title: Monitoring changes in circulating tumour cells as a prognostic indicator of overall survival and treatment response in patients with metastatic melanoma.
abstract: BACKGROUND
  New effective treatments for metastatic melanoma greatly improve survival in a proportion of patients. However biomarkers to identify patients that are more likely to benefit from a particular treatment are needed. We previously reported on a multimarker approach for the detection of heterogenous melanoma circulating tumour cells (CTCs). Here we evaluated the prognostic value of this multimarker quantification of CTCs and investigated whether changes in CTC levels during therapy can be used as a biomarker of treatment response and survival outcomes.
  
  
  METHODS
  CTCs were captured by targeting the melanoma associated markers MCSP and MCAM as well as the melanoma stem cell markers ABCB5 and CD271. CTCs were quantified in 27 metastatic melanoma patients treated by surgery or with vemurafenib, ipilimumab or dacarbazine. Patients were enrolled prospectively and CTC counts performed at baseline (prior to treatment), during and after treatment.
  
  
  RESULTS
  Baseline CTC numbers were not found to be prognostic of overall survival nor of progression free survival. However, a low baseline CTC number was associated with a rapid response to vemurafenib therapy. A decrease in CTCs after treatment initiation was associated with response to treatment and prolonged overall survival in vemurafenib treated patients.
  
  
  CONCLUSIONS
  Measuring changes in CTC numbers during treatment is useful for monitoring therapy response in melanoma patients and for providing prognostic information relating to overall survival. Further studies with larger sample sizes are required to confirm the utility of CTC quantification as a companion diagnostic for metastatic melanoma treatment.
authors.forename: Dragana
authors.initials: D
authors.lastname: Klinac
authors.affiliation: School of Medical Sciences, Edith Cowan University (ECU), 270 Joondalup Drive, Joondalup, Perth, WA 6027, Australia. e.gray@ecu.edu.au.
authors.forename: Elin S
authors.initials: ES
authors.lastname: Gray
authors.forename: James B
authors.initials: JB
authors.lastname: Freeman
authors.forename: Anna
authors.initials: A
authors.lastname: Reid
authors.forename: Samantha
authors.initials: S
authors.lastname: Bowyer
authors.forename: Michael
authors.initials: M
authors.lastname: Millward
authors.forename: Melanie
authors.initials: M
authors.lastname: Ziman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage; D008297:Male; D008545:Melanoma / Q000097:blood* / Q000188:drug therapy / Q000473:pathology; D008875:Middle Aged; D009360:Neoplastic Cells, Circulating; D011379:Prognosis; D012878:Skin Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000473:pathology; D013449:Sulfonamides / Q000008:administration & dosage; D016896:Treatment Outcome; D000077484:Vemurafenib
chemical_list: D014408:Biomarkers, Tumor; D007211:Indoles; D013449:Sulfonamides; D000077484:Vemurafenib