{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T14:51:21Z","timestamp":1791903081957,"version":"4.3.4"},"reference-count":83,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:00:00Z","timestamp":1791417600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:00:00Z","timestamp":1791417600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Immune checkpoint inhibitors (ICIs) have transformed the treatment of non-small-cell lung cancer (NSCLC), yet predicting durable benefit and detecting resistance remain major challenges. As immunotherapy expands across disease stages, minimally invasive tools are increasingly needed to monitor response and inform treatment personalization. Liquid biopsy enables serial assessment of circulating tumor DNA (ctDNA) and other blood-based biomarkers, complementing tissue analysis and imaging. This review critically synthesizes evidence across resectable, locally advanced, and metastatic NSCLC, integrating ctDNA dynamics with emerging multi-omics approaches. Its contribution is to distinguish the prognostic value of circulating biomarkers from evidence that using them to guide treatment improves patient outcomes, while identifying priorities for clinical translation. Across the reviewed studies, ctDNA clearance is associated with favorable outcomes, whereas persistent or rising ctDNA signals an increased risk of recurrence or progression, sometimes before radiological detection. Methylation, fragmentomics, plasma proteomics, and immune-cell profiling may provide complementary information on tumor-immune interactions. However, low tumor shedding, clonal hematopoiesis, assay variability, and unvalidated intervention thresholds limit routine use. The expansion of perioperative immunotherapy and emerging interest in biomarker-guided treatment adaptation make this synthesis timely. Prospective interventional trials are needed to determine whether liquid biopsy can safely guide treatment escalation, de-escalation, or discontinuation. By clarifying both the promise and the limitations of longitudinal monitoring, this review informs research aimed at detecting ineffective treatment earlier and reducing unnecessary treatment exposure while preserving cancer control.<\/jats:p>","DOI":"10.3390\/cancers18193240","type":"journal-article","created":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T15:16:52Z","timestamp":1791472612000},"page":"3240","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Dynamic Role of Liquid Biopsy in Patients with Non-Small Cell Lung Cancer Receiving Immune Checkpoint Inhibitors: Emerging Opportunities and Clinical Challenges"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-5595-3924","authenticated-orcid":false,"given":"Tancredi Didier","family":"Bazan Russo","sequence":"first","affiliation":[{"name":"Department of Precision Medicine in Medical, Surgical and Critical Care (Me.Pre.C.C.), University of Palermo, 90127 Palermo, Italy"},{"name":"Division of Medical Oncology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center-Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerio","family":"Gristina","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine in Medical, Surgical and Critical Care (Me.Pre.C.C.), University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2803-9586","authenticated-orcid":false,"given":"Francesco","family":"Pepe","sequence":"additional","affiliation":[{"name":"Department of Public Health, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Scimone","sequence":"additional","affiliation":[{"name":"Department of Public Health, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Busuito","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine in Medical, Surgical and Critical Care (Me.Pre.C.C.), University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domenico","family":"Cozzolino","sequence":"additional","affiliation":[{"name":"Department of Public Health, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Sarracino","sequence":"additional","affiliation":[{"name":"Department of Public Health, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppina","family":"Ratto","sequence":"additional","affiliation":[{"name":"Department of Public Health, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1199-7286","authenticated-orcid":false,"given":"Lorena","family":"Incorvaia","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine in Medical, Surgical and Critical Care (Me.Pre.C.C.), University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia","family":"Barraco","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine in Medical, Surgical and Critical Care (Me.Pre.C.C.), University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2478-8838","authenticated-orcid":false,"given":"Giuseppe","family":"Badalamenti","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine in Medical, Surgical and Critical Care (Me.Pre.C.C.), University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4365-5683","authenticated-orcid":false,"given":"Antonio","family":"Galvano","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine in Medical, Surgical and Critical Care (Me.Pre.C.C.), University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viviana","family":"Bazan","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Neuroscience and Advanced Diagnostic (Bi.N.D.), University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4370-2008","authenticated-orcid":false,"given":"Antonio","family":"Russo","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine in Medical, Surgical and Critical Care (Me.Pre.C.C.), University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1630-5805","authenticated-orcid":false,"given":"Giancarlo","family":"Troncone","sequence":"additional","affiliation":[{"name":"Department of Public Health, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3211-9957","authenticated-orcid":false,"given":"Umberto","family":"Malapelle","sequence":"additional","affiliation":[{"name":"Department of Public Health, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,10,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Fankuchen, O., Punekar, S., and Velcheti, V. 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