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Background: For adult patients with grade 1–3 gliomas, identifying patients with an indication for proton therapy (PT) can be challenging due to sparse evidence supporting its benefits. In this study, we aimed to ensure national consensus and develop a decision support tool to aid clinicians in identifying patients with grade 1–3 gliomas eligible for PT. Methods: Sixty-one historic patients referred for postoperative radiotherapy for glioma grade 1–3 were included in this study and had new photon therapy and PT plans calculated. These plans along with clinical parameters were presented to neurooncologists with experience in treating brain tumours. The patients were presented at three workshops (WSs), where each neurooncologist individually had to choose between photon and proton therapy. Important parameters were selected using cross validation. Multivariable logistic regression was used to predict the neurooncologists’ treatment modality choice. Results: At the three WSs 23, 24 and 19 randomly selected patients were presented. Seventy-five percent of the neurooncologists agreed for 14 patients (61%), 16 patients (67%) and 15 patients (79%) at WS1, WS2 and WS3. Age at radiotherapy and difference in mean dose (ΔDmean) to the residual brain were significant predictors of the choice of treatment modality, p

Aims: The number of Proton Therapy (PT) facilities is still limited worldwide, and the access to treatment could be characterized by patients’ logistic and economic challenges. Aim of the present survey is to assess the support provided to patients undergoing PT across Europe. Methods: Through a personnel contact, an online questionnaire (62 multiple-choice and open-ended questions) via Microsoft Forms was administered to 10 European PT centers. The questionnaire consisted of 62 questions divided into 6 sections: i) personal data; ii) general information on clinical activity; iii) fractionation, concurrent systemic treatments and technical aspects of PT facility; iv) indication to PT and reimbursement policies; v) economic and/ or logistic support to patients vi) participants agreement on statements related to the possible limitation of access to PT. A qualitative analysis was performed and reported. Results: From March to May 2022 all ten involved centers filled the survey. Nine centers treat from 100 to 500 patients per year. Paediatric patients accounted for 10–30%, 30–50% and 50–70% of the entire cohort for 7, 2 and 1 center, respectively. The most frequent tumours treated in adult population were brain tumours, sarcomas and head and neck carcinomas; in all centers, the mean duration of PT is longer than 3 weeks. In 80% of cases, the treatment reimbursement for PT is supplied by the respective country’s Health National System (HNS). HNS also provides economic support to patients in 70% of centers, while logistic and meal support is provided in 20% and 40% of centers, respectively. PT facilities offer economic and/or logistic support in 90% of the cases. Logistic support for parents of pediatric patients is provided by HNS only in one-third of centers. Overall, 70% of respondents agree that geographic challenges could limit a patient’s access to proton facilities and 60% believe that additional support should be given to patients referred for PT care. Conclusions: Relevant differences exist among European countries in supporting patients referred to PT in their logistic and economic challenges. Further efforts should be made by HNSs and PT facilities to reduce the risk of inequities in access to cancer care with protons.

Aim: This study aimed to explore associations between radiation dose and patient-reported outcomes in patients with a primary non-glioblastoma brain tumour treated with radiation therapy (RT), with a focus on health-related quality-of-life (HRQoL) and self-reported cognitive function. Methods: In this cross-sectional study, 78 patients who had received RT for a non-glioblastoma primary brain tumour, underwent neuropsychological testing and completed questionnaires on HRQoL, cognitive function, fatigue, depression, anxiety and perceived stress. The study explores the association between HRQoL scores, self-reported cognitive function and radiation doses to total brain, brainstem, hippocampus, thalamus, temporal lobes and frontal lobes. In addition, we examined correlations between neuropsychological test scores and self-reported cognitive function. Results: The median time between RT and testing was 4.6 years (range 1–9 years). Patients who had received high mean radiation doses to the total brain had low HRQoL scores (Cohen’s d = 0.50, p = 0.04), brainstem (d = 0.65, p = 0.01) and hippocampus (d = 0.66, p = 0.01). High mean doses to the total brain were also associated with low scores on self-reported cognitive functioning (Cohen’s d = 0.64, p = 0.02), brainstem (d = 0.55, p = 0.03), hippocampus (d = 0.76, p

