title: Cytokeratin 19-fragments (CYFRA 21-1) as a novel serum biomarker for response and survival in patients with advanced pancreatic cancer.
abstract: BACKGROUND
  CYFRA 21-1 serves as biomarker in several epithelial malignancies. However, its role in pancreatic cancer (PC) has not yet been investigated.
  
  
  METHODS
  Within a prospective single-centre study serial blood samples were collected from patients with confirmed advanced PC. Pre-treatment values and weekly measurements of CYFRA 21-1, carbohydrate antigen 19-9 (CA 19-9) and carcinoembryonic antigen (assessed by Elecsys 2010, Roche Diagnostics) during palliative first-line chemotherapy were obtained. Biomarker data were correlated with objective response (determined by RECIST) as well as time to progression (TTP) and overall survival (OS) using uni- and multivariate analyses.
  
  
  RESULTS
  Seventy-eight patients were included, 45% of these received treatment in prospective clinical trials. Median TTP was 3.9 months, median OS 7.7 months. Pre-treatment CYFRA 21-1 levels were significantly associated with performance status (P=0.0399) and stage of disease (P=0.0001). Marker values before chemotherapy and at the 2-month staging of all three markers were considered significant predictors for objective treatment response. Pre-treatment CYFRA 21-1 levels, as well as CA 19-9 values, could be applied to define subgroups (categorised by tertiles) with a different OS outcome (CYFRA: 14.8 vs 7.1 vs 4.8 months, CA 19-9: 14.2 vs 7.1 vs 5.2 months; P<0.0001). CYFRA 21-1 and CA 19-9 (both as categorised and as continuous variables) showed a highly significant correlation with TTP and OS at nearly all-time points assessed in univariate analysis. In multivariate analysis, only CYFRA 21-1 and performance status were independent predictors for OS.
  
  
  CONCLUSIONS
  CYFRA 21-1 may serve as a valuable tool for monitoring treatment response and assessing prognosis in advanced PC.
authors.affiliation: Department of Internal Medicine III and Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, Munich, Germany. stefan.boeck@med.uni-muenchen.de
authors.forename: S
authors.initials: S
authors.lastname: Boeck
authors.forename: C
authors.initials: C
authors.lastname: Wittwer
authors.forename: V
authors.initials: V
authors.lastname: Heinemann
authors.forename: M
authors.initials: M
authors.lastname: Haas
authors.forename: C
authors.initials: C
authors.lastname: Kern
authors.forename: P
authors.initials: P
authors.lastname: Stieber
authors.forename: D
authors.initials: D
authors.lastname: Nagel
authors.forename: S
authors.initials: S
authors.lastname: Holdenrieder
mesh_terms: D000328:Adult; D000368:Aged; D000418:Albumins / Q000627:therapeutic use; D000951:Antigens, Neoplasm / Q000097:blood*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000077784:Axitinib; D014408:Biomarkers, Tumor / Q000097:blood*; D018395:CA-19-9 Antigen / Q000097:blood; D000069287:Capecitabine; D002272:Carcinoembryonic Antigen / Q000097:blood; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D018572:Disease-Free Survival; D000069347:Erlotinib Hydrochloride; D000068338:Everolimus; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage; D007191:Indazoles / Q000008:administration & dosage; D053539:Keratin-19 / Q000097:blood*; D008875:Middle Aged; D015999:Multivariate Analysis; D010091:Oximes; D017239:Paclitaxel / Q000627:therapeutic use; D010166:Palliative Care; D010190:Pancreatic Neoplasms / Q000097:blood* / Q000188:drug therapy*; D010879:Piperazines / Q000008:administration & dosage; D011446:Prospective Studies; D011799:Quinazolines / Q000008:administration & dosage; D020123:Sirolimus / Q000008:administration & dosage / Q000031:analogs & derivatives; D013449:Sulfonamides / Q000008:administration & dosage; D015996:Survival Rate; D000093542:Gemcitabine
chemical_list: C520255:130-nm albumin-bound paclitaxel; D000418:Albumins; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D018395:CA-19-9 Antigen; D002272:Carcinoembryonic Antigen; D007093:Imidazoles; D007191:Indazoles; D053539:Keratin-19; D010091:Oximes; D010879:Piperazines; D011799:Quinazolines; D013449:Sulfonamides; C102012:antigen CYFRA21.1; D003841:Deoxycytidine; D000069287:Capecitabine; D000068338:Everolimus; D000077784:Axitinib; D000069347:Erlotinib Hydrochloride; D017239:Paclitaxel; C580590:upamostat; D005472:Fluorouracil; D020123:Sirolimus; D000093542:Gemcitabine