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dc.contributor.authorElander, NO
dc.contributor.authorAughton, K
dc.contributor.authorGhaneh, P
dc.contributor.authorNeoptolemos, JP
dc.contributor.authorPalmer, DH
dc.contributor.authorCox, TF
dc.contributor.authorCampbell, F
dc.contributor.authorCostello, E
dc.contributor.authorHalloran, CM
dc.contributor.authorMackey, JR
dc.contributor.authorScarfe, AG
dc.contributor.authorValle, JW
dc.contributor.authorMcDonald, AC
dc.contributor.authorCarter, R
dc.contributor.authorTebbutt, NC
dc.contributor.authorGoldstein, D
dc.contributor.authorShannon, J
dc.contributor.authorDervenis, C
dc.contributor.authorGlimelius, B
dc.contributor.authorDeakin, M
dc.contributor.authorCharnley, RM
dc.contributor.authorAnthoney, A
dc.contributor.authorLerch, MM
dc.contributor.authorMayerle, J
dc.contributor.authorOlah, A
dc.contributor.authorBuechler, MW
dc.contributor.authorGreenhalf, W
dc.date.accessioned2020-12-18T04:22:07Z
dc.date.available2020-12-18T04:22:07Z
dc.date.issued2018-04-01
dc.identifierpii: 10.1038/s41416-018-0004-2
dc.identifier.citationElander, 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. ,... Greenhalf, W. (2018). Expression of dihydropyrimidine dehydrogenase (DPD) and hENT1 predicts survival in pancreatic cancer. BRITISH JOURNAL OF CANCER, 118 (7), pp.947-954. https://doi.org/10.1038/s41416-018-0004-2.
dc.identifier.issn0007-0920
dc.identifier.urihttp://hdl.handle.net/11343/256164
dc.description.abstractBACKGROUND: 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.
dc.languageEnglish
dc.publisherNATURE PUBLISHING GROUP
dc.titleExpression of dihydropyrimidine dehydrogenase (DPD) and hENT1 predicts survival in pancreatic cancer
dc.typeJournal Article
dc.identifier.doi10.1038/s41416-018-0004-2
melbourne.affiliation.departmentSurgery (Austin & Northern Health)
melbourne.source.titleBritish Journal of Cancer
melbourne.source.volume118
melbourne.source.issue7
melbourne.source.pages947-954
dc.rights.licenseCC BY
melbourne.elementsid1312770
melbourne.contributor.authorTebbutt, Niall
dc.identifier.eissn1532-1827
melbourne.accessrightsOpen Access


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