{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T10:52:58Z","timestamp":1781866378815,"version":"3.54.5"},"reference-count":30,"publisher":"Springer Science and Business Media LLC","issue":"7","license":[{"start":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T00:00:00Z","timestamp":1770595200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T00:00:00Z","timestamp":1770595200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"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>Objective<\/jats:title>\n                    <jats:p>Blinded Independent Central Review (BICR) with double reads and adjudication is crucial in imaging-based clinical trials to ensure quality data. However, discrepancies in double reading can affect trial outcomes, particularly in assessing disease progression in phase 3 oncology studies using RECIST 1.1 criteria. This study examined discordance in the date of progressive disease (DoPD) across RECIST components: target lesion (TL), non-target lesion (nTL), new lesion (NL), exploring its impact on survival curves and whether discrepancies stem from timing differences or true\/false PD detection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>We retrospectively analyzed data from five clinical trials using BICR with double reads plus adjudication, involving 1932 lung cancer patients on immunotherapy or targeted therapy. RECIST components were examined to assess DoPD concordance, discrepancies, adjudicator acceptance, detection timing, and impact on survival curves.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Readers showed a 39.3% discordance rate in DoPD assessments, with agreement on 17.3% of DoPD cases and 43.4% of non-PD cases. In 54.2% of concordant cases, multiple RECIST components contributed to PD. Discordance was primarily caused by NL (41.4%), sum of TL diameter increase (33.3%), nTL (11.8%), or multiple components (13.4%). In 49.2% of discrepant cases, PD was reported late, usually within one treatment cycle (79.8%). 62.5% of disputed PD cases were accepted by adjudication.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Different RECIST components vary in their likelihood of causing discordance and being accepted or refuted by adjudicators. NL detection is key for identifying progression but also the main source of disagreement. Using multiple RECIST components enhances the reliability of PD assessment.<\/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>How does discordance across RECIST components\u2014especially new lesion detection\u2014influence progression assessment timing and potentially alter survival outcomes in oncology clinical trials?<\/jats:italic>\n                    <\/jats:p>\n                    <jats:p>\n                      <jats:bold>\n                        <jats:italic>Findings<\/jats:italic>\n                      <\/jats:bold>\n                      <jats:italic>Reader disagreement on progression dates is common, driven mainly by new lesion detection; incorporating multiple RECIST components increases alignment and strengthens PD determination reliability.<\/jats:italic>\n                    <\/jats:p>\n                    <jats:p>\n                      <jats:bold>\n                        <jats:italic>Clinical relevance<\/jats:italic>\n                      <\/jats:bold>\n                      <jats:italic>Imaging endpoints guide cancer treatment decisions. RECIST 1.1 is the standard, inter-reader variability can undermine PFS accuracy. By evaluating RECIST component reliability, this work aims to improve trial precision, enabling faster, more confident decisions that ultimately benefit patients.<\/jats:italic>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00330-025-12234-4","type":"journal-article","created":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T16:43:50Z","timestamp":1770655430000},"page":"6159-6169","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["What are RECIST 1.1 progressions made of? Variability in double-read oncology trials"],"prefix":"10.1007","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7624-8956","authenticated-orcid":false,"given":"Hubert","family":"Beaumont","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Cantini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamal S.","family":"Saini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Faye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ritu","family":"Gill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoine","family":"Iannessi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,9]]},"reference":[{"key":"12234_CR1","doi-asserted-by":"crossref","unstructured":"Matsumoto T, Furukawa A, Machida K et al (2004) Methods of evaluating