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Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Elizabeth Covingham is chair of AAPM Task Group TG-263U1. Michael Duchateau is an employee of MIM Software Inc. Nicholas Hardcastle receives research grant funding from Varian Medical Systems and Reflexion Medical and consultancy fees from SeeTreat Medical. All remaining authors have declared no conflicts of interest.

Introduction: Reirradiation has gained increasing interest, as advances in systemic therapy increase the survival of patients with cancer, and modern radiation techniques allow more precise treatments. However, high-quality prospective evidence on the safety and efficacy of reirradiation to guide clinical practice remains scarce. This systematic review evaluates ongoing prospective studies on reirradiation to identify research gaps and priorities., Methods: A systematic review of ClinicalTrials.gov was conducted on July 11, 2024, using search terms related to reirradiation. Inclusion criteria were prospective studies that were "recruiting," "not yet recruiting," or "active, not recruiting." Studies with published results, retrospective, and in-silico studies were excluded. The review followed PRISMA 2020 guidelines and recommendations for systematic searches of clinical trial registries., Results: Among 1026 identified studies, 307 were screened, 99 were included. Fourty (40%) focused on central nervous system (CNS), 23 (23%) head and neck, and 17 (17%) on pelvic reirradiation. Most studies (90%) were interventional, with 32 (32%) phase II and 4 (4%) phase III trials. Sixteen trials were randomized (RCTs), including the 4 phase III trials for recurrent glioblastoma, rectal and nasopharyngeal cancer. Ten dose escalation trials focus on recurrent prostate, rectal, and non-small cell lung cancer as well as glioma. Modern high-precision radiotherapy techniques were frequently used, with 21 (21%) studies using stereotactic radiotherapy and 17 (17%) using particle therapy. Combinations with systemic therapies were investigated in 41 (41%) studies., Conclusion: Ongoing studies most frequently focus on CNS, head and neck, and pelvic reirradiation. There remains a critical need for RCTs, in particular for lung, breast, and gynecological cancers. Dose escalation trials, application of precision radiation techniques and combinations with modern systemic therapy may help define the optimal multimodality treatment schedules., Competing Interests: Declaration of competing interest 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., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background and Purpose: Intensity modulated proton therapy (IMPT) enables generation of conformal dose plans with organ at risk (OAR) sparing potential. However, pelvic IMPT robustness is challenged by inter-fraction motion caused by constant anatomical variations. In this study, the dosimetric impact of inter-fraction motion on target coverage and dose to OAR was quantified in the prospective phase II study ReRad-II on dose-escalated proton reirradiation for locally recurrent rectal cancer (LRRC)., Materials and Methods: The inter-fraction motion robustness was assessed for the initial twelve patients enrolled in the ReRad-II study. Patients with resectable LRRC were assessed for neoadjuvant IMPT (55 Gy(RBE)/44Fx) and unresectable recurrences for definitive IMPT (57.5-65 Gy(RBE)/ 46-52Fx). Target coverage and dose to OAR were assessed for robustly optimised three-field IMPT, on 12 plan computerized tomography (CT) scans (pCT) - and 47 repetitive control CT scans (cCTs) during the treatment. The target coverage and doses to OAR were re-calculated on each cCT and the mean dose ratio (pCT/cCT-ratio) and target coverage (V 95% ) was evaluated., Results: The target coverage was robust with a mean dose pCT/cCT-ratio of 1.00 (+/-1%). The V 95% target coverage for every cCT were above the accepted worst-case scenario in the robust evaluation. Considerable variation in bladder-, bowel bag-, and bowel loop volume was observed. The OAR with the largest variation in ratio was the bladder (pCT/cCT-ratio: 1.3 (range: 0.5-4.7)., Conclusions: IMPT for dose-escalated reirradiation of LRRC provided anatomically robust target coverage despite OAR changes. Inter-fraction motion resulted in OAR doses varying within clinically acceptable range., 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., (© 2024 The Authors. Published by Elsevier B.V. on behalf of European Society of Radiotherapy & Oncology.)

