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They can be used to aid in diagnosing and selecting an agent for treatment and can possibly be used to monitor disease response to treatment. In this report, we present a patient who initially presented with lower abdominal pain. Imaging showed extensive retroperitoneal lymphadenopathy and lymph node biopsy demonstrated poorly differentiated carcinoma. Further workup did not reveal a primary lesion, but his genetic analysis revealed a BRAF V600E mutation and CD274 amplification which was used to guide treatment of the adenocarcinoma as a melanoma of unknown primary. He was initiated on ipilimumab and nivolumab and his ctDNA levels showed rapid improvement. After treatment was stopped due to adverse events, he was monitored via ctDNA, with an increase prompting repeat imaging that demonstrated enlargement of his lesions prompting a resumption of treatment.<\/jats:p>","DOI":"10.1136\/bcr-2024-264469","type":"journal-article","created":{"date-parts":[[2025,5,26]],"date-time":"2025-05-26T23:25:22Z","timestamp":1748301922000},"page":"e264469","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Using liquid biopsies to guide treatment and monitor response in BRAF V600E positive adenocarcinoma of unknown primary"],"prefix":"10.1136","volume":"18","author":[{"given":"Philip N","family":"Papayanis","sequence":"first","affiliation":[{"name":"Internal Medicine, Rush University Medical Center, Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cherry","family":"Au","sequence":"additional","affiliation":[{"name":"Internal Medicine, Rush University Medical Center, Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Jelinek","sequence":"additional","affiliation":[{"name":"Hematology, Oncology and Cellular Therapy, Rush University Medical Center, Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6350-5917","authenticated-orcid":false,"given":"Alan","family":"Tan","sequence":"additional","affiliation":[{"name":"Hematology Oncology, Vanderbilt University Medical Center, Nashville, TN, USA"},{"name":"Vanderbilt University Medical Center, Nashville, TN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2025,5,26]]},"reference":[{"key":"2025082623462028000_18.5.e264469.1","unstructured":"Scott JF , Gerstenblith MR . 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