{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T20:32:29Z","timestamp":1779136349147,"version":"3.51.4"},"reference-count":78,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T00:00:00Z","timestamp":1773619200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Government, Ministry of Health"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Soft-tissue sarcomas (STSs) comprise a rare, heterogeneous group of mesenchymal malignancies in which histologic grade remains the strongest determinant of outcome, metastatic risk, and therapeutic strategy. Intermediate\/high-grade STSs exhibit a pronounced propensity for early distant relapse, yet growing evidence indicates that metastatic behaviour is not uniform. Within this spectrum, an oligometastatic phenotype, characterised by a limited number of metastases, often confined to the lung, has emerged as a clinically and biologically distinct state associated with more indolent metastatic kinetics and improved survival when treated with aggressive local interventions. However, the criteria that define true oligometastatic STSs remain unsettled, and prospective evidence is lacking. Emerging molecular and immunological correlates provide a potential framework for biological triage. Low genomic complexity (low-risk CINSARC), a B-cell\/TLS-rich tumour microenvironment, high immune-cytotoxic signatures, and persistently low or undetectable circulating tumour DNA (ctDNA) are each linked to reduced metastatic competence and may underpin oligometastatic trajectories. Conversely, high chromosomal instability, immunosuppressive microenvironments, and elevated ctDNA levels align with covertly polymetastatic biology despite limited radiographic disease. In this context, artificial intelligence and machinelearning approaches applied to computational genomics, immune profiling, imaging, and liquid-biopsy data offer a powerful strategy to integrate these multi-dimensional features and refine predictions of metastatic behaviour in STS. Oligometastatic STS therefore represents a biologically definable subset amenable to multimodal management integrating local ablative therapies, systemic agents, and immune-based strategies. Prospective, biomarker-stratified trials are needed to validate selection frameworks and optimise treatment sequencing in this evolving therapeutic space.<\/jats:p>","DOI":"10.3390\/genes17030323","type":"journal-article","created":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T13:32:07Z","timestamp":1773667927000},"page":"323","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Emerging Genomic and Immunological Correlates Defining Oligometastatic Trajectories in Intermediate\/High-Grade Soft-Tissue Sarcomas"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2901-3855","authenticated-orcid":false,"given":"Alessandro","family":"Ottaiano","sequence":"first","affiliation":[{"name":"Istituto Nazionale Tumori di Napoli, IRCCS \u201cG. Pascale\u201d, Via Mariano Semmola, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6431-8278","authenticated-orcid":false,"given":"Francesco","family":"Sabbatino","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery, and Dentistry, University of Salerno, 84081 Baronissi, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmine","family":"Picone","sequence":"additional","affiliation":[{"name":"Istituto Nazionale Tumori di Napoli, IRCCS \u201cG. Pascale\u201d, Via Mariano Semmola, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nadia","family":"Di Carluccio","sequence":"additional","affiliation":[{"name":"Department of Economics, University of Foggia, 71121 Foggia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Igino","family":"Simonetti","sequence":"additional","affiliation":[{"name":"Istituto Nazionale Tumori di Napoli, IRCCS \u201cG. Pascale\u201d, Via Mariano Semmola, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9128-3186","authenticated-orcid":false,"given":"Annabella","family":"Di Mauro","sequence":"additional","affiliation":[{"name":"Istituto Nazionale Tumori di Napoli, IRCCS \u201cG. Pascale\u201d, Via Mariano Semmola, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3019-354X","authenticated-orcid":false,"given":"Salvatore","family":"Tafuto","sequence":"additional","affiliation":[{"name":"Istituto Nazionale Tumori di Napoli, IRCCS \u201cG. Pascale\u201d, Via Mariano Semmola, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"73","DOI":"10.3949\/ccjm.89a.21078","article-title":"Soft tissue sarcoma: Recognizing a rare disease","volume":"89","author":"Ardakani","year":"2022","journal-title":"Clevel. Clin. