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.

IMPORTANCETo 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 PARTICIPANTSThis 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 MEASURESTotal 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 RELEVANCEIn 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.

BackgroundDuring the COVID-19 outbreak, healthcare professionals (HCP) are at the frontline of clinical management and at increased risk for infection. The SARS-CoV-2 seroprevalence of oncological HCP and their patients has significant implications for oncological care.MethodsHCP and patients with cancer at the Division of Oncology, Medical University of Vienna were included between 21 March and 4 June and tested for total antibodies against SARS-CoV-2 employing the Roche Elecsys Anti-SARS-CoV-2 immunoassay. Reactive samples were confirmed or disproved by the Abbott SARS-CoV-2 IgG test. Additionally, a structured questionnaire regarding basic demographic parameters, travel history and COVID-19-associated symptoms had to be completed by HCP.Results146 subjects (62 HCP and 84 patients with cancer) were enrolled. In the oncological HCP cohort, 20 (32.3%) subjects were medical oncologists, 28 (45.2%) nurses at our ward and 14 (22.6%) fulfil other functions such as study coordinators. In the patient cohort, most individuals are on active anticancer treatment (96.4%). 26% of the HCP and 6% of the patients had symptoms potentially associated with COVID-19 since the end of February 2020. However, only in 2 (3.2%) HCP and in 3 (3.6%) patients, anti-SARS-Cov-2 total antibodies were detected. The second assay for anti-SARS-Cov-2 IgG antibodies confirmed the positive result in all HCP and in 2 (2.4%) patients, suggesting an initial assay’s unspecific reaction in one case. In individuals with a confirmed test result, an active COVID-19 infection was documented by a positive SARS-CoV-2 RNA PCR test.ConclusionSpecific anti-SARS-CoV-2 antibodies were found solely in persons after a documented SARS-CoV-2 viral infection, thus supporting the test methods’ high sensitivity and specificity. The low prevalence of anti-SARS-CoV-2 antibodies in our cohorts indicates a lack of immunity against SARS-CoV-2. It highlights the need for continued strict safety measures to prevent uncontrolled viral spread among oncological HCPs and patients with cancer.

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.

ObjectivePost‐traumatic stress disorder (PTSD) is a severe psychiatric disorder, which might develop after a traumatic event, like cancer diagnosis, and threatens the patient's psychological and/or physiological integrity. Anxiety, depression, and mental distress are known to be common in cancer patients; however, the frequency of PTSD was not investigated thoroughly in this patient group so far. Here, we aim to screen cancer patients for PTSD symptoms and determine a possible correlation with anxiety, depression, and distress.MethodsThe study was performed at the Divisions of Hematology and Oncology of the Medical University of Vienna from 2010 to 2018. Following written consent, patients were asked to fill out the validated self‐assessment questionnaire for PTSS‐10 and HADS. The study was approved by the institutional ethics committee of the Medical University of Vienna (EC Nr: 2255/2016).ResultsA total of 1017 adult cancer patients (513 male, 504 female) were included in a cross‐sectional single‐center study. Mean age was 57.6 years (SD 14.4 years); 31.7%, 14.6%, 13.2%, and 27.4% of patients outscored the predefined thresholds for self‐assessed cases of PTSD, anxiety, depression, and distress, respectively. Compared with men, women showed a higher prevalence of symptoms for PTSD (38.9% vs 24.5%; P < .001) and anxiety (20.4% vs 8.6%; P < .001). The scores of HADS‐A, HADS‐D, and the combined HADS score (distress) were significantly correlated with PTSS‐10 scores (P < .01). No differences in age were observed among the different score groups.ConclusionThe study shows a significant prevalence as well as a correlation of PTSD symptoms with anxiety, depression, and distress among cancer patients. Findings underscore the necessity of a serious screening for psychiatric disorders, especially in female patients. In order to enable multidisciplinary care for cancer patients and to reduce the burden for psychiatric disorders, interdisciplinary screening and treatment concepts, which take into account gender aspects, are urged.

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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.

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. Keywords Gastric. Esophagus. Gastroesophageal. Hyperthyroidism. Thyroxine Abbreviations BMI Body mass index fT3 Free triiodothyronine fT4 Free thyroxine GI Gastrointestinal NTIS Nonthyroidal illness syndrome