Caren van Roekel

263 Discussion In the second line, there may also be a place for radioembolization, possibly combined with a radiosensitizer such as irinotecan. There are a few studies reporting on overall survival in patients treated with radioembolization in the second line, with median overall survival ranging from 12.0-14.7 months (43-45). The combination of treatment with irinotecan and radioembolization was analyzed in 25 patients. A favorable response rate of 48% was found, while the incidence of toxicity was comparable to treatment with irinotecan alone (46). Another study compared the combination of various systemic treatment options with radioembolization versus radioembolization alone and found an improved response rate (45% versus 27%) as well, with acceptable toxicity (47). These results support the possibility of radioembolization as a second-line treatment. In the EPOCH trial, the safety and efficacy of second- line chemotherapy alone versus radioembolization combined with second- line chemotherapy in mCRC patients are investigated. Patient enrollment has finished, but the results are still awaited (48). These results are expected to be of great importance in the role of radioembolization in the second line, especially since this study accounts for prognostic patient-factors such as tumor load, KRAS status and prior first-line chemotherapy. The study will also shed a light on the tolerability of radioembolization combined with second- line chemotherapy, which will likely have important consequences for clinical decision making. In the third line, patients are often treated with TAS-102. However, an early study showed only a marginal benefit of treatment with TAS102 versus placebo, with a median survival gain of only 1.8 months (median overall survival 7.1 months versus 5.3 months) (49). A more recent study compared the use of TAS102 combined with bevacizumab versus TAS102 alone in the third line. The addition of bevacizumab increased median overall survival by 2.7 months (median overall survival 9.4 months versus 6.7 months) (50). So even with the addition of bevacizumab, overall survival after treatment with TAS102 is limited. Moreover, the incidence of grade 3 or higher adverse events was high: 69% with combined therapy and 30% with monotherapy (49, 50). These data raise questions on the benefit/harm ratio of this treatment. As stated before, toxicity after radioembolization is usually mild and median overall survival rates after two lines of chemotherapy are comparable (44, 45, 51). Therefore, there may be a role for radioembolization in the third line. 10