Abstract: 10571 Background: Tumor patients (pts.) are considered susceptible to severe COVID-19 after SARS-CoV-2 infection. However, they represent a heterogeneous group of individuals with variable risk. Identification of vulnerable subgroups is important for prioritization of vaccination strategies and possible early therapeutic intervention after infection. Methods: Tumor pts. with PCR-confirmed SARS-CoV-2 infection were included in the multicentric ADHOK registry by 22 institutions. Detailed information about tumor disease and treatment, as well as routine laboratory parameters determined at least 10 days prior to SARS-CoV-2 infection, was collected retrospectively. The primary endpoint was defined as the outcome of the SARS-CoV-2 infection, graded according to the WHO: asymptomatic, mild, moderate, severe, critical, and COVID-19-related death. Results: Until Feb. 5, 2021, 215 pts. (67% with solid tumors, 33% with hematological neoplasms) were included in the registry. 74% of the pts. had an active malignancy. The course of SARS-CoV-2 infection was rather variable: 66% of the pts. remained asymptomatic or showed a mild-to-moderate course, while the rest developed severe or critical disease. The COVID-19-related mortality rate was 24%. Pre-infection routine laboratory values were available for 104 pts., obtained at a median of 21 days before SARS-CoV-2 infection. Compared to COVID-19 survivors, COVID-19 non-survivors showed significantly higher median levels of absolute neutrophil count (ANC: 3.6 vs. 6.4 /nL; p = 0.006, n = 91), neutrophil-to-lymphocyte ratio (NLR: 2.2 vs. 7.2; p = 0.005, n = 75), C-reactive protein (CRP: 9.9 vs. 42.0 mg/L; p = 0.001, n = 104), and lactate dehydrogenase (LDH: 213.0 vs. 267.0 U/L; p = 0.016, n = 78). When categorized by a median split, COVID-19 mortality was significantly higher in pts. with ANC 〉 4.4 /nL (4% vs. 55%, p 〈 0.001), NLR 〉 4.1 (5% vs. 58%, p 〈 0.001), CRP 〉 15.4 mg/L (18% vs. 46%, p = 0.003), LDH 〉 236 U/L (15% vs. 49%, p = 0.003) and lymphocytes 〈 1.3 /nL (41% vs. 11% p = 0.002). In multivariable analysis, ANC and CRP showed a strong and significant association with COVID-19-related death (OR 23.0 and 7.7, p = 0.007 and 0.029, respectively). To develop an easy-to-apply pre-infection score, we combined ANC and CRP and were able to separate three groups of pts. with significantly different COVID-19 outcomes (p 〈 0.001) (Table). Conclusions: Our results unveil subgroups of tumor pts. who may be at increased risk of severe COVID-19 and point to pre-infection routine laboratory parameters with potential prognostic power: ANC and CRP may help identify pts. at risk for severe COVID-19 before SARS-CoV-2 infection.[Table: see text]

Abstract: Background. Lactococcus garvieae (LG) is a gram-positive coccus known to be a major pathogen in aqua farming, which is responsible for severe outbreaks. Its incidence in humans is extremely rare. Prior to 1985, all bacteria in the genus Lactococcus were included in the Streptococcus genus. The first human infection was documented in 1991, and since then, the relevance and clinical significance in humans has increased. Case Description. We present the clinical course of an LG endocarditis in a 78-year-old man who had a history of exertional dyspnea. The patient’s blood tests showed increased inflammation values, and a transesophageal ultrasound (TEE) showed a stenosis of the prosthetic aortic valve. Blood cultures were positive for LG, leading to a diagnosis of infective endocarditis. After 6 weeks of intravenous antibiotics and a prosthetic aortic valve replacement, the patient made a good recovery. Review of the Literature. After the first documented case in 1991 to 2018, 25 cases of LG endocarditis have been described in PubMed and MEDLINE. We reviewed all reported cases of LG endocarditis, commenting on predisposing risk factors, the course and outcome of the disease. Conclusion. LG endocarditis is a rare disease. Consumption of raw fish, abnormalities of the digestive tract, immune deficiency, and underlying cardiac conditions appear to be risk factors for an infective endocarditis due to LG. Improved determination techniques are likely to lead to a better and faster identification of the bacterium. This identification allows a faster and individualized therapy, which in turn affects the outcome.

