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• W2110434510 abstract "No AccessJournal of UrologyNew Technology and Techniques1 Sep 2015Circulating Tumor Cells as Potential Biomarkers in Bladder Cancer Ajjai Alva, Terence Friedlander, Melanie Clark, Tamara Huebner, Stephanie Daignault, Maha Hussain, Cheryl Lee, Khaled Hafez, Brent Hollenbeck, Alon Weizer, Gayatri Premasekharan, Tony Tran, Christine Fu, Cristian Ionescu-Zanetti, Michael Schwartz, Andrea Fan, and Pamela Paris Ajjai AlvaAjjai Alva Division of Hematology and Oncology, Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan More articles by this author , Terence FriedlanderTerence Friedlander Division of Hematology and Medical Oncology, Helen Diller Family Comprehensive Cancer Center, University of California-San Francisco, San Francisco, California Financial interest and/or other relationship with Fluxion Biosciences. More articles by this author , Melanie ClarkMelanie Clark Division of Hematology and Oncology, Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan More articles by this author , Tamara HuebnerTamara Huebner Division of Hematology and Oncology, Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan More articles by this author , Stephanie DaignaultStephanie Daignault Division of Hematology and Oncology, Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan Financial interest and/or other relationship with Fluxion Biosciences. More articles by this author , Maha HussainMaha Hussain Division of Hematology and Oncology, Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan More articles by this author , Cheryl LeeCheryl Lee Department of Urology, University of Michigan, Ann Arbor, Michigan More articles by this author , Khaled HafezKhaled Hafez Department of Urology, University of Michigan, Ann Arbor, Michigan More articles by this author , Brent HollenbeckBrent Hollenbeck Department of Urology, University of Michigan, Ann Arbor, Michigan Financial interest and/or other relationship with Elsevier. More articles by this author , Alon WeizerAlon Weizer Department of Urology, University of Michigan, Ann Arbor, Michigan More articles by this author , Gayatri PremasekharanGayatri Premasekharan Department of Urology, Helen Diller Family Comprehensive Cancer Center, University of California-San Francisco, San Francisco, California Financial interest and/or other relationship with Fluxion Biosciences. More articles by this author , Tony TranTony Tran Fluxion Biosciences, San Francisco, California Financial interest and/or other relationship with Fluxion Biosciences. More articles by this author , Christine FuChristine Fu Fluxion Biosciences, San Francisco, California Financial interest and/or other relationship with Fluxion Biosciences. More articles by this author , Cristian Ionescu-ZanettiCristian Ionescu-Zanetti Fluxion Biosciences, San Francisco, California Financial interest and/or other relationship with Fluxion Biosciences. More articles by this author , Michael SchwartzMichael Schwartz Fluxion Biosciences, San Francisco, California Financial interest and/or other relationship with Fluxion Biosciences. More articles by this author , Andrea FanAndrea Fan Fluxion Biosciences, San Francisco, California Financial interest and/or other relationship with Fluxion Biosciences. More articles by this author , and Pamela ParisPamela Paris Department of Urology, Helen Diller Family Comprehensive Cancer Center, University of California-San Francisco, San Francisco, California Financial interest and/or other relationship with Fluxion Biosciences. More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.2951AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: We explored the diagnostic use of circulating tumor cells in patients with neoadjuvant bladder cancer using enumeration and next generation sequencing. Materials and Methods: A total of 20 patients with bladder cancer who were eligible for cisplatin based neoadjuvant chemotherapy were enrolled in an institutional review board approved study. Subjects underwent blood draws at baseline and after 1 cycle of chemotherapy. A total of 11 patients with metastatic bladder cancer and 13 healthy donors were analyzed for comparison. Samples were enriched for circulating tumor cells using the novel IsoFlux™ System microfluidic collection device. Circulating tumor cell counts were analyzed for repeatability and compared with Food and Drug Administration cleared circulating tumor cells. Circulating tumor cells were also analyzed for mutational status using next generation sequencing. Results: Median circulating tumor cell counts were 13 at baseline and 5 at followup in the neoadjuvant group, 29 in the metastatic group and 2 in the healthy group. The concordance of circulating tumor cell levels, defined as low—fewer than 10, medium—11 to 30 and high—greater than 30, across replicate tubes was 100% in 15 preparations. In matched samples the IsoFlux test showed 10 or more circulating tumor cells in 4 of 9 samples (44%) while CellSearch® showed 0 of 9 (0%). At cystectomy 4 months after baseline all 3 patients (100%) with medium/high circulating tumor cell levels at baseline and followup had unfavorable pathological stage disease (T1-T4 or N+). Next generation sequencing analysis showed somatic variant detection in 4 of 8 patients using a targeted cancer panel. All 8 cases (100%) had a medium/high circulating tumor cell level with a circulating tumor cell fraction of greater than 5% purity. Conclusions: This study demonstrates a potential role for circulating tumor cell assays in the management of bladder cancer. The IsoFlux method of circulating tumor cell detection shows increased sensitivity compared with CellSearch. A next generation sequencing assay is presented with sufficient sensitivity to detect genomic alterations in circulating tumor cells. References 1 Surveillance, Epidemiology, and End Results Program: SEER Stat Fact Sheets: Bladder Cancer. Available at http://seer.cancer.gov/statfacts/html/urinb.html. Accessed July 23, 2014. Google Scholar 2 : Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer. N Engl J Med2003; 349: 859. 