Circulating tumor cells and tumor DNA - patient-specific biomarkers for clinical decision support and tailored relapse diagnostics in neuroendocrine tumors and hepatocellular carcinoma

Circulating tumor cells and tumor DNA - patient-specific biomarkers for clinical decision support and tailored relapse diagnostics
Background
Cancer treatment and surveillance is associated with significant personal costs for patients and a socioeconomic burden as well. This increases the demand for a personalized surveillance and a precise individually targeted treatment. No biomarker with the potential to predict relapse and prognosis in patients with neuroendocrine tumors (NET) or hepatocellular carcinoma (HCC) has been identified.
Biopsy of the liver is an invasive procedure, and repeated biopsies for surveillance is not desirable. Circulating tumor DNA (ctDNA), DNA with tumor specific mutations, can be detected in a blood sample from patients with cancer. Monitoring the amount ctDNA and specific mutations, may be of value in the clinical management of surveillance. Another approach is identification of circulating tumor cells (CTC). While ctDNA is a bystander phenomenon in cancer, CTC are a crucial step in the dissemination of cancer. First line therapy for disseminated HCC, Sorafenib, has side effects and often impair the patient's
quality of life. In order to spare patients from an ineffective treatment, we investigate whether ctDNA can predict survival and response to Sorafenib.
The long-term goal is that a blood sample can serve as a "liquid biopsy", improving the accuracy of diagnosis, optimizing clinical surveillance and predict the response to therapy.
We hypothesize that:
 The presence of ctDNA/CTC predict progression or recurrence of NET and HCC before they are apparent by conventional imaging and biomarkers
 CTC and ctDNA complement each other in the diagnosis of progression/relapse
 Tumor mutation profile and changes in the amount of tumor DNA can predict treatment response in patients.
 CTC and ctDNA mutation profiles correlate to mutation profiles in tumor biopsies
Materials and methods
We aim to include 130 patients in the following categories:
- 70 patients diagnosed with small intestinal or pancreatic NET patients referred for treatment
- 30 HCC patients undergoing potential curative treatment
- 30 HCC patients treated with Sorafenib
Perspectives
The project aims to elucidate the clinical utility of CTC and ctDNA to predict the course of disease, ensure effective individualized relapse diagnostics and potentially predict response to therapy.