In recent years, self-supervised learning has made tremendous progress in closing the gap to supervised learning due to the rapid development of more sophisticated approaches like SimCLR, MoCo, and SwAV. However, these achievements are primarily evaluated on common benchmark datasets. In this paper, we focus on evaluating self-supervised learning for semantic segmentation of industrial burner flames. Our goal is to build an intuition on how self-supervision performs in a scenario relevant for industrial application where training labels and the opportunities for hyperparameter tuning are limited. We demonstrate that self-supervised pre-training can constitute an alternative to the state-of-the-art approach of pre-training on ImageNet. Across all scenarios, the self-supervised approaches are less susceptible to sub-optimal learning rates and achieve higher mean accuracies than ImageNet pre-training, especially when training labels are scarce.

This study focuses on detecting vehicle crossings (events) with ground-based interferometric radar (GBR) time series data recorded at bridges in the course of critical infrastructure monitoring. To address the challenging event detection and time series classification task, we rely on a deep learning (DL) architecture. The GBR-displacement data originates from real-world measurements at two German bridges under normal traffic conditions. As preprocessing, we only apply a low-pass filter. We develop and evaluate a one-dimensional convolutional neural network (CNN) to achieve a solely data-driven event detection. As a baseline machine learning approach, we use a Random Forest (RF) with a selected feature-based input. Both models’ performance is evaluated on two datasets by focusing on identifying events and pure bridge oscillations. Generally, the event classification results are promising, and the CNN outperforms the RF with an overall accuracy of 94.7% on the test subset. By relying on an entirely unknown second dataset, we focus on the models’ performances regarding the distinction between events and decays. On this dataset, the CNN meets this challenge successfully, while the feature-based RF classifies the majority of non-event decays as events. To sum up, the presented results reveal the potential of a data-driven DL approach concerning the detection of bridge crossing events in GBR-based displacement time series data. Based on such an event detection, a prospective assessment of bridge conditions seems feasible as an extension to previous structural health monitoring approaches.

El presente trabajo tiene como finalidad, hacer un estudio de factibilidad de los métodos que se utilizan para el cálculo del geoide, específicamente para obtener un geoide local en Venezuela, considerando la información disponible que pueda ser utilizable para el objetivo propuesto. El estudio de factibilidad se hace en base a los parámetros Costo, Tiempo y Exactitud estimados a partir de unos proyectos planificados en una zona del territorio nacional integrada por los Estados Zulia, Táchira, Mérida y Trujillo, la cual presenta diferentes condiciones topográficas. Del análisis de los resultados del estudio de factibilidad, se hacen las recomendaciones respectivas acerca del método más conveniente para el cálculo del geoide, haciéndose extensivas para el resto del país.

Background and Purpose: Radiation induced image changes (IC) on MRI have been observed after proton therapy for brain tumours. This study aims to create predictive models, with and without taking into account patient variation, based on dose, linear energy transfer (LET) and periventricular zone (PVZ) in a national cohort of patients with glioma treated with pencil beam scanning (PBS)., Materials and Methods: A cohort of 87 consecutive patients with oligodendroglioma or astrocytoma (WHO grade 2-4) treated with PBS from January 2019 to December 2021 was included. All patients were treated with three to four beams. Monte Carlo calculations of dose and LET were performed for all treatment plans. Lesion weighted as well as mixed effect logistic regression models were developed to predict IC in a voxel., Results: 12 patients (14 %) developed ICs on the follow-up MR-scans. Mixed effect modelling accounting for interpatient variation was justified by the non-negligible inter class correlation coefficient (ICC = 0.33). The two approaches identified similar model features and marginal improvement in model performance was found, when increasing model parameters from two (AUC = 0.92/0.94) to three (AUC = 0.93/0.95) parameters. Univariate analysis showed that patients treated with narrow beam configurations had an increased incidence of IC (p = 0.01)., Conclusion: 14% of patients developed IC following PT. Lesion-weighted and mixed effect models resulted in similar model performance confirming increased risk of IC with increasing LET. The beam arrangement seems to influence the risk of IC and needs further investigation., 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 © 2025 The Author(s). Published by Elsevier B.V. All rights reserved.)