the effectiveness of double-checking in interpreting mass screening images. Proc SPIE. Medical Imaging 2004, San Diego, California, United States. p 496","DOI":"10.1117\/12.536304"},{"key":"12234_CR2","unstructured":"FDA, U.S. Department of Health and Human Services, Center for Drug Evaluation and Research, Center for Biologics Evaluations and Research (2004) Guidance for industry developing medical imaging drug and biologic products. Part 3: Design, analysis, and interpretation of clinical studies. https:\/\/downloads.regulations.gov\/FDA-1998-D-0035-0013\/attachment_1.pdf"},{"key":"12234_CR3","unstructured":"FDA, US Department of Health and Human Services, Center for Drug Evaluation and Research, Center for Biologics Evaluations and Research (2015) Clinical trial imaging endpoints process standards guidance for industry draft. https:\/\/downloads.regulations.gov\/FDA-2011-D-0586-0026\/attachment_1.pdf"},{"key":"12234_CR4","unstructured":"US Food and Drug Administration (2018) Clinical trial imaging endpoint process standards: guidance for industry. https:\/\/www.fda.gov\/files\/drugs\/published\/Clinical-Trial-Imaging-Endpoint-Process-Standards-Guidance-for-Industry.pdf"},{"key":"12234_CR5","doi-asserted-by":"publisher","unstructured":"Schmid AM, Raunig DL, Miller CG et al (2021) Radiologists and clinical trials: Part 1 The truth about reader disagreements. Ther Innov Regul Sci. https:\/\/doi.org\/10.1007\/s43441-021-00316-6","DOI":"10.1007\/s43441-021-00316-6"},{"key":"12234_CR6","doi-asserted-by":"publisher","first-page":"1707","DOI":"10.1038\/s41416-020-0805-y","volume":"122","author":"L Belin","year":"2020","unstructured":"Belin L, Tan A, De Rycke Y, Dechartres A (2020) Progression-free survival as a surrogate for overall survival in oncology trials: a methodological systematic review. Br J Cancer 122:1707\u20131714. https:\/\/doi.org\/10.1038\/s41416-020-0805-y","journal-title":"Br J Cancer"},{"key":"12234_CR7","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1016\/j.ejca.2008.10.026","volume":"45","author":"EA Eisenhauer","year":"2009","unstructured":"Eisenhauer EA, Therasse P, Bogaerts J et al (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45:228\u2013247. https:\/\/doi.org\/10.1016\/j.ejca.2008.10.026","journal-title":"Eur J Cancer"},{"key":"12234_CR8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fonc.2021.800547","volume":"11","author":"L Fournier","year":"2022","unstructured":"Fournier L, de Geus-Oei LF, Regge D et al (2022) Twenty years on: RECIST as a biomarker of response in solid tumours an EORTC Imaging Group\u2013ESOI Joint Paper. Front Oncol 11:1\u201317. https:\/\/doi.org\/10.3389\/fonc.2021.800547","journal-title":"Front Oncol"},{"key":"12234_CR9","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fimmu.2023.1173546","volume":"14","author":"R Kumar","year":"2023","unstructured":"Kumar R, Qi T, Cao Y, Topp B (2023) Incorporating lesion-to-lesion heterogeneity into early oncology decision making. Front Immunol 14:1\u20139. https:\/\/doi.org\/10.3389\/fimmu.2023.1173546","journal-title":"Front Immunol"},{"key":"12234_CR10","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41467-023-38837-3","volume":"14","author":"E Garralda","year":"2023","unstructured":"Garralda E, Laurie SA, Seymour L, de Vries EGE (2023) Towards evidence-based response criteria for cancer immunotherapy. Nat Commun 14:1\u20134. https:\/\/doi.org\/10.1038\/s41467-023-38837-3","journal-title":"Nat Commun"},{"key":"12234_CR11","doi-asserted-by":"publisher","unstructured":"Ford RR, O\u2019 Neal M, Moskowitz SC, Fraunberger J (2016) Adjudication rates between readers in blinded independent central review of oncology studies. J Clin Trials. https:\/\/doi.org\/10.4172\/2167-0870.1000289","DOI":"10.4172\/2167-0870.1000289"},{"key":"12234_CR12","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fonc.2023.988784","volume":"13","author":"A Iannessi","year":"2023","unstructured":"Iannessi A, Beaumont H (2023) Breaking down the RECIST 1.1 double read variability in lung trials: what do baseline assessments tell us? Front Oncol 13:1\u201314. https:\/\/doi.org\/10.3389\/fonc.2023.988784","journal-title":"Front Oncol"},{"key":"12234_CR13","doi-asserted-by":"publisher","first-page":"2613","DOI":"10.1158\/1078-0432.CCR-12-2938","volume":"19","author":"R Sridhara","year":"2013","unstructured":"Sridhara R, Mandrekar SJ, Dodd LE (2013) Missing data and measurement variability in assessing progression-free survival endpoint in randomized clinical trials. Clin Cancer Res 19:2613\u20132620. https:\/\/doi.org\/10.1158\/1078-0432.CCR-12-2938","journal-title":"Clin Cancer Res"},{"key":"12234_CR14","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1148\/rg.2018170107","volume":"38","author":"LP