Background: The PAOLA-1/ENGOT-ov25 trial showed that maintenance olaparib plus bevacizumab increases survival of advanced ovarian cancer patients with homologous recombination deficiency (HRD). However, decentralized solutions to test for HRD in clinical routine are scarce. The goal of this study was to retrospectively validate on tumor samples from the PAOLA-1 trial, a decentralized HRD test based on low coverage shallow Whole Genome Sequencing (sWGS). Methods: The study comprised 368 patients from the PAOLA-1 trial. The sWGS test was compared to the Myriad MyChoice HRD test (Myriad Genetics), and results were analyzed with respect to Progression-Free Survival (PFS). Results: We found a 95% concordance between the HRD status of the two tests (95% Confidence Interval (CI) 92%-97%). The Positive Percentage Agreement (PPA) of the sWGS test was 95% (95% CI; 90%-97%) like its Negative Percentage Agreement (NPA) (95% CI; 89%-98%). Only 1% (95% CI; 0-3%) of its results were inconclusive. In patients with HRD-positive tumors treated with olaparib plus bevacizumab, the PFS Hazard Ratio (HR) was 0.38 (95% CI; 0.26-0.54) with sWGS and 0.32 (95% CI; 0.22-0.45) with the Myriad assay. In patients with HRD-negative tumors, HR was 0.98 (95% CI; 0.68-1.41) and 1.05 (95% CI; 0.70-1.57) with sWGS and Myriad tests. Among patients with BRCA-wildtype tumors, those with HRD-positive tumors, benefited from olaparib plus bevacizumab maintenance, with HR of 0.48 (95% CI: 0.29-0.79) and of 0.38 (95% CI: 0.23 to 0.63) with sWGS and Myriad test. Conclusion: The SeqOne sWGS HRD assay offers a clinically validated approach to detect HRD.

Clinical evaluation of a low-coverage whole-genome test for detecting homologous recombination deficiency in ovarian cancer

The PAOLA-1/ENGOT-ov25 trial showed that maintenance olaparib plus bevacizumab increases survival of advanced ovarian cancer patients with homologous recombination deficiency (HRD). However, decentralized solutions to test for HRD in clinical routine are scarce. The goal of this study was to retrospectively validate on tumor samples from the PAOLA-1 trial, the decentralized SeqOne assay, which relies on shallow Whole Genome Sequencing (sWGS) to capture genomic instability and targeted sequencing to determine BRCA status.The study comprised 368 patients from the PAOLA-1 trial. The SeqOne assay was compared to the Myriad MyChoice HRD test (Myriad Genetics), and results were analyzed with respect to Progression-Free Survival (PFS).We found a 95% concordance between the HRD status of the two tests (95% Confidence Interval (CI); 92%-97%). The Positive Percentage Agreement (PPA) of the sWGS test was 95% (95% CI; 91%-97%) like its Negative Percentage Agreement (NPA) (95% CI; 89%-98%). In patients with HRD-positive tumors treated with olaparib plus bevacizumab, the PFS Hazard Ratio (HR) was 0.38 (95% CI; 0.26-0.54) with SeqOne assay and 0.32 (95% CI; 0.22-0.45) with the Myriad assay. In patients with HRD-negative tumors, HR was 0.99 (95% CI; 0.68-1.42) and 1.05 (95% CI; 0.70-1.57) with SeqOne and Myriad assays. Among patients with BRCA-wildtype tumors, those with HRD-positive tumors, benefited from olaparib plus bevacizumab maintenance, with HR of 0.48 (95% CI: 0.29-0.79) and of 0.38 (95% CI: 0.23 to 0.63) with the SeqOne and Myriad assay.The SeqOne assay offers a clinically validated approach to detect HRD. 

925P Analytical performance of a next-generation sequencing (NGS) assay kit for assessing homologous recombination deficiency (HRD) from solid tumor samples

<h3>Introduction</h3> Dupilumab demonstrates efficacy in treating a variety of Type-2 disorders refractory to conventional therapies. Improvement in clinical outcomes establishes a need to investigate mechanistic pathways of potential immunomodulation. <h3>Methods</h3> 11 patients, two with moderate-to-severe asthma and 9 with moderate-top-severe AD were recruited to give blood samples pre and three months post-Dupilumab. Longitudinal phenotyping of leukocytes using mass cytometry (CyTOF) and lineage tracing of single-cells using mitochondrial single-cell ATAC-seq (mt-scATAC-seq) was conducted in PBMC and purified T-cells. Clones were inferred using a community-based detection algorithm to cluster cells based on mitochondrial variant allele-frequency (VAF). Gene scores were computed based on open-chromatin regions in the gene and promoter. Differential expression pre- and post-dupilumab was done for each cell cluster population. <h3>Results</h3> CyTOF immunophenotyping showed increased Th1 and Th17 cells following dupilumab, consistent with increased activity of IL-6, TNF, IFNa, and IFNg genes in lymphocytes by mt-scATAC-Seq. Rebalancing of adaptive immunity was accompanied by upregulation of Myc, E2F, MTORC1, PI3K-AKT, and p53 signaling intermediates, and was associated with upregulation of genes controlling apoptosis, unfolded protein response, and oxidative phosphorylation. Changes in frequency of T-cell clonal lineages <i>in vivo</i> were detected following dupilumab. <h3>Conclusion</h3> Data supports clone-specific effects of dupilumab in pediatric Type-2 disorders. This approach enables analysis of changes in gene networks in T-cell clones and populations following treatment. Upregulation of non-Type-2 signaling and changes at the clonal level suggest Dupilumab restores balance to the immune response. 

Dupilumab rebalances immune response in pediatric type-2 disorders: impacts on t-cell clones and functionality

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

J. Lee

Author Tools

Chat about Author

Papers

925P Analytical performance of a next-generation sequencing (NGS) assay kit for assessing homologous recombination deficiency (HRD) from solid tumor samples

Dupilumab rebalances immune response in pediatric type-2 disorders: impacts on t-cell clones and functionality