{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T06:25:17Z","timestamp":1787034317966,"version":"build-2736575974"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>Leptomeningeal metastasis (LM) from ERBB2-mutant lung adenocarcinoma is difficult to treat and monitor because systemic disease and leptomeningeal disease may evolve discordantly. Evidence regarding cerebrospinal fluid (CSF) genomic profiling and serial CSF tumor marker monitoring in ERBB2-mutant non-small cell lung cancer with LM remains limited. We report a 48-year-old woman initially diagnosed with stage IB mucinous lung adenocarcinoma harboring an ERBB2 exon 20 p.G776delinsVC mutation. After surgery and adjuvant chemotherapy, she developed nodal recurrence and later presented with lower back pain and lower-limb numbness. LM was clinically diagnosed based on neurological symptoms, magnetic resonance imaging and CSF cytopathology. She received craniospinal irradiation, systemic therapy and subsequent intrathecal treatment. At month 33, CSF CA19\u20139 was markedly elevated despite no clear radiographic systemic progression. CSF\u00a0next-generation sequencing(NGS) detected the same ERBB2 exon 20\u00a0p.G776delinsVC mutation as the primary lung tumor, with a higher variant allele\u00a0fraction in CSF than in lung tissue.The patient subsequently received trastuzumab\u00a0deruxtecan and sequential intrathecal therapy with pemetrexed, etoposide,\u00a0cytarabine and pemetrexed rechallenge. Intrathecal treatment was adjusted according to serial CSF CA19\u20139 levels, neurological status, imaging findings, systemic disease activity and treatment-related toxicities. CSF CA19\u20139 was not used as a stand-alone criterion for progression or treatment modification.At the latest follow-up, she remained alive more than 36 months after the clinical diagnosis of LM. This case suggests that CSF NGS and serial CSF CA19\u20139 may provide further insights into disease activity within the integrated assessment of systemic and leptomeningeal disease. Their clinical applicability is still under investigation and necessitates future validation.<\/jats:p>","DOI":"10.3389\/fonc.2026.1925627","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:28:37Z","timestamp":1787027317000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Serial CSF CA19\u20139 monitoring and CSF genomic profiling in ERBB2-mutant lung adenocarcinoma with leptomeningeal metastasis: a case report"],"prefix":"10.3389","volume":"16","author":[{"given":"Qilin","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Oncology, Affiliated Hospital of North Sichuan Medical College","place":["Nanchong, China"]},{"name":"North Sichuan Medical College","place":["Nanchong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Wen","sequence":"additional","affiliation":[{"name":"Department of Oncology, Affiliated Hospital 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