F Van den Heuvel

Beam energy considerations for gold nano-particle enhanced radiation treatment

A novel approach using nano-technology enhanced radiation modalities is investigated. The proposed methodology uses antibodies labeled with organically inert metals with a high atomic number. Irradiation using photons with energies in the kilo-electron volt (keV) range shows an increase in dose due to a combination of an increase in photo-electric interactions and a pronounced generation of Auger and/or Coster-Krönig (A-CK) electrons. The dependence of the dose deposition on various factors is investigated using Monte Carlo simulation models. The factors investigated include agent concentration, spectral dependence looking at mono-energetic sources as well as classical bremsstrahlung sources. The optimization of the energy spectrum is performed in terms of physical dose enhancement as well as the dose deposited by Auger and/or Coster-Krönig electrons and their biological effectiveness. A quasi-linear dependence on concentration and an exponential decrease within the target medium is observed. The maximal dose enhancement is dependent on the position of the target in the beam. Apart from irradiation with low-photon energies (10-20 keV) there is no added benefit from the increase in generation of Auger electrons. Interestingly, a regular 110 kVp bremsstrahlung spectrum shows a comparable enhancement in comparison with the optimized mono-energetic sources. In conclusion we find that the use of enhanced nano-particles shows promise to be implemented quite easily in regular clinics on a physical level due to the advantageous properties in classical beams.

Calibrating page sized Gafchromic EBT3 films

PURPOSE The purpose is the development of a novel calibration method for dosimetry with Gafchromic EBT3 films. The method should be applicable for pretreatment verification of volumetric modulated arc, and intensity modulated radiotherapy. Because the exposed area on film can be large for such treatments, lateral scan errors must be taken into account. The correction for the lateral scan effect is obtained from the calibration data itself. METHODS In this work, the film measurements were modeled using their relative scan values (Transmittance, T). Inside the transmittance domain a linear combination and a parabolic lateral scan correction described the observed transmittance values. The linear combination model, combined a monomer transmittance state (T(0)) and a polymer transmittance state (T(∞)) of the film. The dose domain was associated with the observed effects in the transmittance domain through a rational calibration function. On the calibration film only simple static fields were applied and page sized films were used for calibration and measurements (treatment verification). Four different calibration setups were considered and compared with respect to dose estimation accuracy. The first (I) used a calibration table from 32 regions of interest (ROIs) spread on 4 calibration films, the second (II) used 16 ROIs spread on 2 calibration films, the third (III), and fourth (IV) used 8 ROIs spread on a single calibration film. The calibration tables of the setups I, II, and IV contained eight dose levels delivered to different positions on the films, while for setup III only four dose levels were applied. Validation was performed by irradiating film strips with known doses at two different time points over the course of a week. Accuracy of the dose response and the lateral effect correction was estimated using the dose difference and the root mean squared error (RMSE), respectively. RESULTS A calibration based on two films was the optimal balance between cost effectiveness and dosimetric accuracy. The validation resulted in dose errors of 1%-2% for the two different time points, with a maximal absolute dose error around 0.05 Gy. The lateral correction reduced the RMSE values on the sides of the film to the RMSE values at the center of the film. CONCLUSIONS EBT3 Gafchromic films were calibrated for large field dosimetry with a limited number of page sized films and simple static calibration fields. The transmittance was modeled as a linear combination of two transmittance states, and associated with dose using a rational calibration function. Additionally, the lateral scan effect was resolved in the calibration function itself. This allows the use of page sized films. Only two calibration films were required to estimate both the dose and the lateral response. The calibration films were used over the course of a week, with residual dose errors ≤2% or ≤0.05 Gy.

