Widespread Adoption of Precision Anticancer Therapies After Implementation of Pathologist-Directed Comprehensive Genomic Profiling Across a Large US Health System.

Purpose: Precision therapies and immunotherapies have revolutionized cancer care, with novel genomic biomarker-associated therapies being introduced into clinical practice rapidly, resulting in notable gains in patient survival. Despite this, there is significant variability in the utilization of tumor molecular profiling that spans the timing of test ordering, comprehensiveness of gene panels, and clinical decision support through therapy and trial recommendations.

Methods: To standardize testing, we designed a pathologist-directed test ordering system at the time of diagnosis using a 523-gene DNA/RNA hybrid comprehensive genomic profiling (CGP) panel and extensive clinical decision support tools.

Real-World Impact of Comprehensive Genomic Profiling on Biomarker Detection, Receipt of Therapy, and Clinical Outcomes in Advanced Non-Small Cell Lung Cancer.

Purpose: Therapeutic decision making for patients with advanced non-small cell lung cancer (aNSCLC) includes a growing number of options for genomic, biomarker-guided, targeted therapies. We compared actionable biomarker detection, targeted therapy receipt, and real-world overall survival (rwOS) in patients with aNSCLC tested with comprehensive genomic profiling (CGP) versus small panel testing (SP) in real-world community health systems.

Methods: Patients older than 18 years diagnosed with aNSCLC between January 1, 2015, and December 31, 2020, who received biomarker testing were followed until death or study end (September 30, 2021), and categorized by most comprehensive testing during follow-up: SP (≤52 genes) or CGP (>52 genes).

Status May Differentiate Two Distinct Pathways of Gastric Adenocarcinoma Carcinogenesis.

Background: We evaluated the phenotype of sporadic gastric cancer based on HP status and binding of a tumor risk marker monoclonal, Adnab-9.

Methods: We compared a familial GC kindred with an extremely aggressive phenotype to HP-positive (HP+) and -negative (HP-) sporadic gastric adenocarcinoma (GC) patients in the same community to determine if similar phenotypes exist. This might facilitate gene discovery to understand the pathogenesis of aggressive GC phenotypes, particularly with publications implicating immune-related gene-based signatures, and the development of techniques to gauge the stance of the innate immune system (InImS), such as the FERAD ratio (blood ferritin:fecal Adnab-9 binding OD-background binding).

Post collision analyzer to study charge-exchange processes in ion-molecule collisions.

We have designed an electrostatic charge state analyzer for ion beams having energies in the range of 5-20 keV/q. It is primarily built to investigate the different ionization processes involved in the slow (v < 1 a.u.

A novel methylated cell-free DNA marker panel to monitor treatment response in metastatic prostate cancer.

This study examined circulating cell-free DNA (cfDNA) biomarkers associated with androgen treatment resistance in metastatic castration resistance prostate cancer (mCRPC). We designed a panel of nine candidate cfDNA methylation markers using droplet digital PCR (Methyl-ddPCR) and assessed methylation levels in sequentially collected cfDNA samples from patients with mCRPC. Increased cfDNA methylation in eight out of nine markers during androgen-targeted treatment correlated with a faster time to clinical progression.

Investigating Urinary Circular RNA Biomarkers for Improved Detection of Renal Cell Carcinoma.

Renal cell carcinomas (RCC) are usually asymptomatic until late stages, posing several challenges for early detection of malignant disease. Non-invasive liquid biopsy biomarkers are emerging as an important diagnostic tool which could aid with routine screening of RCCs. Circular RNAs (circRNAs) are novel non-coding RNAs that play diverse roles in carcinogenesis.

Combining CAPRA-S With Tumor IDC/C Features Improves the Prognostication of Biochemical Recurrence in Prostate Cancer Patients.

Background: Intraductal carcinoma and cribriform (IDC/C) tumor features are well-established prognosticators of biochemical recurrence (BCR), metastasis, and prostate cancer (PCa)-specific mortality. However, approximately 70% of PCa patients undergoing a radical prostatectomy are IDC/C negative, yet up-to 20% of these patients progress and experience BCR. Thus, tumor histopathologic characteristics such as IDC/C alone are limited in their ability to predict disease progression.

Distinct DNA methylation patterns associated with treatment resistance in metastatic castration resistant prostate cancer.

