Serial monitoring of circulating melanoma cells during neoadjuvant biochemotherapy for stage III melanoma: outcome prediction in a multicenter trial.
OBJECTIVE
Circulating tumor cells (CTCs) in blood may be important in assessing tumor progression and treatment response. We hypothesized that quantitative real-time reverse transcriptase polymerase chain reaction using multimarker mRNA assays could detect CTCs and be used as a surrogate predictor of outcome in patients receiving neoadjuvant biochemotherapy (BC) for melanoma.


METHODS
Blood specimens were collected at four sampling points from 63 patients enrolled on a prospective multicenter phase II trial of BC before and after surgical treatment of American Joint Committee on Cancer stage III melanoma. Each specimen was assessed by quantitative real-time reverse transcriptase polymerase chain reaction for expression of four melanoma-associated markers: melanoma antigen recognized by T cells 1; beta1 --> 4-N-acetylgalactosaminyltransferase; paired box homeotic gene transcription factor 3; and melanoma antigen gene-A3 family, and the changes of CTCs during treatment and prognostic effect of CTCs after overall treatment on recurrence and survival were investigated.


RESULTS
At a median postoperative follow-up time of 30.4 months, 44 (70%) patients were clinically disease free. In relapse-free patients, the number of detected markers significantly decreased during preoperative BC (P = .036), during postoperative BC (P = .002), and during overall treatment (P < .0001). Marker detection after overall treatment was associated with significant decreases in relapse-free and overall survival (P < .0001). By multivariate analysis using a Cox proportional-hazards model, the number of markers detected after overall treatment was a significant independent prognostic factor for overall survival (risk ratio, 12.6; 95% CI, 3.16 to 50.5; P = .0003).


CONCLUSIONS
Serial monitoring of CTCs in blood may be useful for indicating systemic subclinical disease and predicting outcome of patients receiving neoadjuvant BC for metastatic melanoma.
Koyanagi
Kazuo
K
Department of Molecular Oncology, John Wayne Cancer Institute, Santa Monica, CA 90404, USA.
O'Day
Steven J
SJ
Gonzalez
Rene
R
Lewis
Karl
K
Robinson
William A
WA
Amatruda
Thomas T
TT
Wang
He-Jing
HJ
Elashoff
Robert M
RM
Takeuchi
Hiroya
H
Umetani
Naoyuki
N
Hoon
Dave S B
DS
D000293:Adolescent; D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000097:blood* / Q000235:genetics; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D003606:Dacarbazine / Q000008:administration & dosage; D005260:Female; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage; D007376:Interleukin-2 / Q000008:administration & dosage; D058965:MART-1 Antigen; D008297:Male; D008545:Melanoma / Q000097:blood* / Q000188:drug therapy / Q000473:pathology; D008875:Middle Aged; D017350:N-Acetylgalactosaminyltransferases / Q000097:blood / Q000235:genetics; D020360:Neoadjuvant Therapy; D009361:Neoplasm Invasiveness / Q000473:pathology; D009363:Neoplasm Proteins / Q000097:blood / Q000235:genetics; D009364:Neoplasm Recurrence, Local / Q000097:blood* / Q000188:drug therapy / Q000473:pathology; D009360:Neoplastic Cells, Circulating / Q000378:metabolism* / Q000473:pathology; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors / Q000097:blood / Q000235:genetics; D011446:Prospective Studies; D012333:RNA, Messenger / Q000097:blood / Q000235:genetics; D012334:RNA, Neoplasm / Q000097:blood / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D012878:Skin Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000473:pathology; D015996:Survival Rate; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D016898:Interferon-alpha; D007376:Interleukin-2; C072013:MAGEA3 protein, human; D058965:MART-1 Antigen; C548667:MLANA protein, human; D009363:Neoplasm Proteins; D000072041:PAX3 Transcription Factor; C489409:PAX3 protein, human; D051761:Paired Box Transcription Factors; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D014747:Vinblastine; D003606:Dacarbazine; D017350:N-Acetylgalactosaminyltransferases; D002945:Cisplatin