@inproceedings{AppenzellerBartholomaeusBreitschwerdtetal.2021, author = {Appenzeller, Arno and Bartholom{\"a}us, Sebastian and Breitschwerdt, R{\"u}diger and Claussen, Carsten and Geisler, Sandra and Hartz, Tobias and Kachel, Philipp and Krempel, Erik and Robert, Sebastian and Ruth Zeissig, Sylke}, title = {Towards Distributed Healthcare Systems - Virtual Data Pooling Between Cancer Registries as Backbone of Care and Research}, series = {2021 IEEE/ACS 18th International Conference on Computer Systems and Applications (AICCSA)}, booktitle = {2021 IEEE/ACS 18th International Conference on Computer Systems and Applications (AICCSA)}, pages = {1 -- 8}, year = {2021}, abstract = {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.}, language = {en} } @inproceedings{PhilippBeckerRobertetal.2019, author = {Philipp, Patrick and Becker, Silvia and Robert, Sebastian and Hempel, Dirk and Beyerer, J{\"u}rgen}, title = {Modeling of Medical Treatment Processes for an Interactive Assistance Based on the Translation of UML Activities into PROforma}, series = {2019 International Conference on Computational Science and Computational Intelligence (CSCI)}, booktitle = {2019 International Conference on Computational Science and Computational Intelligence (CSCI)}, pages = {972 -- 976}, year = {2019}, abstract = {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.}, language = {en} } @inproceedings{PhilippBommersheimRobertetal.2019, author = {Philipp, Patrick and Bommersheim, Marie and Robert, Sebastian and Beyerer, J{\"u}rgen}, title = {Probabilistic Estimation of Human Interaction Needs in Context of a Robotic Assistance in Geriatrics}, series = {Current Directions in Biomedical Engineering}, booktitle = {Current Directions in Biomedical Engineering}, organization = {Proceedings of the 2019 Annual Meeting of the German Society of Biomedical Engineering}, pages = {433 -- 436}, year = {2019}, abstract = {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.}, language = {en} } @inproceedings{MuchaJacobiRobert2019, author = {Mucha, Henrik and Jacobi, Ricarda and Robert, Sebastian}, title = {Partizipation und K{\"u}nstliche Intelligenz}, series = {Mensch und Computer 2019 - Workshopband}, booktitle = {Mensch und Computer 2019 - Workshopband}, organization = {Gesellschaft f{\"u}r Informatik e.V.}, pages = {19 -- 21}, year = {2019}, abstract = {Der Einsatz k{\"u}nstlicher Intelligenz (KI) wird unsere Lebenswirklichkeit nachhaltig beeinflussen. Mittels technischer Verfahren maschinellen Lernens oder tiefer neuronaler Netze k{\"o}nnen Modelle aus existierenden Datenbest{\"a}nden 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 k{\"u}nstlicher Intelligenz besch{\"a}ftigen. Wir betten dies schlaglichtartig in den Kontext der aktuellen Debatte {\"u}ber die Entwicklung und Gestaltung von KI Systemen ein. Im Zuge dessen umreißen wir Herausforderungen und Chancen f{\"u}r die partizipative und sozialverantwortliche Technologieentwicklung von komplexen und auf Verfahren der k{\"u}nstlichen Intelligenz basierenden Systemen. Schließlich fokussieren wir dabei auf die Arbeitsebene und beschreiben kurz, welche konkreten Aktivit{\"a}ten wir planen und stellen diese zur Diskussion.}, language = {de} } @article{HempelVelosodeOliveiraGaumannetal.2021, author = {Hempel, Louisa and Veloso de Oliveira, Julia and Gaumann, Andreas and Milani, Valeria and Schweneker, Katrin and Schenck, Kristina and Fleischmann, Bastian and Philipp, Patrick and Mederle, Stefanie and Garg, Arun and Piehler, Armin and Gandorfer, Beate and Schick, Cordula and Kleespies, Axel and Sellmann, Ludger and Bartels, Marius and Goetze, Thorsten O. and Stein, Alexander and Goekkurt, Eray and Pfitzner, Lucia and Robert, Sebastian and Hempel, Dirk}, title = {Landscape of Biomarkers and Actionable Gene Alterations in Adenocarcinoma of GEJ and Stomach - A Real World Data Analysis}, series = {Cancers}, volume = {13}, journal = {Cancers}, number = {17}, pages = {4453}, year = {2021}, abstract = {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.}, language = {en} } @article{HempelMolnarGaumannetal.2021, author = {Hempel, Louisa and Molnar, Jakob and Gaumann, Andreas and Robert, Sebastian and Scheiber, Josef and Kleespies, Axel and Riedmann, Kristina and Schreiber, Susanne and Gandorfer, Beate and Piehler, Armin and Hempel, Dirk}, title = {Detection of acquired resistance mutation ALK G1202R after treatment with alectinib and response of lorlatinib}, series = {memo - Magazine of European Medical Oncology}, journal = {memo - Magazine of European Medical Oncology}, year = {2021}, abstract = {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.