Personalised versus standard dosimetry approach of selective internal radiation therapy in patients with locally advanced hepatocellular carcinoma (DOSISPHERE-01): a randomised, multicentre, open-label phase 2 trial

Background All randomised phase 3 studies of selective internal radiation therapy for advanced hepatocellular carcinoma published to date have reported negative results. However, these did not use personalised dosimetry. We aimed compare the efficacy a versus standard dosimetry approach with yttrium-90-loaded glass microspheres in patients carcinoma. Methods DOSISPHERE-01 was randomised, multicentre, open-label 2 trial done at four health-care centres France. Patients were eligible if they aged 18 years or older and had unresectable locally carcinoma, least one measurable lesion 7 cm more size, hepatic reserve 30% after therapy, no extrahepatic spread (other than lymph nodes hilum, <2 size), contraindications as assessed by technetium-99m macro-aggregated albumin scan. randomly assigned (1:1) permutated block method, sizes without stratification, receive either (120 ± 20 Gy) targeted perfused lobe; group) (≥205 Gy index lesion; group). Investigators, patients, study staff masked treatment. The primary endpoint investigator-assessed objective response rate lesion, according European Association Study Liver criteria, months modified intention-to-treat population. Safety all who received injection, analysed on basis treatment actually (defined central assessment). is registered ClinicalTrials.gov, NCT02582034, has been completed. Findings Between Dec 5, 2015, Jan 4, 2018, 93 eligibility. Of 60 assigned: 31 group 29 (intention-to-treat population). 56 (93%) (28 each treated (modified In population, (71% [95% CI 51–87]) 28 ten (36% [19–56]) an (p=0·0074). safety analysis serious adverse event seven (20%) 35 dosimetry, (33%) 21 most frequent (ie, occurring >5% patients) grade higher events ascites (one [3%] patient vs two [10%] dosimetry), failure (two [6%] none), lymphopenia (12 [34%] nine [43%]), increased aspartate aminotransferase concentrations (three [9%] [10%]), alanine anaemia [5%]), gastrointestinal haemorrhage (none icterus [10%]). One treatment-related death occurred group. Interpretation Compared significantly improved results this suggest that likely improve outcomes clinical practice should be used future trials therapy. Funding Biocompatibles UK, Boston Scientific Group company.