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SummaryRecent innovative advances, especially concerning immunotherapeutic agents and targeted therapies, have changed the face of modern oncology. The year 2020 represents a milestone in the treatment of gastroesophageal cancer because several trials showed promising survival benefits, at least for a specific subgroup of patients. Not only immunotherapeutic agents, but also targeted therapies seem to be beneficial, particularly when the target is well defined and the threshold value is selected appropriately. Thus, many new innovative treatment strategies are underway and might lead to a further paradigm change in the therapy of patients with advanced gastric tumors. This review gives a concise overview of these new therapeutic options and recently approved strategies as well as ongoing studies.

SummaryThe prognosis of patients with metastatic gastroesophageal cancer remains poor despite numerous promising clinical trials, and the clinical benefit of systemic therapies is under critical review. This case report of a patient with human epidermal growth factor receptor 2 (HER2)-positive metastatic gastric adenocarcinoma is an impulse for the importance of individual decision making and molecular guided treatment options.

Immunotherapy with check-point inhibitors serves as a promising treatment strategy in patients with upper gastrointestinal (GI) tumors. Human epidermal growth factor receptor 2 (HER2) is the only identified therapeutic target in upper GI tumors, whose potential interaction with programmed death-ligand 1 (PD-L1) is unknown. The aim of this study was the investigation of PD-L1 and HER2 in upper GI tumors. We retrospectively identified patients with HER2 positive gastroesophageal cancers and matched them with a HER2 negative group. We investigated the tumor specimens for HER2 status and PD-L1 expression, with the following assessments being performed: i) staining of tumor cells in terms of tumor proportion score (TPS), ii) staining for tumor-associated immune cells (TAIs), iii) interface pattern and iv) combined positive score (CPS). Both HER2 positive and negative group consisted of 59 patients. Expression of PD-L1 in TAIs and interface pattern were associated with a favorable outcome (p = 0.02, HR = 0.8; p = 0.04, HR = 0.39; respectively) in patients with localized disease, whereas TPS was associated with an unfavorable outcome in patients with advanced tumor (p = 0.02, HR = 1.4). These effects were HER2 independent. PD-L1 expression in its different assessment is equally observed in HER2 positive and negative patients. Future studies will show whether dual inhibition of HER2 and PD-L1 improves survival of this selected patient population. Electronic supplementary material The online version of this article (10.1007/s12253-020-00814-2) contains supplementary material, which is available to authorized users.

The overall survival expectancy of localized gastroesophageal cancer patients still remains under 5 years despite advances in neoadjuvant and adjuvant treatment strategies in recent years. For almost a decade, immunotherapy has been successfully implemented as a first-line treatment for various oncological diseases in advanced stages. In the case of advanced gastroesophageal cancer, 2021 witnessed several approvals of immune checkpoint inhibitor therapies by different authorities. Although it is still a debate whether this treatment should be restricted to a certain subgroup of patients based on biomarker selection, immunotherapy agents are making remarkable steps in resectable settings as well. The Checkmate-577 study demonstrated significant benefits of nivolumab as an adjuvant treatment for resectable esophageal and gastroesophageal junction tumors and thereby obtained approvals both from U.S. American and European authorities. First results of further potential practice-changing clinical trials are expected in 2023, which might change the treatment armamentarium for resectable gastroesophageal cancers significantly. This review aims to demonstrate the advances of immunotherapy and targeted therapies in treatment of localized gastric, gastroesophageal junction and esophageal tumors and gives a short summary on promising ongoing clinical trials.

