{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T07:26:05Z","timestamp":1788852365599,"version":"build-2803163510"},"reference-count":57,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,12,19]],"date-time":"2023-12-19T00:00:00Z","timestamp":1702944000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["22K15571"],"award-info":[{"award-number":["22K15571"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Of the drugs used in second\u2010line chemotherapy for soft tissue sarcoma (STS), trabectedin is effective for liposarcoma and leiomyosarcoma (L\u2010sarcoma), eribulin for liposarcoma, and pazopanib for non\u2010liposarcoma. The indications for these drugs in STS other than L\u2010sarcoma have not been established. Here we explored the prognosis, mutation profiles, and drug\u2010response factors in STS using real\u2010world big data. Clinicogenomic data on 1761 patients with sarcoma who underwent FoundationOne CDx were obtained from a national database in Japan. Patients with\n                    <jats:italic>TP53<\/jats:italic>\n                    and\n                    <jats:italic>KDM2D<\/jats:italic>\n                    mutations had a significantly shorter survival period of 253 (95% CI, 99\u2013404) and 330 (95% CI, 20\u2013552) days, respectively, than those without mutations. Non\u2010supervised clustering based on mutation profiles generated 13 tumor clusters. The response rate (RR) to trabectedin was highest in an\n                    <jats:italic>MDM2<\/jats:italic>\n                    \u2010amplification cluster (odds ratio [OR]: 2.2;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.2). The RR was lowest for eribulin in an\n                    <jats:italic>MDM2<\/jats:italic>\n                    \u2010amplification cluster (OR: 0.4;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.03) and highest in a\n                    <jats:italic>TERT<\/jats:italic>\n                    \u2010mutation cluster (OR: 3.0;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.03). The RR was highest for pazopanib in a\n                    <jats:italic>PIK3CA<\/jats:italic>\n                    \/\n                    <jats:italic>PTEN<\/jats:italic>\n                    \u2010wild type cluster (OR: 2.1;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.03). In particular, patients harboring mutations in genes regulating the PI3K\/Akt\/mTOR pathway had a lower RR than patients without mutations (OR: 0.3;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.04). In STS, mutation profiles were more useful in predicting the drug response than histology. The present study demonstrated the potential of tailored therapy guided by mutation profiles established by comprehensive genomic profiling testing in optimizing second\u2010line chemotherapy for STS. The findings of this study will hopefully contribute some valuable insights into enhancing STS treatment strategies and outcomes.\n                  <\/jats:p>","DOI":"10.1111\/cas.16050","type":"journal-article","created":{"date-parts":[[2023,12,20]],"date-time":"2023-12-20T00:50:41Z","timestamp":1703033441000},"page":"575-588","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Factors predictive of second\u2010line chemotherapy in soft tissue sarcoma: An analysis of the National Genomic Profiling Database"],"prefix":"10.1111","volume":"115","author":[{"given":"Takao","family":"Mochizuki","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery, Saitama Medical Center Jichi Medical University  Saitama Japan"},{"name":"Department of Musculoskeletal Oncology Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0491-7142","authenticated-orcid":false,"given":"Masachika","family":"Ikegami","sequence":"additional","affiliation":[{"name":"Department of Musculoskeletal Oncology Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital  Tokyo Japan"},{"name":"Division of Cellular Signaling National Cancer Center Research Institute  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toru","family":"Akiyama","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Saitama Medical Center Jichi Medical University  Saitama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,12,19]]},"reference":[{"key":"e_1_2_12_2_1","volume-title":"WHO Classification of Tumours. 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