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1016\/j.suc.2016.05.005","article-title":"Epidemiology and Etiology of Sarcomas","volume":"96","author":"Hui","year":"2016","journal-title":"Surg. Clin. N. Am."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Zhou, J., Xu, S., Long, Y., He, R., Cai, J., Ding, N., and Su, Y. (2025). Global burden of soft tissue sarcomas in 204 countries and territories from 1990 to 2021: Data from the global burden of disease study 2021. BMC Public Health, 25.","DOI":"10.1186\/s12889-025-22782-5"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/2045-3329-2-14","article-title":"The epidemiology of sarcoma","volume":"2","author":"Burningham","year":"2012","journal-title":"Clin. Sarcoma Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1002\/pbc.23252","article-title":"Soft tissue sarcoma across the age spectrum: A population-based study from the Surveillance Epidemiology and End Results database","volume":"57","author":"Ferrari","year":"2011","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.currproblcancer.2019.06.005","article-title":"Contemporary management of metastatic soft tissue sarcoma","volume":"43","author":"Bui","year":"2019","journal-title":"Curr. Probl. Cancer"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1448","DOI":"10.5858\/2006-130-1448-GOSTSR","article-title":"Grading of soft tissue sarcomas: Review and update","volume":"130","author":"Coindre","year":"2006","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1097\/PAT.0000000000000048","article-title":"Grading of soft tissue sarcomas: From histological to molecular assessment","volume":"46","author":"Neuville","year":"2014","journal-title":"Pathology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1914","DOI":"10.1002\/1097-0142(20010515)91:10<1914::AID-CNCR1214>3.0.CO;2-3","article-title":"Predictive value of grade for metastasis development in the main histologic types of adult soft tissue sarcomas: A study of 1240 patients from the French Federation of Cancer Centers Sarcoma Group","volume":"91","author":"Coindre","year":"2001","journal-title":"Cancer"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1007\/s12032-011-9970-4","article-title":"A retrospective statistical analysis of high-grade soft tissue sarcomas","volume":"29","author":"Kolovich","year":"2012","journal-title":"Med. Oncol."},{"key":"ref_11","first-page":"67","article-title":"Soft Tissue Sarcoma of Extremities: Descriptive Epidemiological Analysis According to National Population-based Study","volume":"10","author":"Ebrahimpour","year":"2022","journal-title":"Arch. Bone Jt. Surg."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1404","DOI":"10.1002\/cam4.288","article-title":"Epidemiology and survivorship of soft tissue sarcomas in adults: A national cancer database report","volume":"3","author":"Corey","year":"2014","journal-title":"Cancer Med."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Han, Y., Shah, A., Yao, Y., Mutter, R.W., and Xu-Welliver, M. (2025). Clinical Differences Among Histological Categories of Sarcoma: Insights from 97,062 Patients. Cancers, 17.","DOI":"10.3390\/cancers17101706"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"42","DOI":"10.21037\/cco.2018.08.02","article-title":"Advances of systemic treatment for adult soft-tissue sarcoma","volume":"7","author":"Liu","year":"2018","journal-title":"Chin. Clin. Oncol."},{"key":"ref_15","first-page":"1","article-title":"Soft tissue sarcoma. Epidemiology and prognosis in 508 patients","volume":"259","author":"Gustafson","year":"1994","journal-title":"Acta Orthop. Scand. Suppl."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1200\/JCO.1995.13.1.8","article-title":"Oligometastases","volume":"13","author":"Hellman","year":"1995","journal-title":"J. Clin. Oncol."},{"key":"ref_17","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_18","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_19","doi-asserted-by":"crossref","unstructured":"Roeder, F. (2020). Radiation Therapy in Adult Soft Tissue Sarcoma\u2014Current Knowledge and Future Directions: A Review and Expert Opinion. Cancers, 12.","DOI":"10.3390\/cancers12113242"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1007\/s11547-018-0912-5","article-title":"Stereotactic body radiotherapy for oligometastatic soft tissue sarcoma","volume":"123","author":"Loi","year":"2018","journal-title":"Radiol. Med."