Michael L Pearl1, Huan Dong2, Shaun Tulley2, Qiang Zhao2, Marc Golightly3, Stanley Zucker4, Wen-Tien Chen5. 1. Division of Gynecologic Oncology, Stony Brook Medicine, Stony Brook, NY 11794, USA. 2. Division of Gynecologic Oncology, Stony Brook Medicine, Stony Brook, NY 11794, USA; Vitatex Inc., 25 Health Sciences Drive, Stony Brook, NY 11790, USA. 3. Department of Pathology, Stony Brook Medicine, Stony Brook, NY 11794, USA. 4. Department of Medicine, Stony Brook Medicine, Stony Brook, NY 11794, USA; Department of Medicine and Research, Veterans Affairs Medical Center, Northport, NY 11768, USA. 5. Division of Gynecologic Oncology, Stony Brook Medicine, Stony Brook, NY 11794, USA; Vitatex Inc., 25 Health Sciences Drive, Stony Brook, NY 11790, USA. Electronic address: wentien@vitatex.com.
Abstract
GOALS: Contemporary management of epithelial ovarian cancer (EOC) uses biomarkers to monitor response to therapy. This study evaluates the role of invasive circulating tumor cells (iCTCs) in monitoring EOC treatment in comparison with serum cancer antigen 125 (CA125). METHODS: Molecular and microscopic analyses were used to identify seprase and CD44 as tumor progenitor (TP) markers. The iCTC flow cytometry assay was optimized using blood donated by 64 healthy donors, 49 patients with benign abdominal diseases and 123 EOC patients. Serial changes in iCTCs and CA125 were measured in 129 blood and 169 serum samples, respectively, from 31 EOC patients to assess their concordance during therapy and their relationship with risk of progressive disease (PD). RESULTS: The assay had 97% specificity and 83% sensitivity for detecting iCTCs in blood of EOC patients. iCTCs were detected in each monitoring patient (31/31, 100%) and in 110 of the 129 blood samples (85.3%). The concordance between changes in iCTCs/CA125 levels and changes in the intervals associated with no evidence of disease (NED) were markedly stronger (specificity: CA125 93.8%; iCTCs 90.6%), whereas increases in iCTCs (79.5%) were more sensitive than increases in CA125 (67.6%) to predict PD or relapse. Among the six patients who had greater than 6 measurements, iCTCs but not CA125 antedated changes in clinical status from PD to NED during and after chemotherapy and predated relapse. CONCLUSION: Serial measurements of iCTCs could predict therapeutic responsiveness in 31 EOC patients who underwent standard taxol/carboplatin therapy.
GOALS: Contemporary management of epithelial ovarian cancer (EOC) uses biomarkers to monitor response to therapy. This study evaluates the role of invasive circulating tumor cells (iCTCs) in monitoring EOC treatment in comparison with serum cancer antigen 125 (CA125). METHODS: Molecular and microscopic analyses were used to identify seprase and CD44 as tumor progenitor (TP) markers. The iCTC flow cytometry assay was optimized using blood donated by 64 healthy donors, 49 patients with benign abdominal diseases and 123 EOC patients. Serial changes in iCTCs and CA125 were measured in 129 blood and 169 serum samples, respectively, from 31 EOC patients to assess their concordance during therapy and their relationship with risk of progressive disease (PD). RESULTS: The assay had 97% specificity and 83% sensitivity for detecting iCTCs in blood of EOC patients. iCTCs were detected in each monitoring patient (31/31, 100%) and in 110 of the 129 blood samples (85.3%). The concordance between changes in iCTCs/CA125 levels and changes in the intervals associated with no evidence of disease (NED) were markedly stronger (specificity: CA125 93.8%; iCTCs 90.6%), whereas increases in iCTCs (79.5%) were more sensitive than increases in CA125 (67.6%) to predict PD or relapse. Among the six patients who had greater than 6 measurements, iCTCs but not CA125 antedated changes in clinical status from PD to NED during and after chemotherapy and predated relapse. CONCLUSION: Serial measurements of iCTCs could predict therapeutic responsiveness in 31 EOC patients who underwent standard taxol/carboplatin therapy.
Authors: Joyce F Liu; David Kindelberger; Courtney Doyle; Alarice Lowe; William T Barry; Ursula A Matulonis Journal: Gynecol Oncol Date: 2013-08-13 Impact factor: 5.482
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