{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T15:58:22Z","timestamp":1753891102295,"version":"3.41.2"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,4,3]],"date-time":"2025-04-03T00:00:00Z","timestamp":1743638400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Immune checkpoint inhibitors (ICIs) have significantly improved the overall survival for patients with different solid tumors. However, there is an urgent need for predictive biomarkers to identify patients with metastatic melanoma who do not benefit from treatment with ICIs, to prevent unnecessary immune related adverse events (irAEs). Electronic noses (eNoses) showed promising results in the detection of cancer as well as the prediction of response outcome in patients with cancer. In this feasibility study, we aimed to investigate whether the breath pattern measured using eNose can be used as a simple biomarker to predict clinical benefit to first-line treatment with ICIs in patients with metastatic melanoma.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this prospective, observational single-center feasibility study, patients with metastatic melanoma performed a breath test using Aeonose\u2122 before start of first-line treatment with ICIs. The detected exhaled breath pattern of volatile organic compounds (VOC) was used for machine learning in a training set to develop a model to identify patients who do not benefit from treatment with ICIs. Lack of clinical benefit was defined as progressive disease according to best tumor response using RECIST v1.1. Primary outcome measures were sensitivity, specificity and accuracy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The eNose showed a distinct breath pattern between patients with and without clinical benefit from ICIs. To identify patients who do not benefit from first-line ICIs treatment, breath pattern analysis using the eNose resulted in a sensitivity of 88%, specificity of 79%, and accuracy of 85%.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Exhaled breath analysis using eNose can identify patients with metastatic melanoma who will not benefit from first-line treatment with ICIs and guide treatment strategies. When validated in an external cohort, eNose could be a useful tool to select these patients for alternative treatment strategies in clinical practice.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1564463","type":"journal-article","created":{"date-parts":[[2025,4,3]],"date-time":"2025-04-03T05:25:55Z","timestamp":1743657955000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Exhaled breath analysis with the use of an electronic nose to predict response to immune checkpoint inhibitors in patients with metastatic melanoma: melaNose trial"],"prefix":"10.3389","volume":"16","author":[{"given":"Brigit","family":"van Dijk","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ivonne J. H.","family":"Schoenaker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Astrid A. 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