ArticleThe journal of liquid biopsy2026
The incremental value of liquid biopsy in the initial evaluation of patients with metastatic non-small cell lung cancer undergoing tissue-based molecular testing.
Article in The journal of liquid biopsy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Not yet cited in PubMed.
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Corrections and comments
- Erratum issued
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10 authors.
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Abstract
Introduction: 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. Methods: 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. Results: 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. Conclusions: 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.
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