Artificial intelligence (AI) has made a tremendous impact in the space of healthcare, and proton therapy is not an exception. Proton therapy has witnessed growing popularity in oncology over recent decades, and researchers are increasingly looking to develop AI and machine learning tools to aid in various steps of the treatment planning and delivery processes. This review delves into the emergent role of AI in proton therapy, evaluating its development, advantages, intended clinical contexts, and areas of application. Through the analysis of 76 studies, we aim to underscore the importance of AI applications in advancing proton therapy and to highlight their prospective influence on clinical practices., Competing Interests: Declaration of Competing Interest BAJF received speaker fees from Roche, Bayer, Janssen, Ipsen, Accuray, Astellas, Elekta, IBA and Astra Zeneca (all outside the current project). EGCT is member of the scientific advisory board of IBA and received speaker fees from Elekta (all outside the current manuscript). M.G.V received a research fellowship from the Associazione Italiana per la Ricerca sul Cancro (AIRC) entitled “Radioablation ± hormonotherapy for prostate cancer oligorecurrences (RADIOSA trial): potential of imaging and biology” registered at Clinical Trials.gov NCT03940235, approved by the Ethics Committee of IEO and Centro Cardiologico Monzino (IEO-997). GC reports speakers fee and advisory board from Roche, Novartis, Lilly, Pfizer, Astra Zeneca, Daichii Sankyo, Ellipsis, Veracyte, Exact Science, Celcuity, Merck, BMS, Gilead, Sanofi, Menarini. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results. The remaining authors declare no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: This study investigates different strategies for estimating internal liver tumor motion during radiotherapy based on continuous monitoring of external respiratory motion combined with sparse internal imaging., Methods: Fifteen patients underwent three-fraction stereotactic liver radiotherapy. The 3D internal tumor motion (INT) was monitored by electromagnetic transponders while a camera monitored the external marker block motion (EXT). The ability of four external-internal correlation models (ECM) to estimate INT as function of EXT was investigated: a simple linear model (ECM1), an augmented linear model (ECM2), an augmented quadratic model (ECM3), and an extended quadratic model (ECM4). Each ECM was constructed by fitting INT and EXT during the first 60s of each fraction. The fit accuracy was calculated as the root-mean-square error (RMSE) between ECM-estimated and actual tumor motion. Next, the RMSE of the ECM-estimated tumor motion throughout the fractions was calculated for four simulated ECM update strategies: (A) no update, 0.33Hz internal sampling with continuous update of either (B) all ECM parameters based on the last 2 minutes samples or (C) only the baseline term based on the last 5 samples, (D) full ECM update every minute using 20s continuous internal sampling., Results: The augmented quadratic ECM3 had best fit accuracy with mean (± SD)) RMSEs of 0.32 ± 0.11mm (left-right, LR), 0.79 ± 0.30mm (cranio-caudal, CC) and 0.56 ± 0.31mm (anterior-posterior, AP). However, the simpler augmented linear ECM2 combined with frequent baseline updates (update strategy C) gave best motion estimations with mean RMSEs of 0.41 ± 0.14mm (LR), 1.02 ± 0.33mm (CC) and 0.78 ± 0.48mm (AP). This was significantly better than all other ECM-update strategy combinations for CC motion (Wilcoxon signed rank p<0.05)., Conclusion: The augmented linear ECM2 combined with frequent baseline updates provided the best compromise between fit accuracy and robustness towards irregular motion. It allows accurate internal motion monitoring by combining external motioning with sparse 0.33Hz kV imaging, which is available at conventional linacs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Samadi Miandoab, Worm, Hansen, Weber, Høyer, Saramad, Setayeshi and Poulsen.)