Abstract: ABEMACARE: Abemaciclib in Combination with Endocrine Therapy as First Line Therapy in Metastatic Breast Cancer Patients with Symptomatic Visceral Metastases or High Tumor Burden – A prospective Multicenter Observational Study Sophia Ramsperger, Franziska Kotzur, Lothar Müller, Stephan Seitz, Peter A. Fasching, Stefanie Jilg, Dorothea Fischer, Silvia Egert-Schwender, Victoria Kehl, Ute Reuning, Lukas Rief, Romina Rösch, Holger Bronger, Christof Winter, Marion Kiechle, Johannes Ettl Background: Combined endocrine therapy with Cyclin-dependent kinase 4 and 6 (CDK 4/6) inhibitors and aromatase inhibitor (AI) or Fulvestrant has become standard of care in first line therapy of estrogen receptor (ER) positive, HER2 negative metastatic breast cancer. Numeral trials have shown excellent results regarding disease control and survival while maintaining quality of life for patients. In the MONARCH 2 and MONARCH 3 trials, patients with liver metastases derived a particularly large benefit from the use of Abemaciclib. Nevertheless, in real world many patients with endocrine sensitive metastatic breast cancer are still being treated with chemotherapy in first line. Symptomatic visceral disease and/or high tumor burden are often seen as reasons for upfront chemotherapy even in the absence of visceral crisis. In this specific patient population Abemacare aims at determining the efficacy of Abemaciclib in combination with endocrine therapy as first line treatment. Further, the question is addressed, whether circulating tumor DNA might serve as a predictive biomarker for early tumor response. Study Design: Abemacare is a prospective multicenter noninterventional, observational study. 96 patients in 10 German cancer centers who receive first line Abemaciclib in combination with AI or Fulvestrant are planned to be enrolled. Recruitment started in December 2020. As of July 1st 2022, 51 patients have been included in six study sites. Patients with documented ER-positive, HER2-negative metastatic breast cancer and measurable visceral disease are eligible if they fulfill one of the following inclusion criteria: Presence of clinical signs or symptoms of visceral disease (e.g. pleural effusion, ascites, abdominal pain from liver or peritoneal metastases, dyspnea from pleural effusion or lymphangiosis of the lung, elevated liver enzymes or bilirubin level ( & gt; 2x ULN)) or signs of high tumor burden (e.g. LDH & gt; 399 U/l with K+ in normal range, abnormal CEA or CA 15-3 level ( & gt; 2x ULN), radiographic signs of lymphangiosis of the lung, cytologically proven bone marrow infiltration). Patients with prior therapy with a CDK 4/6 inhibitor in any setting or first line therapy for metastatic disease are excluded from the trial. Primary endpoint is best objective response rate (ORR) defined by the proportion of patients who are evaluated using RECIST V1.1 as having partial (PR) or complete response (CR) while being on study treatment. ORR will be analyzed using the one group χ2 test at the 5% significance level. The test hypotheses are as follows: H0: ORR = 0.43, HA: ORR ≠ 0.43. In addition, ORR will be reported with a 95% CI. Several additional endpoints regarding disease control and patient reported outcomes will also be evaluated. Plasma samples for ctDNA are being collected at d1 and d15 of cycle 1 and d1 of cycle 2 and 3. Contact information: For further information please contact the leading physician Dr. Johannes Ettl via johannes.ettl@tum.de This study is supported by Eli Lilly and Company. NCT04681768 a & gt;Disclosure(s): Johannes Ettl, n/a: Amgen, Celgene, Eisai, Myriad, Teva.: Consulting Fees (e.g., advisory boards) (Ongoing); Novartis: Consulting Fees (e.g., advisory boards) (Ongoing); Pfizer, Pierre Fabre, Lilly, Roche, AstraZeneca, Daiichi, Gilead, Seagen: Consulting Fees (e.g., advisory boards) (Ongoing) Ramsperger Sophia, n/a: No financial relationships to disclose Franziska Kotzur, n/a: No financial relationships to disclose Lothar Müller, n/a: No financial relationships to disclose Stephan Seitz, n/a: AstraZeneca: Consulting Fees (e.g., advisory boards) (Ongoing), Fees for Non-CME Services Received Directly from Commercial Interest or their Agents (e.g., speakers’ bureaus) (Ongoing); GE; Gedeon-Richter; GSK; Lilly;: Consulting Fees (e.g., advisory boards) (Ongoing) Peter A. Fasching, MD: Agendia: Consulting Fees (e.g., advisory boards) (Ongoing); AstraZeneca: Consulting Fees (e.g., advisory boards) (Ongoing); Biontech: Contracted Research (Ongoing); Cepheid: Contracted Research (Ongoing); Daiichi Sankyo: Consulting Fees (e.g., advisory boards) (Ongoing); Eisai: Consulting Fees (e.g., advisory boards) (Ongoing); Genentech: Consulting Fees (e.g., advisory boards) (Ongoing); Gilead: Consulting Fees (e.g., advisory boards) (Ongoing); Lilly: Consulting Fees (e.g., advisory boards) (Ongoing); Merck Sharp & Dohme: Consulting Fees (e.g., advisory boards) (Ongoing); Novartis: Consulting Fees (e.g., advisory boards) (Ongoing); Pfizer: Consulting Fees (e.g., advisory boards) (Ongoing); Pierre Fabre: Consulting Fees (e.g., advisory boards) (Ongoing); Roche: Consulting Fees (e.g., advisory boards) (Ongoing); Sanofi Aventis: Consulting Fees (e.g., advisory boards) (Ongoing); SeaGen: Consulting Fees (e.g., advisory boards) (Ongoing) Stefanie Jilg, n/a: No financial relationships to disclose Dorothea Fischer, n/a: No financial relationships to disclose Silvia Egert-Schwender, n/a: No financial relationships to disclose Kehl Victora, n/a: No financial relationships to disclose Ute Reuning, n/a: No financial relationships to disclose Romina Rösch, n/a: No financial relationships to disclose Lukas Rief, n/a: No financial relationships to disclose Holger Bronger, n/a: No financial relationships to disclose Christof Winter, n/a: No financial relationships to disclose Marion Kiechle, n/a: Myriad Genetics, Bavarian KVB, DKMS Life, BLAEK, TEVA, Exeltis. Equity owner: Therawis Diagnostic GmbH, AIM GmbH.: Consulting Fees (e.g., advisory boards) (Ongoing), Contracted Research (Ongoing), Fees for Non-CME Services Received Directly from Commercial Interest or their Agents (e.g., speakers’ bureaus) (Ongoing) & lt;/a & gt; Citation Format: Johannes Ettl, Ramsperger Sophia, Franziska Kotzur, Lothar Müller, Stephan Seitz, Peter A. Fasching, Stefanie Jilg, Dorothea Fischer, Silvia Egert-Schwender, Kehl Victora, Ute Reuning, Romina Rösch, Lukas Rief, Holger Bronger, Christof Winter, Marion Kiechle. ABEMACARE: Abemaciclib in Combination with Endocrine Therapy as First Line Therapy in Metastatic Breast Cancer Patients with Symptomatic Visceral Metastases or High Tumor Burden – A prospective multicenter observational study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT2-01-09.

Abstract: Background . Obesity is related to coronary artery disease (CAD) and worse outcomes in coronary artery bypass graft (CABG) patients. Adipose tissue itself is an endocrine organ that secretes many humoral mediators, such as adipokines, which can induce or reduce inflammation and oxidative stress. Objectives . We investigate the relationship between the body mass index (BMI), inflammation, and oxidative stress by measuring serum levels of leptin, interleukin-6, and 3-nitrotyrosine in CABG patients and correlate their levels to the cardiovascular and operative risk profiles. Methods and Results . 45 men ( 〈 75 years) with a median BMI of 29 (21-51) kg/m 2 , who were diagnosed with CAD and scheduled for elective CABG, were included after applying the following exclusion criteria: prior myocardial infarction, reoperation, female gender, and smoking. Patients’ blood samples were taken preoperatively. Several markers were measured. We found significant correlations between leptin and BMI p 〈 0.0001 as well as between leptin and 3-nitrotyrosine p = 0.006 . Interleukin-6 was correlated with C-reactive protein p 〈 0.0001 and with the incidence of insulin-dependent diabetes mellitus p = 0.036 , arterial hypertension p = 0.044 , reduced left ventricular function p = 0.003 , and severe coronary calcification p = 0.015 . It was also associated with significantly longer extracorporeal bypass time p = 0.009 . Postoperative deep sternal wound infections could be predicted by a higher BMI p = 0.003 and leptin level p = 0.001 . Conclusions . There seems to be a correlation between inflammatory processes and cardiovascular morbidity in our cohort. Further, the incidence of deep sternal wound infections is related to a higher BMI and leptin serum level.

