Liquid biopsies in patients with peritoneal metastases of colorectal cancer.

Rationale: Patient selection and follow-up after cytoreductive surgery and HIPEC (Hyperthermic IntraPEritoneal Chemotherapy) for peritoneal metastases (PM) of colorectal origin are hampered by limitations of diagnostic modalities. Conventional radiological imaging has a low sensitivity for detection of peritoneal metastases and is unable to detect the extensiveness of the disease. The HIPEC procedure is significantly more effective in early disease but unfortunately due to limitations of tests peritoneal metastases are often diagnosed in an advanced stage, limiting treatment options. Circulating tumour DNA (ctDNA) in plasma (also called: Liquid Biopsies) has shown promising preliminary results for diagnosis and follow-up of patients with colorectal cancer. The use of ctDNA could potentially improve detection of PM, improve patient selection for HIPEC and possibly detect recurrent disease during follow-up at an earlier stage. Currently the ctDNA tests have not been evaluated in patients with PM.

Objective: To evaluate feasibility of ctDNA detection in patients with PM undergoing cytoreductive surgery and HIPEC.

Study design: Prospective feasibility study

Study population: Patients with known PM and planned to undergo cytoreductive surgery and HIPEC for PM of colorectal origin.

Intervention (if applicable): Not applicable

Main study parameters/endpoints: Main study parameter is the presence of detectable mutated ctDNA in the patient’s plasma at time of diagnosis. Secondly the quantity is evaluated after cytoreductive therapy 2-4 weeks postoperatively to evaluate treatment effect.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness:

This study has no benefits for the patient. Also participation does not add any burden or risks, other than the minor complications related to venapunction. These include: hematoma or puncture related anxiety.

Primary Objective:

- To evaluate the detection of circulating tumor DNA (ctDNA) in patients with peritoneal metastases (PM) of colorectal origin undergoing cytoreductive surgery and hyperthermic intraperitoneal chemohterapy (HIPEC) at time of diagnosis in a feasibility trial (N=20 patients).



Secondary Objective:

- To evaluate a potential decrease of levels of ctDNA decrease after cytoreductive surgery and HIPEC





Feasibility; The study is feasible if the following criteria are met

1. If in at least 70% of the patients ctDNA status correlates with mutational status of the tissue specimen preoperatively (qualitative)

2. If at least 50% of the patients with detectable mutated ctDNA show decreased levels of ctDNA after treatment (quantitative)

Plasma levels of ctDNA preoperatively: day of HIPEC surgery, prior to surgery.

Plasma levels of ctDNA postoperatively: 2-4 weeks after HIPEC surgery.

This is an observational cohort study to assess the correlation between ctDNA and cytoreductive surgery. No interventions are performed.

Treatment and follow-up of patients will not be influenced by ctDNA results.

Two additional viles of blood (2*9mL Streck) are taken before (on the day of HIPEC surgery) and after cytoreductive surgery and HIPEC (2-4 weeks after HIPEC surgery).