Backgrounds/aims: Although access to proton beam therapy (PBT) is limited worldwide, its use for the treatment of hepatocellular carcinoma (HCC) is gradually increasing with the expansion of new facilities. Therefore, we conducted a systematic review and metaanalysis to investigate the updated evidence of PBT for HCC., Methods: The MEDLINE, EMBASE, Cochrane Library, and Web of Science databases were systematically searched for studies that enrolled patients with liver-confined HCC that were treated with PBT for a cure up to February 2024., Results: A total of 1,858 HCC patients receiving PBT from 22 studies between 2004 and 2023 were selected for this meta-analysis. The median proportion of Child-Pugh class A was 86% (range, 41-100), and the median tumor size was 3.6 cm (range, 1.2-9.0). The median total dose ranged from 55 GyE to 76 GyE (median, 69). The pooled rates of 3- and 5-year local progression-free survival after PBT were 88% (95% confidence interval [CI], 85-91) and 86% (95% CI, 82-90), respectively. The pooled 3- and 5-year overall rates were 60% (95% CI, 54-66) and 46% (95% CI, 38-54), respectively. The pooled rates of grade 3 hepatic toxicity, classic radiationinduced liver disease (RILD), and non-classic RILD were 1%, 2%, and 1%, respectively., Conclusions: The current study supports PBT for HCC and demonstrates favorable long-term survival and low hepatic toxicities compared with other published studies on other radiotherapy modalities. However, further studies are needed to identify the subgroups that will benefit from PBT.

Background: Cognitive impairment is a common late effect in child and adult brain cancer survivors (BCS). Still, there is a dearth of research aimed at therapeutic interventions and no standard treatment options for most BCS., Objective: To describe 1) a novel neuropsychological rehabilitation program for BCS - the "I'm aware: Patients And Carers Together" (ImPACT) program, and 2) two studies that aim to assess the feasibility of the ImPACT program in child and adult BCS, respectively. The program adapts the holistic neuropsychological approach pioneered by Leonard Diller and Yehuda Ben-Yishay to an outpatient setting., Methods: Two feasibility studies are described: 1) A single-armed study with 15 child BCS (10-17 years) (ImPACT Child); and 2) a randomized waitlist-controlled trial with 26 adult BCS (>17 years) (ImPACT Adult). In both studies, patients will undergo an 8-week program together with a cohabiting carer. Primary outcomes (i.e., cognitive and neurobehavioral symptoms), and secondary outcomes (i.e., behavioral and psychological symptoms, e.g., quality of life, fatigue) will be assessed at four time points: pre-, mid-, and post intervention, and 8 weeks follow-up. Adult waitlist controls will be assessed at equivalent time points and will be included in the intervention group after all study assessments. Semi-structured interviews will be conducted at follow-up., Expected Outcomes: Results will provide feasibility data in support of future larger scale trials., Discussion: The findings could potentially improve the management of cognitive impairment in BCS and transform available services. The program can be delivered in-person or remotely and harnesses existing resources in patients' lives., 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 © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The benefit of combining immunotherapy with photon irradiation has been shown pre-clinically and clinically. This current pre-clinical study was designed to investigate the anti-tumour action of combining immunotherapy with protons., Materials and Methods: Male CDF1 mice, with a C3H mammary carcinoma inoculated on the right rear foot, were locally irradiated with single radiation doses when tumours reached 200mm 3 . Radiation was delivered with an 83-107MeV pencil scanning proton beam in the centre of a 3 cm spread out Bragg peak. Following irradiation (day 0), mice were injected intraperitoneal with anti-CTLA-4, anti-PD-1, or anti-PD-L1 (10 mg/kg) twice weekly for two weeks. Endpoints were tumour growth time (TGT3; time to reach 3 times treatment volume) or local tumour control (percent of mice showing tumour control at 90 days). A Student's T-test (tumour growth) or Chi-squared test (tumour control) were used for statistical analysis; significance levels of p  < 0.05., Results: Untreated tumours had a mean (± 1 S.E.) TGT3 of 4.6 days (± 0.4). None of the checkpoint inhibitors changed this TGT3. A linear increase in TGT3 was seen with increasing radiation doses (5-20 Gy), reaching 17.2 days (± 0.7) with 20 Gy. Anti-CTLA-4 had no effect on radiation doses up to 15 Gy, but significantly enhanced 20 Gy; the TGT3 being 23.0 days (± 1.3). Higher radiation doses (35-60 Gy) were investigated using a tumour control assay. Logit analysis of the dose response curve, resulted in a TCD50 value (radiation dose causing 50% tumour control; with 95% confidence intervals) of 48 Gy (44-53) for radiation only. This significantly decreased to 43 Gy (38-49) when mice were treated with anti-CTLA-4. Neither anti-PD-1 nor anti-PD-L1 significantly affected tumour control., Conclusion: Checkpoint inhibitors enhanced the response of this C3H mammary carcinoma to proton irradiation. However, this enhancement depended on the checkpoint inhibitor and radiation dose.

