The validity and predictive value of blood-based biomarkers in prediction of response in the treatment of non-small cell lung cancer: A systematic review

e15053 Background: With the introduction of targeted therapies and immunotherapy, molecular diagnostics gained a more profound role in the management of non-small cell lung cancer (NSCLC). Currently, tissue biopsies (TB) are used as primary source for molecular testing and generally require an invasive procedure. The introduction of liquid biopsies (LB) not only decreases patient burden, but it also allows for more frequent testing. Which might be of value in the monitoring of treatment response. This study aimed to systematically search for studies reporting on the use of LB, the correlation between LB and TB, and finally the predictive value in the management of NSCLC. Methods: A systematic literature search was performed using Scopus and PubMed, including results published in English after 01-01-2014. Articles were included when 1) describing the predictive value of a LB with regard to overall and/or progression-free survival, or 2) describing the validity of a marker by comparing LBs to TBs regarding sensitivity, specificity, or concordance. Results: 1705 articles were identified in the search, 1323 articles were excluded after title and abstract screening, leaving 382 articles for full-text evaluation. Of the 137 articles included after full-text evaluation, 78 articles described the validity, and 65 articles described the predictive value of LBs. In studies describing the predictive value of LBs, the majority of articles reported on the predictive value of biomarkers in relation to targeted therapies (n = 31). In studies describing the validity of LBs, the majority of studies report on EGFR mutations including, exon 19 deletion (n = 23) and L858R (n = 26). Looking at the validity of LBs, we saw a large variation in reported sensitivity (range 20-100%), specificity (range 30-100%), and concordance (range 40-99%). Conclusions: Although a variety of blood-based biomarkers has been investigated, most studies have limited their evaluation to sensitivity and specificity of liquid biopsies to determine EGFR mutation status compared to tissue and the subsequent targeting of EGFR tyrosine kinase inhibitors based on the mutation status found in LBs of NSCLC patients. The first adoption of LBs in practice is expected to involve the detection of EGFR mutations by LB analysis in addition to TBs.