Cell survival following exposure to spatially modulated beams, as created by intensity-modulated radiotherapy (IMRT), is investigated. In vitro experiments were performed using malignant melanoma cells (MM576) exposed to a therapeutic megavoltage photon beam. We compared cell survival in modulated fields with cell survival in uniform control fields. Three different spatial modulations of the field were used: a control 'uniform' field in which all cells in a flask were uniformly exposed; a 'quarter' field in which 25% of cells at one end of the flask were exposed and a 'striped' field in which 25% of cells were exposed in three parallel stripes. The cell survival in both the shielded and unshielded regions of the modulated fields, as determined by a clonogenic assay, were compared to the cell survival in the uniform field. We have distinguished three ways in which cell survival is influenced by the fate of neighbouring cells. The first of these (type I effect) is the previously reported classical Bystander effect, where cell survival is reduced when communicating with irradiated cells. We find two new types of Bystander effect. The type II effect is an observed increase in cell survival when nearby cells receive a lethal dose. The type III effect is an increase in the survival of cells receiving a high dose of radiation, when nearby cells receive a low dose. These observations of the Bystander effects emphasize the need for improved radiobiological models, which include communicated effects and account for the effects of modulated dose distribution.
Backscatter factors are important parameters in the determination of dose for kilovoltage x-ray beams. However, backscatter factors are difficult to measure experimentally, and tabulated values are based largely on Monte Carlo calculations. In this study we have determined new backscatter factors by both experimental and Monte Carlo methods, and compared them with existing backscatter factors published in the AAPM TG-61 protocol. The purpose of this study is twofold: (1) to evaluate the overall effectiveness of using Gafchromic EBT film for backscatter factor measurements and (2) to determine whether existing Monte Carlo-calculated backscatter factors need to be updated. We measured backscatter factors using Gafchromic EBT film for three field sizes (2, 4 and 6 cm diameter cones) and three kilovoltage beam qualities, including 280 kVp for which similar measurements have not previously been reported. We also present new Monte Carlo-calculated backscatter factors obtained using the EGSnrc/BEAMnrc code system to simulate the Pantak kilovoltage x-ray unit used in our measurements. The results were compared with backscatter factors tabulated in the AAPM TG-61 protocol for kilovoltage x-ray dosimetry. The largest difference between our measured and calculated backscatter factors and the AAPM TG-61 values was found to be 2.5%. This agreement is remarkably good, considering that the AAPM TG-61 values consist of a combination of experimental and Monte Carlo calculations obtained over 20 years ago using different measurement techniques, as well as older Monte Carlo code and cross-section data. Furthermore, our Monte Carlo-calculated backscatter factors agree within 1% with the AAPM TG-61 values for all beam qualities and field sizes. Our Gafchromic film measurements had slightly larger differences with the AAPM TG-61 backscatter factors, up to approximately 2% for the 6 cm diameter cone at a beam quality of 50 kVp. The largest difference in backscatter factors, of 2.5%, was found between Monte Carlo-calculated and Gafchromic film-measured data for the 100 kVp x-ray beam with the 4 cm diameter cone. The differences in backscatter factors between the three data sets (measurements, calculations and published values) are all within the uncertainties from our Gafchromic film measurements and Monte Carlo calculations. Our results demonstrate the suitability of using Gafchromic EBT film to measure equipment-specific backscatter factors for kilovoltage x-ray beams over the entire energy range and also confirm that backscatter factors published in kilovoltage dosimetry protocols still remain valid.
Relative to an open field, survival of normal cells in a 2.5 mm striped field was the same, while the survival of both cancer cell lines was significantly lower. A mathematical model was developed to incorporate dose gradients of the spatial modulation into the standard linear quadratic model. Our new bystander extended LQ model assumes spatial gradients drive the diffusion of soluble factors that influence survival through bystander effects, successfully predicting the experimental results that show an increased therapeutic ratio. Our results challenge conventional radiotherapy practice and propose that additional gain can be realized by prescribing spatially modulated treatments to harness the bystander effect.
Aim: This study aims to compare conventional simultaneous integrated boost (SIB) planning technique with a hybrid SIB intensity-modulated radiation therapy (IMRT) technique with varying open tangent to IMRT field dose ratios. Furthermore, we investigated which of the dose ratios proves the most favourable as a class solution across a sample. Methods:In total, 15 patients with conventional SIB treatment plans were re-planned with hybrid SIB IMRT technique using three differing open field:IMRT dose ratios, that is, 80:20, 70:30 and 60:40. Plans were compared using dosimetric comparison of organs at risk (OARs) and homogeneity and conformity indexes across target structures.Results: All hybrid plans reduced dose maximums and showed a reduction of high doses to both lungs but increased lower doses, that is, V5, with similar results discovered for the heart. Contralateral breast dose was shown to decrease V5 and V1 measures by hybrid arms, whereas increasing the V2. Left anterior descending artery dose and non-irradiated structures were reduced by all hybrid arms. The homogeneity and conformity increased across all hybrid arms. Qualitative assessment of all plans also favoured hybrid plans.Findings: Hybrid plans produced superior dose conformity, homogeneity, reduced dose maximums and showed an improvement in most OAR parameters. The 70:30 hybrid technique exhibited greater benefits as a class solution to the sample than conventional plans due to superior dose conformity and homogeneity to target volumes.
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