Caren van Roekel

154 Chapter 5 radioembolization was used in a salvage setting, outcome was likely muddled by the effect of other, previous therapies (Table 1). However, since patients were selected for radioembolization based on their chemo-resistant tumors, the contribution of this variation in our patient population on the outcome of our study was considered minimal. Third, all patients were discussed in a multidisciplinary tumor board before treatment. Based on available imaging, the primary tumor was assessed for stability and the extrahepatic disease load was assessed for extent, however, not for stability. Also, although radioembolization is nowadays often performed in a lobar approach, a large fraction of patients that we studied received whole-liver treatment. Whole-liver treatment was in large part dictated by study protocols. Furthermore, three types of microspheres were used in our dataset. The differences with regard to the embolic nature of the treatment, the specific activity of the microspheres, the administered activities, and the absorbed doses may have influenced the incidence of early progressive disease, and potentially also the mode of progression, although our analyses did not show a significant difference between microsphere types. Last, KRAS status was unknown in 42% of the patients, making the number of patients for the subgroup analyses for KRAS rather small. Proper selection of patients seems fundamental for the cost-effectiveness of radioembolization treatment. Future prospective studies in the salvage setting should therefore be conservative with regard to the acceptance of extrahepatic disease. Accurate baseline imaging, including FDG-PET, may aid patient selection (66). This will avoid futile treatments and unnecessary toxicity. However, the effect of radioembolization in patients with extrahepatic disease should be evaluated in prospective studies comparing radioembolization with best supportive care, before a firm statement can be made about the exclusion of patients with extrahepatic disease from treatment. Also, considering the development of new lesions as the major cause of progressive disease, a study in the third line, comparing TAS-102 or regorafenib with and without radioembolization would be interesting. The study of Hendlisz et al. showed that radioembolization combined with chemotherapy was safe and effective (58). Based on the results of this study, chemotherapy in addition to radioembolization was therefore recommended in the refractory setting.