Social supports in patients with cancer attending an Irish cancer center: a cross-sectional study.

A positive association has been demonstrated between social supports, quality of life, and survival outcomes in cancer. This study assessed levels of social supports among patients with cancer in an Irish institution, with an age- and gender-specific stratification. The study highlights relatively low levels of perceived socio-emotional support and social connectedness, but good levels of tangible and informational support in our cohort of patients with cancer.

Evaluation of ABT-751, a novel anti-mitotic agent able to overcome multi-drug resistance, in melanoma cells.

Purpose: Drug efflux transporter associated multi-drug resistance (MDR) is a potential limitation in the use of taxane chemotherapies for the treatment of metastatic melanoma. ABT-751 is an orally bioavailable microtubule-binding agent capable of overcoming MDR and proposed as an alternative to taxane-based therapies.

Methods: This study compares ABT-751 to taxanes in vitro, utilizing seven melanoma cell line models, publicly available gene expression and drug sensitivity databases, a lung cancer cell line model of MDR drug efflux transporter overexpression (DLKP-A), and drug efflux transporter ATPase assays.

miRNAs as biomarkers of therapeutic response to HER2-targeted treatment in breast cancer: A systematic review.

Breast cancer is the most common type of lethal cancer in women globally. Women have a 1 in 8 chance of developing breast cancer in their lifetime. Among the four primary molecular subtypes (luminal A, luminal B, HER2+, and triple-negative), HER2+ accounts for 20-25 % of all breast cancer and is rather aggressive.

Acanthosis Nigricans in a Patient with Urothelial Carcinoma Treated with PD-L1 Inhibitor Avelumab, and Secondary Adrenal Insufficiency.

Acanthosis nigricans (AN) describes hyperkeratotic and hyperpigmented skin changes and its pathophysiology is linked to the activation of epidermal growth factor receptors. Current literature shows that AN is most commonly diagnosed at the time of the underlying pathology, which may occur under benign or malignant conditions. This case presentation demonstrates the occurrence of AN in a patient following the diagnosis of urothelial carcinoma and ongoing treatment with PD-L1 inhibitor immunotherapy.

Clinical and Genomic Characterization of Bladder Carcinomas With Glandular Phenotype.

Purpose: To compare oncologic outcomes and genomic alteration profiles in patients with bladder and urachal adenocarcinoma, urothelial carcinoma (UC) with glandular differentiation, and UC, not otherwise specified (NOS) undergoing surgical resection, with emphasis on response to systemic therapy.

Methods: We identified patients with bladder cancer with glandular variants who underwent surgical resection at Memorial Sloan Kettering from 1995 to 2018 (surgical cohort) and/or patients who had tumor sequencing using a targeted next-generation sequencing platform (genomics cohort). Pathologic complete and partial response rates to neoadjuvant chemotherapy (NAC) and recurrence-free and cancer-specific survival were measured.

Adenoid cystic carcinoma of the prostate - A rare case of genitourinary malignancy.

A 72 year old was referred to the Urology department with lower urinary tract symptoms (LUTS), an abnormal prostate on digital examination and a serum prostate specific antigen (PSA) level within normal limits. A flexible cystoscopy revealed no abnormality of the urethra and an obstructive prostate. Magnetic resonance imaging (MRI) revealed a 4.

The prognostic value of the derived neutrophil-to-lymphocyte ratio (dNLR) in patients treated with immune checkpoint inhibitors.

Background: The (derived) neutrophil-to-lymphocyte ratio (dNLR) is a potential predictive biomarker in the era of checkpoint inhibitors (CPI). An elevated dNLR is associated with worse outcomes across several malignancies. However, there is no clearly defined cut-off in the clinical setting.

Pregnancy-associated breast cancer: evaluating maternal and foetal outcomes. A national study.

Purpose: Pregnancy-associated breast cancer (PABC) is defined as breast cancer diagnosed during the gestational period (gp-PABC) or in the first postpartum year (pp-PABC). Despite its infrequent occurrence, the incidence of PABC appears to be rising due to the increasing propensity for women to delay childbirth. We have established the first retrospective registry study of PABC in Ireland to examine specific clinicopathological characteristics, treatments, and maternal and foetal outcomes.

