| 1. |
- Qatarneh, Sharif, 1972-
(författare)
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Development of a Whole Body Atlas for Radiation Therapy Planning and Treatment Optimization
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The main objective of radiation therapy is to obtain the highest possible probability of tumor cure while minimizing adverse reactions in healthy tissues. A crucial step in the treatment process is to determine the location and extent of the primary tumor and its loco regional lymphatic spread in relation to adjacent radiosensitive anatomical structures and organs at risk. These volumes must also be accurately delineated with respect to external anatomic reference points, preferably on surrounding bony structures. At the same time, it is essential to have the best possible physical and radiobiological knowledge about the radiation responsiveness of the target tissues and organs at risk in order to achieve a more accurate optimization of the treatment outcome.A computerized whole body Atlas has therefore been developed to serve as a dynamic database, with systematically integrated knowledge, comprising all necessary physical and radiobiological information about common target volumes and normal tissues. The Atlas also contains a database of segmented organs and a lymph node topography, which was based on the Visible Human dataset, to form standard reference geometry of organ systems. The reference knowledgebase and the standard organ dataset can be utilized for Atlas-based image processing and analysis in radiation therapy planning and for biological optimization of the treatment outcome. Atlas-based segmentation procedures were utilized to transform the reference organ dataset of the Atlas into the geometry of individual patients. The anatomic organs and target volumes of the database can be converted by elastic transformation into those of the individual patient for final treatment planning. Furthermore, a database of reference treatment plans was started by implementing state-of-the-art biologically based radiation therapy planning techniques such as conformal, intensity modulated, and radiobiologically optimized treatment planning.The computerized Atlas can be viewed as a central framework that contains different forms of optimal treatment plans linked to all the essential information needed in treatment planning, which can be adapted to a given patient, in order to speed up treatment plan convergence. The Atlas also offers a platform to synthesize the results of imaging studies through its advanced geometric transformation and segmentation procedures. The whole body Atlas is anticipated to become a physical and biological knowledgebase that can facilitate, speed up and increase the accuracy in radiation therapy planning and treatment optimization.
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| 2. |
- 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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| 3. |
- 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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| 4. |
- 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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| 5. |
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| 6. |
- Andisheh, Bahram, 1967-, et al.
(författare)
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Clinical and radiobiological advantages of single-dose stereotactic light-ion radiation therapy for large intracranial arteriovenous malformations. Technical note
- 2009
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Ingår i: Journal of Neurosurgery. - : Journal of Neurosurgery Publishing Group (JNSPG). - 0022-3085 .- 1933-0693. ; 111:5, s. 919-926
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Tidskriftsartikel (refereegranskat)abstract
- OBJECT:Radiation treatment of large arteriovenous malformations (AVMs) remains difficult and not very effective, even though seemingly promising methods such as staged volume treatments have been proposed by some radiation treatment centers. In symptomatic patients harboring large intracranial AVMs not amenable to embolization or resection, single-session high-dose stereotactic radiation therapy is a viable option, and the special characteristics of high-ionization-density light-ion beams offer several treatment advantages over photon and proton beams. These advantages include a more favorable depth-dose distribution in tissue, an almost negligible lateral scatter of the beam, a sharper penumbra, a steep dose falloff beyond the Bragg peak, and a higher probability of vascular response due to high ionization density and associated induction of endothelial cell proliferation and/or apoptosis. Carbon ions were recently shown to be an effective treatment for skull-base tumors. Bearing that in mind, the authors postulate that the unique physical and biological characteristics of light-ion beams should convey considerable clinical advantages in the treatment of large AVMs. In the present meta-analysis the authors present a comparison between light-ion beam therapy and more conventional modalities of radiation treatment with respect to these lesions.METHODS:Dose-volume histograms and data on peripheral radiation doses for treatment of large AVMs were collected from various radiation treatment centers. Dose-response parameters were then derived by applying a maximum likelihood fitting of a binomial model to these data. The present binomial model was needed because the effective number of crucial blood vessels in AVMs (the number of vessels that must be obliterated to effect a cure, such as large fistulous nidus vessels) is low, making the Poisson model less suitable. In this study the authors also focused on radiobiological differences between various radiation treatments.RESULTS:Light-ion Bragg-peak dose delivery has the precision required for treating very large AVMs as well as for delivering extremely sharp, focused beams to irregular lesions. Stereotactic light-ion radiosurgery resulted in better angiographically defined obliteration rates, less white-matter necrosis, lower complication rates, and more favorable clinical outcomes. In addition, in patients treated by He ion beams, a sharper dose-response gradient was observed, probably due to a more homogeneous radiosensitivity of the AVM nidus to light-ion beam radiation than that seen when low-ionization-density radiation modalities, such as photons and protons, are used.CONCLUSIONS:Bragg-peak radiosurgery can be recommended for most large and irregular AVMs and for the treatment of lesions located in front of or adjacent to sensitive and functionally important brain structures. The unique physical and biological characteristics of light-ion beams are of considerable advantage for the treatment of AVMs: the densely ionizing beams of light ions create a better dose and biological effect distribution than conventional radiation modalities such as photons and protons. Using light ions, greater flexibility can be achieved while avoiding healthy critical structures such as diencephalic and brainstem nuclei and tracts. Treatment with the light ion He or Li is more suitable for AVMs
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| 7. |
- Andisheh, Bahram, 1967-, et al.
