{"id":7987,"date":"2024-04-19T09:00:47","date_gmt":"2024-04-19T08:00:47","guid":{"rendered":"https:\/\/www.library.sath.nhs.uk\/research\/?p=7987"},"modified":"2025-07-29T09:54:27","modified_gmt":"2025-07-29T08:54:27","slug":"a-hypoxia-biomarker-does-not-predict-benefit-from-giving-chemotherapy-with-radiotherapy-in-the-bc2001-randomised-controlled-trial-2024","status":"publish","type":"post","link":"https:\/\/www.library.sath.nhs.uk\/research\/2024\/04\/19\/a-hypoxia-biomarker-does-not-predict-benefit-from-giving-chemotherapy-with-radiotherapy-in-the-bc2001-randomised-controlled-trial-2024\/","title":{"rendered":"A hypoxia biomarker does not predict benefit from giving chemotherapy with radiotherapy in the BC2001 randomised controlled trial (2024)"},"content":{"rendered":"<p><strong>Type of publication:<\/strong><br \/>\nRandomised controlled trial<\/p>\n<p><strong>Author(s):<\/strong><br \/>\nSmith, Tim A D; West, Catharine M L; Joseph, Nuradh; Lane, Brian; Irlam-Jones, Joely; More, Elisabet; Mistry, Hitesh; Reeves, Kimberley J; Song, Yee Pei; Reardon, Mark; Hoskin, Peter J; Hussain, Syed A; *Denley, Helen; Hall, Emma; Porta, Nuria; Huddart, Robert A; James, Nick D; Choudhury, Ananya.<\/p>\n<p><strong>Citation:<\/strong><br \/>\nEBioMedicine. 101:105032, 2024 Feb 21.<\/p>\n<p><strong>Abstract:<\/strong><br \/>\nBACKGROUND: 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.<\/p>\n<p><a title=\"Original URL: https:\/\/libkey.io\/libraries\/1791\/articles\/606814305\/full-text-file. Click or tap if you trust this link.\" href=\"https:\/\/libkey.io\/libraries\/1791\/articles\/606814305\/full-text-file\" target=\"_blank\" rel=\"noopener noreferrer\" data-auth=\"Verified\" data-linkindex=\"0\">Link to full-text<\/a> [open access - no password required]<\/p>\n<p><strong>Altmetrics:<\/strong><\/p>\n<div class=\"altmetric-embed\" data-badge-details=\"right\" data-badge-type=\"medium-donut\" data-pmid=\"38387404\" data-hide-no-mentions=\"true\"><\/div>\n<p><script type='text\/javascript' src='https:\/\/d1bxh8uas1mnw7.cloudfront.net\/assets\/embed.js'><\/script><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Type of publication: Randomised controlled trial Author(s): Smith, Tim A D; West, Catharine M L; Joseph, Nuradh; Lane, Brian; Irlam-Jones, Joely; More, Elisabet; Mistry, Hitesh; Reeves, Kimberley J; Song, Yee Pei; Reardon, Mark; Hoskin, Peter J; Hussain, Syed A; *Denley,<span class=\"ellipsis\">&hellip;<\/span><\/p>\n<div class=\"read-more\"><a href=\"https:\/\/www.library.sath.nhs.uk\/research\/2024\/04\/19\/a-hypoxia-biomarker-does-not-predict-benefit-from-giving-chemotherapy-with-radiotherapy-in-the-bc2001-randomised-controlled-trial-2024\/\">Read more <span class=\"screen-reader-text\">A hypoxia biomarker does not predict benefit from giving chemotherapy with radiotherapy in the BC2001 randomised controlled trial (2024)<\/span><span class=\"meta-nav\"> &#8250;<\/span><\/a><\/div>\n<p><!-- end of .read-more --><\/p>\n","protected":false},"author":12,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"content-type":"","footnotes":""},"categories":[1001,200],"tags":[1050,256,1002,353,602],"class_list":["post-7987","post","type-post","status-publish","format-standard","hentry","category-open-access","category-staff-publication","tag-1050","tag-chemotherapy","tag-gold-open-access","tag-oncology","tag-radiotherapy"],"_links":{"self":[{"href":"https:\/\/www.library.sath.nhs.uk\/research\/wp-json\/wp\/v2\/posts\/7987","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.library.sath.nhs.uk\/research\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.library.sath.nhs.uk\/research\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.library.sath.nhs.uk\/research\/wp-json\/wp\/v2\/users\/12"}],"replies":[{"embeddable":true,"href":"https:\/\/www.library.sath.nhs.uk\/research\/wp-json\/wp\/v2\/comments?post=7987"}],"version-history":[{"count":3,"href":"https:\/\/www.library.sath.nhs.uk\/research\/wp-json\/wp\/v2\/posts\/7987\/revisions"}],"predecessor-version":[{"id":8824,"href":"https:\/\/www.library.sath.nhs.uk\/research\/wp-json\/wp\/v2\/posts\/7987\/revisions\/8824"}],"wp:attachment":[{"href":"https:\/\/www.library.sath.nhs.uk\/research\/wp-json\/wp\/v2\/media?parent=7987"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.library.sath.nhs.uk\/research\/wp-json\/wp\/v2\/categories?post=7987"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.library.sath.nhs.uk\/research\/wp-json\/wp\/v2\/tags?post=7987"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}