{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,14]],"date-time":"2025-12-14T12:05:59Z","timestamp":1765713959970,"version":"3.48.0"},"reference-count":25,"publisher":"BMJ","issue":"9","license":[{"start":{"date-parts":[[2024,9,24]],"date-time":"2024-09-24T00:00:00Z","timestamp":1727136000000},"content-version":"unspecified","delay-in-days":23,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2024,9,6]]},"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Postoperative pancreatic fistula (POPF) occurs in 25% of patients undergoing a high-risk pancreatoduodenectomy (PD) and is a driving cause of major morbidity, mortality, prolonged hospital stay and increased costs after PD. There is a need for perioperative methods to decrease these risks. In recent studies, preoperative chemoradiotherapy in patients with pancreatic ductal adenocarcinoma (PDAC) reduced the rate of POPF seemingly due to radiation-induced pancreatic fibrosis. However, patients with a high risk of POPF mostly have a non-pancreatic periampullary tumour and do not receive radiotherapy. Prospective studies using radiotherapy specifically to reduce the risk of POPF have not been performed. We aim to assess the safety, feasibility and preliminary efficacy of preoperative stereotactic radiotherapy on the future pancreatic neck transection margin to reduce the rate of POPF.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>In this multicentre, single-arm, phase II trial, we aim to assess the feasibility and safety of a single fraction of preoperative stereotactic radiotherapy (12\u2009Gy) to a 4\u2009cm area around the future pancreatic neck transection margin in patients at high risk of developing POPF after PD aimed to reduce the risk of grade B\/C POPF. Adult patients scheduled for PD for malignant and premalignant periampullary tumours, excluding PDAC, with a pancreatic duct diameter \u22643 mm will be included in centres participating in the Dutch Pancreatic Cancer Group. The primary outcome is the safety and feasibility of single-dose preoperative stereotactic radiotherapy before PD. The most relevant secondary outcomes are grade B\/C POPF and the difference in the extent of fibrosis between the radiated and non-radiated (uncinate margin) pancreas. Evaluation of endpoints will be performed after inclusion of 33 eligible patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>Ethical approval was obtained by the Amsterdam UMC\u2019s accredited Medical Research Ethics Committee (METC). All included patients are required to have provided written informed consent. The results of this trial will be used to determine the need for a randomised controlled phase III trial and submitted to a high-impact peer-reviewed medical journal regardless of the study outcome.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>\n                      NL72913 (Central Committee on Research involving Human Subjects Registry) and\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT05641233\">NCT05641233<\/jats:ext-link>\n                      (ClinicalTrials).\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2024-087193","type":"journal-article","created":{"date-parts":[[2024,9,24]],"date-time":"2024-09-24T13:51:19Z","timestamp":1727185879000},"page":"e087193","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":3,"title":["Feasibility, safety and preliminary efficacy of preoperative stereotactic radiotherapy on the future pancreatic neck transection margin to reduce the risk of pancreatic fistula after high-risk pancreatoduodenectomy (FIBROPANC): protocol for a multicentre, single-arm trial"],"prefix":"10.1136","volume":"14","clinical-trial-number":[{"clinical-trial-number":"nct05641233","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct05641233","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"J. Annelie","family":"Suurmeijer","sequence":"first","affiliation":[{"name":"Surgery, Amsterdam UMC, location University of Amsterdam, Amsterdam, the Netherlands"},{"name":"Cancer Center Amsterdam, Amsterdam, the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7009-7034","authenticated-orcid":false,"given":"Leonoor V.","family":"Wismans","sequence":"additional","affiliation":[{"name":"Surgery, Erasmus MC, University Medical Center, Rotterdam, the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tessa E.","family":"Hendriks","sequence":"additional","affiliation":[{"name":"Surgery, Amsterdam UMC, location University of Amsterdam, Amsterdam, the Netherlands"},{"name":"Cancer Center Amsterdam, Amsterdam, the Netherlands"},{"name":"Surgery, Leiden University Medical Center, Leiden, the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna M.","family":"Bruynzeel","sequence":"additional","affiliation":[{"name":"Cancer Center Amsterdam, Amsterdam, the Netherlands"},{"name":"Radiation Oncology, Amsterdam UMC, location VU University, Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joost