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With the increasing need for minimally invasive procedures based on lower complication rates, higher patient acceptance, and technical developments, there is a growing focus on the sound interventional training of young radiologists. This survey aimed to analyze the current situation in interventional radiology (IR) training in Germany to detect shortcomings and identify areas for improvement.From November 1-30, 2020, an online questionnaire was distributed to representative radiological associations and societies with the request to forward it to radiology residents and radiologists 40 years. The 44 questions covered six distinct areas from personal working conditions to the characterization of the IR department, training conditions, role of women in IR, and attendance at congresses/external training.A total of 330 participants completed the questionnaire. 77 % of participants expressed a high interest in IR, and 47 % could even imagine subspecializing in interventional radiology. Most institutions provided the necessary learning conditions and infrastructure. The rate of overall satisfaction with IR training conditions was 45 % (vs. a dissatisfaction rate of 39 %). However, females showed a lower satisfaction rate with their training environment than male participants (28 % vs. 51 %; P = 0.06). Positive correlations with work satisfaction were found for the presence and duration of the IR rotation, the number of partly independently/mentored performed interventions, and structured feedback. Moreover, the need for a structured training curriculum was expressed by 67 % of participants.Radiological residents and young radiologists expressed a high interest in interventional radiology, and they rate the infrastructure of German hospitals regarding IR as sufficient. However, they expressed the need for consistent IR rotations and better-structured resident and postgraduate education (curriculainterviews).Interest in interventional radiology among radiological residents and young radiologists in Germany is high, but satisfaction with interventional radiology training leaves room for improvement. The most frequently mentioned aspects that can improve IR training were · organized rotations of at least 6 months. · structured curriculums with face-to-face feedback. · structured guidance by senior interventionists during procedures. CITATION FORMAT: · Sieren M, Katoh M, Mahnken AH et al. Work and Training Conditions of German Residents and Young Radiologists in Interventional Radiology - A Nationwide Survey. Fortschr Röntgenstr 2022; 194: 1346 - 1357.Die fundierte interventionelle Ausbildung junger RadiologInnen gerät durch den zunehmenden Bedarf an minimal-invasiven Prozeduren immer mehr in den Fokus. Ziel dieser Umfrage war es, die aktuelle Situation der Ausbildung in der Interventionellen Radiologie (IR) in Deutschland zu analysieren, um Defizite aufzudecken und Verbesserungsmöglichkeiten zu identifizieren.Vom 1. bis 30. November 2020 wurde ein Online-Fragebogen an repräsentative radiologische Verbände und Gesellschaften versandt mit der Bitte, ihn an AssistenzärztInnen und RadiologInnen 40 Jahre weiterzuleiten. Die 44 Fragen deckten 6 verschiedene Bereiche ab, von den persönlichen Arbeitsbedingungen bis zur Charakterisierung der IR-Abteilung, den Ausbildungsbedingungen, der Rolle der Frauen in der IR und der Teilnahme an Kongressen/externen Fortbildungen.Insgesamt haben 330 TeilnehmerInnen den Fragebogen ausgefüllt. 77 % der TeilnehmerInnen bekundeten ein hohes Interesse an der IR und 47 % konnten sich sogar eine Subspezialisierung in der interventionellen Radiologie vorstellen. Die Mehrheit der Institutionen stellten die notwendigen Rahmenbedingungen und Infrastruktur bereit. Insgesamt lag die Zufriedenheit über die interventionsradiologische Weiterbildung bei 45 % (vs. 39 % Unzufriedenheit), wobei die Zufriedenheit mit den Ausbildungsbedingungen bei Teilnehmerinnen geringer ausfiel als bei den Teilnehmern (28 % vs. 51 %; P = 0,06). Positive Korrelationen mit der Arbeitszufriedenheit wurden für das Vorhandensein und die Dauer der IR-Rotation, die Anzahl der teilweise selbstständig/supervidiert durchgeführten Eingriffe und ein institutionalisiertes, strukturiertes Feedback festgestellt. Darüber hinaus äußerten 67 % der Teilnehmer den Wunsch nach einem strukturierten Ausbildungscurriculum.AssistenzärztInnen und junge RadiologInnen zeigen ein hohes Interesse an der Interventionellen Radiologie und bewerten die Infrastruktur deutscher Krankenhäuser im Bereich der IR als ausreichend. Sie äußerten jedoch den Bedarf an konsistenten IR-Rotationen und einer besser strukturierten grundlegenden und weiterführenden Ausbildung (CurriculaInterviews).Das Interesse an der Interventionellen Radiologie ist bei Assistenzärzten und jungen Radiologen in Deutschland hoch, die Zufriedenheit mit der Ausbildung in der Interventionellen Radiologie ist geringer. Die am häufigsten genannten Aspekte, die die IR-Ausbildung verbessern können, waren · organisierte Rotationen von mindestens 6 Monaten Dauer. · strukturierte Curricula mit persönlichem Feedback. · strukturierte Anleitung durch erfahrene Interventionisten während der Eingriffe.