}, language = {en} } @inproceedings{MuchaRobertBreitschwerdtetal.2021, author = {Mucha, Henrik and Robert, Sebastian and Breitschwerdt, Ruediger and Fellmann, Michael}, title = {Interfaces for Explanations in Human-AI Interaction: Proposing a Design Evaluation Approach}, series = {Extended Abstracts of the 2021 CHI Conference on Human Factors in Computing Systems. Association for Computing Machinery, New York, NY, USA}, booktitle = {Extended Abstracts of the 2021 CHI Conference on Human Factors in Computing Systems. Association for Computing Machinery, New York, NY, USA}, pages = {327}, year = {2021}, abstract = {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.}, language = {en} } @inproceedings{MuchaMevissenRobertetal.2020, author = {Mucha, Henrik and Mevißen, Dennis and Robert, Sebastian and Jacobi, Ricarda and Meyer, Kirsten and Heusler, Winfried and Arztmann, Daniel}, title = {Co-Design Futures for AI and Space: A Workbook Sprint}, series = {Extended Abstracts of the 2020 CHI Conference on Human Factors in Computing Systems (CHI EA '20). Association for Computing Machinery, New York, NY, USA}, booktitle = {Extended Abstracts of the 2020 CHI Conference on Human Factors in Computing Systems (CHI EA '20). Association for Computing Machinery, New York, NY, USA}, pages = {1 -- 8}, year = {2020}, abstract = {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.}, language = {en} } @article{HempelMolnarRobertetal.2021, author = {Hempel, Louisa and Molnar, Jakob and Robert, Sebastian and Veloso, Julia and Trepotec, Zeljka and Englisch, Sofie and Weinzierl, Philip and Schick, Cordula and Milani, Valeria and Schweneker, Katrin and Fleischmann, Bastian and Scheiber, Josef and Gandorfer, Beate and Kleespies, Axel and Hempel, Dirk and Riedmann, Kristina and Piehler, Armin}, title = {Rare SARS-CoV-2 antibody development in cancer patients}, series = {Seminars in Oncology}, volume = {48}, journal = {Seminars in Oncology}, number = {2}, pages = {160 -- 165}, year = {2021}, abstract = {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.}, language = {en} } @inproceedings{MuchaRobertBreitschwerdtetal.2020, author = {Mucha, Henrik and Robert, Sebastian and Breitschwerdt, R{\"u}diger and Fellmann, Michael}, title = {Towards Participatory Design Spaces for Explainable AI Interfaces in Expert Domains}, series = {CEUR Workshop Proceedings XI-ML 2020}, booktitle = {CEUR Workshop Proceedings XI-ML 2020}, year = {2020}, abstract = {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.}, language = {en} } @article{HempelPiehlerPfaffletal.2020, author = {Hempel, Louisa and Piehler, Armin and Pfaffl, Michael W. and Molnar, Jakob and Kirchner, Benedikt and Robert, Sebastian and Veloso, Julia and Gandorfer, Beate and Trepotec, Zeljka and Mederle, Stefanie and Keim, Sabine and Milani, Valeria and Ebner, Florian and Schweneker, Katrin and Fleischmann, Bastian and Kleespies, Axel and Scheiber, Josef and Hempel, Dirk and Zehn, Dietmar}, title = {SARS-CoV-2 infections in cancer outpatients—Most infected patients are asymptomatic carriers without impact on chemotherapy}, series = {Cancer Medicine}, volume = {9}, journal = {Cancer Medicine}, number = {21}, pages = {8020 -- 8028}, year = {2020}, abstract = {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.}, language = {en} } @article{BurkartRobertHuber2021, author = {Burkart, Nadia and Robert, Sebastian and Huber, Marco F.}, title = {Are you sure? Prediction revision in automated decision-making}, series = {Expert Systems}, volume = {38}, journal = {Expert Systems}, number = {1}, pages = {e12577}, year = {2021}, abstract = {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.}, language = {en} } @inproceedings{MuchaRobert2020, author = {Mucha, Henrik and Robert, Sebastian}, title = {Emerging Perspectives on Medical Decision Support: Co-Designing XAI}, series = {Fair \& Responsible AI Workshop, Conference on Human Factors in Computing Systems (CHI), 2020, Honolulu, Hawaii}, booktitle = {Fair \& Responsible AI Workshop, Conference on Human Factors in Computing Systems (CHI), 2020, Honolulu, Hawaii}, year = {2020}, abstract = {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.}, language = {en} } @inproceedings{PhilippMoralesGeorgiBeyereretal.2019, author = {Philipp, Patrick and Morales Georgi, Rafael X. and Beyerer, J{\"u}rgen and Robert, Sebastian and Beyerer, J{\"u}rgen}, title = {Analysis of Control Flow Graphs Using Graph Convolutional Neural Networks}, series = {2019 6th International Conference on Soft Computing \& Machine Intelligence (ISCMI)}, booktitle = {2019 6th International Conference on Soft Computing \& Machine Intelligence (ISCMI)}, pages = {73 -- 77}, year = {2019}, abstract = {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.