Introduction: As thyroid hormones modulate proliferative pathways it is surmised that they can be associated with cancer development. Since the potential association of gastroesophageal cancer and thyroid disorders has not been addressed so far, the aim of this study was to investigate the association of thyroid hormone parameters with the outcome of these patients, so novel prognostic and even potentially therapeutic markers can be defined. Material and Methods: Clinical and endocrinological parameters of patients with resectable gastroesophageal cancer treated between 1990 and 2018 at the Vienna General Hospital, Austria, including history of endocrinological disorders and laboratory analyses of thyroid hormones at first cancer diagnosis were investigated and correlated with the overall survival (OS). Results: In a total of 865 patients, a tendency towards prolonged OS in hypothyroid patients (euthyroid, n = 647: median OS 29.7 months, hyperthyroid, n = 50: 23.1 months, hypothyroid, n = 70: 47.9 months, p = 0.069) as well as a significant positive correlation of thyroid hormone replacement therapy with the OS was observed (without, n = 53: median OS 30.6 months, with, n = 67: 51.3 months, p = 0.017). Furthermore, triiodothyronine (T3) levels were also associated with the OS (median OS within the limit of normal: 23.4, above: 32.4, below: 9.6 months, p = 0.045). Conclusions: Thyroid disorders and their therapeutic interventions might be associated with the OS in patients with resectable gastroesophageal cancer. As data on the correlation of these parameters is scarce, this study proposes an important impulse for further analyses concerning the association of thyroid hormones with the outcome in patients with gastroesophageal tumors.

Importance: To our knowledge, little is known about antibody development after SARS-CoV-2 vaccination in immunocompromised individuals, such as patients with cancer. Objective: To determine whether hematooncological patients develop anti-SARS-CoV-2 antibodies after vaccination. Design, Setting, and Participants: This retrospective cohort study included 2 independent cohorts of patients who were treated for hematological and solid malignant tumors between October 2020 and May 2021, comprising 901 samples from 595 patients and 58 health care workers (HCWs). Serum samples were collected from patients who were treated at an academic center and a community hospital in a rural area and a control group of HCWs, all of whom received SARS-CoV-2 vaccination. Main Outcomes and Measures: Total anti-SARS-CoV-2 nucleocapsid (anti-NC) and antispike protein (anti-S) antibodies were measured retrospectively. Results: In total, 595 patients (320 women [53.8%] and 275 men [46.2%]; median [range] age, 67 [19-96] years) and 58 HCWs (40 women [69.0%] and 18 men [31.0%]; median [range] age, 42 [24-60] years) were included. Previous SARS-CoV-2 infection was documented in 43 of 595 (7.2%), while anti-NC antibodies that suggested previous infections were observed in 49 of 573 evaluable patients (8.6%). In both cohorts, anti-S antibody levels were higher in fully vaccinated patients compared with patients who received 1 dose. After the first vaccination, patients with hematological cancer who received B cell-targeting agents had lower anti-S levels (median, 1.6 AU/mL; range: 0-17 244 AU/mL) than patients who received other therapies (median, 191.6 AU/mL; range, 0-40 000; P < .001) or patients with solid tumors (median, 246.4 AU/mL; range, 0-40 000 AU/mL; P < .001). Anti-S levels after the first vaccination differed according to ongoing antineoplastic treatment modalities, with the lowest median levels in patients who received chemotherapy alone (157.7 AU/mL; range, 0-40 000 AU/mL) or in combination with immunotherapy (118.7 AU/mL; range, 14.1-38 727 AU/mL) and the highest levels in patients with no ongoing antineoplastic treatment (median, 634.3 AU/mL; range, 0-40 000 AU/mL; P = .01). Antibody levels after full immunization were higher in HCWs (median, 2500 U/mL; range, 485-2500 U/mL) than in patients with cancer (median, 117.0 U/mL; range, 0-2500 U/mL; P < .001). Conclusions and Relevance: In this cohort study of patients with hematooncological diseases and a control group of HCWs, anti-SARS-CoV-2 antibodies after vaccination could be detected in patients with cancer. Lower antibody levels compared with HCWs and differences in seroconversion in specific subgroups underscore the need for further studies on SARS-CoV-2 vaccination in patients with hematooncological disease.

