Than, Nguwah 
ORCID: 0000-0003-4991-5431
(2025)
An investigation of the use of contact X-ray brachytherapy in the organ-preserving management of rectal cancer
PhD thesis, University of Liverpool.
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Abstract
An investigation of the use of contact X-ray brachytherapy in the organ-preserving management of rectal cancer Colorectal cancer is the third most common type of cancer and the second leading cause of cancer death globally, in which rectal cancer is the most common tumour site (31%). The current standard of care for rectal cancer is total mesorectal excision (TME) surgery with/without neoadjuvant therapy. This offers high cure rates, but poses risks of mortality, morbidity, and long-term functional issues, especially in older or medically complex patients. With more early-stage rectal cancers being detected via screening and a higher incidence of this disease in older and comorbid populations, interest in organ-preserving treatment approaches has grown among both patients and clinicians. These approaches include local surgical excision and non-surgical options such as external beam (chemo)radiation (EBRT/EBCRT) and/or endocavitary radiotherapies. Such treatments aim to reduce surgery-related complications, preserve rectal function, and maintain quality of life without reducing cure rates. Since its introduction nearly 80 years ago, Contact X-ray Brachytherapy (CXB) has been used in rectal cancer treatment as a standalone or adjuvant therapy after local excision in stage I disease, as a boost with EBRT/EBCRT in locally advanced cancers, or as salvage for luminal regrowth during watch-and-wait after EBRT/EBCRT alone. However, robust data on its efficacy, safety, and post-treatment functional outcomes in large patient cohorts remain limited. These queries have been examined through several independent but interconnected studies in this thesis. The multi-centre study evaluating CXB as a standalone therapy in relatively older patients (median age 78 [IQR: 67–84] years) with stage I rectal cancer revealed a high 3-year local tumour control rate of 84% (75–95%), local tumour regrowth in 18% (8–29%), distant relapse in 3%, and no nodal relapse with acceptable 5-year disease-free survival (DFS) [66% (48–78%)] and overall survival (OS) [58% (44–75%)] rates. In the propensity score matching and inverse probability treatment weighting analysis of 251 patients with small rectal cancer (≤3 cm), upfront CXB instead of EBRT/EBCRT was associated with significant improved OS (85% vs 77%, p=0.02, [HR:0.58(95%CI:0.37-0.91)]), but a higher risk of grade 1-2 rectal bleeding (26% vs 6%, p=0.08). The efficacy and safety of CXB as a boost radiotherapy were assessed in high-risk locally advanced rectal cancer patients. The outcomes of CXB boost after EBRT/EBCRT between high- and low/intermediate-risk rectal cancer patients showed no significant differences in terms of complete response rate, local tumour regrowth, or toxicities, except for higher distant relapse in high-risk cases (21.2% vs 10.7%, p=0.01). Organ preservation, 5-year DFS, and OS rates were also comparable. CXB can be used as a salvage alternative to TME for local regrowth after EBRT/EBCRT and surveillance, especially in patients who were unfit or unwilling to undergo surgery. Early-stage tumour regrowth had a better local control rate than late-stage recurrences (48% vs 20%) after 37 months of follow-up, with minimal toxicity and good long-term outcomes. Delaying surgical salvage after CXB did not compromise long-term outcomes. In the one-year prospective study of rectal cancer patients treated with CXB and EBRT/EBCRT, most patients maintained stable health-related quality of life (HRQOL) during the subsequent year after CXB, even those who experienced local tumour regrowth or underwent salvage surgery. The endoscopic image study found that exophytic rectal tumours and those showing strong regression during CXB, scored independently and blindly by two independent reviewers, were associated with higher clinical complete response rates. These endoscopic features, when combined with digital rectal examination and MRI, may help guide decisions on organ preservation management. This project has therefore provided a comprehensive assessment of the oncological and clinical effectiveness of CXB across diverse treatment scenarios. It will serve as a foundation for evidence-based clinical decision-making, especially for rectal cancer patients who are not suitable candidates for surgery or those who prefer to avoid a colostomy.
| Item Type: | Thesis (PhD) |
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| Uncontrolled Keywords: | Contact X-ray Brachytherapy, Organ preserving management, Papillon, Rectal cancer |
| Divisions: | Faculty of Health & Life Sciences Faculty of Health & Life Sciences > Inst. Systems, Molec & Integrative Biology Faculty of Health & Life Sciences > Inst. Systems, Molec & Integrative Biology > Inst. Systems, Molec & Integrative Biology |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 01 Dec 2025 11:54 |
| Last Modified: | 01 Dec 2025 11:54 |
| DOI: | 10.17638/03194842 |
| Supervisors: |
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| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3194842 |
| Disclaimer: | The University of Liverpool is not responsible for content contained on other websites from links within repository metadata. Please contact us if you notice anything that appears incorrect or inappropriate. |
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