Robust Optimization for Prostate Radiation Therapy: Assessment of Delivered Dose by Incorporating Intrafraction Prostate Position Deviations.

Purpose: To assess the robustness of the dose delivered to the clinical target volume (CTV) between planning target volume (PTV)-based and robust optimization planning approaches in localized prostate cancer radiation therapy. Methods and Materials: Retrospective data of 20 patients with prostate cancer, including radiation therapy and real-time prostate position, were analyzed. Two sets of volumetric modulated arc therapy plans were generated per patient: PTV-based and robust optimization. PTV-based planning used a 7-mm CTV-PTV margin, whereas robust planning considered same-magnitude position deviations. Differences in CTV dose delivered to 99% volume (D99), PTV dose delivered to 95% volume (D95), and bladder and rectum V40 (volume receiving 40 Gy) and V60 (volume receiving 60 Gy) values were evaluated. The target position, determined by in-house position monitoring system, was incorporated for dose assessment with and without position deviation correction. Results: In the robust optimization approach, compared with PTV-based planning, the mean (standard deviation) V40 and V60 values of the bladder were reduced by 5.2% (4.1%) and 5.1% (1.9%), respectively. Similarly, for the rectum, the reductions were 0.8% (0.5%) and 0.6% (0.6%). In corrected treatment scenarios, both planning approaches resulted in a mean (standard deviation) CTV D99 difference of 0.1 Gy (0.1 Gy). In the not corrected scenario, PTV-based planning reduced CTV D99 by 0.1 Gy (0.5 Gy), whereas robust planning reduced it by 0.2 Gy (0.6 Gy). There was no statistically significant difference observed in the planned and delivered rectum and bladder dose for both corrected and not corrected scenarios. Conclusions: Robust optimization resulted in lower V40 and V60 values for the bladder compared with PTV-based planning. However, no difference in CTV dose accuracy was found between the 2 approaches.

Dose-Effect Relationship of Kidney Function After SABR for Primary Renal Cell Carcinoma.

PURPOSE: Stereotactic ablative body radiotherapy (SABR) is a novel option to treat primary renal cell carcinoma. However, a high radiation dose may be received by the treated kidney, which may affect its function posttreatment. This study investigates the dose-effect relationship of kidney SABR with posttreatment renal function. METHODS AND MATERIALS: This was a prespecified secondary endpoint of the multicenter FASTRACK II (Focal Ablative STereotactic RAdiotherapy for Cancers of the Kidney phase II) clinical trial (National Clinical Trial 02613819). Patients received either 26 Gy in a single fraction (SF) for tumors with a maximal diameter of 4 cm or less or 42 Gy in 3 fractions (multifraction [MF]) for larger tumors. To determine renal function change, 99mTc-dimercaptosuccinic acid (DMSA) single-photon emission computed tomography/computed tomography (SPECT/CT) scans were acquired, and the glomerular filtration rate was estimated at baseline, 12, and 24 months posttreatment. Imaging data sets were rigidly registered to the planning CT where kidneys were segmented to calculate dose-response curves. RESULTS: From 71 enrolled patients, 36 (51%) and 26 (37%) patients were included in this study based on availability of posttreatment data at 12 and 24 months, respectively. The ipsilateral kidney glomerular filtration rate decreased from baseline by 42% and 39% in the SF cohort and by 45% and 62% in the MF cohort, at 12 and 24 months, respectively (P < .03). The loss in renal function was 3.6%/Gy ± 0.8%/Gy and 4.5%/Gy ± 1.0%/Gy in the SF cohort and 1.7%/Gy ± 0.1%/Gy and 1.7%/Gy ± 0.2%/Gy in the MF cohort at 12 and 24 months, respectively. The major loss in renal function occurred in high-dose regions, where dose-response curves converged to a plateau. CONCLUSIONS: For the first time in a multicenter study, the dose-effect relationship at 12 and 24 months post-SABR treatment for primary renal cell carcinoma was quantified. Kidney function reduces linearly with dose up to 100 Gy BED3.

Evaluating the relationship between contouring variability and modelled treatment outcome for prostate bed radiotherapy.

