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Serial monitoring of circulating melanoma cells during neoadjuvant biochemotherapy for stage III melanoma: outcome prediction in a multicenter trial.

AbstractPURPOSE:
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.
PATIENTS AND 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).
CONCLUSION:
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.
AuthorsKazuo Koyanagi, Steven J O'Day, Rene Gonzalez, Karl Lewis, William A Robinson, Thomas T Amatruda, He-Jing Wang, Robert M Elashoff, Hiroya Takeuchi, Naoyuki Umetani, Dave S B Hoon
JournalJournal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 23 Issue 31 Pg. 8057-64 (Nov 01 2005) ISSN: 0732-183X [Print] United States
PMID16258104 (Publication Type: Journal Article, Multicenter Study, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • Interferon-alpha
  • Interleukin-2
  • MAGEA3 protein, human
  • MART-1 Antigen
  • MLANA protein, human
  • Neoplasm Proteins
  • PAX3 Transcription Factor
  • PAX3 protein, human
  • Paired Box Transcription Factors
  • RNA, Messenger
  • RNA, Neoplasm
  • Vinblastine
  • Dacarbazine
  • N-Acetylgalactosaminyltransferases
  • Cisplatin
Topics
  • Adolescent
  • Adult
  • Aged
  • Antigens, Neoplasm (blood, genetics)
  • Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
  • Biomarkers, Tumor (metabolism)
  • Chemotherapy, Adjuvant
  • Cisplatin (administration & dosage)
  • Dacarbazine (administration & dosage)
  • Female
  • Humans
  • Interferon-alpha (administration & dosage)
  • Interleukin-2 (administration & dosage)
  • MART-1 Antigen
  • Male
  • Melanoma (blood, drug therapy, pathology)
  • Middle Aged
  • N-Acetylgalactosaminyltransferases (blood, genetics)
  • Neoadjuvant Therapy
  • Neoplasm Invasiveness (pathology)
  • Neoplasm Proteins (blood, genetics)
  • Neoplasm Recurrence, Local (blood, drug therapy, pathology)
  • Neoplastic Cells, Circulating (metabolism, pathology)
  • PAX3 Transcription Factor
  • Paired Box Transcription Factors (blood, genetics)
  • Prospective Studies
  • RNA, Messenger (blood, genetics)
  • RNA, Neoplasm (blood, genetics)
  • Reverse Transcriptase Polymerase Chain Reaction
  • Risk Factors
  • Skin Neoplasms (blood, drug therapy, pathology)
  • Survival Rate
  • Treatment Outcome
  • Vinblastine (administration & dosage)

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