| 1. |
- Toma-Dasu, Iuliana, et al.
(författare)
-
Theoretical simulation of tumour hypoxia measurements
- 2006
-
Ingår i: Advances in Experimental Medicine and Biology. - : Springer US. - 0065-2598 .- 2214-8019. ; 578, s. 369-374
-
Tidskriftsartikel (refereegranskat)abstract
- Our simulations suggested that measurements performed in a limited number of points in the tumour can be representative for the situation in the whole tumour. It has further been shown that the polarographic electrode cannot be used to measure small regions of hypoxia. In fact it has been suggested that the most important factor that determines the efficiency of the polarographic electrode is the spatial distribution of the hypoxic cells and not their type, and therefore the polarographic electrode cannot be used to make the distinction between acute and chronic hypoxia. The simulations have also shown that it is reasonable to assume that the electrode measurement can be correlated to the situation in the whole tissue, even though the correlation is only qualitative. And because the electrode measurements are greatly influenced by the averaging process, the quantitative use of the electrode measurements may lead to erroneous results, especially for modelling the treatment response.
|
|
| 2. |
- Glimelius, B., et al.
(författare)
-
Number of patients potentially eligible for proton therapy
- 2005
-
Ingår i: Acta Oncol. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 44:8, s. 836-49
-
Tidskriftsartikel (refereegranskat)abstract
- A group of Swedish radiation oncologists and hospital physicists have estimated the number of patients in Sweden suitable for proton beam therapy in a facility where one of the principal aims is to facilitate randomized and other studies in which the advantage of protons can be shown and the magnitude of the differences compared with optimally administered conventional radiation treatment, also including intensity-modulated radiation therapy (IMRT) and brachytherapy, can be shown. The estimations have been based on current statistics of tumour incidence in Sweden, number of patients potentially eligible for radiation treatment, scientific support from clinical trials and model dose planning studies and knowledge of the dose-response relations of different tumours together with information on normal tissue complication rates. In Sweden, it is assessed that between 2200 and 2500 patients annually are eligible for proton beam therapy, and that for these patients the potential therapeutic benefit is so great as to justify the additional expense of proton therapy. This constitutes between 14-15% of all irradiated patients annually.
|
|
| 3. |
- Karlsson, Mikael, et al.
(författare)
-
"Distributed proton radiation therapy"--a new concept for advanced competence support.
- 2006
-
Ingår i: Acta oncologica (Stockholm, Sweden). - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 45:8, s. 1094-101
-
Tidskriftsartikel (refereegranskat)abstract
- The increased interest in high precision radiation therapy is to a large extent driven by the potential of modern imaging technology. The aim of this project was to analyse how an expensive proton facility best could support a multi-centre health care system. We have developed a model for distributed expert collaboration where all clinical experts will work close to their patients in regional centres. Patients who are candidates for proton therapy will be examined and dose-planned at their regional clinic, discussed in a fully information supported video conference and digitally made available at the proton treatment facility. The proton facility itself will be placed near a communication centre easily reached by all patients where they will be treated under full responsibility of their own physician at the home clinic. This concept has been analysed in detail both with respect to the overall functionality and with respect to possible weaknesses. It was found that the concept of distributed radiation therapy, as proposed here, will offer a stable clinical solution for advanced radiation therapy. It will support the spread of knowledge, serve as a fully developed backup system and the concept will further serve as an efficient base for clinical research.
|
|
| 4. |
|
|
| 5. |
- Daşu, Alexandru, et al.