Background and Purpose: Safe reirradiation relies on assessment of cumulative doses to organs at risk (OARs) across multiple treatments. Different clinical pathways can result in inconsistent estimates. Here, we quantified the consistency of cumulative dose to OARs across multi-centre clinical pathways., Material and Methods: We provided DICOM planning CT, structures and doses for two reirradiation cases: head & neck (HN) and lung. Participants followed their standard pathway to assess the cumulative physical and EQD2 doses (with provided α/β values), and submitted DVH metrics and a description of their pathways. Participants could also submit physical dose distributions from Course 1 mapped onto the CT of Course 2 using their best available tools. To assess isolated impact of image registrations, a single observer accumulated each submitted spatially mapped physical dose for every participating centre., Results: Cumulative dose assessment was performed by 24 participants. Pathways included rigid (n = 15), or deformable (n = 5) image registration-based 3D dose summation, visual inspection of isodose line contours (n = 1), or summation of dose metrics extracted from each course (n = 3). Largest variations were observed in near-maximum cumulative doses (25.4 - 41.8 Gy for HN, 2.4 - 33.8 Gy for lung OARs), with lower variations in volume/dose metrics to large organs. A standardised process involving spatial mapping of the first course dose to the second course CT followed by summation improved consistency for most near-maximum dose metrics in both cases., Conclusion: Large variations highlight the uncertainty in reporting cumulative doses in reirradiation scenarios, with implications for outcome analysis and understanding of published doses. Using a standardised workflow potentially including spatially mapped doses improves consistency in determination of accumulated dose in reirradiation scenarios., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Nicholas Hardcastle receives research grant funding from Varian Medical Systems and Reflexion Medical for work unrelated to the current project. Nicholas Hardcastle receives consultancy fees from SeeTreat Medical. Theresa Hemminger is an employee of Brainlab AG.]., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Inter-fractional anatomical changes challenge robust delivery of whole-pelvic proton therapy for high-risk prostate cancer. Pre-treatment robust evaluation (PRE) takes uncertainties in isocenter shifts and distal beam edge in treatment plans into account. Using weekly control computed tomography scans (cCTs), the aim of this study was to evaluate the PRE strategy by comparing to an off-line during-treatment robust evaluation (DRE) while also assessing plan robustness with respect to protocol planning constraints., Material and Methods: Treatment plans and cCTs from ten patients included in the pilot phase of the PROstate PROTON Trial 1 were analysed. Treatment planning followed protocol guidelines with 78 Gy to the primary clinical target volume (CTVp) and 56 Gy to the elective target (CTVe) in 39 fractions. Recalculations of the treatment plans were performed for a total of 64 cCTs and dose/volume measures corresponding to clinical constraints were evaluated for this DRE against the simulated scenario interval from the PRE., Results: Of the 64 cCTs, 59 showed DRE CTVp measures within the robustness range from the PRE; this was also the case for 39 of the cCTs for the CTVe measures. However, DRE CTVe coverage was still within constraints for 57 of the 64 cCTs. DRE dose/volume measures for CTVp fulfilled target coverage constraints in 59 of 64 cCTs. All DRE measures for the rectum, bladder, and bowel were inside the PRE range in 63, 39, and 31 cCTs, respectively., Conclusion: The PRE strategy predicted the DRE scenarios for CTVp and rectum. CTVe, bladder, and bowel showed more complex anatomical variations than simulated by the PRE isocenter shift. Both original and recalculated nominal treatment plans showed robust treatment delivery in terms of target coverage.

Background: Patients with stage II seminoma have traditionally been treated with photons to the retroperitoneal and iliac space, which leads to a substantial dose bath to abdominal and pelvic organs at risk (OAR). As these patients are young and with excellent prognosis, reducing dose to OAR and thereby the risk of secondary cancer is of utmost importance. We compared IMPT to opposing IMRT fields and VMAT, assessing dose to OAR and both overall and organ-specific secondary cancer risk., Material and Methods: A comparative treatment planning study was conducted on planning CT-scans from ten patients with stage II seminoma, treated with photons to a 'dog-leg' field with doses ranging from 20 to 25 Gy and a 10 Gy sequential boost to the metastatic lymph node(s). Photon plans were either 3-4 field IMRT (Eclipse) or 1-2 arc VMAT (Pinnacle). Proton plans used robust (5 mm; 3.5%) IMPT (Eclipse), multi field optimization with 3 posterior fields supplemented by 2 anterior fields at the level of the iliac vessels. Thirty plans were generated. Mean doses to OARs were compared for IMRT vs IMPT and VMAT vs IMPT. The risk of secondary cancer was calculated according to the model described by Schneider, using excess absolute risk (EAR, per 10,000 persons per year) for body outline, stomach, duodenum, pancreas, bowel, bladder and spinal cord., Results: Mean doses to all OARs were significantly lower with IMPT except similar kidney (IMRT) and spinal cord (VMAT) doses. The relative EAR for body outline was 0.59 for IMPT/IMRT ( p  < .05) and 0.33 for IMPT/VMAT ( p  < .05). Organ specific secondary cancer risk was also lower for IMPT except for pancreas and duodenum., Conclusion: Proton therapy reduced radiation dose to OAR compared to both IMRT and VMAT plans, and potentially reduce the risk of secondary cancer both overall and for most OAR.