Comparison of puncture deviation and puncture duration between computed tomography (CT)- and C-arm CT (CACT)-guided puncture performed by residents in training (RiT).In a cohort of 25 RiTs enrolled in a research training program either CT- or CACT-guided puncture was performed on a phantom. Prior to the experiments, the RiT's level of training, experience playing a musical instrument, video games, and ball sports, and self-assessed manual skills and spatial skills were recorded. Each RiT performed two punctures. The first puncture was performed with a transaxial or single angulated needle path and the second with a single or double angulated needle path. Puncture deviation and puncture duration were compared between the procedures and were correlated with the self-assessments.RiTs in both the CT guidance and CACT guidance groups did not differ with respect to radiologic experience (p = 1), angiographic experience (p = 0.415), and number of ultrasound-guided puncture procedures (p = 0.483), CT-guided puncture procedures (p = 0.934), and CACT-guided puncture procedures (p = 0.466). The puncture duration was significantly longer with CT guidance (without navigation tool) than with CACT guidance with navigation software (p 0.001). There was no significant difference in the puncture duration between the first and second puncture using CT guidance (p = 0.719). However, in the case of CACT, the second puncture was significantly faster (p = 0.006). Puncture deviations were not different between CT-guided and CACT-guided puncture (p = 0.337) and between the first and second puncture of CT-guided and CACT-guided puncture (CT: p = 0.130; CACT: p = 0.391). The self-assessment of manual skills did not correlate with puncture deviation (p = 0.059) and puncture duration (p = 0.158). The self-assessed spatial skills correlated positively with puncture deviation (p = 0.011) but not with puncture duration (p = 0.541).The RiTs achieved a puncture deviation that was clinically adequate with respect to their level of training and did not differ between CT-guided and CACT-guided puncture. The puncture duration was shorter when using CACT. CACT guidance with navigation software support has a potentially steeper learning curve. Spatial skills might accelerate the learning of image-guided puncture.· The CT-guided and CACT-guided puncture experience of the RiTs selected as part of the program "Researchers for the Future" of the German Roentgen Society was adequate with respect to the level of training.. · Despite the lower collective experience of the RiTs with CACT-guided puncture with navigation software assistance, the learning curve regarding CACT-guided puncture may be faster compared to the CT-guided puncture technique.. · If the needle path is complex, CACT guidance with navigation software assistance might have an advantage over CT guidance..· Meine TC, Hinrichs JB, Werncke T et al. Phantom study for comparison between computed tomography- and C-Arm computed tomography-guided puncture applied by residents in radiology. Fortschr Röntgenstr 2022; 194: 272 - 280.ZIEL: Vergleich der Punktionsabweichung und -dauer zwischen Computertomografie (CT) – und C-Arm-CT (CACT) -gesteuertem Punktionsverfahren bei Anwendung durch Assistenzärzte in Weiterbildung (AiW).In einer Kohorte von 25 AiW, die Teil einer wissenschaftlichen Förderung waren, wurden entweder CT- oder CACT-gesteuerte Punktionen an einem Phantom durchgeführt. Vor Beginn wurden der Weiterbildungsstand, die Erfahrung mit Spielen eines Musikinstruments, mit Videospielen und mit Ballsportarten und die Selbsteinschätzung von manueller Geschicklichkeit und räumlichem Denkvermögen abgefragt. Jede/r AiW führte 2 Punktionen durch, wobei die 1. Punktion mit einem transaxialen bzw. einfach angulierten Nadelpfad und die 2. Punktion mit einem einfach bzw. doppelt angulierten Nadelpfad erfolgte. Punktionsabweichung und -dauer wurden zwischen den Verfahren verglichen und mit den Selbsteinschätzungen korreliert.Die beiden Gruppen der AiW zeigten keine Unterschiede in der Erfahrung in der Radiologie (p = 1), in der Angiografie (p = 0.415) und in der Anzahl bereits durchgeführter Punktionen gesteuert durch Ultraschall (p = 0,483), CT (p = 0,934) und CACT (p = 0,466). In der CT (ohne Navigationssoftware) war die Punktionsdauer signifikant länger als mit der CACT-Bildsteuerung mit Navigationssoftware (p 0,001). Bei der Punktionsdauer zeigten sich keine signifikanten Unterschiede zwischen der 1. und 2. Punktion im CT (p = 0,719), während die 2. Punktion mit CACT schneller durchgeführt werden konnte (p = 0,006). Die Punktionsabweichung war weder signifikant zwischen CT- und CACT-Bildsteuerung (p = 0,337), noch zwischen der 1. und 2. Punktion der jeweiligen Verfahren (CT: p = 0,130; CACT: p = 0,391). Die Selbsteinschätzung der manuellen Geschicklichkeit korrelierte nicht mit der Punktionsabweichung (p = 0,059) und -dauer (p = 0,158). Das subjektive räumliche Denkvermögen zeigte eine moderate positive Korrelation zur Punktionsabweichung (p = 0,011), aber nicht zur -dauer (p = 0,541).Die AiW erreichten eine dem Ausbildungsstand entsprechende, klinisch adäquate Punktionsabweichung unter CT- und CACT-Bildsteuerung. Die CACT-gesteuerten Punktionen mit Unterstützung durch Navigationssoftware wurden schneller durchgeführt, und auch die Lernkurve war mit CACT-Bildsteuerung steiler. Räumliches Denkvermögen kann möglicherweise das Erlernen bildgesteuerter Punktionen beschleunigen.· Die Erfahrung mit Punktionen war in einer Gruppe von AiW, die im Rahmen des Programms der Deutschen Röntgengesellschaft e. V. „Forscher-für-die-Zukunft“ ausgesucht wurden, dem Weiterbildungsstand entsprechend.. · Trotz kollektiv geringerer Erfahrung der radiologischen AiW mit der CACT-gesteuerten Punktion mit Navigationssoftwareunterstützung ist die Lernkurve gegenüber der einfachen CT-Punktion möglicherweise steiler.. · Bei schwierigen Punktionswegen könnte die CACT-Bildsteuerung mit Softwareunterstützung einen Vorteil in der Durchführung gegenüber der konventionellen CT-Bildsteuerung haben..· Meine TC, Hinrichs JB, Werncke T et al. Phantom study for comparison between computed tomography- and C-Arm computed tomography-guided puncture applied by residents in radiology. Fortschr Röntgenstr 2022; 194: 272 – 280.

