In vivo PDX CRISPR/Cas9 screens reveal mutual therapeutic targets to overcome heterogeneous acquired chemo-resistance.

Resistance towards cancer treatment represents a major clinical obstacle, preventing cure of cancer patients. To gain mechanistic insights, we developed a model for acquired resistance to chemotherapy by treating mice carrying patient derived xenografts (PDX) of acute lymphoblastic leukemia with widely-used cytotoxic drugs for 18 consecutive weeks. In two distinct PDX samples, tumors initially responded to treatment, until stable disease and eventually tumor re-growth evolved under therapy, at highly similar kinetics between replicate mice.

Atezolizumab plus nab-paclitaxel for unresectable, locally advanced or metastatic breast cancer: real-world results from a single academic center in Austria.

Purpose: IMpassion130 led to the approval of atezolizumab plus nab-paclitaxel as first-line treatment for patients with unresectable locally advanced or metastatic triple-negative, PD-L1 immune-cell positive breast cancer (BC) by the European Medicines Agency (EMA). The objective of the present study was to investigate the implementation, safety and efficacy of this combination in the initial phase after approval.

Methods: A retrospective data analysis including all BC patients who received atezolizumab and nab-paclitaxel between 1.

Eribulin in Patients with Liposarcoma and Leiomyosarcoma: A Retrospective Single-Center Experience.

Introduction: Soft tissue sarcomas are rare and heterogenous malignancies with a poor prognosis in advanced disease stages. Eribulin is used in metastatic liposarcoma (LPS) patients, who have failed first-line chemotherapy and has been approved for use in patients with LPS in the USA and Europe due to its efficacy in this histological subtype in a phase 3 trial. We have evaluated efficacy and tolerability of eribulin in LPS and leiomyosarcoma (LMS) patients in the routine clinical setting at our department.

'It needs experience and courage': Awareness towards end of life communication practices in oncologists: A mixed methods study.

Objective: End of life communication (EOLC) is generally regarded as a challenging aspect of the medical profession, with high influences of culture, the physician's experience and awareness. The aim of the current study was to assess the awareness of Austrian oncologists towards EOLC practices in their daily clinical routine and to identify limiting and supporting factors of these conversations.

Methods: Overall, 45 oncologists participated in the assessment in this cross-sectional, mixed-method design using semi-structured interviews and questionnaire.

Hemostasis and cancer: Impact of haemostatic biomarkers for the prediction of clinical outcomes in patients with cancer.

Patients with cancer are characterized by a dysregulation of the hemostatic system and systemic hypercoagulability. Different components of the hemostatic system are involved in tumor-promoting mechanisms including primary tumor growth, cancer cell invasion, immune evasion, angiogenesis, and the metastatic process. Therefore, different degrees of systemic hemostatic activation in patients with cancer can reflect distinct underlying biological phenotypes of cancer and seem to correlate with cancer aggressiveness.

Heme Biosynthesis Factors and 5-ALA Induced Fluorescence: Analysis of mRNA and Protein Expression in Fluorescing and Non-fluorescing Gliomas.

Objective: The intraoperative visualization of adult-type diffuse gliomas with 5-aminolevulinic acid (5-ALA) induced fluorescence is widely used in the neurosurgical field. While visible 5-ALA induced fluorescence is found in the majority of high-grade gliomas, most low-grade gliomas lack visible fluorescence during surgery. Recently, the heme biosynthesis pathway was identified as crucial influencing factor for presence of visible fluorescence since it metabolizes 5-ALA to fluorescing Protoporphyrin IX (PpIX).

The Impact of Postoperative Tumor Burden on Patients With Brain Metastases.

Background: Brain metastases were considered to be well-defined lesions, but recent research points to infiltrating behavior. Impact of postoperative residual tumor burden (RTB) and extent of resection are still not defined enough.

Patients And Methods: Adult patients with surgery of brain metastases between April 2007 and January 2020 were analyzed.

