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

Int J Radiat Oncol Biol Phys. 2013 May 1;86(1):96-101. doi: 10.1016/j.ijrobp.2012.11.020. Epub 2012 Dec 19.

Abstract

Purpose: 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 and materials: 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.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenocarcinoma / blood
  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / pathology
  • Adenocarcinoma / radiotherapy*
  • CA-19-9 Antigen / blood*
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives*
  • Disease-Free Survival
  • Female
  • Gemcitabine
  • Humans
  • Male
  • Middle Aged
  • Pancreatic Neoplasms / blood
  • Pancreatic Neoplasms / drug therapy
  • Pancreatic Neoplasms / mortality
  • Pancreatic Neoplasms / pathology
  • Pancreatic Neoplasms / radiotherapy*
  • Prognosis
  • Proportional Hazards Models
  • Prospective Studies
  • Radiation-Sensitizing Agents / administration & dosage*
  • Radiotherapy Dosage
  • Radiotherapy, Intensity-Modulated / methods*
  • Regression Analysis
  • Sex Factors
  • Tumor Burden

Substances

  • CA-19-9 Antigen
  • Radiation-Sensitizing Agents
  • Deoxycytidine
  • Gemcitabine