An In-Depth Evaluation of the Validity and Logistics Surrounding the Testing of AR-V7 mRNA Expression in Circulating Tumor Cells.

Recent reports have emphasized the clinical relevance of detecting AR-V7 in circulating tumor cells (CTCs). Our aim was to set up a validated multicenter pipeline to measure AR-V7 by quantitative RT-PCR (RT-qPCR) in RNA isolated from CellSearch-enriched CTCs to provide an AR-V7-positive or AR-V7-negative score in a clinically acceptable time range. CellSearch-enirched CTCs from patients with metastatic castration-resistant prostate cancer were characterized by RT-qPCR.

Immune Infiltration in Invasive Lobular Breast Cancer.

Background: Invasive lobular breast cancer (ILC) is the second most common histological subtype of breast cancer after invasive ductal cancer (IDC). Here, we aimed at evaluating the prevalence, levels, and composition of tumor-infiltrating lymphocytes (TILs) and their association with clinico-pathological and outcome variables in ILC, and to compare them with IDC.

Methods: We considered two patient series with TIL data: a multicentric retrospective series (n = 614) and the BIG 02-98 study (n = 149 ILC and 807 IDC).

Circulating tumor cells and survival in abiraterone- and enzalutamide-treated patients with castration-resistant prostate cancer.

Background: The outcome to treatment administered to patients with metastatic castration-resistant prostate cancer (mCRPC) greatly differs between individuals, underlining the need for biomarkers guiding treatment decision making.

Objective: To investigate the prognostic value of circulating tumor cell (CTC) enumeration and dynamics, in the context of second-line endocrine therapies (ie, abiraterone acetate or enzalutamide), irrespective of prior systemic therapies.

Design, Settings, And Participants: In a prospective, multicentre study blood samples for CTC enumeration were collected from patients with mCRPC at baseline (n = 174).

How glucose, glutamine and fatty acid metabolism shape blood and lymph vessel development.

Recently, endothelial cell metabolism has emerged as an essential driver and regulator of both blood and lymph vessel development. Evidence rapidly builds that metabolism is not only necessary for endothelial cell function, but moreover controls several aspects of the (lymph)-angiogenic process. So far, the best-characterized metabolic pathways to have an impact on angiogenesis are glycolysis, fatty acid oxidation and glutamine metabolism.

Differential impact of RB status on E2F1 reprogramming in human cancer.

The tumor suppressor protein retinoblastoma (RB) is mechanistically linked to suppression of transcription factor E2F1-mediated cell cycle regulation. For multiple tumor types, loss of RB function is associated with poor clinical outcome. RB action is abrogated either by direct depletion or through inactivation of RB function; however, the basis for this selectivity is unknown.

Hepatic safety analysis of trabectedin: results of a pharmacokinetic study with trabectedin in patients with hepatic impairment and experience from a phase 3 clinical trial.

Purpose Trabectedin is metabolized by the liver and has been associated with transient, noncumulative transaminase elevation. Two recent studies further characterize hepatic tolerability with trabectedin therapy: a phase 1 pharmacokinetic study (Study #1004; NCT01273493) in patients with advanced malignancies and hepatic impairment (HI), and a phase 3 study (Study #3007; NCT01343277) of trabectedin vs. dacarbazine in patients with advanced sarcomas and normal hepatic function.

Estrogen receptor mutations and splice variants determined in liquid biopsies from metastatic breast cancer patients.

Mutations and splice variants in the estrogen receptor (ER) gene, ESR1, may yield endocrine resistance in metastatic breast cancer (MBC) patients. These putative endocrine resistance markers are likely to emerge during treatment, and therefore, its detection in liquid biopsies, such as circulating tumor cells (CTCs) and cell-free DNA (cfDNA), is of great interest. This research aimed to determine whether ESR1 mutations and splice variants occur more frequently in CTCs of MBC patients progressing on endocrine treatment.

Avelumab, an anti-PD-L1 antibody, in patients with locally advanced or metastatic breast cancer: a phase 1b JAVELIN Solid Tumor study.

Purpose: Agents targeting programmed death receptor 1 (PD-1) or its ligand (PD-L1) have shown antitumor activity in the treatment of metastatic breast cancer (MBC). The aim of this study was to assess the activity of avelumab, a PD-L1 inhibitor, in patients with MBC.

Methods: In a phase 1 trial (JAVELIN Solid Tumor; NCT01772004), patients with MBC refractory to or progressing after standard-of-care therapy received avelumab intravenously 10 mg/kg every 2 weeks.

