Macrovascular tumor infiltration and circulating tumor cell cluster dynamics in patients with cancer approaching the end of life
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.
Authors
- Tobias Keck (ORCID: https://orcid.org/0000-0001-7651-6183)
- John D. Karalis (ORCID: https://orcid.org/0000-0001-7601-5776)
- Herbert N. Prince
- Carol Abousaab
- Sarah Reeves
- Dario Ghersi (ORCID: https://orcid.org/0000-0002-0630-0843)
- Megan Wachsmann (ORCID: https://orcid.org/0000-0003-4343-9892)
- Lauren L. Ozimski (ORCID: https://orcid.org/0009-0004-2329-4256)
- Zhikai Chi (ORCID: https://orcid.org/0000-0002-3601-3351)
- Giada Pontecorvi (ORCID: https://orcid.org/0000-0001-8866-8555)
- Alexander Ring (ORCID: https://orcid.org/0000-0002-0092-1323)
- Elena Crecca (ORCID: https://orcid.org/0000-0002-5712-7964)
- Patricio Marcelo Polanco (ORCID: https://orcid.org/0000-0002-1719-1208)
- Manuel Nüesch
- Bich Doan Nguyen-Sträuli (ORCID: https://orcid.org/0000-0003-1290-830X)
- Magdalena K. Sznurkowska (ORCID: https://orcid.org/0000-0001-5306-2385)
- Malte Maria Sieren (ORCID: https://orcid.org/0000-0002-3669-2892)
- Kristina Goff (ORCID: https://orcid.org/0000-0003-3048-1661)
- Carlos L. Arteaga (ORCID: https://orcid.org/0000-0003-0870-9586)
- K. H. Naumann
- Lukáš Müller (ORCID: https://orcid.org/0000-0002-8626-4044)
- William Gasper
- Kelley Newcomer (ORCID: https://orcid.org/0000-0002-8995-9837)
- Simran Asawa (ORCID: https://orcid.org/0000-0001-9015-254X)
- Francesc Castro-Giner (ORCID: https://orcid.org/0000-0001-6111-0754)
- Roman Kloeckner (ORCID: https://orcid.org/0000-0001-5492-4792)
- Herbert J. Zeh (ORCID: https://orcid.org/0000-0003-2017-1934)
- Matteo Ligorio (ORCID: https://orcid.org/0000-0001-8865-0881)
- Selina Budinjas (ORCID: https://orcid.org/0009-0002-1968-2622)
- Suzanne Cole (ORCID: https://orcid.org/0000-0001-8390-6315)
- Louisa Bolm (ORCID: https://orcid.org/0000-0002-1612-1857)
- Ilona Krol (ORCID: https://orcid.org/0009-0001-8967-3038)
- Nicola Aceto (ORCID: https://orcid.org/0000-0001-9579-6918)
- Ana Gvozdenovic (ORCID: https://orcid.org/0000-0002-6013-0355)
- William S. Moore (ORCID: https://orcid.org/0000-0002-5672-8100)
- Nafeesah Fatimah (ORCID: https://orcid.org/0000-0003-0855-5708)
- Alessandro Bifolco
- Song Zhang (ORCID: https://orcid.org/0000-0002-9364-4053)
- Raghav Chandra (ORCID: https://orcid.org/0000-0002-8729-0551)
- Xue Zheng (ORCID: https://orcid.org/0009-0008-7764-5452)
- Sung‐Hee Choi
- Abbas Zaki (ORCID: https://orcid.org/0009-0002-2867-2549)
- Benedikt Färber
- Meike ten Winkel
- Angelique Fokkema
Institutions
- University of Nebraska at Omaha (US)
- Johannes Gutenberg University Mainz (DE)
- ETH Zurich (CH)
- University Medical Center of the Johannes Gutenberg University Mainz (DE)
- Southwestern Medical Center (US)
- VA North Texas Health Care System (US)
- University Hospital Schleswig-Holstein (DE)
- The University of Texas Southwestern Medical Center (US)
- University of Lübeck (DE)
Publication Details
- Journal
- Nature Medicine
- Published
- 2025-10-16
- DOI
- https://doi.org/10.1038/s41591-025-03966-3
- Citations
- 6
- Primary Topic
- Cancer Cells and Metastasis
- Type
- article
- Field-Weighted Citation Impact
- 6.27