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Determining the response of rectal cancers to neoadjuvant chemoradiation using circulating tumour DNA from liquid biopsies

Dates

Funding Stream

Amount

05/01/2021 to 31/03/2023

A&B Bowel Cancer Legacy 2020-21

 £29,134.63

Chief Investigator

Adam Chambers,  University of Bristol

Summary

Rectal cancer is the most common form of bowel cancer. 1 in 10 people with this type of bowel cancer present with disease that is challenging to completely remove by surgery and has a high risk of recurring. To reduce this risk, patients are given chemotherapy and radiotherapy before they undergo surgery. Patients respond to this therapy differently: ranging from a complete response, with complete shrinkage of the tumour; to poor response, with no significant shrinkage of the tumour. However, predicting how well people will respond to therapy prior to surgery is very challenging.

In this study, we will use patient blood samples to detect response to therapy before surgery, using DNA shed by their cancer into the blood. This information could be used to inform treatment options for rectal cancer in the future. 75 plasma samples have been sequenced using the funds from this project. This funding has led onto the design and introduction of a newer study - SectR and signficant further funding and applications.

There are significant benefits for patients and the NHS from understanding who has responded to therapy before surgery. By tailoring treatment for each patient, it will ensure that patients are offered the type of treatment that gives them the best chance of a cure while reducing the risk of treatment side effects.

Main findings

We have been able to determine the levels of circulating tumour DNA (ctDNA) in patients blood in pre-therapy and post therapy samples. The levels in pre-therapeutic samples appear to correlate with response to therapy as measured with pathological tumour regression grade. We have also been able to introduce new bioinformatics software that enables the analysis of nucleosome depleted regions in ctDNA. This will enable the analysis of ctDNA for epigenetic differences such as chromatin compaction and understand which genes are being actively regulated that could help our understanding of what drives therapy response for these patients. The analysis of these data is ongoing and will be available in due course.

Project outputs

Prizes

  • Bristol Cancer Research Network - Early Career Event Oral Prize
  • ACPGBI South West Chapter - Oral prize

Research Degrees

  • Glen Roarke - MSc Bioinformatics, University of Bristol 2022-23
  • Teja Yarra - MSc Bioinformatics, University of Bristol, 2022-23
  • Jayden Gittens - MSc Health Sciences, University of Bristol 2021-22

Abstracts

  • South West ACPGBI Chapter Surgical forum, March 2022 - 'The use of ctDNA to understand response to therapy in locally advanced rectal cancer'
  • Bristol Cancer Network Early Career Researchers forum, June 2022 - ' Novel NF-kB signalling clusters predict DFS and OS following neoadjuvant therapy in rectal cancer'

Papers

  • Predicting clinical response to neoadjuvant chemoradiotherapy in rectal cancer using ctDNA. In preparation.