Diagnostic Accuracy of Next Generation Sequencing Panel using Circulating Tumor DNA in Patients with Advanced Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis

Abstract

Background/Objectives: Until now, no meta-analysis has been published to evaluate the diagnostic performance of next-generation sequencing (NGS) panel using circulating tumor (ctDNA) in patients with advanced non-small cell lung cancer (aNSCLC). The aim of the study was to carry out a systematic review and a meta-analysis in order to determine the accuracy of NGS of ctDNA to detect six oncogenic driver alterations: epidermal growth factor receptor (EGFR); anaplastic lymphoma kinase (ALK); ROS proto-oncogene 1, receptor tyrosine kinase (ROS-1); serine/threonine-protein kinase B-RAF (BRAF); RET proto-oncogene (RET); and MET proto-oncogene, receptor tyrosine kinase (MET) exon 14 in patients with aNSCLC. Methods: MEDLINE/PubMed, Cochrane Library, Latin American and Caribbean Health Sciences Literature (LILACS), and Centre for Reviews and Dissemination databases and articles obtained from other sources were searched for relevant studies that evaluate the accuracy (sensitivity and specificity) of NGS using ctDNA in patients with aNSCLC. The studies were eligible when NGS of ctDNA was compared with tissue tests to detect at least one of the six oncogenic driver alterations. Diagnostic measures (sensitivity and specificity) were pooled with a bivariate diagnostic random effect. All statistical analyses were performed with software R, v.4.0.0. Results: Ten studies were eligible for data extraction. The overall pooled estimates of sensitivity and specificity were 0.766 (95% CI: 0.678-0.835); 0.999 (95% CI: 0.990-1.000), respectively. Conclusions: The analysis has demonstrated that the NGS panel using ctDNA has a high accuracy to identify the six actionable oncogenic driver alterations in patients with aNSCLC. Therefore, it can be considered a reliable alternative to guide the patients with aNSCLC to the right treatment who cannot undergo an invasive procedure or have insufficient tissue material for molecular tests.

Clinical validity and utility of circulating tumor DNA (ctDNA) testing in advanced non-small cell lung cancer (aNSCLC): a systematic literature review and meta-analysis

“…Previous meta-analyses mostly reported ctDNA performance at the patient level 18,22,23 or did not specify the data level. 19,20 We used sample-level data to facilitate diagnostic performance by driver mutation as well as mutation class, which allows for a more detailed assessment of the CV of ctDNA testing and more mutation-specific information.…”

“…Relevant studies published between January 2012 and July 2023 were identified by searching MEDLINE and Embase databases with predefined search strategies (Supplementary File, Table S2) through the Embase platform. Furthermore, the official websites of three commonly used ctDNA tests (Guardant360 ® CDx, InvisionFirst ® -Lung, and FoundationOne ® Liquid CDx) as well as reference lists of included studies and previous systematic literature reviews [18][19][20][21][22][23][24][25][26] were searched for additional potentially eligible studies.…”

“…Previous systematic literature reviews have examined the CV of ctDNA testing in aNSCLC patients but findings have been inconsistent due to varied review focus and inclusion criteria. [18][19][20][21][22][23][24][25][26] Most of the previous systematic literature reviews and/or meta-analyses 18,19,22,23,25,26 did not specify sequencing technologies, which could potentially explain the observed heterogeneity in findings and limit their clinical implications in relation to the currently more recommended NGS tests.…”

Different Liquid Biopsies for the Management of Non-Small Cell Lung Cancer in the Mutational Oncology Era

“…Non-small cell lung cancer (NSCLC) accounts for approximately 87% of all lung cancer patients [ 2 ]. Among these, 40% are adenocarcinoma, 25–30% are squamous carcinoma and 10–15% are large cell carcinomas [ 3 ].…”

“…In the era of precision medicine, NSCLC has become an eminent example of how therapeutic decision making is based on the identification of specific biomarkers, called oncogenic drivers, designed by the National Comprehensive Cancer Network (NCCN) guidelines, such as the epidermal growth factor (EGFR), rearrangements of anaplastic lymphoma kinase (ALK), ROS proto-oncogene1 (ROS1), serine/threonine-protein kinase B-Raf (BRAF), ERBB2, MET proto-oncogene, receptor tyrosine kinase (MET) exon 14 skipping, RET proto-oncogene (RET) and PDL-1 (programmed death ligand 1) [ 4 , 5 ] present in approximately 30% of NSCLC patients [ 3 , 6 , 7 ]. More recently, the G12C missense mutation of the Kirsten rat sarcoma viral oncogene homolog (KRAS) gene has been added to these and new therapeutic agents (i.e., adagrasib, sotorasib) have been developed [ 8 ].…”