Human intravital microscopy in the study of sarcomas: an early trial of feasibility

Our plain-English summary of Human intravital microscopy in the study of sarcomas: an early trial of feasibility, by E.M. Gabriel, K. Sukniam, K. Popp, et al (Frontiers in Oncology, 2023).

The study

• Authors: E.M. Gabriel, K. Sukniam, K. Popp, S.P. Bagaria
• Journal: Frontiers in Oncology
• Published: 2023;13:1151255
• Cited by: 2 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Unlabelled: Sarcomas comprise a vast and heterogenous group of rare tumors. Because of their diversity, it is challenging to study sarcomas as a whole with regard to their biological and molecular characteristics. This diverse set of tumors may also possess differences related to their tumor-associated vasculature, which in turn may impact the ability to deliver systemic therapies (e.g., chemotherapy, targeted therapies, and immunotherapy). Consequently, response to systemic treatment may also be variable as these depend on the ability of the therapy to reach the tumor target via the tumor-associated vasculature. There is a paucity of data regarding sarcoma-related tumor vessels, likely in part to the rarity and heterogeneity of this cancer as well as the previously limited ability to image tumor-associated vessels in real time. Our group has previously utilized confocal fluorescent imaging technology to observe and characterize tumor-associated vessels in real time during surgical resection of tumors, including cutaneous melanoma and carcinomatosis implants derived from gastrointestinal, gynecological, or primary peritoneal (e.g., mesothelioma) tumors. Our prior studies have demonstrated the feasibility of real-time, human intravital microscopy in the study of these tumor types, leading to early but important new data regarding tumor vessel characteristics and their potential implications on drug delivery and efficacy. In this brief report, we present our latest descriptive findings in a cohort of patients with sarcoma who underwent surgical resection and real-time, intravital microscopy of their tumors. Overall, intravital imaging was feasible during the surgical resection of large sarcomas.

Clinical Trial Registrations: ClinicalTrials.gov, identifier NCT03517852; ClinicalTrials.gov, identifier NCT03823144.

Copyright © 2023 Gabriel, Sukniam, Popp and Bagaria.

In plain English

This brief research report described a small, single-center, nonrandomized trial at Mayo Clinic in Jacksonville, Florida. It tested whether a fluorescent microscope could be used during surgery to watch the small blood vessels of sarcomas in real time. Ten patients with sarcoma, enrolled between January 2018 and December 2022, were studied; five had retroperitoneal liposarcomas. Fluorescein dye was injected, and tumor areas were compared with non-tumor control areas. Tumor areas had a higher density of non-functional vessels (vessels that took up no dye) and a higher share of them: on average 35.69 percent in tumor areas versus 4.59 percent in control areas. Blood flow in functional vessels was slower in tumor areas. The density of functional vessels did not differ significantly. The authors concluded that imaging was feasible during surgery for large sarcomas and that the findings supported vessel differences between tumor types. They noted that the group was small, the tumor types were varied, the study could not link vessel findings to outcomes, and only tumor surfaces could be imaged. The study did not concern asbestos.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Brief research report of a descriptive feasibility analysis within single-center, nonrandomized clinical trials using real-time intraoperative intravital microscopy
• Who was studied: 10 patients with sarcoma (5 retroperitoneal liposarcoma, 2 gastrointestinal stromal tumor, 1 uterine leiomyosarcoma, 1 pleomorphic sarcoma, 1 leiomyosarcoma; 7 male, 3 female; mean age 62.1 years) undergoing surgical resection at Mayo Clinic, Jacksonville, Florida, enrolled January 1, 2018 to December 31, 2022
• Main results:
  • Intravital imaging was feasible during surgical resection of large sarcomas
  • Compared with non-tumor control areas, tumor areas had a higher density of non-functional vessels (mean 1.02 vs 0.11; p = 0.0018 in the table) and a higher percentage of non-functional vessels (mean 35.69 vs 4.59; p = 0.0032 in the table)
  • Mean blood flow velocity of functional vessels was slower in tumor areas than in control areas (286.77 vs 430.49, units printed as mm/s; p < 0.0001)
  • No statistically significant differences between tumor and control areas in the density of functional vessels (p = 0.92) or the diameter of functional vessels (p = 0.35)
  • Non-functional vessels were larger in diameter in tumor areas than in control areas (mean 21.34 vs 14.11; p = 0.034 in the table)
• The authors' conclusion: The authors concluded that this was the first in-human real-time study of sarcoma-associated vessels, and that differences from their earlier peritoneal carcinomatosis trial supported vascular heterogeneity between tumors and the feasibility of observing it during surgery
• Limitations the authors state:
  • The sarcoma cohort was small
  • Tumor histologies were diverse
  • The study was not powered to analyze associations between vessel characteristics and outcomes such as treatment response or survival
  • Only the tumor surface could be imaged
  • In larger sarcomas, the most grossly abnormal tumor areas could not all be observed

Topics

Medical terms in this study, explained in our Lexicon: Sarcoma, Chemotherapy, Immunotherapy, Surgical Resection, Mesothelioma.

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