TY - CHAP A1 - Appenzeller, Arno A1 - Bartholomäus, Sebastian A1 - Breitschwerdt, Rüdiger A1 - Claussen, Carsten A1 - Geisler, Sandra A1 - Hartz, Tobias A1 - Kachel, Philipp A1 - Krempel, Erik A1 - Robert, Sebastian A1 - Ruth Zeissig, Sylke T1 - Towards Distributed Healthcare Systems – Virtual Data Pooling Between Cancer Registries as Backbone of Care and Research T2 - 2021 IEEE/ACS 18th International Conference on Computer Systems and Applications (AICCSA) N2 - German cancer registries offer a systematic approach for the collection, storage, and management of data on patients with cancer and related diseases. Much hope in research and healthcare in general is depending on such register-based analyses in order to comprehensively consider the features of a highly diverse population. Next to the data collection the cancer registries are responsible for data protection. To fulfill legal regulations, access to data has to be controlled in a strict way leading to sometimes bureaucratic and slow processes. The situation is especially complicated in Germany, since cancer data is distributed over numerous federal cancer registries. If a nationwide data evaluation is conducted a research team has to negotiate a separate contract with each cancer registry.In a joint work in progress effort of cancer registries, technical, medical, and economical experts we propose a different solution for cooperative data processing. Our approach aims for combining data in a virtual pool based on the selection criteria of individual requests from researchers. To achieve our goal, we adapt the Fraunhofer Medical Data Space as enabling technology. The architecture we propose will allow us to pool data of multiple partners regulated by data access policies. In doing so, each of the data sources can introduce its own rules and specifications on how data is used. Additionally, we add a digital consent management that will allow individual patients to decide how their data is used. Finally, we show the high potential of the cooperative analysis of distributed cancer data supported by the proposed solution in our approach. KW - Systematics KW - Space technology KW - Soft sensors KW - Sociology KW - Distributed databases KW - Process control KW - Medical services Y1 - 2021 UR - https://doi.org/10.1109/AICCSA53542.2021.9686918 SP - 1 EP - 8 ER - TY - CHAP A1 - Philipp, Patrick A1 - Becker, Silvia A1 - Robert, Sebastian A1 - Hempel, Dirk A1 - Beyerer, Jürgen T1 - Modeling of Medical Treatment Processes for an Interactive Assistance Based on the Translation of UML Activities into PROforma T2 - 2019 International Conference on Computational Science and Computational Intelligence (CSCI) N2 - In modern medicine, Clinical Practice Guidelines (CPGs) are well-established resources for the appropriate treatment of diseases. Evidence-based CPGs contain recommendations which are based on the state of the art and which have been achieved by consensus of several experts. Nevertheless, there is a potential for problems in translating guideline documents into specific actions for physicians. Therefore we propose to formalize the treatment process in an understandable representation as UML activities together with a domain expert. This formalization serves as a basis for the transfer of knowledge into a model, in this case PROforma, which directly allows execution in an interactive assistance software. The results of this work are part of an ongoing research project on the treatment of colon cancer based on the corresponding evidence-based CPG. KW - Clinical Practice Guidelines KW - Medical Treatment KW - Assistance Y1 - 2021 UR - https://doi.org/10.1109/CSCI49370.2019.00184 SP - 972 EP - 976 ER - TY - CHAP A1 - Philipp, Patrick A1 - Bommersheim, Marie A1 - Robert, Sebastian A1 - Beyerer, Jürgen T1 - Probabilistic Estimation of Human Interaction Needs in Context of a Robotic Assistance in Geriatrics T2 - Current Directions in Biomedical Engineering N2 - The key purpose of assistance robots is to help people coping with work-related or everyday tasks. To ensure an intuitive and effective support by an assistance robot, its expectation conform behavior is essential. In particular, when using assistance robots in geriatrics to assist elderly patients, special attention to the human-robot interaction should be paid. In order to help elderly patients maintain their independence and abilities as much as possible, the robot should only intervene when its support is needed. Therefore, the continuous estimation of the patient’s need for interaction is of particular importance. For enabling suitable models to estimate this need, we elaborate the use of Bayesian Networks. The analysis of our results seems promising, yielding a robust and practical