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Background: Proton radiotherapy (RT) is an attractive tool to deliver local therapy with minimal dose to uninvolved tissue, however, not suitable for all patients. The aim was to explore complications, especially severe late complications (grades 3-4), following proton RT delivered to a complete Swedish cohort of paediatric patients aged <18 years treated 2008-2019. Material and Methods: Data was downloaded from a national registry. Complications with a possible causation with RT are reported. Proton treatments until July 2015 was performed with a fixed horizontal 172 MeV beam (The Svedberg Laboratory (TSL), Uppsala) in a sitting position and thereafter with gantry-based pencil-beam scanning technique (Skandion Clinic, Uppsala) in a supine position. Results: 219 courses of proton RT (77 at TSL and 142 at Skandion) were delivered to 212 patients (mean age 9.2 years) with various tumour types (CNS tumours 58%, sarcomas 26%, germ cell tumours 7%). Twenty-five patients had severe acute complications (skin, mucous membrane, pharynx/oesophagus, larynx, upper gastrointestinal canal, lower gastrointestinal canal, eyes, ears). Fifteen patients had severe late complications; with increased proportion over time: 4% at 1-year follow-up (FU), 5% at 3-year, 11% at 5-year. Organs affected were skin (1 patient), subcutaneous tissue (4), salivary glands (1), upper GI (1), bone (7), joints (2), CNS (2), PNS (1), eyes (1) and ears (5). Twenty-one of the 28 patients with 10-year FU had at least one late complication grades 1-4 and fourteen of them had more than one (2-5 each). Conclusion: The most important result of our study is the relatively low proportion of severe late complications, comparable with other proton studies on various tumours. Furthermore, the numbers of late complications are lower than our own data set on a mixed population of photon and proton treated paediatric patients, assuring the safety of using proton therapy also in the clinical practice. [ABSTRACT FROM AUTHOR]

The Danish Breast Cancer Group (DBCG) Proton Trial randomizes breast cancer patients selected on high mean heart dose (MHD) or high lung dose (V20Gy/V17Gy) in the photon plan between photon and proton therapy. This study presents the proton plans and adaptation strategy for the first 43 breast cancer patients treated with protons in Denmark. Forty-four proton plans (one patient with bilateral cancer) were included; 2 local and 42 loco-regional including internal mammary nodes (IMN). Nineteen patients had a mastectomy and 25 a lumpectomy. The prescribed dose was either 50 Gy in 25 fractions (n = 30) or 40 Gy in 15 fractions (n = 14) wherefrom five received simultaneous integrated boost to the tumor bed. Using 2-3 en face proton fields, single-field optimization, robust optimization and a 5 cm range shifter ensured robustness towards breathing motion, setup- and range uncertainties. An anatomical evaluation was performed by evaluating the dose after adding/removing 3 mm and 5 mm tissue to/from the body-outline and used to define treatment tolerances for anatomical changes. The nominal and robust criteria were met for all patients except two. The median MHD was 1.5 Gy (0.5–3.4 Gy, 50 Gy) and 1.1 Gy (0.0–1.5 Gy, 40 Gy). The anatomical evaluations showed how 5 mm shrinkage approximately doubled the MHD while 5 mm swelling reduced target coverage of the IMN below constraints. Ensuring 3–5 mm robustness toward swelling was prioritized but not always achieved by robust optimization alone emphasizing the need for a distal margin. Twenty-eight patients received plan adaptation, eight patients received two, and one received five. This proton planning strategy ensured robust treatment plans within a pre-defined level of acceptable anatomical changes that fulfilled the planning criteria for most of the patients and ensured low MHD. [ABSTRACT FROM AUTHOR]

Objectives: To assess the interaction between comorbidity and breast cancer (BC) on the rate of venous thromboembolism (VTE) beyond what can be explained by the independent effects of BC and comorbidity. Design: Population-based matched cohort study. Setting: Denmark. Participants: Danish patients with BC (n=62 376) diagnosed in 1995-2010 and a comparison cohort of women without BC (n=304 803) from the general population were matched to the patients with BC on year of birth in 5-year intervals and on the specific diseases included in the Charlson Comorbidity Index (CCI) and atrial fibrillation and obesity. Measures: The rate ratios of VTE per 1000 person-years (PY) were computed by comorbidity levels using the CCI, and interaction contrasts (IC) were calculated as a measure of the excess or deficit VTE rate not explained by the independent effects of BC and comorbidity. Results: Among patients with BC with a CCI score of 1, the 0-1 year VTE rate was 12/1000 PY, and interaction accounted for 10% of the rate (IC=3.2, 95% CI 0.5 to 5.9). Among patients with BC with CCI ≥4, the VTE rate was 17, and interaction accounted for 8% of the rate (IC=1.2, 95% CI -1.8 to 4.2). There was no interaction during 2-5 years of follow-up. Conclusions: There was only little interaction between BC and the CCI score on the rate of VTE. [ABSTRACT FROM AUTHOR]

