Presence of tumour capsule on contrast-enhanced CT is associated with improved outcomes of stereotactic body radiation therapy in hepatocellular carcinoma patients

Purpose Stereotactic body radiation therapy (SBRT) is a novel local therapy for the treatment of hepatocellular carcinoma (HCC). While effective, there is currently noreliable radiological marker to guide patient selection. In this study, we investigated the prognostic value of capsule appearanceon contrast-enhanced computed tomography (CT) for patients undergoing SBRT. Materials and Methods Between 2006 and 2017, 156 consecutive patients with Child-Pugh score class A/B and HCC ≥5cm that underwent SBRT were retrospectively analysed. Baseline triple-phase CTs of the abdomen were reviewed for the presence of capsule appearances and correlated with objective response rate (ORR), overall survival (OS), and pattern of treatment failure. Results Capsule appearance on CT was present in 83 (53.2%) patients.It was associated with improved ORR by Response Evaluation Criteria in Solid Tumours (RECIST) (60.2% vs 24.7%; p<0.001) andModified Response Evaluation Criteria in Solid Tumours(mRECIST) (ORR 78.3% vs 34.2%; p<0.001). The presence of a capsule was also associated with superior 2-year local control (89.1% vs. 51.4%; p<0.001) and 2-year OS (34.1% vs. 14.8%, p<0.01). Hepatic out-field failure was the dominant mode of progression, which was less common in patients with intact capsule (54.2% vs. 60.3%, p=0.01). Conclusion Capsule appearance on CT could potentially be a non-invasive prognostic marker for selecting HCC patients undergoing SBRT. Larger cohort is warranted to validate our findings

Nusinersen versus Sham Control in Later-Onset Spinal Muscular Atrophy

International audienceBACKGROUND Nusinersen is an antisense oligonucleotide drug that modulates pre-messenger RNA splicing of the survival motor neuron 2 (SMN2) gene. It has been developed for the treatment of spinal muscular atrophy (SMA). METHODS We conducted a multicenter, double-blind, sham-controlled, phase 3 trial of nusinersen in 126 children with SMA who had symptom onset after 6 months of age. The children were randomly assigned, in a 2: 1 ratio, to undergo intrathecal administration of nusinersen at a dose of 12 mg (nusinersen group) or a sham procedure (control group) on days 1, 29, 85, and 274. The primary end point was the least-squares mean change from baseline in the Hammersmith Functional Motor Scale-Expanded (HFMSE) score at 15 months of treatment; HFMSE scores range from 0 to 66, with higher scores indicating better motor function. Secondary end points included the percentage of children with a clinically meaningful increase from baseline in the HFMSE score (>= 3 points), an outcome that indicates improvement in at least two motor skills. RESULTS In the prespecified interim analysis, there was a least-squares mean increase from baseline to month 15 in the HFMSE score in the nusinersen group (by 4.0 points) and a least-squares mean decrease in the control group (by -1.9 points), with a significant between-group difference favoring nusinersen (least-squares mean difference in change, 5.9 points; 95% confidence interval, 3.7 to 8.1; P< 0.001). This result prompted early termination of the trial. Results of the final analysis were consistent with results of the interim analysis. In the final analysis, 57% of the children in the nusinersen group as compared with 26% in the control group had an increase from baseline to month 15 in the HFMSE score of at least 3 points (P< 0.001), and the overall incidence of adverse events was similar in the nusinersen group and the control group (93% and 100%, respectively). CONCLUSIONS Among children with later-onset SMA, those who received nusinersen had significant and clinically meaningful improvement in motor function as compared with those in the control group. (Funded by Biogen and Ionis Pharmaceuticals; CHERISH ClinicalTrials. gov number, NCT02292537.