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).)

Background: Pencil beam scanning (PBS) proton therapy can provide highly conformal target dose distributions and healthy tissue sparing. However, proton therapy of hepatocellular carcinoma (HCC) is prone to dosimetrical uncertainties induced by respiratory motion. This study aims to develop intra-treatment tumor motion monitoring during respiratory gated proton therapy and combine it with motion-including dose reconstruction to estimate the delivered tumor doses for individual HCC treatment fractions., Methods: Three HCC-patients were planned to receive 58 GyRBE (n=2) or 67.5 GyRBE (n=1) of exhale respiratory gated PBS proton therapy in 15 fractions. The treatment planning was based on the exhale phase of a 4-dimensional CT scan. Daily setup was based on cone-beam CT (CBCT) imaging of three implanted fiducial markers. An external marker block (RPM) on the patient's abdomen was used for exhale gating in free breathing. This study was based on 5 fractions (patient 1), 1 fraction (patient 2) and 6 fractions (patient 3) where a post-treatment control CBCT was available. After treatment, segmented 2D marker positions in the post-treatment CBCT projections provided the estimated 3D motion trajectory during the CBCT by a probability-based method. An external-internal correlation model (ECM) that estimated the tumor motion from the RPM motion was built from the synchronized RPM signal and marker motion in the CBCT. The ECM was then used to estimate intra-treatment tumor motion. Finally, the motion-including CTV dose was estimated using a dose reconstruction method that emulates tumor motion in beam's eye view as lateral spot shifts and in-depth motion as changes in the proton beam energy. The CTV homogeneity index (HI) The CTV homogeneity index (HI) was calculated as D 2 %  -  D 98 % D 50 %   × 100 % ., Results: The tumor position during spot delivery had a root-mean-square error of 1.3 mm in left-right, 2.8 mm in cranio-caudal and 1.7 mm in anterior-posterior directions compared to the planned position. On average, the CTV HI was larger than planned by 3.7%-points (range: 1.0-6.6%-points) for individual fractions and by 0.7%-points (range: 0.3-1.1%-points) for the average dose of 5 or 6 fractions., Conclusions: A method to estimate internal tumor motion and reconstruct the motion-including fraction dose for PBS proton therapy of HCC was developed and demonstrated successfully clinically., Competing Interests: PP is co-inventor on a patent on the 3D motion estimation method applied in this study. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.​, (Copyright © 2023 Nankali, Worm, Thomsen, Stick, Bertholet, Høyer, Weber, Mortensen and Poulsen.)

