Feasibility of extreme dose escalation for glioblastoma multiforme using 4π radiotherapy

BACKGROUND: Glioblastoma multiforme (GBM) frequently recurs at the same location after radiotherapy. Further dose escalation using conventional methods is limited by normal tissue tolerance. 4π non-coplanar radiotherapy has recently emerged as a new potential method to deliver highly conformal radiation dose using the C-arm linacs. We aim to study the feasibility of very substantial GBM dose escalation while maintaining normal tissue tolerance using 4π. METHODS: 11 GBM patients previously treated with volumetric modulated arc therapy (VMAT/RapidArc) on the NovalisTx™ platform to a prescription dose of either 59.4 Gy or 60 Gy were included. All patients were replanned with 30 non-coplanar beams using a 4π radiotherapy platform, which inverse optimizes both beam angles and fluence maps. Four different prescriptions were used including original prescription dose and PTV (4πPTV(PD)), 100 Gy to the PTV and GTV (4πPTV(100Gy)), 100 Gy to the GTV only while maintaining prescription dose to the rest of the PTV (4πGTV(100Gy)), and a 5 mm margin expansion plan (4πPTV(PD+5mm)). OARs included in the study are the normal brain (brain – PTV), brainstem, chiasm, spinal cord, eyes, lenses, optical nerves, and cochleae. RESULTS: The 4π plans resulted in superior dose gradient indices, as indicated by >20% reduction in the R50, compared to the clinical plans. Among all of the 4π cases, when compared to the clinical plans, the maximum and mean doses were significantly reduced (p < 0.05) by a range of 47.01-98.82% and 51.87-99.47%, respectively, or unchanged (p > 0.05) for all of the non-brain OARs. Both the 4πPTV(PD) and 4π GTV(100GY)plans reduced the mean normal brain mean doses. CONCLUSIONS: 4π non-coplanar radiotherapy substantially increases the dose gradient outside of the PTV and better spares critical organs. Dose escalation to 100 Gy to the GTV or additional margin expansion while meeting clinical critical organ dose constraints is feasible. 100 Gy to the PTV result in higher normal brain doses but may be tolerated when delivered in proportionally increased treatment fractions. Therefore, 4π non-coplanar radiotherapy on C-arm gantry may provide an accessible tool to improve the outcome of GBM radiotherapy through extreme dose escalation.