{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T06:27:00Z","timestamp":1786688820006,"version":"build-2736575974"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"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. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Durable benefit from first-line PD-1\/PD-L1 inhibitor-based therapy remains heterogeneous in advanced non-small cell lung cancer (NSCLC). Baseline biomarkers, including PD-L1 tumor proportion score, tumor mutational burden, and static inflammatory indices, only partly capture this heterogeneity and may not reflect host response. We evaluated whether a cycle 2 immune-inflammatory and nutritional recovery signature from blood markers was associated with durable clinical benefit (DCB), early progression, and survival.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This single-center retrospective cohort included 420 patients with advanced NSCLC treated with first-line PD-1\/PD-L1 inhibitor-based therapy at Chengdu Third People\u2019s Hospital between January 2019 and September 2025, with data cutoff on March 31, 2026. The primary analytic cohort comprised 409 patients with a rule-derived cycle 2 dynamic recovery signature: favorable recovery, intermediate, or persistent failure. DCB at 6\u202fmonths and early progression within 3\u202fmonths were the primary endpoints. Associations were estimated using Firth-type penalized logistic regression and Cox models adjusted for clinical covariates and baseline NLR, PNI, and ALI. Model performance was assessed using discrimination, calibration, decision curves, and bootstrap optimism correction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 409 classifiable patients, 141 (34.5%), 115 (28.1%), and 153 (37.4%) had favorable recovery, intermediate, and persistent failure signatures. DCB occurred in 61.7, 43.5, and 33.3%, and early progression occurred in 11.3, 18.3, and 23.5%, respectively. Compared with favorable recovery, persistent failure was associated with lower DCB (adjusted odds ratio [OR], 0.34; 95% CI, 0.21\u20130.56), higher early progression (adjusted OR, 2.15; 95% CI, 1.13\u20134.07), and shorter progression-free survival (adjusted hazard ratio [HR], 3.34; 95% CI, 2.40\u20134.64). Its adjusted association with overall survival was weaker (HR, 1.22; 95% CI, 0.86\u20131.72). The clinical plus dynamic signature model had optimism-corrected AUCs of 0.619 for DCB and 0.562 for early progression. The composite signature did not outperform individual continuous dynamic biomarkers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>A rule-derived cycle 2 immune-inflammatory and nutritional recovery signature was independently associated with DCB and progression-free survival, but discrimination was modest, early-progression performance was weak, and no robust adjusted overall survival association was observed. It should be interpreted as an exploratory risk-stratification summary, not a clinically ready prediction tool. External validation and prospective evaluation are required before clinical use.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1900721","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T05:32:08Z","timestamp":1786685528000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Early dynamic immune-inflammatory and nutritional recovery signature is associated with durable benefit and early progression in advanced non-small cell lung cancer receiving first-line PD-1\/PD-L1 inhibitor-based therapy: a real-world retrospective cohort study"],"prefix":"10.3389","volume":"13","author":[{"given":"Tingting","family":"Zhan","sequence":"first","affiliation":[{"name":"Department of Oncology, The Third People\u2019s Hospital of Chengdu","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hang","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Oncology, The Third People\u2019s Hospital of Chengdu","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,14]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2020","journal-title":"CA Cancer J Clin"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1016\/S0140-6736(21)00312-3","article-title":"Lung cancer","volume":"398","author":"Thai","year":"2021","journal-title":"Lancet"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"e1","DOI":"10.1200\/JCO.22.02121","article-title":"Therapy for stage IV non-small-cell lung Cancer without driver alterations: ASCO living guideline, version 2022.2","volume":"41","author":"Owen","year":"2023","journal-title":"J Clin Oncol"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"249","DOI":"10.6004\/jnccn.2204.0023","article-title":"Non-small cell lung Cancer, version 4.2024, NCCN clinical practice guidelines in oncology","volume":"22","author":"Riely","year":"2024","journal-title":"J Natl Compr Cancer Netw"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"1823","DOI":"10.1056\/NEJMoa1606774","article-title":"Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer","volume":"375","author":"Reck","year":"2016","journal-title":"N Engl J Med"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"2078","DOI":"10.1056\/NEJMoa1801005","article-title":"Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer","volume":"378","author":"Gandhi","year":"2018","journal-title":"N Engl J Med"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"2040","DOI":"10.1056\/NEJMoa1810865","article-title":"Pembrolizumab plus chemotherapy for squamous non-small-cell lung cancer","volume":"379","author":"Paz-Ares","year":"2018","journal-title":"N Engl J Med"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"1819","DOI":"10.1016\/S0140-6736(18)32409-7","article-title":"Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial","volume":"393","author":"Mok","year":"2019","journal-title":"Lancet"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"1992","DOI":"10.1200\/JCO.22.01989","article-title":"Pembrolizumab plus pemetrexed and platinum in nonsquamous non-small-cell lung cancer: 5-year outcomes from the phase 3 KEYNOTE-189 study","volume":"41","author":"Garassino","year":"2023","journal-title":"J Clin Oncol"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"1999","DOI":"10.1200\/JCO.22.01990","article-title":"Pembrolizumab plus chemotherapy in squamous non-small-cell lung cancer: 5-year update of the phase III KEYNOTE-407 study","volume":"41","author":"Novello","year":"2023","journal-title":"J Clin Oncol"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1126\/science.aaa1348","article-title":"Cancer immunology. 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