Details

Autor(en) / Beteiligte

• Elander, N. O.
• Aughton, K.
• Ghaneh, P.
• Neoptolemos, J. P.
• Palmer, D. H.
• Cox, T. F.
• Campbell, F.
• Costello, E.
• Halloran, C. M.
• Mackey, J. R.
• Scarfe, A. G
• Valle, J. W.
• McDonald, A. C.
• Carter, R.
• Tebbutt, N. C.
• Goldstein, D.
• Shannon, J.
• Dervenis, C.
• Glimelius, B.
• Deakin, M.
• Charnley, R. M.
• Anthoney, Alan
• Lerch, M. M.
• Mayerle, J.
• Oláh, A.
• Büchler, M. W.
• Greenhalf, W.

Titel

Expression of dihydropyrimidine dehydrogenase (DPD) and hENT1 predicts survival in pancreatic cancer

Ist Teil von

• British journal of cancer, 2018-04, Vol.118 (7), p.947-954

Ort / Verlag

London: Nature Publishing Group UK

Erscheinungsjahr

2018

Quelle

MEDLINE

Beschreibungen/Notizen

• ABSTRACT 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.