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 - 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 - 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, 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 - 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 -