SummaryAlthough several large clinical trials have been conducted in order to investigate targeted inhibition of several molecular pathways in gastric cancer, only a limited number of targeted therapies have been introduced in clinical routine. Besides scientific interest, international guidelines recommend investigation of some distinct molecular alterations, which are associated with therapeutic consequences. These are (i) human epidermal growth factor receptor 2 (HER2), (ii) programmed death receptor 1 (PD-L1) and (iii) microsatellite instability (MSI). There are some emerging markers, such as Epstein–Barr virus (EBV), which might also be associated with a favorable response to immunotherapy. These routine and potential markers will be further discussed in the scope of this short review.

Patients with unprovoked deep-vein thrombosis (DVT) of the leg or pulmonary embolism (PE) have a high recurrence risk. How often these recurrences are provoked by a temporary risk condition is unknown. In a cohort of patients with unprovoked venous thromboembolism (VTE), we evaluated the clinical circumstances of recurrence. We studied patients with DVT of the leg and/or PE. End point was recurrence of objectively verified symptomatic VTE. Provoked recurrence was defined according to guidance criteria. 1188 patients were followed for a median of 8.9 years after withdrawal of oral anticoagulants. 312 patients had recurrent VTE, which was provoked in 42 (13%). Recurrence was related to a major risk factor in 19, to a minor risk factor in 22, and to a persistent risk factor in one patient(s). 14 recurrences occurred after major surgery and 5 during hospitalization. Ten recurrences occurred after minor surgery, eight after trauma and three during female hormone intake. Four recurrences occurred during heparin prophylaxis. The incidence of provoked VTE recurrence appears to be low. VTE can recur when prevention is stopped or even during thromboprophylaxis. Surgery and trauma are frequent risk factors.

Purpose: As thyroid hormones modulate proliferative pathways, it is surmised that they can be associated with cancer development. Since the potential association of gastroesophageal cancer and thyroid disorders has not been addressed so far, the aim of this study was to investigate the association of thyroid hormone parameters with the outcome of these patients, so novel prognostic and even potentially therapeutic markers can be defined. Methods: Clinical and endocrinological parameters of patients with resectable gastroesophageal cancer treated between 1990 and 2018 at the Vienna General Hospital, Austria including history of endocrinological disorders and laboratory analyses of thyroid hormones at first cancer diagnosis were investigated and correlated with the overall survival (OS).Results: In a total of 865 patients, a tendency towards prolonged OS in hypothyroid patients (euthyroid, n=647: median OS 29.7 months; hyperthyroid, n=50: 23.1 months; hypothyroid, n=70: 47.9 months; p=0.069) as well as a significant positive correlation of thyroid hormone replacement therapy with the OS was observed (without, n=53: median OS 30.6 months; with, n=67: 51.3 months; p=0.017). Furthermore, triiodothyronine (T3) levels were also associated with the OS (median OS within limit of normal: 23.4, above: 32.4, below: 9.6 months; p=0.045).Conclusion: Thyroid disorders and their therapeutic interventions might be associated with the OS in patients with resectable gastroesophageal cancer. As data on the correlation of these parameters is scarce, this study proposes an important impulse for further analyses concerning the association of thyroid hormones with the outcome in patients with gastroesophageal tumors.

Abstract: Immunotherapy represents one of the biggest breakthroughs of the 21st century and redefined modern cancer treatment. Despite this new approach changing the treatment paradigm in various cancer entities, including lung and head-and-neck cancer, the efficacy of these treatment regimens varies in different patient subgroups, and so far, these treatment regimens have failed to meet the high expectations of gastroesophageal cancer patients. This review discusses new treatment approaches concerning immunotherapy in gastroesophageal cancer patients and sheds some light on ongoing trials and new treatment combinations.

