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Background and Purpose: Over the past decade, tools for automation of various sub-tasks in radiotherapy planning have been introduced, such as auto-contouring and auto-planning. The purpose of this study was to benchmark what degree of automation is possible., Materials and Methods: A challenge to perform automated treatment planning for prostate and prostate bed radiotherapy was set up. Participants were provided with simulation CTs and a treatment prescription and were asked to use automated tools to produce a deliverable radiotherapy treatment plan with as little human intervention as possible. Plans were scored for their adherence to the protocol when assessed using consensus expert contours., Results: Thirteen entries were received. The top submission adhered to 81.8% of the minimum objectives across all cases using the consensus contour, meeting all objectives in one of the ten cases. The same system met 89.5% of objectives when assessed with their own auto-contours, meeting all objectives in four of the ten cases. The majority of systems used in the challenge had regulatory clearance (Auto-contouring: 82.5%, Auto-planning: 77%). Despite the 'hard' rule that participants should not check or edit contours or plans, 69% reported looking at their results before submission., Conclusions: Automation of the full planning workflow from simulation CT to deliverable treatment plan is possible for prostate and prostate bed radiotherapy. While many generated plans were found to require none or minor adjustment to be regarded as clinically acceptable, the result indicated there is still a lack of trust in such systems preventing full automation., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [MJG is shareholder and director of Inpictura Ltd. TGU has institutional funding from Therapanacea for research project (completed). All remaining authors have declared no conflicts of interest]., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background and Purpose: Introducing moderately hypofractionated salvage radiotherapy (SRT) following prostatectomy obligates investigation of its effects on clinical target volume (CTV) coverage and organ-at-risk (OAR) doses. This study assessed interfractional volume and dose changes in OARs and CTV in moderately hypofractionated SRT and evaluated the 8-mm planning target volume (PTV) margin., Materials and Methods: Twenty patients from the PERYTON-trial were included; 10 received conventional SRT (35 × 2 Gy) and 10 hypofractionated SRT (20 × 3 Gy). OARs were delineated on 539 pre-treatment Cone Beam CT (CBCT) scans to compare interfractional OAR volume changes. CTVs for the hypofractionated group were delineated on 199 CBCTs. Dose distributions with 4 and 6 mm PTV margins were generated using voxel-wise minimum robustness evaluation of the original 8-mm PTV plan, and dose changes were assessed., Results: Median volume changes for bladder and rectum were -26 % and -10 %, respectively. OAR volume changes were not significantly different between the two treatment schedules. The 8-mm PTV margin ensured optimal coverage for prostate bed and vesicle bed CTV (V95 = 100 % in >97 % fractions). However, bladder V60 <25 % was not achieved in 5 % of fractions, and rectum V60 <5 % was unmet in 33 % of fractions. A 6-mm PTV margin resulted in CTV V95 = 100 % in 92 % of fractions for prostate bed, and in 86 % for vesicle bed CTV., Conclusions: Moderately hypofractionated SRT yielded comparable OAR volume changes to conventionally fractionated SRT. Interfractional changes remained acceptable with a PTV margin of 6 mm for prostate bed and 8 mm for vesicle bed., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The PERYTON-trial is sponsored by Dutch Cancer Society (KWF Kanker Bestrijding grant number 12649). S. Aluwini reports a role as Chair of the LPRU (Landelijk Platform Radiotherapie Urologische Tumoren). J.A. Langendijk reports a relationship with Dutch Cancer Society that includes: funding grants. J.A. Langendijk reports a relationship with Global Scientific Advisory Board of IBA. That includes: board membership. J.A. Langendijk reports a relationship with RayCare International Advisory Board of RaySearch that includes: board membership. J.A. Langendijk reports a relationship with IBA that includes: speaking and lecture fees. J.A. Langendijk reports a relationship with the Netherlands Society for Radiation Oncology that includes: board membership., (© 2024 The Authors. Published by Elsevier B.V. on behalf of European Society of Radiotherapy & Oncology.)

