Human tumour vessel heterogeneity in ovarian cancer and its association with response to neoadjuvant chemotherapy

• Published in: Clinical and translational medicine Vol. 14; no. 4; pp. e1633 - n/a
• Main Authors: Gabriel, Emmanuel M., Sukniam, Kulkaew, Popp, Kyle, Kowkabany, Gabrielle, Manaise, Harsheen K., Attwood, Kristopher, George, Anthony, Zhai, Qihui, Bagaria, Sanjay P., Knutson, Keith L., Skitzki, Joseph J., Robertson, Matthew W., Dinh, Tri A.
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.04.2024; John Wiley and Sons Inc; Wiley
• Subjects: Blood vessels; Chemotherapy; Clinical outcomes; Clinical trials; Female; Humans; Letter to the Journal; Microscopy; Neoadjuvant Therapy; Ovarian cancer; Ovarian Neoplasms - drug therapy; Standard deviation; Surgery
• ISSN: 2001-1326; 2001-1326
• DOI: 10.1002/ctm2.1633

Others have investigated the importance of tumour-associated vessels specifically in ovarian cancer, whereby tumour vessel density and stability during disease progression were associated with poorer survival outcomes.6 In our own earlier trials, we were unable to detect statistically significant differences in treatment-related outcomes, including response to neoadjuvant chemotherapy (NCT) and disease-specific survival (DSS), likely because our previous studies were underpowered. Variable Overall N 25 (100%) Age Mean/Standard deviation 64.0/11.0 Median 63.0 Race White 21 (84.0%) Non-White 4 (16.0%) Body mass index Mean/Standard deviation 28.1/6.8 Median/Minimum/Maximum 26.9/17.4/46.7 Smoking status Never 21 (84.0%) Former/Current 4 (16.0%) Diabetes None 21 (84.0%) Type II 4 (16.0%) Subtype Serous 24 (96.0%) Clear Cell 1 (4.0%) Grade Low 4 (16.0%) High 21 (84.0%) Recurrence No (initial) 19 (76.0%) Yes 6 (24.0%) Prior surgery None 11 (44.0%) Yes 14 (56.0%) Approach Open 20 (80.0%) Robotic 4 (16.0%) Laparoscopic 1 (4.0%) Peritoneal carcinomatosis index Mean/Standard deviation 9.8/7.7 Median 8.0 Completeness of cytoreduction Mean/Standard deviation 0.2/0.4 Median 0.0 Adjuvant chemotherapy No 4 (16.0%) Yes 21 (84.0%) Complications None 22 (88.0%) Yes (infection) 3 (12.0%) Our methods for intraoperative HIVM have previously been described.4 Similar to our previous trials, statistically significant differences between tumour and normal blood vessels were observed. CPR/PR* n = 14 (56.0%) SD/PD† n = 11 (44.0%) Variable Mean (Standard deviation) Mean (Standard deviation) p-Value # Functional vessels (per observed area) Control 18.6 (8.3) 24.8 (9.5) .079 Tumour 15.4 (6.3) 7.0 (4.6) .0027 # Non-functional vessels (per observed area) Control 2.7 (2.3) 3.2 (3.0) .73 Tumour 6.8 (1.9) 16.6 (6.6) < .001 Density of functional vessels Control 2.7 (0.9) 2.7 (0.8) .93 Tumour 1.9 (1.1) 0.6 (0.3) < .001 Density of non-functional vessels Control 0.4 (0.3) 0.3 (0.3) .63 Tumour 0.9 (0.5) 1.6 (0.6) .004 % Non-functional vessels Control 36.8 (11.6) 30.4 (4.2) .3 Tumour 25.1 (9.7) 20.5 (8.4) .50 Diameter of functional vessels (μm) Control 13.7 (10.6) 16.8 (11.8) .48 Tumour 20.3 (5.6) 15.1 (4.7) .029 Diameter of non-functional vessels (μm) Control 12.7 (10.4) 9.9 (7.8) .48 Tumour 32.3 (14.4) 22.2 (8.6) .19 Velocity of functional vessels (μm/s) Control 294.3 (135.7) 356.1 (130.3) .20 Tumour 97.0 (39.6) 99.5 (40.2) .87 * CPR = complete pathologic response, PR = partial response (per RECIST). † SD = stable disease, PD = progressive disease. [...]this is the first time that tumour vessel heterogeneity as observed by real-time HIVM has been shown to correlate with response to systemic treatment and represents a significant advance from our prior clinical trials.