The nucleoside trifluridine/tipiracil (TAS-102) and the multikinase inhibitor regorafenib significantly improved survival in metastatic colorectal cancer patients (mCRC). Both treatments are characterized by different treatment-related adverse events but detailed analyses of predictive side effects are rare. In this retrospective, observational, real-life study, clinical data on mCRC patients treated with trifluridine/tipiracil or regorafenib at the Medical University of Vienna, Austria and the University Hospital Zurich, Switzerland were collected. The correlation between adverse events and response or survival rates were calculated performing Fisher&rsquo, s exact test and log-rank test, respectively. Common adverse events of any grade included fatigue (52%), nausea/vertigo (34%), anemia (26%), and leukopenia (22%) in trifluridine/tipiracil patients and fatigue (42%), hand-foot-skin syndrome (36%) and hoarseness (34%) in patients upon regorafenib treatment. In trifluridine/tipiracil patients the prevalence of leukopenia (p = 0.044) and weight loss (p = 0.044) was prognostic, whereas leukopenia (p = 0.044) and neutropenia (p = 0.043) predicted PFS. The disease control rate was not significantly affected. In regorafenib-treated patients, the prevalence of nausea (p = 0.001) was prognostic, while oral mucositis predicted PFS (p = 0.032) as well as the DCR (p = 0.039). In conclusion, we underline the efficacy of trifluridine/tipiracil and regorafenib in the real-life setting. We describe predictive adverse events like neutropenia/leukopenia, which might be used as surrogate marker in anticancer therapy beyond second line treatment.

Background The clinical behaviour and outcome of young patients with gastroesophageal tumours (GET) is surmised to differ from older patients, yet data on the comparison of these two patient subgroups is scarce. This study focuses on the investigation of the clinical characteristics and survival outcome of younger-age people with GET, when compared to older patients. Methods Patients diagnosed with GET at the Medical University of Vienna between 2004 and 2016 were included in this study. Clinical parameters and the overall survival (OS) were compared between young (≤ 45 years) and elderly (≥ 65 years) patients. Results Among 796 patients, who were eligible for this analysis, fifty-eight patients (7%) were ≤ 45 years at the initial onset of the disease. These 58 young patients were then matched to elderly patients based on the gender, tumour stage, histology and tumour location. The number of metastatic lesions was significantly higher among young patients (p p = 0.028). Furthermore, young patients with extensive metastatic disease (2 or more metastatic site) had a significantly poorer OS than elderly patients (median 450 versus 646 days, p = 0.033). Conclusion These results indicate that young patients might be diagnosed very late, which might lead to the development of a more aggressive disease compared to older patients, but a relatively long OS when diagnosed and treated in a non-metastatic setting. Thus, screening methods for younger patients might be considerable to enhance the outcome of young patients with GET.

Introduction The prognostic value of symptoms at disease presentation of advanced gastro-oesophageal cancer is unknown. Thus, the aim of this study was to characterise these symptoms and correlate them with the outcome, so new prognostic markers can be defined. Methods We analysed clinical data including symptoms, therapies and survival of patients with stage IV gastro-oesophageal cancer treated between 2002 and 2018 at the Vienna General Hospital, Austria. Initial symptoms as well as stenosis in endoscopy and HER2 positivity were evaluated in a cross-validation model to ascertain the impact of each variable on patient survival. Results In total, 258 patients were evaluated. Five factors (stenosis in endoscopy, weight loss, HER2 positivity, dyspepsia, ulcer or active bleeding) have proven to be statistically relevant prognostic factors and were given a count of +1 and −1, if applicable. The resulting score ranges between −3 and +2. The survival probability for 180 days with a score of −3/–2, −1, 0, +1 and +2 is 90%, 80%, 73%, 72% and 42%, whereas for 2 years, it is 30%, 30%, 8%, 7% and 3%, respectively. The median overall survival of a score of −3/–2, −1, 0, +1 and +2 was 579 (95% CI 274 to not measurable), 481 (95% CI 358 to 637), 297 (95% CI 240 to 346), 284 (95% CI 205 to 371), 146 (95% CI 120 to 229) days, respectively. Conclusion The data from this retrospective study indicate that the Viennese risk prediction score for Advanced Gastroesophageal carcinoma based on Alarm Symptoms score provides independent prognostic information that may support clinical decision making at diagnosis of advanced gastro-oesophageal cancer. Our findings should be evaluated in prospective studies.

