{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,21]],"date-time":"2026-06-21T08:25:46Z","timestamp":1782030346068,"version":"3.54.5"},"reference-count":47,"publisher":"BMJ","issue":"3","license":[{"start":{"date-parts":[[2024,3,8]],"date-time":"2024-03-08T00:00:00Z","timestamp":1709856000000},"content-version":"unspecified","delay-in-days":7,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100023262","name":"Jon Moulton Charity Trust","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/501100023262","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Yorkshire Cancer Research","award":["L375PA"],"award-info":[{"award-number":["L375PA"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2024,2,15]]},"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Glioblastoma (GBM) is the most common adult primary malignant brain tumour. The condition is incurable and, despite aggressive treatment at first presentation, almost all tumours recur after a median of 7 months. The aim of treatment at recurrence is to prolong survival and maintain health-related quality of life (HRQoL). Chemotherapy is typically employed for recurrent GBM, often using nitrosourea-based regimens. However, efficacy is limited, with reported median survivals between 5 and 9 months from recurrence. Although less commonly used in the UK, there is growing evidence that re-irradiation may produce survival outcomes at least similar to nitrosourea-based chemotherapy. However, there remains uncertainty as to the optimum approach and there is a paucity of available data, especially with regards to HRQoL. Brain Re-Irradiation Or Chemotherapy (BRIOChe) aims to assess re-irradiation, as an acceptable treatment option for recurrent IDH-wild-type GBM.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>BRIOChe is a phase II, multi-centre, open-label, randomised trial in patients with recurrent GBM. The trial uses Sargent\u2019s three-outcome design and will recruit approximately 55 participants from 10 to 15 UK radiotherapy sites, allocated (2:1) to receive re-irradiation (35\u2009Gy in 10 daily fractions) or nitrosourea-based chemotherapy (up to six, 6-weekly cycles). The primary endpoint is overall survival rate for re-irradiation patients at 9 months. There will be no formal statistical comparison between treatment arms for the decision-making primary analysis. The chemotherapy arm will be used for calibration purposes, to collect concurrent data to aid interpretation of results. Secondary outcomes include HRQoL, dexamethasone requirement, anti-epileptic drug requirement, radiological response, treatment compliance, acute and late toxicities, progression-free survival.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>BRIOChe obtained ethical approval from Office for Research Ethics Committees Northern Ireland (reference no. 20\/NI\/0070). Final trial results will be published in peer-reviewed journals and adhere to the ICMJE guidelines.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"isrctn\" xlink:href=\"ISRCTN60524\">ISRCTN60524<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2023-078926","type":"journal-article","created":{"date-parts":[[2024,3,8]],"date-time":"2024-03-08T21:57:23Z","timestamp":1709935043000},"page":"e078926","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":8,"title":["Brain Re-Irradiation Or Chemotherapy: a phase II randomised trial of re-irradiation and chemotherapy in patients with recurrent glioblastoma (BRIOChe) \u2013 protocol for a multi-centre open-label randomised trial"],"prefix":"10.1136","volume":"14","clinical-trial-number":[{"clinical-trial-number":"isrctn60524","registry":"10.18810\/isrctn"},{"clinical-trial-number":"nct01730950","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8758-7163","authenticated-orcid":false,"given":"Eleanor M","family":"Hudson","sequence":"first","affiliation":[{"name":"Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha","family":"Noutch","sequence":"additional","affiliation":[{"name":"Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne","family":"Webster","sequence":"additional","affiliation":[{"name":"Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7975-7537","authenticated-orcid":false,"given":"Sarah R","family":"Brown","sequence":"additional","affiliation":[{"name":"Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florien