title: Can determination of circulating endothelial cells and serum caspase-cleaved CK18 predict for response and survival in patients with advanced non-small-cell lung cancer receiving endostatin and paclitaxel-carboplatin chemotherapy? a retrospective study.
abstract: BACKGROUND
  Early prediction of the efficacy of a combination of an antiangiogenic drug with cytotoxic chemotherapy is a significant challenge. In that regard, circulating endothelial cells (CECs) and cytokeratins (CKs) seem to reflect their roles in both tumor angiogenesis and tumor cell death.
  
  
  METHODS
  Patients with advanced, previously untreated non-small-cell lung cancer were randomly assigned to an endostatin treatment group (paclitaxel + carboplatin + endostatin) and a control group (paclitaxel + carboplatin + placebo). A total of 122 patients were evaluated, of whom 107 had measurements of blood CECs, CK8, caspase-cleaved CK18 (ccCK18), and uncleaved CK18 (CK18) before and at weeks 3 and 6 of treatment, respectively.
  
  
  RESULTS
  Higher baseline CECs in patients with a tumor response (partial remission + stable disease, p = 0.002 for the entire group; p = 0.000 for the treatment group) were observed. The number of CECs decreased significantly after endostatin treatment (p = 0.000), whereas CK levels increased. Increased levels of ccCK18 and CK18, but not CK8, reached significance (p = 0.001 and p = 0.048, respectively) when compared with the baseline. Tumor response showed a strong correlation with reduction of CECs (p = 0.000) and increase of ccCK18 (p = 0.040) after endostatin therapy. Cutoff values of changes of CECs and ccCK18 for prediction of survival were 0.58/μl and 19.6 ng/ml, respectively. Reduction of CECs and increase of ccCK18 significantly correlated with longer median survival (p = 0.013 and p = 0.016 for progression-free survival; p = 0.009 and p = 0.012 for overall survival, respectively).
  
  
  CONCLUSIONS
  CECs and CKs could be biomarkers for selecting patients with non-small-cell lung cancer who will benefit from treatment with endostatin in combination with paclitaxel plus carboplatin.
authors.affiliation: Department of Pulmonology, Shanghai Chest Hospital, Jiaotong University, Shanghai, China.
authors.forename: Tian-Qing
authors.initials: TQ
authors.lastname: Chu
authors.affiliation: Department of Radiation Oncology, Eye, Ear, Nose & Throat Hospital, Fudan University, Shanghai, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Ding
authors.affiliation: Medical Department, Pro-Med Cancer Centers, Shanghai, China.
authors.forename: David H
authors.initials: DH
authors.lastname: Garfield
authors.affiliation: Department of Pulmonology, Shanghai Chest Hospital, Jiaotong University, Shanghai, China.
authors.forename: Ai-Qin
authors.initials: AQ
authors.lastname: Gu
authors.affiliation: Department of Pulmonology, Shanghai Chest Hospital, Jiaotong University, Shanghai, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Pei
authors.affiliation: Division of Surgical Oncology and Thoracic Surgery, University Medical Center Mannheim, University of Heidelberg, Mannheim, Germany.. Electronic address: weidongdu@hotmail.com.
authors.forename: Wei-Dong
authors.initials: WD
authors.lastname: Du
authors.affiliation: Department of Pulmonology, Shanghai Chest Hospital, Jiaotong University, Shanghai, China. Electronic address: hbhxkyy@gmail.com.
authors.forename: Bao-Hui
authors.initials: BH
authors.lastname: Han
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics*; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology; D016022:Case-Control Studies; D020169:Caspases / Q000097:blood*; D004311:Double-Blind Method; D043169:Endostatins / Q000008:administration & dosage; D004730:Endothelium, Vascular / Q000473:pathology*; D005260:Female; D006801:Humans; D053538:Keratin-18 / Q000378:metabolism*; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000473:pathology; D009367:Neoplasm Staging; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D017239:Paclitaxel / Q000008:administration & dosage; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D043169:Endostatins; D053538:Keratin-18; D016190:Carboplatin; D020169:Caspases; D017239:Paclitaxel