Pancreatic cancer hENT1 expression and survival from gemcitabine in patients from the ESPAC-3 trial

William Greenhalf; Paula Ghaneh; John P. Neoptolemos; Daniel H. Palmer; Trevor F. Cox; Richard F. Lamb; Elizabeth Garner; Fiona Campbell; John R. MacKey; Eithne Costello; Malcolm J. Moore; Juan W. Valle; Alexander C. McDonald; Ross Carter; Niall C. Tebbutt; David Goldstein; Jennifer Shannon; Christos Dervenis; Bengt Glimelius; Mark Deakin; Richard M. Charnley; François Lacaine; Andrew G. Scarfe; Mark R. Middleton; Alan Anthoney; Christopher M. Halloran; Julia Mayerle; Attila Oláh; Richard Jackson; Charlotte L. Rawcliffe; Aldo Scarpa; Claudio Bassi; Markus W. Büchler

doi:10.1093/jnci/djt347

Pancreatic cancer hENT1 expression and survival from gemcitabine in patients from the ESPAC-3 trial

William Greenhalf, Paula Ghaneh, John P. Neoptolemos, Daniel H. Palmer, Trevor F. Cox, Richard F. Lamb, Elizabeth Garner, Fiona Campbell, John R. MacKey, Eithne Costello, Malcolm J. Moore, Juan W. Valle, Alexander C. McDonald, Ross Carter, Niall C. Tebbutt, David Goldstein, Jennifer Shannon, Christos Dervenis, Bengt Glimelius, Mark DeakinRichard M. Charnley, François Lacaine, Andrew G. Scarfe, Mark R. Middleton, Alan Anthoney, Christopher M. Halloran, Julia Mayerle, Attila Oláh, Richard Jackson, Charlotte L. Rawcliffe, Aldo Scarpa, Claudio Bassi, Markus W. Büchler

Research output: Contribution to journal › Article › peer-review

Abstract

BackgroundHuman equilibrative nucleoside transporter 1 (hENT1) levels in pancreatic adenocarcinoma may predict survival in patients who receive adjuvant gemcitabine after resection.MethodsMicroarrays 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.ResultsThree 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 (χ2 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 (χ21= 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 (χ21 = 0.83; P =. 36). hENT1 levels were not predictive of survival for the 28 patients of the observation group (χ21 = 0.37; P =. 54). Multivariable analysis confirmed hENT1 expression as a predictive marker in gemcitabine-treated (Wald χ2 = 9.16; P =. 003) but not 5-fluorouracil-treated (Wald χ2 = 1.22; P =. 27) patients.ConclusionsSubject to prospective validation, gemcitabine should not be used for patients with low tumor hENT1 expression. © 2013 The Author.

Original language	English
Article number	djt347
Journal	Journal of the National Cancer Institute
Volume	106
Issue number	1
DOIs	https://doi.org/10.1093/jnci/djt347
Publication status	Published - 2014

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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. Journal of the National Cancer Institute, 106(1), Article djt347. https://doi.org/10.1093/jnci/djt347

@article{963abd6e00a94517adcc8940a841f3d8,

title = "Pancreatic cancer hENT1 expression and survival from gemcitabine in patients from the ESPAC-3 trial",

abstract = "BackgroundHuman equilibrative nucleoside transporter 1 (hENT1) levels in pancreatic adenocarcinoma may predict survival in patients who receive adjuvant gemcitabine after resection.MethodsMicroarrays 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.ResultsThree 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 (χ2 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 (χ21= 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 (χ21 = 0.83; P =. 36). hENT1 levels were not predictive of survival for the 28 patients of the observation group (χ21 = 0.37; P =. 54). Multivariable analysis confirmed hENT1 expression as a predictive marker in gemcitabine-treated (Wald χ2 = 9.16; P =. 003) but not 5-fluorouracil-treated (Wald χ2 = 1.22; P =. 27) patients.ConclusionsSubject to prospective validation, gemcitabine should not be used for patients with low tumor hENT1 expression. {\textcopyright} 2013 The Author.",

author = "William Greenhalf and Paula Ghaneh and Neoptolemos, {John P.} and Palmer, {Daniel H.} and Cox, {Trevor F.} and Lamb, {Richard F.} and Elizabeth Garner and Fiona Campbell and MacKey, {John R.} and Eithne Costello and Moore, {Malcolm J.} and Valle, {Juan W.} and McDonald, {Alexander C.} and Ross Carter and Tebbutt, {Niall C.} and David Goldstein and Jennifer Shannon and Christos Dervenis and Bengt Glimelius and Mark Deakin and Charnley, {Richard M.} and Fran{\c c}ois Lacaine and Scarfe, {Andrew G.} and Middleton, {Mark R.} and Alan Anthoney and Halloran, {Christopher M.} and Julia Mayerle and Attila Ol{\'a}h and Richard Jackson and Rawcliffe, {Charlotte L.} and Aldo Scarpa and Claudio Bassi and B{\"u}chler, {Markus W.}",

