The incremental value of liquid biopsy in the initial evaluation of patients with metastatic non-small cell lung...

Actionable genetic alterations (AGAs) are present in many patients with non-squamous, metastatic non-small cell lung cancer (mNSCLC) and guide the selection of targeted therapies. Guidelines support concurrent tissue- and plasma-based molecular sequencing at diagnosis to optimize detection of AGAs. Some patients with mNSCLC have alterations detected in plasma-based molecular testing but not in tissue. The mechanisms underlying this discordance, and associated patient- and tumor-specific features remain uncertain.

We conducted a single-center retrospective cohort study using electronic health record data. The cohort included treatment-naïve patients with newly diagnosed non-squamous mNSCLC who underwent concurrent tissue- and plasma-based molecular sequencing between 01/01/2019 and 3/31/2022.

358 patients underwent concurrent tissue- and plasma-based molecular sequencing, 173 (48.3%) were found to harbor AGAs. 113 (65.3%) had alterations identified on both tissue- and plasma-based testing, 42 (24.3%) in tissue-based testing alone, and 18 (10.4%) in plasma-based testing alone. Amongst these 18 patients, 9 (50%) had AGAs in plasma-based sequencing alone due to tissue samples unsuitable for comprehensive testing, 4 (22%) had incomplete tissue-based molecular sequencing panels ordered, and 5 (28%) had no AGAs detected in tissue-based sequencing despite appropriate testing on adequate samples, constituting true tissue-negative cases. The disease control rate by RECIST 1.1 criteria was 100% for the 6 patients with plasma-only AGAs treated with first-line targeted therapy.

Concurrent tissue- and plasma-based molecular profiling enhances AGA detection in patients with non-squamous mNSCLC. Concurrent testing may compensate for inadequate solid tumor tissue samples and tumor heterogeneity to enhance the comprehensiveness of molecular sequencing.