dc.contributor.author | Smith, TAD | |
dc.contributor.author | West, CML | |
dc.contributor.author | Joseph, N | |
dc.contributor.author | Lane, B | |
dc.contributor.author | Irlam-Jones, J | |
dc.contributor.author | More, E | |
dc.contributor.author | Mistry, H | |
dc.contributor.author | Reeves, KJ | |
dc.contributor.author | Song, YP | |
dc.contributor.author | Reardon, M | |
dc.contributor.author | Hoskin, PJ | |
dc.contributor.author | Hussain, SA | |
dc.contributor.author | Denley, H | |
dc.contributor.author | Hall, E | |
dc.contributor.author | Porta, N | |
dc.contributor.author | Huddart, RA | |
dc.contributor.author | James, ND | |
dc.contributor.author | Choudhury, A | |
dc.coverage.spatial | Netherlands | |
dc.date.accessioned | 2024-03-07T11:35:37Z | |
dc.date.available | 2024-03-07T11:35:37Z | |
dc.date.issued | 2024-02-21 | |
dc.identifier | 105032 | |
dc.identifier | S2352-3964(24)00067-7 | |
dc.identifier.citation | EBioMedicine, 2024, 101 pp. 105032 - | |
dc.identifier.issn | 2352-3964 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/6176 | |
dc.identifier.eissn | 2352-3964 | |
dc.identifier.eissn | 2352-3964 | |
dc.identifier.doi | 10.1016/j.ebiom.2024.105032 | |
dc.identifier.doi | 10.1016/j.ebiom.2024.105032 | |
dc.description.abstract | BACKGROUND: 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. METHODS: 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). PRIMARY ENDPOINT: invasive loco-regional control (ILRC); secondary overall survival. FINDINGS: 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. INTERPRETATION: 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. FUNDING: Cancer Research UK, NIHR, MRC. | |
dc.format | Print-Electronic | |
dc.format.extent | 105032 - | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | ELSEVIER | |
dc.relation.ispartof | EBioMedicine | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.subject | 5FU/mitomycin C | |
dc.subject | Bladder cancer | |
dc.subject | Gene signature | |
dc.subject | Hypofractionation | |
dc.subject | Hypoxia | |
dc.subject | Radiotherapy | |
dc.title | A hypoxia biomarker does not predict benefit from giving chemotherapy with radiotherapy in the BC2001 randomised controlled trial. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2024-02-08 | |
dc.date.updated | 2024-03-04T13:40:48Z | |
rioxxterms.version | AM | |
rioxxterms.versionofrecord | 10.1016/j.ebiom.2024.105032 | |
rioxxterms.licenseref.startdate | 2024-02-21 | |
rioxxterms.type | Journal Article/Review | |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/38387404 | |
pubs.organisational-group | ICR | |
pubs.organisational-group | ICR/Primary Group | |
pubs.organisational-group | ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | ICR/Primary Group/ICR Divisions/Clinical Studies | |
pubs.organisational-group | ICR/Primary Group/ICR Divisions/Clinical Studies/Clinical Trials & Statistics Unit | |
pubs.publication-status | Published online | |
pubs.publisher-url | http://dx.doi.org/10.1016/j.ebiom.2024.105032 | |
pubs.volume | 101 | |
icr.researchteam | Clin Trials & Stats Unit | |
dc.contributor.icrauthor | Hall, Emma | |
dc.contributor.icrauthor | Porta, Nuria | |
dc.contributor.icrauthor | Huddart, Robert | |
icr.provenance | Deposited by Ms Jessica Perry (impersonating Prof Emma Hall) on 2024-03-04. Deposit type is initial. No. of files: 1. Files: eBiomedicine Smith et al2024 final.pdf | |