Complementing Tissue Testing With Plasma Mutation Profiling Improves Therapeutic Decision-Making for Patients With Lung Cancer

Yukti Choudhury; Min-Han Tan; Jun Li Shi; Augustine Tee; Kao Chin Ngeow; Jonathan Poh; Ruth Rosalyn Goh; Jamie Mong

doi:10.3389/fmed.2022.758464

Complementing Tissue Testing With Plasma Mutation Profiling Improves Therapeutic Decision-Making for Patients With Lung Cancer

Front Med (Lausanne). 2022 Feb 11:9:758464. doi: 10.3389/fmed.2022.758464. eCollection 2022.

Authors

Yukti Choudhury¹, Min-Han Tan², Jun Li Shi³, Augustine Tee⁴, Kao Chin Ngeow¹, Jonathan Poh¹, Ruth Rosalyn Goh^{1

5}, Jamie Mong⁶

Affiliations

¹ Lucence Diagnostics Pte. Ltd., Singapore, Singapore.
² Lucence Health Inc, Palo Alto, CA, United States.
³ Institute of Bioengineering and Nanotechnology, Singapore, Singapore.
⁴ Department of Respiratory and Critical Care Medicine, Changi General Hospital, Singapore, Singapore.
⁵ Faculty of Medicine, Imperial College London, London, United Kingdom.
⁶ Institute of Bioengineering and Bioimaging, Singapore, Singapore.

Abstract

Background: Tissue biopsy is an integral part of the diagnostic approach to lung cancer. It is however invasive and limited by heterogeneity. Liquid biopsies may complement tissue testing by providing additional molecular information and may be particularly helpful in patients from whom obtaining sufficient tissue for genomic profiling is challenging.

Methods: Patients with suspected lung cancer (n = 71) were prospectively recruited. Blood and diagnostic tissue samples were collected within 48 h of each other. Plasma cell-free DNA (cfDNA) testing was done using an ultrasensitive amplicon-based next-generation sequencing (NGS) panel (plasma NGS testing). For cases diagnosed as non-small cell lung carcinoma (NSCLC) via histology or cytology, targeted testing for epidermal growth factor receptor (EGFR) mutations was performed using tissue biopsy samples (tissue EGFR testing), where available. Concordance of clinically actionable mutations between methods and sample types was assessed.

Results: For confirmed NSCLC cases (n = 54), tissue EGFR test results were available only for 70.3% (38/54) due to sample inadequacies, compared to blood samples for 98.1% (53/54) cases. Tissue EGFR testing identified sensitizing EGFR (L858R or exon 19 deletion) mutation in 31.6% (12/38) of cases. Plasma NGS identified clinically actionable mutations in 37.7% (20/53) of cases, including EGFR mutations in two cases with no tissue EGFR results, and mutations in KRAS, BRAF, and MET. The overall sensitivity of sensitizing EGFR mutation detection by plasma NGS was 75% (9/12), and specificity was 100% (25/25) in patients tested in both tissue EGFR and plasma NGS (n = 37). In this cohort of patients, tissue EGFR testing alone informed clinical decisions in 22.2% (12/54) of cases. Adding plasma NGS to tissue EGFR testing increased the detection rate of actionable mutations to 42.6% (23/54), representing a 1.9-fold increase in clinically relevant findings. The average turnaround time of plasma NGS was shorter than standard tissue testing (10 vs. 29.9 days, p < 0.05).

Conclusions: In the first-line setting, plasma NGS was highly concordant with tissue EGFR testing. Plasma NGS increases the detection of actionable findings with a shorter time to results. This study outlines the clinical utility of complementary plasma mutation profiling in the routine management of lung cancer patients.

Keywords: NGS panel testing; amplicon-based NGS; liquid biopsy and circulating tumor DNA; next generation sequencing; non-small cell lung cancer (NSCLC); plasma-first; tumor heterogeneity.