73: Human tumor vessel heterogeneity in ovarian cancer and its association with response to neoadjuvant chemotherapy

For ovarian cancer with carcinomatosis, systemic therapy followed by HIPEC is the mainstay of treatment. However, aberrancies in the tumor vasculature (data almost entirely obtained from animal models) create barriers to systemic drug delivery, which negatively impact drug efficacy and response. The purpose was to determine the association between human tumor vessel characteristics observed in real time during HIPEC and response to neoadjuvant chemotherapy (NCT).


Methods:

Subjects were enrolled in one of two single center, nonrandomized pilot studies of human intravital microscopy (HIVM) observation for either peritoneal carcinomatosis (NCT03517852) or solid tumors (NCT03823144). We used an ultra-high definition confocal laser endomicroscopy device (Cellvizio System, Mauna Kea Technologies) to obtain the HIVM observations during cytoreduction and HIPEC. Tumor vessel characteristics were measured and analyzed with response to NCT and disease-specific survival (DSS).


Results:

A total of 25 subjects with ovarian carcinomatosis who received NCT and HIPEC were included. Two patients achieved a complete pathologic response (CPR), 42.1% achieved a partial response (PR), 31.6% had stable disease (SD), and 26.3% had progressive disease (PD). The median follow-up period was 20.2 months. The median DSS was 25.2 months (95% CI 14.4, not reached). The attached table shows the measured or calculated tumor vessel characteristics and their associations with response to NCT and DSS. Statistically significant worse outcomes were demonstrated with increased tumor vessel non-functionality (as directly observed by the absence of blood flow and identification of well-established structural aberrancies) and tumor vessel diameter (with smaller diameters associated with worse response to NCT and worse DSS). Increased numbers and density of functional vessels within the tumor were associated with improved responses to NCT. Importantly, pathologic analysis of tumor vessels also correlated with the HIVM vessel characteristics (tumor vessel density, functionality, and diameter) as well as response to NCT.


Conclusions:

For the first time, we have demonstrated a significant correlation between tumor vessel heterogeneity and clinically meaningful outcomes (response to NCT and DSS) in human subjects with ovarian carcinomatosis. This may have important implications for systemic treatment strategies as they pertain to drug delivery through tumor-associated vessels, which are the focus of our ongoing translational studies.