(författare)
-
The effects of hypoxia on the theoretical modelling of tumour control probability
- 2005
-
Ingår i: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 44:6, s. 563-571
-
Tidskriftsartikel (refereegranskat)abstract
- Theoretical modelling of tumour response is increasingly used for the prediction of treatment result and has even been proposed as ranking criteria in some algorithms for treatment planning. Tumour response to radiation is greatly influenced by the details of tumour microenvironment, especially hypoxia, that unfortunately are not always taken into consideration for these simulations. This paper intends to investigate the effects of various assumptions regarding hypoxia distribution in tumours on the predictions of treatment outcome. A previously developed model for simulating theoretically the oxygenation in biologically relevant tissues, including results from oxygen diffusion, consumption and perfusion limitations in tumours, was used to investigate the effects of the different aspects of hypoxia on the predictions of treatment outcome. Thus, both the continuous distribution of values and the temporal variation of hypoxia patterns were taken into consideration and were compared with a 'black-and-white' simplification with a fully hypoxic compartment and a fully oxic one. It was found that the full distribution of oxygenation in the tissue is needed for accurate results. The 'black-and-white' simplification, while showing the same general trends for the predictions of radiation response, could lead to serious over-estimations of the tumour control probability. It was also found that the presence of some hypoxia for every treatment fraction leads to a decrease in the predicted local control, regardless of the change of the hypoxic pattern throughout the duration of the whole treatment. The results thus suggest that the assumptions regarding tumour hypoxia influence very much the predictions of treatment outcome and therefore they have to be very carefully incorporated into the theoretical modelling.
|
|
| 6. |
- Daşu, Alexandru, et al.
(författare)
-
The use of risk estimation models for the induction of secondary cancers following radiotherapy
- 2005
-
Ingår i: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 44:4, s. 339-347
-
Tidskriftsartikel (refereegranskat)abstract
- Theoretical predictions of cancer risk from radiotherapy may be used as a complementary criterion for the selection of successful treatment plans together with the classical approach of estimating the possible deterministic effects. However, any such attempts must take into consideration the specific features of radiation treatment. This paper explores several possible methods for estimating the risk of cancer following radiotherapy in order to investigate the influences of the fractionation and the non-uniformity of the dose to the irradiated organ. The results indicate that dose inhomogeneity plays an important role in predicting the risk for secondary cancer and therefore for predictive purposes it must be taken into account through the use of the dose volume histograms. They also suggest that the competition between cell killing and the induction of carcinogenic mutations has to be taken into consideration for more realistic risk estimations. Furthermore, more realistic parameters could be obtained if this competition is also included in analyses of epidemiological data from radiotherapy applications.
|
|
| 7. |
- Daşu, Alexandru, et al.
(författare)
-
Theoretical simulation of tumour oxygenation and results from acute and chronic hypoxia
- 2003
-
Ingår i: Physics in Medicine and Biology. - : IOP Publishing. - 0031-9155 .- 1361-6560. ; 48:17, s. 2829-2842
-
Tidskriftsartikel (refereegranskat)abstract
- The tumour microenvironment is considered to be responsible for the outcome of cancer treatment and therefore it is extremely important to characterize and quantify it. Unfortunately, most of the experimental techniques available now are invasive and generally it is not known how this influences the results. Non-invasive methods on the other hand have a geometrical resolution that is not always suited for the modelling of the tumour response. Theoretical simulation of the microenvironment may be an alternative method that can provide quantitative data for accurately describing tumour tissues. This paper presents a computerized model that allows the simulation of the tumour oxygenation. The model simulates numerically the fundamental physical processes of oxygen diffusion and consumption in a two-dimensional geometry in order to study the influence of the different parameters describing the tissue geometry. The paper also presents a novel method to simulate the effects of diffusion-limited (chronic) hypoxia and perfusion-limited (acute) hypoxia. The results show that all the parameters describing tissue vasculature are important for describing tissue oxygenation. Assuming that vascular structure is described by a distribution of inter-vessel distances, both the average and the width of the distribution are needed in order to fully characterize the tissue oxygenation. Incomplete data, such as distributions measured in a non-representative region of the tissue, may not give relevant tissue oxygenation. Theoretical modelling of tumour oxygenation also allows the separation between acutely and chronically hypoxic cells, a distinction that cannot always be seen with other methods. It was observed that the fraction of acutely hypoxic cells depends not only on the fraction of collapsed blood vessels at any particular moment, but also on the distribution of vessels in space as well. All these suggest that theoretical modelling of tissue oxygenation starting from the basic principles is a robust method that can be used to quantify the tissue oxygenation and to provide input parameters for other simulations.
|
|
| 8. |
- Toma-Dasu, Iuliana, et al.