The Danish Prostate Cancer Group is launching the randomized trial, PROstate PROTON Trial 1 (NCT05350475), that compares photons and protons to the prostate and pelvic lymph nodes in treatment of high-risk prostate cancer. The aim of the work described in this paper was, in preparation of this trial, to establish a strategy for conventionally fractionated proton therapy of prostate and elective pelvic lymph nodes that is feasible and robust. Proton treatments are image-guided based on gold fiducial markers and on-board imaging systems in line with current practice. Our established proton beam configuration consists of four coplanar fields; two posterior oblique fields and two lateral oblique fields, chosen to minimize range uncertainties associated with penetrating a varying amount of material from both treatment couch and patient body. Proton plans are robustly optimized to ensure target coverage while keeping normal tissue doses as low as is reasonably achievable throughout the course of treatment. Specific focus is on dose to the bowel as a reduction in gastrointestinal toxicity is the primary endpoint of the trial. Strategies have been established using previously treated patients and will be further investigated and evaluated through the ongoing pilot phase of the 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 Author(s).)

Introduction. Internal organ motion and deformations may cause dose degradations in proton therapy (PT) that are challenging to resolve using conventional image-guidance strategies. This study aimed to investigate the potential of range guidance using water-equivalent path length (WEPL) calculations to detect dose degradations occurring in PT. Materials and methods . Proton ranges were estimated using WEPL calculations. Field-specific isodose surfaces in the planning CT (pCT), from robustly optimised five-field proton plans (opposing lateral and three posterior/posterior oblique beams) for locally advanced prostate cancer patients, were used as starting points. WEPLs to each point on the field-specific isodoses in the pCT were calculated. The corresponding range for each point was found in the repeat CTs (rCTs). The spatial agreement between the resulting surfaces in the rCTs (hereafter referred to as iso-WEPLs) and the isodoses re-calculated in rCTs was evaluated for different dose levels and Hausdorff thresholds (2-5 mm). Finally, the sensitivity and specificity of detecting target dose degradation (V95% < 95%) using spatial agreement measures between the iso-WEPLs and isodoses in the pCT was evaluated. Results . The spatial agreement between the iso-WEPLs and isodoses in the rCTs depended on the Hausdorff threshold. The agreement was 65%-88% for a 2 mm threshold, 83%-96% for 3 mm, 90%-99% for 4 mm, and 94%-99% for 5 mm, across all fields and isodose levels. Minor differences were observed between the different isodose levels investigated. Target dose degradations were detected with 82%-100% sensitivity and 75%-80% specificity using a 2 mm Hausdorff threshold for the lateral fields. Conclusion . Iso-WEPLs were comparable to isodoses re-calculated in the rCTs. The proposed strategy could detect target dose degradations occurring in the rCTs and could be an alternative to a fully-fledged dose re-calculation to detect anatomical variations severely influencing the proton range., (Creative Commons Attribution license.)

Background: Proton therapy (PT) is sensitive towards anatomical changes that may occur during a treatment course. The aim of this study was to investigate if anatomically robust PT (ARPT) plans incorporating patient-specific target motion improved target coverage while still sparing normal tissues, when applied on locally advanced prostate cancer patients where pelvic irradiation is indicated., Material and Methods: A planning computed tomography (CT) scan used for dose calculation and two additional CTs (acquired on different days) were used to make patient-specific targets for the ARPT plans on the eight included patients. The plans were compared to a conventional robust PT plan and a volumetric modulated arc therapy (VMAT) photon plan, which were derived from the planning CT (pCT). Worst-case robust optimisation was used for all proton plans with a setup uncertainty of 5 mm and a range uncertainty of 3.5%. Target coverage (V95% and D95%) and normal tissue doses (V5-75 Gy) were evaluated on 6-8 rCTs per patient., Results: The ARPT plans improved the prostate target coverage for the most challenging patient compared to conventional robust PT plans (20% point increase for V95% and 31 Gy increase for D95%). Across the whole cohort the estimated mean value for V95% was 97% for the ARPT plans and 95% for the conventional robust PT plans. The ARPT plans had a slight, statistically insignificant increase in normal tissue doses compared to the conventional robust proton plans. Compared to VMAT, the ARPT plans significantly reduced the normal tissue doses in the low-to-intermediate dose range., Conclusions: While both proton plans reduced the low-to-intermediate normal tissue doses compared to VMAT, ARPT plans improved the target coverage for the most challenging patient without significantly increasing the normal tissue doses compared to conventional robust PT plans.

