A proof of concept kilovoltage intensity modulated radiotherapy platform for the treatment of glioblastoma multiforme

Abstract

To develop a compact, proof-of-concept kilovoltage intensity modulated radiotherapy platform to deliver contrast-enhanced radiotherapy (CERT). Methods: The proof-of-concept requirements were threefold: (i) develop a compact means to generate a kilovoltage x-ray broadbeam capable of targeting the K-edge of heavy metal contrast, (ii) investigate the potential clinical application of such a beam in silico, and (iii) construct a limited working prototype of the platform to identify weaknesses in the approach. The x-ray broadbeam was created with a standard kilovoltage x-ray tube heavily filtered with 0.156 mm tungsten. Depth dose and treatment characteristics of the beam were investigated using GEANT4 Monte Carlo framework. The working prototype included a miniaturized multi-rod collimator (MRC) constructed with tungsten carbide rods, 3D-printed gear rack, and an in-house GUI/microprocessor assembly. Measurements of simulated treatments were made with EBT3 radiochromic film. Results: Monte Carlo simulations of pseudo-clinical treatments on a homogeneous spherical Lucite phantom produced dose distributions that indicated surface dose was less than target dose. When simulated-bone was added to the calculations, dose-to-bone was found to be the probable limiting factor in clinical treatment. Nevertheless, when iodine contrast enhancement was accounted for, dose was escalated in the tumor compared to standard megavoltage treatments even with dose-to-bone limitations. Experimentally, after commissioning the MRC and calibrating the radiochromic film, surface dose was compared to maximum dose measured on each film. Surface dose measurements were higher than those in a megavoltage beam, but below the skin toxicity threshold. Dose at depth was reasonable despite increased beam attenuation at these energies from photoelectric interactions in bone. IMRT and non-coplanar dose falloffs around the target were steeper than kV 3D conformal dose falloff. Conclusions: The compact kilovoltage treatment platform presented here proved clinically feasible in both simulation and measurement. It is reasonable to pursue this modality further as a potential CERT platform.

In silico analysis of optimum photon energy spectra and beam parameters for iodine nanoparticle–aided orthovoltage radiation therapy of brain tumors

“…Another source of error in MC simulations of the NPs stems from the electron transport algorithm and electron energy cut-offs. The authors believe that using a new version of MCNP code with a more accurate electron transport method of ''single-event'' and lower energy cuff-off of 10 eV 21 gave rise to more reliable values compared to previous studies of Schultz et al 10 and Loughery et al 13 Our results demonstrate the feasibility of NP-aided RT with orthovoltage beams in a clinical setting. More importantly, if the higher targeting capabilities of the INPs for tumor cells were achieved, it would create a significant opportunity for INPs to be accumulated inside the tumor cells and irradiated by orthovoltage beams more accurately than other modalities.…”

“…Another source of error in MC simulations of the NPs stems from the electron transport algorithm and electron energy cut-offs. The authors believe that using a new version of MCNP code with a more accurate electron transport method of “single-event” and lower energy cuff-off of 10 eV 21 gave rise to more reliable values compared to previous studies of Schultz et al 10 and Loughery et al 13…”

“…In the comprehensive study by Loughery et al, 13 both MC and experimental dosimetry methods were utilized to validate the kilovoltage intensity–modulated radiotherapy for the treatment of GBM tumors. In an MC study, 17 cross-firing beams were employed to treat a centrally located tumor in the brain.…”

“…Recently, Loughery et al 13 introduced a novel technique for the treatment of GBM tumors, which employed an iodine contrast agent as a radiosensitizer and orthovoltage intensity–modulated photon beams. In their study, the skull dose was found to be a limiting factor in dose escalation for iodine-loaded brain tumors.…”

External beam radiation therapy with kilovoltage x-rays

“…In 2019, a group at Wayne State University presented a MC computer model and a proof-of-principle experiment for a kilovoltage intensity modulated radiotherapy (IMRT) for the treatment of GBM by means of CERT with iodine [57]. They used Geant4 to simulate dose deposition in a 15-cm diameter spherical water phantom with a 1.4-cm thick spherical shell mimicking the skull and a target of 1.8-cm in diameter filled with 10 mg/mL of iodine.…”