(författare)
-
Conversion of polarographic electrode measurements--a computer based approach
- 2005
-
Ingår i: Physics in Medicine and Biology. - : IOP Publishing. - 0031-9155 .- 1361-6560. ; 50:19, s. 4581-4591
-
Tidskriftsartikel (refereegranskat)abstract
- The polarographic measurement of tissue oxygenation is one of the most widely used methods in clinical practice for the quantification of tumour hypoxia. However, due to the particular features of the electrode measuring process, the results of the measurements do not accurately reflect the tumour oxygenation. This study aimed to find a correlation between the electrode measurements and the tumour oxygenation in an attempt to improve the accuracy of the predictions regarding the response to treatment based on electrode measurements. A previously developed computer model that allows the simulation of tumour tissue and electrode measurements was used. The oxygenation of a large number of tumours with biologically relevant distributions of blood vessels was theoretically calculated. Simulations of electrode measurements allowed the comparison between the real tissue oxygenation and the results obtained with the electrode. A semi-empirical relationship between the hypoxic fraction measured by the electrode and the real hypoxic fraction in the tissue has been found. The impact of the correction of the electrode measurements in terms of predictions for tumour control probability was estimated for a few clinical examples. The range of possible true values corresponding to one measurement has also proven useful for explaining the apparently unexpected response to the treatment of some patients. The corrected hypoxic fraction which is believed to be closer to the real value of tissue hypoxia predicts much smaller control probabilities than the raw electrode measurements. This could provide an explanation for the apparently unexpected failure to respond to the treatment of some of the patients with apparently favourable tumour oxygenation. This also means that the electrode measurements cannot be used directly for the quantitative modelling of tumour response to the treatment. The conversion method proposed in this paper might however strengthen the statistical power of the correlations between the electrode measurements and the treatment outcome.
|
|
| 9. |
- Toma-Dasu, Iuliana, et al.
(författare)
-
The relationship between temporal variation of hypoxia, polarographic measurements and predictions of tumour response to radiation
- 2004
-
Ingår i: Physics in Medicine and Biology. - : IOP Publishing. - 0031-9155 .- 1361-6560. ; 49:19, s. 4463-4475
-
Tidskriftsartikel (refereegranskat)abstract
- The polarographic oxygen sensor is one of the most used devices for in vivo measurements of oxygen and many other measurement techniques for measuring tumour hypoxia are correlated with electrode measurements. Little is known however about the relationship between electrode measurements and the real tissue oxygenation. This paper investigates the influence of the temporal change of the hypoxic pattern on the electrode measurements and the tumour response. Electrode measurements and tumour response were simulated using a computer program that allows both the calculation of the tissue oxygenation with respect to the two types of hypoxia that might arise in tumours and the virtual insertion of the electrode into the tissue. It was therefore possible to control the amount of each type of hypoxia in order to investigate their influence on the measurement results. Tissues with several vascular architectures ranging from well oxygenated to poorly oxygenated were taken into consideration as might be seen in practice. The influence of the electrode measurements on the treatment outcome was estimated by calculating the tumour control probability for the tumours characterized either by the real or by the measured tumour oxygenation. We have simulated electrode oxygen measurements in different types of tissues, covering a wide range of tumour oxygenations. The results of the simulations showed that the measured distribution depends on the details of the vascular network and not on the type of hypoxia. We have also simulated the effects of the temporal change of the acute hypoxic pattern due to the opening and the closure of different blood vessels during a full fractionated treatment. The results of this simulation suggested that the temporal variation of the hypoxic pattern does not lead to significantly different results for the electrode measurements or the predicted tumour control probabilities. In conclusion, it was found that the averaging effect of the electrode leads to a systematic deviation between the actual oxygen distribution and the measured distribution. However, as the electrode reflects the general trends of the tissue oxygenation it has the potential of being used for the general characterization of tumour hypoxia even if the actual type of hypoxia measured by the electrode cannot be determined. Indeed, the change in time of the acute hypoxic region does not compensate for the lack of oxygenation at a specific moment and therefore does not influence the polarographic oxygen measurements.
|
|
| 10. |
|
|