Abstract: Diffuse large B cell lymphomas (DLBCL) are the most common neoplasia of the lymphatic system. Circulating cell-free DNA released from tumor cells (ctDNA) has been studied in many tumor entities and successfully used to monitor treatment and follow up. Studies of ctDNA in DLBCL so far have mainly focused on tracking mutations in peripheral blood initially detected by next-generation sequencing (NGS) of tumor tissue from one lymphoma manifestation site. This approach, however, cannot capture the mutational heterogeneity of different tumor sites in its entirety. In this case report, we present repetitive targeted next-generation sequencing combined with digital PCR out of peripheral blood of a patient with DLBCL relapse. By combining both detection methods, we were able to detect a new dominant clone of ctDNA correlating with the development of secondary therapy-related acute myeloid leukemia (t-AML) during the course of observation. Conclusively, our case report reinforces the diagnostic importance of ctDNA in DLBCL as well as the importance of repeated ctDNA sequencing combined with focused digital PCR assays to display the dynamic mutational landscape during the clinical course.

Abstract: Infection with SARS‐CoV‐2 leads to COVID‐19, the course of which is highly variable and depends on numerous patient‐specific risk factors. Patients with tumor diseases are considered to be more susceptible to severe COVID‐19; however, they also represent a heterogeneous group of individuals with variable risk. Identifying specific risk factors for a severe course of COVID‐19 in patients with cancer is of great importance. Methods Patients diagnosed with solid tumors or hematological malignancies and PCR‐confirmed SARS‐CoV‐2 infection were included into the multicentric ADHOK (Arbeitsgemeinschaft der Hämatologen und Onkologen im Krankenhaus e.V.) coronavirus tumor registry. Detailed information about the patients’ cancer disease, treatment, and laboratory parameters prior to infection, was collected retrospectively. The outcome of the SARS‐CoV‐2 infection was graded according to the WHO. Results A total of 195 patients (68% with solid neoplasms and 32% with hematological malignancies) were included in the registry. Overall, the course of the SARS‐CoV‐2 infection varied greatly, as 69% of all patients were either asymptomatic or encountered a mild to moderate course, while 23% of the cohort died from COVID‐19. In multivariable analysis, preinfection laboratory parameters (determined at least 10 days and a median of 21 days before the first documentation of SARS‐CoV‐2 infection) significantly correlated with severe course of the disease. Out of these, the absolute neutrophil count prior to infection showed the strongest association with COVID‐19‐related death. Conclusion The course of COVID‐19 in patients with tumor diseases is highly variable. Preinfection laboratory parameters may aid to identify patients at risk for severe COVID‐19 at an early stage prior to infection with the virus. German Clinical Trials Register identification: DRKS00023012.

