Nada Tomic

Optimizing the dynamic range extension of a radiochromic film dosimetry system

The authors present a radiochromic film dosimetry protocol for a multicolor channel radiochromic film dosimetry system consisting of the external beam therapy (EBT) model GAFCHROMIC film and the Epson Expression 1680 flat-bed document scanner. Instead of extracting only the red color channel, the authors are using all three color channels in the absorption spectrum of the EBT film to extend the dynamic dose range of the radiochromic film dosimetry system. By optimizing the dose range for each color channel, they obtained a system that has both precision and accuracy below 1.5%, and the optimized ranges are 0-4 Gy for the red channel, 4-50 Gy for the green channel, and above 50 Gy for the blue channel.

Absorption spectra time evolution of EBT‐2 model GAFCHROMIC™ film

PURPOSE One of the major drawbacks of the current radiochromic film dosimetry protocols is the postirradiation waiting time. In this article, the authors study the postirradiation time evolution of the absorption spectrum of radiochromic EBT-2 GAFCHROMIC film model. METHODS Postirradiation scanning times range from 3 min to 5 days and a dose range extends from 0 to 6 Gy. The authors compare the results of absorption spectra measurements for the latest GAFCHROMIC EBT-2 film model to the absorption spectra of the previous EBT GAFCHROMIC film model. The authors also describe a method that can establish the time error constraints on the postirradiation scanning time that will still provide an acceptable dose error for clinical applications if the protocol employing the shorter postirradiation scanning time is implemented in the clinic. RESULTS The two film models experience the very same dose change in net absorbance with sensitivity of the latest EBT-2 model GAFCHROMIC film being slightly lower than its predecessor. The authors show that for two postirradiation scanning times of 30 min and 24 h, the 1% dose error can be achieved if the scanning time window is less than +/- 5 min and +/- 2 h, respectively. CONCLUSIONS By comparing the resultant change in net absorbance between the latest EBT-2 and previous EBT GAFCHROMIC film models, the authors conclude that the addition of the yellow marker dye to the sensitive layer does not affect dosimetric properties of the latest film model. The authors also describe a procedure by which one can establish an acceptable time window around chosen postirradiation scanning time protocol that would provide an acceptable dose error for practical purposes.

Reference radiochromic film dosimetry: Review of technical aspects

For decades, film was used as a powerful two-dimensional (2D) dosimetry tool for radiotherapy treatment verification and quality assurance. Unlike the old silver-halide based radiographic films, radiochromic films change its color upon irradiation without the need for chemical development. Radiation dose deposited within a sensitive layer of the radiochromic film initiates polymerization of the active component, the degree of which depends on the amount of energy deposited. Response of the film to radiation is commonly expressed in terms of optical density change, which can be easily measured by any photometric device. However, a number of factors may have an impact on the signal detected by the measuring device. This review summarizes technical aspects associated with the establishment of reference radiochromic film dosimetry and its subsequent use for either clinical or research applications.

Linearization of dose-response curve of the radiochromic film dosimetry system.

PURPOSE Despite numerous advantages of radiochromic film dosimeter (high spatial resolution, near tissue equivalence, low energy dependence) to measure a relative dose distribution with film, one needs to first measure an absolute dose (following previously established reference dosimetry protocol) and then convert measured absolute dose values into relative doses. In this work, we present result of our efforts to obtain a functional form that would linearize the inherently nonlinear dose-response curve of the radiochromic film dosimetry system. METHODS Functional form [ζ = (-1)[middle dot]netOD((2∕3))∕ln(netOD)] was derived from calibration curves of various previously established radiochromic film dosimetry systems. In order to test the invariance of the proposed functional form with respect to the film model used we tested it with three different GAFCHROMIC™ film models (EBT, EBT2, and EBT3) irradiated to various doses and scanned on a same scanner. For one of the film models (EBT2), we tested the invariance of the functional form to the scanner model used by scanning irradiated film pieces with three different flatbed scanner models (Epson V700, 1680, and 10000XL). To test our hypothesis that the proposed functional argument linearizes the response of the radiochromic film dosimetry system, verification tests have been performed in clinical applications: percent depth dose measurements, IMRT quality assurance (QA), and brachytherapy QA. RESULTS Obtained R(2) values indicate that the choice of the functional form of the new argument appropriately linearizes the dose response of the radiochromic film dosimetry system we used. The linear behavior was insensitive to both film model and flatbed scanner model used. Measured PDD values using the green channel response of the GAFCHROMIC™ EBT3 film model are well within ±2% window of the local relative dose value when compared to the tabulated Cobalt-60 data. It was also found that criteria of 3%∕3 mm for an IMRT QA plan and 3%∕2 mm for a brachytherapy QA plan are passing 95% gamma function points. CONCLUSIONS In this paper, we demonstrate the use of functional argument to linearize the inherently nonlinear response of a radiochromic film based reference dosimetry system. In this way, relative dosimetry can be conveniently performed using radiochromic film dosimetry system without the need of establishing calibration curve.

