Adequacy of small biopsy and cytology specimens for comprehensive genomic profiling of patients with non-small-cell lung cancer to determine eligibility for immune checkpoint inhibitor and targeted therapy

J Clin Pathol. 2022 Sep;75(9):612-619. doi: 10.1136/jclinpath-2021-207597. Epub 2021 May 5.

Abstract

Aims: In advanced-stage non-small-cell lung cancer (NSCLC), incomplete genotyping for guideline-recommended genomic biomarkers poses a significant challenge to making informed and timely clinical decisions. We report our institution's experience in assessing the adequacy of small specimens for comprehensive genomic profiling for guideline-recommended lung cancer biomarker testing.

Methods: We performed a retrospective evaluation of all image-guided procedures for NSCLC performed in our institution between October 2016 and July 2018, including core needle biopsy (CNB) and fine-needle aspiration (FNA) in patients who had undergone genomic profiling for lung cancer. Lung cancer biomarker adequacy, defined as successful testing of guideline-recommended biomarkers including, epidermal growth factor receptor (EGFR); serine/threonine protein kinase B-Raf (BRAF); anaplastic lymphoma kinase (ALK); proto-oncogene tyrosine protein kinase ROS (ROS1); Rearranged during Transfection (RET); Tyrosine protein kinase Met (MET); and programmed cell death ligand 1 (PD-L1), was evaluated.

Results: A total of 865 cases were evaluated in this study, 785 of which included testing of all lung cancer biomarkers. Lung tissue was adequate for biomarker testing in 84% of cases; this rate increased to 87% when biomarker testing was combined with concurrently acquired FNA or CNB specimens. Biomarker testing success correlated strongly with DNA concentration (p<0.0001) and the use of 22G needles in endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) procedures (p=0.0035). Biomarker testing of CNB specimens showed a significantly higher success rate than did biomarker testing of cytology FNA specimens (p=0.0005). The adequacy of EBUS-TBNA samples was not significantly different from that of the transthoracic needle aspiration samples (p=0.40). Variables such as age, gender, lesion size, site, diagnosis and number of needle passes showed no significant correlation with success rates in lung cancer biomarker testing.

Conclusion: The growing numbers of therapeutic biomarkers in NSCLC requires judicious triage of limited-volume tissue from small specimens. Our study showed that thoracic small tissue specimens can be used successfully to provide prognostic and predictive information for the current guideline-recommended biomarkers for NSCLC in most cases.

Keywords: carcinoma; cytological techniques; lung; lung neoplasms; molecular biology.

MeSH terms

  • Biomarkers, Tumor / genetics
  • Carcinoma, Non-Small-Cell Lung* / diagnosis
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Carcinoma, Non-Small-Cell Lung* / therapy
  • Endoscopic Ultrasound-Guided Fine Needle Aspiration / methods
  • Genomics
  • Humans
  • Immune Checkpoint Inhibitors
  • Lung Neoplasms* / diagnosis
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / therapy
  • Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins / genetics
  • Retrospective Studies

Substances

  • Biomarkers, Tumor
  • Immune Checkpoint Inhibitors
  • Proto-Oncogene Proteins
  • Protein-Tyrosine Kinases