ESMO 2021-my top three abstracts in breast cancer.

The congress of the European Society of Medical Oncology (ESMO) that recently took place virtually was marked by highlights in many different cancer types. New therapeutic options especially in metastatic breast cancer will hopefully bring a longer life to thousands of patients all over the world. These include new antibody-drug conjugates (ADCs) and checkpoint inhibitors as well as cyclin-dependent kinase (CDK)4/6 inhibitors prolonging overall survival.

Hematological prognosticators in metastatic renal cell cancer treated with immune checkpoint inhibitors: a meta-analysis.

We aimed to assess the prognostic value of pretreatment hematological biomarkers in patients with metastatic renal cell carcinoma (mRCC) treated with immune checkpoint inhibitors (ICIs). PubMed, Web of Science and Scopus databases were searched for articles according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Fifteen studies comprising 1530 patients were eligible for meta-analysis.

ABO blood group type and risk of venous thromboembolism in patients with cancer.

Venous thromboembolism (VTE) is common in patients with cancer. Although in the general population blood type non-O is associated with increased VTE risk, the impact of ABO blood type on risk of cancer-associated VTE has not been clarified. To determine the influence of ABO blood type on cancer-associated VTE risk, we conducted an analysis within the Vienna Cancer and Thrombosis Study, a prospective cohort study including patients with newly diagnosed or recurrent cancer observed for the primary outcome VTE.

Effect of concomitant statin treatment in postmenopausal patients with hormone receptor-positive early-stage breast cancer receiving adjuvant denosumab or placebo: a post hoc analysis of ABCSG-18.

Background: Statins are cholesterol-lowering drugs prescribed for the prevention and treatment of cardiovascular disease. Moreover, statins may possess anticancer properties and interact with receptor activator of nuclear factor κB ligand expression. We aimed at evaluating a hypothetical synergistic effect of statins with denosumab in early-stage breast cancer (BC) patients from the Austrian Breast and Colorectal Cancer Study Group (ABCSG) trial 18.

Efficacy, Outcome, and Safety of Elderly Patients with Glioblastoma in the 5-ALA Era: Single Center Experience of More Than 10 Years.

Background: In the next decades, the incidence of patients with glioblastoma (GBM) will increase due to the growth of the elderly population. Fluorescence-guided resection using 5-aminolevulinic acid (5-ALA) is widely applied to achieve maximal safe resection of GBM and is identified as a novel intraoperative marker for diagnostic tissue during biopsies. However, detailed analyses of the use of 5-ALA in resections as well as biopsies in a large elderly cohort are still missing.

Sensitive and robust liquid biopsy-based detection of PIK3CA mutations in hormone-receptor-positive metastatic breast cancer patients.

Background: The benefit of alpelisib in hormone-receptor-positive (HR+) metastatic breast cancer patients provided clinical evidence for the increasing importance of PIK3CA testing. We performed a comparison of liquid biopsy and tissue-based detection of PIK3CA mutations.

Materials And Methods: PIK3CA hotspot mutation analysis using a high-resolution SiMSen-Seq assay was performed in plasma from 93/99 eligible patients with HR+/HER2- breast cancer.

Integrated Molecular-Morphologic Meningioma Classification: A Multicenter Retrospective Analysis, Retrospectively and Prospectively Validated.

Purpose: Meningiomas are the most frequent primary intracranial tumors. Patient outcome varies widely from benign to highly aggressive, ultimately fatal courses. Reliable identification of risk of progression for individual patients is of pivotal importance.

Hemostatic Biomarkers and Venous Thromboembolism Are Associated With Mortality and Response to Chemotherapy in Patients With Pancreatic Cancer.

Objective: Pancreatic cancer activates coagulation and increases risk of venous thromboembolism (VTE). We aimed at characterizing the association of hemostatic biomarkers and VTE with mortality and chemotherapy response.

