Point-of-care monitoring of head and neck cancer treatment response and recurrence development using nanopore-based ctDNA consensus sequencing

Circulating tumor DNA (ctDNA) in blood may become a generic biomarker for non-invasive cancer diagnosis and monitoring. However, detection of ctDNA is challenged by the presence of many circulating DNA molecules from healthy cells. We found that single ctDNA molecules can be sequenced with high accuracy by a three-step process consisting of capturing, copying and concatenation of the original double-stranded ctDNA molecules. This innovative approach - called CyclomicsSeq - is unparalleled by any other method in terms of cost-efficiency and speed, allowing point-of-care cancer diagnostics. Within this CPOC, subsidized by the Oncode institute, we have applied our CyclomicsSeq ctDNA test in patients with advanced head and neck cancer squamous cell carcinoma (HNSCC). Head and neck cancer (HNSCC) accounts for 380,000 cancer-related deaths worldwide. For these patients, determining whether a patient responds to the primary chemoradiation treatment is challenging, and non-responders are sometimes identified when other treatment options are no longer possible. By measuring the ctDNA levels in the blood of these patients prior to and during treatment, we aim to identify non-responders at an earlier stage. This dataset contains base calls of TP53 of 47 nanopore sequencing runs. We included 10 patients and 7 controls. For the patients, we have samples of multiple time points (0 = prior to treatment, 1 = 1 week after treatment initiation, etc).This research was funded by the Oncode Institut