Immune checkpoint inhibitors in mCRPC - rationales, challenges and perspectives.

The advancement of immune-therapeutics in cancer treatment has proven to be promising in various malignant diseases. However, in castration resistant prostate cancer (mCRPC) major Phase III trials have been unexpectedly disappointing. To contribute to a broader understanding of the role and use of immune-therapeutics in mCRPC, we conducted a systematic review.

Ex vivo properties of plasma clot formation and lysis in patients with cancer at risk for venous thromboembolism, arterial thrombosis, and death.

A prothrombotic state is frequently observed in patients with cancer and contributes to the risks of venous thromboembolism (VTE), arterial thromboembolism (ATE), tumor progression, and death. Altered ex vivo properties of plasma clot formation and lysis have been observed in patients with cancer. The aim of this prospective study was to comprehensively characterize the relationship between plasma clot properties, inflammation, hypercoagulability, thrombotic complications, and mortality in patients with cancer using a tissue-factor-based turbidimetric assay of clot formation and lysis.

The PERSONS score: A new tool for cancer patients' symptom assessment in simultaneous care and home care settings.

Background: Scientific societies recommend early interaction between oncologic and supportive care, but there is still a lack of systematic evaluations regarding symptoms from the perspective of oncologists.

Patients And Methods: The aim of this prospective study was to evaluate the PERSONS score, in both "simultaneous care" and "supportive care" settings using the Edmonton Symptom Assessment Scale (ESAS) as a comparator.

Results: From November 2017 to April 2018, 67 and 110 consecutive patients were enrolled in outpatient and home care cohorts, respectively.

Immune checkpoint inhibitor treatment in patients with oncogene- addicted non-small cell lung cancer (NSCLC): summary of a multidisciplinary round-table discussion.

The introduction of targeted treatments and more recently immune checkpoint inhibitors (ICI) to the treatment of metastatic non-small cell lung cancer (NSCLC) has dramatically changed the prognosis of selected patients. For patients with oncogene-addicted metastatic NSCLC harbouring an epidermal growth factor receptor () or v-Raf murine sarcoma viral oncogene homologue B1 () mutation or an anaplastic lymphoma kinase () or ROS proto-oncogene 1, receptor tyrosine kinase () gene alteration (translocation, fusion, amplification) mutation-specific tyrosine kinase inhibitors (TKI) are already first-line standard treatment, while targeted treatment for other driver mutations affecting human epidermal growth factor receptor ( 2, tropomyosin receptor kinases () 1-3 and others are currently under investigation. The role of ICI in these patient subgroups is currently under debate.

The role of ADAMTS-13 and von Willebrand factor in cancer patients: Results from the Vienna Cancer and Thrombosis Study.

Background: Cancer-associated venous thromboembolism (VTE) is an important complication in the course of a malignant disease. Low ADAMTS-13 (a disintegrin-like and metalloproteinase with thrombospondin type 1 motif 13) and increased von Willebrand Factor (VWF) levels in cancer patients have been described numerously.

Objectives: Investigation of the influence of ADAMTS-13 and VWF on the probability of VTE and survival in malignancy.

Prolonged follow-up on lenalidomide-based treatment for mucosa-associated lymphoid tissue lymphoma (MALT lymphoma)-Real-world data from the Medical University of Vienna.

Based on results of two pilot trials, lenalidomide (LEN) was found to be active and safe as monotherapy and showed an increased response rate of 80% in combination with rituximab (R) for patients with mucosa-associated lymphoid tissue (MALT) lymphoma. While initial results were promising, there are currently no data on long-term outcome, and larger international phase II/III trials on LEN for indolent lymphoma lack specific subgroup analyses. Thus, we have systematically analyzed 50 patients treated with LEN-based therapy (LEN-monotherapy n = 16, R-LEN n = 34) at the Medical University of Vienna 2009 to 2019 and investigated long-term outcome and relapse patterns.

