{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T12:31:55Z","timestamp":1786365115899,"version":"build-2736575974"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T00:00:00Z","timestamp":1782345600000},"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:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Obesity, hyperinsulinemia, and type 2 diabetes mellitus (T2DM) are considered adverse metabolic conditions in cancer, although exceptions like the \u201cobesity paradox\u201d have been reported. Their prognostic significance in advanced lung adenocarcinoma (LUAD), particularly in patients receiving tyrosine kinase inhibitor (TKI) therapy, remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We prospectively analyzed 133 consecutive patients with newly diagnosed stage IV LUAD and ECOG performance status 0\u20131 enrolled between 2020 and 2024. All had \u22653 months of follow-up and T2DM status. BMI was available in 104 patients, glucose and fasting insulin in 46 patients. Primary endpoint was overall survival (OS), assessed using Kaplan\u2013Meier and multivariable Cox regression. Propensity score and interaction analyses evaluated TKI, immune checkpoint inhibitor (ICI), and anti-VEGF therapies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      High BMI, hyperglycemia, hyperinsulinemia, and T2DM were not associated with worse outcomes. In contrast, low BMI (&amp;lt;22.1 kg\/m\u00b2;\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.007, HR 2.56, 95%CI 1.29 - 5.08) and low fasting insulin (\u226434 pmol\/L;\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&amp;lt;\u00a00.001, HR 10.02, 95%CI 2.73\u201336.8) were independently associated with shorter OS, while EGFR\u2013TKI therapy was associated with improved survival (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.02, HR 0.52). Patients with combined BMI &amp;lt;22.1 kg\/m\u00b2 and insulin &amp;lt;34 pmol\/L also derived survival benefit from EGFR\u2013TKI therapy; however, absence of EGFR\u2013TKI in this subgroup was associated with very poor 3-year OS (35%). ICI and anti-VEGF outcomes were not significantly affected.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Low BMI and low fasting insulin identify a metabolically depleted subgroup with poor prognosis in stage IV LUAD, with worse outcomes observed in patients not receiving EGFR\u2013TKI therapy. These parameters may improve risk stratification and support early nutritional and exercise-based interventions.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1742177","type":"journal-article","created":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T09:37:28Z","timestamp":1782380248000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Body mass index and fasting insulin predict survival and EGFR\u2013TKI benefit in Stage IV lung adenocarcinoma"],"prefix":"10.3389","volume":"16","author":[{"given":"Huiru","family":"Guo","sequence":"first","affiliation":[{"name":"Department VI of Medical Oncology, Longhua University Hospital","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingshuang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department VI of Medical Oncology, Longhua University Hospital","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan P. 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