AKT1 E17K Inhibits Cancer Cell Migration by Abrogating β-Catenin Signaling.

Mutational activation of the PI3K/AKT pathway is among the most common pro-oncogenic events in human cancers. The clinical utility of PI3K and AKT inhibitors has, however, been modest to date. Here, we used CRISPR-mediated gene editing to study the biological consequences of AKT1 E17K mutation by developing an AKT1 E17K-mutant isogenic system in a -null background.

Second-line chemotherapy in advanced biliary cancers: A retrospective, multicenter analysis of outcomes.

Background: Although gemcitabine plus platinum chemotherapy is the established first-line regimen for advanced biliary cancer (ABC), there is no standard second-line therapy. This study evaluated current practice and outcomes for second-line chemotherapy in patients with ABC across 3 US academic medical centers.

Methods: Institutional registries were reviewed to identify patients who had received second-line chemotherapy for ABC from April 2010 to March 2015 along with their demographics, diagnoses and staging, treatment histories, and clinical outcomes.

Harnessing Clinical Sequencing Data for Survival Stratification of Patients with Metastatic Lung Adenocarcinomas.

Purpose: Broad panel sequencing of tumors facilitates routine care of people with cancer as well as clinical trial matching for novel genome-directed therapies. We sought to extend the use of broad panel sequencing results to survival stratification and clinical outcome prediction.

Patients And Methods: Using sequencing results from a cohort of 1,054 patients with advanced lung adenocarcinomas, we developed OncoCast, a machine learning tool for survival risk stratification and biomarker identification.

Tumor mutational load predicts survival after immunotherapy across multiple cancer types.

Immune checkpoint inhibitor (ICI) treatments benefit some patients with metastatic cancers, but predictive biomarkers are needed. Findings in selected cancer types suggest that tumor mutational burden (TMB) may predict clinical response to ICI. To examine this association more broadly, we analyzed the clinical and genomic data of 1,662 advanced cancer patients treated with ICI, and 5,371 non-ICI-treated patients, whose tumors underwent targeted next-generation sequencing (MSK-IMPACT).

Obesity and cardiovascular risk in an oncology day ward population.

Introduction: The burden of obesity and risk of cardiovascular (CV) disease amongst an oncology population receiving active treatment is ill-defined. We performed a retrospective analysis assessing the incidence of obesity and cardiovascular (CV) risk factors in this group (grp) of patients as well as the predicted 10-year risk of a CV event.

Methods: Data from all patients (pts) receiving intravenous chemotherapy in an Irish oncology satellite unit over an 18-month period was extracted from chemotherapy prescriptions and electronic patient records.

Helicase Domain Mutations Confer Nucleotide Excision Repair Deficiency and Drive Cisplatin Sensitivity in Muscle-Invasive Bladder Cancer.

Purpose: DNA-damaging agents comprise the backbone of systemic treatment for many tumor types; however, few reliable predictive biomarkers are available to guide use of these agents. In muscle-invasive bladder cancer (MIBC), cisplatin-based chemotherapy improves survival, yet response varies widely among patients. Here, we sought to define the role of the nucleotide excision repair (NER) gene as a biomarker predictive of response to cisplatin in MIBC.

amplification is a mechanism of acquired resistance to EGFR inhibitors identified by transposon mutagenesis and clinical genomics.

In ∼30% of patients with -mutant lung adenocarcinomas whose disease progresses on EGFR inhibitors, the basis for acquired resistance remains unclear. We have integrated transposon mutagenesis screening in an -mutant cell line and clinical genomic sequencing in cases of acquired resistance to identify mechanisms of resistance to EGFR inhibitors. The most prominent candidate genes identified by insertions in or near the genes during the screen were , a gene whose amplification is known to mediate resistance to EGFR inhibitors, and the gene encoding the Src family kinase YES1.

Comprehensive Molecular Profiling of Intrahepatic and Extrahepatic Cholangiocarcinomas: Potential Targets for Intervention.

