{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T20:32:24Z","timestamp":1779136344787,"version":"3.51.4"},"reference-count":35,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T00:00:00Z","timestamp":1757376000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Swiss Sarcoma Network"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Sarcoma surveillance guidelines still apply uniform imaging intervals based on tumor grade and stage that ignore histotype-specific metastatic behavior. We prospectively analyzed metastatic timing, organ tropism, and lesion burden across a real-world sarcoma cohort to generate an evidence base for risk-adapted follow-up and treatment stratification. Methods: In a prospective multicenter study, 1850 patients with suspected sarcoma were screened. SHAPEHub, a real-world-time data warehouse, captured clinicopathological variables and imaging. Adults with histologically confirmed soft-tissue or bone sarcoma (n = 295) formed the analytic cohort. Metastases were classified as synchronous (\u22646 months) or metachronous (&gt;6 months), lung-only versus multi-organ, and oligometastatic (\u22645 lesions, \u22642 organs) versus polymetastatic. TTME was illustrated with Kaplan\u2013Meier curves for the full cohort (descriptive); where subgroup comparisons are shown, log-rank tests are reported. Results: Ninety-three patients (31.5%) developed metastases after a median follow-up of 20.9 months. Metastatic risk was front-loaded: 36.6% were synchronous, and 67.8% of metachronous events occurred within year 1. The lung was the initial site in 62.4% of events, bone in 18.3%, and liver in 11.8%. Half of the lung-metastatic patients remained pulmonary-confined; the remainder followed a multi-organ route involving bone and lymph nodes. Oligometastatic spread predominated in the lung-only subgroup (61%) versus multi-organ (28%). Histotype influenced both timing and tropism: angiosarcoma and Ewing sarcoma metastasized earliest (median 3.7 and 5.0 months) and multi-organ; leiomyosarcoma and UPS were lung-dominant; Ewing sarcoma and epithelioid haemangioendothelioma were bone-tropic; and angiosarcoma was liver-tropic. Conclusions: Metastatic sarcoma displays three intersecting dimensions\u2014early versus late onset, organ-specific tropism, and oligo- versus polymetastatic burden\u2014none of which are addressed by the current \u201cone-size-fits-all\u201d surveillance. Recognizing these patterns delineates windows for tailored imaging and stratified therapy selection (e.g., local ablation for oligometastatic lung disease, intensified systemic regimens for early, polymetastatic spread). These findings lay the groundwork for precision-adapted surveillance and treatment protocols. Pattern-stratified trials and health-economic evaluations are now needed to assess whether this approach improves outcomes and optimizes resource allocation.<\/jats:p>","DOI":"10.3390\/cancers17182944","type":"journal-article","created":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T12:15:17Z","timestamp":1757420117000},"page":"2944","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Triangulating Timing, Tropism and Burden of Sarcoma Metastases: Toward Precision Surveillance and Therapy in a Real-World-Time Cohort"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5090-4935","authenticated-orcid":false,"given":"Philip","family":"Heesen","sequence":"first","affiliation":[{"name":"Faculty of Medicine, University of Zurich, Raemistrasse 71, 8006 Zurich, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dario","family":"Feusi","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Zurich, Raemistrasse 71, 8006 Zurich, Switzerland"},{"name":"Faculty of Health Sciences & Medicine, University of Lucerne, Frohburgstrasse 3, 6002 Luzern, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bettina","family":"Vogel","sequence":"additional","affiliation":[{"name":"Swiss Sarcoma Network SSN, LUKS Sarcoma-IPU, University Teaching Hospital LUKS, Spitalstrasse, 6000 Lucerne, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8780-7701","authenticated-orcid":false,"given":"Gabriela","family":"Studer","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences & Medicine, University of Lucerne, Frohburgstrasse 3, 6002 Luzern, Switzerland"},{"name":"Department of Radiation Oncology, LUKS Sarcoma-IPU, University Teaching Hospital LUKS, Spitalstrasse, 6000 Lucerne, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6453-3947","authenticated-orcid":false,"given":"Bruno","family":"Fuchs","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences & Medicine, University of Lucerne, Frohburgstrasse 3, 6002 Luzern, Switzerland"},{"name":"Department of Orthopaedics and Trauma, LUKS Sarcoma-IPU, University Teaching Hospital LUKS, Spitalstrasse, 6000 Lucerne, Switzerland"},{"name":"Department of Orthopaedics and Trauma, Kantonsspital Winterthur, KSW Sarcoma Center, Brauerstrasse 15, 8400 Winterthur, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"on behalf of the Swiss Sarcoma Network","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,9]]},"reference":[{"key":"ref_1","unstructured":"Antonescu, C., and Blay, J. (2020). WHO Classification of Tumours: Soft Tissue and Bone Tumours, World Health Organization. [5th ed.]