{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T17:24:37Z","timestamp":1781889877066,"version":"3.54.5"},"reference-count":19,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T00:00:00Z","timestamp":1766966400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T00:00:00Z","timestamp":1766966400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Cancer Res Clin Oncol"],"DOI":"10.1007\/s00432-025-06291-x","type":"journal-article","created":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T17:22:58Z","timestamp":1767028978000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Subgroup analyses of the phase 3 FOCUS study of melphalan\/hepatic delivery system in patients with unresectable metastatic uveal melanoma"],"prefix":"10.1007","volume":"152","author":[{"given":"Jonathan S.","family":"Zager","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marlana","family":"Orloff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pier Francesco","family":"Ferrucci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junsung","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Eschelman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evan S.","family":"Glazer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aslam","family":"Ejaz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erika","family":"Richtig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Ochsenreither","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunil A.","family":"Reddy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael C.","family":"Lowe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgia M.","family":"Beasley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja","family":"Gesierich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Gschnell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reinhard","family":"Dummer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Arance","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen William","family":"Fenwick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph J.","family":"Sacco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johnny","family":"John","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Wheater","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian H.","family":"Ottensmeier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,12,29]]},"reference":[{"issue":"11","key":"6291_CR1","doi-asserted-by":"publisher","first-page":"2364","DOI":"10.1038\/s41591-022-02015-7","volume":"28","author":"RD Carvajal","year":"2022","unstructured":"Carvajal RD, Butler MO, Shoushtari AN et al (2022) Clinical and molecular response to tebentafusp in previously treated patients with metastatic uveal melanoma: a phase 2 trial. Nat Med 28(11):2364\u20132373","journal-title":"Nat Med"},{"issue":"2","key":"6291_CR2","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1038\/s41571-022-00714-1","volume":"20","author":"RD Carvajal","year":"2023","unstructured":"Carvajal RD, Sacco JJ, Jager MJ et al (2023) Advances in the clinical management of uveal melanoma. Nat Rev Clin Oncol 20(2):99\u2013115","journal-title":"Nat Rev Clin Oncol"},{"key":"6291_CR3","unstructured":"Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. Published: May 28, 2009 (v4.03: June 14, 2010). U.S. Department of Health and Human Services: National Institutes of Health, National Cancer Institute. Available at: https:\/\/evs.nci.nih.gov\/ftp1\/CTCAE\/CTCAE_4.03\/CTCAE_4.03_2010-06-14_QuickReference_8.5x11.pdf"},{"issue":"8","key":"6291_CR4","doi-asserted-by":"publisher","first-page":"1196","DOI":"10.1007\/s00270-017-1630-4","volume":"40","author":"EM de Leede","year":"2017","unstructured":"de Leede EM, Burgmans MC, Meijer TS et al (2017) Prospective clinical and pharmacological evaluation of the Delcath system\u2019s second-generation (GEN2) hemofiltration system in patients undergoing percutaneous hepatic perfusion with melphalan. Cardiovasc Intervent Radiol 40(8):1196\u20131205","journal-title":"Cardiovasc Intervent Radiol"},{"issue":"2","key":"6291_CR5","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(2):228\u2013247","journal-title":"Eur J Cancer"},{"issue":"24","key":"6291_CR6","doi-asserted-by":"publisher","first-page":"2256","DOI":"10.1056\/NEJMoa2304753","volume":"389","author":"JC Hassel","year":"2023","unstructured":"Hassel