Prediction of response to percutaneous sclerotherapy in patients with venous malformations (VM) is currently not possible with baseline clinical or imaging characteristics. This prospective single-center study aimed to predict treatment outcome of percutaneous sclerotherapy as measured by quality of life (QoL) by using radiomic analysis of diffusion-weighted (dw) magnetic resonance imaging (MRI) before and after first percutaneous sclerotherapy. In all patients (n = 16) pre-interventional (PRE-) and delta (DELTA-) radiomic features (RF) were extracted from dw-MRI before and after first percutaneous sclerotherapy with ethanol gel or polidocanol foam, while QoL was assessed using the Toronto Extremity Salvage Score (TESS) and the 36-Item Short Form Survey (SF-36) health questionnaire. For selecting features that allow differentiation of clinical response, a stepwise dimension reduction was performed. Logistic regression models were fitted and selected PRE-/DELTA-RF were tested for their predictive value. QoL improved significantly after percutaneous sclerotherapy. While no common baseline patient characteristics were able to predict response to percutaneous sclerotherapy, the radiomics signature of VMs (independent PRE/DELTA-RF) revealed high potential for the prediction of clinical response after percutaneous sclerotherapy. This proof-of-concept study provides first evidence on the potential predictive value of (delta) radiomic analysis from diffusion-weighted MRI for Quality-of-Life outcome after percutaneous sclerotherapy in patients with venous malformations.

BackgroundThe inflammatory tumor microenvironment (TME) is formed by various immune cells, being closely associated with tumorigenesis. Especially, the interaction between tumor-infiltrating T-cells and macrophages has a crucial impact on tumor progression and metastatic spread. The purpose of this study was to investigate whether oscillating-gradient diffusion-weighted MRI (OGSE-DWI) enables a cell size-based discrimination between different cell populations of the TME.MethodsSine-shaped OGSE-DWI was combined with the Imaging Microstructural Parameters Using Limited Spectrally Edited Diffusion (IMPULSED) approach to measure microscale diffusion distances, here relating to cell sizes. The accuracy of IMPULSED-derived cell radii was evaluated using in vitro spheroid models, consisting of either pure cancer cells, macrophages, or T-cells. Subsequently, in vivo experiments aimed to assess changes within the TME and its specific immune cell composition in syngeneic murine breast cancer models with divergent degrees of malignancy (4T1, 67NR) during tumor progression, clodronate liposome-mediated depletion of macrophages, and immune checkpoint inhibitor (ICI) treatment. Ex vivo analysis of IMPULSED-derived cell radii was conducted by immunohistochemical wheat germ agglutinin staining of cell membranes, while intratumoral immune cell composition was analyzed by CD3 and F4/80 co-staining.ResultsOGSE-DWI detected mean cell radii of 8.8±1.3 µm for 4T1, 8.2±1.4 µm for 67NR, 13.0±1.7 for macrophage, and 3.8±1.8 µm for T-cell spheroids. While T-cell infiltration during progression of 4T1 tumors was observed by decreasing mean cell radii from 9.7±1.0 to 5.0±1.5 µm, increasing amount of intratumoral macrophages during progression of 67NR tumors resulted in increasing mean cell radii from 8.9±1.2 to 12.5±1.1 µm. After macrophage depletion, mean cell radii decreased from 6.3±1.7 to 4.4±0.5 µm. T-cell infiltration after ICI treatment was captured by decreasing mean cell radii in both tumor models, with more pronounced effects in the 67NR tumor model.ConclusionsOGSE-DWI provides a versatile tool for non-invasive profiling of the inflammatory TME by assessing the dominating cell type T-cells or macrophages.

Purpose Extracellular vesicles, small vesicles carrying inter alia proteins, miRNA and RNA, are important mediators of intercellular communication. The purpose of this study was to assess the distribution of extracellular vesicles from highly malignant breast cancer and their subsequent effect on the immune cell infiltrate in target organs of metastasis. Procedures Extracellular vesicles were isolated from the tissue culture supernatant of highly malignant 4T1 breast cancer cells or the serum of healthy BALB/c mice. The purity of the isolate was verified by electron microscopy and western blotting. Extracellular vesicles were additionally subjected to proteome analysis. After labeling with the fluorescent dye DiR, extracellular vesicles were injected into healthy BALB/c mice and their in vivo distribution was assessed using fluorescence reflectance imaging (FRI). Following ex vivo imaging of the organs, lung tissue samples were analyzed for extracellular vesicle-mediated changes of myeloid cells and T cell numbers, using flow cytometry. Proteome analysis revealed major differences in the cargo of tumor cell–derived versus extracellular vesicles from healthy serum. Results In contrast to control extracellular vesicles, DiR-labeled extracellular vesicles from tumor cells preferentially accumulated in lung, liver, and spine. Subsequent flow cytometry of the immune cell composition of lung tissue samples revealed an increase of cytotoxic CD8+ T cells and a decrease of CD4+ T-helper cells as well as an increase in mature macrophages in response to tumor cell EV. Conclusions In conclusion, distribution of tumor cell–derived extracellular vesicles follows a specific pattern and can be monitored, using dedicated imaging. Extracellular vesicles alter the immune cell composition in target organs of metastasis, using a specific proteome cargo.

