An investigation into the influence of the systemic inflammatory response on treatment response to neoadjuvant chemoradiotherapy in rectal cancer

Nair, Harikrishnan S. (2025) An investigation into the influence of the systemic inflammatory response on treatment response to neoadjuvant chemoradiotherapy in rectal cancer. MD thesis, University of Glasgow.

Abstract

An abnormal systemic inflammatory response is associated with adverse short and long term outcomes in cancer. Systemic inflammation can be a surrogate maker of the interaction between host immune response and tumour. Systemic inflammation can influence treatment response to chemoradiotherapy. At present there is no reliable biomarker of response to chemoradiotherapy in rectal cancer. This thesis examines the influence of the systemic inflammatory response on treatment response to neoadjuvant chemoradiotherapy in rectal cancer.

A dataset of patients receiving neoadjuvant long course chemoradiotherapy (CRT) for non metastatic disease followed by potentially curative resection for rectal cancer was compiled from two prospectively databases of patients treated at Glasgow Royal Infirmary from 2008-2014 and the wider West of Scotland between 2014-2016. Blood results and clinic-pathological data for these patients were collected from electronic patient records to create a comprehensive dataset. Biomarkers of systemic inflammation included: differential blood count; neutrophil to lymphocyte ratio (NLR); haemoglobin; C reactive protein; albumin; and modified Glasgow Prognostic Score(mGPS). Treatment response to chemoradiotherapy was quantified with tumour regression grade, pathological complete response and the neoadjuvant rectal score.

I observed white cell count (WCC), NLR and mGPS were not associated with treatment response. Lower haemoglobin and elevated CEA were associated with poorer tumour response. There was no association with changes in WCC, NLR, CRP and tumour
response. I observed the development of lymphopenia during treatment but no association with tumour response. I observed baseline anaemia was associated with poorer tumour response and an association between anaemia and systemic inflammation. A significant proportion of my time was in the recruitment and coordination of sample collection for a novel pilot study for the feasibility of protocolised blood and tumour sampling during neoadjuvant therapy.

I have not demonstrated an association between serum markers of systemic inflammation and treatment response. I have demonstrated anaemia is a marker of poor response and the association between anaemia and systemic inflammation. This highlights the difficulty in measurements of the systemic inflammatory response from routine blood tests and the importance of more detailed study of markers of systemic inflammatory response which are being done in research settings rather than routine clinical practice. This would help identify reliable biomarkers of treatment response to neoadjuvant chemotherapy and organ preservation strategies.

• Item Type: Thesis (MD)
• Qualification Level: Doctoral
• Additional Information: Funding for the study has been secured from the Beatson Cancer Charity.
• Subjects: Q Science > QH Natural history > QH301 Biology; Q Science > QH Natural history > QH345 Biochemistry; Q Science > QR Microbiology > QR180 Immunology
• Colleges/Schools: College of Medical Veterinary and Life Sciences
• Funder's Name: Beatson Cancer Charity (BEATCANC)
• Supervisor's Name: Roxburgh, Professor Campbell and Edwards, Professor Joanne
• Date of Award: 2025
• Depositing User: Theses Team
• Unique ID: glathesis:2025-85351
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 16 Jul 2025 10:29
• Last Modified: 16 Jul 2025 10:29
• URI: https://theses.gla.ac.uk/id/eprint/85351