Shannon Grabosch1, George Tseng2, Robert P Edwards3, Heather A Lankes4, Kathleen Moore5, Kunle Odunsi6, Anda Vlad7, Tianzhou Ma8, Mary Strange9, Joan Brozick10, Amit Lugade11, Angela Omilian12, Wiam Bshara13, Ashley R Stuckey14, Joan L Walker15, Michael Birrer16. 1. Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Magee-Womens Research Institute, Pittsburgh, PA, USA; Magee-Womens Hospital of UPMC, Pittsburgh, PA, USA. Electronic address: graboschsm@mwri.magee.edu. 2. Department of Biostatistics, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA, USA. Electronic address: ctseng@pitt.edu. 3. Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Magee-Womens Research Institute, Pittsburgh, PA, USA; Magee-Womens Hospital of UPMC, Pittsburgh, PA, USA. Electronic address: edwarp@mail.magee.edu. 4. Statistics & Data Management Center, NRG Oncology/Gynecologic Oncology Group, Roswell Park Cancer Institute, Buffalo, NY, USA. Electronic address: hlankes@gogstats.org. 5. Stephenson Oklahoma Cancer Center, University of Oklahoma, Oklahoma City, OK, USA. Electronic address: Kathleen-Moore@ouhsc.edu. 6. Division of Gynecologic Oncology, Roswell Park Cancer Institute, Buffalo, NY, USA. Electronic address: Kunle.odunsi@roswellpark.org. 7. Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Magee-Womens Research Institute, Pittsburgh, PA, USA. Electronic address: avlad@mwri.magee.edu. 8. Department of Biostatistics, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA, USA. Electronic address: tim28@pitt.edu. 9. Magee-Womens Research Institute, Pittsburgh, PA, USA. Electronic address: mstrange@mwri.magee.edu. 10. Magee-Womens Research Institute, Pittsburgh, PA, USA. Electronic address: jbrozick@mwri.magee.edu. 11. Center for Immunotherapy, Roswell Park Cancer Institute, Buffalo, NY, USA. Electronic address: amit.lugade@roswellpark.org. 12. Department of Pathology, Roswell Park Cancer Institute, Buffalo, NY, USA. Electronic address: angela.omilian@roswellpark.org. 13. Department of Pathology, Roswell Park Cancer Institute, Buffalo, NY, USA. Electronic address: wiam.bshara@roswellpark.org. 14. The Program in Women's Oncology, Women and Infants Hospital, Providence, RI, USA. Electronic address: AStuckey@Wihri.org. 15. Stephenson Oklahoma Cancer Center, University of Oklahoma, Oklahoma City, OK, USA. Electronic address: joan-walker@ouhsc.edu. 16. Department of Oncology, Massachusetts General Hospital Gillette Center, Boston, MA, USA. Electronic address: mbirrer@mgh.harvard.edu.
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 30mL 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 1.6mL and 3.1mL 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.
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 30mL 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 1.6mL and 3.1mL 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.
Authors: W G McCluggage; R W Lyness; R J Atkinson; S P Dobbs; I Harley; H R McClelland; J H Price Journal: J Clin Pathol Date: 2002-01 Impact factor: 3.411
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Authors: Anda M Vlad; Raluca A Budiu; Diana E Lenzner; Yun Wang; Julia A Thaller; Kelly Colonello; Peggy A Crowley-Nowick; Joseph L Kelley; Fredric V Price; Robert P Edwards Journal: Cancer Immunol Immunother Date: 2010-02 Impact factor: 6.968