Dataset Information

Comprehensive cross-platform comparison of methods for non-invasive EGFR mutation testing: results of the RING observational trial.

ABSTRACT: Several platforms for noninvasive EGFR testing are currently used in the clinical setting with sensitivities ranging from 30% to 100%. Prospective studies evaluating agreement and sources for discordant results remain lacking. Herein, seven methodologies including two next-generation sequencing (NGS)-based methods, three high-sensitivity PCR-based platforms, and two FDA-approved methods were compared using 72 plasma samples, from EGFR-mutant non-small-cell lung cancer (NSCLC) patients progressing on a first-line tyrosine kinase inhibitor (TKI). NGS platforms as well as high-sensitivity PCR-based methodologies showed excellent agreement for EGFR-sensitizing mutations (K = 0.80-0.89) and substantial agreement for T790M testing (K = 0.77 and 0.68, respectively). Mutant allele frequencies (MAFs) obtained by different quantitative methods showed an excellent reproducibility (intraclass correlation coefficients 0.86-0.98). Among other technical factors, discordant calls mostly occurred at mutant allele frequencies (MAFs) ? 0.5%. Agreement significantly improved when discarding samples with MAF ? 0.5%. EGFR mutations were detected at significantly lower MAFs in patients with brain metastases, suggesting that these patients risk for a false-positive result. Our results support the use of liquid biopsies for noninvasive EGFR testing and highlight the need to systematically report MAFs.

SUBMITTER: Romero A

PROVIDER: S-EPMC7782072 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Comprehensive cross-platform comparison of methods for non-invasive EGFR mutation testing: results of the RING observational trial.

Romero Atocha A Jantus-Lewintre Eloisa E García-Peláez Beatriz B Royuela Ana A Insa Amelia A Cruz Patricia P Collazo Ana A Pérez Altozano Javier J Vidal Oscar Juan OJ Diz Pilar P Cobo Manuel M Hernández Berta B Vázquez Estevez Sergio S Benítez Gretel G Guirado Maria M Majem Margarita M Bernabé Reyes R Ortega Ana Laura AL Blasco Ana A Bosch-Barrera Joaquim J Jurado Jose M JM García González Jorge J Viteri Santiago S Garcia Giron Carlos C Massutí Bartomeu B Lopez Martín Ana A Rodriguez-Festa Alejandro A Calabuig-Fariñas Silvia S Molina-Vila Miguel Ángel MÁ Provencio Mariano M

Molecular oncology 20201113 1

Several platforms for noninvasive EGFR testing are currently used in the clinical setting with sensitivities ranging from 30% to 100%. Prospective studies evaluating agreement and sources for discordant results remain lacking. Herein, seven methodologies including two next-generation sequencing (NGS)-based methods, three high-sensitivity PCR-based platforms, and two FDA-approved methods were compared using 72 plasma samples, from EGFR-mutant non-small-cell lung cancer (NSCLC) patients progressin ...[more]

PMID: 33107189

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Project description:BackgroundIn order to establish the workflows required to implement a real-time process involving multi-omic analysis of patient samples to support precision-guided therapeutic intervention, a tissue acquisition and analysis trial was implemented. This report describes our findings to date, including the frequency with which mutational testing led to precision-guided therapy and outcome for those patients.MethodsEligible patients presenting to Oregon Health and Science University Knight Cancer Institute were enrolled on the study. Patients with biopsy proven metastatic or locally advanced unresectable prostate cancer, breast cancer, pancreatic adenocarcinoma, or refractory acute myelogenous leukemia receiving standard of care therapy were eligible. Metastatic site biopsies were collected and analyzed using the Knight Diagnostic Lab GeneTrails comprehensive solid tumor panel (124 genes). CLIA certified genomic information was made available to the treating physician.ResultsBetween 1/26/2017 and 5/30/2018, 38 patients were enrolled, with 28 successfully undergoing biopsy. Of these, 25 samples yielded sufficient tumor for analysis. The median biopsy cellularity and number of cores collected were 70% (15-90%) and 5 (2-20), respectively. No procedure-related complications occurred. GeneTrails analysis revealed that 22 of 25 (88%) tumor samples harbored at least one potentially actionable mutation, and 18 (72%) samples harbored 2 or more potentially actionable mutations. The most common genetic alterations identified involved: DNA damage repair genes, cell cycle regulating genes, PIK3CA/Akt/mTOR pathway, and FGF gene family. To date, CLIA certified genomic results were used by treating physicians for precision-guided therapy in 5 (23%) patients.ConclusionWe report the feasibility of real-time tissue acquisition and analysis to support a successful translational oncology platform. The workflow will provide the foundation to improve access and accrual to biomarker driven precision oncology trials.

Project description:Study objectivesThe objective of the study is to validate the performance of Belun Ring Platform, a novel home sleep apnea testing system using a patented pulse oximeter sensor and a proprietary cloud-based neural networks algorithm.MethodsThe Belun Ring captures oxygen saturation, photoplethysmography, and accelerometer signals. The Belun Ring total sleep time is derived from features extracted from accelerometer, oxygen saturation, and photoplethysmography signals. The Belun Ring respiratory event index is derived from Belun Ring total sleep time and features extracted from heart rate variability and oxygen saturation changes. A total of 50 adults without significant cardiopulmonary or neuromuscular comorbidities and heart rate affecting medications were evaluated. In-lab sleep studies were performed simultaneously with the Ring and the studies were manually scored using the American Academy of Sleep Medicine Scoring Manual 4% desaturation criteria.ResultsThe Belun Ring respiratory event index correlated well with the polysomnography-apnea-hypopnea index (AHI; r = .894, P < .001). The sensitivity and specificity in categorizing AHI ≥ 15 events/h were 0.85 and 0.87, respectively, and the positive predictive value and negative predictive value were 0.88 and 0.83, respectively. The Belun Ring total sleep time also correlated well with the polysomnography-total sleep time (r = .945, P < .001). Although the Belun Ring Platform has a good overall performance, it tends to overestimate AHI in individuals with AHI under 15 events/h and underestimate AHI in those with AHI over 15 events/h. Conclusions: In this proof-of-concept study, the Belun Ring Platform demonstrated a reasonable accuracy in predicting AHI and total sleep time in patients without significant comorbidities and heart rate-affecting medications.Clinical trial registrationRegistry: ClinicalTrials.gov; Name: Validation of a Novel Device for Screening Patients With Symptoms of Obstructive Sleep Apnea; URL: https://clinicaltrials.gov/ct2/show/NCT04121923; Identifier: NCT04121923.

Dataset Information

Comprehensive cross-platform comparison of methods for non-invasive EGFR mutation testing: results of the RING observational trial.

Publications

Comprehensive cross-platform comparison of methods for non-invasive EGFR mutation testing: results of the RING observational trial.

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