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Lopes-Br\u00e1s, R., Mu\u00f1oz, P., Netto, E., Fern\u00e1ndez, J.\u00c1., Serradilla-Mart\u00edn, M., Lozano, P., Esperan\u00e7a-Martins, M., Blanco-Fern\u00e1ndez, G., Gonz\u00e1lez-L\u00f3pez, J.A., and Mu\u00f1oz-Casares, F.C. (2025). Ibero-American Consensus for the Management of Liver Metastases of Soft Tissue Sarcoma: Updated Review and Clinical Recommendations. Cancers, 17.","DOI":"10.3390\/cancers17081295"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1038\/nm.2174","article-title":"Validated prediction of clinical outcome in sarcomas and multiple types of cancer on the basis of a gene expression signature related to genome complexity","volume":"16","author":"Chibon","year":"2010","journal-title":"Nat. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"5480","DOI":"10.1038\/s41598-017-05726-x","article-title":"The CINSARC signature as a prognostic marker for clinical outcome in multiple neoplasms","volume":"7","author":"Lesluyes","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Filleron, T., Le Guellec, S., Chevreau, C., Cabarrou, B., Lesluyes, T., Lodin, S., Massoubre, A., Mounier, M., Poublanc, M., and Chibon, F. (2020). Value of peri-operative chemotherapy in patients with CINSARC high-risk localized grade 1 or 2 soft tissue sarcoma: Study protocol of the target selection phase III CHIC-STS trial. BMC Cancer, 20.","DOI":"10.1186\/s12885-020-07207-3"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1038\/s41586-019-1906-8","article-title":"B cells are associated with survival and immunotherapy response in sarcoma","volume":"577","author":"Petitprez","year":"2020","journal-title":"Nature"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Kendal, J.K., Shehata, M.S., Lofftus, S.Y., and Crompton, J.G. (2023). Cancer-Associated B Cells in Sarcoma. Cancers, 15.","DOI":"10.3390\/cancers15030622"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e003687","DOI":"10.1136\/jitc-2021-003687","article-title":"Immunologic constant of rejection signature is prognostic in soft-tissue sarcoma and refines the CINSARC signature","volume":"10","author":"Bertucci","year":"2022","journal-title":"J. Immunother. Cancer"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1002\/cac2.12461","article-title":"Clinical utility of circulating tumor DNA sequencing with a large panel in patients with advanced soft-tissue sarcomas","volume":"43","author":"Blanchi","year":"2023","journal-title":"Cancer Commun."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1722","DOI":"10.1007\/s10147-025-02813-2","article-title":"Advances in liquid biopsy for bone and soft-tissue sarcomas","volume":"30","author":"Wang","year":"2025","journal-title":"Int. J. Clin. Oncol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3406","DOI":"10.1038\/s41467-022-30496-0","article-title":"Clinical genomic profiling in the management of patients with soft tissue and bone sarcoma","volume":"13","author":"Gounder","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e002345","DOI":"10.1136\/jitc-2021-002345","article-title":"Anti-PD-1 elicits regression of undifferentiated pleomorphic sarcomas with UV-mutation signatures","volume":"9","author":"Cheung","year":"2021","journal-title":"J. Immunother. Cancer"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"105220","DOI":"10.1016\/j.ebiom.2024.105220","article-title":"Spatial distribution of tumour immune infiltrate predicts outcomes of patients with high-risk soft tissue sarcomas after neoadjuvant chemotherapy","volume":"106","author":"Pasquali","year":"2024","journal-title":"eBioMedicine"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Heesen, P., Feusi, D., Vogel, B., Studer, G., Fuchs, B., and On Behalf Of The Swiss Sarcoma Network (2025). Triangulating Timing, Tropism and Burden of Sarcoma Metastases: Toward Precision Surveillance and Therapy in a Real-World-Time Cohort. Cancers, 9.","DOI":"10.3390\/cancers17182944"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/S1470-2045(16)00010-3","article-title":"Development and external validation of two nomograms to predict overall survival and occurrence of distant metastases in adults after surgical resection of localised soft-tissue sarcomas of the extremities: A retrospective