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A hypoxia biomarker does not predict benefit from giving chemotherapy with radiotherapy in the BC2001 randomised controlled trial. / Smith, Tim; West, Catharine; Joseph, Nuradh et al.
Yn: eBioMedicine, Cyfrol 101, 105032, 01.03.2024, t. 105032.

Allbwn ymchwil: Cyfraniad at gyfnodolynErthygladolygiad gan gymheiriaid

HarvardHarvard

Smith, T, West, C, Joseph, N, Lane, B, Irlam-Jones, J, More, E, Mistry, H, Reeves, K, Song, YP, Reardon, M, Hoskin, P, Hussain, S, Denley, H, Hall, E, Porta, N, Huddart, R, James, N & Choudhury, A 2024, 'A hypoxia biomarker does not predict benefit from giving chemotherapy with radiotherapy in the BC2001 randomised controlled trial', eBioMedicine, cyfrol. 101, 105032, tt. 105032. https://doi.org/10.1016/j.ebiom.2024.105032

APA

Smith, T., West, C., Joseph, N., Lane, B., Irlam-Jones, J., More, E., Mistry, H., Reeves, K., Song, Y. P., Reardon, M., Hoskin, P., Hussain, S., Denley, H., Hall, E., Porta, N., Huddart, R., James, N., & Choudhury, A. (2024). A hypoxia biomarker does not predict benefit from giving chemotherapy with radiotherapy in the BC2001 randomised controlled trial. eBioMedicine, 101, 105032. Erthygl 105032. https://doi.org/10.1016/j.ebiom.2024.105032

CBE

Smith T, West C, Joseph N, Lane B, Irlam-Jones J, More E, Mistry H, Reeves K, Song YP, Reardon M, et al. 2024. A hypoxia biomarker does not predict benefit from giving chemotherapy with radiotherapy in the BC2001 randomised controlled trial. eBioMedicine. 101:105032. https://doi.org/10.1016/j.ebiom.2024.105032

MLA

VancouverVancouver

Smith T, West C, Joseph N, Lane B, Irlam-Jones J, More E et al. A hypoxia biomarker does not predict benefit from giving chemotherapy with radiotherapy in the BC2001 randomised controlled trial. eBioMedicine. 2024 Maw 1;101:105032. 105032. Epub 2024 Chw 21. doi: 10.1016/j.ebiom.2024.105032

Author

Smith, Tim ; West, Catharine ; Joseph, Nuradh et al. / A hypoxia biomarker does not predict benefit from giving chemotherapy with radiotherapy in the BC2001 randomised controlled trial. Yn: eBioMedicine. 2024 ; Cyfrol 101. tt. 105032.

RIS

TY - JOUR

T1 - A hypoxia biomarker does not predict benefit from giving chemotherapy with radiotherapy in the BC2001 randomised controlled trial

AU - Smith, Tim

AU - West, Catharine

AU - Joseph, Nuradh

AU - Lane, Brian

AU - Irlam-Jones, Joely

AU - More, Elisabet

AU - Mistry, Hitesh

AU - Reeves, Kimberley

AU - Song, Yee Pei

AU - Reardon, Mark

AU - Hoskin, Peter

AU - Hussain, Syed

AU - Denley, Helen

AU - Hall, Emma

AU - Porta, Nuria

AU - Huddart, Robert

AU - James, Nicholas

AU - Choudhury, Ananya

N1 - Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.

