A health-system-scale, episode-resolved multimodal atlas of cancer cachexia

Castillon, Venise Jan, Xie, Amy X, Boscenco, Sonia, Tse, Ethan, Ruthen, Neil, Wang, Jamie, Bakouny, Ziad, Waters, Michele, Fu, Chenlian, Fong, Christopher, Saleh, Mustafa, Baroud, Tarek, Park, Wungki, Shah, Urvi A, Hakimi, A Ari, Iyengar, Puneeth, Jee, Justin, White, Eileen, Gusev, Alexander, Janowitz, Tobias, Goncalves, Marcus D, Reznik, Ed (October 2026) A health-system-scale, episode-resolved multimodal atlas of cancer cachexia. Nature Medicine. ISSN 1078-8956

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Abstract

Cancer cachexia is a wasting syndrome with outsized impact on morbidity and mortality, yet its drivers and systemic consequences remain poorly defined. In this study, we repurposed longitudinal clinicogenomic data from 52,236 patients with cancer profiled by MSK-IMPACT (2010-2024) at Memorial Sloan Kettering Cancer Center to define episode-resolved trajectories of consensus-defined cachectic weight loss and linked these events to outcomes, serology and tumor genotypes. Cachectic episodes clustered near periods of disease progression and were associated with inferior outcomes in nearly all cancer types. Across diverse malignancies, cachectic weight loss episodes exhibited a consistent serologic signature characterized by lower albumin and hemoglobin and higher levels of liver enzymes. Numerous somatic tumor genotypes, including TP53 mutation across several diseases, were also associated with more frequent onset of cachectic episodes. Motivated by these observations, we developed a multivariate model to predict impending risk of cachectic weight loss in patients with lung, colorectal and prostate cancer, validated in an independent, external cohort from Dana-Farber Cancer Institute (n = 5,785). Routine clinicogenomic data are, therefore, a scalable resource for discovery in cancer cachexia.

Item Type:	Paper
Subjects:	diseases & disorders diseases & disorders > nutritional and metabolic diseases diseases & disorders > nutritional and metabolic diseases > cachexia
CSHL Authors:	Janowitz, Tobias
Communities:	CSHL labs > Janowitz lab
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	12 October 2026
Date Deposited:	15 Oct 2026 15:29
Last Modified:	15 Oct 2026 15:29
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/42342

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