Simple Summary Recent studies concerning immunotherapeutic agents are bound to revolutionize therapeutic strategies for esophageal cancer patients. This review aims to summarize novel clinical data and provide a critical view of potential restrictions for the implementation of immunotherapy for unselected patient populations. Abstract The prognosis of advanced esophageal cancer is dismal, and treatment options are limited. Since the first promising data on second-line treatment with checkpoint inhibitors in esophageal cancer patients were published, immunotherapy was surmised to change the face of modern cancer treatment. Recently, several studies have found this to be true, as the checkpoint inhibitors nivolumab and pembrolizumab have achieved revolutionary response rates in advanced as well as resectable settings in esophageal cancer patients. Although the current results of large clinical trials promise high efficacy with tolerable toxicity, desirable survival rates, and sustained quality of life, some concerns remain. This review aims to summarize the novel clinical data on immunotherapeutic agents for esophageal cancer and provide a critical view of potential restrictions for the implementation of these therapies for unselected patient populations.

As endocrinological parameters such as thyroid hormones modulate proliferative, metabolic, and angiogenic pathways, it is surmised that their levels can be associated with cancer development and progression. Most patients with gastroesophageal cancer are diagnosed very late and have a poor prognosis, yet the association with endocrinological parameters has not been addressed so far. The aim of this study was to correlate hormones with the outcome, so new prognostic and potentially therapeutic markers can be defined. We analyzed clinical and endocrinological parameters including history of thyroid disorders and laboratory analyses of thyroid hormones and correlated these with the overall survival in a large European cohort of patients with inoperable locally advanced or metastatic gastroesophageal cancer treated between 2002 and 2018 at the Vienna General Hospital, Austria. In total, the survival outcome of 258 patients was evaluated. Higher levels of fT4 (p = 0.041, HR = 2.202) and lower levels of T3 (p = 0,003, HR = 0,141) were associated with significantly shorter survival. However, the overall survival of patients with known thyroid disorders did not differ significantly from euthyroid patients (euthyroid, 283 days; hyperthyroid, 354 days; hypothyroid, 284 days; p = 0.472). Elevated fT4 levels are associated with poorer overall survival of patients with gastroesophageal cancer in advanced stages. Since data on the correlation of endocrinological parameters and gastroesophageal cancer are scarce, this analysis is an important impulse for further studies concerning the impact of thyroxine on patients with cancer of the upper GI tract.

The success of immunotherapy in many disease entities is limited to a specific subpopulation of patients. To overcome this problem, dual blockade treatments mainly against cytotoxic T-lymphocyte-associated protein 4 (CTLA4) and programmed cell death receptor (ligand) 1 (PD-(L)1) axis were developed. However, due to high toxicity rates and treatment resistance, alternative pathways and novel strategies were desperately needed. Lymphocyte-associated gene 3 (LAG3) represents an inhibitory receptor, which is mainly found on activated immune cells and involved in the exhaustion of T cells in malignant diseases. Its co-expression with other inhibitory receptors, particularly with PD-1 leads to an extensive research on the blockade of LAG3 and PD-1 in preclinical settings. Interestingly, several in-vivo approaches demonstrated a highly significant clinical benefit under dual blockade, whereas the efficacy was very low in case of single agent targeting. Moreover, human tumour tissues showed co-expression of LAG3 and PD-1 in infiltrated lymphocytes, which again generated a rationale for blocking these both molecules in clinical settings. The ongoing clinical studies mainly use dual blockage of LAG3/PD-1, which demonstrated promising survival benefits and long duration of response rates. The following review focuses on the biological background and rationale of combining LAG3 with other agents and serves as an update on the state of clinical research on LAG3 targeting.

