{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T19:33:47Z","timestamp":1791228827734,"version":"4.1.0"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"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. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Brainstem metastasis from small-cell lung cancer (SCLC) is exceedingly rare and is associated with a dismal prognosis. This study presents a case of brainstem metastasis from SCLC treated with the TMEp-CI-M platform, achieving no evidence of disease (NED) for more than 20 months. The TMEp-CI-M platform is designed to overcome resistance in immunologically \u201ccold\u201d tumors through sequential tumor microenvironment priming (TMEp), checkpoint inhibition (CI), and microbiome modulation. We have previously reported its efficacy in pancreatic neuroendocrine carcinoma, hepatocellular carcinoma, pancreatic ductal adenocarcinoma, non-small cell lung cancer (NSCLC), and colorectal cancer.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case introduction<\/jats:title>\n                    <jats:p>A 60-year-old male with programmed death ligand 1 (PD-L1)-negative extensive-stage small-cell lung cancer (ES-SCLC) and brainstem metastasis received the TMEp-CI-M regimen. The TMEp phase integrated stereotactic body radiotherapy (SBRT), low-dose etoposide, and anlotinib, followed by CI with the programmed death 1 (PD-1)\/cytotoxic T lymphocyte antigen 4 (CTLA-4) bispecific antibody cadonilimab and concurrent probiotic supplementation. The patient\u2019s pro-gastrin-releasing peptide (ProGRP) level normalized after the first cycle (from 1803 pg\/mL to 23.71 pg\/mL) during a total of 6 treatment cycles. At the time of this report (20 months after treatment initiation), the patient remains NED, with only Grade 1 hypothyroidism as an adverse event.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The TMEp-CI-M platform may enhance the efficacy of immunotherapy in ES-SCLC, enabling durable responses even in patients with brainstem metastases. Although this platform has demonstrated promise across multiple tumor types, further prospective and mechanistic studies are warranted to confirm its clinical utility.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1807865","type":"journal-article","created":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T05:24:39Z","timestamp":1780291479000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Sustained complete response to TMEp-CI-M platform in refractory small-cell lung cancer with brainstem metastasis: a case report with over 20 months of disease-free survival"],"prefix":"10.3389","volume":"17","author":[{"given":"Yating","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Oncology, The Cangshan District of the 900th Hospital","place":["Fuzhou, Fujian, 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