Objectives.Contouring similarity metrics are often used in studies of inter-observer variation and automatic segmentation but do not provide an assessment of clinical impact. This study focused on post-prostatectomy radiotherapy and aimed to (1) identify if there is a relationship between variations in commonly used contouring similarity metrics and resulting dosimetry and (2) identify the variation in clinical target volume (CTV) contouring that significantly impacts dosimetry.Approach.The study retrospectively analysed CT scans of 10 patients from the TROG 08.03 RAVES trial. The CTV, rectum, and bladder were contoured independently by three experienced observers. Using these contours reference simultaneous truth and performance level estimation (STAPLE) volumes were established. Additional CTVs were generated using an atlas algorithm based on a single benchmark case with 42 manual contours. Volumetric-modulated arc therapy (VMAT) treatment plans were generated for the observer, atlas, and reference volumes. The dosimetry was evaluated using radiobiological metrics. Correlations between contouring similarity and dosimetry metrics were calculated using Spearman coefficient (Γ). To access impact of variations in planning target volume (PTV) margin, the STAPLE PTV was uniformly contracted and expanded, with plans created for each PTV volume. STAPLE dose-volume histograms (DVHs) were exported for plans generated based on the contracted/expanded volumes, and dose-volume metrics assessed.Mainresults. The study found no strong correlations between the considered similarity metrics and modelled outcomes. Moderate correlations (0.5 <Γ< 0.7) were observed for Dice similarity coefficient, Jaccard, and mean distance to agreement metrics and rectum toxicities. The observations of this study indicate a tendency for variations in CTV contraction/expansion below 5 mm to result in minor dosimetric impacts.Significance. Contouring similarity metrics must be used with caution when interpreting them as indicators of treatment plan variation. For post-prostatectomy VMAT patients, this work showed variations in contours with an expansion/contraction of less than 5 mm did not lead to notable dosimetric differences, this should be explored in a larger dataset to assess generalisability.

Prostate Virtual High-dose-rate Brachytherapy Boost: 5-Year Results from the PROMETHEUS Prospective Multicentre Trial.

BACKGROUND AND OBJECTIVE: Despite the high efficacy of high-dose-rate brachytherapy boost (HDRB) in the management of prostate cancer (PC), use of this approach is declining. Similar dosimetry can be achieved using stereotactic body radiotherapy or "virtual HDRB" (vHDRB). The aim of the multicentre, single-arm, phase 2 PROMETHEUS trial (ACTRN12615000223538) was to evaluate the safety and efficacy of vHDRB in patients with PC. METHODS: Patients with intermediate-risk PC or selected patients with high-risk PC were eligible for inclusion. vHDRB was given as 19-20 Gy in two fractions, delivered 1 wk apart, followed by conventionally fractionated external beam radiotherapy (EBRT) at 46 Gy in 23 fractions or 36 Gy in 12 fractions. The primary endpoint was the biochemical/clinical relapse-free rate (bcRFR). Toxicity was graded using Common Terminology Criteria for Adverse Events version 4 and quality of life (QoL) data were collected used the Expanded Prostate Cancer Index Composite-26 questionnaire. KEY FINDINGS AND LIMITATIONS: From March 2014 to December 2018, 151 patients (74% intermediate risk, 26% high risk) with a median age of 69 yr were treated across five centres. Median follow-up was 60 mo. The 5-yr bcRFR was 94.1% (95% confidence interval [CI] 90-98%) and the local control rate was 98.7%. Acute grade 2 gastrointestinal (GI) and genitourinary (GU) toxicity occurred in 6.6% and 23.2% of patients, respectively, with no acute grade 3 toxicity. At 60 mo after treatment, the prevalence of late grade ≥2 GI toxicity was 1.7% (95% CI 0.3-6.5%) and the prevalence of late grade ≥2 GU toxicity was 3.3% (95% CI 1.1-8.8%). Between baseline and 60 mo, QoL improved for urinary obstructive and hormonal domains, was stable for the bowel domain, and deteriorated slightly for the sexual and urinary incontinence domains. CONCLUSIONS: Delivery of gantry-based vHDRB followed by conventionally fractionated EBRT is feasible in a multicentre setting, with high 5-yr bcRFR and low toxicity. This approach is being compared with prostate ultrahypofractionated radiotherapy in the TROG 18.01 NINJA randomised trial (ACTRN12618001806257). PATIENT SUMMARY: The PROMETHEUS trial investigated noninvasive high-dose precision radiotherapy combined with conventional radiotherapy in patients with prostate cancer. We found that this new technique was well tolerated and resulted in better cancer control outcomes than historically reported.

