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Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): The project is part of the STOPSTORM.eu consortium and has partially received funding from the European Union’s horizon 2020 research and innovation program Background Stereotactic arrhythmia radioablation (STAR) has been recently introduced for the management of ventricular tachycardia (VT) refractory to antiarrhythmic drugs and catheter ablation (CA). VT recurrences have been reported after STAR but the mechanisms remain largely unknown. Purpose We analyzed recurrences in the Swiss Cohort after STAR for refractory VT in order to assess their location related to the irradiated volume. Methods From 09.2017 to 01.2020, 20 patients (68±8y, LVEF 37±15%) suffering from refractory VT were enrolled. The underlying cardiopathy was ischemic in 6, inflammatory in 4, neoplastic in 1 and idiopathic in 9 patients. Sixteen out of 20 patients had a history of at least 1 electrical storm. Before STAR, an invasive electro-anatomical mapping (Carto3) of the VT substrate was performed. A mean dose of 23±2Gy was delivered to the planning target volume (PTV). Results The median ablation volume was 26 ml (range 14-115) and involved the interventricular septum (IVS) in 75% of patients. During the first 6 months after STAR, VT burden decreased by 92% (median value, from 108 to 10 VT/semester, p Conclusion STAR is a precious new tool available for the treatment of therapy-refractory VT, allowing for a significant reduction of VT burden. VT recurrences are common during follow-up, but no recurrences were observed inside the PTV. Local efficacy was supported by a significant decrease in both bipolar and unipolar signal amplitude.

The EU Horizon 2020 Framework-funded Standardized Treatment and Outcome Platform for Stereotactic Therapy Of Re-entrant tachycardia by a Multidisciplinary (STOPSTORM) consortium has been established as a large research network for investigating STereotactic Arrhythmia Radioablation (STAR) for ventricular tachycardia (VT). The aim is to provide a pooled treatment database to evaluate patterns of practice and outcomes of STAR and finally to harmonize STAR within Europe. The consortium comprises 31 clinical and research institutions. The project is divided into nine work packages (WPs): (i) observational cohort; (ii) standardization and harmonization of target delineation; (iii) harmonized prospective cohort; (iv) quality assurance (QA); (v) analysis and evaluation; (vi, ix) ethics and regulations; and (vii, viii) project coordination and dissemination. To provide a review of current clinical STAR practice in Europe, a comprehensive questionnaire was performed at project start. The STOPSTORM Institutions' experience in VT catheter ablation (83% ≥ 20 ann.) and stereotactic body radiotherapy (59% > 200 ann.) was adequate, and 84 STAR treatments were performed until project launch, while 8/22 centres already recruited VT patients in national clinical trials. The majority currently base their target definition on mapping during VT (96%) and/or pace mapping (75%), reduced voltage areas (63%), or late ventricular potentials (75%) during sinus rhythm. The majority currently apply a single-fraction dose of 25 Gy while planning techniques and dose prescription methods vary greatly. The current clinical STAR practice in the STOPSTORM consortium highlights potential areas of optimization and harmonization for substrate mapping, target delineation, motion management, dosimetry, and QA, which will be addressed in the various WPs.

Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): Horizon 2020 research and innovation programme Background/Introduction In patients with structural heart disease (SHD), ventricular tachycardia (VT) plays a decisive role in sudden cardiac death. VT patients are often treated with antiarrhythmic medication and catheter ablation. For refractory VTs, STereotactic Arrhythmia Radioablation (STAR) delivered to the underlying VT substrate has recently been introduced and showed promising results for otherwise untreatable patients. [1] Purpose The purpose of the STOPSTORM consortium is to harmonize and optimize STAR across Europe. It consists of 31 members including 24 electrophysiology and 22 radiation oncology departments performing or participating in STAR throughout eight European countries. To obtain initial overview of organization, equipment, procedures, experiences, and quality levels for STAR, a detailed survey was circulated among STOPSTORM members. Methods The survey included questions for electrophysiology (18 questions), radiation oncology (24 questions) and medical physics (23 questions). The survey was the first step for accreditation of the centres and therefore mandatory for all consortium members. Results All centres participating in STOPSTORM completed the survey. 16 centres performed a total of 84 STAR treatments until May 2021 and 11 centres already participate in clinical trials for STAR. Annual number of VT ablations in SHD: less than 20 (17%), 20-50 (50%), 50-100 (21%), more than 100 (12%) and epicardial: less than 20 (71%), 20-50 (17%), n/s (12%). An overview of the availability of a clinical program for catheter ablation of ventricular arrhythmia with certification of the respective national cardiology society and the practice of general quality audits for ablation is given in figure 1. Participation in multicentre clinical trials in cardiology/EP were indicated by 19 departments (79%). Target volume definition is based on invasive electroanatomical mapping during VT (96%), pace mapping (75%), reduced voltage areas (63%) and/or late ventricular potentials (75%). Half of the centres includes the clinical VT substrate, while the other half includes the whole arrhythmogenic substrate. Non-invasive surface ECG mapping has so far found little application: used clinically (13%), research purposes (8%) and evaluation (4%). Stereotactic Body Radiotherapy experience (> 10 years: 82%, > 200 p.a.: 59%) is high. In all but one clinic, a dose of 25 Gy in a single fraction is applied. The prescription method, planning technique and inhomogeneity in the target volume, however, varies greatly. All departments perform patient-specific plan verifications for STAR, but with various evaluation criteria. Conclusion Experience in STAR within the STOPSTORM consortium is adequate, while the survey shows areas of harmonization and optimization need for substrate mapping, target delineation, dosimetry and quality assurance which will be addressed in the STOPSTORM project work-packages.

Background Normofractionated radiation regimes for definitive prostate cancer treatment usually extend over 7–8 weeks. Recently, moderate hypofractionation with doses per fraction between 2.2 and 4 Gy has been shown to be safe and feasible with oncologic non-inferiority compared to normofractionation. Radiobiologic considerations lead to the assumption that prostate cancer might benefit in particular from hypofractionation in terms of tumor control and toxicity. First data related to ultrahypofractionation demonstrate that the overall treatment time can be reduced to 5–7 fractions with single doses > 6 Gy safely, even with simultaneous focal boosting of macroscopic tumor(s). With MR-guided linear accelerators (MR-linacs) entering clinical routine, invasive fiducial implantations become unnecessary. The aim of the multicentric SMILE study is to evaluate the use of MRI-guided stereotactic radiotherapy for localized prostate cancer in 5 fractions regarding safety and feasibility. Methods The study is designed as a prospective, one-armed, two-stage, multi-center phase-II-trial with 68 patients planned. Low- and intermediate-risk localized prostate cancer patients will be eligible for the study as well as early high-risk patients (cT3a and/or Gleason Score ≤ 8 and/or PSA ≤ 20 ng/ml) according to d’Amico. All patients will receive definitive MRI-guided stereotactic radiation therapy with a total dose of 37.5 Gy in 5 fractions (single dose 7.5 Gy) on alternating days. A focal simultaneous integrated boost to MRI-defined tumor(s) up to 40 Gy can optionally be applied. The primary composite endpoint includes the assessment of urogenital or gastrointestinal toxicity ≥ grade 2 or treatment-related discontinuation of therapy. The use of MRI-guided radiotherapy enables online plan adaptation and intrafractional gating to ensure optimal target volume coverage and protection of organs at risk. Discussion With moderate hypofractionation being the standard in definitive radiation therapy for localized prostate cancer at many institutions, ultrahypofractionation could be the next step towards reducing treatment time without compromising oncologic outcomes and toxicities. MRI-guided radiotherapy could qualify as an advantageous tool as no invasive procedures have to precede in therapeutic workflows. Furthermore, MRI guidance combined with gating and plan adaptation might be essential in order to increase treatment effectivity and reduce toxicity at the same time.

