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At least 1,603 records · Page 89

Optimal beam margins in linac-based VMAT stereotactic ablative body radiotherapy: a Pareto front analysis for liver metastases

We explored the Pareto fronts mathematical strategy to determine the optimal block margin and prescription isodose for stereotactic body radiotherapy (SBRT) treatments of liver metastases using the volumetric-modulated arc therapy (VMAT) technique. Three targets (planning target volumes [PTVs] = 20, 55, and 101 cc) were selected. A single fraction dose of 26 Gy was prescribed (prescription dose [PD]). VMAT plans were generated for 3 different beam energies. Pareto fronts based on (1) different multileaf collimator (MLC) block margin around PTV and (2) different prescription isodose lines (IDL) were produced. For each block margin, the greatest IDL fulfilling the criteria (95% of PTV reached 100%) was considered as providing the optimal clinical plan for PTV coverage. Liver D{sub mean}, V7Gy, and V12Gy were used against the PTV coverage to generate the fronts. Gradient indexes (GI and mGI), homogeneity index (HI), and healthy liver irradiation in terms of D{sub mean}, V7Gy, and V12Gy were calculated to compare different plans. In addition, each target was also optimized with a full-inverse planning engine to obtain a direct comparison with anatomy-based treatment planning system (TPS) results. About 900 plans were calculated to generate the fronts. GI and mGI show a U-shaped behavior as a function of beam margin with minimal values obtained with a +1 mm MLC margin. For these plans, the IDL ranges from 74% to 86%. GI and mGI show also a V-shaped behavior with respect to HI index, with minimum values at 1 mm for all metrics, independent of tumor dimensions and beam energy. Full-inversed optimized plans reported worse results with respect to Pareto plans. In conclusion, Pareto fronts provide a rigorous strategy to choose clinical optimal plans in SBRT treatments. We show that a 1-mm MLC block margin provides the best results with regard to healthy liver tissue irradiation and steepness of dose fallout.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Mthfr gene ablation enhances susceptibility to arsenic prenatal toxicity

Background: In utero exposure to arsenic is known to adversely affect reproductive outcomes. Evidence of arsenic teratogenicity varies widely and depends on individual genotypic differences in sensitivity to As. In this study, we investigated the potential interaction between 5,10-methylenetetrahydrofolate reductase (Mthfr) genotype and arsenic embryotoxicity using the Mthfr knockout mouse model. Methods: Pregnant dams were treated with sodium arsenate, and reproductive outcomes including: implantation, resorption, congenital malformation and fetal birth weight were recorded at E18.5. Results: When the dams in Mthfr{sup +/−} × Mthfr{sup +/−} matings were treated with 7.2 mg/kg As, the resorption rate increased to 43.4%, from a background frequency of 7.2%. The As treatment also induced external malformations (40.9%) and significantly lowered the average fetal birth weight among fetuses, without any obvious toxic effect on the dam. When comparing the pregnancy outcomes resulting from different mating scenarios (Mthfr{sup +/+} × Mthfr{sup +/−}, Mthfr{sup +/−} × Mthfr{sup +/−} and Mthfr{sup −/−} × {sup Mthfr+/−}) and arsenic exposure; the resorption rate showed a linear relationship with the number of null alleles (0, 1 or 2) in the Mthfr dams. Fetuses from nullizygous dams had the highest rate of external malformations (43%) and lowest average birth weight. When comparing the outcomes of reciprocal matings (nullizygote × wild-type versus wild-type × nullizygote) after As treatment, the null dams showed significantly higher rates of resorptions and malformations, along with lower fetal birth weights. Conclusions: Maternal genotype contributes to the sensitivity of As embryotoxicity in the Mthfr mouse model. The fetal genotype, however, does not appear to affect the reproductive outcome after in utero As exposure. - Highlights: • An interaction between Mthfr genotype and arsenic embryotoxicity is presented. • Maternal Mthfr genotype contributes to the sensitivity of As embryotoxicity. • Fetal Mthfr genotype does not affect the reproductive outcome after As exposure.

60 APPLIED LIFE SCIENCES↗