Natural killer (NK) cells are key effectors in cancer immunosurveillance and posttransplant immunity, but deficiency of environmental signals and insufficient tumor recognition may limit their activity. We hypothesized that the antibody-mediated anchoring of interleukin-2 (IL-2) to a spliced isoform of the extracellular matrix (ECM) glycoprotein tenascin-C would potentiate NK-cell–mediated antibody-dependent cellular cytotoxicity against leukemic blasts. In this novel-novel combination, dose-escalation, phase 1 trial, we enrolled patients with posttransplant acute myeloid leukemia (AML) relapse to evaluate the safety, pharmacokinetics, pharmacodynamics, and preliminary activity of the antibody-cytokine fusion F16IL2 (10 3 106 to 20 3 106 IU IV; days 1, 8, 15, and 22 of each 28-day cycle) in combination with the anti-CD33 antibody BI 836858 (10-40 mg IV, 2 days after each F16IL2 infusion). Among the 15 patients (median [range] age, 50 [20-68] years) treated across 4 dose levels (DLs), 6 (40%) had received 2 or 3 prior transplantations. The most frequent adverse events were pyrexia, chills, and infusion-related reactions, which were manageable, transient and of grade #2. One dose-limiting toxicity occurred at each of DLs 3 (pulmonary edema) and 4 (graft-versus-host disease). Three objective responses were observed among 7 patients treated at the 2 higher DLs, whereas no responses occurred at the 2 starting DLs. Combination therapy stimulated the expansion and activation of NK cells, including those expressing the FcgRIIIA/CD16 receptor. ECM-targeted IL-2 combined with anti-CD33 immunotherapy represents an innovative approach associated with acceptable safety and encouraging biologic and clinical activity in posttransplant AML relapse. This trial was registered at EudraCT as 2015-004763-37., Blood advances, 6 (12)

Purpose To compare the safety and outcome of transjugular versus percutaneous technique in recanalization of non-cirrhotic, non-malignant portal vein thrombosis. Methods We present a retrospective bicentric analysis of 21 patients with non-cirrhotic, non-malignant PVT, who were treated between 2016 and 2021 by interventional recanalization via different access routes (percutaneous [PT] vs. transjugular in transhepatic portosystemic shunt [TIPS] technique). Complication rates with a focus on periprocedural bleeding and patency as well as outcome were compared. Results Of the 21 patients treated (median age 48 years, range of 19–78), seven (33%) patients had an underlying prothrombotic condition. While 14 (57%) patients were treated for acute PVT, seven (43%) patients had progressive thrombosis with known chronic PVT. Nine patients underwent initial recanalization via PT access and twelve via TIPS technique. There was no significant difference in complete technical success rate according to initial access route (55.5% in PT group vs. 83.3% in TIPS group, p = 0.331). However, creation of an actual TIPS was associated with higher technical success in restoring portal venous flow (86.6% vs. 33.3%, p = 0.030). 13 (61.9%) patients received thrombolysis. Nine (42.8%) patients experienced hemorrhagic complications. In a multivariate analysis, thrombolysis (p = 0.049) and PT access as the first procedure (p = 0.045) were significant risk factors for bleeding. Conclusion Invasive recanalization of the portal vein in patients with PVT and absence of cirrhosis and malignancy offers a good therapeutic option with high recanalization and patency rates. Bleeding complications result predominantly from a percutaneous access and high amounts of thrombolytics used; therefore, recanalization via TIPS technique should be favored.

Background: Immune cells show distinct motion patterns that change upon inflammatory stimuli. Monocytes patrol the vasculature to screen for pathogens, thereby exerting an early task of innate immunity. Here, we aimed to non-invasively analyse single patrolling monocyte behaviour upon inflammatory stimuli. Methods: We used time-lapse Magnetic Resonance Imaging (MRI) of the murine brain to dynamically track single patrolling monocytes within the circulation distant to the actual site of inflammation in different inflammatory conditions, ranging from a subcutaneous pellet model to severe peritonitis and bacteraemia. Findings: Single patrolling immune cells with a velocity of

Iron oxide nanoparticles (ION) are highly sensitive probes for magnetic resonance imaging (MRI) that have previously been used for in vivo cell tracking and have enabled implementation of several diagnostic tools to detect and monitor disease. However, the in vivo MRI signal of ION can overlap with the signal from endogenous iron, resulting in a lack of detection specificity. Therefore, the long-term fate of administered ION remains largely unknown, and possible tissue deposition of iron cannot be assessed with established methods. Herein, we combine nonradioactive 57Fe-ION MRI with ex vivo laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) imaging, enabling unambiguous differentiation between endogenous iron (56Fe) and iron originating from applied ION in mice. We establish 57Fe-ION as an in vivo MRI sensor for cell tracking in a mouse model of subcutaneous inflammation and for assessing the long-term fate of 57Fe-ION. Our approach resolves the lack of detection specificity in ION imaging by unambiguously recording a 57Fe signature.