Highlights • Re-irradiation of the brain is feasible with an encouraging overall survival. • Treatment related toxicity was low within the reported dose range. • EQD2 cumulative dose distributions were calculated using rigid registration. • Dose-Response-Modelling with logistic regression showed a correlation of the D1cc brain with any grade of acute toxicity., Introduction The use of cranial re-irradiation is growing with improving overall survival and the advent of high-precision radiotherapy techniques. Still the value of re-irradiation needs careful evaluation regarding safety and efficacy. We analyzed dosimetric and clinical data of patients receiving cranial re-irradiation using EQD2 sum plans. Methods and material We retrospectively analyzed the data of 76 patients who received repeated cranial radiotherapy from 02/2013 to 09/2016. 34 patients suffered from recurrent primary brain tumors, 42 from brain metastases. Dosimetric analysis was performed accumulating EQD2 dose distributions based on rigid image registration. Clinical and radiological data was collected at follow-ups including toxicity, local control and overall survival. Results In total 76 patients had at least 2 courses of intracranial radiotherapy. The median accumulated prescription EQD2 dose was 96.5 Gy2 for all radiation courses combined. The median D(0.1 cc) of the brain for patients receiving more than 100 Gy2 was 114 Gy2 with a highest dose of 161.5 Gy2. 74% of patients suffered from low grade (G1–G2) acute toxicity, only two high grade (>G3) toxicities were recorded. Median overall survival from the time of first re-irradiation was 57 weeks (range 4–186 weeks). The median time to local failure for patients with a primary brain tumor was not reached and 24 weeks (range 1–77 weeks) for patients with brain metastases. Conclusion Repeated radiotherapy appears both safe and efficient in patients with recurrent primary or secondary brain tumors with doses to the brain up to 120 Gy2 EQD2, doses below 100 Gy2 for brainstem and doses below 75 Gy2 EQD2 to chiasm and optic nerves.

Objectives: Chemo-radiotherapy (CRT) and concurrent PD-1 inhibition has shown promising results in preclinical models. So far, the feasibility of delivering concurrent CRT and PD-1/PD-L1 inhibition has never been assessed in a clinical trial.Material and methods: NICOLAS is a phase-II trial evaluating the safety and efficacy of nivolumab combined with CRT in stage III NSCLC. Patients received 3 cycles of platinum-based chemotherapy and concurrent RT (66 Gy/33fractions). Nivolumab started concurrently with RT. The primary endpoint was 6-month post-RT rate of grade- >= 3-pneumonitis. A formal interim safety analysis (IA) was scheduled when the first 21 patients reached 3 months follow-up post-RT. An early positive safety conclusion would be reached at IA if there were no grade >= 3-pneumonitis in those patients. Efficacy evaluation was planned provided the safety conclusion was reached.Results and conclusion: As of 13 December 2018, 82 patients were recruited with median follow-up of 13.4 months. The most frequent adverse events (AEs) were anaemia, fatigue and pneumonitis. No unexpected AEs or increased toxicities were observed. For the first 21 patients, no grade- >= 3-pneumonitis was observed by the end of the 3-month post-RT follow-up period.The early safety IA provides evidence that the addition of nivolumab to concurrent CRT is safe and tolerable regarding the 6-month rate of pneumonitis grade >= 3 at the one-sided significance level of 5%. Following that, the 1-year progression-free survival will be evaluated in an expanded patient cohort NICOLAS trial creates the opportunity for assessing the activity of the combination of checkpoint with concurrent CRT in larger prospective trials for locally advanced NSCLC.

