Mactier, Karen Elizabeth (2026) Prediction of local relapse of high-risk oropharyngeal squamous cell carcinoma following radical (chemo)-irradiation using a multi-omics approach. PhD thesis, University of Glasgow.
Due to Embargo and/or Third Party Copyright restrictions, this thesis is not available in this service.Abstract
Background
Oropharyngeal cancer (OPSCC) incidence has risen dramatically in Western countries over the last 3 decades. The mainstay of treatment for locally advanced disease is (chemo-) radiotherapy (ChT-RT), but despite advances in treatment planning and delivery, approximately two thirds of patients are left with at least moderate long-term toxicity. Relapse rates remain suboptimal even with maximal non-surgical management, with survival closely correlated with radiatioten response in the treated tumour volumes. Tobaccosmoking associated disease and lack of association with the human papillomavirus (HPV) are long-established risk factors for radiation resistance, however mechanisms of resistance in these high-risk groups are poorly understood.
Methods
Clinical, radiomic, bulk RNAseq and multiplex immunofluorescence histochemistry datasets were used to explore potential predictors of relapse after radical ChT-RT. Data was drawn from a cohort of 86 patients treated at the Beatson West of Scotland Cancer Centre.
Results
Tumour shrinkage during RT appeared to be predictive of long-term control, although there were limited radiomic textural differences between relapse and response tumours. Comparably, the transcriptomes of relapse and response tumours were similar, with more variation noted between HPV-positive (HPV+ve) and HPV-negative (HPV-ve) tumours. In HPV+ve subgroup analysis relapsing tumours displayed a phenotype more in keeping with HPV-ve tumours: partial epithelial-mesenchymal transition enrichment, higher percentage of fibroblasts and lower lymphocytes. High-stroma, low lymphocyte tumours were associated with poorer overall survival, regardless of HPV status.
Discussion
This study demonstrated early markers of radiation resistance in a homogeneous cohort of high-risk OPSCC. Tumour volume changes and tumour microenvironment analysis could be easily incorporated into the current clinical treatment pathway.
| Item Type: | Thesis (PhD) |
|---|---|
| Qualification Level: | Doctoral |
| Additional Information: | Supported by funding from the Beatson and Edinburgh Cancer Centre Endowment funds. |
| Subjects: | R Medicine > R Medicine (General) R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer) |
| Colleges/Schools: | College of Medical Veterinary and Life Sciences > School of Cancer Sciences |
| Supervisor's Name: | Inman, Professor Gareth and Paterson, Dr. Claire |
| Date of Award: | 2026 |
| Embargo Date: | 7 May 2028 |
| Depositing User: | Theses Team |
| Unique ID: | glathesis:2026-85956 |
| Copyright: | Copyright of this thesis is held by the author. |
| Date Deposited: | 22 May 2026 11:13 |
| Last Modified: | 22 May 2026 12:22 |
| Thesis DOI: | 10.5525/gla.thesis.85956 |
| URI: | https://theses.gla.ac.uk/id/eprint/85956 |
| Related URLs: |
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