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

Cancer cachexia is a wasting syndrome with outsized impact on morbidity and mortality. Neither the etiology of cachexia, nor its consequences on patient physiology and outcomes, are well-understood. Here, we repurposed longitudinal clinicogenomic data from 59,493 cancer patients to define episode-resolved trajectories of cachexia and linked them to serology, tumor genotypes, and clinical outcomes. Cachexia risk concentrated around periods of disease progression and associated with inferior outcomes in nearly all cancer types. Across cancers, cachectic episodes exhibited a consistent serologic signature characterized by low albumin and hemoglobin and high levels of liver enzymes. Numerous somatic tumor genotypes, including TP53 mutation across several diseases, were associated with elevated cachexia risk. Motivated by these observations, we developed a multivariate model to predict impending risk of cachexia in lung and colorectal cancer patients. Routine clinicogenomic data is therefore a powerful resource for discovery in cachexia and other cancer-associated pathophysiologies.