{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T15:19:49Z","timestamp":1786979989040,"version":"build-2736575974"},"reference-count":28,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T00:00:00Z","timestamp":1761004800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T00:00:00Z","timestamp":1761004800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","award":["01GM1909E"],"award-info":[{"award-number":["01GM1909E"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur Radiol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Annual whole-body MRI (WB-MRI) is recommended for early cancer detection in individuals with Li-Fraumeni syndrome (LFS). However, there is no agreement on a standardized MRI protocol. This study evaluated the diagnostic performance of different MRI sequences to suggest an optimized protocol for LFS surveillance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>In this prospective bicentric study, 113 participants with LFS underwent annual WB-MRI and were included in the analysis. The protocol comprised turbo-spin echo (TSE) T1-weighted and inversion-recovery T2-weighted (TIRM) images of the whole body in coronal orientation, and T2-weighted (HASTE), diffusion-weighted (DWI), and T1-weighted DIXON images (pre- and post-contrast agent administration) from head to thighs in axial orientation. An additional fluid-attenuated inversion recovery (FLAIR) sequence imaged the skull only. Initial clinical interpretation was conducted by staff radiologists. The visibility of reported mass lesions was independently graded in all sequences by three experienced radiologists using a Likert scale. Sequence combinations were compared to inform the design of an optimal MRI protocol.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Over 30 months, 189 WB-MRI examinations were performed in 113 participants (mean age 40 years, \u00b112.7 years [standard deviation], 91 women). 188 mass lesions were detected and confirmed as malignant (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200938), benign (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009120) or ambiguous (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200930). In the multi-reader analysis, all new malignant lesions could have been detected by a combination of cranial FLAIR, whole-body DWI, and whole-body HASTE in the axial direction.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>A shortened, contrast-agent-free WB-MRI protocol combining cranial FLAIR, WB-HASTE, and WB-DWI promises to be an effective and patient-friendly approach for annual cancer surveillance in LFS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Points<\/jats:title>\n                    <jats:p>\n                      <jats:bold>\n                        <jats:italic>Question<\/jats:italic>\n                      <\/jats:bold>\n                      <jats:italic>Annual whole-body MRI (WB-MRI) is recommended for early cancer detection for individuals with Li-Fraumeni syndrome (LFS), but a standardized sequence protocol has yet to be established<\/jats:italic>\n                      .\n                    <\/jats:p>\n                    <jats:p>\n                      <jats:bold>\n                        <jats:italic>Findings<\/jats:italic>\n                      <\/jats:bold>\n                      <jats:italic>The combination of cranial FLAIR, whole-body HASTE, and whole-body DWI in the axial plane enabled visualization of all newly developed malignant lesions in our study cohort<\/jats:italic>\n                      .\n                    <\/jats:p>\n                    <jats:p>\n                      <jats:bold>\n                        <jats:italic>Clinical relevance<\/jats:italic>\n                      <\/jats:bold>\n                      <jats:italic>A shortened, standardized WB-MRI protocol enables efficient, sensitive early cancer detection in individuals with LFS, minimizing patient burden by reducing examination time and contrast agent use. This approach may improve surveillance participation while enhancing comparability across centers<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Graphical Abstract<\/jats:title>\n                  <\/jats:sec>","DOI":"10.1007\/s00330-025-11880-y","type":"journal-article","created":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T13:23:56Z","timestamp":1761053036000},"page":"2401-2412","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Optimizing whole-body MRI for early cancer detection in Li-Fraumeni syndrome: a prospective bicentric study"],"prefix":"10.1007","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4447-5636","authenticated-orcid":false,"given":"Myriam Margareta","family":"Keymling","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix Tobias","family":"Kurz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tristan Anselm","family":"Kuder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Bickelhaupt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Hielscher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Hog","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresa","family":"Mokry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tawfik Moher","family":"Alsady","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Schott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Kratz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane Miriam","family":"Renz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heinz-Peter","family":"Schlemmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,10,21]]},"reference":[{"key":"11880_CR1","doi-asserted-by":"publisher","first-page":"3673","DOI":"10.1002\/cncr.30248","volume":"122","author":"PL Mai","year":"2016","unstructured":"Mai PL, Best AF, Peters JA et al (2016) Risks of first and subsequent cancers among TP53 mutation carriers in the National Cancer Institute Li-Fraumeni syndrome cohort. Cancer 122:3673\u20133681","journal-title":"Cancer"},{"key":"11880_CR2","doi-asserted-by":"publisher","first-page":"654","DOI":"10.1002\/humu.22559","volume":"35","author":"J Kamihara","year":"2014","unstructured":"Kamihara J, Rana HQ, Garber JE (2014) Germline TP 53 mutations and the changing landscape of Li-Fraumeni syndrome. Hum Mutat 35:654\u2013662","journal-title":"Hum Mutat"},{"key":"11880_CR3","doi-asserted-by":"crossref","unstructured":"Malkin D (2010) Li\u2013Fraumeni syndrome. In: Adrenocortical carcinoma: basic science and clinical concepts. New York: Springer, pp 173\u2013191","DOI":"10.1007\/978-0-387-77236-3_11"},{"key":"11880_CR4","doi-asserted-by":"crossref","unstructured":"Daly MB, Pal T, Maxwell KN, Churpek J, Darlow SD et al (2023). NCCN Guidelines\u00ae Insights: Genetic\/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic, Version 2.2024: Featured Updates to the NCCN Guidelines. J Natl Compr Canc Netw 21:1000\u20131010","DOI":"10.6004\/jnccn.2023.0051"},{"key":"11880_CR5","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1097\/CCO.0000000000000200","volume":"27","author":"ML Ballinger","year":"2015","unstructured":"Ballinger ML, Mitchell G, Thomas DM (2015) Surveillance recommendations for patients with germline TP53 mutations. Curr Opin Oncol 27:332\u2013337","journal-title":"Curr Opin Oncol"},{"key":"11880_CR6","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1038\/nrclinonc.2014.41","volume":"11","author":"KA McBride","year":"2014","unstructured":"McBride KA, Ballinger ML, Killick E et al (2014) Li-Fraumeni syndrome: cancer risk assessment and clinical management. Nat Rev Clin Oncol 11:260\u2013271","journal-title":"Nat Rev Clin Oncol"},{"key":"11880_CR7","doi-asserted-by":"publisher","first-page":"1295","DOI":"10.1016\/S1470-2045(16)30249-2","volume":"17","author":"A Villani","year":"2016","unstructured":"Villani A, Shore A, Wasserman JD et al (2016) Biochemical and imaging surveillance in germline TP53 mutation carriers with Li-Fraumeni syndrome: 11 year follow-up of a prospective observational study. Lancet Oncol 17:1295\u20131305","journal-title":"Lancet Oncol"},{"key":"11880_CR8","doi-asserted-by":"publisher","first-page":"e38","DOI":"10.1158\/1078-0432.CCR-17-0408","volume":"23","author":"CP Kratz","year":"2017","unstructured":"Kratz CP, Achatz MI, Brugi\u00e8res L et al (2017) Cancer screening recommendations for individuals with Li-Fraumeni syndrome. Clin Cancer Res 23:e38\u2013e45","journal-title":"Clin Cancer Res"},{"key":"11880_CR9","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1007\/s10549-020-05612-7","volume":"181","author":"AN Le","year":"2020","unstructured":"Le AN, Harton J, Desai H et al (2020) Frequency of radiation-induced malignancies post-adjuvant radiotherapy for breast cancer in patients with Li-Fraumeni syndrome. Breast Cancer Res Treat 181:181\u2013188","journal-title":"Breast Cancer Res Treat"},{"key":"11880_CR10","doi-asserted-by":"publisher","first-page":"400","DOI":"10.2214\/AJR.14.13663","volume":"205","author":"SA Anupindi","year":"2015","unstructured":"Anupindi SA, Bedoya MA, Lindell RB et al (2015) Diagnostic performance of whole-body MRI as a tool for cancer screening in children with genetic cancer-predisposing conditions. AJR Am J Roentgenol 205:400\u2013408","journal-title":"AJR Am J Roentgenol"},{"key":"11880_CR11","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1016\/j.mric.2018.06.003","volume":"26","author":"G Petralia","year":"2018","unstructured":"Petralia G, Padhani AR (2018) Whole-body magnetic resonance imaging in oncology: uses and indications. Magn Reson Imaging Clin 26:495\u2013507","journal-title":"Magn Reson Imaging