Inherited Cancer Early Diagnosis (ICED) Study Liquid Biopsy Screening for Early Diagnosis of Cancers in Patients With Cancer-predisposition Syndromes

Heritable genetic alterations play a major role in up to 10% of all cancers. There are more than 50 hereditary cancer syndromes identified which predispose an individual to developing certain tumours, resulting in high mortality when the cancer has been diagnosed at an advanced stage. Currently there are established surveillance guidelines for majority of these syndromes, however these imply frequent clinical, laboratory, radiological studies and invasive investigations that are costly, time consuming and might omit detection of early tumours. It has been shown that by diagnosing a cancer before metastasis, cancer-related deaths could be potentially reduced by 15% within 5 years.

Limitations of clinical and radiological surveillance in patients with genetic conditions At present, the only recommendation for a full-body scan in a cancer predisposition syndrome is for patients with a germline TP53 mutation. Whole body-MRI (WB-MRI) is an expensive technique and requires access to specialist radiologists. Whilst it can detect a malignant process, WB-MRI also has a high rate of detection of benign lesions which will require further tests, accounting for considerable additional distress and waiting time for patients. However, in the UK, access to whole-body MRI is variable across the country and not routinely funded. The NHS breast screening programme (BSP) offers surveillance for breast cancer with mammography or breast MRIs to women carrying a germline mutated BRCA1, BRCA2, TP53, A-T homozygotes, PALB2, PTEN, STK11 or CDH1. (15). This targeted screening might reduce the incidence of a breast cancer however it does not screen for any other potential tumours which may arise in a woman with a germline mutation of the beforementioned genes. Colonoscopy can detect early colorectal cancer, although, it is an invasive, expensive and time-consuming procedure. Finally, clinical examination is often not sufficient in detecting asymptomatic tumours and most patients unfortunately will present with advanced malignancies when curative treatment is no longer feasible.

There is a clear need for newer approaches for early detection of cancer in these high-risk cohorts, which are less invasive for the patient, less resource-intensive and of improved sensitivity.

This study will inform whether the use of peripheral blood ctDNA and the detection of genetic and epigenetic changes could serve as a blood biomarker to detect tumour development in patients at high-risk of cancer for earlier diagnosis of such tumours.

Data Acquisition