title: Prognostic significance of carbohydrate antigen 19-9 in unresectable locally advanced pancreatic cancer treated with dose-escalated intensity modulated radiation therapy and concurrent full-dose gemcitabine: analysis of a prospective phase 1/2 dose escalation study.
abstract: OBJECTIVE
  Although established in the postresection setting, the prognostic value of carbohydrate antigen 19-9 (CA19-9) in unresectable locally advanced pancreatic cancer (LAPC) is less clear. We examined the prognostic utility of CA19-9 in patients with unresectable LAPC treated on a prospective trial of intensity modulated radiation therapy (IMRT) dose escalation with concurrent gemcitabine.
  
  
  METHODS
  Forty-six patients with unresectable LAPC were treated at the University of Michigan on a phase 1/2 trial of IMRT dose escalation with concurrent gemcitabine. CA19-9 was obtained at baseline and during routine follow-up. Cox models were used to assess the effect of baseline factors on freedom from local progression (FFLP), distant progression (FFDP), progression-free survival (PFS), and overall survival (OS). Stepwise forward regression was used to build multivariate predictive models for each endpoint.
  
  
  RESULTS
  Thirty-eight patients were eligible for the present analysis. On univariate analysis, baseline CA19-9 and age predicted OS, CA19-9 at baseline and 3 months predicted PFS, gross tumor volume (GTV) and black race predicted FFLP, and CA19-9 at 3 months predicted FFDP. On stepwise multivariate regression modeling, baseline CA19-9, age, and female sex predicted OS; baseline CA19-9 and female sex predicted both PFS and FFDP; and GTV predicted FFLP. Patients with baseline CA19-9 ≤ 90 U/mL had improved OS (median 23.0 vs 11.1 months, HR 2.88, P<.01) and PFS (14.4 vs 7.0 months, HR 3.61, P=.001). CA19-9 progression over 90 U/mL was prognostic for both OS (HR 3.65, P=.001) and PFS (HR 3.04, P=.001), and it was a stronger predictor of death than either local progression (HR 1.46, P=.42) or distant progression (HR 3.31, P=.004).
  
  
  CONCLUSIONS
  In patients with unresectable LAPC undergoing definitive chemoradiation therapy, baseline CA19-9 was independently prognostic even after established prognostic factors were controlled for, whereas CA19-9 progression strongly predicted disease progression and death. Future trials should stratify by baseline CA19-9 and incorporate CA19-9 progression as a criterion for progressive disease.
authors.affiliation: Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan, USA. jvainsh@med.umich.edu
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Vainshtein
authors.forename: Matthew
authors.initials: M
authors.lastname: Schipper
authors.forename: Mark M
authors.initials: MM
authors.lastname: Zalupski
authors.forename: Theodore S
authors.initials: TS
authors.lastname: Lawrence
authors.forename: Ross
authors.initials: R
authors.lastname: Abrams
authors.forename: Isaac R
authors.initials: IR
authors.lastname: Francis
authors.forename: Gazala
authors.initials: G
authors.lastname: Khan
authors.forename: William
authors.initials: W
authors.lastname: Leslie
authors.forename: Edgar
authors.initials: E
authors.lastname: Ben-Josef
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy*; D018395:CA-19-9 Antigen / Q000097:blood*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000097:blood / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage*; D011879:Radiotherapy Dosage; D050397:Radiotherapy, Intensity-Modulated / Q000379:methods*; D012044:Regression Analysis; D012737:Sex Factors; D047368:Tumor Burden; D000093542:Gemcitabine
chemical_list: D018395:CA-19-9 Antigen; D011838:Radiation-Sensitizing Agents; D003841:Deoxycytidine; D000093542:Gemcitabine