W","family":"Boele","sequence":"additional","affiliation":[{"name":"Leeds Institute of Medical Research at St James\u2019s, University of Leeds, Leeds, UK"},{"name":"Leeds Institute of Health Sciences, University of Leeds, Leeds, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar","family":"Al-Salihi","sequence":"additional","affiliation":[{"name":"Guy\u2019s and St Thomas\u2019 Hospitals NHS Trust, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Baines","sequence":"additional","affiliation":[{"name":"National Radiotherapy Trials QA (RTTQA) Group, Mount Vernon Cancer Centre, Northwood, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Bulbeck","sequence":"additional","affiliation":[{"name":"Brainstrust, Cowes, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart","family":"Currie","sequence":"additional","affiliation":[{"name":"Department of Radiology, Leeds General Infirmary, Leeds, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon","family":"Fernandez","sequence":"additional","affiliation":[{"name":"Leeds Institute of Medical Research at St James\u2019s, University of Leeds, Leeds, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane","family":"Hughes","sequence":"additional","affiliation":[{"name":"Leeds Institute of Medical Research at St James\u2019s, University of Leeds, Leeds, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Lilley","sequence":"additional","affiliation":[{"name":"Department of Medical Physics, Leeds Cancer Centre, Leeds, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Smith","sequence":"additional","affiliation":[{"name":"Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Parbutt","sequence":"additional","affiliation":[{"name":"Pharmacy, Leeds Teaching Hospitals NHS Trust, Leeds, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Finbar","family":"Slevin","sequence":"additional","affiliation":[{"name":"Leeds Institute of Medical Research at St James\u2019s, University of Leeds, Leeds, UK"},{"name":"Department of Clinical Oncology, Leeds Cancer Centre, Leeds, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Short","sequence":"additional","affiliation":[{"name":"Leeds Institute of Medical Research at St James\u2019s, University of Leeds, Leeds, UK"},{"name":"Department of Clinical Oncology, Leeds Cancer Centre, Leeds, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Sebag-Montefiore","sequence":"additional","affiliation":[{"name":"Leeds Institute of Medical Research at St James\u2019s, University of Leeds, Leeds, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise","family":"Murray","sequence":"additional","affiliation":[{"name":"Leeds Institute of Medical Research at St James\u2019s, University of Leeds, Leeds, UK"},{"name":"Department of Clinical Oncology, Leeds Cancer Centre, Leeds, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2024,3,8]]},"reference":[{"key":"2025121601011214000_14.3.e078926.1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa043330"},{"key":"2025121601011214000_14.3.e078926.2","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1007\/s11764-017-0602-7","article-title":"Life beyond a diagnosis of glioblastoma: a systematic review of the literature","volume":"11","author":"Gately","year":"2017","journal-title":"J Cancer Surviv"},{"key":"2025121601011214000_14.3.e078926.3","doi-asserted-by":"crossref","first-page":"71","DOI":"10.12703\/P6-71","article-title":"Palliative care and quality of life in neuro-oncology","volume":"6","author":"Mummudi","year":"2014","journal-title":"F1000Prime Rep"},{"key":"2025121601011214000_14.3.e078926.4","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/nou060"},{"key":"2025121601011214000_14.3.e078926.5","doi-asserted-by":"publisher","DOI":"10.1097\/00002060-200105000-00005"},{"key":"2025121601011214000_14.3.e078926.6","doi-asserted-by":"crossref","first-page":"37","DOI":"10.2217\/cns.13.65","article-title":"Symptom management and quality of life in glioma patients","volume":"3","author":"Boele","year":"2014","journal-title":"CNS Oncol"},{"key":"2025121601011214000_14.3.e078926.