Transcatheter hepatic therapy with irinotecan eluting beads (DEBIRI) for the treatment of colorectal liver metastases

Jones, Robert ORCID: 0000-0001-5608-001X Transcatheter hepatic therapy with irinotecan eluting beads (DEBIRI) for the treatment of colorectal liver metastases. PhD thesis, University of Liverpool.

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Abstract

Background There is growing interest in preoperative chemotherapy for patients with colorectal liver metastases (CRLM) but personalising treatments to maximise response and minimise toxicity remains a challenge. Transcatheter hepatic therapy with irinotecan-eluting beads (DEBIRI) allows targeted delivery of irinotecan direct to CRLM. However, the safety and efficacy of DEBIRI in a preoperative setting has not yet been defined. In addition, very little is understood about why response to DEBIRI varies between patients. Aims This thesis had 2 key aims: (1) To assess the safety and efficacy of neoadjuvant DEBIRI (2) To investigate inter-patient variations in treatment response. Methods Patients with resectable CRLM received a single treatment with DEBIRI 1 month prior to surgery (maximal dose 200mg). The primary end-point of the study was R0 tumour resectability. Hepatic parenchyma and CRLM were sampled at the time of resection. Hepatic expression of key metabolising enzymes was assessed using mass spectrometry based proteomics. Hepatic irinotecan metabolism was characterised and correlated with tumour response. Results DEBIRI was successfully administered in 40 patients. 1 patient (3%) developed post-DEBIRI pancreatitis. All 40 proceeded to surgery, with 38 undergoing resection. 30 day operative mortality was 5%, morbidity 27.5% (Clavien-Dindo 1-4). 63 discreet lesions were targeted, with 74% R0 resection rate. Histopathological examination found no residual tumour in 17% of lesions, 50% tumour in 24%. 91% of treated lesions demonstrated stable disease by RECIST, with 9% demonstrating disease progression. RECIST was a poor predictor of pathological response or long-term outcome. At a median follow up of 293 days, fourteen patients (36%) had disease recurrence. On multivariate analysis, only tumour KRAS status was predictive of long-term outcome (p=0.02). There was a strong correlation between hepatic CES-2 expression and irinotecan activation (p

Item Type:	Thesis (PhD)
Additional Information:	Date: 2013-07 (completed)
Uncontrolled Keywords:	Chemotherapy cancer surgery
Divisions:	Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User:	Symplectic Admin
Date Deposited:	09 Mar 2015 15:30
Last Modified:	16 Dec 2022 04:42
DOI:	10.17638/00018693
Supervisors:	Ghaneh, Paula Kitteringham, Neil
URI:	https://livrepository.liverpool.ac.uk/id/eprint/18693