eprintid: 10188606 rev_number: 7 eprint_status: archive userid: 699 dir: disk0/10/18/86/06 datestamp: 2024-03-07 10:54:34 lastmod: 2024-03-07 10:54:34 status_changed: 2024-03-07 10:54:34 type: article metadata_visibility: show sword_depositor: 699 creators_name: Mahmood, Umair creators_name: Muhamad Faizul, Elisya creators_name: Howlett, Sarah creators_name: Amin, Zahir creators_name: Hochhauser, Daniel creators_name: Shiu, Kai-Keen creators_name: Bridgewater, John creators_name: Khan, Khurum title: Comprehensive Examination of Cholangiocarcinoma Patients Treated with Novel Targeted Therapies after Extended Molecular Profiling on Liquid Biopsies ispublished: pub divisions: UCL divisions: B02 divisions: C10 divisions: D19 divisions: G98 divisions: G99 keywords: Cholangiocarcinoma; targeted therapies; personalised medicine; liquid biopsy note: Copyright © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). abstract: Background: Cholangiocarcinoma (CCA) is associated with poor outcomes and limited treatment options, leading to increased use of targeted therapies for its management. Here, we performed one of the largest single-centre reviews evaluating outcomes following personalised targeted agents in CCA patients. Methods: All consecutive CCA patients receiving systemic therapy between January 2010 and April 2023 at UCLH were included. The primary objective of this study was to evaluate treatment response, survival outcomes and predictors of clinical benefit in CCA patients treated with molecularly guided therapies. Patient demographic factors, disease characteristics and survival outcomes were evaluated using the Kaplan–Meier method and Cox proportional-hazards models. Results: Of the 227 consecutive CCA patients, 162 (71%) had molecular profiling, of whom 56 (35%) were eligible and 55 received molecular-targeted treatment. CCA histological classifications comprised intrahepatic (N = 32), extrahepatic (N = 11), hilar (N = 4) and unknown (N = 9) subtypes. Most patients received targeted agents based on genomic profiling in a second treatment line setting (N = 34). Frequently observed genomic alterations occurred in the FGFR2 (N = 21), IDH1 (N = 7) and BRCA2 (N = 6) genes. Median progression-free survival (PFS) following first-, second- and third-line systemic therapy and overall survival (OS) were 8.44 (95% CI, 7.49–12.78), 5.65 (95% CI, 3.71–7.13), 5.55 (2.79–12.58) and 29.01 (24.21–42.91) months, respectively. CCA subtype and FGFR/BRCA molecular aberration status were not associated with PFS or OS. However, a prior CCA-related surgical history was predictive of OS (p = 0.02). Stratification by best overall response to second-line targeted agents demonstrated an association with PFS (p = 0.002) and OS (p = 0.02). Duration of treatment with second-line targeted therapy was associated with OS (p < 0.001). Conclusions: Patients receiving targeted therapeutics achieved promising outcomes, especially those attaining a favourable treatment response and those receiving targeted agents for longer periods. Liquid biopsies can reliably provide information on extended molecular profiling to aid patient selection for personalised therapies. date: 2024-02-02 date_type: published publisher: MDPI AG official_url: http://dx.doi.org/10.3390/cancers16040697 oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 2254232 doi: 10.3390/cancers16040697 medium: Electronic pii: cancers16040697 lyricists_name: Bridgewater, John lyricists_name: Howlett, Sarah lyricists_id: JABRI52 lyricists_id: SHOWL11 actors_name: Flynn, Bernadette actors_id: BFFLY94 actors_role: owner full_text_status: public publication: Cancers volume: 16 number: 4 article_number: 697 event_location: Switzerland issn: 2072-6694 citation: Mahmood, Umair; Muhamad Faizul, Elisya; Howlett, Sarah; Amin, Zahir; Hochhauser, Daniel; Shiu, Kai-Keen; Bridgewater, John; Mahmood, Umair; Muhamad Faizul, Elisya; Howlett, Sarah; Amin, Zahir; Hochhauser, Daniel; Shiu, Kai-Keen; Bridgewater, John; Khan, Khurum; - view fewer <#> (2024) Comprehensive Examination of Cholangiocarcinoma Patients Treated with Novel Targeted Therapies after Extended Molecular Profiling on Liquid Biopsies. Cancers , 16 (4) , Article 697. 10.3390/cancers16040697 <https://doi.org/10.3390/cancers16040697>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10188606/1/cancers-16-00697-v2.pdf