{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T02:43:48Z","timestamp":1792205028061,"version":"4.4.0"},"reference-count":43,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2021,7,13]],"date-time":"2021-07-13T00:00:00Z","timestamp":1626134400000},"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>To examine the extent of the evaluation required to achieve diagnostic resolution and the test performance characteristics of a targeted methylation cell-free DNA (cfDNA)-based multi-cancer early detection (MCED) test, ~6200 participants \u226550 years with (cohort A) or without (cohort B) \u22651 of 3 additional specific cancer risk factors will be enrolled in PATHFINDER (NCT04241796), a prospective, longitudinal, interventional, multi-center study. Plasma cfDNA from blood samples will be analyzed to detect abnormally methylated DNA associated with cancer (i.e., cancer \u201csignal\u201d) and a cancer signal origin (i.e., tissue of origin). Participants with a \u201csignal detected\u201d will undergo further diagnostic evaluation per guiding physician discretion; those with a \u201csignal not detected\u201d will be advised to continue guideline-recommended screening. The primary objective will be to assess the number and types of subsequent diagnostic tests needed for diagnostic resolution. Based on microsimulations (using estimates of cancer incidence and dwell times) of the typical risk profiles of anticipated participants, the median (95% CI) number of participants with a \u201csignal detected\u201d result is expected to be 106 (87\u2013128). Subsequent diagnostic evaluation is expected to detect 52 (39\u201367) cancers. The positive predictive value of the MCED test is expected to be 49% (39\u201358%). PATHFINDER will evaluate the integration of a cfDNA-based MCED test into existing clinical cancer diagnostic pathways. The study design of PATHFINDER is described here.<\/jats:p>","DOI":"10.3390\/cancers13143501","type":"journal-article","created":{"date-parts":[[2021,7,13]],"date-time":"2021-07-13T22:25:31Z","timestamp":1626215131000},"page":"3501","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":100,"title":["The PATHFINDER Study: Assessment of the Implementation of an Investigational Multi-Cancer Early Detection Test into Clinical Practice"],"prefix":"10.3390","volume":"13","author":[{"given":"Lincoln D.","family":"Nadauld","sequence":"first","affiliation":[{"name":"Hematology\/Oncology, Intermountain Healthcare, St. George, UT 84790, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"III","given":"Charles H.","family":"McDonnell","sequence":"additional","affiliation":[{"name":"Sutter Health, Sacramento, CA 95816, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomasz M.","family":"Beer","sequence":"additional","affiliation":[{"name":"Hematology\/Medical Oncology, Oregon Health & Science University Knight Cancer Institute, Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minetta C.","family":"Liu","sequence":"additional","affiliation":[{"name":"Departments of Oncology and Laboratory Medicine & Pathology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric A.","family":"Klein","sequence":"additional","affiliation":[{"name":"Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Hudnut","sequence":"additional","affiliation":[{"name":"Sutter Health, Sacramento, CA 95816, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard A.","family":"Whittington","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Intermountain Healthcare, Salt Lake City, UT 84111, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce","family":"Taylor","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Intermountain Healthcare, Salt Lake City, UT 84111, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geoffrey R.","family":"Oxnard","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Division of Population Sciences, Dana-Farber Cancer Institute, Boston, MA 02215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4671-5813","authenticated-orcid":false,"given":"Jafi","family":"Lipson","sequence":"additional","affiliation":[{"name":"Radiology Department, Stanford Hospital and Clinics, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margarita","family":"Lopatin","sequence":"additional","affiliation":[{"name":"GRAIL, Inc., Menlo Park, CA 94025, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita","family":"Shaknovich","sequence":"additional","affiliation":[{"name":"GRAIL, Inc., Menlo Park, CA 94025, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4170-8390","authenticated-orcid":false,"given":"Karen C.","family":"Chung","sequence":"additional","affiliation":[{"name":"GRAIL, Inc., Menlo Park, CA 94025, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric T.","family":"Fung","sequence":"additional","affiliation":[{"name":"GRAIL, Inc., Menlo Park, CA 94025, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah","family":"Schrag","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Division of Population Sciences, Dana-Farber Cancer Institute, Boston, MA 02215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9128-3012","authenticated-orcid":false,"given":"Catherine R.","family":"Marinac","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Division of Population Sciences, Dana-Farber Cancer Institute, Boston, MA 02215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"279","DOI":"10.7326\/M15-2886","article-title":"Screening for Breast Cancer: U.S. Preventive Services Task Force Recommendation Statement","volume":"164","author":"Siu","year":"2016","journal-title":"Ann. 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