Emergence of Circulating Tumor DNA as a Precision Biomarker in Lung Cancer Radiation Oncology and Beyond.

Circulating tumor DNA (ctDNA) is emerging as a transformative biomarker in the management of non-small cell lung cancer (NSCLC). This review focuses on its role in detecting minimal residual disease (MRD), predicting treatment response, and guiding therapeutic decision-making in radiation oncology and immunotherapy. Key studies demonstrate ctDNA's prognostic value, particularly in identifying relapse risk and refining patient stratification for curative-intent and consolidative treatments.

Sensitive MRD Detection from Lymphatic Fluid after Surgery in HPV-Associated Oropharyngeal Cancer.

Purpose: Our goal was to demonstrate that lymphatic drainage fluid (lymph) has improved sensitivity in quantifying postoperative minimal residual disease (MRD) in locally advanced human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) compared with plasma, and leverage this novel biofluid for patient risk stratification.

Experimental Design: We prospectively collected lymph samples from neck drains of 106 patients with HPV (+) OPSCC, along with 67 matched plasma samples, 24 hours after surgery. PCR and next-generation sequencing were used to quantify cancer-associated cell-free HPV (cf-HPV) and tumor-informed variants in lymph and plasma.

Genomic approaches to cancer and minimal residual disease detection using circulating tumor DNA.

Liquid biopsies using cell-free circulating tumor DNA (ctDNA) are being used frequently in both research and clinical settings. ctDNA can be used to identify actionable mutations to personalize systemic therapy, detect post-treatment minimal residual disease (MRD), and predict responses to immunotherapy. ctDNA can also be isolated from a range of different biofluids, with the possibility of detecting locoregional MRD with increased sensitivity if sampling more proximally than blood plasma.

Genomic Patterns of Malignant Peripheral Nerve Sheath Tumor (MPNST) Evolution Correlate with Clinical Outcome and Are Detectable in Cell-Free DNA.

Unlabelled: Malignant peripheral nerve sheath tumor (MPNST), an aggressive soft-tissue sarcoma, occurs in people with neurofibromatosis type 1 (NF1) and sporadically. Whole-genome and multiregional exome sequencing, transcriptomic, and methylation profiling of 95 tumor samples revealed the order of genomic events in tumor evolution. Following biallelic inactivation of NF1, loss of CDKN2A or TP53 with or without inactivation of polycomb repressive complex 2 (PRC2) leads to extensive somatic copy-number aberrations (SCNA).

Correction: Urine tumor DNA detection of minimal residual disease in muscle-invasive bladder cancer treated with curative-intent radical cystectomy: A cohort study.

[This corrects the article DOI: 10.1371/journal.pmed.

Cell-free DNA ultra-low-pass whole genome sequencing to distinguish malignant peripheral nerve sheath tumor (MPNST) from its benign precursor lesion: A cross-sectional study.

Background: The leading cause of mortality for patients with the neurofibromatosis type 1 (NF1) cancer predisposition syndrome is the development of malignant peripheral nerve sheath tumor (MPNST), an aggressive soft tissue sarcoma. In the setting of NF1, this cancer type frequently arises from within its common and benign precursor, plexiform neurofibroma (PN). Transformation from PN to MPNST is challenging to diagnose due to difficulties in distinguishing cross-sectional imaging results and intralesional heterogeneity resulting in biopsy sampling errors.

Urine tumor DNA detection of minimal residual disease in muscle-invasive bladder cancer treated with curative-intent radical cystectomy: A cohort study.

Background: The standard of care treatment for muscle-invasive bladder cancer (MIBC) is radical cystectomy, which is typically preceded by neoadjuvant chemotherapy. However, the inability to assess minimal residual disease (MRD) noninvasively limits our ability to offer bladder-sparing treatment. Here, we sought to develop a liquid biopsy solution via urine tumor DNA (utDNA) analysis.

ctDNA MRD Detection and Personalized Oncogenomic Analysis in Oligometastatic Colorectal Cancer From Plasma and Urine.

