{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T15:14:01Z","timestamp":1785510841650,"version":"3.56.0"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T00:00:00Z","timestamp":1760659200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["1K08CA237832"],"award-info":[{"award-number":["1K08CA237832"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004917","name":"Cancer Prevention and Research Institute of Texas","doi-asserted-by":"publisher","award":["RR20007"],"award-info":[{"award-number":["RR20007"]}],"id":[{"id":"10.13039\/100004917","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune neurologic condition causing progressive muscle weakness that can occur as a paraneoplastic disorder, most commonly in patients with small cell lung cancer (SCLC). In limited prospective and retrospective studies, LEMS incidence in SCLC populations ranges 3-6%. Because LEMS may present a diagnostic challenge, we determined the prevalence of LEMS in a large, real-world, U.S.-based SCLC cohort.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p>We conducted a retrospective analysis of administrative data from Symphony Health\u2019s PatientSource<jats:sup>\u00ae<\/jats:sup>, which represents over 300 million U.S. patients. In the primary analysis, we identified claims for LEMS (available starting in 2014) among patients with lung cancer claims between 2017 and 2022 who received etoposide and platinum-based chemotherapy (a validated approach to SCLC case identification).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among 867,170 patients with lung cancer claims, 46,995 (5.4%) received platinum-etoposide-based therapy (putative SCLC cohort), of whom 77 (0.16%) had LEMS claims. In a subset of 8,513 patients with \u226512 months of claims preceding and following lung cancer diagnosis, 16 (0.19%) had LEMS claims. LEMS cases were more frequently diagnosed by neurologists (30%) than by oncologists (13%).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In a large real-world cohort of patients with lung cancer, LEMS is diagnosed far less frequently than would be expected and rarely by oncologists. Because LEMS may convey substantial morbidity and specific LEMS treatments are available, further efforts to understand and address this discrepancy are warranted.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fonc.2025.1650373","type":"journal-article","created":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T04:14:08Z","timestamp":1760674448000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Marked under-diagnosis of Lambert-Eaton myasthenic syndrome in small cell lung cancer: an analysis of real-world claims data"],"prefix":"10.3389","volume":"15","author":[{"given":"Benjamin J.","family":"Drapkin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Morrell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Regina","family":"Grebla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guy","family":"Shechter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David E.","family":"Gerber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,10,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2010.32.0440","article-title":"Clinical Dutch-English Lambert-Eaton Myasthenic syndrome (LEMS) tumor association prediction score accurately predicts small-cell lung cancer in the LEMS","volume":"29","author":"Titulaer","year":"2011","journal-title":"J Clin Oncol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1987.tb51317.x","article-title":"The course of myasthenia gravis and therapies affecting outcome","volume":"505","author":"Grob","year":"1987","journal-title":"Ann N Y Acad Sci"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.20.6169","article-title":"SOX antibodies in small-cell lung cancer and Lambert-Eaton myasthenic syndrome: frequency and relation with survival","volume":"27","author":"Titulaer","year":"2009","journal-title":"J Clin Oncol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-017-8541-9","article-title":"Lambert-Eaton myasthenic syndrome (LEMS): a rare autoimmune presynaptic disorder often associated with cancer","volume":"264","author":"Schoser","year":"2017","journal-title":"J Neurol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"27","DOI":"10.2147\/DNND.S192588","article-title":"Lambert-Eaton Myasthenic syndrome: early diagnosis is key","volume":"9","author":"Ivanovski","year":"2019","journal-title":"Degener Neurol Neuromuscul Dis"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0270136","article-title":"The flipped classroom is effective for medical students to improve deep tendon reflex examination skills: A mixed-method study","volume":"17","author":"Uchida","year":"2022","journal-title":"PloS One"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1186\/1472-6920-10-49","article-title":"Attitudes of US medical trainees towards neurology education: \u201cNeurophobia\u201d - a global issue","volume":"10","author":"Zinchuk","year":"2010","journal-title":"BMC Med Educ"},{"key":"B8","unstructured":"Small Cell Lung Cancer\n          \n          \n          \n          2026"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000001721","article-title":"Paraneoplastic neurologic disorders in small cell lung carcinoma: A prospective study","volume":"85","author":"Gozzard","year":"2015","journal-title":"Neurology"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1097\/JTO.0b013e3181c3f4f1","article-title":"Prospective