Androgens are a major driver of prostate cancer (PCa) and continue to be a critical treatment target for advanced disease, which includes castration therapy and antiandrogens. However, resistance to these therapies leading to metastatic castration-resistant prostate cancer (mCRPC), and the emergence of treatment-induced neuroendocrine disease (tNEPC) remains an ongoing challenge. Instability of the DNA methylome is well established as a major hallmark of PCa development and progression.

Coincident angle-resolved state-selective photoelectron spectroscopy of acetylene molecules: a candidate system for time-resolved dynamics.

The acetylene-vinylidene system serves as a benchmark for investigations of ultrafast dynamical processes where the coupling of the electronic and nuclear degrees of freedom provides a fertile playground to explore the femto- and sub-femto-second physics with coherent extreme-ultraviolet (EUV) photon sources both on the table-top as well as free-electron lasers. We focus on detailed investigations of this molecular system in the photon energy range 19-40 eV where EUV pulses can probe the dynamics effectively. We employ photoelectron-photoion coincidence (PEPICO) spectroscopy to uncover hitherto unrevealed aspects of this system.

A 38-gene model comprised of key TET2-associated genes shows additive utility to high-risk prostate cancer cases in the prognostication of biochemical recurrence.

Background: Early treatment of patients at risk for developing aggressive prostate cancer is able to delay metastasis and reduce mortality; as such, up-front identification of these patients is critical. Several risk classification systems, including CAPRA-S, are currently used for disease prognostication. However, high-risk patients identified by these systems can still exhibit wide-ranging disease outcomes, leading to overtreatment of some patients in this group.

Dynamics of the cell-free DNA methylome of metastatic prostate cancer during androgen-targeting treatment.

We examined methylation changes in cell-free DNA (cfDNA) in metastatic castration-resistant prostate cancer (mCRPC) during treatment. Genome-wide methylation analysis of sequentially collected cfDNA samples derived from mCRPC patients undergoing androgen-targeting therapy was performed. Alterations in methylation states of genes previously implicated in prostate cancer progression were observed and patients that maintained methylation changes throughout therapy tended to have a longer time to clinical progression.

Penning spectroscopy and structure of acetylene oligomers in He nanodroplets.

Embedded atoms or molecules in a photoexcited He nanodroplet are well-known to be ionized through inter-atomic relaxation in a Penning process. In this work, we investigate the Penning ionization of acetylene oligomers occurring from the photoexcitation bands of He nanodroplets. In close analogy to conventional Penning electron spectroscopy by thermal atomic collisions, the n = 2 photoexcitation band plays the role of the metastable atomic 1s2s 3,1S He*.

Frequency and Causes of Burnout in US Community Oncologists in the Era of Electronic Health Records.

Background: Physician burnout, characterized by exhaustion of physical or emotional strength, cynicism, and lack of achievement, has become a worsening phenomenon in medicine, contributing to higher health care costs and patient/physician dissatisfaction. How burnout has affected hematologists and oncologists is not well studied.

Methods: US community oncologists/hematologists were queried via a Web-based survey from September-November 2018.

Development of a multivariable risk model integrating urinary cell DNA methylation and cell-free RNA data for the detection of significant prostate cancer.

Background: Prostate cancer exhibits severe clinical heterogeneity and there is a critical need for clinically implementable tools able to precisely and noninvasively identify patients that can either be safely removed from treatment pathways or those requiring further follow up. Our objectives were to develop a multivariable risk prediction model through the integration of clinical, urine-derived cell-free messenger RNA (cf-RNA) and urine cell DNA methylation data capable of noninvasively detecting significant prostate cancer in biopsy naïve patients.

Methods: Post-digital rectal examination urine samples previously analyzed separately for both cellular methylation and cf-RNA expression within the Movember GAP1 urine biomarker cohort were selected for a fully integrated analysis (n = 207).

Hindered alignment in ultrashort, intense laser-induced fragmentation of O.

Molecules ionized by intense (10-100 TW/cm) and ultrashort (tens of femtoseconds) laser fields undergo rotation and alignment mediated through their polarizability. The expected alignment is indeed observed in the case of O molecules ionized by intense laser pulses of 800 nm wavelength and 25 fs duration, as observed through velocity imaging of the fragments. Strikingly, when 35 fs pulses of 400 nm wavelength of comparable intensity are employed, an anomalous hindering of this alignment is observed.

