A pilot trial of intravital microscopy in the study of the tumor vasculature of patients with peritoneal carcinomatosis

Autor: Emmanuel M. Gabriel, Minhyung Kim, Daniel T. Fisher, Catherine Mangum, Kristopher Attwood, Wenyan Ji, Debabrata Mukhopadhyay, Sanjay P. Bagaria, Matthew W. Robertson, Tri A. Dinh, Keith L. Knutson, Joseph J. Skitzki, Michael B. Wallace
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Scientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
Druh dokumentu: article
ISSN: 2045-2322
DOI: 10.1038/s41598-021-84430-3
Popis: Abstract Aberrancies in the tumor microvasculature limit the systemic delivery of anticancer agents, which impedes tumor response. Using human intravital microscopy (HIVM), we hypothesized that HIVM would be feasible in patients with peritoneal carcinomatosis (PC). During cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for PC, HIVM was performed in both tumor and non-tumor areas. The primary outcome was HIVM feasibility to measure vessel characteristics. We secondarily evaluated associations between HIVM vessel characteristics and oncologic outcomes (RECIST response to neoadjuvant therapy and disease-specific survival). Thirty patients with PC were enrolled. Nineteen patients (63.3%) received neoadjuvant therapy. HIVM was feasible in all patients. Compared to non-tumor (control) areas, PC areas had a lower density of functional vessels, higher proportion of non-functional vessels, smaller lumenal diameters, and lower blood flow velocity. Qualitative differences in these vessel characteristics were observed among patients who had partial response, stable disease, or progressive disease after receiving neoadjuvant therapy. However, no statistically significant relationships were found between HIVM vessel characteristics and oncologic outcomes. These novel findings comprise the first-in-human, real-time evidence of the microscopic differences between normal and tumor-associated vessels and form the basis for our larger, ongoing clinical trial appropriately powered to determine the clinical utility of HIVM (NCT03823144).
Databáze: Directory of Open Access Journals
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