primary tumor at any time point from diagnosis to death. Kaplan-Meier analyses generated OS data. The association between LRT and OS was evaluated in univariate (UV) and multivariate (MV) Cox regression models.Results Overall 300 patients were identified; 192 patients (64%) experienced local symptoms at some point during their disease course; 72 patients received LRT (56.9% TURP, 52.7% RT). None of the patients were treated with prostatectomy. LRT was more frequently performed in patients with low volume disease (35.4% vs. 16.2%; P < .001), lower prostate-specific antigen (PSA) level at diagnosis (median PSA: 75 vs. 184 ng/mL; P = .005) and local symptoms (34.2% vs. 4.8%; P < .001). LRT was associated in UV and MV analysis with longer OS (62.1 vs. 55.8 months; hazard ratio [HR], 0.74; P = .044), which remained significant for RT (69.4 vs. 55.1 months; HR, 0.54; P = .002) but not for TURP. RT was associated with better OS independent of disease volume at diagnosis.Conclusion These data support the conduct of randomized phase III trials to evaluate the benefit of local control in patients with M1 disease at diagnosis..

.

.

.

Dose escalated radiotherapy improves outcomes for men with prostate cancer. A plateau for benefit from dose escalation using EBRT may not have been reached for some patients with higher risk disease. The use of increasingly conformal techniques, such as step and shoot IMRT or more recently VMAT, has allowed treatment intensification to be achieved whilst minimising associated increases in toxicity to surrounding normal structures. To support further safe dose escalation, the uncertainties in the treatment target position will need be minimised using optimal planning and image-guided radiotherapy (IGRT). In particular the increasing usage of profoundly hypo-fractionated stereotactic therapy is predicated on the ability to confidently direct treatment precisely to the intended target for the duration of each treatment. This article reviews published studies on the influences of varies types of motion on daily prostate position and how these may be mitigated to improve IGRT in future. In particular the role that MRI has played in the generation of data is discussed and the potential role of the MR-Linac in next-generation IGRT is discussed..

Background and purpose Delivering selected parts of volumetric modulated arc therapy (VMAT) plans using step-and-shoot intensity modulated radiotherapy (IMRT) beams has the potential to increase plan quality by allowing specific aperture positioning. This study investigates the quality of treatment plans and the accuracy of in vivo portal dosimetry in such a hybrid approach for the case of prostate radiotherapy.Material and methods Conformal and limited-modulation VMAT plans were produced, together with five hybrid IMRT/VMAT plans, in which 0%, 25%, 50%, 75% or 100% of the segments were sequenced for IMRT, while the remainder were sequenced for VMAT. Integrated portal images were predicted for the plans. The plans were then delivered as a single hybrid beam using an Elekta Synergy accelerator with Agility head to a water-equivalent phantom and treatment time, isocentric dose and portal images were measured.Results Increasing the IMRT percentage improves dose uniformity to the planning target volume (p<0.01 for 50% IMRT or more), substantially reduces the volume of rectum irradiated to 65Gy (p=0.02 for 25% IMRT) and increases the monitor units (p<0.001). Delivery time also increases substantially. All plans show accurate delivery of dose and reliable prediction of portal images.Conclusions Hybrid IMRT/VMAT can be efficiently planned and delivered as a single beam sequence. Beyond 25% IMRT, the delivery time becomes unacceptably long, with increased risk of intrafraction motion, but 25% IMRT is an attractive compromise. Integrated portal images can be used to perform in vivo dosimetry for this technique..

Dose escalation to the prostate improves tumor control but at the expense of increased rectal toxicity. Modern imaging can be used to detect the most common site of recurrence, the intraprostatic lesion (IPL), which has led to the concept of focusing dose escalation to the IPL in order to improve the therapeutic ratio. Imaging must be able to detect lesions with adequate sensitivity and specificity to accurately delineate the IPL. This information must be carefully integrated into the radiotherapy planning process to ensure the dose is targeted to the IPL. This review will consider the role and challenges of multiparametric MRI and PET computed tomography in delineating a tumor boost to be delivered by external beam radiotherapy..

.

.

.

.

.

.

.

.

The management of metastatic solid tumours has historically focused on systemic treatment given with palliative intent. However, radical surgical treatment of oligometastases is now common practice in some settings. The development of stereotactic body radiotherapy (SBRT), building on improvements in delivery achieved by intensity-modulated and image-guided radiotherapy, now allows delivery of ablative doses of radiation to extracranial sites. Many non-randomised studies have shown that SBRT for oligometastases is safe and effective, with local control rates of about 80%. Importantly, these studies also suggest that the natural history of the disease is changing, with 2-5 year progression-free survival of about 20%. Although complete cure might be possible in a few patients with oligometastases, the aim of SBRT in this setting is to achieve local control and delay progression, and thereby also postpone the need for further treatment. We review published work showing that SBRT offers durable local control and the potential for progression-free survival in non-liver, non-lung oligometastatic disease at a range of sites. However, to test whether SBRT really does improve progression-free survival, randomised trials will be essential..

