{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T00:27:16Z","timestamp":1793147236337,"version":"4.5.0"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T00:00:00Z","timestamp":1784073600000},"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>Tumor budding is an adverse histopathological feature in colorectal cancer, but its role in colorectal liver metastases (CRLM) remains insufficiently defined. This study explored the association between tumor budding density and clinical outcomes in resected synchronous and metachronous CRLM.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This single-center ambispective cohort included 77 patients who underwent R0 resection of CRLM between 2007 and 2017. Tumor budding density was assessed in liver metastases and classified as low (0\u20139 buds per field) or high (\u226510 buds per field). Outcomes were analyzed according to tumor budding density, metastatic timing, and preoperative regimen.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Forty-one patients had synchronous and 36 had metachronous CRLM. Overall, 64 patients received preoperative systemic therapy, including FOLFOX4 in 38 and FOLFOX4 plus bevacizumab in 26. Low tumor budding density was associated with better 2-year overall survival in synchronous CRLM, both in the pooled cohort (95.2% vs. 65.0%, p = 0.015) and in patients treated with FOLFOX4 (90.9% vs. 55.6%, p = 0.049) or FOLFOX4 plus bevacizumab (100.0% vs. 66.7%, p = 0.048). No significant association was observed in metachronous CRLM. Kaplan-Meier analyses of time to progression and 5-year overall survival did not show significant differences by tumor budding density.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Tumor budding density showed an exploratory association with 2-year overall survival in patients with synchronous resected colorectal liver metastases, but this association was not consistently observed in metachronous disease or in long-term time-to-event analyses. These findings suggest that tumor budding may reflect aggressive metastatic biology, but larger standardized studies are required before it can be considered an independent prognostic marker.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1901885","type":"journal-article","created":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T04:48:02Z","timestamp":1784090882000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Exploratory analysis of tumor budding density in resected synchronous and metachronous colorectal liver metastases"],"prefix":"10.3389","volume":"16","author":[{"given":"Nemanja","family":"Petrovi\u0107","sequence":"first","affiliation":[{"name":"Faculty of Medicine Novi Sad, University of Novi Sad","place":["Novi Sad, Serbia"]},{"name":"Clinic of Internal Oncology, Oncology Institute of Vojvodina","place":["Sremska Kamenica, 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Kamenica, Serbia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivana","family":"Kolarov Bjelobrk","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Novi Sad, University of Novi Sad","place":["Novi Sad, Serbia"]},{"name":"Clinic of Internal Oncology, Oncology Institute of Vojvodina","place":["Sremska Kamenica, Serbia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jelena","family":"Radi\u0107","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Novi Sad, University of Novi Sad","place":["Novi Sad, Serbia"]},{"name":"Clinic of Internal Oncology, Oncology Institute of Vojvodina","place":["Sremska Kamenica, Serbia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandar","family":"\u0110ermanovi\u0107","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Novi Sad, University of Novi Sad","place":["Novi Sad, Serbia"]},{"name":"Clinic of Internal Oncology, Oncology Institute of Vojvodina","place":["Sremska Kamenica, Serbia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Nikoli\u0107","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Novi Sad, University of Novi Sad","place":["Novi Sad, Serbia"]},{"name":"Clinic of Internal Oncology, Oncology Institute of Vojvodina","place":["Sremska Kamenica, Serbia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21834","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA: A Cancer J For Clin"},{"key":"B2","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1016\/j.annonc.2022.10.003","article-title":"Metastatic colorectal cancer: ESMO Clinical Practice Guideline for diagnosis, 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