Defining Radiotherapy Target Volumes Using 18F-Fluoro-Deoxy-Glucose Positron Emission Tomography/Computed Tomography: Still a Pandora's Box?

PURPOSE We discuss the effect of (18)F-fluoro-deoxy-glucose (FDG) positron emission tomography (PET)/computed tomography (CT) data on target volume definition for radiotherapy planning. We compared the effect of various thresholding methods on the PET-based target volume vs. the standard CT-based tumor volume. METHODS AND MATERIALS Different thresholding methods were reviewed and compared to our PET-based gross tumor volume data obtained from a cohort of 31 non-small-cell lung carcinoma patients who had undergone preoperative PET/CT scans for staging. The feasibility and limitations of FDG-based PET/CT data on target volume delineation in radiotherapy planning have been demonstrated with frequently used approaches for target outlining such as the qualitative visual method and the fixed 15% or 40% of the maximal iso-uptake value threshold methods. RESULTS The relationship between PET-based and CT-based volumes generally suffers from poor correlation between the two image data sets, expressed in terms of a large statistical variation in gross tumor volume ratios, irrespective of the threshold method used. However, we found that the maximal signal/background ratios in non-small-cell lung carcinoma patients correlated well with the pathologic results, with an average ratio for adenocarcinoma, large cell carcinoma, and squamous cell carcinoma of 10.5 ± 3.5, 12.6 ± 2.8, and 14.1 ± 5.9, respectively. CONCLUSION The fluctuations in tumor volume using different quantitative PET thresholding approaches did not depend on the thresholding method used. They originated from the nature of functional imaging in general and PET imaging in particular. Functional imaging will eventually be used for biologically tailored target radiotherapy volume definition not as a replacement of CT- or magnetic resonance imaging-based anatomic gross tumor volumes but with the methods complementing each other in a complex mosaic of distinct biologic target volumes.

Radiochromic film dosimetry of HDR 192Ir source radiation fields

PURPOSE A radiochromic film based dosimetry system for high dose rate (HDR) Iridium-192 brachytherapy source was described. A comparison between calibration curves established in water and Solid Water™ was provided. METHODS Pieces of EBT-2 model GAFCHROMIC™ film were irradiated in both water and Solid Water™ with HDR (192)Ir brachytherapy source in a dose range from 0 to 50 Gy. Responses of EBT-2 GAFCHROMIC™ film were compared for irradiations in water and Solid Water™ by scaling the dose between media through Monte Carlo calculated conversion factor for both setups. To decrease uncertainty in dose delivery due to positioning of the film piece with respect to the radiation source, traceable calibration irradiations were performed in a parallel-opposed beam setup. RESULTS The EBT-2 GAFCHROMIC™ film based dosimetry system described in this work can provide an overall one-sigma dose uncertainty of 4.12% for doses above 1 Gy. The ratio of dose delivered to the sensitive layer of the film in water to the dose delivered to the sensitive layer of the film in Solid Water™ was calculated using Monte Carlo simulations to be 0.9941 ± 0.0007. CONCLUSIONS A radiochromic film based dosimetry system using only the green color channel of a flatbed document scanner showed superior precision if used alone in a dose range that extends up to 50 Gy, which greatly decreases the complexity of work. In addition, Solid Water™ material was shown to be a viable alternative to water in performing radiochromic film based dosimetry with HDR (192)Ir brachytherapy sources.

Evaluation of EBT‐2 model GAFCHROMIC™ film performance in water

PURPOSE The authors present results of the measurements on the impact of radiochromic film immersion in water. The impact of film piece size, initial optical density, postimmersion waiting time prior to scanning, and the time film was kept in water has been investigated. The authors also investigated the pathways of water penetration into the film during the film immersion in water. METHODS To study the impact of water immersion on change in optical density, the authors used various sizes of the latest EBT-2 model GAFCHROMICTM film: 2 x 2, 4 x 4, and 8 x 8 in.2. In addition, to test any existing dependence of the films optical density on water diffusion, the authors used two sets of films: Unexposed (0 Gy) and film pieces exposed to a dose of 3 Gy. Times that film pieces were left in water ranged from 30 min to 24 h, and once the film was permanently removed from water, the authors also studied the impact of the scanning time (deltat) that ranged from 0 (films scanned right after removal from water) to 72 h postimmersion. RESULTS While the penetration depth can reach as much as 9 mm around the edges of the EBT-2 GAFCHROMIC film, the anticipated dose error due to the change in optical density due to the water immersion appears to be negligible for the short immersions of the order of 30 min. However, as the immersion time increases, the anticipated dose error may reach 22 cGy on a 2 x 2 in.2 piece of film, which corresponds to 7% dose error at 3 Gy of measured dose. CONCLUSIONS In this work, the authors report on an undoubted impact of radiochromic film immersion in water on the measured change in optical density, which may lead to systematic errors in dose measurements if the film is kept in water for longer periods of time. The magnitude of the impact depends on many parameters: Size of the film piece, initial optical density, postimmersion waiting time prior to scanning (defined by the current radiochromic film dosimetry protocol in. place), and the time film was kept in water. The authors also suggested various approaches in correcting for the change in netOD due to water penetration into the film, but the authors believe that the use of the control film piece would be the most appropriate.