approach. KW - Bayesian Networks KW - Virtual Evidence KW - Robotics KW - Gerontology KW - Social Robot KW - Assistance Technology Y1 - 2021 UR - https://doi.org/10.1515/cdbme-2019-0109 SP - 433 EP - 436 ER - TY - CHAP A1 - Mucha, Henrik A1 - Jacobi, Ricarda A1 - Robert, Sebastian T1 - Partizipation und Künstliche Intelligenz T2 - Mensch und Computer 2019 - Workshopband N2 - Der Einsatz künstlicher Intelligenz (KI) wird unsere Lebenswirklichkeit nachhaltig beeinflussen. Mittels technischer Verfahren maschinellen Lernens oder tiefer neuronaler Netze können Modelle aus existierenden Datenbeständen gelernt und Vorhersagen abgeleitet werden. Wir stellen skizzenartig zwei aktuelle Projekte vor, die sich u.a. mit den Potentialen und der menschzentrierten Gestaltung von Systemen künstlicher Intelligenz beschäftigen. Wir betten dies schlaglichtartig in den Kontext der aktuellen Debatte über die Entwicklung und Gestaltung von KI Systemen ein. Im Zuge dessen umreißen wir Herausforderungen und Chancen für die partizipative und sozialverantwortliche Technologieentwicklung von komplexen und auf Verfahren der künstlichen Intelligenz basierenden Systemen. Schließlich fokussieren wir dabei auf die Arbeitsebene und beschreiben kurz, welche konkreten Aktivitäten wir planen und stellen diese zur Diskussion. KW - Partizipation KW - Künstliche Intelligenz KW - Design Y1 - 2021 UR - https://doi.org/10.18420/muc2019-ws-413 SP - 19 EP - 21 ER - TY - JOUR A1 - Hempel, Louisa A1 - Veloso de Oliveira, Julia A1 - Gaumann, Andreas A1 - Milani, Valeria A1 - Schweneker, Katrin A1 - Schenck, Kristina A1 - Fleischmann, Bastian A1 - Philipp, Patrick A1 - Mederle, Stefanie A1 - Garg, Arun A1 - Piehler, Armin A1 - Gandorfer, Beate A1 - Schick, Cordula A1 - Kleespies, Axel A1 - Sellmann, Ludger A1 - Bartels, Marius A1 - Goetze, Thorsten O. A1 - Stein, Alexander A1 - Goekkurt, Eray A1 - Pfitzner, Lucia A1 - Robert, Sebastian A1 - Hempel, Dirk T1 - Landscape of Biomarkers and Actionable Gene Alterations in Adenocarcinoma of GEJ and Stomach - A Real World Data Analysis JF - Cancers N2 - After several years of negative phase III trials in gastric and esophageal cancer, a significant breakthrough in the treatment of metastatic adenocarcinomas of the gastroesophageal junction (GEJ) and stomach (GC) is now becoming evident with the emerging of precision oncology and implementation of molecular targets in tumor treatment. In addition, new generation studies such as umbrella and basket trials are focused on these molecular targets, which makes an early molecular diagnosis based on IHC/ISH and NGS necessary. The required companion diagnostics of Her2neu overamplification or PD-L1 expression is based on immunohistochemistry (IHC) or additionally in situ hybridization (ISH) in case of an IHC Her2neu score of 2+. However, there are investigator-dependent differences in the assessment of Her2neu amplification and different PD-L1 scoring systems obtained by IHC/ISH. The use of high-throughput technologies such as next-generation sequencing (NGS) holds the potential to standardize the analysis and thus make them more comparable. In the presented study, real-world multigene sequencing data of 72 Caucasian patients diagnosed with metastatic adenocarcinomas of GEJ and stomach were analyzed. In the clinical companion diagnostics, we found ESCAT level I molecular targets in one-third of our patients, which directly determined the therapy. In addition, we found potential targets in 14/72 patients (19.4%) who potentially qualify for precision therapies in corresponding molecular studies. The study highlights the importance of comprehensive molecular profiling for precision treatment of GEJ/GC and indicates that a biomarker evaluation should be performed for all patients with metastatic adenocarcinomas before the initiation of first-line treatment and during second-line or subsequent treatment. KW - GEJ KW - GC KW - next-generation sequencing KW - Her2neu KW - PD-L1 KW - personalized medicine KW - molecular target KW - checkpoint inhibitors KW - actionable gene variants Y1 - 2021 UR - https://doi.org/10.3390/cancers13174453 VL - 13 IS - 17 SP - 4453 ER - TY - JOUR A1 - Hempel, Louisa A1 - Molnar, Jakob A1 - Gaumann, Andreas A1 - Robert, Sebastian A1 - Scheiber, Josef A1 - Kleespies, Axel A1 - Riedmann, Kristina A1 - Schreiber, Susanne A1 - Gandorfer, Beate A1 - Piehler, Armin A1 - Hempel, Dirk T1 - Detection of acquired resistance mutation ALK G1202R after treatment with alectinib and response of lorlatinib BT - A case report JF - memo - Magazine of European Medical Oncology N2 - In the era of personalized medicine, the identification of driver mutations has paved the way towards targeted therapy. With the identification of anaplastic lymphoma