e14527 Background: Immune suppressive treatment is associated with an increased cancer risk due to its negative impact on immunosurveillance. We analyzed the association of immune suppressive treatment with the inflammatory tumor microenvironment and systemic inflammation parameters in patients with solid cancers after lung transplantation. Methods: Systemic inflammation was measured by neutrophil-to-lymphocyte ratio (NLR), leucocyte-to-lymphocyte ratio (LLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR) and CRP/albumin ratio (CRP/Alb) and analyzed at time of lung transplantation and time of tumor diagnosis. In tumor samples, the expression of tumor infiltrating lymphocytes (TIL) including CD3, CD8, CD45RO and PD-L1 using the Ventana Benchmark Ultra system for immunohistochemistry were investigated. Automated tissue analyses were performed for CD3, CD8 and CD45RO TIL (Definiens software). PD-L1 expression was determined by using the combined positive score (CPS). Results: 28 patients with cancer (10 lung cancer, 4 colorectal cancer, 2 renal cell carcinoma, 2 gastric cancer, 2 pancreatic cancer, 2 head&neck tumor, and others) were included in the study. Median time from transplantation to cancer diagnosis was 45 months (range 29-61). 57% (16/28) experienced a period of transplant rejection between transplantation and tumor diagnosis. Therefore, 25% (7/28) of the patients received intensified immunosuppression up to 8 weeks before tumor diagnosis. Median density of CD3+TIL was 5742 cells/ mm2 (range 3,203-8,429), median density of CD8+TIL was 6,363 cells/ mm2 (range 3,643-8,190), median density of CD45RO TIL was 72 cells/ mm2 (range 4-635) and median expression of PD-L1 was 60 (range 5-100) in tumor samples. No statistically significant changes in systemic inflammation were observed from time of transplantation to time of tumor diagnosis (p>0.05; Wilcoxon Signed-Rank Test). Furthermore, a history of transplant rejection before tumor diagnosis was not statistically significant associated with changes in TIL densities or systemic inflammation parameters (p>0.05; Mann Whitney U test). Conclusions: An activated local inflammatory tumor microenvironment as well as stable systemic inflammation characteristics were observed in our cohort. These results support the further development of immunotherapy as treatment approach also in cancer patients under immunosuppression after lung transplantation.[Table: see text]

Background: The frequency of endoscopically apparent gastrointestinal tract (GI) involvement in patients with mantle cell lymphoma (MCL) at diagnosis is thought to be in the range of 30%. While reports on GI involvement in MCL patients exist, most series lack a strict GI assessment due to the often asymptomatic nature of GI involvement. Owing to the standardized staging routine at our institution including GI assessment at diagnosis, we have analyzed the rate and prognostic impact of GI involvement in MCL. Methods: In this retrospective single-center evaluation, we have investigated GI involvement in 85 consecutive patients with MCL. All data were collected from clinical records. Results: MCL with and without endoscopically detectable GI involvement was reported in 29 (34%) patients and 56 patients (66%), respectively. The colon was involved in 21 (72%) and the stomach in 8 (28%). Eight of 29 patients (28%) had symptomatic GI involvement, and the primary diagnosis had been established in the GI tract in 3/29 (10%) of our patients. No statistical differences could be observed between both groups in terms of gender (p = 0.474), Eastern Cooperative Oncology Group (0.428), and MCL international prognostic index (0.543). Overall survival was longer in patients with GI involvement (116.0 vs. 74 months), but not statistically significant (p = 0.825). Conclusions: In our single center cohort, we did not find a clinical impact of GI involvement on the clinical course of MCL and no GI complications occurred during chemotherapy in these patients. As most patients were also asymptomatic, these data argue against a routine GI assessment in patients diagnosed with MCL.