Background and Purpose: Stereotactic body radiotherapy (SBRT) is increasingly applied for pelvic lymph node recurrence. Thus far, knowledge on pelvic lymph node motion during CBCT-guided SBRT is lacking and the applied margins vary between institutions. This study evaluated pelvic lymph node motion during CBCT-guided SBRT and assessed the currently applied PTV margins of 3 and 5 mm., Material and Methods: In total, 45 pelvic lymph node metastases were included. One observer delineated 45 GTVs on planning CT, 224 GTVs on pre-fraction and 216 on post-fraction CBCT. The GTV centroid coordinates were derived from all images for inter- and intrafraction motion analysis. Additionally, we assessed the influence of treatment time and lesion location on lesion motion. The expected coverage of a 3-mm and 5-mm PTV margin was assessed using the inclusiveness index for GTVs on pre- and post-fraction CBCT., Results: Lymph node interfraction motion was limited to 5 mm in 96-97 % of fractions for all translational directions and intrafraction lesion motion was limited to 3 mm in 97-100 % of fractions. Para-rectal lesions (11 %) were associated with significantly larger inter- and intrafraction motion compared to other pelvic locations and treatment duration showed no correlation with lesion motion. The mean (sd) lesion inclusiveness index was 99 % (5 %) for the 5-mm PTV margin and 96 % (9 %) for the 3-mm margin., Conclusion: Pelvic lymph node motion during CBCT-guided stereotactic radiotherapy was within the widely applied PTV margin of 5 mm, providing an opportunity to reduce this margin for pelvic lymph node SBRT., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The ADOPT clinical trial (Principal Investigator S. Aluwini, NCT04302454) has been funded by the Dutch Cancer Society (KWF, Amsterdam, Grant number 12448). The department of Radiation Oncology of the University Medical Center Groningen has research contracts with IBA, RaySearch, Siemens, Elekta, Leoni, and Mirada, and has received grants from the Dutch Cancer Society and the European Union., (© 2024 The Authors.)

Purpose: Prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) scan is the standard imaging procedure for biochemical recurrent prostate cancer postprostatectomy because of its high detection rate at low serum prostate-specific antigen levels. However, existing guidelines for clinical target volume (CTV) in prostate bed salvage external beam radiation therapy (sEBRT) are primarily based on experience-based clinical consensus and have been validated using conventional imaging modalities. Therefore, this study aimed to optimize CTV definition in sEBRT by using PSMA PET/CT-detected local recurrences (LRs)., Methods and Materials: Patients with suspected LR on PSMA PET/CT postprostatectomy were retrospectively enrolled in 9 Dutch centers. Anonymized scans were centrally reviewed by an expert nuclear medicine physician. Each boundary of the CTV guideline from the Groupe Francophone de Radiothérapie en Urologie (GFRU) was evaluated and adapted to improve the accuracy and coverage of the area at risk of LR (CTV) on PSMA PET/CT. The proposed CTV adaptation was discussed with the radiation oncologists of the participating centers, and final consensus was reached. To assess reproducibility, the participating centers were asked to delineate 3 new cases according to the new PERYTON-CTV, and the submitted contours were evaluated using the Dice similarity coefficient (DSC)., Results: After central review, 93 LRs were identified on 83 PSMA PET/CTs. The proposed CTV definition improved the coverage of PSMA PET/CT-detected LRs from 67% to 96% compared with the GFRU-CTV, while reducing the GFRU-CTV by 25%. The new CTV was highly reproducible, with a mean DSC of 0.82 (range, 0.81-0.83)., Conclusions: This study contributes to the optimization of CTV definition in postprostatectomy sEBRT by using the pattern of LR detected on PSMA PET/CT. The PERYTON-CTV is highly reproducible across the participating centers and ensures coverage of 96% LRs while reducing the GFRU-CTV by 25%., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: The PERYTON trial is a multicenter randomized controlled trial that will investigate whether the treatment outcome of salvage external beam radiation therapy (sEBRT) will be improved with hypofractionated radiation therapy. A pretrial quality assurance (QA) program was undertaken to ensure protocol compliance within the PERYTON trial and to assess variation in sEBRT treatment protocols between the participating centers., Methods and Materials: Completion of the QA program was mandatory for each participating center (N = 8) to start patient inclusion. The pretrial QA program included (1) a questionnaire on the center-specific sEBRT protocol, (2) a delineation exercise of the clinical target volume (CTV) and organs at risk, and (3) a treatment planning exercise. All contours were analyzed using the pairwise dice similarity coefficient (DSC) and the 50th and 95th percentile Hausdorff distance (HD50 and HD95, respectively). The submitted treatment plans were reviewed for protocol compliance., Results: The results of the questionnaire showed that high-quality, state-of-the-art radiation therapy techniques were used in the participating centers and identified variations of the sEBRT protocols used concerning the position verification and preparation techniques. The submitted CTVs showed significant variation, with a range in volume of 29 cm 3 to 167 cm 3 , a mean pairwise DSC of 0.52, and a mean HD50 and HD95 of 2.3 mm and 24.4 mm, respectively. Only in 1 center the treatment plan required adaptation before meeting all constraints of the PERYTON protocol., Conclusions: The pretrial QA of the PERYTON trial demonstrated that high-quality, but variable, radiation techniques were used in the 8 participating centers. The treatment planning exercise confirmed that the dose constraints of the PERYTON protocol were feasible for all participating centers. The observed variation in CTV delineation led to agreement on a new (image-based) delineation guideline to be used by all participating centers within the PERYTON trial., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Stereotactic body radiotherapy (SBRT) is increasingly applied for pelvic oligometastases of prostate cancer, and currently no simple immobilization method is available for cone beam computed tomography (CBCT)-guided treatment. We assessed patient set-up and intrafraction motion using simple immobilization during CBCT-guided pelvic SBRT. Forty patients were immobilized with basic arm- head- and knee support and either a thermoplastic cushion or a foam cushion. Analysis of 454 CBCTs showed mean intrafraction translation <3.0 mm in 94% of fractions and mean intrafraction rotation <1.5° in 95% of fractions. Therefore, simple immobilization ensured stable patient positioning during CBCT-guided pelvic SBRT., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The evaluated patient group is part of the ADOPT clinical trial (Principal Investigator S. Aluwini, NCT04302454), which has been funded by the Dutch Cancer Society (KWF, Amsterdam). The department of Radiation Oncology of the University Medical Center Groningen has research contracts with IBA, RaySearch, Siemens, Elekta, Leoni, and Mirada, and has received grants from the Dutch Cancer Society and the European Union., (© 2023 The Author(s).)

