title: Application of a telomerase-based circulating tumor cell (CTC) assay in bladder cancer patients receiving postoperative radiation therapy: a case study.
abstract: BACKGROUND
  Muscle invasive bladder carcinoma is an often lethal disease that requires aggressive treatment. Improved assays would contribute to better risk prediction and clinical management of this disease. A telomerase-based assay to detect circulating tumor cells (CTCs) may usefully fulfill this role.
  
  
  METHODS
  Two patients (C1 and C2) were enrolled onto an IRB-approved bladder biomarker study before initiating post-operative radiation therapy (RT) for muscle invasive bladder carcinoma. Blood samples were taken at predefined intervals: before, during, and after RT and then retrospectively correlated with imaging studies and disease course.
  
  
  RESULTS
  C1 began RT for positive resection margins on surgical pathology, at which time CTCs were undetectable and pelvic imaging demonstrated no evidence of disease. However, following the completion of treatment, the patient's CTC count was found to have increased to 202 CTCs/mL, and MRI demonstrated new abdominal and pelvic masses consistent with progressive disease. C1 ultimately died of disease with distant and local failure. Conversely, C2 was found to have 632 CTCs/mL before the initiation of RT for positive surgical margins, although imaging demonstrated no visible masses. At the conclusion of RT, repeat imaging showed changes that were indeterminate for either tumor recurrence or post-radiation effects. However, the patient's CTC count had dropped to 184 CTCs/mL. Furthermore, a second follow-up assay performed 6 months later revealed no detectable CTCs and repeat imaging showed complete resolution of worrisome imaging changes, thus excluding tumor progression.
  
  
  CONCLUSIONS
  To our knowledge this is the first report of a telomerase-based assay to identify CTCs in bladder cancer patients. Further studies are required to fully determine the ultimate clinical utility of this assay. However, the two patient vignettes described here illustrate how serial CTC assays may track the disease course and inform the management of bladder cancer patients undergoing adjuvant RT and potentially chemotherapy.
authors.affiliation: Department of Radiation Oncology; Perelman School of Medicine; University of Pennsylvania; Philadelphia, PA USA.
authors.forename: Melody
authors.initials: M
authors.lastname: Ju
authors.affiliation: Department of Radiation Oncology; Perelman School of Medicine; University of Pennsylvania; Philadelphia, PA USA.
authors.forename: Gary D
authors.initials: GD
authors.lastname: Kao
authors.affiliation: Department of Radiation Oncology; Perelman School of Medicine; University of Pennsylvania; Philadelphia, PA USA.
authors.forename: David
authors.initials: D
authors.lastname: Steinmetz
authors.affiliation: Department of Radiation Oncology; Perelman School of Medicine; University of Pennsylvania; Philadelphia, PA USA.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Chandrasekaran
authors.affiliation: Department of Medicine; Division of Hematology/Oncology; Perelman School of Medicine; University of Pennsylvania; Philadelphia, PA USA.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Keefe
authors.affiliation: Department of Surgery; Division of Urology; Perelman School of Medicine; University of Pennsylvania; Philadelphia, PA USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Guzzo
authors.affiliation: Department of Radiation Oncology; Perelman School of Medicine; University of Pennsylvania; Philadelphia, PA USA.
authors.forename: John P
authors.initials: JP
authors.lastname: Christodouleas
authors.affiliation: Department of Radiation Oncology; Perelman School of Medicine; University of Pennsylvania; Philadelphia, PA USA.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Hahn
authors.affiliation: Department of Radiation Oncology; Perelman School of Medicine; University of Pennsylvania; Philadelphia, PA USA.
authors.forename: Jay F
authors.initials: JF
authors.lastname: Dorsey
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002295:Carcinoma, Transitional Cell / Q000175:diagnosis* / Q000201:enzymology / Q000628:therapy; D057075:Enzyme Assays; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009360:Neoplastic Cells, Circulating / Q000378:metabolism*; D018714:Radiotherapy, Adjuvant; D019098:Telomerase / Q000378:metabolism*; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis* / Q000201:enzymology / Q000628:therapy
chemical_list: D014408:Biomarkers, Tumor; D019098:Telomerase
keywords: CTC; CTC assay; bladder cancer; circulating tumor cell; radiation therapy; telomerase