Effect of MLC leaf width and PTV margin on the treatment planning of intensity-modulated stereotactic radiosurgery (IMSRS) or radiotherapy (IMSRT).

We studied the effect of MLC (multileaf collimator) leaf width and PTV (planning target volume) margin on treatment planning of intensity modulated stereotactic radiosurgery (IMSRS) or radiotherapy (IMSRT). Twelve patients previously treated with IMSRS/IMSRT were retrospectively planned with 5- and 3-mm MLC leaf widths and 3- and 2-mm PTV margins using the already contoured clinical target volume and critical structures. The same beam arrangement, planning parameters, and optimization method were used in each of the 4 plans for a given patient. Each plan was normalized so that the prescription dose covered at least 99% of the PTV. Plan indices--D(mean) (mean dose), conformity index (CI), V(70) (volume receiving >or= 70% of the prescription dose), and V(50) (volume receiving >or= 50% of the prescription dose)--were calculated from the dose-volume histograms (DVHs) of the PTV, normal tissue, and organs at risk (OARs). Hypothesis testing was performed on the mean ratios of plan indices to determine the statistical significance of the relative differences. The PTV was well covered for all plans, as no significant differences were observed for D(95), V(95), D(max), D(min), and D(mean) of the PTV. The irradiated volume was approximately 23% smaller when 2-mm instead of 3-mm PTV margin was used, but it was only reduced by approximately 6% when the MLC leaf width was reduced from 5 mm to 3 mm. For normal tissue and brainstem, V(70), V(50), and D(mean) were reduced more effectively by a decrease in MLC width, while D(mean) of optic nerve and chiasm were more sensitive to a change in PTV margin. The DVH statistics for the PTV and normal structures from the treatment plan with 5-mm MLC and 2-mm PTV margin were equal to those with 3-mm MLC and 3-mm PTV margin. PTV margin reduction is more effective in sparing the normal tissue and OARs than a reduction in MLC leaf width. For IMSRS, where highly accurate setup and small PTV margins are routinely employed, the use of 5-mm MLC is therefore less desirable.

Sphingomyelin synthase 2 is one of the determinants for plasma and liver sphingomyelin levels in mice.

BACKGROUND: It has been proposed that plasma sphingomyelin (SM) plays a very important role in plasma lipoprotein metabolism and atherosclerosis. Sphingomyelin synthase (SMS) is the last enzyme for SM de novo biosynthesis. Two SMS genes, SMS1 and SMS2, have been cloned and characterized. METHODS AND RESULTS: To evaluate the in vivo role of SMS2 in SM metabolism, we prepared SMS2 knockout (KO) and SMS2 liver-specific transgenic (LTg) mice and studied their plasma SM and lipoprotein metabolism. On a chow diet, SMS2 KO mice showed a significant decrease in plasma SM levels (25%, P<0.05), but no significant changes in total cholesterol, total phospholipids, or triglyceride, compared with wild-type (WT) littermates. On a high-fat diet, SMS2 KO mice showed a decrease in plasma SM levels (28%, P<0.01), whereas SMS2LTg mice showed a significant increase in those levels (29%, P<0.05), but no significant changes in other lipids, compared with WT littermates. Atherogenic lipoproteins from SMS2LTg mice displayed a significantly stronger tendency toward aggregation after mammalian sphingomyelinase treatment, compared with controls. Moreover, SMS2 deficiency significantly increased plasma apoE levels (2.0-fold, P<0.001), whereas liver-specific SMS2 overexpression significantly decreased those levels (1.8-fold, P<0.01). Finally, SMS2 KO mouse plasma promoted cholesterol efflux from macrophages, whereas SMS2LTg mouse plasma prevented it. CONCLUSIONS: We therefore believe that regulation of liver SMS2 activity could become a promising treatment for atherosclerosis.