Busby","year":"2018","unstructured":"Busby LP, Courtier JL, Glastonbury CM (2018) Bias in radiology: the how and why of misses and misinterpretations. Radiographics 38:236\u2013247. https:\/\/doi.org\/10.1148\/rg.2018170107","journal-title":"Radiographics"},{"key":"12234_CR15","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1148\/radiol.2019182922","volume":"292","author":"HJ Coy","year":"2019","unstructured":"Coy HJ, Douek ML, Ruchalski K et al (2019) Components of radiologic progressive disease defined by RECIST 1.1 in patients with metastatic clear cell renal cell carcinoma. Radiology 292:103\u2013109. https:\/\/doi.org\/10.1148\/radiol.2019182922","journal-title":"Radiology"},{"key":"12234_CR16","doi-asserted-by":"publisher","first-page":"2093","DOI":"10.1148\/rg.317115050","volume":"31","author":"H Chalian","year":"2011","unstructured":"Chalian H, T\u00f6re HG, Horowitz JM, Salem R, Miller FH, Yaghmai V (2011) Radiologic assessment of response to therapy: comparison of recist versions 1.1 and 1.0. Radiographics 31:2093\u20132106. https:\/\/doi.org\/10.1148\/rg.317115050","journal-title":"Radiographics"},{"key":"12234_CR17","first-page":"285","volume":"10","author":"M Shibutani","year":"2019","unstructured":"Shibutani M, Maeda K, Nagahara H et al (2019) Impact of the occurrence of new lesions on the survival of patients who undergo chemotherapy for metastatic colorectal cancer. Mol Clin Oncol 10:285\u2013292","journal-title":"Mol Clin Oncol"},{"key":"12234_CR18","doi-asserted-by":"publisher","DOI":"10.1186\/s40644-018-0186-0","volume":"18","author":"H Beaumont","year":"2018","unstructured":"Beaumont H, Evans TL, Klifa C et al (2018) Discrepancies of assessments in a RECIST 1.1 phase II clinical trial\u2014association between adjudication rate and variability in images and tumors selection. Cancer Imaging 18:50. https:\/\/doi.org\/10.1186\/s40644-018-0186-0","journal-title":"Cancer Imaging"},{"key":"12234_CR19","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1097\/RLI.0000000000001045","volume":"59","author":"TM Tareco Bucho","year":"2024","unstructured":"Tareco Bucho TM, Tissier RLM, Groot Lipman KBW et al (2024) How does target lesion selection affect RECIST? A computer simulation study. Invest Radiol 59:465\u2013471. https:\/\/doi.org\/10.1097\/RLI.0000000000001045","journal-title":"Invest Radiol"},{"key":"12234_CR20","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fonc.2023.1239570","volume":"13","author":"H Beaumont","year":"2023","unstructured":"Beaumont H, Iannessi A (2023) Can we predict discordant RECIST 1.1 evaluations in double read clinical trials? Front Oncol 13:1\u201314. https:\/\/doi.org\/10.3389\/fonc.2023.1239570","journal-title":"Front Oncol"},{"key":"12234_CR21","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1093\/annonc\/mdz003","volume":"30","author":"E Borcoman","year":"2019","unstructured":"Borcoman E, Kanjanapan Y, Champiat S et al (2019) Novel patterns of response under immunotherapy. Ann Oncol 30:385\u2013396. https:\/\/doi.org\/10.1093\/annonc\/mdz003","journal-title":"Ann Oncol"},{"key":"12234_CR22","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1186\/s13244-024-01774-w","volume":"15","author":"A Iannessi","year":"2024","unstructured":"Iannessi A, Beaumont H, Ojango C, Bertrand AS, Liu Y (2024) RECIST 1.1 assessments variability: a systematic pictorial review of blinded double reads. Insights Imaging 15:199. https:\/\/doi.org\/10.1186\/s13244-024-01774-w","journal-title":"Insights Imaging"},{"key":"12234_CR23","doi-asserted-by":"publisher","first-page":"e13545","DOI":"10.1200\/jco.2023.41.16_suppl.e13545","volume":"41","author":"A Gong","year":"2023","unstructured":"Gong A, Daly M, Melendez-Corres G et al (2023) Toward automating RECIST 1.1: improving AI new lesion detection with longitudinal image data. J Clin Oncol 41:e13545. https:\/\/doi.org\/10.1200\/jco.2023.41.16_suppl.e13545","journal-title":"J Clin Oncol"},{"key":"12234_CR24","doi-asserted-by":"publisher","unstructured":"Iannessi A, Beaumont H, Liu Y, Bertrand AS (2021) RECIST 1.1 and lesion selection: how to deal with ambiguity at baseline? Insights Imaging. https:\/\/doi.org\/10.1186\/s13244-021-00976-w","DOI":"10.1186\/s13244-021-00976-w"},{"key":"12234_CR25","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1093\/annonc\/mdy514","volume":"30","author":"A Stone","year":"2019","unstructured":"Stone A, Gebski V, Davidson R, Bloomfield R, Bartlett JW, Sabin A (2019) Exaggeration of PFS by blinded, independent, central review (BICR). Ann Oncol 30:332\u2013338. https:\/\/doi.org\/10.1093\/annonc\/mdy514","journal-title":"Ann