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<p>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 (<i>P</i> &lt; 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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月16日

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  • Kelley Newcomer,
  • Alessandro Bifolco,
  • Sarah Reeves,
  • Giada Pontecorvi,
  • Simran Asawa,
  • Magdalena K. Sznurkowska,
  • Manuel Nüesch,
  • Lauren L. Ozimski,
  • Louisa Bolm,
  • Malte Maria Sieren,
  • Lukas Müller,
  • Zhikai Chi,
  • William Gasper,
  • Megan B. Wachsmann,
  • William 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 L. Goff,
  • Sung-hee Choi,
  • Carol Abousaab,
  • Song Zhang,
  • Suzanne Cole,
  • Kathryn Naumann,
  • Tobias Keck,
  • Patricio M. Polanco,
  • Ana Gvozdenovic,
  • Ilona Krol,
  • Francesc Castro-Giner,
  • Carlos Arteaga,
  • Herbert J. Zeh,
  • Roman Kloeckner,
  • Dario Ghersi,
  • Nicola Aceto,
  • Matteo Ligorio

摘要

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.