Assessing Tumor-Infiltrating Lymphocytes in Solid Tumors: A Practical Review for Pathologists and Proposal for a Standardized Method from the International Immuno-Oncology Biomarkers Working Group: Part 2: TILs in Melanoma, Gastrointestinal Tract Carcinomas, Non-Small Cell Lung Carcinoma and Mesothelioma, Endometrial and Ovarian Carcinomas, Squamous Cell Carcinoma of the Head and Neck, Genitourinary Carcinomas, and Primary Brain Tumors.

Assessment of the immune response to tumors is growing in importance as the prognostic implications of this response are increasingly recognized, and as immunotherapies are evaluated and implemented in different tumor types. However, many different approaches can be used to assess and describe the immune response, which limits efforts at implementation as a routine clinical biomarker. In part 1 of this review, we have proposed a standardized methodology to assess tumor-infiltrating lymphocytes (TILs) in solid tumors, based on the International Immuno-Oncology Biomarkers Working Group guidelines for invasive breast carcinoma.

Assessing Tumor-infiltrating Lymphocytes in Solid Tumors: A Practical Review for Pathologists and Proposal for a Standardized Method From the International Immunooncology Biomarkers Working Group: Part 1: Assessing the Host Immune Response, TILs in Invasive Breast Carcinoma and Ductal Carcinoma In Situ, Metastatic Tumor Deposits and Areas for Further Research.

Assessment of tumor-infiltrating lymphocytes (TILs) in histopathologic specimens can provide important prognostic information in diverse solid tumor types, and may also be of value in predicting response to treatments. However, implementation as a routine clinical biomarker has not yet been achieved. As successful use of immune checkpoint inhibitors and other forms of immunotherapy become a clinical reality, the need for widely applicable, accessible, and reliable immunooncology biomarkers is clear.

Localized prostate cancer and robot-assisted laparoscopic radical prostatectomy: a retrospective, comparative study between pre- and post-operative Gleason scores.

Introduction: To compare the pre- and post-operative Gleason scores (GS) in patients with localized prostate cancer treated with robot-assisted laparoscopic radical prostatectomy.

Materials And Methods: A single center, retrospective comparison between pre- and post-operative GS. Age, prostate volume, PSA, number of biopsies, number of positive cores, biopsy GS, cTNM, final pathology GS and pTNM of 286 patients were retrieved.

The Modified Low Back Pain Disability Questionnaire: Reliability, Validity, and Responsiveness of a Dutch Language Version.

Study Design: Cross-sectional study.

Objective: The goal of this study is to translate the English version of the Modified Low Back Pain Disability Questionnaire (MDQ) into a Dutch version and investigate its clinimetric properties for patients with nonspecific chronic low back pain (CLBP).

Summary Of Background Data: Fritz et al (2001) developed a modified version of the Oswestry Disability Questionnaire (ODI) to assess functional status and named it the MDQ.

Prospective double blind randomized placebo-controlled clinical trial of the pectoral nerves (Pecs) block type II.

Study Objective: The aim of this clinical trial was to test the hypothesis whether adding the pectoral nerves (Pecs) block type II to the anesthetic procedure reduces opioid consumption during and after breast surgery.

Design: A prospective randomized double blind placebo-controlled study.

Setting: A secondary hospital.

The MO-meatocanalplasty: a modification of the M-meatoplasty to address the superior quadrants and the bony canal.

The meatoplasty of the external auditory canal is a frequently performed otologic procedure in recurrent otitis externa, eczema or frequent accumulation of cerumen due to a narrow meatus of the external ear canal. Numerous surgical techniques have been described. The M-meatoplasty described by Mirck for addressing the external meatus is widely used.

Association of Gestational Weight Gain With Maternal and Infant Outcomes: A Systematic Review and Meta-analysis.

Importance: Body mass index (BMI) and gestational weight gain are increasing globally. In 2009, the Institute of Medicine (IOM) provided specific recommendations regarding the ideal gestational weight gain. However, the association between gestational weight gain consistent with theIOM guidelines and pregnancy outcomes is unclear.

Measuring the Dysphonia Severity Index (DSI) in the Program Praat.

Background: The original Dysphonia Severity Index (ie, DSI) weighs and combines four voice markers in a single number to size dysphonia gradation in the clinic: percent jitter (from Multi-Dimensional Voice Program; KayPENTAX Corp., Montvale, NJ), softest intensity and highest fundamental frequency (both from Voice Range Profile; KayPENTAX Corp.), and maximum phonation time.