Stereotactic ablative body radiotherapy for primary kidney cancer (TROG 15.03 FASTRACK II): a non-randomised phase 2 trial.

BACKGROUND: Stereotactic ablative body radiotherapy (SABR) is a novel non-invasive alternative for patients with primary renal cell cancer who do not undergo surgical resection. The FASTRACK II clinical trial investigated the efficacy of SABR for primary renal cell cancer in a phase 2 trial. METHODS: This international, non-randomised, phase 2 study was conducted in seven centres in Australia and one centre in the Netherlands. Eligible patients aged 18 years or older had biopsy-confirmed diagnosis of primary renal cell cancer, with only a single lesion; were medically inoperable, were at high risk of complications from surgery, or declined surgery; and had an Eastern Cooperative Oncology Group performance status of 0-2. A multidisciplinary decision that active treatment was warranted was required. Key exclusion criteria were a pre-treatment estimated glomerular filtration rate of less than 30 mL/min per 1·73 m2, previous systemic therapies for renal cell cancer, previous high-dose radiotherapy to an overlapping region, tumours larger than 10 cm, and direct contact of the renal cell cancer with the bowel. Patients received either a single fraction SABR of 26 Gy for tumours 4 cm or less in maximum diameter, or 42 Gy in three fractions for tumours more than 4 cm to 10 cm in maximum diameter. The primary endpoint was local control, defined as no progression of the primary renal cell cancer, as evaluated by the investigator per Response Evaluation Criteria in Solid Tumours (version 1.1). Assuming a 1-year local control of 90%, the null hypothesis of 80% or less was considered not to be worthy of proceeding to a future randomised controlled trial. All patients who commenced trial treatment were included in the primary outcome analysis. This trial is registered with ClinicalTrials.gov, NCT02613819, and has completed accrual. FINDINGS: Between July 28, 2016, and Feb 27, 2020, 70 patients were enrolled and initiated treatment. Median age was 77 years (IQR 70-82). Before enrolment, 49 (70%) of 70 patients had documented serial growth on initial surveillance imaging. 49 (70%) of 70 patients were male and 21 (30%) were female. Median tumour size was 4·6 cm (IQR 3·7-5·5). All patients enrolled had T1-T2a and N0-N1 disease. 23 patients received single-fraction SABR of 26 Gy and 47 received 42 Gy in three fractions. Median follow-up was 43 months (IQR 38-60). Local control at 12 months from treatment commencement was 100% (p<0·0001). Seven (10%) patients had grade 3 treatment-related adverse events, with no grade 4 adverse events observed. Grade 3 treatment-related adverse events were nausea and vomiting (three [4%] patients), abdominal, flank, or tumour pain (four [6%]), colonic obstruction (two [3%]), and diarrhoea (one [1%]). No treatment-related or cancer-related deaths occurred. INTERPRETATION: To our knowledge, this is the first multicentre prospective clinical trial of non-surgical definitive therapy in patients with primary renal cell cancer. In a cohort with predominantly T1b or larger disease, SABR was an effective treatment strategy with no observed local failures or cancer-related deaths. We observed an acceptable side-effect profile and renal function after SABR. These outcomes support the design of a future randomised trial of SABR versus surgery for primary renal cell cancer. FUNDING: Cancer Australia Priority-driven Collaborative Cancer Research Scheme.

Development of Prostate Bed Delineation Consensus Guidelines for Magnetic Resonance Image-Guided Radiotherapy and Assessment of Its Effect on Interobserver Variability.

