EP201 - Circulating cytokine and chemokine dynamics during chemoradiotherapy in locally advanced rectal cancer

Sunday, May 11, 2025

8:10 AM – 8:15 AM PT

Location: Monitor 1, Sails Pavilion, Upper Level

ePoster Presenter(s)

NG

Norman J. Galbraith, MBChB MSc PhD FRCS

Fellow, Oncologic Colon and Rectal Surgery
MD Anderson
Houston, Texas, United States

All of the relevant financial relationships listed below have been mitigated.
This individual has no financial relationships with ineligible companies.

Author(s)

AS

Annabelle Smith, PhD

Postdoctoral Researcher
University of Glasgow
Glasgow, Scotland, United Kingdom

Disclosure information not submitted.
LH

Lily Hillson, BS

PhD candidate
University of Glasgow
Glasgow, Scotland, United Kingdom

Disclosure information not submitted.
RM

Ross McMahon, MBChB MRCS

Clinical Lecturer in Surgery
University of Glasgow
Glasgow, Scotland, United Kingdom

Disclosure information not submitted.
JQ

Jean A. Quinn, PhD

Research and Teaching Specialist
University of Glasgow
Glasgow, Scotland, United Kingdom

Disclosure information not submitted.
KP

Kathryn AF Pennel, PhD

Postdoctoral Researcher
University of Glasgow
Glasgow, Scotland, United Kingdom

Disclosure information not submitted.
CS

Colin W. Steele, PhD FRCS

Consultant Surgeon & Clinical Senior Lecturer
University of Glasgow
Glasgow, Scotland, United Kingdom

Disclosure information not submitted.
JE

Joanne Edwards, PhD

Professor of Translational Pathology
University of Glasgow
GLASGOW, Scotland, United Kingdom

Disclosure information not submitted.
PH

Paul g. Horgan, PhD FRCS

Professor of Surgery
University of Glasgow
Glasgow, Scotland, United Kingdom

Disclosure information not submitted.
SO

Sean M. O'Cathail, PhD FRCR

Consultant Radiation Oncologist
University College Cork
Cork, Cork, Ireland

Disclosure information not submitted.
SM

Simon Milling, PhD

Professor of Immunology
University of Glasgow
Glasgow, Scotland, United Kingdom

Disclosure information not submitted.

Senior Author(s)

CR

Campbell S. Roxburgh, PhD FRCS

Professor of Surgery
University of Glasgow
Glasgow, Scotland, United Kingdom

All of the relevant financial relationships listed below have been mitigated.
This individual has no financial relationships with ineligible companies.

All of the relevant financial relationships listed below have been mitigated.

Norman J. Galbraith, MBChB MSc PhD FRCS: This individual has no financial relationships with ineligible companies.

Campbell S. Roxburgh, PhD FRCS: This individual has no financial relationships with ineligible companies.

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Purpose/Background: Standard-of -care neoadjuvant therapy for locally advanced rectal cancer (LARC) includes radiotherapy (RT) delivered as either short course (5x5Gy) or long course (28x1.8Gy) format. Complete responses are reported in up to 55% with expanded neoadjuvant regimens. The immune mechanisms governing response are not defined but importantly, immune biomarkers assessed within the tumour prior to treatment relate to treatment response based on previous research (Chatila et al [1] and Galon group). The role of systemic measures of immune activity measured prior to and during radiation therapy has not previously been studied in LARC. Here we investigate systemic immune mediator dynamics during neoadjuvant therapy for LARC, determining potential relationships with response.

[1] Chatila et al, Nat Med 28, 1646–1655 (2022).
[2] El Sissy et al, J Clin Oncol. 2024 Jan 1;42(1):70-80.

Methods/Interventions: A prospective observational cohort study was performed in patients with LARC undergoing neoadjuvant RT. Inclusion criteria were T3-4, N+ or CRM threatening rectal tumors. Peripheral blood was taken at baseline (pre-treatment), and then weeks 2, 6, and 12 during treatment. Plasma was stored at -80C and a 25-plex Immunotherapy cytokine assay using Luminex technology was performed.

Results/Outcomes: From January 2021 to December 2024, 34 patients were included. Mean distance from anal verge was 39.2mm (SD 35.9), with 70.1% of cases defined as T3. Long-course (LC) RT was given to 74.3%, compared with SC RT in 25.7%. 12 patients achieved a clinical complete response and were managed with watch and wait. Of patients who had surgery at the end of treatment 7.1% had a pathological complete response. IL8 decreased by 12 weeks compared with baseline (p < 0.01) but other cytokines remained stable. Pre-operative TNF alpha correlated with PD-L1 levels. No cytokine differences were found between SC and LC regimes. Patients with complete/ near compete responses (defined as cCR or Ryan Tumor Regression Grade 0-1) exhibited lower TNF alpha at baseline, and lower IL8 at 2 weeks, compared to non-responders (defined as TRG2-3). Plasma PD-L1 levels were higher in non-responders at 0, 2 and 6 weeks (p < 0.050)(Figure 1). Early-onset LARC ( < 50 years of age) had lower IL10 and IP10 levels (p < 0.010).

Conclusion/Discussion: Patients who have a complete/near complete clinical response to neoadjuvant therapy with LARC have a distinct systemic immune profile with lower TNF alpha, IL8 and PD-L1 concentrations in plasma. Young-onset LARC patients have decreased IL10 and IP10 levels compared with older onset patients. These differential signals shed new light on the interplay between host systemic immune interaction and the tumor microenvironment during the evolving of response to RT in rectal cancer.