Background MR-guided online adaptive stereotactic body radiation therapy (SBRT) for prostate cancer aims to reduce toxicity by full compensation of interfractional uncertainties. However, the process of online adaptation currently takes approximately 45 min during which intrafractional movements remain unaccounted for. This study aims to analyze the dosimetric benefit of online adaptation and to evaluate its robustness over the duration of one treatment fraction. Methods Baseline MR-scans at a MR-linear accelerator were acquired for ten healthy male volunteers for generation of mock-prostate SBRT plans with a dose prescription of 5 × 7.25 Gy. On a separate day, online MR-guided adaptation (ViewRay® MRIdian) was performed, and thereafter MR images were acquired every 15 min for 1 h to assess the stability of the adapted plan. Results A dosimetric benefit of online MR-guided adaptive re-planning was observed in 90% of volunteers. The median D95CTV- and D95PTV-coverage was improved from 34.8 to 35.5 Gy and from 30.7 to 34.6 Gy, respectively. Improved target coverage was not associated with higher dose to the organs at risk, most importantly the rectum (median D1ccrectum baseline plan vs. adapted plan 33.3 Gy vs. 32.3 Gy). The benefit of online adaptation remained stable over 45 min for all volunteers. However, at 60 min, CTV-coverage was below a threshold of 32.5 Gy in 30% of volunteers (30.6 Gy, 32.0 Gy, 32.3 Gy). Conclusion The dosimetric benefit of MR-guided online adaptation for prostate SBRT was robust over 45 min in all volunteers. However, intrafractional uncertainties became dosimetrically relevant at 60 min and we therefore recommend verification imaging before delivery of MR-guided online adapted SBRT.

Introduction The current phase III EORTC 1420 Best-of trial (NCT02984410) compares the swallowing function after transoral surgery versus intensity modulated radiotherapy (RT) in patients with early-stage carcinoma of the oropharynx, supraglottis and hypopharynx. We report the analysis of the Benchmark Case (BC) procedures before patient recruitment with special attention to dysphagia/aspiration related structures (DARS). Materials and methods Submitted RT volumes and plans from participating centers were analyzed and compared against the gold-standard expert delineations and dose distributions. Descriptive analysis of protocol deviations was conducted. Mean Sorensen-Dice similarity index (mDSI) and Hausdorff distance (mHD) were applied to evaluate the inter-observer variability (IOV). Results 65% (23/35) of the institutions needed more than one submission to achieve Quality assurance (RTQA) clearance. OAR volume delineations were the cause for rejection in 53% (40/76) of cases. IOV could be improved in 5 out of 12 OARs by more than 10 mm after resubmission (mHD). Despite this, final IOV for critical OARs in delineation remained significant among DARS by choosing an aleatory threshold of 0.7 (mDSI) and 15 mm (mHD). Conclusions This is to our knowledge the largest BC analysis among Head and neck RTQA programs performed in the framework of a prospective trial. Benchmarking identified non-common OARs and target delineations errors as the main source of deviations and IOV could be reduced in a significant number of cases after this process. Due to the substantial resources involved with benchmarking, future benchmark analyses should assess fully the impact on patients’ clinical outcome.

Additional file 2: Table S2. Dose Constraints.

Additional file 1: Table S1. Couch shifts; A lateral, B vertical, C axial shifts in cm. Each line represents one volunteer. Bold = median.

Introduction: The NICOLAS study is the first completed single-arm phase II trial in stage III NSCLC evaluating hierarchically first the safety and then the efficacy of adding nivolumab concurrently to standard definitive concurrent chemoradiotherapy. The safety end point was reported earlier; here, we present the efficacy results. Methods: Stage IIIA-B unresectable treatment-naive patients with NSCLC received three cycles of platinum-based chemotherapy and concurrent radiotherapy (66 Gy, 33 fractions), along with nivolumab (360 mg, 3-weekly). Nivolumab was continued as monotherapy consolidation for a maximum of 1 year (480 mg, 4-weekly). The primary end point was 1-year progression-free survival (PFS), with a target improvement compared with historical data of at least 15%, from 45% to 60%. To test this efficacy hypothesis, a sample size of 74 assessable patients provided a power of 83% with a one-sided alpha of 5%. Results: A total of 79 patients were enrolled with a median follow-up of 21.0 months (interquartile range: 15.8–25.8 mo) for the primary PFS analysis. A total of 35.4% of the patients had stage IIIA, and 63.3% had stage IIIB disease. The 1-year PFS was 53.7% (95% confidence interval [CI]: 42.0%–64.0%) and the median PFS was 12.7 months (95% CI: 10.1–22.8 mo). Because 37 PFS events occurred in the first year posttreatment among the first 74 assessable patients, a 1-year PFS rate of at least 45% could not be rejected (p = 0.23). At an extended follow-up (median 32.6 mo), 37 deaths have been recorded, with a median overall survival (OS) of 38.8 months (95% CI: 26.8 mo–not estimable) and a 2-year OS rate of 63.7% (95% CI: 51.9%–73.4%). The OS of patients with stage IIIA disease was found to be significantly higher than patients with stage IIIB disease, with a 2-year OS of 81% and 56%, respectively (p = 0.037). Conclusions: PFS and OS are arithmetically higher in studies involving the same population. However, on the basis of the formal hierarchical efficacy analysis, we could not reject that the 1-year PFS rate is at least 45%. © 2020