PURPOSE: The use of magnetic resonance imaging (MRI) in radiotherapy planning is becoming more widespread, particularly with the emergence of MRI-guided radiotherapy systems. Existing guidelines for defining the prostate bed clinical target volume (CTV) show considerable heterogeneity. This study aimed to establish baseline interobserver variability (IOV) for prostate bed CTV contouring on MRI, develop international consensus guidelines, and evaluate its effect on IOV. METHODS AND MATERIALS: Participants delineated the CTV on 3 MRI scans, obtained from the Elekta Unity MR-Linac, as per their normal practice. Radiation oncologist contours were visually examined for discrepancies, and interobserver comparisons were evaluated against simultaneous truth and performance level estimation (STAPLE) contours using overlap metrics (Dice similarity coefficient and Cohen's kappa), distance metrics (mean distance to agreement and Hausdorff distance), and volume measurements. A literature review of postradical prostatectomy local recurrence patterns was performed and presented alongside IOV results to the participants. Consensus guidelines were collectively constructed, and IOV assessment was repeated using these guidelines. RESULTS: Sixteen radiation oncologists' contours were included in the final analysis. Visual evaluation demonstrated significant differences in the superior, inferior, and anterior borders. Baseline IOV assessment indicated moderate agreement for the overlap metrics while volume and distance metrics demonstrated greater variability. Consensus for optimal prostate bed CTV boundaries was established during a virtual meeting. After guideline development, a decrease in IOV was observed. The maximum volume ratio decreased from 4.7 to 3.1 and volume coefficient of variation reduced from 40% to 34%. The mean Dice similarity coefficient rose from 0.72 to 0.75 and the mean distance to agreement decreased from 3.63 to 2.95 mm. CONCLUSIONS: Interobserver variability in prostate bed contouring exists among international genitourinary experts, although this is lower than previously reported. Consensus guidelines for MRI-based prostate bed contouring have been developed, and this has resulted in an improvement in contouring concordance. However, IOV persists and strategies such as an education program, development of a contouring atlas, and further refinement of the guidelines may lead to additional improvements.

Opioid analgesics for nociceptive cancer pain: A comprehensive review.

Pain is one of the most burdensome symptoms in people with cancer, and opioid analgesics are considered the mainstay of cancer pain management. For this review, the authors evaluated the efficacy and toxicities of opioid analgesics compared with placebo, other opioids, nonopioid analgesics, and nonpharmacologic treatments for background cancer pain (continuous and relatively constant pain present at rest), and breakthrough cancer pain (transient exacerbation of pain despite stable and adequately controlled background pain). They found a paucity of placebo-controlled trials for background cancer pain, although tapentadol or codeine may be more efficacious than placebo (moderate-certainty to low-certainty evidence). Nonsteroidal anti-inflammatory drugs including aspirin, piroxicam, diclofenac, ketorolac, and the antidepressant medicine imipramine, may be at least as efficacious as opioids for moderate-to-severe background cancer pain. For breakthrough cancer pain, oral transmucosal, buccal, sublingual, or intranasal fentanyl preparations were identified as more efficacious than placebo but were more commonly associated with toxicities, including constipation and nausea. Despite being recommended worldwide for the treatment of cancer pain, morphine was generally not superior to other opioids, nor did it have a more favorable toxicity profile. The interpretation of study results, however, was complicated by the heterogeneity in the study populations evaluated. Given the limited quality and quantity of research, there is a need to reappraise the clinical utility of opioids in people with cancer pain, particularly those who are not at the end of life, and to further explore the effects of opioids on immune system function and quality of life in these individuals.

Surgical Training in the United Kingdom's National Health Service: The Challenges for International Medical Graduates.

BACKGROUND: The UK's National Health Service (NHS) is a hub that trainees from all over the world want to join. However, there are many challenges for International Medical Graduates (IMGs). The aim of this study is to raise awareness of these challenges and to attempt to identify areas for improvement in the surgical training experience for international graduates wishing to join the NHS and obtain a National Training Number (NTN). METHODS:  A 33-question survey was designed and distributed to the surgical community via The Upper Gastrointestinal Surgery Society (TUGSS) and social media. Eighty-five respondents, IMGs from 25 countries, participated. RESULTS:  The results showed that 43.5% of doctors had a Master's degree (MSc). Most IMGs joined as locally employed doctors at the senior house officer or registrar level. They all faced many challenges in the UK, including difficulties finding a job in the NHS, obtaining an NTN, and adapting to the differences between UK surgical practice and their home country. More than 50% of doctors did not have a named educational/clinical supervisor, and 63.2% of them felt that the supervisor helped them to become more familiar with the system. The support doctors received from the human resources department of the hospital they joined was poor. In addition, more than half of the IMGs changed their career plans after joining the NHS (56.4%) and would like to stay in the UK (52.9%). The majority of them (43.9%) plan to obtain an NTN. CONCLUSIONS: This study showed that there is a need to support international doctors who wish to start or continue their training in the UK. Furthermore, IMGs should expect to face several challenges when applying to work in the UK NHS.

Pembrolizumab with Chemoradiation as Treatment for Muscle-invasive Bladder Cancer: Analysis of Safety and Efficacy of the PCR-MIB Phase 2 Clinical Trial (ANZUP 1502).

