scholarly journals Clinical utility of reflex testing using focused next-generation sequencing for management of patients with advanced lung adenocarcinoma

2018 ◽  
Vol 71 (12) ◽  
pp. 1108-1115 ◽  
Author(s):  
Tyler E Miller ◽  
Michael Yang ◽  
David Bajor ◽  
Judah D Friedman ◽  
Richard Y C Chang ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Lung Adenocarcinoma ◽  
Targeted Therapies ◽  
Medical Center ◽  
Single Gene ◽  
Cancer Center ◽  
Genomic Testing ◽  
Next Generation ◽  
Reflex Testing ◽  
Generation Sequencing

AimsThe growing number of genomically targeted therapies has made genomic testing an important part of the care for patients with non-small cell lung cancer. However, limited tissue availability, cost and long turnaround times can create barriers to efficient genomic testing and subsequent treatment. Effective approaches to reduce these barriers are needed.Methods302 advanced lung adenocarcinomas from consecutive patients seen at University Hospitals Cleveland Medical Center (UHCMC) were tested inhouse using a hybrid DNA/RNA next-generation sequencing (NGS) panel. Sample testing was reflexed from pathology for all stage III or IV tumours. Genomic alterations were tiered according to their clinical relevance and reported with guideline-recommended therapies. Clinical implications of genomic testing results were assessed by manual chart review.ResultsWith a sample cohort consisting of 64% biopsies, 16% excisions/resections and 20% fine needle aspirations, the assay was reliable with a 95% success rate. The average turnaround time from receipt of unstained formalin-fixed paraffin embedded slides to reporting was 4.8±2.1 days, half of the recommended 10 days and similar to single-gene testing. Alterations with Food and Drug Administration-approved or the National Cancer Center Network guideline-recommended targeted therapies were found in 18% of cases. Within this group, 60% of patients went on genomically driven therapies.ConclusionsWe found our reflexed inhouse NGS assay to be reliable, cost-effective and efficient. Incorporation of reflex testing with our NGS assay led to an expansion of successful genomic profiling for all guideline-recommended alterations, and by including an expanded number of alterations within our panel we obtained clinically useful information outside the guidelines without changing cost or efficiency. This approach has enabled UHCMC clinicians to efficiently initiate genomically driven therapies for patients with lung adenocarcinoma.

Clinical utility of reflex testing using focused next generation sequencing for management of patients with advanced lung adenocarcinoma.

2018 ◽  
Vol 36 (15_suppl) ◽  
pp. e24199-e24199
Author(s):  
Navid Sadri ◽  
Tyler E Miller ◽  
Michael Yang ◽  
Afshin Dowlati ◽  
Judah D. Friedman ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Lung Adenocarcinoma ◽  
Clinical Utility ◽  
Next Generation ◽  
Reflex Testing ◽  
Generation Sequencing

scholarly journals Mutation Profile of Resected EGFR ‐Mutated Lung Adenocarcinoma by Next‐Generation Sequencing

2019 ◽  
Vol 24 (10) ◽  
pp. 1368-1374 ◽  
Author(s):  
Ze‐Rui Zhao ◽  
Yao‐Bin Lin ◽  
Calvin S.H. Ng ◽  
Rong Zhang ◽  
Xue Wu ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Lung Adenocarcinoma ◽  
Next Generation ◽  
Mutation Profile ◽  
Egfr Mutated ◽  
Generation Sequencing

Next-generation sequencing for guiding matched targeted therapies in people with relapsed or metastatic cancer

2021 ◽  
Vol 2021 (10) ◽  
Author(s):  
Farasat Kazmi ◽  
Nipun Shrestha ◽  
Stephen Booth ◽  
David Dodwell ◽  
Francesca Aroldi ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Targeted Therapies ◽  
Metastatic Cancer ◽  
Next Generation ◽  
Generation Sequencing

scholarly journals Next-Generation Sequencing Approach to Non–Small Cell Lung Carcinoma Yields More Actionable Alterations

2017 ◽  
Vol 142 (3) ◽  
pp. 353-357 ◽  
Author(s):  
Mitra Mehrad ◽  
Somak Roy ◽  
Humberto Trejo Bittar ◽  
Sanja Dacic
Keyword(s):  
Next Generation Sequencing ◽  
Lung Adenocarcinoma ◽  
Small Cell ◽  
Gene Panel ◽  
Next Generation ◽  
Small Cell Lung ◽  
Genomic Alterations ◽  
Generation Sequencing ◽  
Gene Alterations ◽  
Cancer Panel