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Ann Oncol2009; 20: 1223. Google Scholar 16 : Circulating tumor cells predict survival benefit from treatment in metastatic castration-resistant prostate cancer. Clin Cancer Res2008; 14: 6302. Google Scholar 17 : Antitumour activity of MDV3100 in castration-resistant prostate cancer: a phase 1-2 study. Lancet2010; 375: 1437. Google Scholar 18 : AR-V7 and resistance to enzalutamide and abiraterone in prostate cancer. N Engl J Med2014; 371: 1028. Google Scholar 19 : Detection of circulating tumor cells in metastatic and clinically localized urothelial carcinoma. Urology2011; 78: 863. Google Scholar 20 : Detection of circulating tumor cells in patients with urothelial cancer. Ann Oncol2009; 20: 305. Google Scholar 21 : Detection of circulating urothelial cancer cells in the blood using the CellSearch System. Cancer2007; 109: 1439. Google Scholar 22 : Prognostic role and HER2 expression of circulating tumor cells in peripheral blood of patients prior to radical cystectomy: a prospective study. Eur Urol2012; 61: 810. Google Scholar 23 Soave A, Minner S, Engel O et al: Implications for circulating tumor cells on adjuvant chemotherapy decision-making in patients with urothelial carcinoma of the bladder treated with radical cystectomy. Presented at annual congress of European Association of Urology, Amsterdam, The Netherlands, April 11-15, 2014; abstract 47554. Google Scholar 24 : mutational analysis of circulating tumor cells using a novel microfluidic collection device and qPCR assay. Transl Oncol2013; 6: 528. Google Scholar 25 : Whole-exome sequencing of circulating tumor cells provides a window into metastatic prostate cancer. Nat Biotechnol2014; 32: 479. Google Scholar © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 194Issue 3September 2015Page: 790-798Supplementary Materials Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.Keywordsneoplastic cellsgenomicscirculatingneoadjuvant therapypathologymolecularurinary bladder neoplasmsAcknowledgmentsKirsten Copren, Kathryn Thompson and Jennifer Dang, University of California-San Francisco, assisted with sequencing. NGS was done at the University of California-San Francisco Genome Core and Thermo Fisher, South San Francisco, California.MetricsAuthor Information Ajjai Alva Division of Hematology and Oncology, Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan More articles by this author Terence Friedlander Division of Hematology and Medical Oncology, Helen Diller Family Comprehensive Cancer Center, University of California-San Francisco, San Francisco, California Financial interest and/or other relationship with Fluxion Biosciences. More articles by this author Melanie Clark Division of Hematology and Oncology, Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan More articles by this author Tamara Huebner Division of Hematology and Oncology, Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan More articles by this author Stephanie Daignault Division of Hematology and Oncology, Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan Financial interest and/or other relationship with Fluxion Biosciences. More articles by this author Maha Hussain Division of Hematology and Oncology, Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan More articles by this author Cheryl Lee Department of Urology, University of Michigan, Ann Arbor, Michigan More articles by this author Khaled Hafez Department of Urology, University of Michigan, Ann Arbor, Michigan More articles by this author Brent Hollenbeck Department of Urology, University of Michigan, Ann Arbor, Michigan Financial interest and/or other relationship with Elsevier. More articles by this author Alon Weizer Department of Urology, University of Michigan, Ann Arbor, Michigan More articles by this author Gayatri Premasekharan Department of Urology, Helen Diller Family Comprehensive Cancer Center, University of California-San Francisco, San Francisco, California Financial interest and/or other relationship with Fluxion Biosciences. More articles by this author Tony Tran Fluxion Biosciences, San Francisco, California Financial interest and/or other relationship with Fluxion Biosciences. More articles by this author Christine Fu Fluxion Biosciences, San Francisco, California Financial interest and/or other relationship with Fluxion Biosciences. More articles by this author Cristian Ionescu-Zanetti Fluxion Biosciences, San Francisco, California Financial interest and/or other relationship with Fluxion Biosciences. More articles by this author Michael Schwartz Fluxion Biosciences, San Francisco, California Financial interest and/or other relationship with Fluxion Biosciences. More articles by this author Andrea Fan Fluxion Biosciences, San Francisco, California Financial interest and/or other relationship with Fluxion Biosciences. More articles by this author Pamela Paris Department of Urology, Helen Diller Family Comprehensive Cancer Center, University of California-San Francisco, San Francisco, California Financial interest and/or other relationship with Fluxion Biosciences. More articles by this author Expand All Advertisement PDF downloadLoading ..." @default.
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• W2110434510 title "Circulating Tumor Cells as Potential Biomarkers in Bladder Cancer" @default.
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