{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T15:30:10Z","timestamp":1784302210171,"version":"3.55.0"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T00:00:00Z","timestamp":1769472000000},"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>Identifying patients who are most likely to benefit from the combination of bevacizumab and chemotherapy (Bev\/CT) is essential for the optimal management of metastatic colorectal cancer (mCRC). The aim of this study is to investigate the utility of chronic inflammatory biomarkers in predicting clinical response to Bev\/CT and outcomes in patients with mCRC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>This study enrolled 364 patients with mCRC undergoing first-line Bev\/CT therapy. The patients were randomly assigned to discovery (n=249) and validation (n=115) cohorts, maintaining an approximate 2:1 ratio. Two machine learning algorithms, least absolute shrinkage and selection operator (LASSO)-penalized Cox regression and random survival forest (RSF), were employed to identify significant inflammatory biomarkers. Logistic regression, Kaplan-Meier survival analysis, and Cox regression analyses were conducted to evaluate the associations between the clinical outcomes and a product of fibrinogen-pre-albumin ratio and systematic inflammatory ratio (SIR) (FPSIR) and clinical outcomes. The primary endpoints included clinical disease control rate (DCR) and progression-free survival (PFS), 2-year overall survival (OS) was designated as a secondary endpoint.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Following the integration of inflammatory biomarkers identified through the LASSO and RSF algorithms, FPSIR was independently associated with PFS in both the discovery (\n                      <jats:italic>p<\/jats:italic>\n                      <jats:sub>log-rank<\/jats:sub>\n                      &amp;lt;0.001, adjusted HR = 1.90, 95%CI=1.40-2.57) and validation cohorts (\n                      <jats:italic>p<\/jats:italic>\n                      <jats:sub>log-rank<\/jats:sub>\n                      =0.01, adjusted HR = 1.89, 95%CI=1.21-2.98). Furthermore, FPSIR-H was significantly associated with worse 2-year OS in the two cohorts (discovery cohort:\n                      <jats:italic>p<\/jats:italic>\n                      <jats:sub>log-rank<\/jats:sub>\n                      &amp;lt;0.001, adjusted HR = 2.15, 95%CI=1.49-3.10; validation cohort:\n                      <jats:italic>p<\/jats:italic>\n                      <jats:sub>log-rank<\/jats:sub>\n                      =0.02, adjusted HR = 1.93, 95%CI=1.06-3.51). Survival nomograms that incorporated CEA, CA19\u20139 and FPSIR (CCF) score, along with peritoneum metastases, number of metastatic sites, surgical intervention, and treatment regimens could effectively estimate 2-year PFS (AUC = 0.83) and 18-month OS (AUC = 0.71) in the discovery cohort, demonstrating robust performance in the validation cohort (AUC = 0.76 and 0.75 for PFS and OS, respectively). Elevated FPSIR was correlated with diminished DCR in Bev\/CT therapy (\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.01, adjusted OR = 2.24, 95% CI = 1.27-3.96). Serial measurements of FPSIR exhibited dynamic changes that effectively monitored the efficacy of Bev\/CT treatment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Pretreatment FPSIR was identified as a robust biomarker for predicting clinical efficacy and prognosis in mCRC patients receiving first-line Bev\/CT, providing a promising strategy to address the long-standing challenge of treatment stratification.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1683928","type":"journal-article","created":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T06:42:13Z","timestamp":1769496133000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["FPSIR predicts clinical therapeutic responses and survival outcomes in patients with metastatic colorectal cancer undergoing 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