With the large-scale introduction of volumetric modulated arc therapy (VMAT), selection of optimal beam angles for coplanar static-beam IMRT has increasingly become obsolete. Due to unavailability of VMAT in current MR-linacs, the problem has re-gained importance. An application for automated IMRT treatment planning with integrated, patient-specific computer-optimization of beam angles (BAO) was used to systematically investigate computer-aided generation of beam angle class solutions (CS) for replacement of computationally expensive patient-specific BAO. Rectal cancer was used as a model case.

MATERIALS AND METHODS:

23 patients treated at a Unity MR-linac were included. BAO_x plans (x=7-12 beams) were generated for all patients. Analyses of BAO₁₂ plans resulted in CS_x class solutions. BAO_x plans, CS_x plans, and plans with equi-angular setups (EQUI_x, x=9-56) were mutually compared.

RESULTS:

For x>7, plan quality for CS_x and BAO_x was highly similar, while both were superior to EQUI_x. E.g. with CS₉, bowel/bladder D_mean reduced by 22% [11%, 38%] compared to EQUI₉ (p<0.001). For equal plan quality, the number of EQUI beams had to be doubled compared to BAO and CS.

CONCLUSIONS:

Computer-generated beam angle CS could replace individualized BAO without loss in plan quality, while reducing planning complexity and calculation times, and resulting in a simpler clinical workflow. CS and BAO largely outperformed equi-angular treatment. With the developed CS, time consuming beam angle re-optimization in daily adaptive MR-linac treatment could be avoided. Further systematic research on computerized development of beam angle class solutions for MR-linac treatment planning is warranted.

2008-06-01·Radiation research3区 · 医学

Profiling Mitochondrial Proteins in Radiation-Induced Genome-Unstable Cell Lines with Persistent Oxidative Stress by Mass Spectrometry

3区 · 医学

Article

作者: Shuangshuang Jin ; John H. Miller ; Umut Aypar ; Austin Yang ; Jonathan S. Peters ; David L. Springer ; Yunhu Wan ; William F. Morgan

Previous work by Morgan and coworkers on radiation-induced genome instability in Chinese hamster ovary (CHO) cell lines showed that unstable LS-12 cells had persistently elevated levels of reactive oxygen species (ROS) that were likely due to dysfunctional mitochondria. To further investigate the correlation between radiation-induced genome instability and dysfunctional mitochondria, we performed quantitative high-throughput mass spectrometry on samples enriched in mitochondrial proteins from three chromosomally unstable CHO cell lines and their stable unirradiated GM10115 parental cell line. Out of several hundred identified proteins, sufficient data were collected on 74 mitochondrial proteins to test for statistically significant differences in their abundance between unstable and stable cell lines. The LS-12 cell line, which exhibited the highest level of ROS among the three unstable cell lines, was characterized by eight significantly down-regulated mitochondrial proteins, all associated with the TCA (tricarboxylic acid). Elevated levels of ROS relative to the unirradiated parental control were also statistically significant for the CS-9 cell line. The protein profile of CS-9 revealed five significantly up-regulated mitochondrial proteins, three of which are involved in oxidative phosphorylation. Elevation of ROS in the unstable 115 cell line was nearly as large as that seen in CS-9 cells but was not statistically significant. The mitochondrial protein profile of 115 cells showed significant down-regulation of acetyl-CoA-acetyltransferase, which was also down-regulated in LS-12, and two other proteins with abundances that were significantly different from control levels but were not directly related to either the TCA or oxidative phosphorylation. These results provide further evidence that elevated ROS and mitochondrial dysfunction are associated with radiation-induced genome instability; however, additional work is required to establish a firm mechanistic relationship between these end points.

100 项与 CS-009 相关的药物交易

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