BACKGROUND

Liquid biopsy approaches, especially the detection of circulating tumor DNA (ctDNA), are emerging as sensitive and reliable surrogates for tumor tissue-based routine diagnostic testing. Here, we retrospectively analyzed serially collected plasma samples of non-small cell lung cancer (NSCLC) patients obtained at first diagnosis to evaluate the added value of ctDNA analysis for detecting therapeutically relevant variants and determining the consequent clinical implications.

METHODS

One hundred eighty plasma samples from consecutively recruited NSCLC patients were included. Circulating cell-free DNA (ccfDNA) was extracted and analyzed with the UltraSEEK Lung Panel v2 on the MassARRAY System. Tumor tissue next-generation sequencing (NGS) data, performed as routine molecular testing in the clinical setting, were retrieved from the national pathology registry for 132 patients.

RESULTS

Here we show that in 82% of the patients, mutations are concordantly detected in tumor tissue and plasma. More mutations are reported with tumor tissue-based NGS in nineteen patients, while in four patients additional mutations are detected in plasma. Tissue-based molecular tumor profiling identifies 60 patients eligible for targeted treatment including fifteen (8%) harboring fusions currently not covered by UltraSEEK. Based on ctDNA analysis, 41 patients (23%) are identified as eligible for BRAF-, EGFR-, or KRAS-targeted therapies. In the absence of tumor tissue NGS data (n = 48), five therapeutically relevant mutations are detected.

CONCLUSIONS

Molecular tumor profiling of ctDNA identifies therapeutically relevant mutations at a comparable rate to tumor tissue-based NGS and might therefore serve as an alternative or complementary test for the detection of actionable variants in plasma.