Synchrotron-based infrared microspectroscopy study on the radiosensitization effects of Gd nanoparticles at megavoltage radiation energies

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

Synchrotron-based infrared microspectroscopy study on the radiosensitization effects of Gd nanoparticles at megavoltage radiation energies

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

Field correction factors for a PTW-31016 pinpoint ionization chamber for both flattened and unflattened beams. Study of the main sources of uncertainties

Purpose The primary aim of this study was to determine correction factors, math formula for a PTW-31016 ionization chamber on field sizes from 0.5 cm × 0.5 cm to 2 cm × 2 cm for both flattened (FF) and flattened filter-free (FFF) beams produced in a TrueBeam clinical accelerator. The secondary objective was the determination of field output factors, math formula over this range of field sizes using both Monte Carlo (MC) simulation and measurements. Methods math formula for the PTW-31016 chamber were calculated by MC simulation for field sizes of 0.5 cm × 0.5 cm, 1 cm × 1 cm, and 2 cm × 2 cm. MC simulations were performed with the PENELOPE code system for the 10 MV FFF Particle Space File from a TrueBeam linear accelerator (LINAC) provided by the manufacturer (Varian Medical Systems, Inc. Palo Alto, CA, USA). Simulations were repeated taking into account chamber manufacturing tolerances and accelerator jaw positioning in order to assess the uncertainty of the calculated correction factors. Output ratios were measured on square fields ranging from 0.5 cm × 0.5 cm to 10 cm × 10 cm for 6 MV and 10 MV FF and FFF beams produced by a TrueBeam using a PTW-31016 ionization chamber; a Sun Nuclear Edge detector (SunNuclear Corp., Melbourne, FL, USA) and TLD–700R (Harshaw, Thermo Scientific, Waltham, MA, USA). The validity of the proposed correction factors was verified using the calculated correction factors for the determination of math formula using a PTW-31016 at the four TrueBeam energies and comparing the results with both TLD-700R measurements and MC simulations. Finally, the proposed correction factors were used to assess the correction factors of the SunNuclear Edge detector. Results The present work provides a set of MC calculated correction factors for a PTW-31016 chamber used on a TrueBeam FF and FFF mode. For the 0.5 cm × 0.5 cm square field size, math formula is equal to 1.17 with a combined uncertainty of 2% (k = 1). A detailed analysis of the most influential parameters is presented in this work. PTW-31016 corrected measurements were used for the determination of math formula for 6 MV and 10 MV FF and FFF and the results were in agreement with values obtained using a TLD-700R detector (differences < 3% for a 0.5 cm square field) for the four energies studied. Uncertainty in field collimation was found to be the main source of influence of math formula and caused differences of up to 15% between calculations and measurements for the 0.5 cm × 0.5 cm field. This was also confirmed by repeating the same measurements at two different institutions. Conclusions This study confirms the need to introduce correction factors when using a PTW-31016 chamber and the hypothesis of their low energy dependence. MC simulation has been shown to be a useful methodology to determine detector correction factors for small fields and to analyze the main sources of uncertainty. However, due to the influence of the LINAC jaw setup for field sizes below or equal to 1 cm, MC methods are not recommended in this range for field output factor calculations

Pretreatment quality assurance of flattening filter free beams on 224 patients for intensity modulated plans: a multicentric study

PURPOSE: Pretreatment quality assurance data from four centers, members of the European TrueBeam council were analyzed with different verification devices to assess reliability of flattening filter free beam delivery for intensity modulated radiotherapy (IMRT) and RapidArc (RA) techniques. METHODS: TrueBeam(®) (Varian Medical System) is a new linear accelerator designed for delivering flattened, as well as flattening filter free beams. Pretreatment dosimetric validation of plan delivery was performed with different verification devices and responses to high dose rates were tested. Treatment planning was done in Eclipse planning system (PRO 8.9, AAA 8.9). γ evaluation was performed with (dose difference) = 3% and (distance to agreement) = 3 mm scoring the gamma agreement index (GAI, % of field area passing the test). Two hundred and twenty-four patients with 1-6 lesions in various anatomical regions and dose per fraction ranging from 1.8 Gy to 25 Gy were included in the study; 88 were treated with 6 MV flattening filter free (X6FFF) beam energy and 136 with 10 MV flattening filter free (X10FFF) beam. Gafchromic films in solid water, delta(4), arccheck, and matrixx phantom were used to verify the dose distributions. Additionally, point measurements were performed using a PinPoint chamber and a Farmer chamber. RESULTS: Dose calculation as well as dose delivery was equally accurate for IMRT and RA delivery (IMRT: GAI = 99.3% (±1.1); RA: GAI = 98.8% (±1.1) as well as for the two beams evaluated (X6FFF: GAI = 99.1% (±1.0); X10FFF: GAI = 98.8% (±1.2). Only small differences were found for the four verification devices. A point dose verification was performed on 52 cases, obtaining a dose deviation of 0.34%. The GAI variations with number of monitor units were statistically significant. CONCLUSIONS: The TrueBeam FFF modality, analyzed with a variety of verification devices and planned with Eclipse planning system is dosimetrically accurate (within the specified limits 3 mm/3%) for both X6FFF and X10FFF beam energy