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VEGF-A comprises several isoforms, including VEGF\n                      <jats:sub>121<\/jats:sub>\n                      and VEGF\n                      <jats:sub>165<\/jats:sub>\n                      . However, the clinical potential as blood biomarkers in EGFR-TKI treatment remains unclear.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We retrospectively analyzed 64 patients with advanced\n                      <jats:italic>EGFR<\/jats:italic>\n                      -mutated NSCLC who received EGFR-TKI monotherapy at Hiroshima University Hospital between November 2009 and August 2023. Pre-treatment serum levels of total VEGF-A (tVEGF-A), VEGF\n                      <jats:sub>121<\/jats:sub>\n                      , and VEGF\n                      <jats:sub>165<\/jats:sub>\n                      were measured using enzyme-linked immunosorbent assays. The association of these biomarkers with the objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) was analyzed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The ORR was 78.1%, and the median PFS and OS were 7.5 and 31.8 months, respectively. Serum VEGF\n                      <jats:sub>121<\/jats:sub>\n                      levels were significantly higher in non-responders than in responders (median, 446.6 vs. 322.1\u00a0pg\/mL,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.043), whereas no significant differences were observed for tVEGF-A and VEGF\n                      <jats:sub>165<\/jats:sub>\n                      levels. Receiver operating characteristic analysis identified an optimal serum VEGF\n                      <jats:sub>121<\/jats:sub>\n                      cut-off level of 339.3\u00a0pg\/mL (AUC: 0.678, sensitivity: 52.0%, specificity: 92.9%). Patients with higher serum VEGF\n                      <jats:sub>121<\/jats:sub>\n                      (&gt;\u2009339.3\u00a0pg\/mL) had significantly lower ORR (64.9% vs. 96.3%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.003), shorter PFS (median, 6.2 vs. 14.4\u00a0months,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.026), and shorter OS (median, 27.6 months vs. not reached,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.040) than those with lower serum VEGF\n                      <jats:sub>121<\/jats:sub>\n                      (\u2264\u2009339.3\u00a0pg\/mL).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Higher levels of serum VEGF\n                      <jats:sub>121<\/jats:sub>\n                      were associated with lower EGFR-TKI efficacy and poorer prognosis in patients with\n                      <jats:italic>EGFR<\/jats:italic>\n                      -mutated NSCLC.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s10147-026-03083-2","type":"journal-article","created":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T11:40:40Z","timestamp":1781005240000},"page":"1696-1705","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical implications of serum total VEGF-A and VEGF-A isoforms in patients with EGFR-mutated advanced non-small cell lung cancer treated with EGFR-TKIs"],"prefix":"10.1007","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-9091-3397","authenticated-orcid":false,"given":"Tetsu","family":"Hirakawa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9117-1934","authenticated-orcid":false,"given":"Kakuhiro","family":"Yamaguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5382-4730","authenticated-orcid":false,"given":"Kiyofumi","family":"Shimoji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinjiro","family":"Sakamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3390-8491","authenticated-orcid":false,"given":"Yasushi","family":"Horimasu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3557-0049","authenticated-orcid":false,"given":"Takeshi","family":"Masuda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0035-674X","authenticated-orcid":false,"given":"Taku","family":"Nakashima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4922-5334","authenticated-orcid":false,"given":"Hiroshi","family":"Iwamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7979-0708","authenticated-orcid":false,"given":"Hironobu","family":"Hamada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noboru","family":"Hattori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,9]]},"reference":[{"key":"3083_CR1","doi-asserted-by":"publisher","first-page":"2380","DOI":"10.1056\/NEJMoa0909530","volume":"362","author":"M Maemondo","year":"2010","unstructured":"Maemondo M, Inoue A, Kobayashi K et al (2010) Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. 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Kakuhiro Yamaguchi reports personal fees from Ono Pharmaceutical Co., Ltd, Chugai Pharmaceutical Co., Ltd, Bristol Myers Squibb, and AstraZeneca K.K., and also reports grants from Shino-Test Corporation. Takeshi Masuda reports personal fees from Daiichi-Sankyo Co., Ltd., Taiho Pharmaceutical Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Kyowa Kirin Co., Ltd., Eli Lilly Japan K.K., Ono Pharmaceutical Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., and AstraZeneca K.K. Noboru Hattori reports personal fees from AstraZeneca K.K., Chugai Pharmaceutical Co., Ltd, and Bristol Myers Squibb, and reports grants from Ono Pharmaceutical Co., Ltd, Chugai Pharmaceutical Co., Ltd., and Shino-test Corporation. The other authors have nothing to disclose.","order":1,"name":"Ethics","label":"Conflicts of interest","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was approved by the Ethics Committee of Hiroshima University Hospital, and all participants provided written informed consent for the use of their medical records (Hiroshima University Hospital [E2004-326]).","order":2,"name":"Ethics","label":"Ethics approval","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Portions of this work were presented at the 66th Annual Meeting of the Japan Lung Cancer Society (Oral Session, November 8, 2025).","order":3,"name":"Ethics","label":"Conference presentation","group":{"name":"EthicsHeading","label":"Declarations"}}]}}