ArticleCancer medicine2022
Longitudinal monitoring by next-generation sequencing of plasma cell-free DNA in ALK rearranged NSCLC patients treated with ALK tyrosine kinase inhibitors.
Article in Cancer medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 2 of them syntheses that pooled it.
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Who cites it
35 citing papers in PubMed, 2 syntheses or guidelines pooled it, 38 citations in OpenAlex.
- The prognostic role of circulating DNA markers in patients with lung malignancies: a systematic review and meta-analysis.Biomarkers in medicine · 2025Pooled it
- Plasma ctDNA kinetics as a predictor of systemic therapy response for advanced non-small cell lung cancer: a systematic review and meta-analysis.The oncologist · 2025Pooled it
- Review
- Circulating-tumour DNA (ctDNA) in NSCLC: mechanisms, evidence and the future of MRD detection.BMJ oncology · 2026Review
- Circulating tumor DNA as prognostic markers of non-small cell lung cancer (NSCLC): a systematic review and meta-analysis.Translational lung cancer research · 2025Article
- ALK-Targeted Therapy: Resistance Mechanisms and Emerging Precision Strategies.Current issues in molecular biology · 2025Review
- Evaluation of gefitinib alone or combined with bevacizumab in patients withTranslational lung cancer research · 2025Article
- Review
- Refining Criteria for Choosing the First-Line Treatment for Real-World Patients with AdvancedInternational journal of molecular sciences · 2025Review
- Longitudinal Tracking ofJTO clinical and research reports · 2025Article
- Emerging molecular testing paradigms in non-small cell lung cancer management-current perspectives and recommendations.The oncologist · 2025Review
- Targeting a cure in anaplastic lymphoma kinase-positive non-small cell lung cancer.Translational lung cancer research · 2024Article
- NGS detection of gene rearrangements and METexon14 mutations in liquid biopsy of advanced NSCLC patients: A study of two Italian centers.The journal of liquid biopsy · 2024Article
- Circulating Tumor DNA Enables Sensitive Detection of Actionable Gene Fusions and Rearrangements Across Cancer Types.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- High efficacy of brigatinib for brain metastases in ALK fusion gene-positive non-small cell lung cancer: A case series.Thoracic cancer · 2024Article
- Unraveling the Potential of ALK-Targeted Therapies in Non-Small Cell Lung Cancer: Comprehensive Insights and Future Directions.Biomedicines · 2024Review
- Clinical applications of circulating biomarkers in non-small cell lung cancer.Frontiers in cell and developmental biology · 2024Review
- Molecular response assessment using circulating tumor DNA (ctDNA) in advanced solid tumors.British journal of cancer · 2023Review
- Detecting ALK, ROS1, and RET fusions and the METΔex14 splicing variant in liquid biopsies of non-small-cell lung cancer patients using RNA-based techniques.Molecular oncology · 2023Article
- Personalized circulating tumor DNA detection to monitor immunotherapy efficacy and predict outcome in locally advanced or metastatic non-small cell lung cancer.Cancer medicine · 2023Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPatients with ALK-rearranged non-small cell lung cancer (ALK+ NSCLC) inevitably acquire resistance to ALK inhibitors. Longitudinal monitoring of cell-free plasma DNA (cfDNA) next-generation sequencing (NGS) could predict the response and resistance to tyrosine kinase inhibitor (TKI) therapy in ALK+ NSCLC.
methodsPatients with ALK+ NSCLC determined by standard tissue testing and planned to undergo TKI therapy were prospectively recruited. Plasma was collected at pretreatment, 2 months-post therapy, and at progression for cfDNA-NGS analysis, Guardant 360.
resultsAmong 92 patients enrolled, circulating tumor DNA (ctDNA) was detected in 69 baseline samples (75%): 43 ALK fusions (62.3%) and two ALK mutations without fusion (2.8%). Two patients showed ALK-resistance mutations after ceritinib; G1202R, and co-occurring G1202R and T1151R. Eight patients developed ALK resistance mutations after crizotinib therapy; L1196M (n = 5), G1269A (n = 1), G1202R (n = 1), and co-occurring F1174L, G1202R, and G1269A (n = 1). Absence of ctDNA at baseline was significantly associated with longer progression-free survival (PFS; median 36.1 vs. 11.4 months, p = 0.0049) and overall survival (OS; not reached vs. 29.3 months, p = 0.0200). ctDNA clearance at 2 months (n = 29) was associated with significantly longer PFS (25.4 vs. 11.6 months, p = 0.0012) and OS (not reached vs. 26.1 months, p = 0.0307) than those without clearance (n = 22). Patients with co-occurring TP53 alterations and ALK fusions at baseline (n = 16) showed significantly shorter PFS (7.28 vs. 13.0 months, p = 0.0307) than those without TP53 alterations (n = 25).
conclusionscfDNA-NGS facilitates detection of ALK fusions and resistance mutations, assessment of prognosis, and monitoring dynamic changes of genomic alterations in ALK+ NSCLC treated with ALK-TKI.
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