Additional file 3: Fig. S1. D1ccrectum for the baseline plan on the MR of the day compared to the adapted plan. Bar = median.

Additional file 1: BC description, protocol predefined criterions for BC review, and corresponding number of all unacceptable criterions.

Background Stereotactic body radiation therapy (SBRT) is emerging as a bail-out treatment in patients suffering from therapy resistant ventricular tachyarrhythmias (VT). Purpose We report the worldwide first cases of real-time magnetic resonance image guided SBRT (MR-SBRT) in recurrent sustained VT and electrical storm (ES) due to dilated cardiomyopathy (DCM). Methods The patients were male, 71- (patient A) and 74-year-old (patients B) suffering from recurrent VT and ES with ICD shocks, despite guideline-directed medical therapy including maximal antiarrhythmic therapy. Patient A had two endocardial radiofrequency catheter ablation (RFA) and one epicardial surgical RFA and patient B had one endocardial RFA prior. An interdisciplinary decision was made to perform MR-SBRT in palliative intent to minimize repetitive ICD shocks. Results Areas of VT-substrate were identified to build a volumetric target using the performed EP studies as well as cardiac MRI and CT. A single fraction of 25Gy at isodose 80% was delivered to a planned target volume of 115.1ml and 73ml in the anterior/anteroseptal basal regions in patients A and B, respectively on a dedicated MR linac using real-time MRI tracking. Patient A developed a prolonged ES interpreted as acute radiation-induced inflammation following the treatment, which ceased two days after administration of high-dose dexamethasone. Patient B had no immediate adverse effects from the treatment. Left-ventricular ejection fraction remained stable in both patients at 25%. Both patients had significant improvement of their quality of life. Patient A died 222 days after MR-SBRT due to recurrent ES at another hospital. Patient B is free from VT over six months after treatment. Conclusion In these first two cases, we demonstrate feasibility, safety and short-term efficacy of MR-SBRT. ICD therapies before and after MR-SBRT Funding Acknowledgement Type of funding source: None

Purpose To externally validate previously published Normal Tissue Complication Probability (NTCP) models developed by separate teams for grade 3 oral mucositis (g3OM). Materials and methods Two models were validated: a logistic model, based on 144 head and neck cancer (HNC) patients receiving induction chemotherapy followed by chemo-IMRT; a multivariable logistic model for prediction of g3OM for 253 patients receiving radical treatment for the head and neck squamous cell carcinoma (HNSCC). The EORTC HNCG-ROG 1219 DAHANCA trial dataset, consisting of 169 patients was used as the validation cohort. This cohort was treated with accelerated fractionated chemo-IMRT, with/without the hypoxic radiosensitizer Nimorazole for HNSCC. External validity was assessed using the scaled Brier score. Calibration was assessed in terms of calibration curves as well as measures of mean and weak calibration. Hosmer-Lemeshow was used for goodness-of-fit test. Discrimination was calculated using the area under the receiver operating curve (AUC-ROC). Results The prevalence of g3OM in the validation cohort (35.5%) was similar to that of two development cohorts, i.e. 38.7% and 31.9% for Bhide logistic and Otter multivariable logistic models respectively. The scaled Brier scores showed good overall model performance. Perfect calibration was observed in the prevalence range of 20% to 40%. AUC-ROC was acceptable in external validation (0.67). The Hosmer-Lemeshow test showed good agreement between predicted and observed outcomes for two models. Conclusion The NTCP models were validated and lead to valid predictions in a wide range of diverse treatment techniques and patient characteristics, also when Nimorazole is added as hypoxic radiosensitizer.

