Abstract 414: Prospective profiling of systemic and loco-regional alterations during intraperitoneal chemotherapy for ovarian cancer, results from GOG 271
Authors: Grabosch Shannon , Vlad Anda M. , Ma Tianzhou , Mony Jyothi T. , Strange Mary , Brozick Joan , Thaller Julia , Tseng George , Huang Xin , Moore Kathleen , Odunsi Kunle , Edwards Robert P. 
Published: August 2015

Objectives: The concept of personalized approaches for recurrence in ovarian cancer has progressed at a modest pace, compared to other cancers. This is partly due to our limited understanding of the local tumor microenvironment during and immediately following chemotherapy-induced tumor involution, which requires sampling of the peritoneal cavity. Most studies to date have focused on chemo-naive tumors and on the more easily accessible peripheral blood samples, yet these are often not reflective of local changes. We hypothesize that sequential sampling and analysis of blood and intraperitoneal (IP) fluid during IP chemotherapy is feasible and will provide molecular insight into chemotherapy-induced systemic and local changes in the tumor environment.

Methods: Peritoneal fluid aspiration or wash and blood samples were obtained from patients (n = 13) at three time points (baseline and following the first and second rounds of chemotherapy, respectively) Nanostring was performed to profile miRNA from peritoneal samples and plasma. RNA extraction from peripheral blood mononuclear cells (PBMC) followed by Nanostring was performed to evaluate changes in 511 immune genes during chemotherapy. Flow cytometry for surface and intracellular immune markers was performed on PBMCs.

Results: From 13 patients, 30 blood, 12 intraperitoneal fluid (PF), and 20 intraperitoneal wash (PW) samples were obtained. Despite small volumes, cell counts were measurable in 7 of 12 (58%) PF and 11 of 20 (55%) PW samples. Nanostring results revealed 12 immune genes and 29 miRNAs differentially expressed during chemotherapy (p&lt;0.05). Additionally, changes amongst miRNA were noted to occur earlier than immune genes in which the majority was differentially expressed only after the second round of chemotherapy. The miRNA tended to be significantly changed, in the same direction, throughout chemotherapy. Bioinformatics analyses revealed the top immune pathways most affected by chemotherapy and included cell-to-cell signaling, immune cell trafficking, and inflammatory response among the top functions.

Conclusions: Sampling of the peritoneal cavity through IP catheters during chemotherapy is feasible and can be implemented through standardized protocols. Despite a small sample size, we were able to identify chemotherapy-induced molecular changes in immune genes and miRNAs systemically and loco-regionally. The findings suggest that miRNA alterations may be more suggestive of early tumor microenvironment alterations compared to immune genes in which changes are seen after subsequent cycles of chemotherapy. Larger studies are needed for validation to assess these changes as therapeutic targets.

Citation Format: Shannon Grabosch, Anda M. Vlad, Tianzhou Ma, Jyothi T. Mony, Mary Strange, Joan Brozick, Julia Thaller, George Tseng, Xin Huang, Kathleen Moore, Kunle Odunsi, Robert P. Edwards. Prospective profiling of systemic and loco-regional alterations during intraperitoneal chemotherapy for ovarian cancer, results from GOG 271. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 414. doi:10.1158/1538-7445.AM2015-414