Context.— Different testing algorithms and platforms for EGFR mutations and ALK rearrangements in advanced-stage lung adenocarcinoma exist. The multistep approach with single-gene assays has been challenged by more efficient next-generation sequencing (NGS) of a large number of gene alterations. The main criticism of the NGS approach is the detection of genomic alterations of uncertain significance. Objective.— To determine the best testing algorithm for patients with lung cancer in our clinical practice. Design.— Two testing approaches for metastatic lung adenocarcinoma were offered between 2012–2015. One approach was reflex testing for an 8-gene panel composed of DNA Sanger sequencing for EGFR, KRAS, PIK3CA, and BRAF and fluorescence in situ hybridization for ALK, ROS1, MET, and RET. At the oncologist's request, a subset of tumors tested by the 8-gene panel was subjected to a 50-gene Ion AmpliSeq Cancer Panel. Results.— Of 1200 non–small cell lung carcinomas (NSCLCs), 57 including 46 adenocarcinomas and NSCLCs, not otherwise specified; 7 squamous cell carcinomas (SCCs); and 4 large cell neuroendocrine carcinomas (LCNECs) were subjected to Ion AmpliSeq Cancer Panel. Ion AmpliSeq Cancer Panel detected 9 potentially actionable variants in 29 adenocarcinomas that were wild type by the 8-gene panel testing (9 of 29, 31.0%) in the following genes: ERBB2 (3 of 29, 10.3%), STK11 (2 of 29, 6.8%), PTEN (2 of 29, 6.8%), FBXW7 (1 of 29, 3.4%), and BRAF G469A (1 of 29, 3.4%). Four SCCs and 2 LCNECs showed investigational genomic alterations. Conclusions.— The NGS approach would result in the identification of a significant number of actionable gene alterations, increasing the therapeutic options for patients with advanced NSCLCs.

scholarly journals 2139. Rickettsia typhi Detection in Clinical Infections by the Karius Test, a Plasma Microbial Cell-free DNA Next-Generation Sequencing Test

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S725-S725
Author(s):  
Fernando H Centeno ◽  
Asim A Ahmed ◽  
David K Hong ◽  
Sudeb Dalai ◽  
Laila Woc-Colburn
Keyword(s):  
Next Generation Sequencing ◽  
Medical Center ◽  
Severe Disease ◽  
Laboratory Data ◽  
Microbial Cell ◽  
Next Generation ◽  
Rickettsia Typhi ◽  
Cell Free Dna ◽  
Free Dna ◽  
Generation Sequencing

Abstract Background Rickettsia typhi typically causes a nonspecific syndrome characterized by fever, rash, and headache but can rarely progress to severe disease. R. typhi is transmitted by the rat flea and there has been an increased incidence in Houston, TX. Establishing the diagnosis can be challenging and is often made by serological studies. Prompt therapy with doxycycline is important especially in severe disease. Methods Karius Test results from the prior 2 years (Redwood City, CA) were reviewed for detections of R. typhi. The Karius Test is a CLIA-certified/CAP-accredited next-generation sequencing (NGS) plasma test that detects microbial cell free DNA (mcfDNA). After mcfDNA is extracted and NGS performed, human sequences are removed and remaining sequences are aligned to a curated pathogen database of >1,000 organisms. Organisms present above a statistical threshold are reported. Chart review was conducted on the cases of R. typhi identified by the Karius Test. Results The Karius Test detected R. typhi in 6 adult patients, 4 women and 2 men, from a medical center in Houston, TX. In 2 patients, R. typhi mcfDNA was present in the raw sequencing data but at an abundance below validated statistical thresholds. R. typhi mcfDNA was not found in negative controls run simultaneously with the samples. All patients presented with fever, 4 presented with headache, 3 presented with gastrointestinal symptoms, 3 developed rash, one presented with hypotension. Laboratory data were available for 5 patients. Four patients developed thrombocytopenia, 5 had anemia, 4 patients had WBC < 5, 4 had transaminase elevation and 3 developed hyponatremia. 3 out of 5 had R. typhi serologies sent; all 3 were positive (including two of the patients with R. typhi mcfDNA levels below threshold). In the two other patients the Karius test was the means of establishing the diagnosis. 3 out of 5 patients where data were available were treated with doxycyline. Conclusion The Karius test was able to detect R. typhi in a cluster of 6 patients in one medical center in Houston, TX. NGS for mcfDNA offers a rapid means of detecting R. typhi infection. Accurate, rapid diagnosis of R. typhi has important public health implications given its vector-borne mechanism of transmission. Disclosures All authors: No reported disclosures.

Sign in / Sign up

Export Citation Format

Share Document