Caren van Roekel

274 Chapter 10 attempt was made to find thresholds for both safety and efficacy. A patient-based threshold for efficacy was established at 90 Gy. However, not only the tumor- absorbed dose is important for personalized dosimetry: to avoid treatment- related complications, the parenchymal-absorbed dose should be taken into account as well. In our study, the incidence of toxicity was low, rendering it difficult to draw a strong conclusion on the maximum tolerable parenchymal- absorbed dose. There was only one patient with radioembolization-induced liver disease who had received 34 Gy to the parenchyma, while patients with much higher parenchymal-absorbed doses did not have much toxicity. Hence, it was concluded that a parenchymal-absorbed dose up to 55 Gy (the highest observed parenchymal-absorbed dose in our cohort) has an acceptable safety profile, depending on individual patient characteristics. For future mCRC patients who are planned for treatment with 166 Ho-radioembolization, it is advised to use a flexible parenchymal-absorbed dose threshold, with a maximum of 55 Gy. Depending an the physicians preference, one can either opt for maximizing tumor-absorbed dose (>90 Gy mean tumor-absorbed dose) by maximizing the parenchymal-absorbed dose up to the safety threshold (=55 Gy) or limiting healthy tissue irradiation (<55 Gy) while maintaining the minimal efficacy threshold for tumor tissue (≥90 Gy). In case the minimal efficacy threshold for tumor tissue is not reached (<90 Gy), while maximizing the healthy tissue absorbed dose (=55 Gy), that particular patient should not be eligible for a radioembolization treatment. In future studies, this personalized treatment approach should be used. How can radioembolization be further improved and why is this needed? Patients with CRC generally have relatively hypovascular hepatic metastases and a suboptimal activity distribution (51, 92). Response rates after radioembolization are modest: in our dose-response study in mCRC patients treated with 166 Ho-radioembolization, response rate was only 30%. In patients treated with 90 Y-radioembolization, comparable results are obtained, with a response rate of 37% (87). These numbers illustrate the need for treatment optimization. As mentioned earlier in this discussion, patient selection and personalized dosimetry are the most important factors to improve radioembolization, but there are other factors that can influence treatment outcome.