BACKGROUND: Radiation may improve the efficacy of immune checkpoint inhibition. This study investigates the combination of pembrolizumab and chemoradiation (CRT) for muscle-invasive bladder cancer (MIBC). OBJECTIVE: To assess the feasibility and safety of pembrolizumab combined with CRT for MIBC. DESIGN, SETTING, AND PARTICIPANTS: A single-arm phase 2 trial was performed with 28 participants having cT2-T4aN0M0 MIBC (Eastern Cooperative Oncology Group performance status 0-1; estimated glomerular filtration rate ≥40 ml/min; no contraindications to pembrolizumab) suitable for CRT. INTERVENTION: Whole bladder radiation therapy (RT; 64 Gy in 32 daily fractions, over 6.5 wk, combined with cisplatin (35 mg/m2 intravenously [IV] weekly, six doses) and pembrolizumab (200 mg IV q3 weeks, seven doses), both starting with RT. Surveillance cystoscopy/biopsy and computerised tomography scans performed 12 and 24 wk after CRT. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was feasibility, determined by a prespecified satisfactory low rate of grade 3 or worse nonurinary toxicity or completion of planned CRT according to defined parameters. Secondary endpoints were complete cystoscopic response, locoregional progression-free survival (LRPFS), distant metastasis-free survival (DMFS), and overall survival (OS). RESULTS AND LIMITATIONS: Twenty-eight patients were enrolled with a 31-mo median follow-up. Six had Grade >3 nonurinary adverse events during/within 12 wk after treatment; three had more than one cisplatin dose reduction. The 24-wk post-CRT complete response (CR) rate was 88%. Eight patients developed metastatic disease, and three had nonmetastatic progression. The DMFS at 2 yr is 78% (95% confidence interval [CI] 54-90%), with LRPFS at 2 yr of 87% (95% CI 64-96%) and median OS of 39 mo (95% CI 17.1-not evaluable). Limitations are the single-arm design and sample size. CONCLUSIONS: Combining pembrolizumab with CRT for MIBC was feasible, with manageable toxicity and promising CR rates. PATIENT SUMMARY: Immunotherapy treats nonmetastatic/metastatic bladder cancer effectively. We combined pembrolizumab with chemotherapy and radiation to assess its safety and impact on treatment delivery. The combination was feasible with encouraging early activity. Further larger trials are warranted.

Assessment of intrafraction motion and its dosimetric impact on prostate radiotherapy using an in-house developed position monitoring system.

Purpose: To implement an in-house developed position monitoring software, SeedTracker, for conventional fractionation prostate radiotherapy, and study the effect on dosimetric impact and intrafraction motion. Methods: Thirty definitive prostate radiotherapy patients with implanted fiducial markers were included in the study. All patients were treated with VMAT technique and plans were generated using the Pinnacle planning system using the 6MV beam model for Elekta linear accelerator. The target dose of 60 Gy in 20 fractions was prescribed for 29 of 30 patients, and one patient was treated with the target dose of 78 Gy in 39 fractions. The SeedTracker position monitoring system, which uses the x-ray images acquired during treatment delivery in the Elekta linear accelerator and associated XVI system, was used for online prostate position monitoring. The position tolerance for online verification was progressively reduced from 5 mm, 4 mm, and to 3 mm in 10 patient cohorts to effectively manage the treatment interruptions resulting from intrafraction motion in routine clinical practice. The delivered dose to target volumes and organs at risk in each of the treatment fractions was assessed by incorporating the observed target positions into the original treatment plan. Results: In 27 of 30 patients, at least one gating event was observed, with a total of 177 occurrences of position deviation detected in 146 of 619 treatment fractions. In 5 mm, 4 mm, and 3 mm position tolerance cohorts, the position deviations were observed in 13%, 24%, and 33% of treatment fractions, respectively. Overall, the mean (range) deviation of -0.4 (-7.2 to 5.3) mm, -0.9 (-6.1 to 15.6) mm, and -1.7 (-7.0 to 6.1) mm was observed in Left-Right, Anterior-Posterior, and Superior-Inferior directions, respectively. The prostate CTV D99 would have been reduced by a maximum value of 1.3 Gy compared to the planned dose if position deviations were uncorrected, but with corrections, it was 0.3 Gy. Similarly, PTV D98 would have been reduced by a maximum value of 7.6 Gy uncorrected, with this difference reduced to 2.2 Gy with correction. The V60 to the rectum increased by a maximum of 1.0% uncorrected, which was reduced to 0.5%. Conclusion: Online target position monitoring for conventional fractionation prostate radiotherapy was successfully implemented on a standard Linear accelerator using an in-house developed position monitoring software, with an improvement in resultant dose to prostate target volume.

