Smart Measurement of Circulating Tumor DNA

Lynch Syndrome (LS) carriers have a predisposition to develop various types of cancer, especially colorectal cancer (CRC) and endometrial cancer (EC). LS patients are advised to undergo surveillance by colonoscopy every 2 year and gynaecological surveillance. This surveillance is deemed burdensome and fails to detect a small part of the developing CRCs and the majority of extra-colonic cancers. To ensure prevention and early detection of cancer, a reliable and accessible test is needed. Recent studies have shown the potential of the detection of tumor-derived DNA fragments (circulating tumor DNA; ctDNA). Various molecular characteristics can be used to discriminate ctDNA from healthy circulating cell-free DNA. Current ctDNA assays with the highest sensitivity and specificity to detect for example minimal residual disease (MRD) after surgery are mostly tumor-informed, which means prior information is needed from the tumor tissue about the molecular alterations present.

As this information is not available for the detection of newly arising tumors, the aim of this study is to evaluate the use of an optimized combination of tumor agnostic ctDNA characteristics for the detection of newly developing tumors.

Inclusion criteria

(suspect) Lynch Syndrome carriers who:

• Have proven Lynch Syndrome (MMR-gene or EPCAM mutation), or have a proven microsatellite instability high (MSI-H)tumor;
• Are at least 18 years old; Have been diagnosed with any form of cancer at the time of inclusion, but have had no treatment yet;
• Have granted informed consent to participate in this study.

Exclusion criteria

(suspect) Lynch Syndrome carriers who:

• Are unwilling to undergo extra blood sampling;
• Are under the age of 18;
• Have no newly diagnosed tumors at time of inclusion;
• Have been treated for their tumor at time of inclusion;
• Are not able to read or understand Dutch language or are mentally not capable.