Perforator free flaps in head and neck reconstruction: a single-center low-volume experience.

Objective: The aim of this article is to investigate the results of free-flap reconstructions in the head and neck area in a secondary low-volume institution and compare these with the literature.

Study Design: A retrospective study was performed of all patients who underwent free-flap reconstructive surgery in our institution from January 9, 2011, to July 12, 2015, by one young surgeon in a one-team approach. The types of flaps applied, defect sites, pathology, anastomotic details, success and complication rates, lengths of stay, and patients' ages and comorbidities were analyzed.

Treating patients with Dynamic Wave Arc: First clinical experience.

Background And Purpose: Dynamic Wave Arc (DWA) is a system-specific noncoplanar arc technique that combines synchronized gantry-ring rotation with D-MLC optimization. This paper presents the clinical workflow, quality assurance program, and reports the geometric and dosimetric results of the first patient cohort treated with DWA.

Methods And Materials: The RayStation TPS was clinically integrated on the Vero SBRT platform for DWA treatments.

Comprehensive Profiling of the Androgen Receptor in Liquid Biopsies from Castration-resistant Prostate Cancer Reveals Novel Intra-AR Structural Variation and Splice Variant Expression Patterns.

Background: Expression of the androgen receptor splice variant 7 (AR-V7) is associated with poor response to second-line endocrine therapy in castration-resistant prostate cancer (CRPC). However, a large fraction of nonresponding patients are AR-V7-negative.

Objective: To investigate if a comprehensive liquid biopsy-based AR profile may improve patient stratification in the context of second-line endocrine therapy.

ATR inhibitors as a synthetic lethal therapy for tumours deficient in ARID1A.

Identifying genetic biomarkers of synthetic lethal drug sensitivity effects provides one approach to the development of targeted cancer therapies. Mutations in ARID1A represent one of the most common molecular alterations in human cancer, but therapeutic approaches that target these defects are not yet clinically available. We demonstrate that defects in ARID1A sensitize tumour cells to clinical inhibitors of the DNA damage checkpoint kinase, ATR, both in vitro and in vivo.

Prognostic Impact of HER2 and ER Status of Circulating Tumor Cells in Metastatic Breast Cancer Patients with a HER2-Negative Primary Tumor.

Background: Preclinical and clinical studies have reported that human epidermal growth factor receptor 2 (HER2) overexpression yields resistance to endocrine therapies. Here the prevalence and prognostic impact of HER2-positive circulating tumor cells (CTCs) were investigated retrospectively in metastatic breast cancer (MBC) patients with a HER2-negative primary tumor receiving endocrine therapy. Additionally, the prevalence and prognostic significance of HER2-positive CTCs were explored in a chemotherapy cohort, as well as the prognostic impact of the estrogen receptor (ER) CTC status in both cohorts.

mRNA expression profiles of colorectal liver metastases as a novel biomarker for early recurrence after partial hepatectomy.

Background: Identification of specific risk groups for recurrence after surgery for isolated colorectal liver metastases (CRLM) remains challenging due to the heterogeneity of the disease. Classical clinicopathologic parameters have limited prognostic value. The aim of this study was to identify a gene expression signature measured in CRLM discriminating early from late recurrence after partial hepatectomy.

Mobile Communication Devices, Ambient Noise, and Acoustic Voice Measures.

Objectives: The ability to move with mobile communication devices (MCDs; ie, smartphones and tablet computers) may induce differences in microphone-to-mouth positioning and use in noise-packed environments, and thus influence reliability of acoustic voice measurements. This study investigated differences in various acoustic voice measures between six recording equipments in backgrounds with low and increasing noise levels.

Methods: One chain of continuous speech and sustained vowel from 50 subjects with voice disorders (all separated by silence intervals) was radiated and re-recorded in an anechoic chamber with five MCDs and one high-quality recording system.

Breast cancer genome and transcriptome integration implicates specific mutational signatures with immune cell infiltration.

A recent comprehensive whole genome analysis of a large breast cancer cohort was used to link known and novel drivers and substitution signatures to the transcriptome of 266 cases. Here, we validate that subtype-specific aberrations show concordant expression changes for, for example, TP53, PIK3CA, PTEN, CCND1 and CDH1. We find that CCND3 expression levels do not correlate with amplification, while increased GATA3 expression in mutant GATA3 cancers suggests GATA3 is an oncogene.