Caren van Roekel

137 Mode of progression after radioembolization in colorectal cancer patients BACKGROUND Approximately 45% of colorectal cancer patients develop metastases (1, 2). Without treatment, the median overall survival for colorectal cancer patients with hepatic metastases (mCRC) is only 4.5 months (3). The liver is the most common site of metastasis: up to 30% of mCRC patients develop hepatic metastases (4, 5). Radioembolization is a loco-regional treatment option for unresectable, systemic therapy-refractory patients with liver-only or liver- dominant disease (6, 7). Intra-arterial administration of radioactive microspheres is proven to be safe and effective (8). Microspheres (approximately 30 um) are loaded with the radioactive isotope yttrium-90 ( 90 Y) or holmium-166 ( 166 Ho) and injected through a microcatheter in the hepatic artery (9). For the treatment of metastatic colorectal cancer, 90 Y-resin microspheres (SIR-Spheres ® , Sirtex) are FDA- and CE-approved. 90 Y -glass microspheres (TheraSphere ® , BTG / Boston Scientific) and 166 Ho microspheres (QuiremSpheres ® , Quirem) are CE-approved for this indication, not FDA-approved. The injected microspheres embolize the microvasculature surrounding the tumor and emit high-energy beta-radiation. The normal liver parenchyma is largely spared since healthy liver tissue is mainly supplied by the portal vein (10-12). Although assessment of metabolic response has proven added benefit over anatomic response, not being hampered by i.e. the presence of intra- tumoral necrosis and cystic changes after treatment (13, 14), response of radioembolization in mCRC patients is still mostly evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST) (15-17). When using these criteria, the results of most clinical studies in metastatic (liver) disease are modest, with many patients experiencing early progressive disease (18-21). Optimized treatment planning could improve response rates (22, 23), but selecting patients who will benefit most is another vital aspect. An important criterion in patient selection is the definition of liver-dominant disease. The extent of extrahepatic disease we are willing to accept is under constant debate at tumor board meetings in our center, but clear guidance is currently missing, due to the lack of data on this matter. Other prognostic factors that are known to influence response after treatment with radioembolization are (among others) KRAS status, primary tumor location, percentage tumor involvement and pre- 5