PURPOSE To evaluate the safety and effectiveness of combined transarterial embolization and percutaneous sclerotherapy in the treatment of refractory and nonresectable aneurysmal bone cysts (ABCs) as assessed by imaging and clinical outcomes. MATERIALS AND METHODS This retrospective, single-center study included 16 consecutive patients (9 women and 7 men; median age, 17 years [range, 6-25 years]) who underwent combined transarterial embolization (using ethylene vinyl alcohol) and percutaneous sclerotherapy (using ethanol gel and polidocanol) for refractory and nonresectable ABCs. The median follow-up was 27.3 months (range, 6.7-47.5 months). Grade of mineralization (5-point Likert scale), grade of fluid-fluid levels (FFLs; 4-point Likert scale), and contrast-enhancing lesion volume were evaluated before and after treatment. The quality of life was determined before and after treatment using the Musculoskeletal Tumor Society (MSTS) score and the 36-Item Short Form Survey (SF-36) health questionnaire. RESULTS A mean of 1.6 ± 0.7 transarterial embolizations and 3.2 ± 1.7 percutaneous sclerotherapies were performed. No adverse events were observed. All patients showed either partial or complete response; no patient showed ABC recurrence. The grade of mineralization (3.7 ± 0.7 after therapy vs 1.4 ± 0.5 at baseline; P < .0001) and grade of FFL (3.5 ± 0.8 after therapy vs 1.9 ± 0.6 at baseline; P < .0001) significantly improved after therapy compared with baseline. The mean contrast-enhancing lesion volume significantly decreased after treatment compared with baseline (45.9 mm³ ± 96.1 vs 156.0 mm³ ± 115.3, respectively; P = .0003). The MSTS scores (28.8 ± 1.8 after treatment vs 14.1 ± 8.6 at baseline; P < .0001) and SF-36 findings revealed a significant improvement in the quality of life after treatment compared with baseline, leaving most patients without relevant constraints. CONCLUSIONS Combined transarterial embolization and percutaneous sclerotherapy is a minimally invasive, safe, and effective treatment option for refractory and nonresectable ABCs. Treatment fostered bone mineralization and significantly improved patients' quality of life.

About 40% of non‐small lung cancer (NSCLC) patients have metastatic disease at the time of diagnosis. However, metastatic NSCLC in the biliary duct system is extremely rare. A high proportion of patients with acute liver failure due to advanced NSCLC do not receive any treatment due to organ dysfunction or poor performance status. Here, we report a case of successful treatment with chemoimmunotherapy in a young woman with obstructive jaundice and acute hepatic failure due to multiple intrahepatic bile duct metastases. Key points Significant findings of the study Chemotherapy in NSCLC patients with liver failure is a therapeutic challenge. Acute hepatic failure are often exclusion criteria for therapy of NSCLC. Some reports showed a benefit of ICIs plus chemotherapy for NSCLC with liver metastases. What this study adds Combination of ICIs and chemotherapy is effective and safe in critically ill patients with lung cancer and impaired liver function., We report a case of successful treatment with chemimmunotherapy in a young woman with obstructive jaundice and acute hepatic failure due to multiple intrahepatic bile duct metastases of NSCLC.

Introduction Natural killer (NK) cells are key effectors in cancer immunosurveillance and posttransplant immunity, but shortage of environmental growth factors and deficient recognition of malignant cells may limit their anticancer efficacy. We hypothesized that the antibody-mediated anchoring of interleukin-2 (IL-2) to the leukemia-modified extracellular matrix (ECM) would increase NK cell abundance and activity to potentiate antibody-dependent cellular cytotoxicity (ADCC) against acute myeloid leukemia (AML) blasts. In this novel-novel combination dose-escalation phase 1 trial, we enrolled patients with AML relapse after allogeneic hematopoietic stem cell transplantation (HSCT) to evaluate the safety, pharmacokinetics, pharmacodynamics, and preliminary activity of F16IL2, an antibody-cytokine fusion protein composed of the human antibody fragment scFv(F16) in diabody format and two molecules of human IL-2, in combination with the Fc-optimized, ADCC-mediating anti-CD33 monoclonal antibody BI 836858. F16 specifically targets the A1 domain of the ECM protein tenascin C (TnC), which is spliced into the TnC molecule during active angiogenesis and tissue remodeling while it is virtually absent in normal tissues. Methods F16IL2 (10 - 20 Mio IU IV) was administered on days 1, 8, 15 and 22 of 28-day cycles, followed by administration of BI 836858 (10 - 40 mg IV) two days after each F16IL2 infusion. Dose escalation was performed over 4 dose levels (DL). Cohort 1 (10 Mio IU F16IL2 and 10 mg BI 836858, n = 5), cohort 2 (10 Mio IU F16IL2 and 20 mg BI 836858, n = 3), cohort 3 (20 Mio IU F16IL2 and 20 mg BI 836858, n = 4), cohort 4 (20 Mio IU F16IL2 and 40 mg BI 836858, n = 3). Safety and tolerability, pharmacodynamics and -kinetics, clinical efficacy and immune effector cell dynamics were investigated. This trial was registered at EudraCT as #2015-004763-37. Results Between December 2016 and March 2020, 15 patients with a median age of 50 years (range, 20 - 68) were enrolled and treated across 4 dose levels. Six patients (40%) had received two or more prior HSCT. The most frequent drug-related AEs (F16IL2 or BI 836858 or combination) were pyrexia (n = 13, 87%), chills (n = 12, 80%) and infusion-related reactions (n = 9, 60%), consistent with the expected toxicity profile of cytokine-armed or naked mAbs. These events were generally manageable, transient and of grade ≤ 2. One dose-limiting toxicity occurred at each of DL 3 (pulmonary edema) and 4 (acute GVHD). No patient died within the first 30 days of treatment initiation. Whereas no formal maximum tolerated dose (MTD) was reached, the maximum tested dose of 20 Mio IU F16IL2 and 40 mg BI 836858 was considered the recommended dose (RD). Three objective responses (1 CR, 1 CRi, 1 PR in extramedullary AML) were observed among 7 patients treated at the two higher DL, whereas no responses occurred at the two starting DL. Median OS among all 15 patients was 4.8 months (1.5 - 12.9), with a 6- and 12-month OS of 40% and 27%, respectively. Among those 7 patients whose AML was at least temporarily controlled with study treatment (CR/CRi, PR, SD), 12-month OS was 67% vs. 0% in non-responders. Combination therapy stimulated the expansion and activation of NK cells in bone marrow and peripheral blood. Conclusions To the best of our knowledge, this is the first study demonstrating that the strategy of potentiating ADCC with tumor-targeted immunocytokines is feasible in humans. In the difficult-to-treat situation of posttransplant AML relapse, responses were observed at higher DL, even in patients with extramedullary disease. The antibody-mediated targeted delivery of IL-2 to the ECM combined with anti-CD33 immunotherapy represents an innovative experimental approach associated with acceptable safety and encouraging biologic and clinical activity in posttransplant AML relapse. Disclosures Wermke: Novartis, Roche, Pfizer, BMS: Consultancy, Honoraria, Research Funding. Hemmerle: Philogen S.p.A.: Current Employment. Schäfers: Philogen S.p.A.: Research Funding. Rossig: BMS and Celgene: Honoraria; Pfizer: Honoraria; Novartis: Honoraria; AdBoards by Amgen: Honoraria. Stelljes: Pfizer: Consultancy, Research Funding, Speakers Bureau; Kite/Gilead: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; MSD: Consultancy, Speakers Bureau; Celgene/BMS: Consultancy, Speakers Bureau; Medac: Speakers Bureau; Amgen: Consultancy, Speakers Bureau. Rueter: Boehringer Ingelheim Pharma GmbH & Co. KG: Current Employment. Neri: Philogen S.p.A.: Current Employment, Current equity holder in publicly-traded company, Divested equity in a private or publicly-traded company in the past 24 months, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties: Multiple patents on vascular targeting; ETH Zurich: Patents & Royalties: CD117xCD3 TEA. Berdel: Philogen S.p.A.: Consultancy, Current equity holder in publicly-traded company, Honoraria, Membership on an entity's Board of Directors or advisory committees. Schliemann: Roche: Consultancy; Philogen S.p.A.: Consultancy, Honoraria, Research Funding; Astellas: Consultancy; Pfizer: Consultancy; BMS: Consultancy, Other: travel grants; Boehringer-Ingelheim: Research Funding; Novartis: Consultancy; Jazz Pharmaceuticals: Consultancy, Research Funding; AstraZeneca: Consultancy; Abbvie: Consultancy, Other: travel grants.

