Macrovascular tumor infiltration and circulating tumor cell cluster dynamics in patients with cancer approaching the end of life

作者：Kelley Newcomer, Alessandro Bifolco, Sarah Reeves, Giada Pontecorvi, Simran Asawa, Magdalena K. Sznurkowska, Manuel Nüesch, Lauren L. Ozimski, Louisa Bolm, Malte Maria Sieren, Lukáš Müller, Zhikai Chi, William Gasper, Megan Wachsmann, William S. Moore, Xue Zheng, Angelique Fokkema, Alexander Ring, Bich Doan Nguyen-Sträuli, Selina Budinjas, Meike ten Winkel, Benedikt Färber, Abbas Zaki, Nafeesah Fatimah, Elena Crecca, John D. Karalis, Raghav Chandra, Hillary Prince, Kristina Goff, Sung‐Hee Choi, Carol Abousaab, Song Zhang, Suzanne Cole, K. H. Naumann, Tobias Keck, Patricio M. Polanco, Ana Gvozdenovic, Ilona Krol, Francesc Castro-Giner, Carlos L. Arteaga, Herbert J. Zeh, Roman Kloeckner, Dario Ghersi, Nicola Aceto, Matteo Ligorio · 发表于：Nature Medicine · 年份：2025 · DOI：10.1038/s41591-025-03966-3 · 被引用次数：9 · 研究领域：Cancer Cells and Metastasis、Management of metastatic bone disease、Glioma Diagnosis and Treatment

End-of-life events related to carcinoma lethality are poorly characterized. Herein we conducted an observational, prospective, case–control study enrolling 21 patients with solid tumors and 10 patients without known malignancy, complemented by a retrospective validation cohort of 1,250 patients with cancer. In our prospective cohort, we observed spikes in circulating tumor cell (CTC) counts, particularly clusters, immediately before death (P < 0.0001), as well as pathological evidence of macrovascular infiltration and large-vessel occlusion obtained through rapid autopsy. In the validation cohort, radiological evidence of macrovascular infiltration emerged as the strongest predictor of poor survival—independent of metastasis—in treatment-homogeneous patients with colorectal, lung, ovarian, hepatocellular or pancreatic cancer (hazard ratios = 4.0–22.4). Collectively, these findings suggest that macrovascular infiltration and spikes in CTC clusters with consequent vascular failure could be pivotal end-of-life events associated with cancer lethality, providing a rationale for future trials aimed at curbing infiltration into large vessels. This prospective cohort study of patients with cancer incorporated antemortem follow-up visits and rapid autopsy analyses, and reports that spikes—rapidly increasing levels—of circulating tumor cell clusters, observed immediately before and at the time of death, along with tumor masses infiltrating large vessels, were cancer-related events asso...