Signet Ring Cell Carcinoma of the Lung: A Diagnostic Pitfall in Pregnancy.

Lung cancer during pregnancy represents a rare disease. In this case report, we present a patient at advanced and metastasized stage of signet ring cell carcinoma who presented in the 22 week of gestation.

New emerging targets in cancer immunotherapy: the role of Cluster of Differentiation 40 (CD40/TNFR5).

Cluster of differentiation 40 (CD40) is a member of the tumour necrosis factor family and a new immune-modulating target in cancer treatment. B cells, myeloid cells and dendritic cells can express CD40 and mediate via the ligand cluster of differentiation 40 ligand (CD40L) cytotoxic T cell priming under physiological conditions. Therapeutically, recombinant CD40L molecules, intratumour application of adenoviral vectors leading to CD40L expression and agonistic monoclonal CD40 antibodies are currently tested in various cancer entities for their immune-modulating potential.

How we treat patients with leptomeningeal metastases.

The goal of treatment of leptomeningeal metastasis is to improve survival and to maintain quality of life by delaying neurological deterioration. Tumour-specific therapeutic options include intrathecal pharmacotherapy, systemic pharmacotherapy and focal radiotherapy. Recently, improvement of leptomeningeal disease-related progression-free survival by adding intrathecal liposomal cytarabine to systemic treatment versus systemic treatment alone has been observed in a randomised phase III trial for patients with breast cancer with newly diagnosed leptomeningeal metastasis.

DNA methylation profiling to predict recurrence risk in meningioma: development and validation of a nomogram to optimize clinical management.

Background: Variability in standard-of-care classifications precludes accurate predictions of early tumor recurrence for individual patients with meningioma, limiting the appropriate selection of patients who would benefit from adjuvant radiotherapy to delay recurrence. We aimed to develop an individualized prediction model of early recurrence risk combining clinical and molecular factors in meningioma.

Methods: DNA methylation profiles of clinically annotated tumor samples across multiple institutions were used to develop a methylome model of 5-year recurrence-free survival (RFS).

Transformed mucosa-associated lymphoid tissue lymphomas: A single institution retrospective study including polymerase chain reaction-based clonality analysis.

Given the lack of consistent data regarding the clinico-pathological features and clonal lymphomagenesis of patients with mucosa-associated lymphoid tissue (MALT) lymphoma and histological transformation (HT), we have systematically analysed 379 patients (32% gastric, 68% extra-gastric; median follow-up 52 months) diagnosed with HT at the Medical University Vienna 1999-2017, and reassessed tissues of identified patients by polymerase chain reaction (PCR)-based clonality analysis. HT was documented in 12/379 patients (3·2%) and occurred at a median time of 22 months (range; 6-202 months) after diagnosis of MALT lymphoma. By PCR-based clonality analysis, we detected a clear-cut clonal relationship of MALT lymphoma and diffuse large B-cell lymphoma (DLBCL) in 8 of 11 analysed cases proving that the large majority of DLBCL following MALT lymphoma are clonally-related and constitute a real transformation.

Association of complete blood count parameters, d-dimer, and soluble P-selectin with risk of arterial thromboembolism in patients with cancer.

Background: Patients with cancer are at risk of developing arterial thromboembolism (ATE). With the prevalence of cancer and cardiovascular diseases on the rise, the identification of risk factors for ATE in patients with cancer is of emerging importance.

Objectives: As data on the association of potential biomarkers with risk of ATE in patients with cancer are scarce, we conducted a cohort study with the aim to identify blood-based biomarkers for ATE risk prediction in patients with cancer.

EGFR Controls Hair Shaft Differentiation in a p53-Independent Manner.

Epidermal growth factor receptor (EGFR) signaling controls skin development and homeostasis in mice and humans, and its deficiency causes severe skin inflammation, which might affect epidermal stem cell behavior. Here, we describe the inflammation-independent effects of EGFR deficiency during skin morphogenesis and in adult hair follicle stem cells. Expression and alternative splicing analysis of RNA sequencing data from interfollicular epidermis and outer root sheath indicate that EGFR controls genes involved in epidermal differentiation and also in centrosome function, DNA damage, cell cycle, and apoptosis.