Objective Stand-alone minimally invasive approaches for the surgical management of spinal dumbbell tumors carry the risk of incomplete resections and impaired hemostasis. More-extensive approaches require subsequent instrumentation with metal artifacts impairing follow-up imaging. Here, we present a technical note on percutaneous instrumentation using carbon fiber–reinforced polyether ether ketone (CFR-PEEK) hardware combined with a minimally invasive posterolateral approach for tumor resection. Methods We present a Technical Note and according case series of 7 patients with dumbbell tumors in the lumbar and thoracolumbar spine operated on between 2017 and 2020. CFR-PEEK pedicle screws and rods were inserted percutaneously. Afterwards, a dedicated self-standing retractor for posterolateral approaches was connected to the screws. Following a unilateral facetectomy, the tumor was resected in a microsurgical fashion. Clinical data are reported with respect to the Preferred Reporting Of CasE Series in Surgery (PROCESS) guidelines. Results Four patients presented with de novo tumors. Three patients were treated for residual tumor mass after previous surgeries. Gross total resection was achieved in all 7 cases, as demonstrated by early postoperative magnetic resonance imaging. Histopathology demonstrated 5 World Health Organization grade I schwannomas, 1 grade II hemangiopericytoma, and 1 cavernous hemangioma. No postoperative complications were observed. CFR-PEEK hardware allowed unambiguous visualization of the resection cavity on follow-up imaging. Conclusions Resection of dumbbell tumors via a minimally invasive posterolateral approach and instrumentation with CFR-PEEK hardware allows maximal and safe resection. Due to lack of major metal artifacts, carbon fiber hardware improves the interpretation of follow-up imaging as well as planning of radiation if required for tumor recurrence.

Objective To evaluate the effectiveness of interventional therapy in acute, non-malignant, non-cirrhotic portal vein thrombosis. Methods We present a retrospective study of eight consecutive patients who presented with an acute non-malignant, non-cirrhotic portal vein thrombosis and were treated by mechanical recanalization using an escalating scheme including local aspiration, thrombolysis, rheolysis and the implantation of transjugular intrahepatic portosystemic shunt or other visceral stents. Results Recanalization rates applying the escalating scheme were good, with a success rate of 75%. However, major complications occurred in 50% of patients, mostly due to bleeding at the percutaneous access site, and minor complications in 12.5% of patients. Conclusion Interventional therapy is effective in acute portal vein thrombosis, but should only be performed at specialized centers and based on an individual treatment decision.