Background: More than 60% of oligo-recurrent prostate cancer (PCa) patients treated with metastasis-directed radiotherapy (MDRT) develop biochemical recurrence within 2 years. This recurrence rate emphasises the need for improved treatment and patient selection. In line with the treatment of primary PCa, the efficacy of MDRT may be enhanced when combined with androgen-deprivation therapy (ADT). Furthermore, the availability of PSMA PET/CT offers an excellent tool for optimal patient selection for MDRT. This phase III randomised controlled trial will investigate the role of the addition of ADT to MDRT in oligo-recurrent PCa patients selected with PSMA PET/CT to enhance oncological outcome., Methods: Two hundred and eighty patients will be randomised in a 1:1 ratio to the standard treatment arm (MDRT alone) or the experimental arm (MDRT + 6 months ADT). Patients with biochemical recurrence after primary treatment of PCa presenting with ≤ 4 metastases will be included. The primary endpoint is the 2.5-year metastases progression-free survival (MPFS). Secondary endpoints are acute and late toxicity, quality of life, biochemical progression-free survival, overall survival, and the sensitivity of the PSMA PET/CT for detecting oligometastases at low PSA-levels. So far, between March 2020 and December 2021, one hundred patients have been included., Discussion: This phase III randomised controlled trial will assess the possible benefit of the addition of 6 months ADT to MDRT on metastases progression-free survival, toxicity, QoL and survival in PCa patients with 1-4 recurrent oligometastatic lesions., Trial Registration: ClinicalTrials.gov, NCT04302454 . Registered 10 March 2020., (© 2022. The Author(s).)

Background: Salvage external beam radiotherapy (sEBRT) for patients with a biochemical recurrence (BCR) after radical prostatectomy provides a 5-year biochemical progression-free survival up to 60%. Multiple studies have shown that dose escalation to the primary prostate tumour improves treatment outcome. However, data is lacking on the role of dose escalation in the recurrent salvage setting. The main objective of the PERYTON-trial is to investigate whether treatment outcome of sEBRT for patients with a BCR after prostatectomy can be improved by increasing the biological effective radiation dose using hypofractionation. Moreover, patients will be staged using the PSMA PET/CT scan, which is superior to conventional imaging modalities in detecting oligometastases., Methods: The PERYTON-study is a prospective multicentre open phase III randomised controlled trial. We aim to include 538 participants (269 participants per treatment arm) with a BCR after prostatectomy, a PSA-value of < 1.0 ng/mL and a recent negative PSMA PET/CT scan. Participants will be randomised in a 1:1 ratio between the conventional fractionated treatment arm (35 × 2 Gy) and the experimental hypofractionated treatment arm (20 × 3 Gy). The primary endpoint is the 5-year progression-free survival after treatment. The secondary endpoints include toxicity, quality of life and disease specific survival., Discussion: Firstly, the high rate of BCR after sEBRT may be due to the presence of oligometastases, for which local sEBRT is inappropriate. With the use of the PSMA PET/CT before sEBRT, patients with oligometastases will be excluded from intensive local treatment to avoid unnecessary toxicity. Secondly, the currently applied radiation dose for sEBRT may be too low to achieve adequate local control, which may offer opportunity to enhance treatment outcome of sEBRT by increasing the biologically effective radiotherapy dose to the prostate bed., Trial Registration: This study is registered at ClinicalTrials.gov (Identifier: NCT04642027 ). Registered on 24 November 2020 - Retrospectively registered. The study protocol was approved by the accredited Medical Ethical Committee (METc) of all participating hospitals (date METc review: 23-06-2020, METc registration number: 202000239). Written informed consent will be obtained from all participants., (© 2022. The Author(s).)