.

.

.

.

.

Introduction In the United Kingdom fiducial marker IGRT is the second most common verification method employed in radical prostate radiotherapy yet little evidence exists to support centres introducing or developing this practice. We developed a survey to elicit current fiducial marker practices adopted in the UK, to recommend standardisation of practice.Methods A 16 question survey was distributed across UK Radiotherapy centres via promotion at the British Uro-Oncology Group Conference, 2016. Included were questions relating to workforce planning, patient preparation, insertion procedure and verification methods. The survey was open from September 2016 to January 2017.Results Results from 15 centres routinely inserting fiducial markers for prostate IGRT are presented. Eleven professional groups insert fiducial markers across the UK. Fourteen centres insert fiducial markers trans-rectally; one trans-perineally. Centres adopting a trans-rectal approach administer prophylactic ciprofloxacin as a single agent or combined with gentamicin or metronidazole; poor agreement between regimes presented. One centre has introduced targeted antibiotic prophylaxis. Five brands of fiducial markers are utilised nationally. Fourteen centres standardly insert three single fiducial markers, two common configurations emerged. Coupled fiducial markers are routinely implanted by one centre. All centres delay at least one week between fiducial marker insertion and planning CT; seven centres wait two weeks. The most common fiducial verification method is two-dimensional, paired kilo Voltage imaging.Conclusion Variation in fiducial marker practice across the UK is considerable. Standardisation is required to support centres and healthcare professionals developing this service. Seven recommendations, to unify practice, have been proposed based on survey results and literature..

Purpose During a global pandemic, the benefit of routine visits and treatment of patients with cancer must be weighed against the risks to patients, staff, and society. Prostate cancer is one of the most common cancers radiation oncology departments treat, and efficient resource utilization is essential in the setting of a pandemic. Herein, we aim to establish recommendations and a framework by which to evaluate prostate radiation therapy management decisions.Methods and materials Radiation oncologists from the United States and the United Kingdom rapidly conducted a systematic review and agreed upon recommendations to safely manage patients with prostate cancer during the COVID-19 pandemic. A RADS framework was created: remote visits, and avoidance, deferment, and shortening of radiation therapy was applied to determine appropriate approaches.Results Recommendations were provided by the National Comprehensive Cancer Network risk group regarding clinical node-positive, postprostatectomy, oligometastatic, and low-volume M1 disease. Across all prostate cancer stages, telemedicine consultations and return visits were recommended when resources/staff available. Delays in consultations and return visits of between 1 and 6 months were deemed safe based on stage of disease. Treatment can be avoided or delayed until safe for very low, low, and favorable intermediate-risk disease. Unfavorable intermediate-risk, high-risk, clinical node-positive, recurrence postsurgery, oligometastatic, and low-volume M1 disease can receive neoadjuvant hormone therapy for 4 to 6 months as necessary. Ultrahypofractionation is preferred for localized, oligometastatic, and low-volume M1, and moderate hypofractionation is preferred for postprostatectomy and clinical node positive disease. Salvage is preferred to adjuvant radiation.Conclusions Resources can be reduced for all identified stages of prostate cancer. The RADS (remote visits, and avoidance, deferment, and shortening of radiation therapy) framework can be applied to other disease sites to help with decision making in a global pandemic..

External beam radiotherapy for prostate cancer is an optimal treatment choice for men with localised prostate cancer and is associated with long term disease control in most patients. Image-guided prostate radiotherapy is standard of care, however, current techniques can include invasive procedures with imaging of poor soft tissue resolution, thus limiting accuracy. MRI is the imaging of choice for local prostate cancer staging and in radiotherapy planning has been shown to reduce target volume and reduce inter-observer prostate contouring variability. The ultimate aim would be to have a MR-only workflow for prostate radiotherapy. Within this article, we discuss these opportunities and challenges, relevant due to the increasing availability of MR-guided radiotherapy. Prospective multi-centre studies are underway to determine the feasibility of MR-guided prostate radiotherapy and daily adaptive replanning. In parallel, development and adaptation of the existing radiotherapy multidisciplinary workforce is essential to enable an efficient and effective MR-guided radiotherapy workflow. This technology potentially provides us with the anatomical and biological information to further improve outcomes for our patients..