TH‐E‐BRB‐03: Incorporating a Lateral Scan Effect Correction in a EBT3 Calibration Protocol

Purpose: To use the new EBT3 Gafchromic films for large modulated field dosimetry, a lateral scan correction needs to be performed. We propose a lateral correction built in in the calibration curve. The feasibility of this calibration methodology is evaluated. Methods: The relative scan value (Transmittance, T) is associated with the dose using a rational function with three parameters: T0 the unirradiated transmittance, Tmax the maximal transmittance, and b3 a parameter scaling the impact of the dose. Because, the lateral scan effect is inherent to the scanner transmission system, a parabolic correction is implemented in the calibration function itself, instead of a post calibration correction. To assess a sufficient sampling of both the dose and the lateral dependency in the calibration procedure, eight dose levels are irradiated to two lateral locations on two uncut calibration films (one location per film). The resulting calibration function is validated by delivering known uniform doses on eight strips a single film. The central pixel line of each validation strip is converted to dose for the three (RGB) color channels. To show lateral independence of the measured dose, the central pixel line is divided in five 2 inch ROIs, subsequently, the root mean square error (RMSE) of these ROIs is calculated. Results: The dose errors (1SD) are 2%, 2.2%, and 2% for the red, green, and blue color channel respectively. The red channel dose, without lateral correction, has a maximal RMSE >2.5%, for the outer ROI. The proposed methodology results in a maximal RMSE < 0.5% for all ROIs and all three color channels in a [0.57,4.16]Gy dose range. Conclusions: The scanner‐transmission system with the new EBT3 gafchromic films is calibrated with a calibration protocol incorporating the lateral scan effect. This method reduces the RMSE from 2.5% to 0.5%. Research was supported Ashland Specialty Ingredients Wayne, New Jersey 07470, and PEO Radiation Technology bvba, 2320 Hoogstraten, Belgium. The authors acknowledge David Lewis and Andre Micke for their fruitful discussions.

Image enhancement techniques allowing observation of intra-fractional motion in IMRT treatment for prostate carcinoma

Purpose: To estimate intrafracional motion of the prostate in a routine clinical setting during IMRT treatment and its impact on margin reduction and treatment time.

SU‐FF‐T‐147: Intra Fractional Motion in Clinical IMRT Prostate Treatments, Warrants the Use of Faster Treatment Techniques

Purpose: To estimate intrafracional motion of the prostate in a routine clinical setting and its impact on margin reduction and treatment time. Method and Materials: External beam treatment for cancer of the prostate using an IMRT technique was evaluated. Fifteen patients underwent a marker match procedure ensuring correct positioning at time of treatment. For all fields intra‐treatment images were obtained, yielding 5 to 7 images per fraction. IMRT was delivered using a dynamic sliding window technique. The obtained images were processed to remove IMRT information. The markers were detected in the image using an automated methodology. Every image was timestamped and chronologically adjacent images were backprojected to yield 3D marker coordinates. Allowing to calculate the position of the prostate during the treatment delivery at specific time instances. Using a Poisson model for the probability of movement we can determine the maximal allowable time frame within which to perform this treament. Results: The maximal treament time measured was 1460s, the shortest lasted 343s. The times were measured starting from the last image in the marker‐match procedure and includes the decision and adjustment process. Depending on the elapsed time we noticed an increase in positional confidence level from 5.8mm to 7.6mm. The delivery of the fields are of the order of 250s. Conclusion: We note a significant increase in probability of prostate movement in our treaments as time elapses. This limits the amount of margin reduction possible. There are two strategies possible to reduce this time. 1) Increase the marker match speed, or 2) increase the delivery speed. A good candidate to do this is the use of a volumetric Arc technique (VMAT) which is implemented in our department with RapidArc™. The latter is able to deliver the same or even better dose distribution in under 2 minutes (8 patients).

SU-FF-T-162: Does the Implementation of Electron Monte Carlo Simulation Based Treatment Planning Have Radiobiologically Significant Ramifications?