."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1348","DOI":"10.1016\/j.annonc.2021.07.006","article-title":"Soft tissue and visceral sarcomas: ESMO\u2013EURACAN\u2013GENTURIS Clinical Practice Guidelines for diagnosis, treatment and follow-up","volume":"32","author":"Gronchi","year":"2021","journal-title":"Ann. Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"815","DOI":"10.6004\/jnccn.2022.0035","article-title":"Soft Tissue Sarcoma, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology","volume":"20","author":"Kane","year":"2022","journal-title":"J. Natl. Compr. Cancer Netw."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"102312","DOI":"10.1016\/j.ctrv.2021.102312","article-title":"SELNET clinical practice guidelines for soft tissue sarcoma and GIST","volume":"102","author":"Blay","year":"2022","journal-title":"Cancer Treat. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1016\/j.jos.2021.03.013","article-title":"Impact of surgical resection on survival in patients with metastatic soft tissue sarcoma and comparison between synchronous and metachronous metastases","volume":"27","author":"Outani","year":"2022","journal-title":"J. Orthop. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e6799","DOI":"10.1097\/MD.0000000000006799","article-title":"Clinical analysis and prognosis of synchronous and metachronous multiple primary malignant tumors","volume":"96","author":"Lv","year":"2017","journal-title":"Medicine"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1016\/j.cell.2016.11.037","article-title":"Emerging Biological Principles of Metastasis","volume":"168","author":"Lambert","year":"2017","journal-title":"Cell"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1038\/s41392-020-0134-x","article-title":"Molecular principles of metastasis: A hallmark of cancer revisited","volume":"5","author":"Lambert","year":"2020","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e18","DOI":"10.1016\/S1470-2045(19)30718-1","article-title":"Characterisation and classification of oligometastatic disease: A European Society for Radiotherapy and Oncology and European Organisation for Research and Treatment of Cancer consensus recommendation","volume":"21","author":"Guckenberger","year":"2020","journal-title":"Lancet Oncol."},{"key":"ref_10","first-page":"12","article-title":"Management of oligometastatic disease in soft tissue sarcomas","volume":"9","author":"Gonzalez","year":"2023","journal-title":"J. Cancer Metastasis Treat."},{"key":"ref_11","first-page":"939","article-title":"Multidisciplinary Management of Oligometastatic Soft Tissue Sarcoma","volume":"38","author":"Webber","year":"2018","journal-title":"Am. Soc. Clin. Oncol. Educ. Book"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"423","DOI":"10.12688\/f1000research.52546.3","article-title":"Better survival of patients with oligo compared with polymetastatic cancers: A systematic review and meta-analysis of 173 studies","volume":"10","author":"Petrelli","year":"2021","journal-title":"F1000Research"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1007\/s12032-022-01788-8","article-title":"A critical review on oligometastatic disease: A radiation oncologist\u2019s perspective","volume":"39","author":"Pacifico","year":"2022","journal-title":"Med. Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"8491","DOI":"10.18632\/oncotarget.3455","article-title":"The biology and treatment of oligometastatic cancer","volume":"6","author":"Reyes","year":"2015","journal-title":"Oncotarget"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"493","DOI":"10.5435\/JAAOS-D-21-00944","article-title":"Musculoskeletal Metastasis From Soft-tissue Sarcomas: A Review of the Literature","volume":"30","author":"Seldon","year":"2022","journal-title":"J. Am. Acad. Orthop. Surg."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"849456","DOI":"10.1155\/2012\/849456","article-title":"The molecular biology of soft-tissue sarcomas and current trends in therapy","volume":"2012","author":"Quesada","year":"2012","journal-title":"Sarcoma"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e526","DOI":"10.1634\/theoncologist.2017-0383","article-title":"Minimal Increase in Survival Throughout the Years in Patients with Soft Tissue Sarcoma with Synchronous Metastases: Results of a Population-Based Study","volume":"24","author":"Vos","year":"2019","journal-title":"Oncologist"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1080\/1357714021000022168","article-title":"The treatment and outcome of patients with soft tissue sarcomas and synchronous metastases","volume":"6","author":"Kane","year":"2002","journal-title":"Sarcoma"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"11085","DOI":"10.1007\/s00432-023-05007-3","article-title":"The different clonal origins of metachronous and synchronous