kinase (ALK) as an oncogenic driver mutation, ALK rearrangements became druggable by tyrosine kinase inhibitors and, thus, have improved the prognosis for patients. Nevertheless, these approaches are limited by resistances occurring within the first or second year of administering ALK inhibitors. Among the different ALK resistant mutations, G1202R is the most common mutation, located in the kinase domain of the ALK protein resulting in resistance to treatment with the first- and second-generation kinase inhibitors (e.g., crizotinib, ceritinib, brigatenib and alectinib). Conflicting reports exist regarding the efficacy of lorlatinib, a next generation ALK inhibitor. The aim of this study is to access the potential impact of lorlatinib as a second-line treatment for a metastatic progressive NSCLC disease harboring genomic alteration of ALK G1202R, an AKLi-resistant mutation. The case of a patient with advanced lung cancer and the mentioned mutation is described. KW - NSCLC KW - Next-generation ALK inhibitor KW - Resistance mechanisms KW - Next-generation sequencing KW - Molecular diagnostics Y1 - 2021 UR - https://doi.org/10.1007/s12254-021-00724-2 ER - TY - CHAP A1 - Mucha, Henrik A1 - Robert, Sebastian A1 - Breitschwerdt, Ruediger A1 - Fellmann, Michael T1 - Interfaces for Explanations in Human-AI Interaction: Proposing a Design Evaluation Approach T2 - Extended Abstracts of the 2021 CHI Conference on Human Factors in Computing Systems. Association for Computing Machinery, New York, NY, USA N2 - Explanations in Human-AI Interaction are communicated to human decision makers through interfaces. Yet, it is not clear what consequences the exact representation of such explanations as part of decision support systems (DSS) and working on machine learning (ML) models has on human decision making. We observe a need for research methods that allow for measuring the effect different eXplainable AI (XAI) interface designs have on people’s decision making. In this paper, we argue for adopting research approaches from decision theory for HCI research on XAI interface design. We outline how we used estimation tasks in human-grounded design research in order to introduce a method and measurement for collecting evidence on XAI interface effects. To this end, we investigated representations of LIME explanations in an estimation task online study as proof-of-concept for our proposal. KW - Human-AI Interaction Y1 - 2021 UR - https://doi.org/10.1145/3411763.3451759 SP - 327 ER - TY - CHAP A1 - Mucha, Henrik A1 - Mevißen, Dennis A1 - Robert, Sebastian A1 - Jacobi, Ricarda A1 - Meyer, Kirsten A1 - Heusler, Winfried A1 - Arztmann, Daniel T1 - Co-Design Futures for AI and Space: A Workbook Sprint T2 - Extended Abstracts of the 2020 CHI Conference on Human Factors in Computing Systems (CHI EA '20). Association for Computing Machinery, New York, NY, USA N2 - Artificial Intelligence (AI) is continuously moving into our surroundings. In its various forms, it has the potential to disrupt most aspects of human life. Yet, the discourse around AI has long been by experts and for experts. In this paper, we argue for a participatory approach towards designing human-AI interactions. We outline how we used design methodology to organise an interdisciplinary workshop with a diverse group of students – a workbook sprint with 45 participants from four different programs and 13 countries – to develop speculative design futures in five focus areas. We then provide insights into our findings and share our lessons learned regarding our workshop topic – AI and Space – our process, and our research. We learned that involving non-experts in complex technical discourses – such as AI – through the structural rigour of design methodology is a viable approach. We then conclude by laying out how others might use our findings and initiate their own workbook sprint to explore complex technologies in a human-centred way. KW - Artificial Intelligence Y1 - 2021 UR - https://doi.org/10.1145/3334480.3375203 SP - 1 EP - 8 ER - TY - JOUR A1 - Hempel, Louisa A1 - Molnar, Jakob A1 - Robert, Sebastian A1 - Veloso, Julia A1 - Trepotec, Zeljka A1 - Englisch, Sofie A1 - Weinzierl, Philip A1 - Schick, Cordula A1 - Milani, Valeria A1 - Schweneker, Katrin A1 - Fleischmann, Bastian A1 - Scheiber, Josef A1 - Gandorfer, Beate A1 - Kleespies, Axel A1 - Hempel, Dirk A1 - Riedmann, Kristina A1 - Piehler, Armin T1 - Rare SARS-CoV-2 antibody development in cancer patients JF - Seminars in Oncology N2 - SARS-CoV-2 antibody development and immunity will be crucial for the further course of the pandemic. Until now, it has been assumed that patients who are infected with SARS-CoV-2 will develop antibodies as has been the case with other coronaviruses, like MERS-CoV