Various genetic driver aberrations have been identified among distinct anatomic and clinical subtypes of intrahepatic and extrahepatic cholangiocarcinoma, and these molecular alterations may be prognostic biomarkers and/or predictive of drug response. Tumor samples from patients with cholangiocarcinoma who consented prospectively were analyzed using the MSK-IMPACT platform, a targeted next-generation sequencing assay that analyzes all exons and selected introns of 410 cancer-associated genes. Fisher exact tests were performed to identify associations between clinical characteristics and genetic alterations.

Concurrent Alterations in EGFR-Mutant Lung Cancers Associated with Resistance to EGFR Kinase Inhibitors and Characterization of MTOR as a Mediator of Resistance.

To identify molecular factors that determine duration of response to EGFR tyrosine kinase inhibitors and to identify novel mechanisms of drug resistance, we molecularly profiled -mutant tumors prior to treatment and after progression on EGFR TKI using targeted next-generation sequencing. Targeted next-generation sequencing was performed on 374 consecutive patients with metastatic -mutant lung cancer. Clinical data were collected and correlated with somatic mutation data.

Prospective Evaluation of Germline Alterations in Patients With Exocrine Pancreatic Neoplasms.

Background: Identification of pathogenic germline alterations (PGAs) has important clinical and therapeutic implications in pancreas cancer. We performed comprehensive germline testing (GT) in an unselected prospective cohort of patients with exocrine pancreatic neoplasms with genotype and phenotype association to facilitate identification of prognostic and/or predictive biomarkers and examine potential therapeutic implications.

Methods: Six hundred fifteen unselected patients with exocrine pancreatic neoplasms were prospectively consented for somatic tumor and matched sample profiling for 410-468 genes.

Brain Metastases in Pancreatic Ductal Adenocarcinoma: Assessment of Molecular Genotype-Phenotype Features-An Entity With an Increasing Incidence?

Purpose: To assess clinical characteristics of patients with metastatic pancreas ductal adenocarcinoma (PDAC) and brain metastases (BM), and to assess somatic and germ-line molecular profiles where performed.

Patients And Methods: Patients with PDAC and BM between January 1990 and January 2016 were identified. Molecular characteristics of somatic and germ-line testing where performed in the subset of patients who had provided informed consent.

Case report: primary acinar cell carcinoma of the liver treated with multimodality therapy.

We describe a case of primary acinar cell carcinoma (ACC) originating in the liver in a 54-year-old female, diagnosed following persistent abnormal elevated liver function. Imaging revealed two masses, one dominant lesion in the right hepatic lobe and another in segment IVA. A right hepatectomy was performed to remove the larger lesion, while the mass in segment IVA was unresectable due to its proximity to the left hepatic vein.

Real-Time Genomic Profiling of Pancreatic Ductal Adenocarcinoma: Potential Actionability and Correlation with Clinical Phenotype.

Molecular profiling in cancer has identified potential actionable drug targets that have prompted attempts to discover clinically validated biomarkers to guide therapeutic decision-making and enrollment to clinical trials. We evaluated whether comprehensive genetic analysis of patients with pancreatic adenocarcinoma is feasible within a clinically relevant timeframe and whether such analyses provide predictive and/or prognostic information along with identification of potential targets for therapy. Archival or prospectively acquired FFPE samples and matched normal DNA from = 336 patients with pancreatic cancer were analyzed using a hybridization capture-based, next-generation sequencing assay designed to perform targeted deep sequencing of all exons and selected introns of 410 key cancer-associated genes.

Mutational landscape of metastatic cancer revealed from prospective clinical sequencing of 10,000 patients.

Tumor molecular profiling is a fundamental component of precision oncology, enabling the identification of genomic alterations in genes and pathways that can be targeted therapeutically. The existence of recurrent targetable alterations across distinct histologically defined tumor types, coupled with an expanding portfolio of molecularly targeted therapies, demands flexible and comprehensive approaches to profile clinically relevant genes across the full spectrum of cancers. We established a large-scale, prospective clinical sequencing initiative using a comprehensive assay, MSK-IMPACT, through which we have compiled tumor and matched normal sequence data from a unique cohort of more than 10,000 patients with advanced cancer and available pathological and clinical annotations.