PY - 2024/3/1

Y1 - 2024/3/1

N2 - BC2001 showed combining chemotherapy (5-FU + mitomycin-C) with radiotherapy improves loco-regional disease-free survival in patients with muscle-invasive bladder cancer (MIBC). We previously showed a 24-gene hypoxia-associated signature predicted benefit from hypoxia-modifying radiosensitisation in BCON and hypothesised that only patients with low hypoxia scores (HSs) would benefit from chemotherapy in BC2001. BC2001 allowed conventional (64Gy/32 fractions) or hypofractionated (55Gy/20 fractions) radiotherapy. An exploratory analysis tested an additional hypothesis that hypofractionation reduces reoxygenation and would be detrimental for patients with hypoxic tumours. RNA was extracted from pre-treatment biopsies (298 BC2001 patients), transcriptomic data generated (Affymetrix Clariom-S arrays), HSs calculated (median expression of 24-signature genes) and patients stratified as hypoxia-high or -low (cut-off: cohort median). invasive loco-regional control (ILRC); secondary overall survival. Hypoxia affected overall survival (HR = 1.30; 95% CI 0.99-1.70; p = 0.062): more uncertainty for ILRC (HR = 1.29; 95% CI 0.82-2.03; p = 0.264). Benefit from chemotherapy was similar for patients with high or low HSs, with no interaction between HS and treatment arm. High HS associated with poor ILRC following hypofractionated (n = 90, HR 1.69; 95% CI 0.99-2.89 p = 0.057) but not conventional (n = 207, HR 0.70; 95% CI 0.28-1.80, p = 0.461) radiotherapy. The finding was confirmed in an independent cohort (BCON) where hypoxia associated with a poor prognosis for patients receiving hypofractionated (n = 51; HR 14.2; 95% CI 1.7-119; p = 0.015) but not conventional (n = 24, HR 1.04; 95% CI 0.07-15.5, p = 0.978) radiotherapy. Tumour hypoxia status does not affect benefit from BC2001 chemotherapy. Hypoxia appears to affect fractionation sensitivity. Use of HSs to personalise treatment needs testing in a biomarker-stratified trial. Cancer Research UK, NIHR, MRC. [Abstract copyright: Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.]

AB - BC2001 showed combining chemotherapy (5-FU + mitomycin-C) with radiotherapy improves loco-regional disease-free survival in patients with muscle-invasive bladder cancer (MIBC). We previously showed a 24-gene hypoxia-associated signature predicted benefit from hypoxia-modifying radiosensitisation in BCON and hypothesised that only patients with low hypoxia scores (HSs) would benefit from chemotherapy in BC2001. BC2001 allowed conventional (64Gy/32 fractions) or hypofractionated (55Gy/20 fractions) radiotherapy. An exploratory analysis tested an additional hypothesis that hypofractionation reduces reoxygenation and would be detrimental for patients with hypoxic tumours. RNA was extracted from pre-treatment biopsies (298 BC2001 patients), transcriptomic data generated (Affymetrix Clariom-S arrays), HSs calculated (median expression of 24-signature genes) and patients stratified as hypoxia-high or -low (cut-off: cohort median). invasive loco-regional control (ILRC); secondary overall survival. Hypoxia affected overall survival (HR = 1.30; 95% CI 0.99-1.70; p = 0.062): more uncertainty for ILRC (HR = 1.29; 95% CI 0.82-2.03; p = 0.264). Benefit from chemotherapy was similar for patients with high or low HSs, with no interaction between HS and treatment arm. High HS associated with poor ILRC following hypofractionated (n = 90, HR 1.69; 95% CI 0.99-2.89 p = 0.057) but not conventional (n = 207, HR 0.70; 95% CI 0.28-1.80, p = 0.461) radiotherapy. The finding was confirmed in an independent cohort (BCON) where hypoxia associated with a poor prognosis for patients receiving hypofractionated (n = 51; HR 14.2; 95% CI 1.7-119; p = 0.015) but not conventional (n = 24, HR 1.04; 95% CI 0.07-15.5, p = 0.978) radiotherapy. Tumour hypoxia status does not affect benefit from BC2001 chemotherapy. Hypoxia appears to affect fractionation sensitivity. Use of HSs to personalise treatment needs testing in a biomarker-stratified trial. Cancer Research UK, NIHR, MRC. [Abstract copyright: Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.]

KW - Biomarkers

KW - Disease-Free Survival

KW - Dose Fractionation, Radiation

KW - Humans

KW - Hypoxia

KW - Mitomycin

KW - Treatment Outcome

U2 - 10.1016/j.ebiom.2024.105032

DO - 10.1016/j.ebiom.2024.105032

M3 - Article

C2 - 38387404

VL - 101

SP - 105032

JO - eBioMedicine

JF - eBioMedicine

M1 - 105032

ER -