title: Detection of circulating tumor cells in patients with locally advanced rectal cancer undergoing neoadjuvant therapy followed by curative surgery.
abstract: OBJECTIVE
  Circulating tumor cells (CTCs) represent an independent prognostic factor in metastatic colorectal cancer, while their significance in early stages is still an open issue. The aim of the study is to investigate the role of CTCs in rectal cancer patients undergoing neoadjuvant chemoradiotherapy (CT-RT).
  
  
  METHODS
  In this prospective single institutional study, cT3-4 and/or N+ rectal cancer was treated with neoadjuvant CT-RT. The primary endpoints were as follows: evaluation of CTCs at baseline (t0), after CT-RT (t1), within 7 days after surgery (t2), and at 6 months from surgery (t3) and correlation with main patient/tumor characteristics, CEA, response to neoadjuvant therapy, and disease-free survival (DFS). CTCs were enumerated with the CellSearch System in 22.5 ml peripheral blood. A repeated measure analysis for binary outcome was used to evaluate over time changes in the percentage of CTCs detectable in blood samples.
  
  
  RESULTS
  Of the 90 patients enrolled in this study, 85 were eligible consisting of 52 males and 33 females. Median age was 63 years and median follow-up was 38 months. CTCs were available for all patients at t0, for 67 at t1, for 68 at t2, and for 62 at t3. CTCs >0 were reported on 16 (19%) at t0, on 5 (7.5%) at t1, on 6 (9%) at t2, and on 3 (5%) at t3 (P value for trend 0.039). Only for CT-RT responders, CTCs reduced from t0 to t1. No statistically significant association was found between CTCs and main patient/tumor characteristics and DFS.
  
  
  CONCLUSIONS
  Sixteen patients (19%) had CTCs ≥1 at t0 with reduction in CTC number in case of objective remissions. The proportion of patients with CTCs ≥1 decreased over the time as the therapeutic course proceeded. Much effort should be oriented toward increasing CTC detection rate by enhancing technical tests and achieving better patient characterization.
authors.affiliation: Gastrointestinal and Neuroendocrine Tumors Unit, European Institute of Oncology, via Ripamonti 435, 20141, Milan, Italy, elenamagni@yahoo.com.
authors.forename: Elena
authors.initials: E
authors.lastname: Magni
authors.forename: Edoardo
authors.initials: E
authors.lastname: Botteri
authors.forename: Paola S
authors.initials: PS
authors.lastname: Ravenda
authors.forename: Maria C
authors.initials: MC
authors.lastname: Cassatella
authors.forename: Emilio
authors.initials: E
authors.lastname: Bertani
authors.forename: Antonio
authors.initials: A
authors.lastname: Chiappa
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Luca
authors.forename: Laura
authors.initials: L
authors.lastname: Zorzino
authors.forename: Paolo Pietro
authors.initials: PP
authors.lastname: Bianchi
authors.forename: Laura
authors.initials: L
authors.lastname: Adamoli
authors.forename: Maria T
authors.initials: MT
authors.lastname: Sandri
authors.forename: Maria G
authors.initials: MG
authors.lastname: Zampino
mesh_terms: D000368:Aged; D059186:Chemoradiotherapy, Adjuvant; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D009360:Neoplastic Cells, Circulating / Q000378:metabolism*; D011446:Prospective Studies; D012004:Rectal Neoplasms / Q000097:blood* / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D016019:Survival Analysis