Aims To report the relapse pattern of stereotactic body radiotherapy (SBRT) for oligorecurrent nodal prostate cancer (PCa).Materials and methods PCa patients with ≤3 lymph nodes (N1/M1a) at the time of recurrence were treated with SBRT. SBRT was defined as a radiotherapy dose of at least 5 Gy per fraction to a biological effective dose of at least 80 Gy to all metastatic sites. Distant progression-free survival was defined as the time interval between the first day of SBRT and appearance of new metastatic lesions, outside the high-dose region. Relapses after SBRT were recorded and compared with the initially treated site. Secondary end points were local control, time to palliative androgen deprivation therapy and toxicity scored using the Common Terminology Criteria for Adverse Events v4.0.Results Overall, 89 metastases were treated in 72 patients. The median distant progression-free survival was 21 months (95% confidence interval 16-25 months) with 88% of patients having ≤3 metastases at the time of progression. The median time from first SBRT to the start of palliative androgen deprivation therapy was 44 months (95% confidence interval 17-70 months). Most relapses (68%) occurred in nodal regions. Relapses after pelvic nodal SBRT (n = 36) were located in the pelvis (n = 14), retroperitoneum (n = 1), pelvis and retroperitoneum (n = 8) or in non-nodal regions (n = 13). Relapses after SBRT for extrapelvic nodes (n = 5) were located in the pelvis (n = 1) or the pelvis and retroperitoneum (n = 4). Late grade 1 and 2 toxicity was observed in 17% (n = 12) and 4% of patients (n = 3).Conclusion SBRT for oligometastatic PCa nodal recurrences is safe. Most subsequent relapses are again nodal and oligometastatic..

Introduction Dose escalation to dominant intraprostatic lesions (DILs) is a novel method to increase the therapeutic ratio in localised prostate cancer. The Stereotactic Prostate Augmented Radiotherapy with Cyberknife (SPARC) trial was designed to determine the feasibility of a focal boost defined with multiparametric magnetic resonance imaging (mpMRI) using stereotactic ablative body radiotherapy (SABR).Materials and methods Patients were included with newly diagnosed intermediate to high risk prostate cancer with at least one of: Gleason score 4 + 3, stage T3a, or PSA > 20 ng/ml. Visible disease on mpMRI was mandatory and up to 2 separate nodules were allowed. All patients received androgen deprivation. Patients received 36.25 Gy in 5 fractions using CyberKnife® and the DIL received a simultaneous boost to a maximum of 47.5 Gy, as allowed by OAR constraints. Genitourinary (GU) and gastrointestinal (GI) toxicity was reported using the RTOG scoring criteria. International Index of Erectile Function (IIEF) and EQ-5D global health scores were regularly captured.Results An interim safety analysis was performed on the first 8 patients, recruited between July 2013 and December 2015. Median follow up was 56 months (range 50-74). Median D95 values for the prostate PTV and boost volume were 36.55 Gy (range 35.87-36.99) and 46.62 Gy (range 44.85-48.25) respectively. Of the dose constraints, 10/80 were not achieved but all were minor dose variations. Grade 2+ acute GU and GI toxicities were 37.5% respectively while grade 2+ late GU and GI toxicities were 12.5% and 0% respectively. IIEF and quality of life scores recovered over time and all patients remain in biochemical remission.Conclusion The first patients have been successfully treated with prostate SABR and focal boost on the SPARC trial, with excellent adherence to the planning protocol. Toxicity and efficacy results are promising and further recruitment is underway..

Purpose During a global pandemic, the benefit of routine visits and treatment of patients with cancer must be weighed against the risks to patients, staff, and society. Prostate cancer is one of the most common cancers radiation oncology departments treat, and efficient resource utilization is essential in the setting of a pandemic. Herein, we aim to establish recommendations and a framework by which to evaluate prostate radiation therapy management decisions.Methods and materials Radiation oncologists from the United States and the United Kingdom rapidly conducted a systematic review and agreed upon recommendations to safely manage patients with prostate cancer during the COVID-19 pandemic. A RADS framework was created: remote visits, and avoidance, deferment, and shortening of radiation therapy was applied to determine appropriate approaches.Results Recommendations were provided by the National Comprehensive Cancer Network risk group regarding clinical node-positive, postprostatectomy, oligometastatic, and low-volume M1 disease. Across all prostate cancer stages, telemedicine consultations and return visits were recommended when resources/staff available. Delays in consultations and return visits of between 1 and 6 months were deemed safe based on stage of disease. Treatment can be avoided or delayed until safe for very low, low, and favorable intermediate-risk disease. Unfavorable intermediate-risk, high-risk, clinical node-positive, recurrence postsurgery, oligometastatic, and low-volume M1 disease can receive neoadjuvant hormone therapy for 4 to 6 months as necessary. Ultrahypofractionation is preferred for localized, oligometastatic, and low-volume M1, and moderate hypofractionation is preferred for postprostatectomy and clinical node positive disease. Salvage is preferred to adjuvant radiation.Conclusions Resources can be reduced for all identified stages of prostate cancer. The RADS (remote visits, and avoidance, deferment, and shortening of radiation therapy) framework can be applied to other disease sites to help with decision making in a global pandemic..

