{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T10:42:43Z","timestamp":1792665763807,"version":"4.5.0"},"reference-count":35,"publisher":"Wiley","issue":"20","license":[{"start":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:00:00Z","timestamp":1791936000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:00:00Z","timestamp":1791936000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100031949","name":"Guardant Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100031949","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2026,10,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Comprehensive genomic profiling (CGP) is recommended for advanced cholangiocarcinoma (aCCA). Circulating tumor DNA (ctDNA) testing provides a noninvasive alternative with concordance to tissue. Standard first\u2010line (1L) therapy is gemcitabine and cisplatin (GemCis) with or without immune checkpoint inhibitors (ICIs). Data suggest that patients with isocitrate dehydrogenase 1 (\n                      <jats:italic>IDH1<\/jats:italic>\n                      ) mutations may derive less benefit from ICIs. This study evaluated outcomes with 1L GemCis versus GemCis\u00a0+\u00a0ICI in ctDNA\u2010identified\n                      <jats:italic>IDH1<\/jats:italic>\n                      \u2010mutant (\n                      <jats:italic>IDH1<\/jats:italic>\n                      +) aCCA.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Real\u2010world data were analyzed from the InfinityAI Data Library, which links claims data with CGP results from Guardant360. Patients with\n                      <jats:italic>IDH1<\/jats:italic>\n                      + aCCA identified between April 2019 and February 2025 who received 1L GemCis or GemCis\u00a0+\u00a0ICI were included. Outcomes were real\u2010world time to next treatment (rwTTNT), real\u2010world time to treatment discontinuation (rwTTD), and real\u2010world overall survival (rwOS), compared via Kaplan\u2013Meier estimates and log\u2010rank tests.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among 416\n                      <jats:italic>IDH1<\/jats:italic>\n                      + patients, 155 received GemCis and 113 received GemCis\u00a0+\u00a0ICI. No significant differences were observed in rwTTNT (hazard ratio [HR], 0.75;\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a0.13) or rwTTD (HR, 1.12;\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a0.40); however, rwOS was worse with GemCis\u00a0+\u00a0ICI compared with GemCis alone (16.0 months [95% CI, 13.6\u201319.9 months] vs. 30.0 months [95% CI, 24.1\u201341.0 months]; HR, 0.40;\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a0.001). In the GemCis\u00a0+\u00a0ICI aCCA cohort (\n                      <jats:italic>N<\/jats:italic>\n                      \u00a0=\u00a01150),\n                      <jats:italic>IDH1<\/jats:italic>\n                      + patients (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a0113) had numerically shorter rwOS than non\u2010\n                      <jats:italic>IDH1<\/jats:italic>\n                      + patients (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a01037) (HR, 0.75;\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a0.06).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      In\n                      <jats:italic>IDH1<\/jats:italic>\n                      + aCCA, addition of immunotherapy to GemCis was associated with inferior rwOS. These findings support obtaining ctDNA\u2010based CGP before initiating 1L therapy, and underscore the need for prospective studies.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cncr.70646","type":"journal-article","created":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T05:24:31Z","timestamp":1792041871000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Real\u2010world outcomes in circulating tumor DNA\u2013detected isocitrate dehydrogenase 1\u2013mutant cholangiocarcinoma: First\u2010line gemcitabine and cisplatin with versus without immunotherapy"],"prefix":"10.1002","volume":"132","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8448-844X","authenticated-orcid":false,"given":"Richard D.","family":"Kim","sequence":"first","affiliation":[{"name":"H. Lee Moffitt Cancer Center  Tampa Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-3297-1041","authenticated-orcid":false,"given":"Nikolas","family":"Naleid","sequence":"additional","affiliation":[{"name":"H. Lee Moffitt Cancer Center  Tampa Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8561-1801","authenticated-orcid":false,"given":"Adrian","family":"Bubie","sequence":"additional","affiliation":[{"name":"Guardant Health  Redwood City California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-2706-5838","authenticated-orcid":false,"given":"Nicole","family":"Zhang","sequence":"additional","affiliation":[{"name":"Guardant Health  Redwood City California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2754-1795","authenticated-orcid":false,"given":"Keelia","family":"Clemens","sequence":"additional","affiliation":[{"name":"Guardant Health  Redwood City California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,14]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885\u2010022\u201010286\u2010z"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1158\/1055\u20109965.Epi\u201021\u20100265"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/jso.23762"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2021.12.010"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(23)00727\u20104"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/EVIDoa2200015"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2024.1409132"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1378760"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2022.108111"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2022.09.004"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15133312"},{"key":"e_1_2_9_13_1","volume-title":"NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines\u00ae): Biliary Tract Cancers","author":"National Comprehensive Cancer Network","year":"2025"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3375"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470\u20102045(19)30733\u20108"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2012.315"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.32424"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2022.108170"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2021.3836"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202101230"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1097\/hep.0000000000001185"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2022.10.104"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.Ccr\u201017\u20103831"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.Ccr\u201019\u20101324"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2015\u20100210"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djaf155"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1200\/po.23.00544"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abj5104"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.adl6173"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159\u20108290.Cd\u201021\u20101643"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci129317"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159\u20108290.Cd\u201021\u20101077"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.641428"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19051340"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tranon.2019.12.010"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2019.07.017"}],"container-title":["Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cncr.70646","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cncr.70646","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cncr.70646","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T10:24:14Z","timestamp":1792664654000},"score":1,"resource":{"primary":{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/10.1002\/cncr.70646"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,14]]},"references-count":35,"journal-issue":{"issue":"20","published-print":{"date-parts":[[2026,10,15]]}},"alternative-id":["10.1002\/cncr.70646"],"URL":"https:\/\/doi.org\/10.1002\/cncr.70646","archive":["Portico"],"relation":{},"ISSN":["0008-543X","1097-0142"],"issn-type":[{"value":"0008-543X","type":"print"},{"value":"1097-0142","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,14]]},"assertion":[{"value":"2026-01-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-15","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70646"}}