title: Association between circulating tumor cells and prognosis in patients with stage III melanoma with sentinel lymph node metastasis in a phase III international multicenter trial.
abstract: OBJECTIVE
  The outcomes of patients with melanoma who have sentinel lymph node (SLN) metastases can be highly variable, which has precluded establishment of consensus regarding treatment of the group. The detection of high-risk patients from this clinical setting may be helpful for determination of both prognosis and management. We report the utility of multimarker reverse-transcriptase quantitative polymerase chain reaction (RT-qPCR) detection of circulating tumor cells (CTCs) in patients with melanoma diagnosed with SLN metastases in a phase III, international, multicenter clinical trial.
  
  
  METHODS
  Blood specimens were collected from patients with melanoma (n = 331) who were clinically disease-free after complete lymphadenectomy (CLND) before entering onto a randomized adjuvant melanoma vaccine plus bacillus Calmette-Guérin (BCG) versus BCG placebo trial from 30 melanoma centers (United States and international). Blood was assessed using a verified multimarker RT-qPCR assay (MART-1, MAGE-A3, and GalNAc-T) of melanoma-associated proteins. Cox regression analyses were used to evaluate the prognostic significance of CTC status for disease recurrence and melanoma-specific survival (MSS).
  
  
  RESULTS
  Individual CTC biomarker detection ranged from 13.4% to 17.5%. There was no association of CTC status (zero to one positive biomarkers v two or more positive biomarkers) with known clinical or pathologic prognostic variables. However, two or more positive biomarkers was significantly associated with worse distant metastasis disease-free survival (hazard ratio [HR] = 2.13, P = .009) and reduced recurrence-free survival (HR = 1.70, P = .046) and MSS (HR = 1.88, P = .043) in a multivariable analysis.
  
  
  CONCLUSIONS
  CTC biomarker status is a prognostic factor for recurrence-free survival, distant metastasis disease-free survival, and MSS after CLND in patients with SLN metastasis. This multimarker RT-qPCR analysis may therefore be useful in discriminating patients who may benefit from aggressive adjuvant therapy or stratifying patients for adjuvant clinical trials.
authors.affiliation: John Wayne Cancer Institute at Saint John's Health Center, 2200 Santa Monica Blvd, Santa Monica, CA 90404, USA.
authors.forename: Sojun
authors.initials: S
authors.lastname: Hoshimoto
authors.forename: Tatsushi
authors.initials: T
authors.lastname: Shingai
authors.forename: Donald L
authors.initials: DL
authors.lastname: Morton
authors.forename: Christine
authors.initials: C
authors.lastname: Kuo
authors.forename: Mark B
authors.initials: MB
authors.lastname: Faries
authors.forename: Kelly
authors.initials: K
authors.lastname: Chong
authors.forename: David
authors.initials: D
authors.lastname: Elashoff
authors.forename: He-Jing
authors.initials: HJ
authors.lastname: Wang
authors.forename: Robert M
authors.initials: RM
authors.lastname: Elashoff
authors.forename: Dave S B
authors.initials: DS
authors.lastname: Hoon
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001500:BCG Vaccine / Q000008:administration & dosage; D014408:Biomarkers, Tumor / Q000097:blood; D019496:Cancer Vaccines / Q000008:administration & dosage; D005260:Female; D006801:Humans; D016233:Immunotherapy, Active / Q000379:methods*; D008297:Male; D008545:Melanoma / Q000097:blood* / Q000473:pathology / Q000628:therapy*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D011379:Prognosis; D021701:Sentinel Lymph Node Biopsy / Q000379:methods*; D012878:Skin Neoplasms / Q000097:blood* / Q000473:pathology / Q000628:therapy*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D001500:BCG Vaccine; D014408:Biomarkers, Tumor; D019496:Cancer Vaccines