}, language = {en} } @article{HempelPiehlerGandorferetal.2022, author = {Hempel, Louisa and Piehler, Armin and Gandorfer, Beate and De Oliveira, Julia Veloso and Philipp, Patrick and Robert, Sebastian and Axel, Kleespies and Schick, Cordula and Fleischmann, Bastian and Schweneker, Katrin and Milani, Valeria and Schenk, Kristina and Ebner, Florian and Donhauser, Lara and Zehn, Dietmar and Hempel, Dirk}, title = {Clinical impact of SARS-CoV-2 delta variant infection in tumor patients and the impact of vaccination on different cancer treatment regimens.}, series = {Journal of Clinical Oncology}, volume = {40}, journal = {Journal of Clinical Oncology}, number = {16_suppl}, doi = {10.1200/JCO.2022.40.16_suppl.e18750}, pages = {E18750 -- E18750}, year = {2022}, abstract = {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.}, language = {en} } @article{HempelLapaGaumannetal.2022, author = {Hempel, L.C. and Lapa, C. and Gaumann, A. and Veloso de Oliveira, J. and Scheiber, J. and Philipp, P. and Oyarzun, C. and Wesarg, S. and Robert, Sebastian and Hempel, D.}, title = {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}, series = {Annals of Oncology}, volume = {33}, journal = {Annals of Oncology}, doi = {https://doi.org/10.1016/j.annonc.2022.01.045}, pages = {S17 -- S17}, year = {2022}, abstract = {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.}, language = {en} } @article{HempelLapaDierksetal.2022, author = {Hempel, Louisa and Lapa, Constantin and Dierks, Alexander and Gaumann, Andreas and Scheiber, Josef and Veloso de Oliveira, Julia and Philipp, Patrick and Oyarzun Laura, Cristina and Wesarg, Stefan and Robert, Sebastian and Hempel, Dirk}, title = {A new promising oncogenic target (p.C382R) for treatment with pemigatinib in patients with cholangiocarcinoma}, series = {Therapeutic Advances in Medical Oncology}, volume = {14}, journal = {Therapeutic Advances in Medical Oncology}, doi = {10.1177/17588359221125096}, year = {2022}, abstract = {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.}, language = {en} } @article{MuchaRobertBreitschwerdtetal.2022, author = {Mucha, Henrik and Robert, Sebastian and Breitschwerdt, R{\"u}diger and Fellmann, Michael}, title = {Usability of clinical decision support systems}, series = {Zeitschrift f{\"u}r Arbeitswissenschaft}, journal = {Zeitschrift f{\"u}r Arbeitswissenschaft}, doi = {10.1007/s41449-022-00324-8}, year = {2022}, abstract = {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.}, language = {en} } @incollection{RobertMuchaHempel2022, author = {Robert, Sebastian and Mucha, H. and Hempel, D.}, title = {Clinical Decision Support Systems}, series = {Toolbook Digitale Transformation Krankenhaus}, booktitle = {Toolbook Digitale Transformation Krankenhaus}, editor = {Glocke, P. and Elsner, C. and Schneider, H.}, publisher = {MWV Medizinisch Wissenschaftlicher Verlagsgesellschaft}, address = {Berlin}, publisher = {Technische Hochschule Rosenheim}, year = {2022}, language = {de} } @article{VictoriaDonhauserVelosodeOliveiraSchicketal.2023, author = {Victoria Donhauser, Lara and Veloso de Oliveira, Julia and Schick, Cordula and Manlik, Wenzel and Styblova, Sabrina and Lutzenberger, Sarah and Aigner, Michael and Philipp, Patrick and Robert, Sebastian and Gandorfer, Beate and Hempel, Dirk and Hempel, Louisa and Zehn, Dietmar}, title = {Responses of patients with cancer to mRNA vaccines depend on the time interval between vaccination and last treatment}, series = {Journal for ImmunoTherapy of Cancer}, volume = {11}, journal = {Journal for ImmunoTherapy of Cancer}, number = {9}, doi = {10.1136/jitc-2023-007387}, year = {2023}, abstract = {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.}, language = {en} } @inproceedings{KieselBreitwieserBrettneretal.2023, author = {Kiesel, Theresia and Breitwieser, Anita and Brettner, Stephanie and Schmidle, Stephanie and Bursch, Theresa and Freise, Laura and Schneider, Elena and K{\"o}lzer, Brigitte and Hammerschmidt, Thomas and Robert, Sebastian and Ittlinger, Sabine and Bauer, Petra}, title = {HERO - HEalth University @ TH ROsenheim F{\"o}rderkonzept zur Gewinnung und Entwicklung von wissenschaftlichem, insbesondere professoralem Personal}, series = {Tag der Forschung TH Rosenheim}, booktitle = {Tag der Forschung TH Rosenheim}, year = {2023}, language = {de} }