J.","family":"Nuyttens","sequence":"additional","affiliation":[{"name":"Radiation Oncology, Erasmus MC, University Medical Center, Rotterdm, the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martijn P.W.","family":"Intven","sequence":"additional","affiliation":[{"name":"Radiation Oncology, University Medical Center Utrecht, Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lydi M.J.W.","family":"van Driel","sequence":"additional","affiliation":[{"name":"Gastroenterology and Hepatology, Erasmus Medical Center, Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bas","family":"Groot Koerkamp","sequence":"additional","affiliation":[{"name":"Surgery, Erasmus MC, University Medical Center, Rotterdam, the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olivier R.","family":"Busch","sequence":"additional","affiliation":[{"name":"Surgery, Amsterdam UMC, location University of Amsterdam, Amsterdam, the Netherlands"},{"name":"Cancer Center Amsterdam, Amsterdam, the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaap J.","family":"Stoker","sequence":"additional","affiliation":[{"name":"Radiology and Nuclear Medicine, Amsterdam UMC, location University of Amsterdam, Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joanne","family":"Verheij","sequence":"additional","affiliation":[{"name":"Cancer Center Amsterdam, Amsterdam, the Netherlands"},{"name":"Pathology, Amsterdam UMC, location University of Amsterdam, Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arantza","family":"Farina","sequence":"additional","affiliation":[{"name":"Pathology, Amsterdam UMC, location University of Amsterdam, Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michail","family":"Doukas","sequence":"additional","affiliation":[{"name":"Pathology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ignace H.J.","family":"de Hingh","sequence":"additional","affiliation":[{"name":"Surgery, Catharina Hospital, Catharina Cancer Institute, Eindhoven, the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daan J.","family":"Lips","sequence":"additional","affiliation":[{"name":"Surgery, Medisch Spectrum Twente, Enschede, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erwin","family":"van der Harst","sequence":"additional","affiliation":[{"name":"Surgery, Maasstad Hospital, Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Geertjan","family":"van Tienhoven","sequence":"additional","affiliation":[{"name":"Cancer Center Amsterdam, Amsterdam, the Netherlands"},{"name":"Radiation Oncology, Amsterdam UMC, location University of Amsterdam, Amsterdam, the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc G.","family":"Besselink","sequence":"additional","affiliation":[{"name":"Surgery, Amsterdam UMC, location University of Amsterdam, Amsterdam, the Netherlands"},{"name":"Cancer Center Amsterdam, Amsterdam, the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Casper H.J.","family":"van Eijck","sequence":"additional","affiliation":[{"name":"Surgery, Amsterdam UMC, location University of Amsterdam, Amsterdam, the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2024,9,24]]},"reference":[{"key":"2025121404003577000_14.9.e087193.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.surg.2016.11.014"},{"key":"2025121404003577000_14.9.e087193.2","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.pan.2017.12.008","article-title":"The cost of perioperative complications following pancreaticoduodenectomy: A systematic review","volume":"18","author":"Wang","year":"2018","journal-title":"Pancreatology"},{"key":"2025121404003577000_14.9.e087193.3","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1002\/bjs.11085","article-title":"Variation in pancreatoduodenectomy as delivered in two national audits","volume":"106","author":"Mackay","year":"2019","journal-title":"Br J Surg"},{"key":"2025121404003577000_14.9.e087193.4","doi-asserted-by":"crossref","first-page":"1867","DOI":"10.1016\/S0140-6736(22)00182-9","article-title":"Algorithm-based care versus usual care for the early recognition and management of complications after pancreatic resection in the Netherlands: an open-label, nationwide, stepped-wedge cluster-randomised trial","volume":"399","author":"Smits","year":"2022","journal-title":"Lancet"},{"key":"2025121404003577000_14.9.e087193.5","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1097\/SLA.0000000000005628","article-title":"Outcome of Pancreatic Surgery During the First 6 Years of a Mandatory Audit Within the Dutch Pancreatic Cancer Group","volume":"278","author":"Suurmeijer","year":"2023","journal-title":"Ann Surg"},{"key":"2025121404003577000_14.9.e087193.6","doi-asserted-by":"publisher","DOI":"10.1097\/SLA.0000000000003234"},{"key":"2025121404003577000_14.9.e087193.7","doi-asserted-by":"crossref","first-page":"e597","DOI":"10.1097\/SLA.0000000000004855","article-title":"A Simple Classification of Pancreatic Duct Size and Texture Predicts Postoperative Pancreatic Fistula: A classification of the