Impact of setup errors on the robustness of linac-based single-isocenter coplanar and non-coplanar VMAT plans for multiple brain metastases.

PURPOSE: Patient setup errors have been a primary concern impacting the dose delivery accuracy in radiation therapy. A robust treatment plan might mitigate the effects of patient setup errors. In this reported study, we aimed to evaluate the impact of translational and rotational errors on the robustness of linac-based, single-isocenter, coplanar, and non-coplanar volumetric modulated arc therapy treatment plans for multiple brain metastases. METHODS: Fifteen patients were retrospectively selected for this study with a combined total of 49 gross tumor volumes (GTVs). Single-isocenter coplanar and non-coplanar plans were generated first with a prescribed dose of 40 Gy in 5 fractions or 42 Gy in 7 fractions to cover 95% of planning target volume (PTV). Next, four setup errors (+1  and +2 mm translation, and +1° and +2° rotation) were applied individually to generate modified plans. Different plan quality evaluation metrics were compared between coplanar and non-coplanar plans. 3D gamma analysis (3%/2 mm) was performed to compare the modified plans (+2 mm and +2° only) and the original plans. Paired t-test was conducted for statistical analysis. RESULTS: After applying setup errors, variations of all plan evaluation metrics were similar (p > 0.05). The worst case for V100% to GTV was 92.07% ± 6.13% in the case of +2 mm translational error. 3D gamma pass rates were > 90% for both coplanar (+2 mm and +2°) and the +2 mm non-coplanar groups but was 87.40% ± 6.89% for the +2° non-coplanar group. CONCLUSION: Translational errors have a greater impact on PTV and GTV dose coverage for both planning methods. Rotational errors have a greater negative impact on gamma pass rates of non-coplanar plans. Plan evaluation metrics after applying setup errors showed that both coplanar and non-coplanar plans were robust and clinically acceptable.

Improving radiotherapy safety and efficiency with the customized ARIA oncology information system.

OBJECTIVE: To improve safety and efficiency of radiotherapy process by customizing a Varian ARIA oncology information system following the guidelines provided in AAPM TG-100 report. METHODS: First, failure mode and effects analysis (FMEA) and quality management program were implemented for radiotherapy process. We have customized the visual care path in the ARIA system and set up a series of templates for simulation, prescription, contouring, treatment planning, and multiple checklists. Average time of activities' completion and amount of planning errors were compared before and after the use of the customized ARIA to evaluate its impact on the efficiency and safety of radiotherapy. RESULTS: Completion time and on-time completion rate of the key activities in the care path are improved. The time of OAR/targets contouring decreases from (1.94±1.51) days to (1.64±1.07) days (p = 0.003), with the on-time completion rate increases from 77.4%to 83.3%(p = 0.048). Treatment planning time decreases from (0.81±0.65) days to (0.55±0.51) days (p < 0.001), with the on-time completion rate increases from 96.6%to 98.3%(p = 0.163). Waiting time of patients decreases from (4.50±1.83) days to (4.04±1.34) days (p < 0.001), with the on-time completion rate increases from 81.9%to 89.7%(p = 0.003). In addition, the average plan error rate decreases from 5.5%(2.9%for safety errors and 2.6%for non-normative errors) to 2.4%(1.6%for safety errors and 0.8%for non-normative errors) (p = 0.029). CONCLUSION: Our study demonstrates that the customized ARIA system has the potential to promote efficiency and safety in radiotherapy process management. It is beneficial to organize and accelerate the treatment process with more effective communications and fewer errors.

MIEF2 reprograms lipid metabolism to drive progression of ovarian cancer through ROS/AKT/mTOR signaling pathway.

MIEF2 (mitochondrial elongation factor 2) is one of the key regulators of mitochondrial fission. Bioinformatics analysis indicated that high expression of MIEF2 predicted a poor prognosis in ovarian cancer patients. However, the relationship between MIEF2 and aberrant lipid metabolism in OC remains elusive. In this study, we demonstrated that MIEF2 significantly promoted lipid synthesis, while has no significant effect on fatty acid uptake and oxidation in OC cells. MIEF2 enhanced de novo fatty acid synthesis through up-regulating the expression of sterol regulatory element binding protein 1 (SREBP1) and its transcriptional target lipogenic genes ACC1, FASN and SCD1. Meanwhile, MIEF2-promoted cholesterol biosynthesis through up-regulating the expression of sterol regulatory element binding protein 2 (SREBP2) and its transcriptional target cholesterol biosynthesis genes HMGCS1 and HMGCR. Mechanistically, increased mitochondrial reactive oxygen species (ROS) production and subsequently activation of AKT/mTOR signaling pathway was found to be involved in the up-regulation of SREBP1 and SREBP2 in OC cells. Moreover, cell growth and metastasis assays indicated that MIEF2-regulated fatty acid synthesis and cholesterol biosynthesis played a critical role in the progression of OC. Taken together, our findings indicate that MIEF2 is a critical regulator of lipid synthesis in OC, which provides a strong line of evidence for this molecule to serve as a drug target in the treatment of this malignancy.