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We used longitudinal computed tomography imaging from 4,516 patients to quantify evolution of muscle, adipose, and organs during cachexia. Across two independent institutional cohorts, unsupervised analysis identified three reproducible anatomical subtypes of cachexia, including an inflammatory Type A marked by progressive hepatosplenic enlargement and inferior survival, a Type B dominated by visceral organ atrophy, and a mild Type C. These anatomical subtypes were associated with distinct serological signatures and reflected in molecular phenotypes in tumors and non-cancerous liver tissue, establishing cachexia as discrete anatomical disease states that link whole-body remodeling to systemic and tissue-level biology. This anatomy-first framework for cachexia classification provides a foundation for future patient stratification and development of subtype-specific anti-cachexia therapies.<\/jats:p>","DOI":"10.64898\/2026.05.04.26352250","type":"posted-content","created":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T22:36:37Z","timestamp":1778020597000},"source":"Crossref","is-referenced-by-count":1,"title":["Anatomical dynamics define cancer cachexia subtypes and identify systemic inflammation as a marker of lethal wasting"],"prefix":"10.64898","author":[{"given":"Sonia","family":"Boscenco","sequence":"first","affiliation":[{"name":"Computational Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA"},{"name":"Department of Physiology, Biophysics, and Systems Biology, Weill Cornell Medicine, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Venise Jan","family":"Castillon","sequence":"additional","affiliation":[{"name":"Computational Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie","family":"Wang","sequence":"additional","affiliation":[{"name":"Computational Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA"},{"name":"Department of Physiology, Biophysics, and Systems Biology, Weill Cornell Medicine, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ethan","family":"Tse","sequence":"additional","affiliation":[{"name":"Computational Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA"},{"name":"Department of Physiology, Biophysics, and Systems Biology, Weill Cornell Medicine, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel S.","family":"Freeman","sequence":"additional","affiliation":[{"name":"Computational Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziad","family":"Bakouny","sequence":"additional","affiliation":[{"name":"Computational Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saksham","family":"Mohan","sequence":"additional","affiliation":[{"name":"Computational Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"X. 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