The objective of the study was the construction of a generic curriculum development model for the use of biomedical physics (BMP) educators teaching the non-physics healthcare professions (HCP) in Europe. A comprehensive, qualitative cross-sectional Europe-wide survey of the curricula delivered by BMP in Faculties of Medicine and Health Sciences (FMHS) was carried out. Curricular content was collected from faculty web-sites, curricular documents and textbooks. The survey data was supplemented with semi-structured interviews and direct observation during onsite visits. The number of faculties studied was 118 from 67 universities spread all over Europe, whilst the number of onsite visits/interviews was 15 (geographically distributed as follows: Eastern Europe 6, North Western Europe 5, and South Western Europe 4). EU legislation, recommendations by European national medical councils, educational benchmark statements by higher education quality assurance agencies, research journals concerning HCP education and other documents relevant to standards in clinical practice and undergraduate education were also analyzed. Best practices and BMP learning outcomes were elicited from the curricular materials, interviews and documentation and these were subsequently used to construct the curriculum development model. A structured, comprehensive BMP learning outcomes inventory was designed in the format required by the European Qualifications Framework (EQF). The structures of the inventory and curriculum development model make them ideally suited for use by BMP involved in European curriculum development initiatives for the HCP., (Copyright © 2021. Published by Elsevier Ltd.)

Purpose/objective: Chemo-radiotherapy is an established primary curative treatment for anal cancer, but clinically equal rationale for different target doses exists. If joint preferences (physician and patient) are used to determine acceptable tradeoffs in radiotherapy treatment planning, multiple dose plans must be simultaneously explored. We quantified the degree to which different toxicity priorities might be incorporated into treatment plan selection, to elucidate the feasible decision space for shared decision making in anal cancer radiotherapy., Material and Methods: Retrospective plans were generated for 22 anal cancer patients. Multi-criteria optimization handles dynamically changing priorities between clinical objectives while meeting fixed clinical constraints. Four unique dose distributions were designed to represent a wide span of clinically relevant objectives: high-dose preference (60.2 Gy tumor boost and 50.4 Gy to elective nodes with physician-defined order of priorities), low-dose preference (53.75 Gy tumor boost, 45 Gy to elective nodes, physician-defined priorities), bowel sparing preference (lower dose levels and priority for bowel avoidance) and bladder sparing preference (lower dose levels and priority for bladder avoidance)., Results: Plans satisfied constraints for target coverage. A senior oncologist approved a random subset of plans for quality assurance. Compared to a high-dose preference, bowel sparing was clinically meaningful at the lower prescribed dose [median change in V 45Gy : 234 cm 3 ; inter-quartile range (66; 247); p < .01] and for a bowel sparing preference [median change in V 45Gy : 281 cm 3 ; (73; 488); p < .01]. Compared to a high-dose preference, bladder sparing was clinically meaningful at the lower prescribed dose [median change in V 35Gy : 13.7%-points; (0.3; 30.6); p < .01] and for a bladder sparing preference [median change in V 35Gy : 30.3%-points; (12.4; 43.1); p < .01]., Conclusions: There is decision space available in anal cancer radiotherapy to incorporate preferences, although tradeoffs are highly patient-dependent. This study demonstrates that preference-informed dose planning is feasible for clinical studies utilizing shared decision making.

Introduction: The objective of this study was to examine the accuracy of the Anisotropic Analytical Algorithm (AAA). A variety of different field configurations in homogeneous and in inhomogeneous media (lung geometry) was tested for the AAA algorithm. It was also tested against the present Pencil Beam Convolution (PBC) algorithm., Materials and Methods: Two dimensional (2D) dose distributions were measured for a variety of different field configurations in solid water with a 2D array of ion chambers. The dose distributions of patient specific treatment plans in selected transversal slices were measured in a Thorax lung phantom with Gafchromic dosimetry films. A Farmer ion chamber was used to check point doses in the Thorax phantom. The 2D dose distributions were evaluated with a gamma criterion of 3% in dose and 3 mm distance to agreement (DTA) for the 2D array measurements and for the film measurements., Results: For AAA, all fields tested in homogeneous media fulfilled the criterion, except asymmetric fields with wedges and intensity modulated plans where deviations of 5 and 4%, respectively, were seen. Overall, the measured and calculated 2D dose distributions for AAA in the Thorax phantom showed good agreement -- both for 6 and 15 MV photons. More than 80% of the points in the high dose regions met the gamma criterion, though it failed at low doses and at gradients. For the PBC algorithm only 30-70% of the points met the gamma criterion., Conclusion: The AAA algorithm has been shown to be superior to the PBC algorithm in heterogeneous media, especially for 15 MV. For most treatment plans the deviations in the lung and the mediastinum regions are below 3%. However, the algorithm may underestimate the dose to the spinal cord by up to 7%.