Circulating tumor DNA as a biomarker in perihilar cholangiocarcinoma: a feasibility study

Diagnosis of perihilar cholangiocarcinoma (PHC) is challenging due to low
sensitivity and specificity of current diagnostic tests. 15% of Of all patients
with suspected PHC who undergo surgical resection, 15% have a benign
inflammatory disease at final histopathological diagnosis. Morbidity and
mortality after liver resection for perihilar lesions is high; 8-15% mortality
and 40-70% morbidity. Even for patients with pathologically proven PHC for whom
surgery is the only curative option, this is a considerable risk. Ideally,
patients with benign disease should therefore not be subjected to surgery.
There is an urgent need for a diagnostic tool that is safe and reliably
discriminates between malignant and benign biliary tract disease. Patient*s
blood might be sufficient to provide us with information about the nature of
the disease: a so called *liquid biopsy*. For more than 14 different tumor
types, the presence of cell free circulating tumor DNA (ctDNA) in blood has
been described. The presence of known cancer-causing mutations can distinguish
tumor derived ctDNA from normal DNA. ctDNA has the potential to alter the
management of cancer care, offering a non-invasive method for adequate
diagnosis, identification of disease recurrence, and monitoring of therapy. The
presence of ctDNA in cholangiocarcinoma patients has not been reported before,
but has the potential to be an extremely useful and specific biomarker.

In this study we hope to demonstrate the presence ofthat ctDNA can be reliably
detected in patients with perihilar cholangiocarcinoma.

Observational prospective feasibility study

Risks associated with participation are negligible. For the participating
patients, only 3 4 additional tubes of blood will be drawn subsequently to the
routine preoperative blood tests. The findings of the mutation analyses will
not be shared with the patients