Reducing the margin in prostate radiotherapy: optimizing radiotherapy with a general-purpose linear accelerator using an in-house position monitoring system.

Purpose: To study the feasibility of optimizing the Clinical Target Volume to Planning Target Volume (CTV-PTV) margin in prostate radiotherapy(RT) with a general-purpose linear accelerator using an in-house developed position monitoring system, SeedTracker. Methods: A cohort of 30 patients having definitive prostate radiotherapy treated within an ethics-approved prospective trial was considered for this study. The intrafraction prostate motion and the position deviations were measured using SeedTracker system during each treatment fraction. Using this data the CTV-PTV margin required to cover 90% of the patients with a minimum of 95% of the prescription dose to CTV was calculated using van Herk's formula. The margin calculations were performed for treatment scenarios both with and without applying the position corrections for observed position deviations. The feasibility of margin reduction with real-time monitoring was studied by assessing the delivered dose that incorporates the actual target position during treatment delivery and comparing it with the planned dose. This assessment was performed for plans generated with reduced CTV-PTV margin in the range of 7mm-3mm. Results: With real-time monitoring and position corrections applied the margin of 2.0mm, 2.1mm and 2.1mm in LR, AP and SI directions were required to meet the criteria of 90% population to receive 95% of the dose prescription to CTV. Without position corrections applied for observed position deviations a margin of 3.1mm, 4.0mm and 3.0mm was required in LR, AP and SI directions to meet the same criteria. A mean ± SD reduction of 0.5 ± 1.8% and 3 ± 7% of V60 for the rectum and bladder can be achieved for every 1mm reduction of PTV margin. With position corrections applied, the CTV D99 can be delivered within -0.2 ± 0.3 Gy of the planned dose for plans with a 3mm margin. Without applying corrections for position deviations the CTV D99 was reduced by a maximum of 1.1 ± 1.1 Gy for the 3mm margin plan and there was a statistically significant difference between planned and delivered dose for 3mm and 4mm margin plans. Conclusion: This study demonstrates the feasibility of reducing the margin in prostate radiotherapy with SeedTracker system without compromising the dose delivery accuracy to CTV while reducing dose to critical structures.

Clinical target volume delineation quality assurance for MRI-guided prostate radiotherapy using deep learning with uncertainty estimation.

BACKGROUND AND PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Patterns of practice regarding use of radiation therapy following radical prostatectomy: A survey of Radiation Oncologists and Urologists in Australia and New Zealand.

INTRODUCTION: This study aimed to investigate the patterns of practices of radiation oncologists (ROs) and urologists in Australia and New Zealand with respect to the utilisation of post-prostatectomy radiation therapy (RT) and help guide the development of an update to the existing Faculty of Radiation Oncology Genito-Urinary Group post-prostatectomy guidelines. METHODS: ROs and urologists with subspecialty practice in prostate cancer from Australia and New Zealand were invited to participate in an online survey comprised of clinical scenarios regarding post-prostatectomy RT. RESULTS: Sixty-five ROs and 28 urologists responded to the survey. In the setting of low-risk biochemical relapse, the threshold for initiating RT was lower for ROs than urologists. ROs were more likely than urologists to recommend adjuvant RT for node-positive disease. When salvage RT was advised for a pT3N0R1 recurrence, there was no consensus amongst ROs on whether to add either ADT or nodal treatment over prostate bed RT alone. For a solitary PSMA-avid pelvic lymph node recurrence, whole pelvis RT with androgen deprivation therapy was the preferred treatment option (72% ROs, 43% urologists). Most ROs (92%) recommended conventionally fractionated RT to 66-70 Gy, with a boost to any PSMA PET avid recurrent disease. CONCLUSION: This survey highlights the marked discordance in practice for the management of prostate cancer relapse post-prostatectomy. This is seen not only between specialties but also within the radiation oncology community. This emphasises the need for an updated evidence-based guideline to be produced.

Virtual HDR Boost for Prostate Cancer: Rebooting a Classic Treatment Using Modern Tech.