Clin"},{"key":"11880_CR12","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1007\/s00247-021-05076-x","volume":"52","author":"HE Daldrup-Link","year":"2022","unstructured":"Daldrup-Link HE, Theruvath AJ, Baratto L, Hawk KE (2022) One-stop local and whole-body staging of children with cancer. Pediatr Radiol 52:391\u2013400","journal-title":"Pediatr Radiol"},{"key":"11880_CR13","doi-asserted-by":"publisher","first-page":"946","DOI":"10.1002\/cncr.34631","volume":"129","author":"M Omran","year":"2023","unstructured":"Omran M, Johansson H, Lundgren C et al (2023) Whole-body MRI surveillance in TP53 carriers is perceived as beneficial with no increase in cancer worry regardless of previous cancer: data from the Swedish TP53 study. Cancer 129:946\u2013955","journal-title":"Cancer"},{"key":"11880_CR14","doi-asserted-by":"publisher","first-page":"1634","DOI":"10.1001\/jamaoncol.2017.1968","volume":"3","author":"ML Ballinger","year":"2017","unstructured":"Ballinger ML, Best A, Mai PL et al (2017) Baseline surveillance in Li-Fraumeni syndrome using whole-body magnetic resonance imaging: a meta-analysis. JAMA Oncol 3:1634\u20131639","journal-title":"JAMA Oncol"},{"key":"11880_CR15","doi-asserted-by":"publisher","first-page":"494","DOI":"10.1148\/radiol.2021201740","volume":"299","author":"G Petralia","year":"2021","unstructured":"Petralia G, Koh D-M, Attariwala R et al (2021) Oncologically relevant findings reporting and data system (ONCO-RADS): guidelines for the acquisition, interpretation, and reporting of whole-body MRI for cancer screening. Radiology 299:494\u2013507","journal-title":"Radiology"},{"key":"11880_CR16","doi-asserted-by":"crossref","unstructured":"Keymling M, Schlemmer H-P, Kratz C et al (2022) Li-Fraumeni syndrome. Radiologie 62:1026\u20131032","DOI":"10.1007\/s00117-022-01071-x"},{"key":"11880_CR17","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1148\/radiology.168.2.3393671","volume":"168","author":"D Le Bihan","year":"1988","unstructured":"Le Bihan D, Breton E, Lallemand D, Aubin ML, Vignaud J, Laval-Jeantet M (1988) Separation of diffusion and perfusion in intravoxel incoherent motion MR imaging. Radiology 168:497\u2013505","journal-title":"Radiology"},{"key":"11880_CR18","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1007\/s12149-018-1307-3","volume":"33","author":"H Sasamori","year":"2019","unstructured":"Sasamori H, Uno K, Wu J (2019) Usefulness of both PET\/CT with F18-FDG and whole-body diffusion-weighted imaging in cancer screening: a preliminary report. Ann Nucl Med 33:78\u201385","journal-title":"Ann Nucl Med"},{"key":"11880_CR19","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s40644-018-0187-z","volume":"19","author":"RC Dresen","year":"2019","unstructured":"Dresen RC, De Vuysere S, De Keyzer F et al (2019) Whole-body diffusion-weighted MRI for operability assessment in patients with colorectal cancer and peritoneal metastases. Cancer Imaging 19:1\u201310","journal-title":"Cancer Imaging"},{"key":"11880_CR20","doi-asserted-by":"publisher","first-page":"1124","DOI":"10.2214\/AJR.09.2520","volume":"193","author":"CH Hunt","year":"2009","unstructured":"Hunt CH, Hartman RP, Hesley GK (2009) Frequency and severity of adverse effects of iodinated and gadolinium contrast materials: retrospective review of 456,930 doses. AJR Am J Roentgenol 193:1124\u20131127","journal-title":"AJR Am J Roentgenol"},{"key":"11880_CR21","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1148\/radiol.2015150337","volume":"275","author":"A Radbruch","year":"2015","unstructured":"Radbruch A, Weberling LD, Kieslich PJ et al (2015) Gadolinium retention in the dentate nucleus and globus pallidus is dependent on the class of contrast agent. Radiology 275:783\u2013791","journal-title":"Radiology"},{"key":"11880_CR22","doi-asserted-by":"publisher","first-page":"516","DOI":"10.1148\/rg.2019180130","volume":"39","author":"RV Gottumukkala","year":"2019","unstructured":"Gottumukkala RV, Gee MS, Hampilos PJ, Greer M-LC (2019) Current and emerging roles of whole-body MRI in evaluation of pediatric cancer patients. Radiographics 39:516\u2013534","journal-title":"Radiographics"},{"key":"11880_CR23","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1007\/s10689-017-9965-1","volume":"16","author":"S Saya","year":"2017","unstructured":"Saya S, Killick E, Thomas S et al (2017) Baseline results from the UK SIGNIFY study: a whole-body MRI screening study in TP53 mutation carriers and matched controls. Fam Cancer 16:433\u2013440","journal-title":"Fam Cancer"},{"key":"11880_CR24","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1148\/radiol.2019181949","volume":"291","author":"C Messiou","year":"2019","unstructured":"Messiou C, Hillengass J, Delorme S et al (2019) Guidelines for acquisition, interpretation, and