Purpose: To quantify differences in dosedeposition between three different methodologies determining the dose delivered by electrons in the treatment of breast carcinoma. The quantification is performed using radio‐biological models and we determine whether the difference is significant on radio‐biological level. Methods: Twenty patients to be treated with chestwall irradiation are planned in a conventional way using electron fields. The treatments are planned using a pencil beam algorithm, a monte carlo simulation based TPS, and manual hand calcs. Using a dose volumes histogram decomposition technique we calculate tumor control probability for the chest wall, the medial supraclavicular‐, and the intra‐mammary lymph nodes. Normal tissue complication probabilities are calculated using different models, including Burman‐Kutcher effective volume and relative seriality Poisson based models. Endpoints are excess of cardiac mortality risk and radiation pneumonitis. Results: We find that there is a significant difference for PB based compared to MC‐based dose calculation for TCP—values. Both methods are lower than the “ideal” case where we assume homogeneous irradiation of the target structure to the prescribed dose level. The TCP for PB calculation is on average 3% (1SD = 1%) higher than the TCP calculated with a MC‐based TPS. Levels of TCP with respect to the ideal case for IM‐MS irradiation are 7%, resp. 10% for PB resp. MC. For NTCP an overall decrease is noted although not significant with the data available at the submission time. Cases with an inverse shift in NTCP are found (i.e. NTCP‐PB < NTCP‐MC). Conclusions: The outcome predicted from the radio‐biological models is dependent on the algorithm used to determine the dosedeposition. This implies that the use of patient data to fit radio‐biological models needs to be accompanied with the type of dose calculation used. Preferably, all such studies should be performed with a gold standard methodology.

SU-F-BRD-04: Robustness Analysis of Proton Breast Treatments Using An Alpha-Stable Distribution Parameterization

Purpose: Currently, planning systems allow robustness calculations to be performed, but a generalized assessment methodology is not yet available. We introduce and evaluate a methodology to quantify the robustness of a plan on an individual patient basis. Methods: We introduce the notion of characterizing a treatment instance (i.e. one single fraction delivery) by describing the dose distribution within an organ as an alpha-stable distribution. The parameters of the distribution (shape(α), scale(γ), position(δ), and symmetry(β)), will vary continuously (in a mathematical sense) as the distributions change with the different positions. The rate of change of the parameters provides a measure of the robustness of the treatment. The methodology is tested in a planning study of 25 patients with known residual errors at each fraction. Each patient was planned using Eclipse with an IBA-proton beam model. The residual error space for every patient was sampled 30 times, yielding 31 treatment plans for each patient and dose distributions in 5 organs. The parameters’ change rate as a function of Euclidean distance from the original plan was analyzed. Results: More than 1,000 dose distributions were analyzed. For 4 of the 25 patients the change in scale rate (γ) was considerably higher than the lowest change rate, indicating a lack of robustness. The sign of the shape change rate (α) also seemed indicative but the experiment lacked the power to prove significance. Conclusion: There are indications that this robustness measure is a valuable tool to allow a more patient individualized approach to the determination of margins. In a further study we will also evaluate this robustness measure using photon treatments, and evaluate the impact of using breath hold techniques, and the a Monte Carlo based dose deposition calculation. A principle component analysis is also planned.

SU‐E‐T‐484: A Closed Parameterization of Microscopic Damage as a Function of Energy in Dose Deposition by Charged Particles

Purpose: To present the derivation and application of a closed formalism for the impact of charged particle radiation on damage induced in DNA. The formalism is valid for all types of charged particles and due to its closed nature is suited to provide fast conversion of dose to DNA‐damage. As photon treatments can be reduced to energy deposition by electrons it is also possible to calculate damage for classical radiation treatments. Methods: A simple geometrical model allows to parameterize the impact of charged particles in terms of single and double strand breaks. The parameters of the model contain: double strand threshold (i.e. the maximal distance two single lesions can have to be categorized as a double strand break), the diameter of the DNA‐strand, and a scaling factor describing distance between ionizing collisions in terms of particle energy. The model is validated using microdosimetric Monte Carlo calculations for electrons and protons. Finally, example applications are constructed calculating Relative Biological Effectratios for proton therapy compared to a therapeutic 6MV beam. Results: For both protons and electrons the model fits the Monte Carlo calculations almost perfectly as assessed by a χ2‐test. The energy scaling factor seems to be the only difference between the modalities of protons and electrons. The RBE‐factor for a mono‐energetic proton beam varies depending on the depth and is of the order of 1.1 rising to almost 2 at the Bragg peak. Conclusions: We have shown that it is possible to provide a generalized expression parameterizing the DNA‐damage induced by different modalities, indicating that the change in biological effect is mainly governed by geometrical considerations rather than a biological impact.

