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Jana K Striefler,1,2 Phung T Binder,2 Franziska Brandes,2 Daniel Rau,3 Silvan Wittenberg,3 David Kaul,4 Siyer Roohani,4 Armin Jarosch,5 Frederik M Schäfer,6 Robert Öllinger,7 Sven Märdian,3 Lars Bullinger,2,8 Kai-Uwe Eckardt,9 Jan Kruse,9 Anne Flörcken2,8 1Department of Internal Medicine II, Oncology/Hematology/BMT/Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; 2Department of Hematology, Oncology, and Tumor Immunology, Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, and Berlin Institute of Health, Berlin, Germany; 3Centre for Musculoskeletal Surgery, Campus Virchow-Klinikum, Charité–Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany; 4Department of Radiation Oncology, Campus Virchow-Klinikum, Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, and Berlin Institute of Health, Berlin, Germany; 5Institute of Pathology, Campus Mitte, Charité–Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany; 6Department of Radiology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität Zu Berlin, Berlin, Germany; 7Department of Surgery, Campus Virchow-Klinikum, Charité–Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany; 8German Cancer Consortium (DKTK), Partner Site Berlin, and German Cancer Research Center (DKFZ), Heidelberg, Baden-Württemberg, Germany; 9Department of Nephrology and Medical Intensive Care, Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, corporate member of Free University Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, GermanyCorrespondence: Jana K Striefler, II. Medizinische Klinik und Poliklinik, Klinik für Onkologie, Hämatologie und Knochenmarktransplantation mit Sektion Pneumologie, Universitätsklinikum Hamburg-Eppendorf, Martinistr. 52, Hamburg, D-20246, Germany, Tel +49 152 228 24370, Fax +49 40 7410-58054, Email j.striefler@uke.dePurpose: Prognosis of sarcoma patients is improving, with a better understanding of sarcomagenesis revealing novel therapeutic targets. However, aggressive chemotherapy remains an essential part of treatment, bearing the risk of severe side effects that require intensive medical treatment. Available data on the characteristics and clinical outcome of sarcoma patients admitted to intensive care units (ICU) are sparse.Patients and Methods: We performed a retrospective analysis of sarcoma patients admitted to the ICU from 2005 to 2022. Patients ≥ 18 years with histologically proven sarcoma were included in our study.Results: Sixty-six patients were eligible for analysis. The following characteristics had significant impact on overall survival: sex (p=0.046), tumour localization (p=0.02), therapeutic intention (p=0.02), line of chemotherapy (p< 0.001), SAPS II score (p=0.03) and SOFA score (p=0.02).Conclusion: Our study confirms the predictive relevance of established sepsis and performance scores in sarcoma patients. For overall survival, common clinical characteristics are also of significant value. Further investigation is needed to optimize ICU treatment of sarcoma patients.Keywords: soft tissue sarcoma, intensive care unit, sepsis and performance scores, SOFA, SAPS II, ICU-specific survival

Soft tissue sarcomas (STSs) are a diverse group of rare malignant soft tissue tumors with a high disease burden. Treatment protocols are complex and, to this day, a precise recommendation for the surgical margin width is lacking. The present study aims to analyze the width of the surgical margins in STS resection specimens and analyze them for local and systemic disease-free survival as well as for most frequent histologic STS subtypes. A total of 169 consecutive patients diagnosed and treated in curative intent in our institution following a primary and localized STS of the extremities or trunk from January 2010 to December 2020 were included in this study regardless of age. Our data reveal that low-grade STSs are best controlled locally by a surgical margin ≥2 mm and in this way also preventing distant metastases effectively. Local recurrence-free survival and metastasis-free survival in high-grade STS were improved by intact muscle fascia or periosteum at the margin when compared only to soft tissue. However, the outcome was independent of the surgical margin width, suggesting a close but negative margin may be safe in high-grade STS subtypes with less invasive growth patterns when combined with adjunct radiochemotherapy.

Soft tissue sarcomas (STSs) are a diverse group of rare malignant soft tissue tumors with a high disease burden. Treatment protocols are complex and, to this day, a precise recommendation for the surgical margin width is lacking. The present study aims to analyze the width of the surgical margins in STS resection specimens and analyze them for local and systemic disease-free survival as well as for most frequent histologic STS subtypes. A total of 169 consecutive patients diagnosed and treated in curative intent in our institution following a primary and localized STS of the extremities or trunk from January 2010 to December 2020 were included in this study regardless of age. Our data reveal that low-grade STSs are best controlled locally by a surgical margin >= 2 mm and in this way also preventing distant metastases effectively. Local recurrence-free survival and metastasis-free survival in high-grade STS were improved by intact muscle fascia or periosteum at the margin when compared only to soft tissue. However, the outcome was independent of the surgical margin width, suggesting a close but negative margin may be safe in high-grade STS subtypes with less invasive growth patterns when combined with adjunct radiochemotherapy.

BackgroundThe antibody targeting platelet-derived growth factor receptor alpha (PDGFRA), olaratumab, was approved in 2016 for metastatic soft tissue sarcoma (STS) in combination with doxorubicin based on promising results of a phase Ib/II trial by the Food and Drug Administration (FDA). However, recently the phase III ANNOUNCE trial could not confirm the additional value of olaratumab in this context.MethodsHere, in a retrospective analysis we share our single-centre experience with olaratumab/doxorubicin in STS by includingn = 32 patients treated with olaratumab/doxorubicin between 2016 and 2019.ResultsMedian progression-free survival (PFS) in the overall cohort was 3.1 months (range 0.6–16.2). A response [complete remission (CR), partial remission (PR) or stable disease (SD)] was seen inn = 11 (34%) cases, whereasn = 21 (66%) patients showed progressive disease (PD). Inn = 9 patients surgery was performed subsequently in an individual therapeutic approach. Out ofn = 5 patients receiving additional regional hyperthermia,n = 3 achieved PR or SD.ConclusionsThis single-centre experience does also not support the promising phase Ib/II results for olaratumab/doxorubicin in STS. However, our findings do not preclude that olaratumab combination therapy could be valuable in a neoadjuvant setting. This warrants further exploration also taking into account the heterogeneous nature of STS.

185 Background: In human pancreatic cancer, expression of cMET is associated with poor survival. So far, activation/expression of cMET by hepatocyte growth factor (HGF) has been shown to induce proliferation and motility in cancer cells. Therefore, we hypothesized that inhibition of cMET in human pancreatic cancer cell lines impairs oncogenic signaling and tumor growth. Methods: Pancreatic cancer cell lines (HPAF-II, MiaPaCa2, L3.6pl, BxPC3, Panc02) and the cMET inhibitor INC280 (Novartis Oncology, Basel) were used. MiaPaCa2 and L3.6pl pancreatic cancer cells were grown with gemcitabine up to 500 and 250 nM, respectively (then called MiaPaCa2(G500) and L3.6pl(G250)). MTT and Boyden Chamber assays were used to determine effects of INC280 on growth and motility of cells in vitro. Expression of growth factor receptors, activation of signaling intermediates and expression of transcription factors were assessed by Western blotting. Finally, in vitro results were validated in an orthotopic tumor model using L3.6pl pancreatic cancer cell line. Results: All pancreatic cancer cell lines showed expression of cMET. In vitro treatment of cancer cells with INC280 led to a minor, dose-dependent inhibition of growth even when cells were supplemented with HGF. In contrast, migration assays showed a significant reduction of cancer cell motility upon INC280 when cells were stimulated with HGF (P