Clinical Utility of Tumor Next-Generation Sequencing Panel Testing to Inform Treatment Decisions for Patients With Advanced Solid Tumors in a Tertiary Care Center.

PURPOSE: There is limited information about the clinical utility of targeted next-generation sequencing (NGS) panel testing to inform decision making for patients with advanced solid tumors. The Ontario-wide Cancer Targeted Nucleic Acid Evaluation (OCTANE) is a prospective study that enrolled more than 4,500 patients with solid tumor for NGS panel testing. We performed a retrospective survey of medical oncologists to evaluate the impact of NGS testing on treatment decisions. METHODS: Patients and treating oncologists were identified at the Princess Margaret Cancer Center between 2016 and 2021. Tumor-only sequencing was performed using a gene panel of either 555 or 161 cancer genes. Oncologists were asked to review testing results and complete a survey indicating whether NGS testing affected treatment decisions. The primary outcome of this study was rate of treatment change on the basis of mutation results. Patient, test, and physician factors were evaluated for association with treatment changes using univariate analyses and a mixed-effects model. RESULTS: Of the 582 surveys sent, 394 (67.7%) were completed. We found that 188 (47.7%) patients had testing results classified as actionable by the oncologist and 62 (15.7%) patients were matched to treatment, of whom 37 (60%) were enrolled in a clinical trial, 13 (21%) received an approved drug, four (6%) were prescribed off-label therapy, and eight (13%) avoided ineffective treatment. Patient, test, and physician characteristics were not significantly associated with treatment change. There was no difference in overall survival between patients who received matched treatment versus those who did not (P = .55, median survival not reached). CONCLUSION: OCTANE testing led to a change in drug treatment in 15.7% of patients, supporting the clinical utility of NGS panel testing for patients with advanced solid tumors.

Tunneled dialysis line-associated hemorrhagic shock following self-inflicted trauma in a hemodialysis patient: A case report.

Complications of tunneled central venous catheters (CVCs) for hemodialysis are frequent, and most commonly include bacteremia, thrombosis, and stenosis. While bleeding is a relatively rare complication of dialysis lines overall, tunneled CVCs may present a unique bleeding risk given their ability to be displaced or damaged as patients have direct access to the equipment in place. Here, we describe the case of a 68-year-old man with end-stage renal disease and neurocognitive disorder, who developed hemorrhagic shock following self-inflicted laceration of his tunneled dialysis catheter proximal to the Y. Examination of the catheter tunnel revealed that the cuff was palpable proximal to the exit site, but the opening was well retracted. In such cases, hemorrhage is particularly difficult to control because the cuff is rigid and poorly amenable to compression, in addition to being difficult to access. This case demonstrates the risk of significant hemorrhage when a tunneled CVC is damaged at this location and the potential need for the urgent removal of the retained component to prevent recurrence of bleeding. It also highlights important patient safety considerations given the risk of self-inflicted trauma in patients with a neurocognitive disorder and a language barrier affecting communication.

Transposable elements have contributed human regulatory regions that are activated upon bacterial infection.

Transposable elements (TEs) are increasingly recognized as important contributors to mammalian regulatory systems. For instance, they have been shown to play a role in the human interferon response, but their involvement in other mechanisms of immune cell activation remains poorly understood. Here, we investigated the profile of accessible chromatin enhanced in stimulated human macrophages using ATAC-seq to assess the role of different TE subfamilies in regulating gene expression following an immune response. We found that both previously identified and new repeats belonging to the MER44, THE1, Tigger3 and MLT1 families provide 14 subfamilies that are enriched in differentially accessible chromatin and found near differentially expressed genes. These TEs also harbour binding motifs for several candidate transcription factors, including important immune regulators AP-1 and NF-κB, present in 96% of accessible MER44B and 83% of THE1C instances, respectively. To more directly assess their regulatory potential, we evaluated the presence of these TEs in regions putatively affecting gene expression, as defined by quantitative trait locus (QTL) analysis, and found that repeats are also contributing to accessible elements near QTLs. Together, these results suggest that a number of TE families have contributed to the regulation of gene expression in the context of the immune response to infection in humans. This article is part of a discussion meeting issue 'Crossroads between transposons and gene regulation'.