JC, Piperno-Neumann S, Rutkowski P et al (2023) Three-year overall survival with tebentafusp in metastatic uveal melanoma. N Engl J Med 389(24):2256\u20132266","journal-title":"N Engl J Med"},{"key":"6291_CR7","unstructured":"HEPZATO KIT Hepatic Delivery System. US Food and Drug Administration Prescribing Information. Delcath Systems Inc. Available at https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2023\/201848s000lbl.pdf. Accessed 11 November 2024"},{"issue":"8","key":"6291_CR8","doi-asserted-by":"publisher","first-page":"1370","DOI":"10.1093\/annonc\/mdz176","volume":"30","author":"L Khoja","year":"2019","unstructured":"Khoja L, Atenafu EG, Suciu S et al (2019) Meta-analysis in metastatic uveal melanoma to determine progression free and overall survival benchmarks: an international rare cancers initiative (IRCI) ocular melanoma study. Ann Oncol 30(8):1370\u20131380","journal-title":"Ann Oncol"},{"key":"6291_CR9","unstructured":"KIMMTRAK (tebentafusp-tebn). US Food and Drug Administration Prescribing Information. Immunocore Ltd. Available at https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2022\/761228s000lbl.pdf. Accessed 11 November 2024"},{"issue":"9","key":"6291_CR10","doi-asserted-by":"publisher","first-page":"981","DOI":"10.1001\/jamaophthalmol.2018.2466","volume":"136","author":"AM Lane","year":"2018","unstructured":"Lane AM, Kim IK, Gragoudas ES (2018) Survival rates in patients after treatment for metastasis from uveal melanoma. JAMA Ophthalmol 136(9):981\u2013986","journal-title":"JAMA Ophthalmol"},{"issue":"6","key":"6291_CR11","doi-asserted-by":"publisher","first-page":"841","DOI":"10.1007\/s00270-019-02177-x","volume":"42","author":"TS Meijer","year":"2019","unstructured":"Meijer TS, Burgmans MC, Fiocco M et al (2019) Safety of percutaneous hepatic perfusion with melphalan in patients with unresectable liver metastases from ocular melanoma using the Delcath Systems\u2019 second-generation hemofiltration system: a prospective non-randomized phase II trial. Cardiovasc Intervent Radiol 42(6):841\u2013852","journal-title":"Cardiovasc Intervent Radiol"},{"issue":"3","key":"6291_CR12","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1016\/S0197-2456(01)00113-1","volume":"22","author":"CS Moy","year":"2001","unstructured":"Moy CS, Albert DM, Diener-West M et al (2001) Cause-specific mortality coding: methods in the Collaborative Ocular Melanoma Study COMS report no. 14. Control Clin Trials 22(3):248\u2013262","journal-title":"Control Clin Trials"},{"issue":"13","key":"6291_CR13","doi-asserted-by":"publisher","first-page":"1196","DOI":"10.1056\/NEJMoa2103485","volume":"385","author":"P Nathan","year":"2021","unstructured":"Nathan P, Hassel JC, Rutkowski P et al (2021) Overall survival benefit with tebentafusp in metastatic uveal melanoma. N Engl J Med 385(13):1196\u20131206","journal-title":"N Engl J Med"},{"key":"6291_CR14","unstructured":"National Comprehensive Cancer Network (NCCN 2025). NCCN clinical practice guidelines in oncology for melanoma: uveal. Version 2.2025. Available at https:\/\/www.nccn.org\/guidelines\/guidelines-detail?category=1&id=1488"},{"issue":"6","key":"6291_CR15","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1097\/00000421-198212000-00014","volume":"5","author":"MM Oken","year":"1982","unstructured":"Oken MM, Creech RH, Tormey DC et al (1982) Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 5(6):649\u2013655","journal-title":"Am J Clin Oncol"},{"issue":"6","key":"6291_CR16","doi-asserted-by":"publisher","first-page":"586","DOI":"10.1200\/JCO.20.00550","volume":"39","author":"JM Piulats","year":"2021","unstructured":"Piulats JM, Espinosa E, Merino LdelaC et al (2021) Nivolumab plus ipilimumab for treatment-na\u00efve metastatic uveal melanoma: an open-label, multicenter, phase II trial by the Spanish Multidisciplinary Melanoma Group (GEM-1402). J Clin Oncol 39(6):586\u2013598","journal-title":"J Clin Oncol"},{"issue":"6","key":"6291_CR17","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1097\/CMR.0000000000000575","volume":"29","author":"ES Rantala","year":"2019","unstructured":"Rantala ES, Hernberg M, Kivel\u00e4 TT (2019) Overall survival after treatment for metastatic uveal melanoma: a systematic review and meta-analysis. Melanoma Res 29(6):561\u2013568","journal-title":"Melanoma