A Medical Physics–Driven Clinical Trial of Temporally Modulated Pulsed Radiotherapy (NRG-CC017)
Abstract
Purpose
To design and validate reliable treatment planning and delivery verification methods for TMPRT in the phase III NRG CC-017 trial, which compares TMPRT to standard radiotherapy in adults with newly diagnosed MGMT-unmethylated glioblastomas, with these methods being generally applicable to all grade 4 gliomas.
Methods
Treatment planning methodologies were developed utilizing both volumetric modulated arc therapy (VMAT) and three-dimensional conformal radiotherapy (3D-CRT), ensuring adherence to the specifications of the NRG CC-017 protocol. Each plan, including individual fields (pulses), underwent evaluation for homogeneity and conformality, measured by the homogeneity index (HI) and Paddick conformality index (CIPaddick); and compliance with organ-at-risk dose constraints. Deliverability of these treatment plans was assessed through a combination of in-phantom ionization chamber measurements and electronic portal imaging device (EPID) verification, specifically at low dose rates (≤100 MU/min). To support protocol compliance, verification methods for temporal modulation were designed to batch-process treatment delivery records exported from both the Aria and the Mosaiq R&V systems. For each delivered treatment, both immediate effective dose rate and fraction-effective dose rate were calculated to confirm that the fraction-effective dose rate did not exceed 0.067 Gy/min.
Results
Single-arc VMAT plans achieved better dose homogeneity (HI ≤ 0.13) and conformality (CIPaddick ≥ 0.84), with sufficient coverage and organ sparing. Multi-arc plans were found to have unacceptably high intra-field heterogeneity. When VMAT was not feasible, 3D-CRT with dynamic or static fields was a suitable fallback. Ionization chamber measurements showed dose accuracy within 1.4%, and EPID gamma analysis (1%/1mm) had pass rates of 91–97%, confirming reliable treatment.
Conclusion
Medical physicists have been involved in developing and conducting radiobiological experiments on radiation hypersensitivity and TMPRT treatments. Uniform planning methods are vital to the NRG CC-017 trial's success. Automated post-treatment record analysis supports protocol compliance and improves clinical reproducibility.