Caren van Roekel

60 Chapter 2 The second study was a phase III trial comparing intravenous fluorouracil infusion alone or with radioembolization in patients with liver-limited metastatic colorectal carcinoma (mCRC). Forty-four patients were treated and median time to liver progression was 2.1 months in the chemotherapy arm, versus 5.5 months in the combination arm. Median OS rates in the treatment arms were 7.3 and 10.0 months, respectively, but this was not significantly different (123). The MORE study was a large retrospective study of mCRC patients treated with radioembolization. The main findings of this study were that radioembolization offered favorable survival benefits for patients with unresectable mCRC, even after several lines of chemotherapy (124). Prognostic factors for poorer survival after radioembolization in this salvage setting were ECOG performance status ≥1, baseline extrahepatic metastases, elevated levels of carcinoembryonic antigen (CEA), high tumor to non-tumor ratio, increased lines of chemotherapy, ascites, impaired liver function, lymphovascular invasion of the primary tumor and KRAS mutation (67, 125, 126). In the first-line setting, three trials investigating the role of radioembolization were performed. In the SIRFLOX, FOXFIRE and FOXFIRE-Global studies, the efficacy of combining first-line chemotherapy (FOLFOX with or without targeted therapy) with radioembolization was evaluated in a randomized setting. The studies were designed for combined analysis of overall survival. Five-hundred forty-nine patients were assigned to FOLFOX alone and 554 patients were assigned to the combination group. The patients that received the combination treatment had a significantly higher objective response (72% versus 63%, p=0.0012), however, this did not translate into a higher median OS. Median OS and overall progression-free survival were comparable between both groups. Therefore, early use of radioembolization in combination with chemotherapy in unselected patients with metastatic colorectal cancer cannot be recommended (127). However, a lot of factors contributing to the result of this combined analysis cannot be ignored, thus the result of these studies should interpreted with caution. The most important factor is the dosimetry. In their study, Wasan et al. have used the BSA method for activity calculation. However, this