Caren van Roekel

261 Discussion The choice of chemotherapy regimens is dependent on many factors, such as RAS/BRAF mutation status, clinical performance status, presence of comorbidities and location of the primary tumor. RAS mutant status is associated with a higher risk of extrahepatic disease, poor response to cetuximab, panitumumab, irinotecan and oxaliplatin and patients with this mutation are less likely to have resectable hepatic metastases (25-27). BRAF mutant status is associated with higher stage disease, higher incidence of extrahepatic metastases and a worse survival after surgery (28). The location of the primary tumor can be divided into right (caecum, ascending colon, hepatic flexure and transverse colon) and left (splenic flexure, descending colon, sigmoid and rectum). In general, patients with right-sided primary tumors have a worse prognosis (29). The most common adverse events include hypersensitivity reactions, cardiac ischemia, thrombosis, hand-foot skin reaction, diarrhea, nausea, vomiting, sensory neuropathy and hematological adverse events such as anemia and neutropenia (21). The use of chemotherapy can also induce liver injury: the so-called chemotherapy-associated liver injury syndrome, with three stages: steatosis, steatohepatitis and sinusoidal obstruction syndrome. Liver injury is mostly associated with the use of oxaliplatin and irinotecan (30, 31). Colorectal cancer mainly occurs in elderly people; the median age at diagnosis is 68 years for men, and 72 years for women (32). Due to age-related function decline and medical comorbidities, patients of older age may experience more adverse events of systemic therapy (33). According to the European Society for Medical Oncology, radioembolization is indicated for ‘patients with liver-limited disease failing the available chemotherapeutic options’. In these patients, ‘radioembolization with yttrium-90 ( 90 Y) microspheres should be considered’ (2). The guidelines from the National Comprehensive Cancer Network adhere to the same indication: radioembolization is indicated in the salvage setting for patients with liver-dominant metastases (34). In The Netherlands, treatment with radioembolization (with either 90 Y or holmium-166 ( 166 Ho) microspheres is reimbursed for patients with unresectable liver metastases with chemo- refractory disease or with unacceptable toxicity after systemic treatment (3). 10