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

作者:Grabosch Shannon; Tseng George; Edwards Robert P*; Lankes Heather A; Moore Kathleen; Odunsi Kunle; Vlad Anda; Ma Tianzhou; Strange Mary; Brozick Joan; Lugade Amit; Omilian Angela; Bshara Wiam; Stuckey Ashley R; Walker Joan L; Birrer Michael
来源:Gynecologic Oncology, 2017, 146(1): 137-145.
DOI:10.1016/j.ygyno.2017.04.008

摘要

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 bio-marker 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.

  • 出版日期2017-7