Re-irradiation can be considered for local recurrence or new tumours adjacent to a previously irradiated site to achieve durable local control for patients with cancer who have otherwise few therapeutic options. With the use of new radiotherapy techniques, which allow for conformal treatment plans, image guidance, and short fractionation schemes, the use of re-irradiation for different sites is increasing in clinical settings. Yet, prospective evidence on re-irradiation is scarce and our understanding of the underlying radiobiology is poor. Our consensus on re-irradiation aims to assist in re-irradiation decision making, and to standardise the classification of different forms of re-irradiation and reporting. The consensus has been endorsed by the European Society for Radiotherapy and Oncology and the European Organisation for Research and Treatment of Cancer. The use of this classification in daily clinical practice and research will facilitate accurate understanding of the clinical implications of re-irradiation and allow for cross-study comparisons. Data gathered in a uniform manner could be used in the future to make recommendations for re-irradiation on the basis of clinical evidence. The consensus document is based on an adapted Delphi process and a systematic review of the literature was done according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)., Competing Interests: Declaration of interests NAn reports grants from ViewRay and Brainlab; honoraria for lectures and reimbursement for travel by ViewRay; personal fees from Debiopharm, AstraZeneca, and ViewRay; and non-financial support from ViewRay. BGB reports an honorarium for travel expenses from a Swiss Academy of Multidisciplinary Oncology meeting; participation in the data safety monitoring board or advisory board for the Multicentre BRIOCHE Trial UK (BRIOChe study: Brain Re-Irradiation Or Chemotherapy: a phase 2 trial of re-irradiation or chemotherapy for recurrent glioblastoma) from the University of Leeds (Leeds, UK); is General Secretary in the Scientific Association of Swiss Radiation Oncology board; and a member of the scientific board of Schweizerische Arbeitsgemeinschaft für Klinische Krebsforschung. MH reports an honorarium for giving a lecture at a symposium arranged by Varian in Copenhagen (Denmark), on May 6, 2022. JAL declares research grants by the European Union and the Dutch Cancer Society; consulting fees paid to UMCG Research BV by IBA; and an honorarium for presentations paid to UMCG Research BV by IBA. JAL is Chair of the safety monitoring committee of the UPGRADE trial from the University Medical Center Nijmegen; a member of the global advisory committee at IBA; a member of the RayCare clinical advisory board at RaySearch; and Chair (unpaid) of the Netherlands Society for Radiation Oncology. PP is a medical adviser of Sordina IORT Technologies SpA. ST-L's husband is an employee at Varian. IM declares occasional small fees (consulting fees) from Novartis, Pfizer, Eli Lilly, Seagen, and Accuray; and occasional small fees (payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events) from Novartis, Pfizer, Eli Lilly, and Seagen. MN declares honoraria and speaker fees from Brainlab, and is a member of the advisory board at Novocure. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objectives: To provide an overview of the impact of the pandemic on the clinical activity and take a snapshot of the contingent challenges that European particle therapy centers are called to face, we surveyed the members of the European Particle Therapy Network (EPTN)., Material and Methods: A 52-question survey was conducted from 4th April 2021 to 30th July 2021 using the Google Forms platform. Three dedicated sections analysed the clinical context of each participating institution, the staff management, and the clinical changes in the oncological workflow., Results: Out of the 23 contacted European hubs of particle radiotherapy, a total of 9 (39%) responded to the survey. The number of in-person first evaluations and follow-up visits decreased, but telemedicine was implemented. Multidisciplinary tumour board discussions continued during the outbreak using web-based solutions. A delay in cancer diagnosis and oncological staging leading to an increment in more advanced diseases at first presentation was generally observed. Even if the total number of treatments (photons and particles) in the responding institutions showed a trend of decrease, there was or a stable situation or slight increase in particle treatments. The clinical treatment choices followed the national and international scientific recommendations and were patient/disease-oriented. Hypofractionation and short-schedule of chemotherapy, when applicable, were preferred., Conclusions: Our findings show a rapid and effective reaction of European particle RT hubs to manage the healthcare crisis. Considering the new waves and virus variants, the vaccination campaign will hopefully reduce the oncological impacts and consequences of the prolonged outbreak., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: J.A. Langendijk is member of International Advisory Board of IBA and RaySearch and honorarium is paid to UMCG Research BV; the department of Radiation Oncology of UMCG has research collaborations with IBA, RaySearch, Siemens, Mirada, Leonie and Elekta. The other authors declare no potential conflict of interest., (© 2022 The Author(s).)

Background and Purpose: Cardiac implantable electronic device (CIED) malfunctions can be induced by secondary neutron dose from spot-scanning proton therapy. A recent in-vitro study investigating secondary neutron dose to CIEDs up to 7 mSv per fraction found that exposure of secondary neutrons in this range was clinically manageable. This study presents decision algorithms proposed by a national expert group for selection of patients with breast and head & neck (H&N) cancer with CIEDs adjacent to target for proton therapy based on the 7 mSv threshold., Methods and Materials: Ten patients with breast cancer and five with H&N cancer were included in the study. Five patients with breast cancer received photon therapy with CIED and proton plans were retrospectively created. The remaining patients received proton therapy without CIED and a worst-case position of a virtual CIED was retrospectively delineated. Secondary neutron dose was estimated as ambient dose equivalent H*(10) using Monte Carlo simulations., Results: For patients with breast cancer and with contralateral CIED, the secondary neutron dose to the CIED was below 7 mSv per fraction for CTV < 1500 cm 3 in 2 Gy fractions and CTV < 1000 cm 3 in 2.67 Gy fractions. The secondary neutron dose to the CIED was below 7 mSv per fraction for all patients with H&N cancer., Conclusions: Simulations of neutron exposure suggest that proton therapy is feasible for most patients with CIED adjacent to target. This forms the basis for decision algorithms for selection of patients with CIED for proton therapy., 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., (© 2022 The Author(s).)