Dosimetric and geometric evaluation of the use of deformable image registration in adaptive intensity-modulated radiotherapy for head-and-neck cancer.

The aim of this study was to carry out geometric and dosimetric evaluation of the usefulness of a deformable image registration algorithm utilized for adaptive head-and-neck intensity-modulated radiotherapy. Data consisted of seven patients, each with a planning CT (pCT), a rescanning CT (ReCT) and a cone beam CT (CBCT). The CBCT was acquired on the same day (± 1 d) as the ReCT (i.e. at Fraction 17, 18, 23, 24 or 29). The ReCT served as ground truth. A deformed CT (dCT) with structures was created by deforming the pCT to the CBCT. The geometrical comparison was based on the volumes of the deformed, and the manually delineated structures on the ReCT. Likewise, the center of mass shift (CMS) and the Dice similarity coefficient were determined. The dosimetric comparison was performed by recalculating the initial treatment plan on the dCT and the ReCT. Dose-volume histogram (DVH) points and a range of conformity measures were used for the evaluation. We found a significant difference in the median volume of the dCT relative to that of the ReCT. Median CMS values were ∼ 2-5 mm, except for the spinal cord, where the median CMS was 8 mm. Dosimetric evaluation of target structures revealed small differences, while larger differences were observed for organs at risk. The deformed structures cannot fully replace manually delineated structures. Based on both geometrical and dosimetrical measures, there is a tendency for the dCT to overestimate the need for replanning, compared with the ReCT.

Pareto front analysis of 6 and 15 MV dynamic IMRT for lung cancer using pencil beam, AAA and Monte Carlo.

The pencil beam dose calculation method is frequently used in modern radiation therapy treatment planning regardless of the fact that it is documented inaccurately for cases involving large density variations. The inaccuracies are larger for higher beam energies. As a result, low energy beams are conventionally used for lung treatments. The aim of this study was to analyze the advantages and disadvantages of dynamic IMRT treatment planning for high and low photon energy in order to assess if deviating from the conventional low energy approach could be favorable in some cases. Furthermore, the influence of motion on the dose distribution was investigated. Four non-small cell lung cancer cases were selected for this study. Inverse planning was conducted using Varian Eclipse. A total number of 31 dynamic IMRT plans, distributed amongst the four cases, were created ranging from PTV conformity weighted to normal tissue sparing weighted. All optimized treatment plans were calculated using three different calculation algorithms (PBC, AAA and MC). In order to study the influence of motion, two virtual lung phantoms were created. The idea was to mimic two different situations: one where the GTV is located centrally in the PTV and another where the GTV was close to the edge of the PTV. PBC is in poor agreement with MC and AAA for all cases and treatment plans. AAA overestimates the dose, compared to MC. This effect is more pronounced for 15 than 6 MV. AAA and MC both predict similar perturbations in dose distributions when moving the GTV to the edge of the PTV. PBC, however, predicts results contradicting those of AAA and MC. This study shows that PB-based dose calculation algorithms are clinically insufficient for patient geometries involving large density inhomogeneities. AAA is in much better agreement with MC, but even a small overestimation of the dose level by the algorithm might lead to a large part of the PTV being underdosed. It is advisable to use low energy as a default for tumor sites involving lungs. However, there might be situations where it is favorable to use high energy. In order to deviate from the recommended low energy convention, an accurate dose calculation algorithm (e.g. MC) should be consulted. The study underlines the inaccuracies introduced when calculating dose using a PB-based algorithm in geometries involving large density variations. PBC, in contrast to other algorithms (AAA and MC), predicts a decrease in dose when the density is increased.

Dose build-up behind air cavities for Co-60, 4, 6 and 8 MV. Measurements and Monte Carlo simulations.

It has been shown in several studies that the build-up in photon beams behind air cavities (such as in the head and neck) increases with energy. In this study this effect is investigated over a broad range of energies that have been used for treating head and neck tumours. The study addresses the question of whether an energy lower than 6 MV is desirable and is based on measurements and Monte Carlo (MC) simulations. In a PMMA phantom containing an air cavity (3 x 16 x 3 cm3 at 3 cm depth) an ionization chamber (Capintec PS-033) was used to measure the dose build-up behind the cavity for 4, 6 and 8 MV beam qualities for different field sizes (from 3 x 6 cm2 to 8 x 8 cm2). MC simulations were made using the EGSnrc code for the same geometry and energies as well as for Co-60. Measurements and MC simulations agree well when the fixed-separation plane-parallel chamber measurements have been corrected for the expected over-response in the build-up region. This work demonstrates that the build-up effect of 6 MV is 'closer' to the build-up effect of 8 MV than to that of 4 MV. This suggests that if the build-up effect is of concern when the target volume is in the vicinity of air cavities, 4 MV should be preferred over both 6 MV and 8 MV. This work also shows that the build-up effect for Co-60 is significantly smaller than that of 4 MV. Moreover, the build-up effect increases as the field size decreases. With the increasing use of IMRT (and radiosurgery), small fields are used more frequently making these issues even more relevant. This should be taken into consideration when choosing the accelerator energies for a radiotherapy department.

Solvent denaturation of globular proteins: unfolding by the monoalkyl- and dialkyl-substituted formamides and ureas.

The effects of the monoalkyl and dialkyl-substituted formamide series of denaturants on the native conformation of sperm whale myoglobin, horse heart cytochrome c, and Glycera dibranciata (single chain) hemoglobin have been investigated by spectral measurements in the Soret region (409 and 422 nm) and optical rotation measurements (265nm). The effectiveness of these two classes of protein denaturants is similar to the other straight-chain compounds of the urea, amide, and alcohol classes, examined in previous investigations from our laboratory. Their denaturing effectiveness is found to increase with increasing chain length or hydrocarbon content of the substituent alkyl groups. Application of the Peller and Flory equation to the denaturation data of the formamides shows that both the polar and the nonpolar group contributions to the protein-denaturant interactions have to be taken into account in order to correctly predict the observed denaturation midpoints. Additivity of the hydrophobic, KHø, and the polar, Kp, group contributions to the binding constants, KB = nKHø + Kp, with n = 1 or 2 for the mono- of the di-alkyl substituted denaturants gave best account of the experimental data. The KHø values used were based on free energy transfer data of various alkyl groups or the Scheraga-Nemethy theory of hydrophobic bonding. The assumption of group contributions of the denaturant to KB were also applied to the denaturation data of the unsubstituted amides and some examples of the monoalkyl and symmetrically substituted dialkyl ureas, taken from the literature.