Background Careful selection of malignant pleural mesothelioma (MPM) patients for curative treatment is of highest importance, as the multimodal treatment regimen is challenging for patients and harbors a high risk of substantial toxicity. Radiomics—a quantitative method for image analysis—has shown its prognostic ability in different tumor entities and could therefore play an important role in optimizing patient selection for radical cancer treatment. So far, radiomics as a prognostic tool in MPM was not investigated. Materials and methods This study is based on 72 MPM patients treated with surgery in a curative intent at our institution between 2009 and 2017. Pre-treatment Fluorine-18 fluorodeoxyglucose (FDG) PET and CT scans were used for radiomics outcome modeling. After extraction of 1404 CT and 1410 FDG PET features from each image, a preselection by principal component analysis was performed to include only robust, non-redundant features for the cox regression to predict the progression-free survival (PFS) and the overall survival (OS). Results were validated on a separate cohort. Additionally, SUVmax and SUVmean, and volume were tested for their prognostic ability for PFS and OS. Results For the PFS a concordance index (c-index) of 0.67 (95% CI 0.52–0.82) and 0.66 (95% CI 0.57–0.78) for the training cohort (n = 36) and internal validation cohort (n = 36), respectively, were obtained for the PET radiomics model. The PFS advantage of the low-risk group translated also into an OS advantage. On CT images, no radiomics model could be trained. SUV max and SUV mean were also not prognostic in terms of PFS and OS. Conclusion We were able to build a successful FDG PET radiomics model for the prediction of PFS in MPM. Radiomics could serve as a tool to aid clinical decision support systems for treatment of MPM in future.

Purpose or Objective: The COVID-19 pandemic has required rapid and repetitive adjustment of radiotherapy practice, hospital and department organization and hygienic measures. This has been in parallel with significant changes in everyone’s private life. In the Department of Radiation Oncology, University Zurich, all employees were invited to participate in weekly assessments of their stress levels, aiming to rapidly and precisely implement anti-stress measures. Materials and Methods: Starting from March 31st 2020, weekly anonymized surveys were distributed to all employees (n=134) of the Department of Radiation Oncology, University of Zurich. Survey Monkey was used, and distribution was performed via email. The survey asked about the profession (clinician, medical physics and dosimetry, RTT, nurse, administration and research) and whether work in the last week was performed in hospital with or without patient contact or in home office. Global stress level during the last week was assessed on a 10-point scale. Additionally, stress was assessed in the sub-categories: concerns about own health;concerns about health of family & friends;concerns about patients` health. Results: Between March 31st 2020 and February 17th 2021, a total of 47 surveys resulted in 1733 responses, 37 responses on average (range 26 and 54). Response rate was 28% on average and did not change over time, overall and in each profession. Averaged over all responses, the global stress level varied substantially between professions, ranging between 2.8 for administration and 6.8 for RTTs. The global stress level was highest for in-hospital work with patient contact with an average of 4.7, whereas stress was similar for in-hospital work without patient contact and home-office with 3.5 and 3.8, respectively. Concerns about health were highest about family & friends with 4.0 on average compared to concerns about the own health and of the patients with average values of 3.1 and 3.5, respectively. Changes of global stress level over the 47 weeks were strongly associated with development of the pandemic (figure). Averaged over all employees, the global stress level stated with 4.8 on average in March 2020 and dropped continuously in the spring and summer months until the second COVID-19 wave started in September 2020 with two peaks in November and December with 5.5 and 5.7 on average, respectively. Interventions against high stress levels were performed for all professions and especially the RTT subgroup with highest stress levels (workshops;meditation room;detailed information about hospital-specific infection rates;information about hospital wide possibilities for coping mechanisms, effectiveness of PPE;team meetings).

