TY  - JOUR
AU  - Elander, NO
AU  - Aughton, K
AU  - Ghaneh, P
AU  - Neoptolemos, JP
AU  - Palmer, DH
AU  - Cox, TF
AU  - Campbell, F
AU  - Costello, E
AU  - Halloran, CM
AU  - Mackey, JR
AU  - Scarfe, AG
AU  - Valle, JW
AU  - McDonald, AC
AU  - Carter, R
AU  - Tebbutt, NC
AU  - Goldstein, D
AU  - Shannon, J
AU  - Dervenis, C
AU  - Glimelius, B
AU  - Deakin, M
AU  - Charnley, RM
AU  - Anthoney, A
AU  - Lerch, MM
AU  - Mayerle, J
AU  - Olah, A
AU  - Buechler, MW
AU  - Greenhalf, W
Y2  - 2020/12/18
Y1  - 2018/04/01
SN  - 0007-0920
UR  - http://hdl.handle.net/11343/256164
AB  - BACKGROUND: Dihydropyrimidine dehydrogenase (DPD) tumour expression may provide added value to human equilibrative nucleoside transporter-1 (hENT1) tumour expression in predicting survival following pyrimidine-based adjuvant chemotherapy. METHODS: DPD and hENT1 immunohistochemistry and scoring was completed on tumour cores from 238 patients with pancreatic cancer in the ESPAC-3(v2) trial, randomised to either postoperative gemcitabine or 5-fluorouracil/folinic acid (5FU/FA). RESULTS: DPD tumour expression was associated with reduced overall survival (hazard ratio, HR = 1.73 [95% confidence interval, CI = 1.21-2.49], p = 0.003). This was significant in the 5FU/FA arm (HR = 2.07 [95% CI = 1.22-3.53], p = 0.007), but not in the gemcitabine arm (HR = 1.47 [0.91-3.37], p = 0.119). High hENT1 tumour expression was associated with increased survival in gemcitabine treated (HR = 0.56 [0.38-0.82], p = 0.003) but not in 5FU/FA treated patients (HR = 1.19 [0.80-1.78], p = 0.390). In patients with low hENT1 tumour expression, high DPD tumour expression was associated with a worse median [95% CI] survival in the 5FU/FA arm (9.7 [5.3-30.4] vs 29.2 [19.5-41.9] months, p = 0.002) but not in the gemcitabine arm (14.0 [9.1-15.7] vs. 18.0 [7.6-15.3] months, p = 1.000). The interaction of treatment arm and DPD expression was not significant (p = 0.303), but the interaction of treatment arm and hENT1 expression was (p = 0.009). CONCLUSION: DPD tumour expression was a negative prognostic biomarker. Together with tumour expression of hENT1, DPD tumour expression defined patient subgroups that might benefit from either postoperative 5FU/FA or gemcitabine.
LA  - English
PB  - NATURE PUBLISHING GROUP
T1  - Expression of dihydropyrimidine dehydrogenase (DPD) and hENT1 predicts survival in pancreatic cancer
DO  - 10.1038/s41416-018-0004-2
IS  - British Journal of Cancer
VL  - 118
IS  - 7
SP  - 947-954
L1  - /bitstream/handle/11343/256164/PMC5931115.pdf?sequence=1&isAllowed=y
ER  -