Deoxycitidine kinase is associated with prolonged survival after adjuvant gemcitabine for resected pancreatic adenocarcinoma.
BACKGROUND
Gemcitabine (2',2'-difluorodeoxycytidine) administration after resection of pancreatic cancer improves both disease-free survival (DFS) and overall survival (OS). Deoxycytidine kinase (dCK) mediates the rate-limiting catabolic step in the activation of gemcitabine. The authors of this report studied patient outcomes according to the expression of dCK after a postoperative gemcitabine-based chemoradiation regimen.


METHODS
Forty-five patients with resected pancreatic adenocarcinoma received adjuvant gemcitabine based-therapy in the context of multicenter phase 2 studies. Their tumors were evaluated retrospectively for dCK protein expression by immunohistochemistry. A composite score based on the percentage of dCK-positive cancer cells and the intensity of staining was generated, and the results were dichotomized at the median values.


RESULTS
The median follow-up was 19.95 months (95% confident interval [CI], 3.3-107.4 months). The lymph node (LN) ratio and dCK protein expression were significant predictors of DFS and OS in univariate analysis. On multivariate analysis, dCK protein expression was the only independent prognostic variable (DFS: hazard ratio [HR], 3.48; 95% CI, 1.66-7.31; P = .001; OS: HR, 3.2; 95% CI,1.44-7.13; P = .004).


CONCLUSIONS
dCK protein expression was identified as an independent and strong prognostic factor in patients with resected pancreatic adenocarcinoma who received adjuvant gemcitabine therapy. The authors concluded that it deserves prospective evaluation as a predictive biomarker for patient selection.
Maréchal
Raphaël
R
Department of Gastroenterology and Hepato-Pancreatology, Free University of Brussels, Brussels, Belgium. rmarecha@ulb.ac.be
Mackey
John R
JR
Lai
Raymond
R
Demetter
Pieter
P
Peeters
Marc
M
Polus
Marc
M
Cass
Carol E
CE
Salmon
Isabelle
I
Devière
Jacques
J
Van Laethem
Jean-Luc
JL
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000201:enzymology* / Q000601:surgery*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D003842:Deoxycytidine Kinase / Q000378:metabolism*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000378:metabolism / Q000401:mortality / Q000601:surgery*; D016896:Treatment Outcome; D000093542:Gemcitabine
D003841:Deoxycytidine; D003842:Deoxycytidine Kinase; D000093542:Gemcitabine