| 1. |
- Adamus-Gorka, Magdalena, et al.
(författare)
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An “Effective functional subunit size” model for the dose response of rat spinal cord paralysis
- 2007
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Ingår i: 13th International Congress of Radiation Research, San Fransisco, USA, July 8-12, 2007.
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Konferensbidrag (populärvet., debatt m.m.)abstract
- Background: Radiobiological models for normal tissue complication probability (NTCP) are more and more commonly used in order to estimate the clinical outcome of radiation therapy. A normal tissue complication probability model to be considered a good and reliable one should fulfill the following two requirements: (a) it should predict the sigmoid shape of the dose-response curve as well as possible and (b) it should duly handle the volume effect. In the work from 2005 (IJROBP 61(3):892-900, 2005) P. van Luijk et al. suggest that none of the existing NTCP models is able to describe the volume effects present in the rat spinal cord during irradiation with small proton beams and they indicate the need for developing such new models.Methods: We have used the experimental data from H. Bijl et al. (IJROBP 52(1):205-211, 2002) to try explaining the change in the fifty percent effective dose (ED50) for different field sizes. We initiated this study to evaluate whether the induction of white matter necrosis in rat spinal cord after irradiation with small proton beams could be explained independent of used NTCP model. We therefore introduced a new concept of effective FSU dose, where a convolution of the original dose distribution with a function describing the effective size of a single FSU results in the average doses in a functional subunit. Such procedure allows determining the ED50 in an FSU of a certain size, within the irradiation field. We have also looked at non uniform dose distributions to see whether using a similar method we can explain the so called “bath and shower experiments” (IJROBP 57(1): 274-281, 2003).Results: Using the least square method to compare the effective doses for different sizes of functional subunits with the experimental data we observe the best fit for about 8 mm length. It seems that this length could be understood as an effective size of functional subunits in rat spinal cord, explaining what is otherwise interpreted as a volume effect. For the non uniform dose distributions an effective FSU length of 5 mm gives the optimal fit with the Probit dose-response model.Conclusions: The concept of an effective FSU length seems to explain at least part of the effects seen when small portions of the rat spinal cord are irradiated. The most likely FSU length for the shower and bath experiments is 5 mm according to these calculations.
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| 2. |
- Adamus-Gorka, Magdalena, et al.
(författare)
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Determination of the dose-response relations of thoracic and cervical myelopathy after external beam radiation therapy
- 2007
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Ingår i: 9th Biennial ESTRO Meeting on Physics and Radiation Technology for Clinical Radiotherapy, Barcelona, Spain, 9-13 September 2007.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Following our previous experience, the relative seriality modelwas fitted to two different sets of clinical data for radiation myelitis concerning thoracic spinal cord after radiation treatment of 43 patients with lung carcinoma and cervical spinal cord after treating 248 patients for malignant disease of head and neck.Individual treatment data were suitably fitted by the relative seriality model. The estimated radiobiological parameters of the model indicate that the probability of inducing this complication after radiation therapy is volume dependent only for the cervical part of spinal cord, whereas for the thoracic part no volume effect could be observed.Two different statistical methods applied to the patient material showed that the radiobiological model and the estimated parameters can be used to closely predict the complication rates observed.
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| 3. |
- Adamus-Górka, Magdalena, 1977-
(författare)
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Improved dose response modeling for normal tissue damage and therapy optimization
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The present thesis is focused on the development and application of dose response models for radiation therapy. Radiobiological models of tissue response to radiation are an integral part of the radiotherapeutic process and a powerful tool to optimize tumor control and minimize damage to healthy tissues for use in clinical trials. Ideally, the models could work as a historical control arm of a clinical trial eliminating the need to randomize patents to suboptimal therapies. In the thesis overview part, some of the basic properties of the dose response relation are reviewed and the most common radiobiological dose-response models are compared with regard to their ability to describe experimental dose response data for rat spinal cord using the maximum likelihood method. For vascular damage the relative seriality model was clearly superior to the other models, whereas for white matter necrosis all models were quite good except possibly the inverse tumor and critical element models. The radiation sensitivity, seriality and steepness of the dose-response relation of the spinal cord is found to vary considerably along its length. The cervical region is more radiation sensitive, more parallel, expressing much steeper dose-response relation and more volume dependent probability of inducing radiation myelitis than the thoracic part. The higher number of functional subunits (FSUs) consistent with a higher amount of white matter close to the brain may be responsible for these phenomena. With strongly heterogeneous dose delivery and due to the random location of FSUs, the effective size of the FSU and the mean dose deposited in it are of key importance and the radiation sensitivity distribution of the FSU may be an even better descriptor for the response of the organ. An individual optimization of a radiation treatment has the potential to increase the therapeutic window and improve cure for a subgroup of patients.
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| 4. |
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| 5. |
- Costa Ferreira, Brigida, et al.
(författare)
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The impact of different dose-response parameters on biologically optimized IMRT in breast cancer.
- 2008
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Ingår i: Physics in Medicine and Biology. - : IOP Publishing. - 0031-9155 .- 1361-6560. ; 53:10, s. 2733-52
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Tidskriftsartikel (refereegranskat)abstract
- The full potential of biologically optimized radiation therapy can only be maximized with the prediction of individual patient radiosensitivity prior to treatment. Unfortunately, the available biological parameters, derived from clinical trials, reflect an average radiosensitivity of the examined populations. In the present study, a breast cancer patient of stage I-II with positive lymph nodes was chosen in order to analyse the effect of the variation of individual radiosensitivity on the optimal dose distribution. Thus, deviations from the average biological parameters, describing tumour, heart and lung response, were introduced covering the range of patient radiosensitivity reported in the literature. Two treatment configurations of three and seven biologically optimized intensity-modulated beams were employed. The different dose distributions were analysed using biological and physical parameters such as the complication-free tumour control probability (P(+)), the biologically effective uniform dose (D), dose volume histograms, mean doses, standard deviations, maximum and minimum doses. In the three-beam plan, the difference in P(+) between the optimal dose distribution (when the individual patient radiosensitivity is known) and the reference dose distribution, which is optimal for the average patient biology, ranges up to 13.9% when varying the radiosensitivity of the target volume, up to 0.9% when varying the radiosensitivity of the heart and up to 1.3% when varying the radiosensitivity of the lung. Similarly, in the seven-beam plan, the differences in P(+) are up to 13.1% for the target, up to 1.6% for the heart and up to 0.9% for the left lung. When the radiosensitivity of the most important tissues in breast cancer radiation therapy was simultaneously changed, the maximum gain in outcome was as high as 7.7%. The impact of the dose-response uncertainties on the treatment outcome was clinically insignificant for the majority of the simulated patients. However, the jump from generalized to individualized radiation therapy may significantly increase the therapeutic window for patients with extreme radio sensitivity or radioresistance, provided that these are identified. Even for radiosensitive patients a simple treatment technique is sufficient to maximize the outcome, since no significant benefits were obtained with a more complex technique using seven intensity-modulated beams portals.
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