Unlabelled: We hypothesized that circulating tumor DNA (ctDNA) molecular residual disease (MRD) analysis without prior mutational knowledge could be performed after neoadjuvant chemotherapy to assess oligometastatic colorectal cancer (CRC) treated surgically with curative intent. We also investigated urine as an alternative analyte for ctDNA MRD detection in this nongenitourinary setting.

Patients And Methods: We applied AVENIO targeted next-generation sequencing to plasma, tumor, and urine samples acquired on the day of curative-intent surgery from 24 prospectively enrolled patients with oligometastatic CRC.

Once-Per-Visit Alerts: A Means to Study Alert Compliance and Reduce Repeat Laboratory Testing.

Background: Clinical decision support alerts for laboratory testing have poor compliance. Once-per-visit alerts, triggered by reorder of a test within the same admission, are highly specific for unnecessary orders and provide a means to study alert compliance.

Methods: Once-per-visit alerts for 18 laboratory orderables were analyzed over a 60-month period from September 2012 to October 2016 at a 1200-bed academic medical center.

Incidence of humoral hypercalcemia of malignancy among hypercalcemic patients with cancer.

Background: Malignancy-associated hypercalcemia (MAHC) is the most common cause of hypercalcemia among hospitalized patients. MAHC can result from the production of parathyroid hormone related peptide (PTHrP) which is known as humoral hypercalcemia of malignancy (HHM). HHM is commonly thought to account for approximately 80% of MAHC.

Short- and Long-term Biologic Variability of Galectin-3 and Other Cardiac Biomarkers in Patients with Stable Heart Failure and Healthy Adults.

Background: Galectin-3 (Gal-3) has been suggested as a prognostic biomarker in heart failure (HF) patients that may better reflect disease progression than traditional markers, including B-type natriuretic peptide (BNP) and cardiac troponins. To fully establish the utility of any biomarker in HF, its biologic variability must be characterized.

Methods: To assess biologic variability, 59 patients were prospectively recruited, including 23 male and 16 female patients with stable HF and 10 male and 10 female healthy individuals.

Impact on Patient Management and Outcome of Switching between 2 Contemporary Sensitive Cardiac Troponin Assays.

Background: Myocardial infarction is characterized by an increase of cardiac troponin I (cTnI) above the 99th percentile of a reference population. Our hospital switched from 1 contemporary cTnI assay to another and observed a doubling of cTnI results above the assays' respective 99th percentile cutoffs. We investigated the potential impact on inpatient management and outcomes.

HuR function and translational state analysis following global brain ischemia and reperfusion.

Prolonged translation arrest in post-ischemic hippocampal CA1 pyramidal neurons precludes translation of induced stress genes and directly correlates with cell death. We evaluated the regulation of mRNAs containing adenine- and uridine-rich elements (ARE) by assessing HuR protein and hsp70 mRNA nuclear translocation, HuR polysome binding, and translation state analysis of CA1 and CA3 at 8 h of reperfusion after 10 min of global cerebral ischemia. There was no difference between CA1 and CA3 at 8 h of reperfusion in nuclear or cytoplasmic HuR protein or hsp70 mRNA, or HuR polysome association, suggesting that neither mechanism contributed to post-ischemic outcome.

Texture analysis of poly-adenylated mRNA staining following global brain ischemia and reperfusion.

Texture analysis provides a means to quantify complex changes in microscope images. We previously showed that cytoplasmic poly-adenylated mRNAs form mRNA granules in post-ischemic neurons and that these granules correlated with protein synthesis inhibition and hence cell death. Here we utilized the texture analysis software MaZda to quantify mRNA granules in photomicrographs of the pyramidal cell layer of rat hippocampal region CA3 around 1h of reperfusion after 10min of normothermic global cerebral ischemia.

Translation arrest and ribonomics in post-ischemic brain: layers and layers of players.

A persistent translation arrest (TA) correlates precisely with the selective vulnerability of post-ischemic neurons. Mechanisms of post-ischemic TA that have been assessed include ribosome biochemistry, the link between TA and stress responses, and the inactivation of translational components via sequestration in subcellular structures. Each of these approaches provides a perspective on post-ischemic TA.