Several clinical trials attempted to identify novel treatment options for advanced gastroesophageal tumours in first, second and further lines. Although results of targeted therapy regimens were mainly disappointing, novel immunotherapy agents showed promising activity, which led to their approval in second and third lines in many countries. This review focuses on the results of recent clinical trials investigating novel agents including targeted therapies, immunotherapy components and chemotherapies and discuss their current impact as well as current approval status on the treatment armamentarium of advanced gastroesophageal tumours.

Introduction Venous thromboembolism is a frequent complication in cancer patients and results in a considerable morbidity and mortality. The underlying mechanisms leading to the increased thrombotic risk are yet poorly understood. We have previously shown that levels of extracellular vesicles (EV) are elevated in patients with colorectal cancer compared to healthy control individuals (Hron et al, Thromb Haemost 2007;97:119-123). EV originate from blood or endothelial cells, or from the underlying tumor itself. They may contribute to coagulation activation and propagation by exposing tissue factor and by providing a surface for the interaction of coagulation factors. In that study, the number of EV was also positively correlated with levels of D-dimer, a fibrin split product and marker of coagulation activation. We hypothesize that number of EV and levels of D-dimer decline with decreasing tumor load during antineoplastic treatment. Therefore, the study aims at evaluating the long-term effect of chemotherapy on hemostatic system activation in patients with advanced colorectal cancer. Methods We conducted a pilot study including patients receiving chemotherapy because of advanced colorectal cancer. All chemotherapy regimens were based on 5-fluorouracilcombined with either oxaliplatin or irinotecan without or with an antibody (bevacizumab in 72%, cetuximab in 11%, and ramucirumab in 5% of patients, respectively). Patients were followed for 3 chemotherapy cycles. The study was approved by the local ethics committee, was conducted according to the Declaration of Helsinki and informed consent was obtained from all study patients. Venous blood was sampled at each cycle immediately before chemotherapy and was centrifuged at 2600 g for 15 minutes. The number of EV was assessed by flow cytometry using a FACSCalibur® flow cytometer with CellQuest™ software (Becton Dickinson) immediately after blood collection and centrifugation in fresh plasma. EV were defined by size (forward scatter, All outcome variables were log-transformed due to skewed distributions. The paired t-test was used to compare baseline (before the 1st chemotherapy) levels with measurements obtained from the 2nd and 3rd blood sampling. In order to provide a clearer legibility, all data is presented in absolute numbers and all values are given as median (quartiles) if not otherwise stated. Results 18 patients completed 3 cycles of chemotherapy. Their mean (± SD) age was 60.5 (± 12.2) years and 14 (78%) were men. None of the patients developed venous thromboembolism. Table 1 shows the levels of coagulation activation markers and the number of EV at baseline and before the 2nd and 3rd cycle of chemotherapy, respectively. D-dimer levels were 1.22 (0.42-2.31) µg mL-1 at baseline and significantly decreased over the course of treatment. D-dimer levels did not correlate with the number of EV either at baseline or at later time points. The number of EV decreased from 474 (312-617) x 103 mL-1 at baseline to 359 (239-474) x 103 mL-1 before the 3rd cycle. The proportion of tissue factor positive EV was small at baseline and throughout treatment. Levels of prothrombin fragment f1.2 did not change during treatment and did not correlate with number of EV at any time point. Conclusions In patients with advanced colorectal cancer chemotherapy attenuates coagulation activation as indicated by a decline of D-dimer levels and number of EV. These findings warrant further studies in a larger patient population and longer observation time. Table 1 Number of extracellular vesicles (EV) and markers of coagulation activation in plasma of colorectal cancer patients before and during chemotherapy Table 1. Number of extracellular vesicles (EV) and markers of coagulation activation in plasma of colorectal cancer patients before and during chemotherapy Disclosures No relevant conflicts of interest to declare.