Title: Earlier detection of NSCLC relapse after surgery with liquid biopsies and frequent community based blood collection
Funder: Cancer Research UK

Abstract: Lung Cancer is the highest cause of cancer related deaths worldwide. Most cases present with incurable Stage IV metastatic disease. In Manchester, low dose CT screening increased detection of Stage I-III disease when surgery is performed with curative intent. However, overall ~40% operable cases relapse within 2 years, most with incurable distant metastases. Our team published pilot data to suggest that liquid biopsies (circulating tumour cells (CTCs)) counted pre-operatively and circulating tumour DNA (ctDNA) assessed periodically after surgery) predict patients who will relapse requiring more intense surveillance and herald relapse prior to standard imaging detection or clinical symptoms. We hypothesise that earlier detection of relapse using frequent liquid biopsies will allow earlier administration of adjuvant therapy to improve patient outcomes and that development of sensitive liquid biopsies for MRD will also support development of tests for earlier detection of lung cancers. Our multidisciplinary team will collect blood samples for liquid biopsy from 100 patients of low socio-economic status in North Manchester at surgery and monthly thereafter. We will subsequently ask whether combination of CTCs, proteomics and/or ctDNA (using assays with superior sensitivity compared to our previous studies) allow earlier detection of relapse. We will collect blood from 50 patients with screen-detected lung cancer (NSCLC, mostly Stage I & II) and 50 patients with non-screen detected NSCLC (more Stage IIIS cases). We will evaluate feasibility of blood sample collection in the community in Lloyds Pharmacies, which we anticipate will result in a high patient compliance. Blood samples will be transported to CRUK Manchester Institute for processing and banking in vans emblazoned with Cancer Research UK logos. We will conduct a patient and public engagement evaluation of acceptability of community blood collection for cancer monitoring and of initiate a public awareness campaign. We will also evaluate quality of life comparing the psychological impact of surgery and follow up disease relapse monitoring for screen detected vs non-screen detected patients. In parallel, led from our CRUK Lung Cancer Centre of Excellence and industry sponsored, we will compare outcomes for patients with ctDNA detected relapse randomised to immunotherapy plus standard of care vs standard of care alone. Our ultimate goal is to develop a Phase III trial implementing community blood collection for sensitive liquid biopsy based early detection of relapsing NSCLC, where earlier treatment with targeted and/or immunotherapies improves patient outcomes. This proposal for sample collection is a first step towards this goal.

Lay abstract: Lung Cancer is the highest cause of cancer related deaths worldwide. Most cases present with incurable Stage IV metastatic disease. In Manchester, low dose CT screening increased detection of Stage I-III disease when surgery is performed with curative intent. However, overall ~40% operable cases relapse within 2 years, most with incurable distant metastases. Our team published pilot data to suggest that liquid biopsies (circulating tumour cells (CTCs)) counted pre-operatively and circulating tumour DNA (ctDNA) assessed periodically after surgery) predict patients who will relapse requiring more intense surveillance and herald relapse prior to standard imaging detection or clinical symptoms. We hypothesise that earlier detection of relapse using frequent liquid biopsies will allow earlier administration of adjuvant therapy to improve patient outcomes and that development of sensitive liquid biopsies for MRD will also support development of tests for earlier detection of lung cancers. Our multidisciplinary team will collect blood samples for liquid biopsy from 100 patients of low socio-economic status in North Manchester at surgery and monthly thereafter. We will subsequently ask whether combination of CTCs, proteomics and/or ctDNA (using assays with superior sensitivity compared to our previous studies) allow earlier detection of relapse. We will collect blood from 50 patients with screen-detected lung cancer (NSCLC, mostly Stage I & II) and 50 patients with non-screen detected NSCLC (more Stage IIIS cases). We will evaluate feasibility of blood sample collection in the community in Lloyds Pharmacies, which we anticipate will result in a high patient compliance. Blood samples will be transported to CRUK Manchester Institute for processing and banking in vans emblazoned with Cancer Research UK logos. We will conduct a patient and public engagement evaluation of acceptability of community blood collection for cancer monitoring and of initiate a public awareness campaign. We will also evaluate quality of life comparing the psychological impact of surgery and follow up disease relapse monitoring for screen detected vs non-screen detected patients. In parallel, led from our CRUK Lung Cancer Centre of Excellence and industry sponsored, we will compare outcomes for patients with ctDNA detected relapse randomised to immunotherapy plus standard of care vs standard of care alone. Our ultimate goal is to develop a Phase III trial implementing community blood collection for sensitive liquid biopsy based early detection of relapsing NSCLC, where earlier treatment with targeted and/or immunotherapies improves patient outcomes. This proposal for sample collection is a first step towards this goal.

Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES;4.5 RESOURCES AND INFRASTRUCTURE (DETECTION)
Health categories: CANCER AND NEOPLASMS