Prostate cancer (PC) is the most common malignancy in men. Internal radiotherapy (brachytherapy) has been used to treat PC successfully for over a century. In particular, there is level-one evidence of the benefits of using brachytherapy to escalate the dose of radiotherapy compared with standard external beam radiotherapy approaches. However, the use of PC brachytherapy is declining, despite strong evidence for its improved cancer outcomes. A method using external beam radiotherapy known as virtual high-dose-rate brachytherapy boost (vHDRB) aims to noninvasively mimic a brachytherapy boost radiation dose plan. In this review, we consider the evidence supporting brachytherapy boosts for PC and the continuing evolution of vHDRB approaches, culminating in the current generation of clinical trials, which will help define the role of this emerging modality.

Genitourinary Quality-of-Life Comparison Between Urethral Sparing Prostate Stereotactic Body Radiation Therapy Monotherapy and Virtual High-Dose-Rate Brachytherapy Boost.

PURPOSE: 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. METHODS AND MATERIALS: 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. RESULTS: 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. CONCLUSIONS: 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.

Encouraging Patients to Ask Questions: Development and Pilot Testing of a Question Prompt List for Patients Undergoing a Biopsy for Suspected Prostate Cancer.

This study assessed the acceptability and feasibility of a question prompt list (QPL) to facilitate informed treatment decision-making in men with suspected localised prostate cancer, which involves values-based choices between options with similar efficacy but different side effects. The QPL was developed through iterative consultation with consumers, clinicians and researchers. Acceptability was assessed using study-specific questions regarding QPL satisfaction and usefulness and qualitative interviews. Feasibility was determined via the proportion of men given the QPL according to medical records and the completion of standardised measures of decisional outcomes. Quantitative data were analysed using descriptive and univariate statistics. Qualitative data were thematically analysed. Fifty-two men consented; 34 provided data for analysis. The QPL recipients reported moderate-high content satisfaction (70.6%) and perceived usefulness in guiding appointments when receiving biopsy results (64.7%). Two main qualitative themes also indicated the QPL acceptability: (1) the freedom to ask-acceptable timing, flexible usage and usefulness of the QPL, and (2) satisfaction with the QPL content. However, only 18.4% of eligible men received the QPL, indicating limited feasibility. The QPL is safe and acceptable, but further research is needed regarding how to facilitate the uptake of the question prompt list in clinical practice.

Implementing online position monitoring for prostate radiotherapy using an in-house position monitoring system: User experience and impact on workforce.

INTRODUCTION: To evaluate the feasibility of prostate intrafraction motion monitoring using the SeedTracker real-time image guidance system in order to improve targeting accuracy in prostate radiotherapy. METHODS: SeedTracker was used to monitor prostate gold fiducial seeds with kV x-ray imaging during radiotherapy in 30 patients. Feedback from radiation therapists was collected via the use of a user evaluation form. The impact on treatment time was established by using a record and verify system. The effective dose and a risk of exposure-induced cancer death (REID) were estimated for a 60-year-old patient when using the SeedTracker system. RESULTS: A total of 22 radiation therapists completed user evaluation forms. The time taken to prepare a reference data set for one patient varied with three (13.6%) radiation therapists taking less than 2 min, 10 (45.5%) between 2 and 4 min, eight (36.4%) between 4 and 6 min and one (4.5%) between 6 and 8 min. The useability of the SeedTracker system was reported as 'easy' by 21 (95.5%) radiation therapists and 'hard' by 1 (4.5%) radiation therapist. Mean treatment time changed from 6 to 7 min with prostate-only radiotherapy treatment and from 6.9 to 10.2 min with prostate and whole pelvis radiotherapy treatments. The maximum effective dose with the SeedTracker was 1.6276 mSv, and increase in REID was 0.007%. CONCLUSION: The SeedTracker real-time image guidance system is a feasible tool to use in radiotherapy departments to monitor and correct for prostate intrafraction motion.

Mechanisms, mitigation, and management of urinary toxicity from prostate radiotherapy.

Urinary toxicity is common following pelvic radiotherapy and can have a substantial negative effect on survivorship. Due to its prevalence and the increasing number of related clinical trials, localised prostate cancer radiotherapy is a useful illustrative tool to explore urinary toxicity. A good understanding of the interplay between anatomy, radiation-sensitive cell populations, and treatment sequencing is necessary for optimal outcomes. Emerging evidence suggests that the prostatic urethra is a radiation-sensitive structure, not only for stricture development, but also chronic irritative symptoms. Tools now exist not only to identify the urethra, but also to direct radiation dose away from the urethra, with early data suggesting that this reduces moderate-to-severe late urinary toxicity. Coupled with new evidence supporting dominant nodule microboosting and ultrahypofractionation as emerging standards of care, urethral sparing radiotherapy is a powerful tool against radiation induced urinary toxicity while also maximising disease control.