International Study Group of Pancreatic Surgery","volume":"277","author":"Schuh","year":"2023","journal-title":"Ann Surg"},{"key":"2025121404003577000_14.9.e087193.8","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1097\/SLA.0000000000003451","article-title":"Textbook Outcome: Nationwide Analysis of a Novel Quality Measure in Pancreatic Surgery","volume":"271","author":"van Roessel","year":"2020","journal-title":"Ann Surg"},{"key":"2025121404003577000_14.9.e087193.9","article-title":"The influence of diagnosis on complications after pancreatoduodenectomy: results from a nationwide audit","volume":"23","author":"van Dam","year":"2021","journal-title":"HPB (Oxford)"},{"key":"2025121404003577000_14.9.e087193.10","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1016\/j.hpb.2017.06.010","article-title":"Nationwide prospective audit of pancreatic surgery: design, accuracy, and outcomes of the Dutch Pancreatic Cancer Audit","volume":"19","author":"van Rijssen","year":"2017","journal-title":"HPB (Oxf)"},{"key":"2025121404003577000_14.9.e087193.11","doi-asserted-by":"publisher","DOI":"10.1007\/s11605-014-2620-3"},{"key":"2025121404003577000_14.9.e087193.12","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1016\/j.hpb.2021.04.027","article-title":"The effect of preoperative chemotherapy and chemoradiotherapy on pancreatic fistula and other surgical complications after pancreatic resection: a systematic review and meta-analysis of comparative studies","volume":"23","author":"van Dongen","year":"2021","journal-title":"HPB (Oxf)"},{"key":"2025121404003577000_14.9.e087193.13","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1097\/SLA.0000000000004313","article-title":"Surgical Complications in a Multicenter Randomized Trial Comparing Preoperative Chemoradiotherapy and Immediate Surgery in Patients With Resectable and Borderline Resectable Pancreatic Cancer (PREOPANC Trial)","volume":"275","author":"van Dongen","year":"2022","journal-title":"Ann Surg"},{"key":"2025121404003577000_14.9.e087193.14","doi-asserted-by":"crossref","first-page":"1580","DOI":"10.1016\/j.surg.2024.01.029","article-title":"Preoperative chemoradiotherapy but not chemotherapy is associated with reduced risk of postoperative pancreatic fistula after pancreatoduodenectomy for pancreatic ductal adenocarcinoma: a nationwide analysis","volume":"175","author":"Wismans","year":"2024","journal-title":"Surgery"},{"key":"2025121404003577000_14.9.e087193.15","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.19.02274"},{"key":"2025121404003577000_14.9.e087193.16","doi-asserted-by":"publisher","DOI":"10.2174\/13894501113149990198"},{"key":"2025121404003577000_14.9.e087193.17","doi-asserted-by":"publisher","DOI":"10.1016\/j.surg.2011.03.001"},{"key":"2025121404003577000_14.9.e087193.18","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1272\/jnms.69.549","article-title":"Relationship between grade of fibrosis in pancreatic stump and postoperative pancreatic exocrine activity after pancreaticoduodenectomy: with special reference to insufficiency of pancreaticointestinal anastomosis","volume":"69","author":"Uchida","year":"2002","journal-title":"J Nippon Med Sch"},{"key":"2025121404003577000_14.9.e087193.19","article-title":"Somatostatin analogues for pancreatic surgery","volume":"2013","author":"Gurusamy","year":"2013","journal-title":"Cochrane Database Syst Rev"},{"key":"2025121404003577000_14.9.e087193.20","doi-asserted-by":"publisher","DOI":"10.1007\/s00432-015-1974-6"},{"key":"2025121404003577000_14.9.e087193.21","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v23.i11.2044"},{"key":"2025121404003577000_14.9.e087193.22","doi-asserted-by":"publisher","DOI":"10.1007\/s00268-017-4073-9"},{"key":"2025121404003577000_14.9.e087193.23","doi-asserted-by":"publisher","DOI":"10.1016\/j.jss.2008.08.022"},{"key":"2025121404003577000_14.9.e087193.24","doi-asserted-by":"publisher","DOI":"10.1111\/liv.12184"},{"key":"2025121404003577000_14.9.e087193.25","doi-asserted-by":"crossref","DOI":"10.1016\/j.ebiom.2024.105089","article-title":"The clinical manifestations and molecular pathogenesis of radiation fibrosis","volume":"103","author":"Fijardo","year":"2024","journal-title":"EBioMedicine"}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2024-087193","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,14]],"date-time":"2025-12-14T12:00:43Z","timestamp":1765713643000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2024-087193"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9]]},"references-count":25,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2024,9,24]]},"published-print":{"date-parts":[[2024,9]]}},"alternative-id":["10.1136\/bmjopen-2024-087193"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2024-087193","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"type":"print","value":"2044-6055"},{"type":"electronic","value":"2044-6055"}],"subject":[],"published":{"date-parts":[[2024,9]]}}}