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 - 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 - 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 - 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 -