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