Beaton, Laura Elizabeth;
(2021)
Vandetanib-eluting radiopaque beads and stereotactic body radiotherapy in the treatment of liver cancers.
Doctoral thesis (M.D(Res)), UCL (University College London).
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Abstract
Background: Current treatment options for unresectable hepatocellular carcinoma (HCC) and colorectal liver metastases (mCRC) include transarterial chemoembolisation (TACE) and stereotactic body radiotherapy (SBRT). The objectives of this project were: 1. To assess a novel drug-eluting bead for TACE / 2. To report on the safety and efficacy of SBRT in HCC / 3. To assess the feasibility of using radiopaque beads as fiducial markers for SBRT / Methods: In Part 1, a first-in-human trial was performed in patients with HCC and mCRC using a novel vandetanib-eluting radiopaque bead, BTG-002814. Primary trial endpoints were safety/tolerability and the concentrations of vandetanib and its major metabolite in plasma and resected tissue. Biomarker studies included blood cytokines and perfusion imaging parameters. In Part 2, the efficacy of SBRT was explored in a retrospective study of 31 patients with HCC tumours ≤5 cm and in a phase II study of 13 patients with larger tumours. In Part 3 the feasibility of using radiopaque beads as fiducial markers for SBRT was investigated. / Results: BTG-002814 was shown to have a satisfactory safety profile in 8 patients. Vandetanib was present in the plasma of all patients 12 days post-TACE, and present in resected liver tissue up to 32 days post-treatment. There were no significant changes in perfusion parameters. Blood biomarker studies showed increases in leptin, osteopontin and sTie2. SBRT offered 1-year local control rates of 94% in small HCCs and 92% in larger tumours. Radiopaque beads were visible on 4D-CT and CBCT images in all 8 cases and matching successfully performed. / Conclusions: The safety profile and pharmacokinetic characteristics for this novel technology are adequate to proceed to a Phase I/II trial. SBRT is an effective local treatment for HCC. The role of radiopaque beads as fiducial markers is feasible and warrants further exploration as a clinical trial of TACE with SBRT.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | M.D(Res) |
| Title: | Vandetanib-eluting radiopaque beads and stereotactic body radiotherapy in the treatment of liver cancers |
| Event: | UCL (University College London) |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2021. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10133651 |
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