(författare)
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Vascular structure and binomial statistics for response modeling in radiosurgery of cerebral arteriovenous malformations
- 2010
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Ingår i: Physics in Medicine and Biology. - : IOP Publishing. - 0031-9155 .- 1361-6560. ; 55:7, s. 2057-2067
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Tidskriftsartikel (refereegranskat)abstract
- Radiation treatment of arteriovenous malformations (AVMs) has a slow and progressive vaso-occlusive effect. Some studies suggested the possible role of vascular structure in this process. A detailed biomathematical model has been used, where the morphological, biophysical and hemodynamic characteristics of intracranial AVM vessels are faithfully reproduced. The effect of radiation on plexiform and fistulous AVM nidus vessels was simulated using this theoretical model. The similarities between vascular and electrical networks were used to construct this biomathematical AVM model and provide an accurate rendering of transnidal and intranidal hemodynamics. The response of different vessels to radiation and their obliteration probability as a function of different angiostructures were simulated and total obliteration was defined as the probability of obliteration of all possible vascular pathways. The dose response of the whole AVM is observed to depend on the vascular structure of the intra-nidus AVM. Furthermore, a plexiform AVM appears to be more prone to obliteration compared with an AVM of the same size but having more arteriovenous fistulas. Finally, a binomial model was introduced, which considers the number of crucial vessels and is able to predict the dose response behavior of AVMs with a complex vascular structure.
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| 8. |
- Brahme, Anders, et al.
(författare)
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A systems biology approach to radiation therapy optimization
- 2010
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Ingår i: Radiation and Environmental Biophysics. - : Springer Science and Business Media LLC. - 0301-634X .- 1432-2099. ; 49:2, s. 111-124
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Tidskriftsartikel (refereegranskat)abstract
- During the last 20 years, the field of cellular and not least molecular radiation biology has been developed substantially and can today describe the response of heterogeneous tumors and organized normal tissues to radiation therapy quite well. An increased understanding of the sub-cellular and molecular response is leading to a more general systems biological approach to radiation therapy and treatment optimization. It is interesting that most of the characteristics of the tissue infrastructure, such as the vascular system and the degree of hypoxia, have to be considered to get an accurate description of tumor and normal tissue responses to ionizing radiation. In the limited space available, only a brief description of some of the most important concepts and processes is possible, starting from the key functional genomics pathways of the cell that are not only responsible for tumor development but also responsible for the response of the cells to radiation therapy. The key mechanisms for cellular damage and damage repair are described. It is further more discussed how these processes can be brought to inactivate the tumor without severely damaging surrounding normal tissues using suitable radiation modalities like intensity-modulated radiation therapy (IMRT) or light ions. The use of such methods may lead to a truly scientific approach to radiation therapy optimization, particularly when invivo predictive assays of radiation responsiveness becomes clinically available at a larger scale. Brief examples of the efficiency of IMRT are also given showing how sensitive normal tissues can be spared at the same time as highly curative doses are delivered to a tumor that is often radiation resistant and located near organs at risk. This new approach maximizes the probability to eradicate the tumor, while at the same time, adverse reactions in sensitive normal tissues are as far as possible minimized using IMRT with photons and light ions.
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| 9. |
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| 10. |
- Ferreira, Brigida Costa, et al.
(författare)
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Effective beam directions using radiobiologically optimized IMRT of node positive breast cancer
- 2006
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Ingår i: Physica medica (Testo stampato). - 1120-1797 .- 1724-191X. ; 22:1, s. 3-15
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to investigate the optimal coplanar beam directions when treating an early breast cancer with locoregional lymphatic spread with a few radiobiologically optimized intensity modulated beams. Also to determine the increase in the probability of complication-free cure with the number of beam portals and the smallest number required to perform a close to optimal treatment for this tumour site. Four test patients with stage II left-sided breast cancer were studied with heart, lung and contralateral breast as principal organs at risk. The clinical target volume consisted of the breast tissue remaining after surgery, the axillary, the internal mammary as well as the supraclavicular lymph nodes. Through an exhaustive search of all possible beam directions the most effective coplanar beams with one to four intensity modulated photon beam portals were investigated. Comparisons with uniform beam treatment techniques and up to 12 intensity modulated beams were also made. The different plans were optimized using the probability of complication-free tumour cure, P+, as biological objective function. When using two intensity modulated beam directions three major sets of suitable directions were identified denoted by A, P and T A corresponds to an anterior oblique pair of beams around 25 degrees and 325 degrees, P is a perpendicular lateral pair at around 50 and 130 whereas T is a more conventional tangential pair at around 155 degrees and 300 degrees. Interestingly, these configurations identify simply three major effective beam directions namely at 30 degrees +/- 20 degrees, 145 degrees +/- 20 degrees and 310 degrees +/- 15 degrees. For the three intensity modulated beam technique a combination of these three effective beam directions generally covered the global maximum of the probability of complication-free tumour control. The improvement in complication-free cure probability with two optimally selected intensity modulated beams is around 10% when compared to a uniform beam technique with three to four beam portals. This increase is mainly due to a reduction by almost 1% in the probability of injury to the heart and an increase of 6% in the probability of local tumour control. When three or four biologically optimized beam portals are used a further increase in the probability of complication-free cure of about 6% can often be obtained. This improvement is caused by a small decrease in the probability of injury to the heart, left lung and other surrounding normal tissue, as well as a slight further increase in the probability of tumour control. The increase in the treatment outcome is minimal when more than four intensity modulated beams are employed. A small increase in dose homogeneity in the target volume and a slight decrease in the normal tissue volume receiving high dose may be seen, but without appreciably improving the complication-free cure probability. For a stage II breast cancer, three and in more complex cases four optimally oriented beams are sufficient to reach close to the maximum probability of complication-free tumour control when biologically optimized intensity modulated dose delivery is used. Angle of incidence optimization may then be advantageous starting from the given most effective three beam directions.
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