Iron oxide nanoparticles (ION) are highly sensitive probes for magnetic resonance imaging (MRI) that have previously been used for in vivo cell tracking and have enabled implementation of several diagnostic tools to detect and monitor disease. However, the in vivo MRI signal of ION can overlap with the signal from endogenous iron, resulting in a lack of detection specificity. Therefore, the long-term fate of administered ION remains largely unknown, and possible tissue deposition of iron cannot be assessed with established methods. Herein, we combine nonradioactive

Owing to improvements in our understanding of the biological principles of tumour initiation and progression, a wide variety of novel targeted therapies have been developed. Developments in biomedical imaging, however, have not kept pace with these improvements and are still mainly designed to determine lesion size alone, which is reflected in the Response Evaluation Criteria in Solid Tumors (RECIST). Imaging approaches currently used for the evaluation of treatment responses in patients with solid tumours, therefore, often fail to detect successful responses to novel targeted agents and might even falsely suggest disease progression, a scenario known as pseudoprogression. The ability to differentiate between responders and nonresponders early in the course of treatment is essential to allowing the early adjustment of treatment regimens. Various imaging approaches targeting a single dedicated tumour feature, as described in the hallmarks of cancer, have been successful in preclinical investigations, and some have been evaluated in pilot clinical trials. However, these approaches have largely not been implemented in clinical practice. In this Review, we describe current biomedical imaging approaches used to monitor responses to treatment in patients receiving novel targeted therapies, including a summary of the most promising future approaches and how these might improve clinical practice. The development of more-targeted cancer therapies has not been matched by more-targeted imaging methods. This discrepancy has, in some scenarios, resulted in inaccurate assessments of the effects of novel therapies. In this Review, the authors describe potential novel imaging approaches that could be adopted to enable improvements in imaging-based monitoring of treatment responses and resistance.

Multispectral optoacoustic tomography (MSOT) represents a new imaging approach revealing functional tissue information without extrinsic contrast agents. Using a clinical combined ultrasound (US)/MSOT device, we investigated the interindividual robustness and impact of intra- and interobserver variability of MSOT values in soft tissue (muscle and subcutaneous fat) of healthy volunteers. Semiquantitative MSOT values for deoxygenated (Hb), oxygenated (HbO2) and total hemoglobin (HbT), as well as oxygen saturation (sO2), were calculated for both forearms in transversal and longitudinal probe orientation (n = 3, 8 measurements per subject). For intraobserver reproducibility, the same examiner investigated three subjects twice. Mean values of left vs. right forearm and transversal vs. longitudinal probe orientation were compared using an unpaired Student’s t test. Bland Altmann plots with 95% limits of agreement for absolute averages and differences were calculated. Intraclass correlation coefficients (ICC 2,k) were computed for three different examiners. We obtained reproducible and consistent MSOT values with small-to-moderate deviation for muscle and subcutaneous fat tissue. Probe orientation and body side had no impact on calculated MSOT values (p > 0.05 each). Intraobserver reproducibility revealed equable mean values with small-to-moderate deviation. For muscular tissue, good ICC was obtained for sO2. Measurements of subcutaneous tissue revealed good-to-excellent ICCs for all calculated values. Thus, in this preliminary study on healthy individuals, clinical MSOT provided consistent and reproducible functional soft tissue characterization, independent on the investigating personnel.

Germ cell tumors (GCTs) are the most frequent malignancy in male patients between 15 and 45 years of age. Cisplatin-based chemotherapy shows excellent cure rates, but patients with cisplatin-resistant GCTs have a poor prognosis. Nintedanib (BIBF 1120, Vargatef) inhibits the receptor classes vascular endothelial growth factor receptor, platelet derived growth factor receptor, and fibroblast growth factor receptor, and has shown activity against many tumors, as well as in idiopathic lung fibrosis and bleomycin-induced lung injury. Here, we investigated the antineoplastic and antiangiogenic properties of nintedanib in cisplatin-resistant and cisplatin-sensitive GCT cells, both alone and in combination with classical cytotoxic agents such as cisplatin, etoposide, and bleomycin. The half-maximal inhibitory concentration (IC50) of nintedanib was 4.5 ± 0.43 μmol/l, 3.1 ± 0.45 μmol/l, and 3.6 ± 0.33 μmol/l in cisplatin-sensitive NTERA2, 2102Ep, and NCCIT cells, whereas the IC50 doses of the cisplatin-resistant counterparts were 6.6 ± 0.37 μmol/l (NTERA2-R), 4.5 ± 0.83 μmol/l (2102Ep-R), and 6.1 ± 0.41 μmol/l (NCCIT-R), respectively. Single treatment with nintedanib induced apoptosis and resulted in a sustained reduction in the capacity of colony formation in both cisplatin-sensitive and cisplatin-resistant GCT cells. Cell cycle analysis showed that nintedanib induced a strong G0/G1-phase arrest in all investigated cell lines. Combination treatment with cisplatin did not result in additive, synergistic, or antagonistic effects. The in-vivo activity was studied using the chorioallantoic membrane assay and indicated the antiangiogenic potency of nintedanib with markedly reduced microvessel density. Topical treatment of inoculated tumor plaques resulted in a significant reduction of the tumor size. This indicates that nintedanib might be a promising substance in the treatment of GCT.

Background: Aminopeptidase N (CD13) is present on tumor vasculature cells and some tumor cells. Truncated tissue factor (tTF) with a C-terminal NGR-peptide (tTF-NGR) binds to CD13 and causes tumor vascular thrombosis with infarction. Methods: We treated 17 patients with advanced cancer beyond standard therapies in a phase I study with tTF-NGR (1-h infusion, central venous access, 5 consecutive days, and rest periods of 2 weeks). The study allowed intraindividual dose escalations between cycles and established Maximum Tolerated Dose (MTD) and Dose-Limiting Toxicity (DLT) by verification cohorts. Results: MTD was 3 mg/m2 tTF-NGR/day &times, 5, q day 22. DLT was an isolated and reversible elevation of high sensitivity (hs) Troponin T hs without clinical sequelae. Three thromboembolic events (grade 2), tTF-NGR-related besides other relevant risk factors, were reversible upon anticoagulation. Imaging by contrast-enhanced ultrasound (CEUS) and dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) showed major tumor-specific reduction of blood flow in all measurable lesions as proof of principle for the mode of action of tTF-NGR. There were no responses as defined by Response Evaluation Criteria in Solid Tumors (RECIST), although some lesions showed intratumoral hemorrhage and necrosis after tTF-NGR application. Pharmacokinetic analysis showed a t1/2(terminal) of 8 to 9 h without accumulation in daily administrations. Conclusion: tTF-NGR is safely applicable with this regimen. Imaging showed selective reduction of tumor blood flow and intratumoral hemorrhage and necrosis.

