{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T14:02:19Z","timestamp":1765980139072,"version":"3.48.0"},"reference-count":34,"publisher":"Harborside Press, LLC","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,12]]},"abstract":"\n Circulating tumor DNA (ctDNA) testing is a minimally invasive alternative to tissue biopsy and is ideal for inaccessible tumors or limited samples. It captures tumor heterogeneity over time and different anatomic locations, unlike the static snapshot provided by a biopsy. In this report, we describe a 68-year-old female with an initial diagnosis of metastatic pancreatic adenocarcinoma (a pancreas head mass with multiple bilateral lung nodules). Mutation profiling of the pancreatic mass biopsy using a comprehensive cancer next-generation sequencing (NGS) panel was unsuccessful due to insufficient tissue. Consequently, ctDNA testing using a pan-cancer NGS panel was performed, and an\n EGFR<\/jats:italic>\n p.L858R variant at 2.15% was identified. Interestingly, this activating variant is highly specific to non\u2013small cell lung cancer (NSCLC), which raised the possibility of a synchronous tumor unrelated to the pancreatic mass. Immunohistochemistry showed the\n EGFR<\/jats:italic>\n variant in station 7 lymph nodes but not in pancreatic biopsy tissue, supporting the inference that the variant originated from the lung mass. Droplet digital PCR on the limited pancreatic biopsy identified a\n KRAS<\/jats:italic>\n p.Q61 variant, which was absent by ctDNA testing, suggesting a pancreatic primary with low ctDNA levels. In addition to diagnosing a primary lung cancer, ctDNA testing guided treatment decisions. With a primary\n EGFR<\/jats:italic>\n p.L858R\u2013mutant NSCLC, osimertinib was administered, resulting in a partial response within 10 months. In addition, given the synchronous primary pancreatic adenocarcinoma, germline testing was performed, revealing a CDKN2A p.I49T variant consistent with melanoma-pancreatic cancer syndrome, prompting comprehensive cancer surveillance and familial testing. This case illustrates how ctDNA testing enabled a comprehensive evaluation by clarifying the diagnosis, identifying actionable biomarkers, and facilitating genetic risk assessment, ultimately having a significant impact on the patient\u2019s clinical management.\n <\/jats:p>","DOI":"10.6004\/jnccn.2025.7098","type":"journal-article","created":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T13:56:19Z","timestamp":1765979779000},"source":"Crossref","is-referenced-by-count":0,"title":["From Diagnosis, Therapy Decision-Making to Genetic Risk Assessment: The Impact of ctDNA Testing on Comprehensive Cancer Management\u2014A Case Report"],"prefix":"10.6004","volume":"23","author":[{"given":"Nisha","family":"Kanwar","sequence":"first","affiliation":[{"name":"Division of Laboratory Genetics and Genomics, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abidoye B.","family":"Seyi","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Internal Medicine, Mayo Clinic, Phoenix, AZ"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nelly","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Radiology, Mayo Clinic, Phoenix, AZ"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlos","family":"Rojas","sequence":"additional","affiliation":[{"name":"Department of Radiology, Mayo Clinic, Phoenix, AZ"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vinicius","family":"Ernani","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Internal Medicine, Mayo Clinic, Phoenix, AZ"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kandelaria M.","family":"Rumilla","sequence":"additional","affiliation":[{"name":"Division of Laboratory Genetics and Genomics, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mitesh J.","family":"Borad","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Internal Medicine, Mayo Clinic, Phoenix, AZ"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gang","family":"Zheng","sequence":"additional","affiliation":[{"name":"Division of Laboratory Genetics and Genomics, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"4047","reference":[{"key":"B1","series-title":"Cancer Med","first-page":"2085","article-title":"Detection of plasma EGFR mutations for personalized treatment of lung cancer patients without pathologic diagnosis","volume":"9","author":"Deng Q","year":"2020","unstructured":"Deng Q, Fang Q, Sun H, Detection of plasma EGFR mutations for personalized treatment of lung cancer patients without pathologic diagnosis. 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JAMA Oncol 2022;8:1328\u20131332."},{"key":"B3","series-title":"Cancer","first-page":"3219","article-title":"Spectrum of driver mutations and clinical impact of circulating tumor DNA analysis in non-small cell lung cancer: analysis of over 8000 cases","volume":"126","author":"Mack PC","year":"2020","unstructured":"Mack PC, Banks KC, Espenschied CR, Spectrum of driver mutations and clinical impact of circulating tumor DNA analysis in non-small cell lung cancer: analysis of over 8000 cases. Cancer 2020;126:3219\u20133228."},{"key":"B4","series-title":"Br J Cancer","first-page":"383","article-title":"Liquid biopsy and non-small cell lung cancer: are we looking at the tip of the iceberg?","volume":"127","author":"Bonanno L","year":"2022","unstructured":"Bonanno L, Dal Maso A, Pavan A, Liquid biopsy and non-small cell lung cancer: are we looking at the tip of the iceberg? Br J Cancer 2022;127:383\u2013393."},{"key":"B5","series-title":"JCO Precis Oncol","first-page":"e2300382","article-title":"Recommendations for the equitable and widespread implementation of liquid biopsy for cancer care","volume":"8","author":"Febbo PG","year":"2024","unstructured":"Febbo PG, Allo M, Alme EB, Recommendations for the equitable and widespread implementation of liquid biopsy for cancer care. JCO Precis Oncol 2024;8:e2300382."},{"author":"Ettinger DS","unstructured":"Ettinger DS, Wood DE, Aisner DL, NCCN Clinical Practice Guidelines in Oncology: Non-Small Cell Lung Cancer. Version 3.2022. Accessed August 28, 2023. To view the most recent version, visit https:\/\/www.nccn.org","article-title":"NCCN Clinical Practice Guidelines in Oncology: Non-Small Cell Lung Cancer. Version 3.2022","key":"B6"},{"author":"Tempero MA","unstructured":"Tempero MA, Malafa MP, Basturk O, NCCN Clinical Practice Guidelines in Oncology: Pancreatic Adenocarcinoma. Version 2.2025. 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