{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T13:08:36Z","timestamp":1776172116712,"version":"3.50.1"},"reference-count":32,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T00:00:00Z","timestamp":1776124800000},"content-version":"vor","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>Background: Minimal residual disease (MRD) assessment is an emerging tool for refining the risk of relapse following definitive therapy in non-small-cell lung cancer (NSCLC). However, data regarding its clinical impact on the decision-making process remain limited. We evaluated MRD feasibility and its impact in the real-world setting. Methods: A pooled retrospective analysis of longitudinal MRD data in NSCLC patients (n = 34: Signatera\u2122 (Exome), n = 25, Guardant Reveal\u2122, n = 9) was implemented. Co-primary endpoints: MRD feasibility and clinical impact on management (changes in surveillance intensity or therapy escalation\/de-escalation). Secondary endpoints: sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy for recurrence detection, and MRD lead time. Results: MRD was feasible in 32\/34 patients (94.1%); longitudinal testing included two samples in 15 patients (44.1%) and three samples in 2 patients (5.9%). Signatera\u2122 (Exome) failed in 2\/25 (8.0%) due to insufficient tissue. MRD influenced management in 20\/34 (58.8%) patients, most commonly supporting therapy de-escalation (15\/34, 44.1%), followed by imaging surveillance modification (3\/34, 8.8%) and therapy escalation (2\/34, 5.9%). In univariable analysis, tumor grade and STAS were associated with MRD-driven management impact, but neither remained significant in multivariable analysis. With a median follow-up of 18.9 months (IQR 8.5\u201330.7), MRD was positive in 6\/32 (18.8%), while recurrence\/progression occurred in 10\/32 (31.3%) patients. MRD yielded 21 true negatives, five true positives, five false negatives (including two isolated brain recurrences), and one false positive, corresponding to a sensitivity of 50.0%, specificity of 95.5%, PPV of 83.3%, NPV of 80.8%, and an accuracy of 81.3%. The median MRD lead time (n = 5) was 1.31 months (range, 0.46\u20135.52). Conclusions: In this real-world cohort, MRD testing was feasible and frequently guided clinical decisions, mainly supporting treatment de-escalation. MRD was highly specific but less sensitive. Prospective studies are needed to define optimal testing intervals and validate MRD-guided strategies.<\/jats:p>","DOI":"10.3390\/cancers18081246","type":"journal-article","created":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T12:23:56Z","timestamp":1776169436000},"page":"1246","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Impact of Minimal Residual Disease (MRD) Testing on the Decision-Making Process in Non-Small-Cell Lung Cancer (NSCLC)"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6226-2573","authenticated-orcid":false,"given":"Roni","family":"Gillis","sequence":"first","affiliation":[{"name":"The Helmsley Cancer Center, The Eisenberg R&D Authority, Shaare Zedek Medical Center, 12 Shmuel Bait St., Jerusalem 9103102, Israel"},{"name":"Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9190500, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tamar","family":"Zahavi","sequence":"additional","affiliation":[{"name":"ProGenetics, 2 HaMatzuda St., Azor 5800146, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nir","family":"Peled","sequence":"additional","affiliation":[{"name":"The Helmsley Cancer Center, The Eisenberg R&D Authority, Shaare Zedek Medical Center, 12 Shmuel Bait St., Jerusalem 9103102, Israel"},{"name":"Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9190500, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adar","family":"Yaacov","sequence":"additional","affiliation":[{"name":"The Helmsley Cancer Center, The Eisenberg R&D Authority, Shaare Zedek Medical Center, 12 Shmuel Bait St., Jerusalem 9103102, Israel"},{"name":"Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9190500, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Basel","family":"Afifi","sequence":"additional","affiliation":[{"name":"The Helmsley Cancer Center, The Eisenberg R&D Authority, Shaare Zedek Medical Center, 12 Shmuel Bait St., Jerusalem 9103102, Israel"},{"name":"Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9190500, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaber","family":"Salim","sequence":"additional","affiliation":[{"name":"The Helmsley Cancer Center, The Eisenberg R&D Authority, Shaare Zedek Medical Center, 12 Shmuel Bait St., Jerusalem 9103102, Israel"},{"name":"Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9190500, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reham","family":"Basheer","sequence":"additional","affiliation":[{"name":"The Helmsley Cancer Center, The Eisenberg R&D Authority, Shaare Zedek Medical Center, 12 Shmuel Bait St., Jerusalem 9103102, Israel"},{"name":"Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9190500, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noam","family":"Asna","sequence":"additional","affiliation":[{"name":"The Helmsley Cancer Center, The Eisenberg R&D Authority, Shaare Zedek Medical Center, 12 Shmuel Bait St., Jerusalem 9103102, Israel"},{"name":"Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9190500, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arnon","family":"Makori","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9190500, Israel"},{"name":"Imaging Services, Assuta Medical Centers, 20 HaBarzel St., Ramat HaHayal, Tel Aviv 6971028, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Peer","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Tel Aviv Medical Center, 6 Weizmann St., Tel Aviv 6423906, Israel"},{"name":"Faculty of Medicine, Tel-Aviv University, P.O. Box 39040, Tel Aviv 6997801, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Evgeni","family":"Gershman","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9190500, Israel"},{"name":"Department of Pulmonology, Kaplan Medical Center, 1 Pasternak St., Rehovot 7661041, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoav","family":"Manaster","sequence":"additional","affiliation":[{"name":"ProGenetics, 2 HaMatzuda St., Azor 5800146, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Osnat","family":"Moreh Rahav","sequence":"additional","affiliation":[{"name":"Imaging Services, Assuta Medical Centers, 20 HaBarzel St., Ramat HaHayal, Tel Aviv 6971028, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6971-3576","authenticated-orcid":false,"given":"Elizabeth","family":"Dudnik","sequence":"additional","affiliation":[{"name":"Thoracic Oncology, Assuta Medical Centers, 20 HaBarzel St., Ramat HaHayal, Tel Aviv 6971028, Israel"},{"name":"Faculty of Health Sciences, Joyce & Irving Goldman Medical School, Ben Gurion University of the Negev, P.O. Box 653, Beer-Sheva 84105, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,14]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1038\/s41586-023-05776-4","article-title":"Tracking early lung cancer metastatic dissemination in TRACERx using ctDNA","volume":"616","author":"Abbosh","year":"2023","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1016\/j.annonc.2022.02.007","article-title":"Residual ctDNA after treatment predicts early relapse in patients with early-stage non-small cell lung cancer","volume":"33","author":"Gale","year":"2022","journal-title":"Ann. 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