{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T06:04:18Z","timestamp":1789538658282,"version":"build-2803163510"},"reference-count":48,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Cancer represents a major cause of death in systemic sclerosis (SSc). Established risk factors are limited to specific subsets, particularly early diffuse anti\u2010RNA polymerase III (POLR3)\u2013positive disease, needing further exploration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed a nested case\u2010control study within the European Scleroderma Trials and Research group: \u201ccases\u201d were defined as patients with SSc who developed cancer at any time point; controls were patients with SSc who were cancer free, matched for age and disease duration. Malignancies were classified as \u201csynchronous\u201d to SSc onset (\u00b13 years), \u201csubsequent\u201d (more than three years after), or \u201cprevious\u201d (more than three years before). Clinical, serologic, and treatment associations, as well as survival rates, were analyzed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 454 patients with SSc with cancer (29% synchronous, 51% subsequent, 20% previous) and 454 controls were identified. Mean age was 55\u2009\u00b1\u200913 years, disease duration was 5\u2009\u00b1\u20092 years; 88% were female, and 27.5% had diffuse SSc; 30.5% had interstitial lung disease (ILD), 32% had anti\u2010topoisomerase, and 10% had anti\u2010POLR3. Synchronous cancers were associated with anti\u2010POLR3 (odds ratio [OR] 2.06, 95% confidence interval [CI] 1.13\u20133.69), U1RNP (OR 3.56, 95% CI 1.03\u201312.3), and smoking (OR 1.57, 95% CI 1.01\u20132.44), but they were negatively associated with digital ulcers (OR 0.55, 95% CI 0.31\u20130.93). Calcinosis was inversely associated with subsequent cancers (OR 0.42, 95% CI 0.17\u20130.93). Breast cancer showed time\u2010dependent associations with anti\u2010POLR3 and anti\u2010PM\/Scl; lung cancer was mainly subsequent and associated with ILD (OR 2.00, 95% CI 1.12\u20133.54), anti\u2010topoisomerase (OR 2.61, 95% CI 1.38\u20135.04), and smoking. Cancers occurred more frequently in patients treated with cyclophosphamide. Malignancy worsened overall survival, particularly when subsequent. Radiation therapy did not impact mortality rate or new\u2010onset ILD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Cancer timing and site identify distinct clinical\u2010serologic associations in SSc, with different prognostic implications. As cancers diagnosed during follow\u2010up are major determinants of death, our findings inform the implementation of stratified cancer surveillance in SSc.<\/jats:p>\n                    <jats:p>\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/art70303-gra-0001-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.70303","type":"journal-article","created":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T10:46:01Z","timestamp":1787913961000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cancer in Systemic Sclerosis: Clinical Associations and Prognostic Impact From the\n                    <scp>EUSTAR<\/scp>\n                    Registry"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-9534-6853","authenticated-orcid":false,"given":"Antonio","family":"Tonutti","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences Humanitas University  Milan Italy"},{"name":"Rheumatology and Clinical Immunology IRCCS Humanitas Research Hospital  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8093-2734","authenticated-orcid":false,"given":"Francesca","family":"Motta","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences Humanitas University  Milan Italy"},{"name":"Rheumatology and Clinical Immunology IRCCS Humanitas Research Hospital  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liala","family":"Moschetti","sequence":"additional","affiliation":[{"name":"Rheumatology and Clinical Immunology Unit and Department of Clinical and Experimental Sciences, ERN ReCONNET ASST Spedali Civili and University of Brescia  Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cosimo","family":"Bruni","sequence":"additional","affiliation":[{"name":"Department of Rheumatology University Hospital Zurich, University of Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carina","family":"Mihai","sequence":"additional","affiliation":[{"name":"Department of Rheumatology University Hospital Zurich, University of Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5686-0127","authenticated-orcid":false,"given":"Claudia","family":"Iannone","sequence":"additional","affiliation":[{"name":"UOC Clinica Reumatologica ASST Gaetano Pini\u2010CTO  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Rosa","family":"Pellico","sequence":"additional","affiliation":[{"name":"UOC Clinica Reumatologica ASST Gaetano Pini\u2010CTO  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Stano","sequence":"additional","affiliation":[{"name":"Rheumatology Unit, Department of Precision and Regenerative Medicine, Jonian Area (DiPReMeJ) University of Bari \u2018Aldo Moro\u2019  Bari Italy"},{"name":"LUM \u2018G. 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