Migrate your mind: the role of palliative care in transcultural cancer treatment : A qualitative analysis.

Background: In increasingly multi-ethnic societies fostering cultural awareness and integration of immigrants is not only a political duty but also an obligation for social and healthcare systems. Importantly, cultural beliefs and needs strongly impact on the quality of life of cancer patients and may become even more crucial at the end of life. However, to date, ethnic and cultural aspects of palliative care are insufficiently researched.

Citrullinated histone H3, a biomarker for neutrophil extracellular trap formation, predicts the risk of mortality in patients with cancer.

Prior studies indicate that neutrophil extracellular traps (NETs) are associated with arterial thromboembolism (ATE) and mortality. We investigated the association between NET formation biomarkers (citrullinated histone H3 [H3Cit], cell-free DNA [cfDNA], and nucleosomes) and the risk of ATE and all-cause mortality in patients with cancer. In this prospective cohort study, H3Cit, cfDNA and nucleosome levels were determined at study inclusion, and patients with newly diagnosed cancer or progressive disease after remission were followed for 2 years for ATE and death.

Renal Cell Carcinoma with Sarcomatoid Features: Finally New Therapeutic Hope?

Renal cell carcinoma (RCC) with sarcomatoid differentiation belongs to the most aggressive clinicopathologic phenotypes of RCC. It is characterized by a high propensity for primary metastasis and limited therapeutic options due to its relative resistance to established systemic targeted therapy. Most trials report on a poor median overall survival of 5 to 12 months.

The circulating form of neprilysin is not a general biomarker for overall survival in treatment-naïve cancer patients.

The transmembrane zink-metalloendopeptidase neprilysin (NEP) is implicated in cardiovascular disease but also tumor biology. The aim of the study was to investigate the relationship of circulating NEP (cNEP) levels with established cardiovascular biomarkers and its effect on overall survival in an unselected cohort of treatment-naïve cancer patients. 555 consecutive cancer patients prior anticancer therapy were enrolled prospectively.

Avelumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma.

Background: In a single-group, phase 1b trial, avelumab plus axitinib resulted in objective responses in patients with advanced renal-cell carcinoma. This phase 3 trial involving previously untreated patients with advanced renal-cell carcinoma compared avelumab plus axitinib with the standard-of-care sunitinib.

Methods: We randomly assigned patients in a 1:1 ratio to receive avelumab (10 mg per kilogram of body weight) intravenously every 2 weeks plus axitinib (5 mg) orally twice daily or sunitinib (50 mg) orally once daily for 4 weeks (6-week cycle).

Gastrointestinal Involvement in Patients with Mantle Cell Lymphoma: A Single Center Experience of Eighty-Five Patients.

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.

Continued Endocrine Therapy Is Associated with Improved Survival in Patients with Breast Cancer Brain Metastases.

Purpose: Brain metastases (BMs) are a rare but devastating condition in estrogen receptor (ER)-positive metastatic breast cancer (MBC). Although endocrine therapy (ET) is the mainstay of treatment in this disease subtype, only case reports have been published concerning the activity of ET in BMs henceforth. Therefore, we aimed to systematically investigate the impact of ET after diagnosis of BM on outcome and clinical course of disease in patients with ER-positive MBC.

ASCO 2018: highlights in HER2-positive metastatic breast cancer.

At the 2018 ASCO Annual Meeting, data from several interesting studies in HER2-positive metastatic breast cancer were presented. While not immediately practice changing, these trials indicate the future directions of drug development in this field. Early phase studies with novel antibody-drug conjugates (ADCs) such as trastuzumab-deruxtecan and trastuzumab-duocarmazine suggest relevant clinical activity of these drugs in pretreated patients; in addition, these ADCs may offer activity in low HER2-expressing tumours as well.