Approach And Results: Pancreatic cancer patients (N=145) were included in a prospective, observational cohort study (CATS [Vienna Cancer and Thrombosis Study]).

A STAT5B-CD9 axis determines self-renewal in hematopoietic and leukemic stem cells.

The transcription factors signal transducer and activator of transcription 5A (STAT5A) and STAT5B are critical in hematopoiesis and leukemia. They are widely believed to have redundant functions, but we describe a unique role for STAT5B in driving the self-renewal of hematopoietic and leukemic stem cells (HSCs/LSCs). We find STAT5B to be specifically activated in HSCs and LSCs, where it induces many genes associated with quiescence and self-renewal, including the surface marker CD9.

Differences in oncological and toxicity outcomes between programmed cell death-1 and programmed cell death ligand-1 inhibitors in metastatic renal cell carcinoma: A systematic review and meta-analysis.

Background: The programmed cell death ligand-1 (PD-L1)/programmed cell death-1 (PD-1) pathway is important in metastatic renal cell carcinoma (mRCC). However, some dissimilarities between anti-PD-1 and anti-PD-L1 inhibitors have emerged. We aimed to assess differences between anti-PD-1 and anti-PD-L1 combination immunotherapies as first-line treatments in mRCC patients.

Thyroid MALT lymphoma: self-harm to gain potential T-cell help.

The development of extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) is driven by chronic inflammatory responses and acquired genetic changes. To investigate its genetic bases, we performed targeted sequencing of 93 genes in 131 MALT lymphomas including 76 from the thyroid. We found frequent deleterious mutations of TET2 (86%), CD274 (53%), TNFRSF14 (53%), and TNFAIP3 (30%) in thyroid MALT lymphoma.

Tissue distribution of epirubicin after severe extravasation in humans.

Purpose: As critical parameter after extravasation of cytotoxic vesicants, anthracyclines were determined in removed tissue from patients requiring surgical intervention due to tissue necrosis. We monitored their distribution within the affected lesion to establish a possible dose-toxicity relation.

Methods: From six patients scheduled for surgery, removed tissue flaps were systematically analysed by HPLC (epirubicin: 5 subjects; doxorubicin: 1 subject).

Treatment of Angiosarcoma with Pazopanib and Paclitaxel: Results of the EVA (Evaluation of Votrient in Angiosarcoma) Phase II Trial of the German Interdisciplinary Sarcoma Group (GISG-06).

We aimed to evaluate the efficacy and toxicity of paclitaxel combined with pazopanib in advanced angiosarcoma (AS). The primary end point was progression-free survival (PFS) rate at six months (PFSR6). Planned accrual was 44 patients in order to detect a PFSR6 of >55%, with an interim futility analysis of the first 14 patients.

Conventional versus reverse sequence of neoadjuvant epirubicin/cyclophosphamide and docetaxel: sequencing results from ABCSG-34.

Background: Preoperative chemotherapy containing anthracyclines and taxanes is well established in early-stage breast cancer. Previous studies have suggested that the chemotherapy sequence may matter but definitive evidence is missing. ABCSG trial 34 evaluated the activity of the MUC1 vaccine tecemotide when added to neoadjuvant treatment; the study provided the opportunity for the second randomisation to compare two different anthracycline/taxane sequences.

Case Report: Afatinib Treatment in a Patient With NSCLC Harboring a Rare Exon 20 Mutation.

Unlike most other primary epidermal growth factor receptor () mutations in non-small cell lung cancer (NSCLC), exon 20 insertions, comprising approximately 4% to 10% of all mutations, are generally considered to be resistant to EGFR tyrosine kinase inhibitors (TKIs). However, exon 20 insertions are structurally and pharmacologically heterogeneous, with variability in their position and size having implications for response to different EGFR TKIs. The second-generation ErbB family blocker, afatinib, is approved for the first-line treatment of mutation-positive NSCLC and has been shown to have a broad inhibitory profile against common and uncommon mutations.