Multiplex profiling identifies distinct local and systemic alterations during intraperitoneal chemotherapy for ovarian cancer: An NRG Oncology/Gynecologic Oncology Group Study

Abstract

OBJECTIVES Ovarian cancer leads to abdominal carcinomatosis and late stage (III/IV) diagnosis in 75% of patients. Three randomized phase III trials have demonstrated that intraperitoneal (IP) chemotherapy improves outcomes in epithelial ovarian cancer. While IP treatment is validated by clinical trials, there is a poor understanding of the mechanism(s) leading to the survival advantage other than the increased concentration of cytotoxic drugs within the tumor microenvironment. A better understanding of this process through analysis of dynamic biomarkers should promote novel approaches that may enhance tumor clearance. We propose this pilot study to confirm the feasibility of collecting serial peritoneal samples from implanted catheters in women receiving IP chemotherapy. We believe these specimens may be used for multiplex analysis to reveal unique biomarker fluctuations when compared to peripheral blood. METHODS From 13 women participating on GOG 252, 30 whole blood, 12 peritoneal fluid (PF), and 20 peritoneal wash (PW) with 30 mL saline were obtained. Samples were requested prior to the first three chemotherapy cycles. Samples were assessed for volume, cell populations, protein, RNA, and miRNA content changes. RESULTS Median volume for PF was 1.6 mL and 3.1 mL for PW. PW is a dilution of PF capable of capturing measurable biomarkers. Peritoneal aspirates contain a unique profile of biomarkers distinct from blood. miRNA undergo earlier alteration with chemotherapy than genes. Flow cytometry does not adequately capture biomarker fluctuations. CONCLUSIONS As a proof of principle study, this trial provides evidence that sampling the peritoneal cavity can be adapted for biomarker analysis.

Cisplatin-induced immune modulation in ovarian cancer mouse models with distinct inflammation profiles

“…RNA was isolated from tumors collected at necropsy and processed as per NanoString (Seattle, WA) guidelines and according to our previous protocols 23, 44 . We used the nCounter Mouse PanCancer Immune Profiling Panel kit containing probes for 751 immune genes.…”

Role of Circulating miRNAs in Therapeutic Response in Epithelial Ovarian Cancer: A Systematic Revision

“…In particular, the first, by Benson et al, evaluated plasmatic miRNA levels in EOC patients treated with a regimen of low dose decitabine-a DNA methyltransferase inhibitor-and carboplatin [48]. The second, published by Grabosch and colleagues, investigated circulating miRNAs in serial peritoneal samples in women receiving intraperitoneal (IP) chemotherapy [47]. The analysis by Benson and collaborators included 14 EOC patients enrolled in the previously described open label phase II clinical trial [62].…”

Increased Immunosuppression Is Related to Increased Amounts of Ascites and Inferior Prognosis in Ovarian Cancer

“…However, conclusions from blood samples cannot be extrapolated to ascites, since the intraperitoneal cavity seems to be unique with concentrations of proteins that are generally higher than those in blood, therefore creating an ideal environment for tumor growth (43,45,46). We join the plea of Grabosch et al to not only systematically collect tumor tissue during surgery but also ascites fluid to monitor the immune response (45). Second, the types and amount of proteins that were measured.…”