SU‐E‐T‐562: Do the Differences Between Photon Dose Distributions in the Breast Have Significant Impact On the Parameters of Radiobiological Models?

PURPOSE The comparison of advanced photon dose calculation algorithms in breast radiotherapy has focused on the physical dose distributions (DDs). Studies on their radiobiological impact are restricted to the normal tissue complication probability (NTCP) of the ipsilateral lung and the heart. The comparisons of the tumor control probability (TCP) and of the NTCP of moderate breast fibrosis are lacking. This study quantifies the radiobiological difference between four photon DDs in the breast. As the clinical outcome should be independent of the photon dose calculation algorithm, significant differences are eliminated by optimization of the model parameters found in literature. METHODS Thirty breast cancer patients, irradiated with two wedged tangential half-beams, were included in the study. Each DD, calculated with the Pencil Beam Convolution algorithm with modified Batho heterogeneity correction (PBC-MB) was recalculated using the Analytical Anisotropic Algorithm (AAA), AcurosXB (dose to medium) and AcurosXB (dose to water) with fixed monitors units (Eclipse, Varian Medical Systems, Inc.). The TCP and the NTCP of each DD were calculated with the Poisson model and the relative seriality model, respectively. The endpoint for the NTCP was moderate breast fibrosis. The differences were checked for significance with the paired t-test. Significant difference was eliminated by minimizing the difference between both the TCPs and the NTCPs. RESULTS AAA-TCP and AAA-NTCP are significantly lower than calculated for PBC-MB: 1.1% and 3.1%, respectively. AAA-TCP and AAA-NTCP are significantly higher than AcurosXB (dose to medium): 0.5% and 1.5%, respectively, and than AcurosXB (dose to water): 1.4% and 2.9%, respectively. New TCP and NTCP model parameters were determined for the radiobiological analysis of the PBC-MB and the AAA DD, respectively. CONCLUSION This study shows that the differences between the photon DDs of advanced dose calculation algorithms have radiobiological significance which can be eliminated by determination of algorithm specific model parameters.

TU‐G‐BRCD‐03: Managing Patient and Organ Motion in Proton Therapy

Background: The advent of proton based therapy has provided excitement in the radiationoncology community. Not in the least due to the theoretically advantageous geometrical properties of the dose deposition by such charged particles. In this presentation I will discuss the some of the challenges, which can make this tool sub‐optimal when used in clinical practice with actual patients. Methodology: Data and analysis on patient setup variations and organ movement, gathered from “classical” photon therapy is projected to this new modality. Inter and intra fractional movement will be covered as well as the notion of margin determination in order to provide adequate coverage and in what way this makes sense. In addition, the time frame with which these uncertainties occur implies that different measures need to be taken and the use of in room imaging might be needed. Further, the advent of scanning techniques again provide an advantage as well as a disadvantage as far as movement is concerned. Conclusions:Proton therapy is a promising technique and exciting on a clinical and scientific level. In order to show significant improvement, knowledge with regard to targfet determination, as well as positioning is more critical in comparison with the classical modalities. Learning Objectives: 1. Knowledge on patient and/or organ movements motion effects. 2. Categorizing the movement in time and space. 3. Reflections on the impact of movement on proton based treatments.