analysis","volume":"17","author":"Callegaro","year":"2016","journal-title":"Lancet Oncol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.ejca.2018.01.071","article-title":"High-risk soft tissue sarcomas treated with perioperative chemotherapy: Improving prognostic classification in a randomised clinical trial","volume":"93","author":"Pasquali","year":"2018","journal-title":"Eur. J. Cancer"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4376","DOI":"10.1245\/s10434-022-11442-2","article-title":"Sarculator is a Good Model to Predict Survival in Resected Extremity and Trunk Sarcomas in US Patients","volume":"29","author":"Voss","year":"2022","journal-title":"Ann. Surg. Oncol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1200\/JCO.2002.20.3.791","article-title":"Postoperative nomogram for 12-year sarcoma-specific death","volume":"20","author":"Kattan","year":"2002","journal-title":"J. Clin. Oncol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1245\/s10434-015-4849-9","article-title":"Validation of a Soft Tissue Sarcoma Nomogram Using a National Cancer Registry","volume":"22","author":"Bagaria","year":"2015","journal-title":"Ann. Surg. Oncol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"8851354","DOI":"10.1155\/2021\/8851354","article-title":"The Influence of Personalised Sarcoma Care (PERSARC) Prediction Modelling on Clinical Decision Making in a Multidisciplinary Setting","volume":"2021","author":"Hagenmaier","year":"2021","journal-title":"Sarcoma"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1002\/jso.26337","article-title":"External validation and adaptation of a dynamic prediction model for patients with high-grade extremity soft tissue sarcoma","volume":"123","author":"Fiocco","year":"2021","journal-title":"J. Surg. Oncol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1016\/j.neo.2019.05.004","article-title":"The FUS-DDIT3 Interactome in Myxoid Liposarcoma","volume":"21","author":"Yu","year":"2019","journal-title":"Neoplasia"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.1016\/j.ccell.2018.05.002","article-title":"The SS18-SSX Fusion Oncoprotein Hijacks BAF Complex Targeting and Function to Drive Synovial Sarcoma","volume":"33","author":"McBride","year":"2018","journal-title":"Cancer Cell"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Kirilin, E.M., Fetisov, T.I., Moiseeva, N.I., Lesovaya, E.A., Laletina, L.A., Makhmudova, L.F., Manikaylo, A.E., Fomina, L.Y., Burov, D.A., and Bokhyan, B.Y. (2022). Soft Tissue Sarcoma Study: Association of Genetic Alterations in the Apoptosis Pathways with Chemoresistance to Doxorubicin. Cancers, 14.","DOI":"10.3390\/cancers14071796"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/s41698-024-00776-7","article-title":"Genetic and epigenetic characterization of sarcoma stem cells across subtypes identifies EZH2 as a therapeutic target","volume":"9","author":"Davis","year":"2025","journal-title":"NPJ Precis. Oncol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1496","DOI":"10.2174\/0113895575270904231129062137","article-title":"Targeted Inhibition of the PI3K\/Akt\/mTOR Signaling Axis: Potential for Sarcoma Therapy","volume":"24","author":"Wani","year":"2024","journal-title":"Mini-Rev. Med. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1002\/path.6140","article-title":"The spectrum and significance of secondary (co-occurring) genetic alterations in sarcomas: The hallmarks of sarcomagenesis","volume":"260","author":"Dermawan","year":"2023","journal-title":"J. Pathol."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Paudel, A., Chattopadhyay, P., Rose, B., Watson, A., D\u2019Amato, G., Trent, J., Bialick, S., and Jonczak, E. (2025). Systemic Treatment in Soft Tissue Sarcomas: Are We Making a Difference?. Cancers, 17.","DOI":"10.3390\/cancers17050889"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1879","DOI":"10.1016\/S0140-6736(12)60651-5","article-title":"Pazopanib for metastatic soft-tissue sarcoma (PALETTE): A randomised, double-blind, placebo-controlled phase 3 trial","volume":"379","author":"Blay","year":"2012","journal-title":"Lancet"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/s11864-017-0457-1","article-title":"Phase III Soft Tissue Sarcoma Trials: Success or Failure?","volume":"18","author":"Lee","year":"2017","journal-title":"Curr. Treat. Options Oncol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1002\/1097-0142(19920201)69:3<662::AID-CNCR2820690311>3.0.CO;2-I","article-title":"Five-year survival after pulmonary metastasectomy for adult soft tissue sarcoma","volume":"69","author":"Casson","year":"1992","journal-title":"Cancer"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"S1305","DOI":"10.21037\/jtd.2017.03.177","article-title":"Survival and prognostic factors following pulmonary metastasectomy for sarcoma","volume":"9","author":"Marulli","year":"2017","journal-title":"J. Thorac. Dis."