Oncol"},{"key":"12234_CR26","doi-asserted-by":"publisher","first-page":"154007","DOI":"10.1109\/ACCESS.2020.3018666","volume":"8","author":"W Cao","year":"2020","unstructured":"Cao W, Wu R, Cao G, He Z (2020) A comprehensive review of computer-aided diagnosis of pulmonary nodules based on computed tomography scans. IEEE Access 8:154007\u2013154023. https:\/\/doi.org\/10.1109\/ACCESS.2020.3018666","journal-title":"IEEE Access"},{"key":"12234_CR27","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fonc.2020.581210","volume":"10","author":"J Zhou","year":"2021","unstructured":"Zhou J, Wang W, Lei B et al (2021) Automatic detection and classification of focal liver lesions based on deep convolutional neural networks: a preliminary study. Front Oncol 10:1\u201311. https:\/\/doi.org\/10.3389\/fonc.2020.581210","journal-title":"Front Oncol"},{"key":"12234_CR28","doi-asserted-by":"publisher","first-page":"1733","DOI":"10.1136\/ijgc-2023-004605","volume":"33","author":"TJ Herzog","year":"2023","unstructured":"Herzog TJ, Wahab SA, Mirza MR et al (2023) Optimizing disease progression assessment using blinded central independent review and comparing it with investigator assessment in the PRIMA\/ENGOT-ov26\/GOG-3012 trial: challenges and solutions. Int J Gynecol Cancer 33:1733\u20131742. https:\/\/doi.org\/10.1136\/ijgc-2023-004605","journal-title":"Int J Gynecol Cancer"},{"key":"12234_CR29","doi-asserted-by":"publisher","first-page":"8","DOI":"10.2478\/v10019-012-0009-z","volume":"46","author":"D Muenzel","year":"2012","unstructured":"Muenzel D, Engels HP, Bruegel M, Kehl V, Rummeny EJ, Metz S (2012) Intra- and inter-observer variability in measurement of target lesions: implication on response evaluation according to RECIST 1.1. Radiol Oncol 46:8\u201318. https:\/\/doi.org\/10.2478\/v10019-012-0009-z","journal-title":"Radiol Oncol"},{"key":"12234_CR30","doi-asserted-by":"publisher","first-page":"3112","DOI":"10.1002\/cam4.5236","volume":"12","author":"H Beaumont","year":"2023","unstructured":"Beaumont H, Faye N, Iannessi A, Chamorey E, Klifa C, Hsieh CY (2023) Differences in sensitivity to new therapies between primary and metastatic breast cancer: a need to stratify the tumor response? Cancer Med 12:3112\u20133122. https:\/\/doi.org\/10.1002\/cam4.5236","journal-title":"Cancer Med"}],"container-title":["European Radiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00330-025-12234-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00330-025-12234-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00330-025-12234-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T10:18:27Z","timestamp":1781864307000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00330-025-12234-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,9]]},"references-count":30,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["12234"],"URL":"https:\/\/doi.org\/10.1007\/s00330-025-12234-4","relation":{},"ISSN":["1432-1084"],"issn-type":[{"value":"1432-1084","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,9]]},"assertion":[{"value":"12 February 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 November 2025","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 December 2025","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 February 2026","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 Hubert Beaumont.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Guarantor"}},{"value":"The authors of this manuscript, Hubert Beaumont, Nathalie Faye, Ritu Gill and Antoine Iannessi, declare relationships with the following companies: Median Technologies. Luca Cantini is an employee of Fortrea Inc. and has stock and\/or other ownership interests in Fortrea Inc. Kamal S. Saini reports on consulting fees from the European Commission and stock and\/or other ownership interests in Fortrea Inc. and Quantum Health Analytics (UK) Ltd, outside the submitted work.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"One of the authors, Hubert Beaumont, has significant statistical expertise.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Statistics and biometry"}},{"value":"Written informed consent was not required for this study because of its retrospective nature.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}},{"value":"Institutional Review Board approval was obtained.","order":6,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Some study subjects or cohorts have been previously reported in: Iannessi and Beaumont [\n                      \n                      ] and Beaumont and Iannessi [\n                      \n                      ].","order":7,"name":"Ethics","group":{"name":"EthicsHeading","label":"Study subjects or cohorts overlap"}},{"order":8,"name":"Ethics","group":{"name":"EthicsHeading","label":"Methodology"}}]}}