Abstract: Background: Cyclin-dependent kinase 4 and 6 (CDK 4/6) inhibitors in combination with endocrine therapy are well established in the therapy of estrogen receptor (ER) positive, HER2 negative metastatic breast cancer. They have shown excellent results regarding disease control and survival in numerous trials while maintaining good quality of life for patients. In the subgroup analysis of the MONARCH 2 and MONARCH 3 trials, patients with liver metastases derived a particularly large benefit from the combined endocrine treatment with Abemaciclib. Despite this evidence, in real world many patients with endocrine sensitive metastatic breast cancer are still being treated with first line chemotherapy. Especially in patients with symptomatic visceral disease and/or high tumor burden, use of upfront chemotherapy remains common even in the absence of visceral crisis. With this study we aim to determine the efficacy of Abemaciclib in combination with endocrine therapy as first line treatment in this specific patient population. Study design: In this prospective multicenter observational study, we intend to enroll 120 patients in 10 German cancer treatment centers who will receive first line therapy with Abemaciclib in combination with endocrine therapy within clinical routine. Recruitment is planned to start in August 2020. Patients with documented ER positive, HER2 negative metastatic breast cancer with measurable visceral disease are eligible if they fulfill one of the following inclusion criteria: Presence of clinical signs or symptoms of visceral disease (e.g. pleural effusion, ascites, abdominal pain from liver or peritoneal metastases, dyspnea from pleural effusion or lymphangiosis of the lung, elevated liver enzymes or bilirubin level ( & gt; 2x ULN)) or signs of high tumor burden (e.g. LDH & gt; 399 U/l with K in normal range, abnormal CEA or CA 15-3 level ( & gt; 2x ULN), radiographic signs of lymphangiosis of the lung, cytologically proven bone marrow infiltration). Patients may have received chemotherapy or endocrine therapy in the adjuvant setting, but no prior therapy with CDK 4/6 inhibitors and no first line therapy for metastatic disease. Primary endpoint is best objective response rate (ORR) defined by the proportion of patients who are evaluated as having partial (PR) or complete response (CR) while being on study treatment using RECIST V1.1. ORR will be analyzed using the one group χ2 test at the 5% significance level. The test hypotheses are as follows: H0: ORR = 0.43, HA: ORR ≠ 0.43. In addition, ORR will be reported with a 95% CI.Several additional endpoints regarding disease control and patient reported outcomes will also be evaluated. At the same time translational research to identify possible early predictive biomarkers for tumor response (e.g. circulating tumor DNA) will be conducted. Contact information: For further information please contact the leading physician Dr. Johannes Ettl via johannes.ettl@tum.de This study is supported by Eli Lilly and Company. Citation Format: Franziska Kotzur, Helen Bidner, Holger Bronger, Silvia Egert, Peter A Fasching, Dorothea Fischer, Victoria Kehl, Hans-Joachim Lück, Lothar Müller, Ute Reuning, Lukas Rief, Romina Rösch, Stephan Seitz, Christof Winter, Marion Kiechle, Johannes Ettl. ABEMACARE: Abemaciclib in combination with endocrine therapy as first line therapy in metastatic breast cancer patients with symptomatic visceral metastases or high tumor burden [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr OT-26-01.

Abstract: (1) Background: Currently, there is no clinically used liquid biomarker in head and neck squamous cell carcinoma (HNSCC) patients. One reason could be the limited shedding of tumor material in early disease stages. Molecular diagnostics assessing both blood and especially saliva could potentially improve the accuracy of biomarkers. In this prospective study, two markers, tissue inhibitor of metalloprotease-1 (TIMP-1) and heat shock protein 70 (Hsp70), were analyzed in HNSCC patients. The purpose of the study was to evaluate differences between saliva and serum as sample material. Further, their prognostic and predictive value and usefulness for early detection was assessed. (2) Methods: A total of 73 HNSCC patients were prospectively monitored by collecting blood and saliva before, during, and after therapy, as well as in the follow-up period between 2018 and 2021. In total, 212 serum and 194 saliva samples were collected. A control group consisting of 40 subjects (15 patients with local infections in the head and neck area and 25 without infections) were examined as well. The collected samples were evaluated for the two proteins by using an enzyme-linked immunosorbent assay (ELISA). (3) RESULTS: The TIMP-1 concentration correlated significantly in blood and saliva, whereas the Hsp70 concentration did not. Saliva TIMP-1 was significantly higher in tumor patients compared to the control group (p = 0.013). High pretreatment TIMP-1 saliva levels were associated with significantly poorer disease-free survival (DFS) (p = 0.02). A high saliva TIMP-1/Hsp70 ratio was significantly associated with poorer DFS (HR: 1.4; 95% CI: 1.04–1.88; p = 0.026) and a high TIMP-1 serum concentration was significantly associated with poorer PFS (HR: 1.9; 95% CI: 1.2, 2.8; p = 0.003) and poorer overall survival (OS) (HR: 2.9; 95% CI: 1.4, 5.9; p = 0.003) in the Cox proportional hazards model. The saliva TIMP-1 to Hsp70 ratio was significantly higher at the time of recurrence (p = 0.015). Conclusion: TIMP-1 in serum is a promising prognostic marker for HNSCC. Saliva TIMP-1 and the saliva TIMP-1 to Hsp70 ratio provides additional information on the disease-free survival.