Background and purpose

Materials and methods

Results

Conclusion

.

Introduction

Methods

Results

Conclusion

Implications for practice

Background and purpose

Methods and materials

Results

Conclusions

Radiation therapy (RT) continues to play an important role in the treatment of cancer. Adaptive RT (ART) is a novel method through which RT treatments are evolving. With the ART approach, computed tomography or magnetic resonance (MR) images are obtained as part of the treatment delivery process. This enables the adaptation of the irradiated volume to account for changes in organ and/or tumor position, movement, size, or shape that may occur over the course of treatment. The advantages and challenges of ART maybe somewhat abstract to oncologists and clinicians outside of the specialty of radiation oncology. ART is positioned to affect many different types of cancer. There is a wide spectrum of hypothesized benefits, from small toxicity improvements to meaningful gains in overall survival. The use and application of this novel technology should be understood by the oncologic community at large, such that it can be appropriately contextualized within the landscape of cancer therapies. Likewise, the need to test these advances is pressing. MR-guided ART (MRgART) is an emerging, extended modality of ART that expands upon and further advances the capabilities of ART. MRgART presents unique opportunities to iteratively improve adaptive image guidance. However, although the MRgART adaptive process advances ART to previously unattained levels, it can be more expensive, time-consuming, and complex. In this review, the authors present an overview for clinicians describing the process of ART and specifically MRgART..

.

The use of stereotactic ablative radiotherapy (SABR) in the UK has expanded over the past decade, in part as the result of several UK clinical trials and a recent NHS England Commissioning through Evaluation programme. A UK SABR Consortium consensus for normal tissue constraints for SABR was published in 2017, based on the existing literature at the time. The published literature regarding SABR has increased in volume over the past 5 years and multiple UK centres are currently working to develop new SABR services. A review and update of the previous consensus is therefore appropriate and timely. It is hoped that this document will provide a useful resource to facilitate safe and consistent SABR practice..

AimsOligoprogression is poorly defined in current literature. Little is known about the natural history and significance of oligoprogression in patients with hormone-resistant prostate cancer on abiraterone or enzalutamide treatment [termed androgen receptor-targeted therapy (ARTT)]. The aim of this study was to determine the prevalence of oligoprogression, describe the characteristics of oligoprogression in a cohort of patients from a single center, and identify the number of patients potentially treatable with stereotactic body radiotherapy (SBRT).MethodsCastration-resistant prostate cancer (CRPC) patients who radiologically progressed while on ARTT were included. Patients with oligoprogressive disease (OPD) (≤3 lesions) on any imaging were identified in a retrospective analysis of electronic patient records. Kaplan–Meier method and log-rank test were used to calculate progression-free and overall survival.ResultsA total of 102 patients with metastatic CRPC on ARTT were included. Thirty (29%) patients presented with oligoprogression (46 lesions in total); 21 (21% of total) patients had lesions suitable for SBRT. The majority of lesions were in the bone (21, 46%) or lymph nodes (15, 33%). Patients with oligoprogression while on ARTT had a significantly better prostate-specific antigen (PSA) response on commencing ARTT as compared to patients who later developed polyprogression. However, PSA doubling time immediately prior to progression did not predict OPD. Median progression-free survival to oligoprogression versus polyprogression was 16.8 vs. 11.7 months. Time to further progression after oligoprogression was 13.6 months in those treated with radiotherapy (RT) for oligoprogression vs. 5.7 months in those treated with the continuation of ARTT alone.ConclusionsIn this study, nearly a third of patients on ARTT for CRPC were found to have OPD. OPD patients had a better PSA response on ART and a longer duration on ARTT before developing OPD as compared to those developing polyprogressive disease (Poly-PD). The majority of patients (70%) with OPD had lesions suitable for SBRT treatment. Prospective randomized control trials are needed to establish if there is a survival benefit of SBRT in oligoprogressive prostate cancer and to determine predictive indicators..

.