and SARS-CoV. In the present study, we analyzed the development of antibodies in 77 patients with an oncologic diagnosis 26 days after positive RT-qPCR testing for SARS-CoV2. RT-qPCR and anti-SARS-CoV2-antibody methods from BGI (MGIEasy Magnetic Beads Virus DNA/RNA Extraction Kit) and Roche (Elecsys Anti-SARS-CoV-2 immunoassay) were used, respectively, according to the manufacturers’ specifications. Surprisingly, antibody development was detected in only 6 of 77 individuals with a confirmed history of COVID-19. Despite multiple testing, the remaining patients did not show measurable antibody concentrations in subsequent tests. These results undermine the previous hypothesis that SARS-CoV2 infections are regularly associated with antibody development and cast doubt on the provided immunity to COVID-19. Understanding the adaptive and humoral response to SARS-CoV2 will play a key role in vaccine development and gaining further knowledge on the pathogenesis. KW - SARS-CoV2 antibody development KW - COVID-19 KW - Cancer KW - Immunity Y1 - 2021 UR - https://doi.org/10.1053/j.seminoncol.2020.12.003 VL - 48 IS - 2 SP - 160 EP - 165 ER - TY - CHAP A1 - Mucha, Henrik A1 - Robert, Sebastian A1 - Breitschwerdt, Rüdiger A1 - Fellmann, Michael T1 - Towards Participatory Design Spaces for Explainable AI Interfaces in Expert Domains T2 - CEUR Workshop Proceedings XI-ML 2020 N2 - In this position paper, we lay out an approach to use participatory and co-design methodology to explore how users perceive and interact with explanations of artificially intelligent decision support systems. We describe how we intend to construct bottom-up participatory design spaces to systematically inform the design of interactive explanations in Human-AI interaction. KW - Explainable AI (XAI) KW - Participatory Design KW - Design Spaces Y1 - 2021 ER - TY - JOUR A1 - Hempel, Louisa A1 - Piehler, Armin A1 - Pfaffl, Michael W. A1 - Molnar, Jakob A1 - Kirchner, Benedikt A1 - Robert, Sebastian A1 - Veloso, Julia A1 - Gandorfer, Beate A1 - Trepotec, Zeljka A1 - Mederle, Stefanie A1 - Keim, Sabine A1 - Milani, Valeria A1 - Ebner, Florian A1 - Schweneker, Katrin A1 - Fleischmann, Bastian A1 - Kleespies, Axel A1 - Scheiber, Josef A1 - Hempel, Dirk A1 - Zehn, Dietmar T1 - SARS-CoV-2 infections in cancer outpatients—Most infected patients are asymptomatic carriers without impact on chemotherapy JF - Cancer Medicine N2 - Oncologic patients are regarded as the population most at risk of developing a severe course of COVID-19 due to the fact that malignant diseases and chemotherapy often weaken the immune system. In the face of the ongoing SARS-CoV-2 pandemic, how particular patients deal with this infection remains an important question. In the period between the 15 and 26 April 2020, a total of 1227 patients were tested in one of seven oncologic outpatient clinics for SARS-CoV-2, regardless of symptoms, employing RT-qPCR. Of 1227 patients, 78 (6.4%) were tested positive of SARS-CoV-2. Only one of the patients who tested positive developed a severe form of COVID-19 with pneumonia (CURB-65 score of 2), and two patients showed mild symptoms. Fourteen of 75 asymptomatic but positively tested patients received chemotherapy or chemo-immunotherapy according to their regular therapy algorithm (±4 weeks of SARS-CoV-2 test), and 48 of 78 (61.5%) positive-tested patients received glucocorticoids as co-medication. None of the asymptomatic infected patients showed unexpected complications due to the SARS-CoV-2 infection during the cancer treatment. These data clearly contrast the view that patients with an oncologic disease are particularly vulnerable to SARS-CoV-2 and suggest that compromising therapies could be continued or started despite the ongoing pandemic. Moreover the relatively low appearance of symptoms due to COVID-19 among patients on chemotherapy and other immunosuppressive co-medication like glucocorticoids indicate that suppressing the response capacity of the immune system reduces disease severity. KW - COVID-19 Y1 - 2021 UR - https://doi.org/10.1002/cam4.3435 VL - 9 IS - 21 SP - 8020 EP - 8028 ER - TY - JOUR A1 - Burkart, Nadia A1 - Robert, Sebastian A1 - Huber, Marco F. T1 - Are you sure? Prediction revision in automated decision-making JF - Expert Systems N2 - With the rapid improvements in machine learning and deep learning, decisions made by automated decision support systems (DSS) will increase. Besides the accuracy of predictions, their explainability becomes more important. The algorithms can construct complex mathematical prediction models. This causes insecurity to the predictions. The insecurity rises the need for equipping the algorithms with explanations. To examine how users trust automated DSS, an experiment was