| 1. |
- Eriksdotter-Jönhagen, Maria, et al.
(författare)
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Encapsulated cell biodelivery of nerve growth factor to the Basal forebrain in patients with Alzheimer's disease.
- 2012
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Ingår i: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1421-9824 .- 1420-8008. ; 33:1, s. 18-28
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Tidskriftsartikel (refereegranskat)abstract
- Degeneration of cholinergic neurons in the basal forebrain correlates with cognitive decline in patients with Alzheimer's disease (AD). Targeted delivery of exogenous nerve growth factor (NGF) has emerged as a potential AD therapy due to its regenerative effects on the basal forebrain cholinergic neurons in AD animal models. Here we report the results of a first-in-man study of encapsulated cell (EC) biodelivery of NGF to the basal forebrain of AD patients with the primary objective to explore safety and tolerability.
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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. |
- Ahlberg, Alexander, et al.
(författare)
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ESOPHAGEAL STRICTURE AFTER RADIOTHERAPY IN PATIENTS WITH HEAD AND NECK CANCER : EXPERIENCE OF A SINGLE INSTITUTION OVER 2 TREATMENT PERIODS
- 2010
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Ingår i: Head and Neck. - : Wiley. - 1043-3074 .- 1097-0347. ; 32:4, s. 452-461
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Tidskriftsartikel (refereegranskat)abstract
- Background. Risk factors for development of a stricture of the upper esophagus after radiotherapy for head and neck cancer are poorly defined. Methods. This was a retrospective case-control study of patients diagnosed and treated for esophageal stricture after radiotherapy for head and neck cancer. Results. The incidence of esophageal stricture after external beam radiation therapy (EBRT) was 3.3%. Seventy patients with stricture and 66 patients without stricture were identified. A multivariate analysis showed that there was increased risk of stricture in receiving enteral feeding during EBRT or in receiving a mean dose of >45 By to the upper esophagus. Conclusions. Enteral feeding during EBRT is strongly associated with the development of stricture of the esophagus, as is a mean dose of >45 Gy to the upper esophagus. Treatment of the stricture with Savary-Gilliard bougienage or through scope balloon dilatation is safe and successful but often has to be repeated.
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| 7. |
- Alevronta, Eleftheria, et al.
(författare)
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Dose-response relations for stricture in the proximal oesophagus from head and neck radiotherapy
- 2010
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Ingår i: Radiotherapy and Oncology. - : Elsevier BV. - 0167-8140 .- 1879-0887. ; 97:1, s. 54-59
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: Determination of the dose-response relations for oesophageal stricture after radiotherapy of the head and neck. Material and methods: In this study 33 patients who developed oesophageal stricture and 39 patients as controls are included. The patients received radiation therapy for head and neck cancer at Karolinska University Hospital, Stockholm, Sweden. For each patient the 3D dose distribution delivered to the upper 5 cm of the oesophagus was analysed. The analysis was conducted for two periods, 1992-2000 and 2001-2005, due to the different irradiation techniques used. The fitting has been done using the relative seriality model. Results: For the treatment period 1992-2005, the mean doses were 49.8 and 33.4 Gy, respectively, for the cases and the controls. For the period 1992-2000, the mean doses for the cases and the controls were 49.9 and 45.9 Gy and for the period 2001-2005 were 49.8 and 21.4 Gy. For the period 2001-2005 the best estimates of the dose-response parameters are D-50 = 61.5 Gy (52.9-84.9 Gy), gamma = 1.4 (0.8-2.6) and s = 0.1 (0.01-0.3). Conclusions: Radiation-induced strictures were found to have a dose response relation and volume dependence (low relative seriality) for the treatment period 2001-2005. However, no dose response relation was found for the complete material.
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| 8. |
- Anderlind, Eva, et al.
(författare)
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Will haptic feedback speed up medical imaging? An application to radiation treatment planning
- 2008
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Ingår i: Acta Oncologica. - OSLO, Norge : Taylor & Francis. - 0284-186X .- 1651-226X. ; 47:1, s. 32-37
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Tidskriftsartikel (refereegranskat)abstract
- Haptic technology enables us to incorporate the sense of touch into computer applications, providing an additional input/output channel. The purpose of this study was to examine if haptic feedback can help physicians and other practitioners to interact with medical imaging and treatment planning systems. A haptic application for outlining target areas (a key task in radiation therapy treatment planning) was implemented and then evaluated via a controlled experiment with ten subjects. Even though the sample size was small, and the application only a prototype, results showed that haptic feedback can significantly increase (p0.05) the speed of outlining target volumes and organs at risk. No significant differences were found regarding precision or perceived usability. This promising result warrants further development of a full haptic application for this task. Improvements to the usability of the application as well as to the forces generated have been implemented and an experiment with more subjects is planned.
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| 9. |
- 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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| 10. |
- Andisheh, Bahram, 1967-
(författare)
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Improving the therapeutic ratio of stereotactic radiosurgery and radiotherapy
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- New methods of high dose delivery, such as intensity modulated radiation therapy (IMRT), stereotactic radiation therapy (SRT) or stereotactic radiosurgery (SRS), hadron therapy, tomotherapy, etc., all make use of a few large fractions. To improve these treatments, there are three main directions: (i) improving physical dose distribution, (ii) optimizing radiosurgery dose-time scheme and (iii) modifying dose response of tumors or normal tissues.Different radiation modalities and systems have been developed to deliver the best possible physical dose to the target while keeping radiation to normal tissue minimum. Although applications of radiobiological findings to clinical practice are still at an early stage, many studies have shown that sublethal radiation damage repair kinetics plays an important role in tissue response to radiation.The purpose of the present thesis is to show how the above-mentioned directions could be used to improve treatment outcomes with special interest in radiation modalities and dose-time scheme, as well as radiobiological modeling. Also for arteriovenous malformations (AVM), the possible impact of AVM network angiostructure in radiation response was studied.
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