{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T22:17:51Z","timestamp":1793657871123,"version":"4.5.1"},"reference-count":14,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:00:00Z","timestamp":1783987200000},"content-version":"vor","delay-in-days":6,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Histologic transformation from non\u2013small cell lung cancer (NSCLC) to small cell lung cancer (SCLC) is a rare mechanism of resistance in anaplastic lymphoma kinase (ALK)\u2013rearranged disease. Diagnosis is traditionally dependent on tissue biopsy, which may be limited by lesion accessibility and low disease burden. We report a case of ALK-rearranged lung adenocarcinoma that underwent small cell transformation, in which methylation-based circulating cell-free DNA (cfDNA) analysis detected a small cell lung cancer signature 5 months prior to tissue confirmation. Serial liquid biopsies demonstrated dynamic changes in tumor fraction and histologic composition that correlated with response to chemoradiation and continuation of ALK-directed therapy. This case highlights the potential utility of methylation-based liquid biopsy for early detection and longitudinal monitoring of histologic transformation in oncogene-driven NSCLC.<\/jats:p>","DOI":"10.1093\/oncolo\/oyag271","type":"journal-article","created":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T11:35:59Z","timestamp":1784028959000},"source":"Crossref","is-referenced-by-count":1,"title":["Methylation\u2013based liquid biopsy facilitates early detection of small cell transformation in\n                    <i>ALK<\/i>\n                    -rearranged non\u2013small cell lung cancer"],"prefix":"10.1093","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5246-6262","authenticated-orcid":false,"given":"Jinesh S","family":"Gheeya","sequence":"first","affiliation":[{"name":"The Ohio State University Comprehensive Cancer Center, Division of Medical Oncology, Columbus, Ohio 43210,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raj","family":"Singh","sequence":"additional","affiliation":[{"name":"The Ohio State University Comprehensive Cancer Center, Department of Radiation Oncology, Columbus, Ohio 43210,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingjia","family":"Li","sequence":"additional","affiliation":[{"name":"The Ohio State University Comprehensive Cancer Center, Division of Medical Oncology, Columbus, Ohio 43210,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saman","family":"Ahmadian","sequence":"additional","affiliation":[{"name":"Department of Pathology, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantin","family":"Shilo","sequence":"additional","affiliation":[{"name":"Department of Pathology, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Triparna","family":"Sen","sequence":"additional","affiliation":[{"name":"The Ohio State University Comprehensive Cancer Center, Division of Medical Oncology, Columbus, Ohio 43210,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7860-8417","authenticated-orcid":false,"given":"Christian","family":"Rolfo","sequence":"additional","affiliation":[{"name":"The Ohio State University Comprehensive Cancer Center, Division of Medical Oncology, Columbus, Ohio 43210,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3002-1921","authenticated-orcid":false,"given":"David P","family":"Carbone","sequence":"additional","affiliation":[{"name":"The Ohio State University Comprehensive Cancer Center, Division of Medical Oncology, Columbus, Ohio 43210,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dwight H","family":"Owen","sequence":"additional","affiliation":[{"name":"The Ohio State University Comprehensive Cancer Center, Division of Medical Oncology, Columbus, Ohio 43210,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R","family":"Gandara","sequence":"additional","affiliation":[{"name":"University of California Davis Comprehensive Cancer Center, Division of Hematology & Oncology, Sacramento, California 95817,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,7,14]]},"reference":[{"key":"2026072801012841000_oyag271-B1","doi-asserted-by":"crossref","first-page":"2240","DOI":"10.1158\/1078-0432.CCR-12-2246","article-title":"Analysis of tumor specimens at the time of acquired resistance to EGFR-TKI therapy in 155 patients with EGFR-mutant lung 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lorlatinib: a case report and literature review","volume":"186","author":"Lingling","year":"2023","journal-title":"Lung Cancer"},{"key":"2026072801012841000_oyag271-B5","first-page":"100536","article-title":"First report of management of sequential small cell transformation and ALK I1171T mutation as resistance mechanisms in a patient with ALK-EML4 fused Non-Small cell lung adenocarcinoma with a novel combination of temozolomide and lorlatinib: a case report","volume":"4","author":"Majeed","year":"2023","journal-title":"JTO Clin Res Rep"},{"key":"2026072801012841000_oyag271-B6","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1186\/s12957-025-03687-4","article-title":"Patients outcomes in lung adenocarcinoma transforming to small-cell lung cancer after tyrosine kinase inhibitor therapy","volume":"23","author":"Wang","year":"2025","journal-title":"World J Surg 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types","volume":"613","author":"Loyfer","year":"2023","journal-title":"Nature"},{"key":"2026072801012841000_oyag271-B10","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1158\/1538-7445.AM2025-1142","article-title":"Abstract 1142: non-invasive cell free DNA (cfDNA) methylation profiling for accurate proportional quantification of lung cancer subtypes","volume":"85","author":"Valouev","year":"2025","journal-title":"Cancer Research"},{"key":"2026072801012841000_oyag271-B11","doi-asserted-by":"crossref","first-page":"S1027","DOI":"10.1016\/j.annonc.2025.08.2548","article-title":"1924P liquid biopsy for molecular lung subtype prediction in advanced non-small cell lung cancer","volume":"36","author":"Garc\u00eda Pardo de Santayana","year":"2025","journal-title":"Annals of Oncology"},{"key":"2026072801012841000_oyag271-B12","first-page":"100623","article-title":"Brief report: comprehensive clinicogenomic profiling of small cell transformation from EGFR-mutant NSCLC informs 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