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejon.2012.04.006"},{"key":"2025121601011214000_14.3.e078926.8","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/nos273"},{"key":"2025121601011214000_14.3.e078926.9","doi-asserted-by":"publisher","DOI":"10.1007\/s11060-017-2564-z"},{"key":"2025121601011214000_14.3.e078926.10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.15406\/jcpcr.2016.06.00204","article-title":"Re-evaluating the efficacy and toxicity of procarbazine, lomustine and vincrsitine (PCV) in relapsed glioblastoma in the concurrent\/ adjuvant temozolamide era","volume":"6","author":"P","year":"2016","journal-title":"JCPCR"},{"key":"2025121601011214000_14.3.e078926.11","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(14)70314-6"},{"key":"2025121601011214000_14.3.e078926.12","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1159\/000431236","article-title":"Second-line chemotherapy in recurrent glioblastoma: a 2-cohort study","volume":"38","author":"Carvalho","year":"2015","journal-title":"Oncol Res Treat"},{"key":"2025121601011214000_14.3.e078926.13","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.27.1932"},{"key":"2025121601011214000_14.3.e078926.14","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1707358"},{"key":"2025121601011214000_14.3.e078926.15","doi-asserted-by":"publisher","DOI":"10.1016\/0959-8049(94)00248-4"},{"key":"2025121601011214000_14.3.e078926.16","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.23.2595"},{"key":"2025121601011214000_14.3.e078926.17","unstructured":"Lombardi G . Updated results of REGOMA: A randomized, multicenter, controlled open-label phase II clinical trial evaluating Regorafenib in Relapsed glioblastoma (GBM) patients (PTS). in Oral Presentation at EANO (Eurpoean Association of Neuro-Oncolgy) Annual conference; 2018"},{"key":"2025121601011214000_14.3.e078926.18","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2015.03.025"},{"key":"2025121601011214000_14.3.e078926.19","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1007\/s11060-016-2310-y","article-title":"Role of surgical resection in recurrent glioblastoma: prognostic factors and outcome evaluation in an observational study","volume":"131","author":"Pessina","year":"2017","journal-title":"J Neurooncol"},{"key":"2025121601011214000_14.3.e078926.20","first-page":"1743","article-title":"The effect of re-operation on survival in patients with recurrent glioblastoma","volume":"35","author":"Franceschi","year":"2015","journal-title":"Anticancer Res"},{"key":"2025121601011214000_14.3.e078926.21","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2012.02.004"},{"key":"2025121601011214000_14.3.e078926.22","doi-asserted-by":"publisher","DOI":"10.1007\/s11060-018-03064-0"},{"key":"2025121601011214000_14.3.e078926.23","first-page":"144","article-title":"Re-irradiation for recurrent high-grade gliomas: a systematic review and analysis of treatment technique with respect to survival and risk of radionecrosis","volume":"6","author":"Shanker","year":"2019","journal-title":"Neurooncol Pract"},{"key":"2025121601011214000_14.3.e078926.24","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1097\/COC.0b013e31815e3fdc","article-title":"Improvement, clinical course, and quality of life after palliative radiotherapy for recurrent glioblastoma","volume":"31","author":"Nieder","year":"2008","journal-title":"Am J Clin Oncol"},{"key":"2025121601011214000_14.3.e078926.25","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.22.00164"},{"key":"2025121601011214000_14.3.e078926.26","doi-asserted-by":"crossref","DOI":"10.1093\/neuonc\/nov283.01","article-title":"UK top 10 clinical research priorities in neuro-oncology","volume":"17","author":"Grant","year":"2015","journal-title":"Neuro Oncol"},{"key":"2025121601011214000_14.3.e078926.27","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1016\/j.clon.2018.05.004","article-title":"A retrospective review of re-irradiating patients' recurrent high-grade gliomas","volume":"30","author":"Klobukowski","year":"2018","journal-title":"Clin Oncol (R Coll Radiol)"},{"key":"2025121601011214000_14.3.e078926.28","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.25.6941"},{"key":"2025121601011214000_14.3.e078926.29","doi-asserted-by":"publisher","DOI":"10.1016\/S0360-3016(98)00416-7"},{"key":"2025121601011214000_14.3.e078926.30","doi-asserted-by":"crossref","DOI":"10.1093\/neuonc\/noz175.075","article-title":"ACTR-32. NRG ONCOLOGY RTOG 1205: randomized phase II trial of concurrent Bevacizumab and re-irradiation vs. bevacizumab alone as treatment for recurrent glioblastoma","volume":"21","author":"Tsien","year":"2019","journal-title":"Neuro-Oncology"},{"key":"2025121601011214000_14.3.e078926.31","unstructured":"RTOG 1205 . Randomized phase II trial of concurrent Bevacizumab and re-irradiation versus bevacizumab alone as treatment of recurrent glioblastoma. 