Caren van Roekel

152 Chapter 5 other studies with a comparable patient population also found that extrahepatic disease was a predictor of survival after radioembolization (24, 45-49). Other known prognostic factors are tumor load, baseline CEA level and location (left- versus right-sidedness) of the primary tumor (24, 49, 50). In our study, only location of the primary tumor showed a clear trend for significance, with the odds ratio for progressive disease being 3.88 (95%CI: 1.00-25.75) for patients with a right-sided primary tumor versus patients with a left-sided primary tumor. Genetics and biomarkers are more and more recognized as prognostic factors. We investigated the possible role of CEA, since this was associated with poorer survival after radioembolization in multiple studies (19, 24, 51). However, just as in the study of Sofocleus et al., in our study no significant correlation between pre-treatment CEA level and disease progression was found (19). Patients with KRAS mutation generally have a worse prognosis after radioembolization than patients with KRAS wild type status (19, 24, 25, 52). In our study, although not significant, the odds ratios for all types of progressive disease showed a clear trend for a worse prognosis for patients with KRAS mutation versus patients with KRAS wild type (Table 2). In The Netherlands, indications for radioembolization include liver-dominant, irresectable, systemic therapy-refractory disease. Patients with significant extrahepatic metastases are not considered eligible, but patients with stable, limited extrahepatic disease (defined by the Dutch National Healthcare Institute as a maximum of 5 lung nodules <1 cm and lymph nodes <2 cm) are eligible (53). This criterion was also used in the patients in this study. The SIRFLOX, FOXFIRE and FOXFIRE-Global (studying the added value of radioembolization to chemotherapy in first-line mCRC patients) used similar inclusion criteria with respect to extrahepatic disease (54). In these studies, no difference in OS or overall progression-free survival (PFS) was observed (55). One may argue that the large percentage of patients with extrahepatic disease in these studies (i.e. 36%) clouded the potential clinical benefit of radioembolization in a more stringent selected subset. In a subgroup of patients with right-sided primary tumors, the presence of extrahepatic metastases at baseline indeed proved to be a negative prognostic factor for OS, with a HR of 1.351 (95%CI 0.96-1.91)