Tailored treatment of metastatic colorectal cancer: clinical and pre-clinical developments

Colorectal cancer is the third leading cause of cancer-related death in males and females in developed countries. Metastases in distant organs, which develop in 50% of colorectal cancer patients, are responsible for the majority of colorectal cancer deaths. Treatment of metastatic disease should therefore be optimized an novel methods for personalized cancer treatment should be developed; which are the main topics of this thesis.
The first part of the thesis focused on the current treatment of peritoneal metastases with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) in the Netherlands. We present the long-term outcome of the cytoreductive surgery and HIPEC in the Netherlands and show an increase of quality of this treatment over time and the learning curve of Dutch HIPEC hospitals. We further analyzed the outcome of cytoreductive surgery and HIPEC in patients with ovarian metastases of colorectal cancer along with peritoneal metastases. In the final chapter of the first part we studied the timing of perioperative systemic chemotherapy with regard to cytoreductive surgery and HIPEC in patients with peritoneal metastasis and positive lymph nodes.
The second part of this thesis focused on the development and validation of a 3D organoid model derived from patient’s colorectal tumors. This 3D model is a more complex in vitro culture model that should mimick a patient’s tumor more closely than a cell line, but is not as high-maintenance as a xenograft. In this part the phenotypes and genetics of tumor biopsies and their equivalent organoid cultures were compared. In the future, this culture system could be used as a discovery and validation platform for the prediction of drug response and discovery of treatment options for personalized therapy.