{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T02:39:17Z","timestamp":1790822357193,"version":"4.1.0"},"reference-count":39,"publisher":"BMJ","issue":"5","license":[{"start":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T00:00:00Z","timestamp":1778112000000},"content-version":"unspecified","delay-in-days":6,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2026,4,10]]},"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Stereotactic body radiotherapy (SBRT) delivered on an MRI-guided linear accelerator (MR-linac) enables highly conformal prostate cancer irradiation. The DESTINATION 2 trial is a federated, randomised phase II\/R-IDEAL 2b study evaluating whether de-escalating the dose to prostate tissue, while maintaining a high dose to MRI-visible tumour(s) in two fractions, reduces genitourinary (GU) treatment-related adverse events (AE) without compromising disease control in men with localised prostate cancer.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>200 men worldwide with localised, MRI-visible prostate cancer will be randomised 1:1 to receive either (1) prescribed uniform dose MR-linac SBRT (27\u2009Gy in two fractions to the whole prostate and seminal vesicles with 0\u2009mm CTV-PTV margin) or (2) de-escalated SBRT (20\u2009Gy in two fractions to whole prostate with 0\u2009mm CTV-PTV margin and 27\u2009Gy in two fractions to MRI-visible tumour(s) with a 4\u2009mm intraprostatic margin applied to the GTV. All treatments are delivered using MRI-guided adaptive Radiotherapy (MRIgRT). The primary endpoint is the absolute and relative risk reduction in acute grade 2+GU\u2009AE (CTCAE v5) within 12\u2009weeks of completing radiotherapy. Secondary endpoints include late GU AE, acute and late gastrointestinal (GI) AE, sexual AE, patient-reported outcomes, dosimetry, technical feasibility and 2-year biochemical relapse-free survival.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>This is a federated trial design in which each centre operates independently with its own sponsor, ethics committee approval and regulatory oversight. Each centre is responsible for obtaining and maintaining local ethics approval in accordance with their national and institutional requirements. The UK centre (The Royal Marsden NHS Foundation Trust) has received ethical approval from the East of England\u2013Cambridge South Research Ethics Committee (REC reference: 24\/EE\/0163; IRAS: 338368). Results will be disseminated via peer-reviewed publications and conference presentations.<\/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=\"clintrialgov\" xlink:href=\"NCT06638541\">NCT06638541<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2025-111791","type":"journal-article","created":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T15:05:42Z","timestamp":1778166342000},"page":"e111791","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Dose dE-eScalaTion IN prostATe radIOtherapy usiNg an MR-Linac in 2 Fractions (DESTINATION 2): protocol for a randomised, phase II\/R-IDEAL2b trial"],"prefix":"10.1136","volume":"16","clinical-trial-number":[{"clinical-trial-number":"nct06638541","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct04075305","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-1016-9841","authenticated-orcid":false,"given":"Sian","family":"Cooper","sequence":"first","affiliation":[{"name":"The Royal Marsden NHS Foundation Trust, London, UK"},{"name":"The Institute of Cancer Research, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Alexander","sequence":"additional","affiliation":[{"name":"The Royal Marsden NHS Foundation Trust, London, UK"},{"name":"The Institute of Cancer Research, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dylan","family":"Breitkreutz","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, 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