conducted. Our research aim is to examine how participants supported by an DSS revise their initial prediction by four varying approaches (treatments) in a between-subject design study. The four treatments differ in the degree of explainability to understand the predictions of the system. First we used an interpretable regression model, second a Random Forest (considered to be a black box [BB]), third the BB with a local explanation and last the BB with a global explanation. We noticed that all participants improved their predictions after receiving an advice whether it was a complete BB or an BB with an explanation. The major finding was that interpretable models were not incorporated more in the decision process than BB models or BB models with explanations. KW - experiment KW - explainable ML KW - interpretability KW - prediction revision Y1 - 2021 UR - https://doi.org/10.1111/exsy.12577 VL - 38 IS - 1 SP - e12577 ER - TY - CHAP A1 - Mucha, Henrik A1 - Robert, Sebastian T1 - Emerging Perspectives on Medical Decision Support: Co-Designing XAI T2 - Fair & Responsible AI Workshop, Conference on Human Factors in Computing Systems (CHI), 2020, Honolulu, Hawaii N2 - Artificial Intelligence (AI) and Machine Learning (ML) promise to significantly enhance the capabilities of decision support systems in medicine. Yet, if these systems fail to providean understandable rationale of the decision making process the adoption of this powerful technology will be difficult. Hence, there is growing interest in Explainable Artificial Intelligence (XAI). Explanations that speak the language of the user are a cornerstone for Fair AI. In this position paper, we reflect on research about XAI and designing decision support in medicine. From there, we lay out an approach to use co-design methodology to explore how users perceive and interact with explanations of decision support systems. KW - XAI KW - Medical Decision Support KW - Co-Design Y1 - 2021 ER - TY - CHAP A1 - Philipp, Patrick A1 - Morales Georgi, Rafael X. A1 - Beyerer, Jürgen A1 - Robert, Sebastian A1 - Beyerer, Jürgen T1 - Analysis of Control Flow Graphs Using Graph Convolutional Neural Networks T2 - 2019 6th International Conference on Soft Computing & Machine Intelligence (ISCMI) N2 - With the digital transformation of companies, ever larger amounts of data are generated and available for analysis. Process mining techniques can be used to extract and analyze process models from these data. Related techniques have quickly developed into an important field with constantly increasing investments in recent years. Thus, the automated analysis of processes has gained an important role in many companies. In this context, graphs have been shown to be an intuitive representation of how the gathered processes are carried out using the aforementioned techniques. For the analysis of these so-called control flow graphs, we investigate the use of convolution neural networks, which are specially designed for graphs: graph convolution networks (GCNs). In our contribution, GCNs are used to perform a regression task based on individual control flows of a process in which farmers apply for specific governmental payments. The approach achieved promising results on this publicly available data set. KW - workflow KW - process analysis KW - process mining KW - convolutional neural networks KW - digital transformation KW - control flow Y1 - 2021 UR - https://doi.org/10.1109/ISCMI47871.2019.9004296 SP - 73 EP - 77 ER - TY - JOUR A1 - Hempel, Louisa A1 - Piehler, Armin A1 - Gandorfer, Beate A1 - De Oliveira, Julia Veloso A1 - Philipp, Patrick A1 - Robert, Sebastian A1 - Axel, Kleespies A1 - Schick, Cordula A1 - Fleischmann, Bastian A1 - Schweneker, Katrin A1 - Milani, Valeria A1 - Schenk, Kristina A1 - Ebner, Florian A1 - Donhauser, Lara A1 - Zehn, Dietmar A1 - Hempel, Dirk T1 - Clinical impact of SARS-CoV-2 delta variant infection in tumor patients and the impact of vaccination on different cancer treatment regimens. JF - Journal of Clinical Oncology N2 - Background: Data on SARS-CoV-2 infections in oncological patients in the outpatient settings are scarce. Methods: During the spread of the delta variant between April 2021 and September 2021, a total of 10.677 patients were tested for SARS-CoV-2 infection by RT-qPCR in seven outpatient clinics in Bavaria, Germany. Results: Within the tested patient cohort, 4.960 patients (46.5%) suffered from a malignant disease (74% solid tumors and 26% malignant hematological diseases). This group was compared with 5.717 patients (53.5%) without a malignant disease (33.1% with other hematological diseases and 66.9% patients without a hematological or oncological disease). During the observation period, 119 (2.4%) patients with malignancies were tested positive (88 patients with solid tumors; 31 patients with malignant hematological diseases) compared to 115 positive patients (2.0%) in the control group. 