year = "2014",

doi = "10.1093/jnci/djt347",

language = "English",

volume = "106",

journal = "Journal of the National Cancer Institute",

issn = "0027-8874",

publisher = "Oxford University Press",

number = "1",

}

Greenhalf, W, Ghaneh, P, Neoptolemos, JP, Palmer, DH, Cox, TF, Lamb, RF, Garner, E, Campbell, F, MacKey, JR, Costello, E, Moore, MJ, Valle, JW, McDonald, AC, Carter, R, Tebbutt, NC, Goldstein, D, Shannon, J, Dervenis, C, Glimelius, B, Deakin, M, Charnley, RM, Lacaine, F, Scarfe, AG, Middleton, MR, Anthoney, A, Halloran, CM, Mayerle, J, Oláh, A, Jackson, R, Rawcliffe, CL, Scarpa, A, Bassi, C & Büchler, MW 2014, 'Pancreatic cancer hENT1 expression and survival from gemcitabine in patients from the ESPAC-3 trial', Journal of the National Cancer Institute, vol. 106, no. 1, djt347. https://doi.org/10.1093/jnci/djt347

TY - JOUR

T1 - Pancreatic cancer hENT1 expression and survival from gemcitabine in patients from the ESPAC-3 trial

AU - Greenhalf, William

AU - Ghaneh, Paula

AU - Neoptolemos, John P.

AU - Palmer, Daniel H.

AU - Cox, Trevor F.

AU - Lamb, Richard F.

AU - Garner, Elizabeth

AU - Campbell, Fiona

AU - MacKey, John R.

AU - Costello, Eithne

AU - Moore, Malcolm J.

AU - Valle, Juan W.

AU - McDonald, Alexander C.

AU - Carter, Ross

AU - Tebbutt, Niall C.

AU - Goldstein, David

AU - Shannon, Jennifer

AU - Dervenis, Christos

AU - Glimelius, Bengt

AU - Deakin, Mark

AU - Charnley, Richard M.

AU - Lacaine, François

AU - Scarfe, Andrew G.

AU - Middleton, Mark R.

AU - Anthoney, Alan

AU - Halloran, Christopher M.

AU - Mayerle, Julia

AU - Oláh, Attila

AU - Jackson, Richard

AU - Rawcliffe, Charlotte L.

AU - Scarpa, Aldo

AU - Bassi, Claudio

AU - Büchler, Markus W.

PY - 2014

Y1 - 2014

N2 - BackgroundHuman equilibrative nucleoside transporter 1 (hENT1) levels in pancreatic adenocarcinoma may predict survival in patients who receive adjuvant gemcitabine after resection.MethodsMicroarrays 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.ResultsThree 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 (χ2 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 (χ21= 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 (χ21 = 0.83; P =. 36). hENT1 levels were not predictive of survival for the 28 patients of the observation group (χ21 = 0.37; P =. 54). Multivariable analysis confirmed hENT1 expression as a predictive marker in gemcitabine-treated (Wald χ2 = 9.16; P =. 003) but not 5-fluorouracil-treated (Wald χ2 = 1.22; P =. 27) patients.ConclusionsSubject to prospective validation, gemcitabine should not be used for patients with low tumor hENT1 expression. © 2013 The Author.

AB - BackgroundHuman equilibrative nucleoside transporter 1 (hENT1) levels in pancreatic adenocarcinoma may predict survival in patients who receive adjuvant gemcitabine after resection.MethodsMicroarrays 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.ResultsThree 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 (χ2 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 (χ21= 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 (χ21 = 0.83; P =. 36). hENT1 levels were not predictive of survival for the 28 patients of the observation group (χ21 = 0.37; P =. 54). Multivariable analysis confirmed hENT1 expression as a predictive marker in gemcitabine-treated (Wald χ2 = 9.16; P =. 003) but not 5-fluorouracil-treated (Wald χ2 = 1.22; P =. 27) patients.ConclusionsSubject to prospective validation, gemcitabine should not be used for patients with low tumor hENT1 expression. © 2013 The Author.

U2 - 10.1093/jnci/djt347

DO - 10.1093/jnci/djt347

M3 - Article

SN - 0027-8874

VL - 106

JO - Journal of the National Cancer Institute

JF - Journal of the National Cancer Institute

IS - 1

M1 - djt347

ER -

Pancreatic cancer hENT1 expression and survival from gemcitabine in patients from the ESPAC-3 trial

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