Radiation therapy plays an important role in the multidisciplinary management of breast cancer. Recent years have seen improvements in breast cancer survival and a greater appreciation of potential long-term morbidity associated with the dose and volume of irradiated organs. Proton therapy reduces the dose to nontarget structures while optimizing target coverage. However, there remain additional financial costs associated with proton therapy, despite reductions over time, and studies have yet to demonstrate that protons improve upon the treatment outcomes achieved with photon radiation therapy. There remains considerable heterogeneity in proton patient selection and techniques, and the rapid technological advances in the field have the potential to affect evidence evaluation, given the long latency period for breast cancer radiation therapy recurrence and late effects. In this consensus statement, we assess the data available to the radiation oncology community of proton therapy for breast cancer, provide expert consensus recommendations on indications and technique, and highlight ongoing trials' cost-effectiveness analyses and key areas for future research. [ABSTRACT FROM AUTHOR]

• Apnea and HFJV at 300–400 Hz induce minimal surrogate marker movement. • Apnea and HFJV at 300–400 Hz induce hypercapnia. • Tidal volume of 80 ml observed with HFJV at 200 Hz results in effective CO 2 removal. • HFJV at 200 Hz is the best compromise between lung immobilization and gas exchange. • Abdominal motion is highly correlated to diaphragm motion. Respiratory-induced motion introduces uncertainties in the delivery of dose in radiotherapy treatments. Various methods are used clinically, e.g. breath-holding, while there is limited experience with other methods such as apneic oxygenation and high frequency jet ventilation (HFJV). This study aims to compare the latter approaches for lung immobilization and their clinical impact on gas exchange in an animal model. Two radiopaque tumor surrogate markers (TSM) were placed in the central (cTSM) and peripheral (dTSM) regions of the lungs in 9 anesthetized and muscle relaxed pigs undergoing 3 ventilatory interventions (1) HFJV at rates of 200 (JV200), 300 (JV300) and 400 (JV400) min−1; (2) apnea at continuous positive airway pressure (CPAP) levels of 0, 8 and 16 cmH 2 O; (3) conventional mechanical ventilation (CMV) as reference mode. cTSM and dTSM were visualized using fluoroscopy and their coordinates were computed. The ventilatory pattern was registered, and oxygen and carbon dioxide (pCO 2) partial pressures were measured. The highest range of TSM motion, and ventilation was found during CMV, the lowest during apnea. During HFJV the amount of motion varied inversely with increasing frequency. The reduction of TSM motion at JV300, JV400 and all CPAP levels came at the cost of increased pCO 2 , however the relatively low frequency of 200 min−1 for HFJV was the only ventilatory setting that enabled adequate CO 2 removal. In this model , HFJV at 200 min−1 was the best compromise between immobilization and gas exchange for sessions of 10-min duration. [ABSTRACT FROM AUTHOR]

• National guidelines for whole heart and cardiac substructures were established. • Inter-observer contour overlap was 78–96% for the heart and four chambers. • The median distance between centers of left main coronary artery was 2–4 mm. • Variance measure for OAR ready for use in auto segmentation. This study presents Danish consensus guidelines for delineation of the heart and cardiac substructures across relevant Danish Multidisciplinary Cancer Groups. Consensus guidelines for the heart and cardiac substructures were reached among 15 observers representing the radiotherapy (RT) committees of four Danish Multidisciplinary Cancer Groups. The guidelines were validated on CT scans of 12 patients, each with five independent contour sets. The Sørensen-Dice similarity coefficient (DSC), the distance between the centers of the arteries and the mean surface distance were used to evaluate the inter-observer variation. National guidelines for contouring the heart and cardiac substructures were achieved. The median DSC was 0.78–0.96 for the heart and the four cardiac chambers. For the four substructures of the left ventricle, the median DSC was 0.35–0.57. The coronary arteries were contoured in ten segments, with the best agreement for the left anterior descending coronary artery segments, with a median distance between the arteries ranging from 2.4–4.4 mm. The median variation was 3.7–12.8 mm for the right coronary artery segments and 3.7–6.2 mm for the left circumflex coronary artery segments, with the most pronounced inter-observer variation in the distal segment for all three coronary arteries. National guidelines for contouring the heart and cardiac substructures were developed across relevant Danish Multidisciplinary Cancer Groups, where RT dose to the heart is of concern. The inter-observer contour overlap was best for the heart and chambers and decreased for smaller structures. [ABSTRACT FROM AUTHOR]