Clinical management patterns of advanced and metastatic gastro-oesophageal carcinoma after fluoropyrimidine/platinum treatment in France, Germany, Spain and the United Kingdom.

Objective: To describe treatment patterns and resource utilisation in France, Germany, Spain and the United Kingdom (UK) in patients with unresectable locally advanced and/or metastatic gastro-oesophageal adenocarcinoma (GEA), who failed first-line fluoropyrimidine/platinum treatment.

Methods: Treating physicians completed a web-based chart review (2013-2015). Eligible patients were ≥ 18 years old; had unresectable locally advanced and/or metastatic gastric adenocarcinoma including the gastro-oesophageal junction; received first-line fluoropyrimidine/platinum-based therapy; and had ≥ 3 months of follow-up after first-line discontinuation.

Methylation Markers in Prostate Biopsies Are Prognosticators for Late Biochemical Recurrence and Therapy after Surgery in Prostate Cancer Patients.

After diagnosis of prostate cancer is confirmed by a positive biopsy, the tumor may be surgically removed via radical prostatectomy (RP). However, many prostate cancer patients experience biochemical recurrence after surgery and/or undergo salvage radiotherapy or hormone therapy. Timely treatment is required to prevent the spread of disease in these cases, and biopsy tissue may hold potential for disease prognostication before surgery is ever performed.

An integrative DNA methylation model for improved prognostication of postsurgery recurrence and therapy in prostate cancer patients.

Purpose: Patients with clinically localized, high-risk prostate cancer are often treated with surgery, but exhibit variable prognosis requiring long-term monitoring. An ongoing challenge for such patients is developing optimal strategies and biomarkers capable of differentiating between men at risk of early recurrence (<3 years) that will benefit from adjuvant therapies and men at risk of late recurrence (>5 years) who will benefit from long-term monitoring and/or salvage therapies.

Patients And Methods: DNA methylation changes for 12 genes associated with disease progression were analyzed in 453 prostate tumors.

GBX2 Methylation Is a Novel Prognostic Biomarker and Improves Prediction of Biochemical Recurrence Among Patients with Prostate Cancer Negative for Intraductal Carcinoma and Cribriform Architecture.

Background: Tumor intraductal carcinoma/cribriform architecture (IDC/C) is associated with an unfavorable prognosis and biochemical recurrence (BCR) in prostate cancer (PCa). Up to 70% of PCa patients are IDC/C-negative, but it is estimated that 20% of these cases still experience BCR. Thus, biomarkers for better detection of aggressive disease in IDC/C-negative patients are required.

Exploring targets of TET2-mediated methylation reprogramming as potential discriminators of prostate cancer progression.

Background: Global DNA methylation alterations are hallmarks of cancer. The tumor-suppressive TET enzymes, which are involved in DNA demethylation, are decreased in prostate cancer (PCa); in particular, TET2 is specifically targeted by androgen-dependent mechanisms of repression in PCa and may play a central role in carcinogenesis. Thus, the identification of key genes targeted by TET2 dysregulation may provide further insight into cancer biology.

epiCaPture: A Urine DNA Methylation Test for Early Detection of Aggressive Prostate Cancer.

Purpose: Liquid biopsies that noninvasively detect molecular correlates of aggressive prostate cancer (PCa) could be used to triage patients, reducing the burdens of unnecessary invasive prostate biopsy and enabling early detection of high-risk disease. DNA hypermethylation is among the earliest and most frequent aberrations in PCa. We investigated the accuracy of a six-gene DNA methylation panel (Epigenetic Cancer of the Prostate Test in Urine [epiCaPture]) at detecting PCa, high-grade (Gleason score greater than or equal to 8) and high-risk (D'Amico and Cancer of the Prostate Risk Assessment] PCa from urine.

Combining urinary DNA methylation and cell-free microRNA biomarkers for improved monitoring of prostate cancer patients on active surveillance.

Purpose: Prostate cancer (CaP) patients with low-grade tumors are enrolled in active surveillance (AS) programs and monitored with digital rectal exams (DREs), prostate-specific antigen (PSA) tests, and periodic invasive biopsies. Patients are "reclassified" with higher-risk disease if they show signs of disease progression. However, AS patients who will reclassify cannot be easily identified upfront and suffer morbidities associated with biopsy.