Evaluating the utility of knowledge-based planning for clinical trials using the TROG 08.03 post prostatectomy radiation therapy planning data.

Background and purpose: Poor quality radiotherapy can detrimentally affect outcomes in clinical trials. Our purpose was to explore the potential of knowledge-based planning (KBP) for quality assurance (QA) in clinical trials. Materials and methods: Using 30 in-house post-prostatectomy radiation treatment (PPRT) plans, an iterative KBP model was created according to the multicentre clinical trial protocol, delivering 64 Gy in 32 fractions. KBP was used to replan 137 plans. The KB (knowledge based) plans were evaluated for their ability to fulfil the trial constraints and were compared against their corresponding original treatment plans (OTP). A second analysis between only the 72 inversely planned OTPs (IP-OTPs) and their corresponding KB plans was performed. Results: All dose constraints were met in 100% of KB plans versus 69% of OTPs. KB plans demonstrated significantly less variation in PTV coverage (Mean dose range: KB plans 64.1 Gy-65.1 Gy vs OTP 63.1 Gy-67.3 Gy, p < 0.01). KBP resulted in significantly lower doses to OARs. Rectal V60Gy and V40Gy were 17.7% vs 27.7% (p < 0.01) and 40.5% vs 53.9% (p < 0.01) for KB plans and OTP respectively. Left femoral head (FH) V45Gy and V35Gy were 0.4% vs 7.4% (p < 0.01) and 7.9% vs 34.9% (p < 0.01) respectively. In the second analysis plan improvements were maintained. Conclusions: KBP created high quality PPRT plans using the data from a multicentre clinical trial in a single optimisation. It is a powerful tool for utilisation in clinical trials for patient specific QA, to reduce dose to surrounding OARs and variations in plan quality which could impact on clinical trial outcomes.

Low conflict and high satisfaction: Decisional outcomes after attending a combined clinic to choose between robotic prostatectomy and radiotherapy for prostate cancer.

BACKGROUND: Decisional conflict and post-treatment decisional regret have been documented in men with localised prostate cancer (LPC). However, there is limited evidence regarding decisional outcomes associated with the choice between robotic-assisted radical prostatectomy (RARP) and radiotherapy, when both treatment options are available in the public health system. There is increasing support for multidisciplinary approaches to guide men with LPC in their decision-making process. This study assessed decisional outcomes in men deciding between RARP or radiotherapy treatment before and after attending a LPC combined clinic (CC). METHODS: Quantitative longitudinal data were collected from 52 men who attended a LPC CC, where they saw both a urologist and radiation oncologist. Patients completed questionnaires assessing involvement in decision-making, decisional conflict, satisfaction and regret before and after the CC, three months, six months and 12 months post-treatment. Urologists and radiation oncologists also reported their perceptions regarding patients' suitability for, openness to, perceived preferences and appropriateness for each treatment. Data was analysed using paired/independent samples t-tests and McNemar's tests. RESULTS: Most participants (n = 37, 71%) opted for RARP over radiotherapy (n = 14, 27%); one participant deferred treatment (2%). Urologists and radiation oncologists reported low agreement (κ = 0.26) regarding the most appropriate treatment for each patient. Participants reported a desire for high levels of control over their decision-making process (77.5% patient-led, 22.5% shared) and high levels of decisional satisfaction (M = 4.4, SD = 0.47) after the CC. Decisional conflict levels were significantly reduced (baseline: M = 29.3, SD = 16.9, post-CC: M = 16.3, SD = 11.5; t = 5.37, P < 0.001) after the CC. Mean decisional regret scores were 'mild' at three-months (M = 16.0, SD = 17.5), six-months (M = 18.8, SD = 18.7) and 12-months (M = 18.2, SD = 15.1) post-treatment completion. CONCLUSION: This is the first Australian study to assess decisional outcomes when patients are offered the choice between RARP and radiotherapy in the public health system. A CC seems to support decision-making in men with LPC and positively impact some decisional outcomes. However, larger-scale controlled studies are needed to confirm these findings.