Definition of gross tumor volume (GTV) in hepatocellular carcinoma (HCC) requires dedicated imaging in multiple contrast medium phases. The aim of this study was to evaluate the interobserver agreement (IOA) in gross tumor delineation of HCC in a multicenter panel. The analysis was performed within the “Stereotactic Radiotherapy” working group of the German Society for Radiation Oncology (DEGRO). The GTVs of three anonymized HCC cases were delineated by 16 physicians from nine centers using multiphasic CT scans. In the first case the tumor was well defined. The second patient had multifocal HCC (one conglomerate and one peripheral tumor) and was previously treated with transarterial chemoembolization (TACE). The peripheral lesion was adjacent to the previous TACE site. The last patient had an extensive HCC with a portal vein thrombosis (PVT) and an inhomogeneous liver parenchyma due to cirrhosis. The IOA was evaluated according to Landis and Koch. The IOA for the first case was excellent (kappa: 0.85); for the second case moderate (kappa: 0.48) for the peripheral tumor and substantial (kappa: 0.73) for the conglomerate. In the case of the peripheral tumor the inconsistency is most likely explained by the necrotic tumor cavity after TACE caudal to the viable tumor. In the last case the IOA was fair, with a kappa of 0.34, with significant heterogeneity concerning the borders of the tumor and the PVT. The IOA was very good among the cases were the tumor was well defined. In complex cases, where the tumor did not show the typical characteristics, or in cases with Lipiodol (Guerbet, Paris, France) deposits, IOA agreement was compromised.

Additional file 1: Stable FDG PET features.

Additional file 2: Figure 1. Cox regression model for volume for OS.

Additional file 3. Details on the multivariate Cox regression model for FDG PET radiomics.

BACKGROUND Venous thromboembolic events are significant complications in patients and possibly associated with an unfavorable outcome. Thrombosis risk is poorly defined for patients with brain metastasis, and available risk calculation scores are not validated for these patients. MATERIAL AND METHODS We identified 811 patients with brain metastasis followed at our institution and screened electronic charts retrospectively for the occurrence of venous thromboembolic events, along with candidate risk factors. Risk factors were tested in uni- and multivariate analyses and finally integrated in a score model for risk prediction. RESULTS Venous thromboembolic events were documented in 97 of 811 patients (12.0%). Primary tumors with high thrombogenicity (p=0.02, odds ratio 1.7, 95% CI 1.1–2.8), dexamethasone (p=0.011, odds ratio 2.27, 95% CI 1.5–4.5), chemotherapy (p=0.005, odds ratio 3.4, 95% CI 1.6–7.5), BMI > 35 kg/m2 (p=0.002, odds ratio 3.4, 95% CI 1.6–7.5) and immobilization (p=0.003, odds ratio 2.4, 95% CI 1.3–4.3) were confirmed as independent predictors of VTE. We derived a score model for venous thromboembolic event prediction, the PICOS (thrombogenic Primary, Immobilization, Chemotherapy, Obesity, Steroids) score (0–7 points). Receiver Operating Characteristic Curve Analysis demonstrated its prognostic accuracy (AUC=0.71, 95% CI 0.64–0.77), and its predictive capability was superior to that of other scores proposed for the evaluation of venous thromboembolic event risk such as the Khorana (AUC=0.51) or CONKO (AUC=0.52) scores. CONCLUSION We report a rate of venous thrombotic events of 12.0% in our cohort of 811 patients with brain metastasis. We define a risk model for prediction in of venous thrombotic events in patients with BM, the PICOS score. It may become a valuable tool for the identification of brain metastasis patients at high risk for venous thromboembolic events and be helpful for guidance of clinicians towards decision whether to start thrombosis prophylaxis. Further, the PICOS score might be used for stratification in controlled studies.