Serial monitoring of circulating tumor cells predicts outcome of induction biochemotherapy plus maintenance biotherapy for metastatic melanoma.
OBJECTIVE
Molecular biomarkers in blood are promising for assessment of tumor progression and treatment response. We hypothesized that serial monitoring of circulating tumor cells (CTC) with the use of multimarker quantitative real-time reverse transcriptase-PCR assays could be a surrogate predictor of outcome for melanoma patients enrolled in a multicenter phase II clinical trial of biochemotherapy (BCT) combined with maintenance biotherapy (mBT).


METHODS
Blood specimens were collected from 87 patients before and during induction BCT and mBT for stage IV melanoma. Expression of five melanoma-associated CTC biomarkers (MART-1, GalNAc-T, PAX-3, MAGE-A3, and Mitf) was assessed by quantitative real-time reverse transcriptase-PCR, and correlated with treatment response and disease outcome.


RESULTS
The number of positive CTC biomarkers decreased overall during induction BCT (P < 0.0001). CTC biomarker detection after two cycles of BCT was correlated with treatment response (P = 0.005) and overall survival (P = 0.001): an increase in the number of CTC biomarkers was associated with poor response (P = 0.006) and overall survival (P < 0.0001). Multivariate analyses with the use of a Cox proportional hazards model identified the change in CTC biomarkers after two cycles of BCT as an independent prognostic factor for disease progression (risk ratio, 12.6; 95% confidence interval, 4.78-33.4; P < 0.0001) and overall survival (risk ratio, 6.11; 95% confidence interval, 2.37-15.7; P = 0.0005).


CONCLUSIONS
Serial monitoring of CTC during induction BCT may be useful for predicting therapeutic efficacy and disease outcome in patients receiving BCT and mBT for stage IV melanoma.
Koyanagi
Kazuo
K
Department of Molecular Oncology, John Wayne Cancer Institute, Santa Monica, California 90404, USA.
O'Day
Steven J
SJ
Boasberg
Peter
P
Atkins
Michael B
MB
Wang
He-Jing
HJ
Gonzalez
Rene
R
Lewis
Karl
K
Thompson
John A
JA
Anderson
Clay M
CM
Lutzky
Jose
J
Amatruda
Thomas T
TT
Hersh
Evan
E
Richards
Jon
J
Weber
Jeffrey S
JS
Hoon
Dave S B
DS
D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D017322:Clinical Trials, Phase II as Topic; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D011446:Prospective Studies; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics*; D012074:Remission Induction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D015996:Survival Rate; D016896:Treatment Outcome; D055815:Young Adult
D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D012334:RNA, Neoplasm