LAUSR

Molecular profiling to aid treatment selection is becoming routine in major cancer centers across the globe. Liquid biopsies for this purpose are increasing because of the challenges that tumor biopsies can present, especially for particular tumor types (e.g., pancreas and lung cancer), for patients with multiple metastases, and when serial sampling is needed to monitor tumor evolution and acquired drug resistance. In Manchester, we have pioneered this approach within the TARGET protocol to support selection of the most appropriate phase I trial for patients at the Christie Hospital. Within the TARGET study, we are profiling DNA from tumor biopsies (archival and/or fresh) and circulating tumor DNA. I will describe the TARGET feasibility study with results from the first 100 patients that focused on the development of our robust ctDNA workflow and bioinformatics pipeline, how ctDNA data correlate with those derived from tumor biopsy, and the matching of molecular profiles with actionable alterations to available trials. I will also describe our biweekly Molecular Tumor Board and the current initiative to provide a "virtual tumor board," where board members can access and discuss laboratory and clinical data remotely. Our ongoing and future goals are to expand TARGET to a further 450 Christie Hospital patients and across the CRUK Experimental Medicines Centres North (ECMC North), bringing opportunities for patients to travel to the most appropriate trial for them across the region. I will then discuss how we are approaching the harder challenge of liquid biopsy for the early detection of cancer, focusing on lung cancer where earlier detection that results in surgery with curative intent would transform patient outcomes. The subject cohort study that will maximize the success of liquid biopsy discovery for lung cancer is termed the "hard to reach, high risk" and typically reside in socially deprived areas, only seeking medical attention when their cancer is at an advanced and usually incurable stage. To address this challenge, we have worked closely with the University Hospital of South Manchester to set up a parallel blood test discovery program alongside the Manchester Community Lung Health Study. Subjects receive invitations from their GP to attend a free Lung Health Check in their communities (in shopping mall carparks), part of which for many subjects is a CT scan in a purpose-built van. This summer (and ongoing) we have collected >600 subject blood samples in vans parked adjacent to the CT scanner van. Samples are brought to our laboratory ED for processing and storage prior to analysis of circulating tumor cells (CTCs) using new technology platforms that examine every cell within the sample, and of ctDNA. Liquid biopsy results will be mapped to CT scan results and with clinical follow-up. Last summer, the CT scan data led to earlier detection of lung cancer cases allowing curative-intent surgery, but this is expensive and generates false-positive calls. Unlike liquid biopsy, multiple repeat CT scanning cannot be offered. We are therefore asking whether liquid biopsies that provide a molecular confirmation of cancer (single CTC or ctDNA profiling) can identify those subjects with a positive CT scan who have a cancer diagnosis and whether liquid biopsies yield earlier detection of cancer. Citation Format: Caroline Dive. Liquid biopsies for the management of cancer patient treatment and for early detection of cancer [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr CN08-03.