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Clinical utility of reflex testing using focused next-generation sequencing for management of patients with advanced lung adenocarcinoma
  1. Tyler E Miller1,
  2. Michael Yang2,
  3. David Bajor3,
  4. Judah D Friedman3,
  5. Richard Y C Chang3,
  6. Afshin Dowlati3,
  7. Joseph E Willis2,
  8. Navid Sadri2
  1. 1 Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
  2. 2 Department of Pathology, University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA
  3. 3 Division of Hematology and Oncology, University Hospitals Seidman Cancer Center, Cleveland, Ohio, USA
  1. Correspondence to Dr Navid Sadri, Department of Pathology, University Hospitals Cleveland Medical Center, Cleveland, OH 44103, USA; navid.sadri{at}


Aims The 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.

Methods 302 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.

Results With 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.

Conclusions We 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.

  • lung cancer
  • molecular genetics
  • molecular oncology
  • molecular pathology
  • tumour markers

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  • Handling editor Runjan Chetty.

  • Contributors TEM analysed the data, created the figures and wrote the manuscript. MY identified the patients and reviewed the histopathology. JEW helped institute reflex testing, got institutional IRB approval and study design. DB, JDF, RYCC and AD identified the patients, contributed samples and provided clinical context. NS conceived and designed the study, analysed the next-generation sequencing data, reviewed the pathology and clinical follow-up, and wrote the manuscript. All authors read and approved the final manuscript.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests TEM training and education was funded by the National Institutes of Health (Grant Number: GM007250) and the National Cancer Institute (Grant Number: CA183510). Other authors have no competing interests to declared.

  • Patient consent Not required.

  • Ethics approval This study was performed and approval were obtained in accordance with the UHCMC Institutional Review Board guidelines.

  • Provenance and peer review Not commissioned; externally peer reviewed.