ABSTRACT
The outcome of radiotherapy can be further improved by combining radiotherapy with nanoparticles. Previous biological studies showed a significant amplification of the biological damage in cells charged with nanoparticles prior to radiotherapy treatments. The rationale has been based on the physical dose enhancement. However, this subject is still a matter of controversy and there are clear indications that biochemical effects may play a key role in the radiosensitization effects of nanoparticles. Within this context, the main goal of our study was to provide new insights into the radiosensitization effects of F98 glioma cells exposed to gadolinium nanoparticles combined with clinical megavoltage beams, and compare them with respect to kilovoltage radiotherapy (commonly used in combination with nanoparticles). For this purpose, we used synchrotron-based Fourier transform infrared microspectroscopy (SR-FTIRM) to provide relevant information on the treatment-induced biochemical changes of the main cell biomolecules. Biochemical differences were evaluated after the treatments to assess cellular damage. Multivariate analysis revealed nanoparticle-dependent changes in megavoltage treated cells. The main spectral variations were related to conformational changes in the protein secondary structures, which might be induced by radiation damage and by changes or rearrangements in the nucleic acid structures due to the initiation of DNA repair mechanisms. We also observed significant changes in the phosphate I and II bands, which concerns DNA damage, while few changes were detected in the lipid region. Spectroscopic data showed that these changes increased as a function of the dose. Finally, PCA analysis did not discriminate clearly between megavoltage and kilovoltage groups treated with nanoparticles, indicating that megavoltage radiosensitization effects might not differ significantly from those in kilovoltage radiotherapy.
ABSTRACT
PURPOSE: Phase-space files for Monte Carlo simulation of the Varian TrueBeam beams have been made available by Varian. The aim of this study is to evaluate the accuracy of the distributed phase-space files for flattening filter free (FFF) beams, against experimental measurements from ten TrueBeam Linacs. METHODS: The phase-space files have been used as input in PRIMO, a recently released Monte Carlo program based on the PENELOPE code. Simulations of 6 and 10 MV FFF were computed in a virtual water phantom for field sizes 3 × 3, 6 × 6, and 10 × 10 cm(2) using 1 × 1 × 1 mm(3) voxels and for 20 × 20 and 40 × 40 cm(2) with 2 × 2 × 2 mm(3) voxels. The particles contained in the initial phase-space files were transported downstream to a plane just above the phantom surface, where a subsequent phase-space file was tallied. Particles were transported downstream this second phase-space file to the water phantom. Experimental data consisted of depth doses and profiles at five different depths acquired at SSD = 100 cm (seven datasets) and SSD = 90 cm (three datasets). Simulations and experimental data were compared in terms of dose difference. Gamma analysis was also performed using 1%, 1 mm and 2%, 2 mm criteria of dose-difference and distance-to-agreement, respectively. Additionally, the parameters characterizing the dose profiles of unflattened beams were evaluated for both measurements and simulations. RESULTS: Analysis of depth dose curves showed that dose differences increased with increasing field size and depth; this effect might be partly motivated due to an underestimation of the primary beam energy used to compute the phase-space files. Average dose differences reached 1% for the largest field size. Lateral profiles presented dose differences well within 1% for fields up to 20 × 20 cm(2), while the discrepancy increased toward 2% in the 40 × 40 cm(2) cases. Gamma analysis resulted in an agreement of 100% when a 2%, 2 mm criterion was used, with the only exception of the 40 × 40 cm(2) field (â¼95% agreement). With the more stringent criteria of 1%, 1 mm, the agreement reduced to almost 95% for field sizes up to 10 × 10 cm(2), worse for larger fields. Unflatness and slope FFF-specific parameters are in line with the possible energy underestimation of the simulated results relative to experimental data. CONCLUSIONS: The agreement between Monte Carlo simulations and experimental data proved that the evaluated Varian phase-space files for FFF beams from TrueBeam can be used as radiation sources for accurate Monte Carlo dose estimation, especially for field sizes up to 10 × 10 cm(2), that is the range of field sizes mostly used in combination to the FFF, high dose rate beams.