study into the incidence of Lambert Eaton myasthenic syndrome in small cell lung cancer","volume":"5","author":"Payne","year":"2010","journal-title":"J Thorac Oncol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.20043","article-title":"Neurologic disorders in 432 consecutive patients with small cell lung carcinoma","volume":"100","author":"Seute","year":"2004","journal-title":"Cancer"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1002\/mus.20332","article-title":"Lambert-Eaton myasthenic syndrome has a more progressive course in patients with lung cancer","volume":"32","author":"Wirtz","year":"2005","journal-title":"Muscle Nerve"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(84)90523-0","article-title":"Paraneoplastic syndromes and constitutional symptoms in prediction of metastatic behavior of small cell carcinoma of the lung","volume":"77","author":"de la Monte","year":"1984","journal-title":"Am J Med"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1111\/1759-7714.14318","article-title":"Gastroesophageal reflux disease and paraneoplastic neurological syndrome associated with long-term survival in limited stage small-cell lung cancer","volume":"13","author":"Ernani","year":"2022","journal-title":"Thorac Cancer"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1002\/mus.25520","article-title":"Lambert-Eaton myasthenic syndrome: Epidemiology and therapeutic response in the national veterans affairs population","volume":"56","author":"Abenroth","year":"2017","journal-title":"Muscle Nerve"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1405.030","article-title":"Lambert-Eaton myasthenic syndrome: tumor versus nontumor forms","volume":"1132","author":"Titulaer","year":"2008","journal-title":"Ann N Y Acad Sci"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2008.05.025","article-title":"The Lambert-Eaton myasthenic syndrome 1988-2008: a clinical picture in 97 patients","author":"Titulaer","year":"2008","journal-title":"J Neuroimmunol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)76153-5","article-title":"Favourable prognosis in Lambert-Eaton myasthenic syndrome and small-cell lung carcinoma","volume":"353","author":"Maddison","year":"1999","journal-title":"Lancet"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000003794","article-title":"Long-term survival in paraneoplastic Lambert-Eaton myasthenic syndrome","volume":"88","author":"Maddison","year":"2017","journal-title":"Neurology"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1809064","article-title":"First-line atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer","volume":"379","author":"Horn","year":"2018","journal-title":"N Engl J Med"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)32222-6","article-title":"Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial","volume":"394","author":"Paz-Ares","year":"2019","journal-title":"Lancet"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-823912-4.00024-4","article-title":"Neurologic manifestations of autoimmunity with immune checkpoint inhibitors","volume":"200","author":"McCombe","year":"2024","journal-title":"Handb Clin Neurol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000010632","article-title":"Neurologic autoimmunity and immune checkpoint inhibitors: Autoantibody profiles and outcomes","volume":"95","author":"Sechi","year":"2020","journal-title":"Neurology"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD003279.pub3","article-title":"Treatment for Lambert-Eaton myasthenic syndrome","volume":"2011","author":"Keogh","year":"2011","journal-title":"Cochrane Database Syst Rev"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1002\/mus.25070","article-title":"Amifampridine phosphate (Firdapse (R)) is effective and safe in a phase 3 clinical trial in LEMS","volume":"53","author":"Oh","year":"2016","journal-title":"Muscle Nerve"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2024.1358562","article-title":"Development of an algorithm to identify small cell lung cancer patients in claims databases","volume":"14","author":"Danese","year":"2024","journal-title":"Front Oncol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.18553\/jmcp.2024.30.2.118","article-title":"Impact of formulary-related pharmacy claim rejections of cariprazine on health care utilization and treatment patterns among patients with bipolar I disorder","volume":"30","author":"Laliberte","year":"2024","journal-title":"J Manag Care Spec Pharm"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1007\/s12325-021-01883-8","article-title":"Real-world adherence to antiretroviral therapy among HIV-1 patients across the United States","volume":"38","author":"McComsey","year":"2021","journal-title":"Adv Ther"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.5665\/sleep.3470","article-title":"Increased mortality in narcolepsy","volume":"37","author":"Ohayon","year":"2014","journal-title":"Sleep"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1007\/s40120-020-00219-y","article-title":"Consequences of insurance denials among U.S. Patients prescribed repository corticotropin injection for acute exacerbations of multiple sclerosis","volume":"10","author":"Rice","year":"2021","journal-title":"Neurol Ther"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0257246","article-title":"Development and validation of a one year predictive model for secondary fractures in osteoporosis","volume":"16","author":"Williams","year":"2021","journal-title":"PloS