metastases","volume":"149","author":"Gofrit","year":"2023","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"100385","DOI":"10.1016\/j.jbo.2021.100385","article-title":"The patterns of distant metastasis and prognostic factors in patients with primary metastatic Ewing sarcoma of the bone","volume":"30","author":"Zhang","year":"2021","journal-title":"J. Bone Oncol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"5098","DOI":"10.1002\/cncr.33189","article-title":"Curability of patients with lymph node metastases from extremity soft-tissue sarcoma","volume":"126","author":"Basile","year":"2020","journal-title":"Cancer"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Acem, I., Martin, E., van Houdt, W.J., van de Sande, M.A.J., Grunhagen, D.J., Verhoef, C., and Monaco, C. (2021). The Association of Metastasis Pattern and Management of Metastatic Disease with Oncological Outcomes in Patients with Malignant Peripheral Nerve Sheath Tumors: A Multicenter Cohort Study. Cancers, 13.","DOI":"10.3390\/cancers13205115"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"7923","DOI":"10.1245\/s10434-021-09946-4","article-title":"Management of Soft Tissue Sarcomas in Extremities: Variation in Treatment Recommendations and Surveillance According to Specialty and Continent","volume":"28","author":"Acem","year":"2021","journal-title":"Ann. Surg. Oncol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"5089","DOI":"10.21873\/anticanres.15325","article-title":"Treatments and Outcomes in Oligometastatic Soft Tissue Soft Sarcoma\u2014A Single Centre Retrospective Analysis","volume":"41","author":"Walls","year":"2021","journal-title":"Anticancer Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e35564","DOI":"10.1002\/cncr.35564","article-title":"Clinical benefit and fragility evaluation of systemic therapy trials for advanced soft tissue sarcoma","volume":"131","author":"Braik","year":"2025","journal-title":"Cancer"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1802","DOI":"10.1158\/2159-8290.CD-23-0153","article-title":"The MDM2-p53 Antagonist Brigimadlin (BI 907828) in Patients with Advanced or Metastatic Solid Tumors: Results of a Phase Ia, First-in-Human, Dose-Escalation Study","volume":"13","author":"LoRusso","year":"2023","journal-title":"Cancer Discov."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1136\/bmjebm-2018-111111","article-title":"Assessing function of electronic health records for real-world data generation","volume":"24","author":"Guinn","year":"2019","journal-title":"BMJ Evid. Based Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00392-016-1025-6","article-title":"Electronic health records to facilitate clinical research","volume":"106","author":"Cowie","year":"2017","journal-title":"Clin. Res. Cardiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"S30","DOI":"10.1097\/MLR.0b013e31829b1dbd","article-title":"Caveats for the use of operational electronic health record data in comparative effectiveness research","volume":"51","author":"Hersh","year":"2013","journal-title":"Med. Care"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1002\/cncr.25538","article-title":"Trends in survival for patients with metastatic soft-tissue sarcoma","volume":"117","author":"Italiano","year":"2011","journal-title":"Cancer"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"7891","DOI":"10.1245\/s10434-021-09942-8","article-title":"Late Local Recurrence and Metastasis in Soft Tissue Sarcoma of the Extremities and Trunk Wall: Better Outcome After Treatment of Late Events Compared with Early","volume":"28","author":"Ghanei","year":"2021","journal-title":"Ann. Surg. Oncol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"7930","DOI":"10.1245\/s10434-024-16103-0","article-title":"The Landmark Series: Multimodal Management of Oligometastatic Sarcoma","volume":"31","author":"Bonvalot","year":"2024","journal-title":"Ann. Surg. Oncol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Szturz, P., Nevens, D., and Vermorken, J.B. (2020). Oligometastatic Disease Management: Finding the Sweet Spot. Front. Oncol., 10.","DOI":"10.3389\/fonc.2020.617793"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.clon.2014.09.010","article-title":"Effect on survival of local ablative treatment of metastases from sarcomas: A study of the French sarcoma group","volume":"27","author":"Falk","year":"2015","journal-title":"Clin. Oncol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Shah, N.K., Yegya-Raman, N., Jones, J.A., and Shabason, J.E. (2021). Radiation Therapy in Metastatic Soft Tissue Sarcoma: From Palliation to Ablation. Cancers, 13.","DOI":"10.3390\/cancers13194775"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/18\/2944\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:42:35Z","timestamp":1760035355000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/18\/2944"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,9]]},"references-count":35,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["cancers17182944"],"URL":"https:\/\/doi.org\/10.3390\/cancers17182944","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,9]]}}}