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2649","DOI":"10.21037\/jtd-2019-pm-13","article-title":"Pulmonary metastasectomy in soft tissue sarcomas: A systematic review","volume":"13","author":"Stamenovic","year":"2021","journal-title":"J. Thorac. Dis."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"109824","DOI":"10.1016\/j.radonc.2023.109824","article-title":"Stereotactic body radiation therapy for sarcoma pulmonary metastases","volume":"187","author":"Lebow","year":"2023","journal-title":"Radiother. Oncol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1186\/s13014-023-02255-y","article-title":"Treatment outcomes of stereotactic body radiation therapy for pulmonary metastasis from sarcoma: A multicenter, retrospective study","volume":"18","author":"Lee","year":"2023","journal-title":"Radiat. Oncol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1186\/s12957-022-02781-1","article-title":"Stereotactic body radiotherapy for recurrent and oligometastatic soft tissue sarcoma","volume":"20","author":"Feng","year":"2022","journal-title":"World J. Surg. Oncol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"17588359211070646","DOI":"10.1177\/17588359211070646","article-title":"Stereotactic radiotherapy for soft tissue and bone sarcomas: Real-world evidence","volume":"14","author":"Teterycz","year":"2022","journal-title":"Ther. Adv. Med. Oncol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1097\/PPO.0000000000000551","article-title":"Stereotactic Body Radiotherapy in Oligomestatic\/Oligoprogressive Sarcoma: Safety and Effectiveness Beyond Intrinsic Radiosensitivity","volume":"27","author":"Greto","year":"2021","journal-title":"Cancer J."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1080\/0284186X.2018.1521986","article-title":"Survival and prognostic factors of pulmonary oligometastases treated with stereotactic body radiotherapy","volume":"58","author":"Sharma","year":"2019","journal-title":"Acta Oncol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1001\/jamaoncol.2020.6146","article-title":"Safety and Survival Rates Associated With Ablative Stereotactic Radiotherapy for Patients With Oligometastatic Cancer: A Systematic Review and Meta-analysis","volume":"7","author":"Lehrer","year":"2021","journal-title":"JAMA Oncol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1007\/s00270-013-0644-9","article-title":"Outcome after radiofrequency ablation of sarcoma lung metastases","volume":"37","author":"Koelblinger","year":"2014","journal-title":"Cardiovasc. Interv. Radiol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"8473","DOI":"10.2147\/CMAR.S333721","article-title":"Clinical Outcome in Soft Tissue Sarcoma Patients with Lung Metastasis Who Received Metastasectomy and\/or Radiofrequency Ablation: Tokai Musculoskeletal Oncology Consortium Study","volume":"13","author":"Nakamura","year":"2021","journal-title":"Cancer Manag. Res."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Aiyer, S., Kim, T.-H., Collier, K., Pollock, R., Verschraegen, C., Stover, D.G., and Tinoco, G. (2025). Unlocking the Potential of ctDNA in Sarcomas: A Review of Recent Advances. Cancers, 17.","DOI":"10.3390\/cancers17061040"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Roulleaux Dugage, M., Nassif, E.F., Italiano, A., and Bahleda, R. (2021). Improving Immunotherapy Efficacy in Soft-Tissue Sarcomas: A Biomarker Driven and Histotype Tailored Review. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.775761"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Kim, N.J., Yoon, J.H., Tuomi, A.C., Lee, J., and Kim, D. (2023). In-situ tumor vaccination by percutaneous ablative therapy and its synergy with immunotherapeutics: An update on combination therapy. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1118845"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1016\/j.ymthe.2023.01.017","article-title":"Immunomodulatory effect of locoregional therapy in the tumor microenvironment","volume":"31","author":"Xie","year":"2023","journal-title":"Mol. Ther."