One"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1093\/crocol\/otad045","article-title":"Persistence and dose escalation during maintenance phase and use of nonbiologic medications among patients with ulcerative colitis initiated on ustekinumab in the United States","volume":"5","author":"Zhdanava","year":"2023","journal-title":"Crohns Colitis 360"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2016.2238","article-title":"Prevalence of autoimmune disease among patients with lung cancer: implications for immunotherapy treatment options","volume":"2","author":"Khan","year":"2016","journal-title":"JAMA Oncol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1200\/CCI.23.00165","article-title":"Validation of an updated algorithm to identify patients with incident non-small cell lung cancer in administrative claims databases","volume":"8","author":"Patel","year":"2024","journal-title":"JCO Clin Cancer Inform"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1185\/030079908x280464","article-title":"Costs associated with intravenous chemotherapy administration in patients with small cell lung cancer: a retrospective claims database analysis","volume":"24","author":"Duh","year":"2008","journal-title":"Curr Med Res Opin"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2017.00883","article-title":"Validation of a case-finding algorithm for identifying patients with non-small cell lung cancer (NSCLC) in administrative claims databases","volume":"8","author":"Turner","year":"2017","journal-title":"Front Pharmacol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000008747","article-title":"Long-term follow-up, quality of life, and survival of patients with Lambert-Eaton myasthenic syndrome","volume":"94","author":"Lipka","year":"2020","journal-title":"Neurology"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.17.5133","article-title":"Screening for small-cell lung cancer: a follow-up study of patients with Lambert-Eaton myasthenic syndrome","volume":"26","author":"Titulaer","year":"2008","journal-title":"J Clin Oncol"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.35281","article-title":"The changing landscape of small cell lung cancer","volume":"130","author":"Cittolin-Santos","year":"2024","journal-title":"Cancer"},{"key":"B40","article-title":"Oral etoposide in small-cell lung cancer","volume":"13","author":"Comis","year":"1986","journal-title":"Semin Oncol"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1016\/j.lungcan.2006.02.005","article-title":"Third-line chemotherapy for small cell lung cancer","volume":"52","author":"de Jong","year":"2006","journal-title":"Lung Cancer"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2021.01.071","article-title":"Second-line nivolumab in relapsed small-cell lung cancer: CheckMate 331(\u2606)","volume":"32","author":"Spigel","year":"2021","journal-title":"Ann Oncol"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.20.02212","article-title":"Nivolumab and ipilimumab as maintenance therapy in extensive-disease small-cell lung cancer: checkMate 451","volume":"39","author":"Owonikoko","year":"2021","journal-title":"J Clin Oncol"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/s0303-8467(02)00054-9","article-title":"Differences in clinical features between the Lambert-Eaton myasthenic syndrome with and without cancer: an analysis of 227 published cases","volume":"104","author":"Wirtz","year":"2002","journal-title":"Clin Neurol Neurosurg"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1097\/00006842-199803000-00006","article-title":"Gender differences in the reporting of physical and somatoform symptoms","volume":"60","author":"Kroenke","year":"1998","journal-title":"Psychosom Med"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.7150\/jca.75622","article-title":"A 2022 update on extensive stage small-cell lung cancer (SCLC)","volume":"13","author":"Oronsky","year":"2022","journal-title":"J Cancer"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1093\/jjco\/hyaa104","article-title":"Impact of reduced smoking rates on lung cancer screening programs in Japan","volume":"50","author":"Hemmi","year":"2020","journal-title":"Jpn J Clin Oncol"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMsa1211127","article-title":"50-year trends in smoking-related mortality in the United States","volume":"368","author":"Thun","year":"2013","journal-title":"N Engl J Med"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-022-01184-0","article-title":"Paraneoplastic autoimmune neurological syndromes and the role of immune checkpoint inhibitors","volume":"19","author":"Duong","year":"2022","journal-title":"Neurotherapeutics"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000000604","article-title":"Increased frequency of anti-Ma2 encephalitis associated with immune checkpoint inhibitors","volume":"6","author":"Vogrig","year":"2019","journal-title":"Neurol Neuroimmunol Neuroinflamm"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2025.1650373\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T04:14:10Z","timestamp":1760674450000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2025.1650373\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,17]]},"references-count":50,"alternative-id":["10.3389\/fonc.2025.1650373"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2025.1650373","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,17]]},"article-number":"1650373"}}