title: Circulating tumor cells predict progression free survival and overall survival in patients with relapsed/recurrent advanced ovarian cancer.
abstract: OBJECTIVE
  Serial circulating tumor cell (CTC) counts have demonstrated predictive and prognostic value in patients with metastatic breast, colorectal, and prostate cancer. In a phase III study of pegylated liposomal doxorubicin (PLD) with trabectedin vs. PLD for relapsed ovarian cancer, we evaluated the correlation, if any, between numbers of CTCs and progression free survival, (PFS) and overall survival (OS).
  
  
  METHODS
  CTCs were isolated from peripheral blood (10 mL) using the CellSearch system and reagents (Veridex). A CTC is defined as EpCAM+, cytokeratin+, CD45-, and is positive for the nuclear stain DAPI. The normal reference range for CellSearch is <2 CTC/7.5 mL of blood. Hazard ratios adjusted for known prognostic factors were estimated by Cox regression.
  
  
  RESULTS
  Two-hundred sixteen patients had baseline CTC measurements of which 111 (51.4%) were randomized to the trabectedin+PLD arm; 143/216 patients (66.2%) were platinum-sensitive. Thirty-one of 216 patients (14.4%) had 2 or more CTCs detected prior to the start of therapy (range 2-566). Univariate Cox regression analyses indicated that patients with ≥2 CTCs prior to therapy had 1.89- (p=0.003) and 2.06-fold (p=0.003) higher risk for progression and death respectively. Multivariate analyses that include baseline CA-125, platinum sensitivity status, largest diameter lesion, number of tumor lesions, ECOG PS, and tumor grade show that patients with elevated baseline CTC had 1.58- (p=0.058) and 1.54-fold (p=0.096) higher risk for progression and death respectively.
  
  
  CONCLUSIONS
  Results from this study indicate that elevated numbers of CTCs impart an unfavorable prognosis for ovarian cancer patients.
authors.affiliation: Fundación Instituto Valenciano de Oncología, Valencia, Spain. apoveda@fivo.org
authors.forename: Andres
authors.initials: A
authors.lastname: Poveda
authors.forename: Stanley B
authors.initials: SB
authors.lastname: Kaye
authors.forename: Robert
authors.initials: R
authors.lastname: McCormack
authors.forename: Songbai
authors.initials: S
authors.lastname: Wang
authors.forename: Trilok
authors.initials: T
authors.lastname: Parekh
authors.forename: Deborah
authors.initials: D
authors.lastname: Ricci
authors.forename: Claudia A
authors.initials: CA
authors.lastname: Lebedinsky
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Tercero
authors.forename: Patrik
authors.initials: P
authors.lastname: Zintl
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Monk
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D004149:Dioxoles / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D006801:Humans; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local / Q000097:blood* / Q000188:drug therapy* / Q000473:pathology; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000097:blood* / Q000188:drug therapy* / Q000473:pathology; D011092:Polyethylene Glycols / Q000008:administration & dosage; D015996:Survival Rate; D044005:Tetrahydroisoquinolines / Q000008:administration & dosage; D000077606:Trabectedin
chemical_list: D004149:Dioxoles; D044005:Tetrahydroisoquinolines; C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D004317:Doxorubicin; D000077606:Trabectedin