reporting of whole-body MRI in myeloma: myeloma response assessment and diagnosis system (MY-RADS). Radiology 291:5\u201313","journal-title":"Radiology"},{"key":"11880_CR25","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1007\/s00247-017-4013-8","volume":"48","author":"AM Smets","year":"2018","unstructured":"Smets AM, Deurloo EE, Slager TJE, Stoker J, Bipat S (2018) Whole-body magnetic resonance imaging for detection of skeletal metastases in children and young people with primary solid tumors\u2014systematic review. Pediatr Radiol 48:241\u2013252","journal-title":"Pediatr Radiol"},{"key":"11880_CR26","doi-asserted-by":"crossref","unstructured":"Kiermeier S, Schott S, Nees J et al (2024) Health\u2010related quality of life and fear of progression in individuals with Li\u2010Fraumeni. J Genet Couns 34:e1859","DOI":"10.1002\/jgc4.1859"},{"key":"11880_CR27","doi-asserted-by":"crossref","unstructured":"Nees J, Kiermeier S, Struewe F et al (2022) Health behavior and cancer prevention among adults with Li-Fraumeni syndrome and relatives in Germany\u2014a cohort description. Curr Oncol 29:7768\u20137778","DOI":"10.3390\/curroncol29100614"},{"key":"11880_CR28","doi-asserted-by":"crossref","unstructured":"Penkert J, Str\u00fcwe FJ, Dutzmann CM et al (2022) Genotype\u2013phenotype associations within the Li-Fraumeni spectrum: a report from the German Registry. J Hematol Oncol 15:107","DOI":"10.1186\/s13045-022-01332-1"}],"container-title":["European Radiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00330-025-11880-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00330-025-11880-y","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00330-025-11880-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T15:20:05Z","timestamp":1774884005000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00330-025-11880-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,21]]},"references-count":28,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["11880"],"URL":"https:\/\/doi.org\/10.1007\/s00330-025-11880-y","relation":{},"ISSN":["1432-1084"],"issn-type":[{"value":"1432-1084","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,21]]},"assertion":[{"value":"5 February 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 June 2025","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 July 2025","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 October 2025","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"The scientific guarantor of this publication is Myriam Margareta Keymling.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Guarantor"}},{"value":"The author Sebastian Bickelhaupt received lecture fees and project support from Siemens Healthineers unrelated to this work. D.M.R. is a junior deputy editor for\n                      European Radiology\n                      , and H.P.S. is a member of the Advisory Editorial Board of\n                      European Radiology\n                      (European Society of Oncologic Imaging). As such, these authors did not participate in the selection or review processes for this article. The remaining authors of this manuscript declare no relationships with any company, whose products or services may be related to the subject matter of the article.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"The author Thomas Hielscher has significant statistical expertise and provided advice on this matter.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Statistics and biometry"}},{"value":"Written informed consent was obtained from all subjects in this study. Approval from the institutional animal care committee was not required because no animals were examined in this study.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}},{"value":"Institutional Review Board approval was obtained in both study locations (numbers: S-131\/2020 and 9196_B0_K_2020).","order":6,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Of the 113 included participants, some were already reported in other articles: 47 participants were previously included in a study dealing with quality of life and fear of progression [\n                      \n                      ], 49 in a paper examining health behavior in individuals with LFS [\n                      \n                      ], and 61 in an analysis of genotype-phenotype associations in LFS [\n                      \n                      ]. None of the previous articles addresses imaging, while our manuscript deals with the optimization of a whole-body MRI protocol for cancer screening in individuals with LFS. There is no content overlap.","order":7,"name":"Ethics","group":{"name":"EthicsHeading","label":"Study subjects or cohorts overlap"}},{"order":8,"name":"Ethics","group":{"name":"EthicsHeading","label":"Methodology"}}]}}