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Radioembolisation with 90Y-microspheres is a new locoregional treatment of hepatic lesions, usually applied as single cycle. Multi-cycle treatments might be considered as a strategy to improve the risk-benefit balance. With the aim to derive suitable information for patient tailored therapy, available patients' dosimetric data were reviewed according to the linear-quadratic model and converted into biological effective dose (BED) values. Single vs. multi-cycle approaches were compared through radiobiological perspective.Twenty patients with metastatic lesions underwent radioembolisation. The 90Y-administered activity (AA) was established in order to respect a precautionary limit dose (40 Gy) for the non-tumoral liver (NTL). BED was calculated setting α/β = 2.5 Gy (NTL), 10 Gy (tumours); T1/2,eff = T1/2,phys = 64.2 h; T1/2,rep = 2.5 h (NTL), 1.5 h (tumours). The BED to NTL was considered as a constraint for multi-cycle approach. The AA for two cycles and the percent variations of AA, tumour dose, BED were estimated.In one-cycle, for a prescribed BED to NTL of 64 Gy (NTL dose = 40 Gy), AA was 1.7 (0.9-3.2) GBq, tumour dose was 130 (65-235) Gy, and tumour BED was 170 (75-360) Gy. Considering two cycles, ˜15% increase was found for AA and dose to NTL, with unvaried BED for NTL. Tumour dose increase was 20 (10-35) Gy; tumour BED increase was 10 (3-11) Gy. In different protocols allowing 80 Gy to NTL, the BED sparing estimated was ˜50 Gy (two cycles) and 65 Gy (three cycles).From a radiobiological perspective, multi-cycle treatments would allow administering higher activities with increased tumour irradiation and preserved radiation effects on NTL. Trials comparing single vs. multiple cycles are suggested.