32 of 119 positively tested patients (26.9%) suffering from malignant disease required hospitalization and 9/32 patients (28.1%) died during the clinical course. Conclusions: These observations are in clear contrast to data from patients we evaluated during the pre-delta variants period between 15 and 26 April 2020 in the same seven outpatient clinics. In this period, a total of 1.227 patients were tested for SARS-CoV-2 by RT-qPCR. 78/1227 patients (6.3%) were tested positive in RT-qPCR and most showed mild symptoms of infection. None of the SARS-CoV-2 infected patients died. These data were analyzed when no vaccination was available. These data were evaluated during a period where no vaccine was available. Vaccination of patients with malignancies with BiontechPfizer's mRNA vaccines was started in April 2021. The response to the vaccine was tested by an antibody assay (Elecsys Anti-SARS-CoV-2 S-immunoassay, Roche) at the earliest four weeks after the second vaccination. To assess the response, we compared five patient cohorts: Patients who received (i) B cell depleting antibodies, (ii) checkpoint inhibitors (ICI), (iii) chemotherapy, or (iv) tyrosin kinase inhibitors (TKIs), and (v) healthy controls. The patients treated with ICI or TKI showed a comparable vaccination response to the healthy patients, while patients receiving Rituximab/Obinutuzumab showed no significant humoral vaccination response at all. The more severe disease course of patients infected by the SARS-CoV-2 delta variant compared to the initial waves of infections strongly underline the importance of vaccination in cancer patients. Y1 - 2022 U6 - https://doi.org/10.1200/JCO.2022.40.16_suppl.e18750 VL - 40 IS - 16_suppl SP - E18750 EP - E18750 ER - TY - JOUR A1 - Hempel, L.C. A1 - Lapa, C. A1 - Gaumann, A. A1 - Veloso de Oliveira, J. A1 - Scheiber, J. A1 - Philipp, P. A1 - Oyarzun, C. A1 - Wesarg, S. A1 - Robert, Sebastian A1 - Hempel, D. T1 - 36P A point mutation replacing cysteine with arginine at position 382 (C382R) in the transmembrane domain of FGFR2 leads to response to FGF2-inhibitor pemigatinib in chemo-refractory intrahepatic cholangiocarcinoma JF - Annals of Oncology N2 - Background To date, targeted tyrosine kinase inhibitors have been approved for FGFR2 and FGFR3 fusions (pemigatinib and erdafitinib, respectively), but the importance of FGFR2 mutations for transformation activity and as a druggable gene variant with response to different FGFR inhibitors is poorly understood. FGFR2 inhibitors present a mainstay of treatment for locally advanced or metastatic intrahepatic cholangiocellular carcinoma (iCCA). Methods A 74-year-old male was diagnosed with iCCA in liver segments seven and eight with infiltration of the hepatic veins and inferior vena cava revealed a C382R mutation of the intramembrane domain of FGRR2 receptor. We performed an in-silico study to understand the potential mode-of-action of the mutant FGFR2 targets. Based on experimentally determined structures we then used a structure generated by AlphaFold2 as the variation in question is located at a position not determined well in the experiments. This revealed that the C382R mutation is located in the trans-membranal domain at a position crucial for signal transduction, both for activation and inhibition of downstream-signaling. The Molecular Tumor Board decided to start the treatment with 13.5 mg pemigatinib once daily for 14 days, followed by 7 days of free therapy interval resulting in a sustained partial response. The patient continues to be treated of 13.5 mg as described above. Results In our case report, we were able to show that the patient in whom an C382R mutation was detected responded to the therapy with pemigatinib. This shows that real-world scenarios differ from the data of the approval studies, thereby illustrating how complex data on patients with FGFR mutations is. One of the main problems of large approval studies is that the functionality of the respective alterations is often disregarded. Conclusions Our results suggest that respective mutation may be successfully targeted by FGFR-selective tyrosine-kinase inhibitors, demonstrating the importance of the functional characterization of mutations. no conflicts of interest. Y1 - 2022 U6 - https://doi.org/https://doi.org/10.1016/j.annonc.2022.01.045 VL - 33 SP - S17 EP - S17 ER - TY - JOUR A1 - Hempel, Louisa A1 - Lapa, Constantin A1 - Dierks, Alexander A1 - Gaumann, Andreas A1 - Scheiber, Josef A1 - Veloso de Oliveira, Julia A1 - Philipp, Patrick A1 - Oyarzun Laura, Cristina A1 - Wesarg, Stefan A1 - Robert, Sebastian A1 - Hempel, Dirk T1 - A new promising oncogenic target (p.C382R) for treatment with pemigatinib in patients with cholangiocarcinoma JF - Therapeutic Advances in Medical Oncology N2 - Point mutations of the fibroblast growth factor receptor (FGFR)2 receptor in intrahepatic cholangiocarcinoma (iCC) are mainly of unknown functional significance compared to FGFR2 fusions. Pemigatinib, a tyrosine kinase inhibitor, is approved for the treatment of cholangiocarcinoma with FGFR2 fusion/rearrangement. Although it is hypothesized that FGFR2 mutations may cause uncontrolled activation of the signaling pathway, the data for targeted therapies for FGFR2 mutations remain unclear. In vitro analyses demonstrated the importance of the p.C382R mutation for ligand-independent constitutive activation of FGFR2 with transforming potential. The following report describes the clinical case of a patient diagnosed with an iCC carrying a FGFR2 p.C382R point mutation which was detected in liquid, as well as in tissue-based biopsies. The patient was treated with pemigatinib, resulting in a sustained complete functional remission in fluorodeoxyglucose-positron emission tomography/computed tomography over 10 months to date. The reported case is the first description of a complete functional remission under the treatment with pemigatinib in a patient with p.C383R mutation. Y1 - 2022 U6 - https://doi.org/10.1177/17588359221125096 VL - 14 ER - TY - JOUR A1 - Mucha, Henrik A1 - Robert, Sebastian A1 - Breitschwerdt, Rüdiger A1 - Fellmann, Michael T1 - Usability of clinical decision support systems JF - Zeitschrift für Arbeitswissenschaft N2 - Usability is considered a major success factor for current and future decision support systems. Such systems are increasingly used to assist human decision-makers in high-stakes tasks in complex domains such as health care, jurisdiction or finance. Yet, many if not most expert systems—especially in health care—fail to deliver the degree of quality in terms of usability that its expert users are used to from their personal digital consumer products. In this article, we focus on clinical decision support systems (CDSS) as an example for how important a human-centered design approach is when designing complex software in complex contexts. We provide an overview of CDSS classes, discuss the importance of systematically exploring mental models of users, and formulate challenges and opportunities of future design work on CDSS. We further provide a case study from a current research project to illustrate how we used codesign as a practical approach to produce usable software in a real-world context. Practical Relevance: We make a point for usability to be considered a major success factor and non-negotiable characteristic of expert software. With software evolving into virtual coworkers in terms of supporting human decision-making in complex, high-risk domains, the necessity of and demand for systems that are unambiguously understandable and interpretable for their expert users have never been higher. We show that this is a real-world problem with high practical relevance by describing our work in the domain of clinical decision support systems (CDSS) as an example. We introduce the topic and a classification of CDSS. Thus, we highlight a conceptual framework of how to approach complex domains from a technology designer’s point of view. We continue by explaining why usability must be regarded as a major goal in software development. We derive challenges and opportunities that may well be transferred to other domains. Finally, be including a real-world example from our own professional work we propose a practical approach towards taking the challenges and exploiting the associated opportunities. N2 - Die Benutzerfreundlichkeit gilt als ein wichtiger Erfolgsfaktor für aktuelle und zukünftige Entscheidungsunterstützungssysteme. Solche Systeme werden zunehmend eingesetzt, um menschliche Entscheidungsträger bei anspruchsvollen Aufgaben in komplexen Bereichen wie dem Gesundheitswesen, der Rechtsprechung oder dem Finanzwesen zu unterstützen. Viele, wenn nicht sogar die meisten Expertensysteme – insbesondere im Gesundheitswesen – bieten jedoch nicht die Qualität in Bezug auf die Benutzerfreundlichkeit, die die Experten von ihren persönlichen digitalen Konsumgütern gewohnt sind. In diesem Artikel konzentrieren wir uns auf klinische Entscheidungsunterstützungssysteme (CDSS) als Beispiel dafür, wie wichtig ein menschenzentrierter Designansatz bei der Entwicklung komplexer Software in komplexen Kontexten ist. Wir geben einen Überblick über CDSS-Klassen, erörtern die Bedeutung der systematischen Erforschung mentaler Modelle von Nutzern und formulieren Herausforderungen und Chancen