},{"key":"ref_66","first-page":"510","article-title":"Local tumour ablative therapies: Opportunities for maximising immune engagement and activation","volume":"1846","author":"Power","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.canlet.2013.08.024","article-title":"The impact of radiation therapy on the antitumor immunity: Local effects and systemic consequences","volume":"356","author":"Lumniczky","year":"2015","journal-title":"Cancer Lett."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2053","DOI":"10.1016\/S0140-6736(24)01812-9","article-title":"Safety and efficacy of pembrolizumab, radiation therapy, and surgery versus radiation therapy and surgery for stage III soft tissue sarcoma of the extremity (SU2C-SARC032): An open-label, randomised clinical trial","volume":"404","author":"Mowery","year":"2024","journal-title":"Lancet"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1186\/s13045-024-01580-3","article-title":"New strategies in soft tissue sarcoma treatment","volume":"17","author":"Ghazzi","year":"2024","journal-title":"J. Hematol. Oncol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.biocel.2018.03.004","article-title":"HDAC inhibitors as epigenetic regulators for cancer immunotherapy","volume":"98","author":"Conte","year":"2018","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"155992","DOI":"10.1016\/j.prp.2025.155992","article-title":"EZH2 regulatory roles in cancer immunity and immunotherapy","volume":"270","author":"Mortezaee","year":"2025","journal-title":"Pathol. Res. Pract."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Van Ijzendoorn, D.G.P., Szuhai, K., Briaire-de Bruijn, I.H., Kostine, M., Kuijjer, M.L., and Bov\u00e9e, J.V.M.G. (2019). Machine learning analysis of gene expression data reveals novel diagnostic and prognostic biomarkers and identifies therapeutic targets for soft tissue sarcomas. PLoS Comput. Biol., 15.","DOI":"10.1371\/journal.pcbi.1006826"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Esperan\u00e7a-Martins, M., Vasques, H., Ravasqueira, M.S., Lemos, M.M., Fonseca, F., Coutinho, D., L\u00f3pez, J.A., Huang, R.S.P., Dias, S., and Gallego-Paez, L. (2025). Transcriptomic-Based Classification Identifies Prognostic Subtypes and Therapeutic Strategies in Soft Tissue Sarcomas. Cancers, 17.","DOI":"10.3390\/cancers17172861"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"6773","DOI":"10.1016\/j.acra.2025.06.027","article-title":"Performance of Radiomics and Deep Learning Models in Predicting Distant Metastases in Soft Tissue Sarcomas: A Systematic Review and Meta-analysis","volume":"32","author":"Mirghaderi","year":"2025","journal-title":"Acad. Radiol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"103131","DOI":"10.1016\/j.ebiom.2020.103131","article-title":"High throughput profiling of undifferentiated pleomorphic sarcomas identifies two main subgroups with distinct immune profile, clinical outcome and sensitivity to targeted therapies","volume":"62","author":"Toulmonde","year":"2020","journal-title":"eBioMedicine"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"145105","DOI":"10.1016\/j.gene.2020.145105","article-title":"Identification of a survival-related signature for sarcoma patients through integrated transcriptomic and proteomic profiling analyses","volume":"764","author":"Zhang","year":"2021","journal-title":"Gene"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.omto.2021.12.007","article-title":"A novel immune-related gene signature predicting survival in sarcoma patients","volume":"24","author":"Ren","year":"2021","journal-title":"Mol. Ther. Oncolytics"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Waqas, A., Tripathi, A., Ramachandran, R.P., Stewart, P.A., and Rasool, G. (2024). Multimodal data integration for oncology in the era of deep neural networks: A review. Front. Artif. Intell., 7.","DOI":"10.3389\/frai.2024.1408843"}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/17\/3\/323\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T13:58:09Z","timestamp":1774533489000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/17\/3\/323"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,16]]},"references-count":78,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["genes17030323"],"URL":"https:\/\/doi.org\/10.3390\/genes17030323","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,16]]}}}