Caren van Roekel

266 Chapter 10 Other important factors in the selection process of patients are age, location of the primary tumor, mutation status and liver function. Age is no contra- indication for treatment with radioembolization. A sub-analysis in patients <70 and ≥70 years treated in the MORE study showed no difference in overall survival (9.7 months versus 9.3 months) or incidence of grade ≥3 adverse events (18.8% versus 16.9%) (41). Most co-morbidities, except for renal insufficiency, do not affect outcome after radioembolization (42). On the other hand, the location of the primary tumor may play a role in the selection process. In general, patients with right-sided primary tumors have a worse prognosis than patients with a left-sided primary tumor. This was reported for systemic treatment, but also for local treatment of hepatic metastases: patients with a right-sided primary tumor had a significantly decreased survival (hazard ratio 1.60, 95%CI 1.30-1.98) and recurrence free-survival (hazard ratio 1.35, 95%CI 1.04-1.77) compared to patients with left-sided primary tumors (60). This could potentially make patients with right-sided primary tumors less favorable candidates for treatment with radioembolization, as they will likely benefit less than patients with left-sided primaries (61). However, before using this as an exclusion criterion, a randomized study in patients with right-sided primary tumors should be performed, comparing best supportive care with radioembolization. Furthermore, the impact of radioembolization in patients with a right-sided primary tumor may be different in the first-line setting. A post-hoc analysis of the SIRFLOX, FOXFIRE and FOXFIRE-Global studies showed that the addition of radioembolization to systemic therapy in the first-line led to a significant survival benefit of almost 5 months (hazard ratio 0.64, 95%CI 0.46-0.89) in patients with right-sided primaries. In patients with a left-sided primary tumor, no significant difference in survival was found (62). The first-line treatment generally has the most impact on prognosis. In patients with a right- sided primary tumor, who have a poor prognosis after standard treatment, an early aggressive approach may be warranted. This could potentially include the addition of radioembolization in the first line (63). Mutation status matters too: patients with KRAS wild type have a longer median overall survival compared with patients with KRAS mutation (9.5 months versus 4.8 months) and also a longer progression-free survival (166 days versus 91 days) after treatment with radioembolization (64, 65).