Res"},{"issue":"9","key":"6291_CR18","doi-asserted-by":"publisher","first-page":"1304","DOI":"10.1007\/s00270-022-03225-9","volume":"45","author":"TML Tong","year":"2022","unstructured":"Tong TML, Samim M, Kapiteijn E et al (2022) Predictive parameters in patients undergoing percutaneous hepatic perfusion with melphalan for unresectable liver metastases from uveal melanoma: a retrospective pooled analysis. Cardiovasc Intervent Radiol 45(9):1304\u20131313","journal-title":"Cardiovasc Intervent Radiol"},{"issue":"8","key":"6291_CR19","doi-asserted-by":"publisher","first-page":"5340","DOI":"10.1245\/s10434-024-15293-x","volume":"31","author":"JS Zager","year":"2024","unstructured":"Zager JS, Orloff M, Ferrucci PF et al (2024) Efficacy and safety of the melphalan\/hepatic delivery system in patients with unresectable metastatic uveal melanoma: results from an open-label, single-arm, multicenter phase 3 study. Ann Surg Oncol 31(8):5340\u20135351","journal-title":"Ann Surg Oncol"}],"container-title":["Journal of Cancer Research and Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00432-025-06291-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00432-025-06291-x","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00432-025-06291-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T06:06:14Z","timestamp":1767074774000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00432-025-06291-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,29]]},"references-count":19,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["6291"],"URL":"https:\/\/doi.org\/10.1007\/s00432-025-06291-x","relation":{},"ISSN":["1432-1335"],"issn-type":[{"value":"1432-1335","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,29]]},"assertion":[{"value":"22 November 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 August 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 December 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Jonathan Zager\u2013global principal investigator in the FOCUS phase 3 study and serves on Delcath Systems Medical Advisory Board. Education and Training grant through Delcath. Marlana Orloff\u2013Advisory Board: Delcath, Replimune. Consultant: Immunocore. Steering Committee: Ideaya. Speaker: Immunocore. David Eschelman\u2013Received\u2009<\u2009$5\u00a0K consulting fees from Delcath. Evan Glazer\u2013My institution was a site for the clinical trial. I received no direct payment. Delcath paid for the clinical trial to my institution. Erika Richtig\u2013Medical University of Graz received payments for conducting the Phase 3 study. Sebastian Ochsenreither\u2013Advice: Immunocore, Delcath, Janssen. Speakers\u2019 bureau: Immunocore. Georgia Beasley\u2013Clinical trial funding paid to institution from Replimune, checkmate pharmaceuticals, Philogen, Delcath. Advisory board BMS 10.2023. Anja Gesierich\u2013University Hospital W\u00fcrzburg received payments for conducting the Phase 3 study. Reinhard Dummer\u2013intermittent, project focused consulting and\/or advisory relationships with Novartis, Merck Sharp & Dhome (MSD), Bristol-Myers Squibb (BMS), Roche, Amgen, Takeda, Pierre Fabre, Sun Pharma, Sanofi, Catalym, Second Genome, Regeneron, Alligator, T3 Pharma, MaxiVAX SA, Pfizer, Sim-cere and touchIME outside the submitted work. Ana Arance\u2013Consulting or advisory role: Pierre- Fabre, Novartis, Roche, BMS, MSD, Biontech. Speakers\u2019 Bureau: Pierre- Fabre, Novartis, Roche, BMS, MSD. Travel, Accommodations, Expenses: BMS, MSD. Stephen Fenwick\u2013Liverpool University Hospitals NHS Trust received support for conducting this Phase 3 study from the trial sponsor. Joseph Sacco\u2013I have been a paid member of advisory boards for Delcath, Replimune and Immunocore. I have received grant funding from Astra Zeneca and BMS (paid to institution). I have had travel and conference attendance paid for by MSD, BMS and Replimune. Johnny John is an employee of Delcath Systems Inc. Matthew Wheater\u2013Institutional (University Hospital Southampton) funding for conducting a commercial trial. Personal funding for participation in advisory board for Delcath. Pier Francesco Ferrucci, Junsung Choi, Aslam Ejaz, Sunil A. Reddy, Michael C. Lowe, Martin Gschnell, and Christian H. Ottensmeier have nothing to disclose.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interests"}}],"article-number":"25"}}