title: Change in CA 19-9 levels after chemoradiotherapy predicts survival in patients with locally advanced unresectable pancreatic cancer.
abstract: OBJECTIVE
  RTOG 9704 demonstrated a prognostic role for postoperative CA 19-9 in patients with resectable pancreatic carcinoma following surgery. Our study aimed to investigate whether CA 19-9 provided similar prognostic information in patients with locally advanced unresectable pancreatic cancer (LAPC) treated with chemoradiotherapy (CRT) and to determine whether such endpoints should therefore be reported in future randomized trials.
  
  
  METHODS
  Between December 1998 and October 2009, 253 patients with LAPC were treated with 5-fluourouracil-based concurrent CRT at our institution. Median radiation dose was 50.4 Gy. Only patients with a bilirubin of less than 2 mg/dL at the time the CA 19-9 was evaluated were included in the analysis to avoid the confounding effect of hyperbilirubinemia. Of the eligible patients, 54 had pre and post CRT CA 19-9 values available. The median age was 68 years and 52% were female. Categorized versions of the first post-CRT CA 19-9 were tested in 50 point increments beginning at <50 to >1,000 and percent change in pre to post-CRT CA 19-9 using cut points of 10% increments from <0% (increased) to >90%. Survival was measured from the date of first post CRT CA 19-9 level until death or last follow-up. Univariate and multivariate statistical methodologies were used to determine significant prognostic factors for overall survival.
  
  
  RESULTS
  Median CA 19-9 prior to CRT was 363 U/mL and post CRT median was 85.5 U/mL. Following CRT, patients with a decrease of >90% from their baseline CA 19-9 level had a significantly improved median survival than those that did not (16.2 vs. 7.5 months, P=0.01). The median survival of patients with a CA 19-9 level lower than the median post CRT value was 10.3 months, compared with 7.1 months for those with a CA 19-9 level greater than the median (P=0.03). Post CRT CA 19-9 less than 50 U/mL and histologic grade I-II also showed prognostic significance (both P=0.03). In multivariate analysis, post CRT CA 19-9 less than the median level of 85.5 U/mL was an independent prognostic factor for overall survival (HR 0.34; 95% CI, 0.13-0.85, P=0.02).
  
  
  CONCLUSIONS
  Our results indicate that post treatment CA 19-9 is predictive for overall survival in patient with LAPC following CRT. We recommend that pre and post treatment CA 19-9 levels be obtained in patients receiving CRT and that these values be considered for prognostic nomograms and future clinical trials.
authors.affiliation: Department of Radiation Medicine, Loma Linda University Medical Center, Loma Linda, California, USA;
authors.forename: Gary Y
authors.initials: GY
authors.lastname: Yang
authors.forename: Nadia K
authors.initials: NK
authors.lastname: Malik
authors.forename: Rameela
authors.initials: R
authors.lastname: Chandrasekhar
authors.forename: Wen-Wee
authors.initials: WW
authors.lastname: Ma
authors.forename: Leayn
authors.initials: L
authors.lastname: Flaherty
authors.forename: Renuka
authors.initials: R
authors.lastname: Iyer
authors.forename: Boris
authors.initials: B
authors.lastname: Kuvshinoff
authors.forename: John
authors.initials: J
authors.lastname: Gibbs
authors.forename: Gregory
authors.initials: G
authors.lastname: Wilding
authors.forename: Graham
authors.initials: G
authors.lastname: Warren
authors.forename: Kilian Salerno
authors.initials: KS
authors.lastname: May
keywords: CA19-9; chemoradiotherapy (CRT); pancreatic cancer