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Our Research: Cancer Precision Medicine

Monitoring residual disease

Liquid biopsy as an early warning sign for cancer relapse.

For those patients where cancer is detected early, surgery may cure them or significantly increase their lifespan. However, for patients with lung cancer, in around 50% cases, tumours recur due to presence of micro-metastatic disease, clinically undetectable at the time of surgery.

If we can detect this so-called ‘minimal residual disease’ (MRD) early, there is potential for more regular check-ups and opportunity for earlier interventions, requiring a sensitive MRD blood test to frequently monitor patients after their surgery. A convenient approach for patients would be to collect MRD blood test samples in their communities.

After successfully leveraging additional grant funding from CRUK, we opened an observational cohort study called COMPASS that invites patients in North and East Manchester and Tameside and Glossop, who have been treated for lung cancer with either surgery or surgery with adjuvant therapy to give monthly blood samples in their communities to test the feasibility of this approach.

COVID restrictions in 2020 prevented our original plans for patients to attend community pharmacies for sample collections. An alternative community collection was sought in 2021 and the North Manchester research nurse team now have a community phlebotomist in place to collect research samples in patient homes with the option for patients to also give their blood samples in mobile lung cancer screening trucks in supermarket carparks. Blood samples are transported to the CRUK Manchester Institute Cancer Biomarker Centre’s laboratories where they are processed and banked for analysis of circulating tumour cells (CTCs) and circulating tumour DNA (ctDNA), ‘so called’ liquid biopsies.

The primary aims of this study are:

  1. To determine the feasibility/acceptability of regular community-based blood collection in patients after lung cancer surgery to detect MRD from both a scientific and patient perspective.
  2. To determine whether MRD can be detected in blood and predict lung cancer recurrence earlier than standard of care clinical surveillance.

Progress to date:

  • • A multidisciplinary team has been established for MRD Monitoring in the community; including surgeons, oncologists, translational scientists.
  • Patient recruitment has resumed following the substantial delay caused by the pandemic restrictions. As of the 13 December 2021, 69 patients have been recruited.
  • Quality of life assessments are ongoing to evaluate quality of life and psychological measures in patients after lung cancer surgery, stratified according to route of diagnosis.
  • Public Patient Involvement Engagement is underway to increase patient awareness of MRD monitoring and understand patient needs.
  • Good progress has been made in development of sensitive MRD blood tests, with new assays for CTCs and methylated ctDNA.

Future work

  • To continue to collect, process and bank longitudinal blood samples from patients in community and hospital clinics for future liquid biopsy analyses.
  • To complete the validation of our liquid biopsy workflows to increase assay sensitivity and sample throughput.
  • To analyse banked samples from COMPASS patients to assess the utility of our new blood tests for MRD detection.
  • To understand patient acceptability and compliance regarding community blood collection for future study designs of community-based MRD monitoring and evaluate patient quality of life/psychological measures.
  • On completion of the pilot study, to launch a clinical trial to determine whether MRD monitoring with community blood collection and liquid biopsy assessment improves patient outcomes, with the view of rolling out community based blood collection to more patients.