Huntington's disease (HD) is caused by an expansion of CAG triplets at the 5¢ end of the HD gene, which encodes a pathologically elongated polyglutamine stretch near the N-terminus of huntingtin. HD is an incurable autosomal-dominant neurodegenerative disease characterized by movement disorder, as well as emotional distress and dementia. The newly discovered roles of the non-coding small RNAs in specific degradation or translational suppression of the targeted mRNAs suggest a potential therapeutic approach of post-transcriptional gene silencing that targets the underlying disease etiology rather than the downstream pathological consequences. From pre-clinical trials in different HD animal models to cells from HD patients, small RNA interference has been applied to 'allele-non-specifically or allele-specifically' silence the mutant HD transgene or endogenous mutant HD allele. Silencing the mutant HD transgene significantly inhibits neurodegeneration, improves motor control, and extends survival of HD mice. With future improvement of mutant allele selectivity (preserving the expression of the neuroprotective wild-type allele), target specificity, efficacy and safety, as well as optimization of delivery methods, small non-coding RNA-based therapeutic applications will be a promising approach to treat HD.
Purpose: To evaluate the dosimetric influence of setup errors on RapidArc‐based SRS for simultaneous irradiation of multiple intracranial targets. Methods: Eight patients previously treated with RapidArc™ technique for multiple intracranial lesions were included in this study. A RapidArc plan was designed to irradiate multiple targets simultaneously with one isocenter and 4 non‐coplanar arcs. 1 mm margin was added to generate PTVs from GTVs. BrainLAB Novalis system was used to position the targets with 6D corrections and monitor patient position during treatment. CBCT was acquired for verification before irradiation. Velocity AI was used for image registration and dose mapping for CBCT, planning CT, contours and dose matrix. The DVHs of targets and critical structures and dose distributions were compared with the planned results and dosimetric influence from setup errors was analyzed. Results: We found that the translational errors were less than 1 mm in the three directions and rotational errors were less than 0.6 degree for all the patients. The overall PTV coverage decreases of ∼10 percent on average while the overall GTV coverage slightly influenced. Although prescribed dosed still covered most of GTVs, there were still some targets with a GTV coverage drop greater than 5 percent even with a 1 mm margin. Most of influenced targets were small targets and relatively far from isocenter. Our study also showed that the dosimetric influence on critical structures was negligible. Conclusions: Although RapidArc technique can generate good plans for effectively treating multiple intracranial lesions simultaneously using stereotactic radiosurgery, this technique is more susceptible to the setup errors, especially rotational errors. 0.5 degree rotational error may Result in non‐ignorable drop in target coverage. Our study show that a 1 mm margin for PTV and 6D positioning are necessary for a successful treatment with this technique.
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