Background and purpose Image guidance is critical in achieving accurate and precise radiation delivery in particle therapy, even more than in photon therapy. However, equipment, quality assurance procedures and clinical workflows for image-guided particle therapy (IGPT) may vary substantially between centres due to a lack of standardization. A survey was conducted to evaluate the current practice of IGPT in European particle therapy centres. Material and methods In 2016, a questionnaire was distributed among 19 particle therapy centres in 12 European countries. The questionnaire consisted of 30 open and 37 closed questions related to image guidance in the general clinical workflow, for moving targets, current research activities and future perspectives of IGPT. Results All centres completed the questionnaire. The IGPT methods used by the 10 treating centres varied substantially. The 9 non-treating centres were in the process to introduce IGPT. Most centres have developed their own IGPT strategies, being tightly connected to their specific technical implementation and dose delivery methods. Conclusions Insight into the current clinical practice of IGPT in European particle therapy centres was obtained. A variety in IGPT practices and procedures was confirmed, which underlines the need for harmonisation of practice parameters and consensus guidelines. [ABSTRACT FROM AUTHOR]

Purpose To determine the inter-observer variation in delineating the coronary arteries as organs at risk (OAR) in breast cancer (BC) radiotherapy (RT) and how this variation affects the estimated coronary artery radiation dose. Method Delineation of the left main and the left anterior descending coronary artery (LMCA and LAD), and the right coronary artery (RCA), by using the heart atlas by Feng et al., was performed by three radiation oncologists in 32 women who had received adjuvant RT for BC. Centres of the arteries were calculated and distances between artery centres were measured and the artery radiation doses were estimated. The intraclass correlation coefficient (ICC) was used to quantify the variability in doses. Results Along the extent of RCA, the median distance between centres of arteries varied from 2 to 9 mm with similar patterns over pairs of oncologists. For the LMCA-LAD the median distance varied from 1 to 4 mm. The estimated maximum radiation doses showed an ICC variation from 0.82 to 0.97. Conclusion The coronary arteries can be reliably identified and delineated as OARs in BC RT. The spatial variance is limited and the total variation in radiation dose is almost completely determined by the between patient variation. [ABSTRACT FROM AUTHOR]

Background and Purpose: To update the digital online atlas for organs at risk (OARs) delineation in neuro-oncology based on high-quality computed tomography (CT) and magnetic resonance (MR) imaging with new OARs., Materials and Methods: In this planned update of the neurological contouring atlas published in 2018, ten new clinically relevant OARs were included, after thorough discussion between experienced neuro-radiation oncologists (RTOs) representing 30 European radiotherapy-oncology institutes. Inclusion was based on daily practice and research requirements. Consensus was reached for the delineation after critical review. Contouring was performed on registered CT with intravenous (IV) contrast (soft tissue & bone window setting) and 3 Tesla (T) MRI (T1 with gadolinium & T2 FLAIR) images of one patient (1 mm slices). For illustration purposes, delineation on a 7 T MRI without IV contrast from a healthy volunteer was added. OARs were delineated by three experienced RTOs and a neuroradiologist based on the relevant literature., Results: The presented update of the neurological contouring atlas was reviewed and approved by 28 experts in the field. The atlas is available online and includes in total 25 OARs relevant to neuro-oncology, contoured on CT and MRI T1 and FLAIR (3 T & 7 T). Three-dimensional (3D) rendered films are also available online., Conclusion: In order to further decrease inter- and intra-observer OAR delineation variability in the field of neuro-oncology, we propose the use of this contouring atlas in photon and particle therapy, in clinical practice and in the research setting. The updated atlas is freely available on www.cancerdata.org., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: For unbiased comparison of different radiation modalities and techniques, consensus on delineation of radiation sensitive organs at risk (OARs) and on their dose constraints is warranted. Following the publication of a digital, online atlas for OAR delineation in neuro-oncology by the same group, we assessed the brain OAR-dose constraints in a follow-up study., Methods: We performed a comprehensive search to identify the current papers on OAR dose constraints for normofractionated photon and particle therapy in PubMed, Ovid Medline, Cochrane Library, Embase and Web of Science. Moreover, the included articles' reference lists were cross-checked for potential studies that met the inclusion criteria. Consensus was reached among 20 radiation oncology experts in the field of neuro-oncology., Results: For the OARs published in the neuro-oncology literature, we summarized the available literature and recommended dose constraints associated with certain levels of normal tissue complication probability (NTCP) according to the recent ICRU recommendations. For those OARs with lacking or insufficient NTCP data, a proposal for effective and efficient data collection is given., Conclusion: The use of the European Particle Therapy Network-consensus OAR dose constraints summarized in this article is recommended for the model-based approach comparing photon and proton beam irradiation as well as for prospective clinical trials including novel radiation techniques and/or modalities., (Copyright © 2018 Elsevier B.V. All rights reserved.)