für die zukünftige Designarbeit an CDSS. Darüber hinaus stellen wir eine Fallstudie aus einem aktuellen Forschungsprojekt vor, um zu veranschaulichen, wie wir Codesign als praktischen Ansatz eingesetzt haben, um brauchbare Software in einem realen Kontext zu entwickeln. Praktische Relevanz: Wir setzen uns dafür ein, dass die Benutzerfreundlichkeit als ein wichtiger Erfolgsfaktor und nicht verhandelbares Merkmal von Expertensoftware angesehen wird. Mit der Entwicklung von Software zu virtuellen Mitarbeitern, die den Menschen bei der Entscheidungsfindung in komplexen, risikoreichen Bereichen unterstützen, sind die Notwendigkeit und die Nachfrage nach Systemen, die für ihre Expertenanwender eindeutig verständlich und interpretierbar sind, so hoch wie nie zuvor. Wir zeigen, dass dies ein reales Problem mit hoher praktischer Relevanz ist, indem wir unsere Arbeit im Bereich der klinischen Entscheidungsunterstützungssysteme (CDSS) als Beispiel beschreiben. Wir stellen das Thema und eine Klassifizierung von CDSS vor. So zeigen wir einen konzeptionellen Rahmen auf, wie man sich komplexen Domänen aus der Sicht eines Technologieentwicklers nähert. Wir fahren fort, indem wir erklären, warum die Benutzerfreundlichkeit als ein Hauptziel bei der Softwareentwicklung angesehen werden muss. Daraus leiten wir Herausforderungen und Möglichkeiten ab, die sich durchaus auf andere Bereiche übertragen lassen. Schließlich schlagen wir anhand eines praktischen Beispiels aus unserer eigenen beruflichen Tätigkeit einen praktischen Ansatz vor, um die Herausforderungen anzunehmen und die damit verbundenen Chancen zu nutzen. KW - Usability KW - Human-centered Design KW - Participatory Design KW - Software Engineering in Expert Domains KW - (Clinical) Decision Support Systems Y1 - 2022 U6 - https://doi.org/10.1007/s41449-022-00324-8 ER - TY - CHAP A1 - Robert, Sebastian A1 - Mucha, H. A1 - Hempel, D. ED - Glocke, P. ED - Elsner, C. ED - Schneider, H. T1 - Clinical Decision Support Systems T2 - Toolbook Digitale Transformation Krankenhaus KW - Clinical Decision Support Systems Y1 - 2022 PB - MWV Medizinisch Wissenschaftlicher Verlagsgesellschaft CY - Berlin ER - TY - JOUR A1 - Victoria Donhauser, Lara A1 - Veloso de Oliveira, Julia A1 - Schick, Cordula A1 - Manlik, Wenzel A1 - Styblova, Sabrina A1 - Lutzenberger, Sarah A1 - Aigner, Michael A1 - Philipp, Patrick A1 - Robert, Sebastian A1 - Gandorfer, Beate A1 - Hempel, Dirk A1 - Hempel, Louisa A1 - Zehn, Dietmar T1 - Responses of patients with cancer to mRNA vaccines depend on the time interval between vaccination and last treatment JF - Journal for ImmunoTherapy of Cancer N2 - Background Personalized mRNA vaccines are promising new therapeutic options for patients with cancer. Because mRNA vaccines are not yet approved for first-line therapy, the vaccines are presently applied to individuals that received prior therapies that can have immunocompromising effects. There is a need to address how prior treatments impact mRNA vaccine outcomes. Method Therefore, we analyzed the response to BioNTech/Pfizer’s anti-SARS-CoV-2 mRNA vaccine in 237 oncology outpatients, which cover a broad spectrum of hematologic malignancies and solid tumors and a variety of treatments. Patients were stratified by the time interval between the last treatment and first vaccination and by the presence or absence of florid tumors and IgG titers and T cell responses were analyzed 14 days after the second vaccination. Results Regardless of the last treatment time point, our data indicate that vaccination responses in patients with checkpoint inhibition were comparable to healthy controls. In contrast, patients after chemotherapy or cortisone therapy did not develop an immune response until 6 months after the last systemic therapy and patients after Cht-immune checkpoint inhibitor and tyrosine kinase inhibitor therapy only after 12 months. Conclusion Accordingly, our data support that timing of mRNA-based therapy is critical and we suggest that at least a 6-months or 12-months waiting interval should be observed before mRNA vaccination in systemically treated patients. Y1 - 2023 U6 - https://doi.org/10.1136/jitc-2023-007387 VL - 11 IS - 9 ER - TY - CHAP A1 - Kiesel, Theresia A1 - Breitwieser, Anita A1 - Brettner, Stephanie A1 - Schmidle, Stephanie A1 - Bursch, Theresa A1 - Freise, Laura A1 - Schneider, Elena A1 - Kölzer, Brigitte A1 - Hammerschmidt, Thomas A1 - Robert, Sebastian A1 - Ittlinger, Sabine A1 - Bauer, Petra T1 - HERO – HEalth University @ TH ROsenheim Förderkonzept zur Gewinnung und Entwicklung von wissenschaftlichem, insbesondere professoralem Personal T2 - Tag der Forschung TH Rosenheim KW - Personalentwicklung KW - professorales Personal KW - FH Personal KW - Förderkonzept Y1 - 2023 ER -