Macrovascular infiltration and spikes in circulating tumor cells in cancer patients approaching end of life

End-of-life neoplastic events related to carcinoma lethality are poorly characterized. With the purpose of exploring biological events in cancer patients nearing death, 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 cancer patients. In our prospective cohort, we observed remarkable spikes in circulating tumor cell (CTC) counts 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 clinical metastasis – in treatment-homogenous patients with colorectal, lung, ovarian, hepatocellular, or pancreatic cancer (hazard ratio range: 4.0 - 22.4). These findings suggest that spikes in CTC formation and consequent macrovascular failure could be pivotal end-of-life events associated with cancer lethality, providing a rationale for future clinical trials aimed at curbing tumor infiltration into large vessels. Blood samples were obtained via blood draw from multiple locations in patients and controls at the moment of the autopsy. CTCs were isolated from blood and sequenced using RNA-seq