title: Prognostic Role of Circulating Tumor Cells during Induction Chemotherapy Followed by Curative Surgery Combined with Postoperative Radiotherapy in Patients with Locally Advanced Oral and Oropharyngeal Squamous Cell Cancer.
abstract: BACKGROUND
  The prognostic role of circulating tumor cells (CTCs) after induction chemotherapy using docetaxel, cisplatin and fluorouracil (TPF) prior to surgery and adjuvant (chemo)radiation in locally advanced oral squamous cell cancer (OSCC) was evaluated.
  
  
  METHODS
  In this prospective study, peripheral blood samples from 40 patients of the phase II study TISOC-1 (NCT01108042) with OSCC before, during, and after treatment were taken. CTCs were quantified using laser scanning cytometry of anti- epithelial cell adhesion molecule-stained epithelial cells. Their detection was correlated with clinical risk factors, recurrence-free (RFS) and overall survival (OS).
  
  
  RESULTS
  Before starting the treatment CTCs were detected in 32 of 40 patients (80%). The median number at baseline was 3295 CTCs/ml. The median maximal number of CTCs during treatment was 5005 CTCs/ml. There was a significant increase of CTCs before postoperative radiotherapy compared to baseline before 1st cycle of IC (p = 0.011), 2nd cycle of IC (p = 0.001), 3rd cycle of IC (p = 0.004), and before surgery (p = 0.002), but not compared to end of therapy (p = 0.118). CTCs at baseline >median was also associated to risk of recurrence (p = 0.014). Maximal CTCs during therapy >median was more frequently observed in tumors of the oral cavity (p=0.022) and related to higher risk of death during follow-up (p = 0.028). Patients with CTCs at baseline >median value had significant lower RFS than patients with CTCs at baseline <median value (p = 0.025). Patients with maximal CTCs values >median during the complete course of therapy had a significantly lower OS than patients with values <median (p = 0.049). Finally, the multivariate analysis revealed that OS was significantly lower in patients with maximal CTCs during treatment higher than the median value (HR=6.151; CI: 1.244-30.420).
  
  
  CONCLUSIONS
  Baseline CTCs and maximal CTCs during therapy both seem to be good prognostic markers for OSCC when treated by TPF induction chemotherapy, surgery, and postoperative (chemo)radiation.
authors.affiliation: Department of Otorhinolaryngology, Jena University Hospital, Jena, Germany.
authors.forename: Johanna
authors.initials: J
authors.lastname: Inhestern
authors.affiliation: Department of Otorhinolaryngology, Jena University Hospital, Jena, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Oertel
authors.affiliation: Department of Otorhinolaryngology, Jena University Hospital, Jena, Germany.
authors.forename: Viola
authors.initials: V
authors.lastname: Stemmann
authors.affiliation: University Tumor Center, Jena University Hospital, Jena, Germany.
authors.forename: Harald
authors.initials: H
authors.lastname: Schmalenberg
authors.affiliation: Department of ENT Surgery, University Medical Center Leipzig, Leipzig, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Dietz
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Ulm University Medical Center, Ulm, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Rotter
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Ulm University Medical Center, Ulm, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Veit
authors.affiliation: Department of Hematology and Oncology, Academic Teaching Hospital Bielefeld, Bielefeld, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Görner
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Academic Teaching Hospital Bielefeld, Bielefeld, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Sudhoff
authors.affiliation: Division of Medicine, Department of Hematology, Oncology and Palliative Medicine, University of Rostock, Rostock, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Junghanß
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Giessen and Marburg, Giessen, Germany.
authors.forename: Claus
authors.initials: C
authors.lastname: Wittekindt
authors.affiliation: Clinic of Internal Medicine II, Division of Hematology and Internal Oncology, Jena University Hospital, Erlanger Allee 101, Jena, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Pachmann
authors.affiliation: Department of Otorhinolaryngology, Jena University Hospital, Jena, Germany.
authors.forename: Orlando
authors.initials: O
authors.lastname: Guntinas-Lichius
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy*; D002452:Cell Count; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D060828:Induction Chemotherapy; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy*; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local / Q000473:pathology; D009367:Neoplasm Staging; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D009959:Oropharyngeal Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy*; D011182:Postoperative Care; D011379:Prognosis; D016016:Proportional Hazards Models; D012307:Risk Factors