{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:59:43Z","timestamp":1792789183048,"version":"4.5.0"},"reference-count":80,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union","award":["PNRR-MAD-2022-12375905"],"award-info":[{"award-number":["PNRR-MAD-2022-12375905"]}],"id":[{"id":"https:\/\/ror.org\/019w4f821","id-type":"ROR","asserted-by":"crossref"}]},{"award":["PNRR-MAD-2022-12375905"],"award-info":[{"award-number":["PNRR-MAD-2022-12375905"]}],"id":[{"id":"https:\/\/ror.org\/019w4f821","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Intrahepatic cholangiocarcinoma (iCCA) is the second most common primary liver cancer, with increasing presentation. Less than one-third of patients are resectable at diagnosis, and the first-line systemic standard, gemcitabine\u2013cisplatin plus durvalumab, yields a modest median overall survival (OS) of approximately 13 months. In liver-dominant iCCA, selective internal radiation therapy (SIRT) with yttrium-90 (90Y) microspheres can deliver a high, parenchyma-sparing tumoricidal dose in loco and, paired with systemic therapy, is a valid treatment option. Methods: This commentary evaluates the retrospective and prospective data, comparative cohorts, registries, and meta-analyses of SIRT with systemic therapy in unresectable iCCA. Results: Across the data sets identified, the efficacy signal is in favor of combined approaches when SIRT is delivered in the first line selectively and concurrently with chemotherapy, reaching a median OS of about 22 months with 98% disease control. Propensity-weighted comparisons describe the added value of SIRT in improving OS and roughly doubling the progression-free survival and secondary resection rate. Downstaging to surgery (in approximately 5\u201319%) and, in highly selected patients with liver predominant disease, transplants can yield favorable longer-term survival with a good safety profile. Conclusions: To date, no completed randomized trial exists on combined locoregional SIRT and systemic therapy in patients with iCCA. SIRT should be considered a multimodal personalized therapeutic treatment option in patients with upfront unresecatable liver predominant disease.<\/jats:p>","DOI":"10.3390\/cancers18183017","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T08:03:17Z","timestamp":1789632197000},"page":"3017","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Combining Selective Internal Radiation Therapy (SIRT) and Systemic Therapy in Intrahepatic Cholangiocarcinoma"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4014-3711","authenticated-orcid":false,"given":"Francesco","family":"De Cobelli","sequence":"first","affiliation":[{"name":"Department of Radiology, IRCCS Ospedale San Raffaele, 20132 Milan, Italy"},{"name":"Vita-Salute San Raffaele University, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4441-7962","authenticated-orcid":false,"given":"Stephanie","family":"Steidler","sequence":"additional","affiliation":[{"name":"Department of Radiology, IRCCS Ospedale San Raffaele, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Casadei-Gardini","sequence":"additional","affiliation":[{"name":"Vita-Salute San Raffaele University, 20132 Milan, Italy"},{"name":"Department of Oncology, IRCCS Ospedale San Raffaele, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Canevari","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, IRCCS Ospedale San Raffaele, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Loria","sequence":"additional","affiliation":[{"name":"Department of Medical Physics, IRCCS Ospedale San Raffaele, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8108-9064","authenticated-orcid":false,"given":"Francesca","family":"Ratti","sequence":"additional","affiliation":[{"name":"Vita-Salute San Raffaele University, 20132 Milan, Italy"},{"name":"Division of Hepatobiliary Surgery, IRCCS Ospedale San Raffaele, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"European Association for the Study of the Liver (2023). 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