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Pancreatic Cancer hENT1 Expression and Survival From Gemcitabine in Patients From the ESPAC-3 Trial
Open accessAbstract
BACKGROUND: Human equilibrative nucleoside transporter 1 (hENT1) levels in pancreatic adenocarcinoma may predict survival in patients who receive adjuvant gemcitabine after resection. METHODS: Microarrays from 434 patients randomized to chemotherapy in the ESPAC-3 trial (plus controls from ESPAC-1/3) were stained with the 10D7G2 anti-hENT1 antibody. Patients were classified as having high hENT1 expression if the mean H score for their cores was above the overall median H score (48). High and low hENT1-expressing groups were compared using Kaplan-Meier curves, log-rank tests, and Cox proportional hazards models. All statistical tests were two-sided. RESULTS: Three hundred eighty patients (87.6%) and 1808 cores were suitable and included in the final analysis. Median overall survival for gemcitabine-treated patients (n = 176) was 23.4 (95% confidence interval [CI] = 18.3 to 26.0) months vs 23.5 (95% CI = 19.8 to 27.3) months for 176 patients treated with 5-fluorouracil/folinic acid (χ(2) 1=0.24; P = .62). Median survival for patients treated with gemcitabine was 17.1 (95% CI = 14.3 to 23.8) months for those with low hENT1 expression vs 26.2 (95% CI = 21.2 to 31.4) months for those with high hENT1 expression (χ(2)₁= 9.87; P = .002). For the 5-fluorouracil group, median survival was 25.6 (95% CI = 20.1 to 27.9) and 21.9 (95% CI = 16.0 to 28.3) months for those with low and high hENT1 expression, respectively (χ(2)₁ = 0.83; P = .36). hENT1 levels were not predictive of survival for the 28 patients of the observation group (χ(2)₁ = 0.37; P = .54). Multivariable analysis confirmed hENT1 expression as a predictive marker in gemcitabine-treated (Wald χ(2) = 9.16; P = .003) but not 5-fluorouracil-treated (Wald χ(2) = 1.22; P = .27) patients. CONCLUSIONS: Subject to prospective validation, gemcitabine should not be used for patients with low tumor hENT1 expression.
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Neoptolemos, J. P., Kleeff, J., Michl, P., Costello, E., Greenhalf, W., & Palmer, D. H. (2018) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-018-0005-x · Cited by 1,170
Self-citationBreastfeeding and maternal health outcomes: A systematic review and meta-analysis
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Metadata
- Authors
- Greenhalf, W., Ghaneh, P., Neoptolemos, J. P., Palmer, D. H., Cox, T. F., Lamb, R. F., Garner, E., Campbell, F., Mackey, J. R., Costello, E., Moore, M. J., Valle, J. W., McDonald, A. C., Carter, R., Tebbutt, N. C., Goldstein, D., Shannon, J., Dervenis, C., Glimelius, B., Deakin, M., Charnley, R. M., Lacaine, F., Scarfe, A. G., Middleton, M. R., Anthoney, A., Halloran, C. M., Mayerle, J., Oláh, A., Jackson, R., Rawcliffe, C. L., Scarpa, A., Bassi, C., & Büchler, M. W.
- Venue
- JNCI: Journal of the National Cancer Institute
- Publisher
- Oxford University Press (OUP)
- Published
- 2013-12-03
- Volume
- 106
- Issue
- 1
- Pages
- djt347-djt347
- ISSN
- 0027-8874 (ISSN-L)
- 1460-2105
- OpenAlex
- W2116313694
- Cited by
- 337
- References
- 30
- FWCI
- 19.45
- Type
- journal article
- Language
- en
- Open access
- green
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- Greenhalf, W., Ghaneh, P., Neoptolemos, J. P., Palmer, D. H., Cox, T. F., Lamb, R. F., Garner, E., Campbell, F., Mackey, J. R., Costello, E., Moore, M. J., Valle, J. W., McDonald, A. C., Carter, R., Tebbutt, N. C., Goldstein, D., Shannon, J., Dervenis, C., Glimelius, B., . . . Büchler, M. W. (2014). Pancreatic Cancer hENT1 Expression and Survival From Gemcitabine in Patients From the ESPAC-3 Trial. JNCI: Journal of the National Cancer Institute. https://doi.org/10.1093/jnci/djt347
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