2016. Available: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT01730950"},{"key":"2025121601011214000_14.3.e078926.32","unstructured":"AstraZeneca . Azd1390 radiation procedure manual. version 1.0; 2017."},{"key":"2025121601011214000_14.3.e078926.33","doi-asserted-by":"publisher","DOI":"10.1016\/S0197-2456(00)00115-X"},{"key":"2025121601011214000_14.3.e078926.34","doi-asserted-by":"crossref","DOI":"10.1136\/bmj.c2697","article-title":"Modified intention to treat reporting in randomised controlled trials: systematic review","volume":"340","author":"Abraha","year":"2010","journal-title":"BMJ"},{"key":"2025121601011214000_14.3.e078926.35","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2012.47.2464"},{"key":"2025121601011214000_14.3.e078926.36","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1007\/BF00172666","article-title":"Efficacy of \u20188-drugs-in-one-day\u2019combination in treatment of recurrent GBM patients","volume":"12","author":"Boiardi","year":"1992","journal-title":"J Neurooncol"},{"key":"2025121601011214000_14.3.e078926.37","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1177\/160940690600500107","article-title":"Demonstrating rigor using thematic analysis: a hybrid approach of Inductive and deductive coding and theme development","volume":"5","author":"Fereday","year":"2006","journal-title":"Int J Qual Methods"},{"key":"2025121601011214000_14.3.e078926.38","unstructured":"Patton M . Pattern, theme, and content analysis, in Qualitative research & evaluation methods. London: Sage Publications Ltd, 2002: 452\u201371."},{"key":"2025121601011214000_14.3.e078926.39","doi-asserted-by":"publisher","DOI":"10.1016\/j.prro.2016.03.007"},{"key":"2025121601011214000_14.3.e078926.40","doi-asserted-by":"crossref","first-page":"iii93","DOI":"10.1093\/annonc\/mdu050","article-title":"High-grade glioma: ESMO clinical practice guidelines for diagnosis, treatment and follow-up","volume":"25 Suppl 3","author":"Stupp","year":"2014","journal-title":"Ann Oncol"},{"key":"2025121601011214000_14.3.e078926.41","unstructured":"NICE, N.I.f.H.a.C.E . Brain tumours (primary) and brain metastases in adults. NICE guideline [Ng99]; 2018."},{"key":"2025121601011214000_14.3.e078926.42","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2009.04.095"},{"key":"2025121601011214000_14.3.e078926.43","doi-asserted-by":"publisher","DOI":"10.1016\/S0360-3016(01)01599-1"},{"key":"2025121601011214000_14.3.e078926.44","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/0360-3016(89)90385-4","article-title":"Repeat megavoltage irradiation of pituitary and suprasellar tumors","volume":"17","author":"Flickinger","year":"1989","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"2025121601011214000_14.3.e078926.45","article-title":"Randomized phase II trial of re-irradiation and concurrent bevacizumab versus bevacizumab alone as treatment for recurrent glioblastoma (NRG oncology\/RTOG 1205): initial outcomes and RT plan quality report","volume":"105","author":"Tsien","year":"2019","journal-title":"IJROBP"},{"key":"2025121601011214000_14.3.e078926.46","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.radonc.2018.10.034","article-title":"Patterns of re-irradiation for recurrent gliomas and validation of a prognostic score","volume":"130","author":"Post","year":"2019","journal-title":"Radiother Oncol"},{"key":"2025121601011214000_14.3.e078926.47","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000133398.11870.9A"}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2023-078926","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T09:01:29Z","timestamp":1765875689000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2023-078926"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3]]},"references-count":47,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2024,3,8]]},"published-print":{"date-parts":[[2024,3]]}},"alternative-id":["10.1136\/bmjopen-2023-078926"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2023-078926","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"value":"2044-6055","type":"print"},{"value":"2044-6055","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3]]}}}