Verification of cell irradiation dose deposition using a radiochromic film.

We describe a technique for the MTT assay that irradiates all cells at once by a combination of couch movement and a step-and-shoot irradiation technique on a linear accelerator with 6 MV and 18 MV photon beams. In two experimental setups, we obtained maximum to minimum dose ranges of 10 for the constant MU/bin (monitor units per bin) setup and 20 for the variable MU/bin technique. The irradiation technique described is dose rate independent and it can be used on any teletherapy irradiation machine. We also employed radiochromic film dosimetry to verify dose delivered in each of the wells within the dish. It is shown that for the lowest doses, relative dose variation within wells reaches a value of 6%. We also demonstrated that the radiochromic film positioned below the 96-well plate does not underestimate dose deposited within each compartment by more than 2% due to the vertical dose gradient.

Characterization of calibration curves and energy dependence GafChromicTM XR‐QA2 model based radiochromic film dosimetry system

PURPOSE The authors investigated the energy response of XR-QA2 GafChromic™ film over a broad energy range used in diagnostic radiology examinations. The authors also made an assessment of the most suitable functions for both reference and relative dose measurements. METHODS Pieces of XR-QA2 film were irradiated to nine different values of air kerma in air, following reference calibration of a number of beam qualities ranging in HVLs from 0.16 to 8.25 mm Al, which corresponds to effective energy range from 12.7 keV to 56.3 keV. For each beam quality, the authors tested three functional forms (rational, linear exponential, and power) to assess the most suitable function by fitting the delivered air kerma in air as a function of film response in terms of reflectance change. The authors also introduced and tested a new parameter χ = netΔR·e(m netΔR) that linearizes the inherently nonlinear response of the film. RESULTS The authors have found that in the energy range investigated, the response of the XR-QA2 based radiochromic film dosimetry system ranges from 0.222 to 0.420 in terms of netΔR at K(air)(air) = 8 cGy. For beam qualities commonly used in CT scanners (4.03-8.25 mm Al), the variation in film response (netΔR at K(air)(air) = 8 cGy) amounts to ± 5%, while variation in K(air)(air) amounts to ± 14%. CONCLUSIONS Results of our investigation revealed that the use of XR-QA2 GafChromic™ film is accompanied by a rather pronounced energy dependent response for beam qualities used for x-ray based diagnostic imaging purposes. The authors also found that the most appropriate function for the reference radiochromic film dosimetry would be the power function, while for the relative dosimetry one may use the exponential response function that can be easily linearized.

Sorafenib in combination with ionizing radiation has a greater anti-tumour activity in a breast cancer model.

High expression of vascular endothelial growth factor (VEGF) in patients with breast cancer has been associated with a poor prognosis, indicating that VEGF could be linked to the efficacy of chemotherapy and radiotherapy. It has also been suggested that radiation resistance is partly due to tumour cell production of angiogenic cytokines, particularly VEGF receptor (VEGFR). This evidence indicates that inhibition of VEGFR might enhance the radiation response. Sorafenib tosylate (Bay 54-9085) is an oral, small-molecule multikinase inhibitor of several targets including RAF/MEK/ERK MAP kinase signalling, VEGFR-2, VEGFR-3 and platelet-derived growth factor receptor-beta. Sorafenib has shown clinical efficacy in treating solid tumours such as renal cell and hepatocellular carcinomas. However, strategies are yet to be identified to prolong and maximize the anticancer effect of this multikinase inhibitor. The objective of this study was to determine whether a combination of Sorafenib and radiation will enhance the treatment response in vitro and in vivo. Radio-modulating effect of Sorafenib was assessed by performing clonogenic assays. In addition, cell cycle analyses as well as annexin-V apoptosis assays were performed 24 and 48 h after treatment, respectively. To confirm our in-vitro results, tumour growth delay assays were performed. Our results showed a strong and supra-additive antitumour effect of radiation combined with Sorafenib in vitro (dose enhancement factor of 1.76). The combined therapy demonstrated a strong and significant G2/M cell cycle arrest (combined treatment vs. irradiated alone: P<0.0008). Moreover, annexin-V staining showed a significant increase in the level of apoptosis (combined treatment vs. irradiated alone: P<0.0004). Study of the syngeneic model demonstrated the superior potency of the Sorafenib combined with radiotherapy. Our results demonstrate that higher antitumour activity can be achieved when radiation and Sorafenib are combined.