Single arc volumetric modulated arc therapy for complex brain gliomas: is there an advantage as compared to intensity modulated radiotherapy or by adding a partial arc?

The objective of this study was to determine if volumetric modulated arc therapy (VMAT) offers advantages over intensity modulated radiotherapy (IMRT) for complex brain gliomas and evaluate the role of an additional partial arc. Twelve patients with glioma involving critical organs at risk (OAR) were selected [six low grade brainstem glioma (BG) and six glioblastoma (GB) cases]. BGs were prescribed 54 Gy/30 fractions (frx), and GB treated to 50 Gy/30 frx to a lower dose PTV (PTV50) with a simultaneous integrated boost delivering a total dose of 60 Gy/30 frx to a higher dose PTV (PTV60). VMAT was planned with a single arc (VMAT1) and with an additional coplanar partial arc spanning 90° (VMAT2). We observed VMATI improving the PTV equivalent uniform dose (EUD) for BG cases (p=0.027), improving the V95 for the PTV50 in GB cases (p=0.026) and resulting in more conformal GB plans (p=0.008) as compare to IMRT. However, for the GB PTV60, IMRT achieved favorable V95 over VMAT1 and VMAT2 (0.0046 and 0.008, respectively). The GB total integral dose (ID) was significantly lower with VMAT1 and VMAT2 (p=0.049 and p=0.006, respectively). Both VMAT1 and VMAT2 reduced the ID, however, only at the 5 Gy threshold for BG cases (p=0.011 and 0.005, respectively). VMAT achieved a lower spinal cord maximum dose and EUD for BG cases and higher optic nerve doses, otherwise no significant differences were observed. VMAT1 yielded the fastest treatment times and least MU. We conclude that VMAT offers faster treatment delivery for complex brain tumors while maintaining similar dosimetric qualities to IMRT. Selective dosimetric advantages in terms of spinal cord sparing and lowering the ID are observed favoring the use of an additional coplanar partial arc.

Slowly inactivating potassium conductance (I(D)): a potential target for stroke therapy.

BACKGROUND AND PURPOSE: Excessive accumulation of extracellular glutamate results in the death of most, but not all, neurons in the central nervous system. Understanding the unique properties of cells that can withstand this excitotoxic challenge may identify specific targets for novel stroke therapies. METHODS: A combination of in vivo methods for analysis of excitotoxic cell death after activation of N-methyl-D-aspartate (NMDA) receptors and in vitro patch-clamp analysis of specific conductances in hypothalamic slices and dissociated cells has been used to assess the roles of specific potassium conductances in delayed cell death after NMDA receptor activation. RESULTS: We report that a specific D-type potassium conductance (I(D)), necessary for the rapid repolarization of the membrane after a strong depolarization, serves such a protective purpose in magnocellular neurons of the paraventricular nucleus. Manipulations that inhibit this current (4-aminopyridine or angiotensin II) increase neuronal excitability and augment cell death after NMDA receptor activation. In addition, this protection is not observed in magnocellular neurons of spontaneously hypertensive rats, and intriguingly it can be reestablished by blocking angiotensin II receptors in these animals. CONCLUSIONS: These observations provide a persuasive experimental explanation for the unexpected finding that therapeutic treatments for hypertension that block central as well as peripheral angiotensin type 1 receptors reduce the severity and occurrence of stroke.