As dental imaging accounts for approximately 40 % of all X-ray examinations in Germany, profound knowledge of this topic is essential not only for the dentist but also for the clinical radiologist. This review focuses on basic imaging findings regarding the teeth. Therefore, tooth structure, currently available imaging techniques and common findings in conserving dentistry including endodontology, periodontology, implantology and dental trauma are presented. Literature research on the current state of dental radiology was performed using Pubmed. Currently, the most frequent imaging techniques are the orthopantomogram (OPG) and single-tooth radiograph, as well as computer tomography (CT) and cone beam CT mainly for implantology (planning or postoperative control) or trauma indications. Especially early diagnosis and correct classification of a dental trauma, such as dental pulp involvement, prevents from treatment delays or worsening of therapy options and prognosis. Furthermore, teeth are commonly a hidden focus of infection.Since radiologists are frequently confronted with dental imaging, either concerning a particular question such as a trauma patient or regarding incidental findings throughout head and neck imaging, further training in this field is more than worthwhile to facilitate an early and sufficient dental treatment. · This review focuses on dental imaging techniques and the most important pathologies.. · Dental pathologies may not only be locally but also systemically relevant.. · Reporting of dental findings is important for best patient care..· Masthoff M, Gerwing M, Masthoff M et al. Dental Imaging - A basic guide for the radiologist. Fortschr Röntgenstr 2019; 191: 192 - 198. Da die dentale Bildgebung etwa 40 % aller Röntgenuntersuchungen in Deutschland ausmacht, sind fundierte Kenntnisse für den klinischen Radiologen auf diesem Gebiet essenziell. Der Fokus dieser Übersichtsarbeit liegt auf der Bildgebung des Zahnes. Hierfür werden Zahnaufbau, derzeit verfügbare Bildgebungstechniken und häufige Befunde der konservierenden Zahnheilkunde einschließlich der Endodontologie, Parodontologie und der Implantologie sowie nach dentalem Trauma vorgestellt. Es erfolgte eine Literaturrecherche zur dentalen Radiologie mittels Pubmed. Bildgebungstechniken erster Wahl sind weiterhin das Orthopantomogramm (OPG) sowie die Einzelzahnaufnahme. Ergänzend werden die Computertomografie (CT) und die digitale Volumentomografie (DVT), vorrangig für die Implantologie (Behandlungsplanung und Verlaufskontrolle) oder verunfallte Patienten, eingesetzt. Insbesondere beim dentalen Trauma vermeidet eine exakte Diagnostik und korrekte Klassifikation, beispielsweise bezüglich einer Beteiligung der Zahnpulpa, Therapieverzögerungen oder deren Prognoseverschlechterung. Zudem können Zähne einen häufigen Infekt-Fokus darstellen.Da Radiologen häufig mit der dentalen Bildgebung konfrontiert werden, sei es als dezidierte Fragestellung bei einem Trauma-Patienten oder bei Zufallsbefunden im Rahmen der Kopf-/ Halsbildgebung, ist eine „Blickschulung“ für häufige Befunde lohnenswert, um frühzeitig eine suffiziente zahnärztliche Behandlung zu bahnen. · Dieser Review behandelt die dentalen Bildgebungstechniken sowie die wichtigsten Zahnpathologien.. · Zahnpathologien können nicht nur lokal, sondern auch systemisch relevant sein.. · Dentale Befunde sollten für eine bestmögliche Patientenversorgung Teil der Befundung sein..· Masthoff M, Gerwing M, Masthoff M et al. Dental Imaging - A basic guide for the radiologist. Fortschr Röntgenstr 2019; 191: 192 – 198.

Cisplatin-based chemotherapy is highly effective in metastasized germ cell tumours (GCT). However, 10-30 % of patients develop resistance to cisplatin, requiring salvage therapy. We investigated the in vitro activity of paclitaxel and the novel taxane cabazitaxel in cisplatin-sensitive and -resistant GCT cell lines.In vitro activity of paclitaxel and cabazitaxel was determined by proliferation assays, and mode of action of cabazitaxel was assessed by western blotting and two screening approaches, i.e. whole proteome analysis and a human apoptosis array.Activity of paclitaxel and cabazitaxel was not affected by cisplatin resistance, suggesting that there is no cross-resistance between these agents in vitro. Cabazitaxel treatment showed a strong inhibitory effect on colony formation capacity. Cabazitaxel induced classical apoptosis in all cell lines, reflected by cleavage of PARP and caspase 3, without inducing specific changes in the cell cycle distribution. Using the proteomic and human apoptosis array screening approaches, differential regulation of several proteins, including members of the bcl-2 family, was found, giving first insights into the mode of action of cabazitaxel in GCT.Cabazitaxel shows promising in vitro activity in GCT cells, independent of levels of cisplatin resistance.