{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T06:08:22Z","timestamp":1788761302566,"version":"build-2803163510"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"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>Pathological response after neoadjuvant chemotherapy is a key treatment milestone in osteosarcoma. We evaluated whether a rule-derived preoperative peripheral inflammatory-lymphocyte recovery phenotype constructed from routinely collected laboratory measurements was associated with poor pathological response.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This single-center retrospective cohort included patients with osteosarcoma who completed neoadjuvant chemotherapy, underwent definitive surgery, had pathological response assessed, and had valid baseline (T0) and preoperative (T3) laboratory measurements. A failure score combined standardized myeloid-inflammatory burden and lymphocyte-nutritional reserve. Patients were classified as favorable recovery, intermediate recovery phenotype, or persistent recovery failure using the primary T0-T3 rule. The primary outcome was tumor necrosis &amp;lt;90%. The primary association was estimated using parsimonious Firth logistic regression, with modified-Poisson risk ratios and standardized absolute risks. Model comparisons used nested full-pipeline repeated cross-validation. Event-related analyses were exploratory.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 162 patients, 88 (54.3%) had poor pathological response; 65 were classified as favorable recovery, 45 as intermediate, and 52 as persistent recovery failure. Persistent failure was associated with poor pathological response versus favorable recovery (Firth OR, 5.72; 95% CI, 2.42-13.53; P&amp;lt;0.001; adjusted RR, 2.10; 95% CI, 1.46-3.01). Standardized risks were 37.2% for favorable recovery and 75.7% for persistent failure, corresponding to a risk difference of 38.6 percentage points (95% CI, 19.7-52.7). In nested full-pipeline cross-validation, the phenotype model had an AUC of 0.641 and did not outperform the continuous T3 score (AUC, 0.665); its out-of-fold calibration slope was 0.587 (95% CI, 0.220-0.953). Exploratory associations were observed for event-free survival (EFS) and pulmonary metastasis, whereas overall survival (OS) was immature with 24 deaths.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>A rule-derived preoperative peripheral inflammatory-lymphocyte recovery phenotype was associated with pathological response among patients who completed neoadjuvant chemotherapy and underwent definitive surgery for osteosarcoma. The association was robust across alternative definitions and sensitivity analyses; however, the categorical phenotype did not outperform the continuous preoperative T3 score, and out-of-fold calibration indicated residual overfitting. Event-related findings and biological interpretation require external validation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1925540","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T05:34:48Z","timestamp":1788759288000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Rule-derived preoperative inflammatory-lymphocyte recovery phenotype and pathological response in resected osteosarcoma: a retrospective cohort study"],"prefix":"10.3389","volume":"17","author":[{"given":"Yang","family":"Liu","sequence":"first","affiliation":[{"name":"The Second Hospital & Clinical Medical School, Lanzhou University","place":["Lanzhou, Gansu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Huang","sequence":"additional","affiliation":[{"name":"The Second Hospital & Clinical Medical School, Lanzhou University","place":["Lanzhou, Gansu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Chengdu Xinhua Hospital Affiliated to North Sichuan Medical College","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daxin","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Neijiang Hospital of Traditional Chinese Medicine","place":["Neijiang, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian","family":"Hao","sequence":"additional","affiliation":[{"name":"The Second Hospital & Clinical Medical School, Lanzhou University","place":["Lanzhou, Gansu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyu","family":"Zhou","sequence":"additional","affiliation":[{"name":"The Second Hospital & Clinical Medical School, Lanzhou University","place":["Lanzhou, Gansu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonghong","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Chengdu Xinhua Hospital Affiliated to North Sichuan Medical College","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3838","article-title":"Translational biology of osteosarcoma","volume":"14","author":"Kansara","year":"2014","journal-title":"Nat Rev Cancer"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-021-00519-8","article-title":"Advancing therapy for osteosarcoma","volume":"18","author":"Gill","year":"2021","journal-title":"Nat Rev Clin Oncol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1056\/nejmra2103423","article-title":"New horizons in the treatment of 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