PubMed Health⌕ Search

Biomedical subjects

P Källman

Publications and source records attributed to P Källman.

10 recordsLinked to original sources
PubMed1995

Volume and heterogeneity dependence of the dose-response relationship for head and neck tumours.

Based on the Poisson statistics of cell kill a model for the response of heterogeneous tumours to non-uniform dose delivery have been developed. The five parameters required to characterize the response are the 50% response dose, D50, the normalized dose-response gradient, gamma, the tumour heterogeneity factor, h, the relative volume, v and the extra daily dose required to counteract the tumour cell proliferation, delta. The model has been fitted to data from a number of clinical investigations to allow the derivation of clinically relevant radiation response parameters for head and neck tumours. The D50 value for T2 larynx cancers is 59.9 Gy in 41 days with a relative standard deviation of 2.1 Gy and the gamma value is 2.9 with a relative standard deviation of 0.3. The value of delta, which is most consistent with the clinical data for laryngeal tumours, is 0.35 Gy/day and this value should be used if the treatment time is changed from the 41 days normalization. The heterogeneity factor, h, is close to zero for laryngeal tumours which indicates that their response is basically governed by Poisson statistics. Nasopharyngeal tumours, on the other hand, exhibit h values around 0.2 which indicates that these tumours are more heterogeneous in their internal organization and so are their responses to radiation.

Algorithms↗
PubMed1995

Repair of DNA double-strand breaks: errors encountered in the determination of half-life times in pulsed-field gel electrophoresis and neutral filter elution.

For theoretical reasons, it is incorrect to define experimentally the half-life times of DNA double-strand breaks (DSBs) as the half-life time of an amount of DNA. This is illustrated by one example of human DNA, where the half-life for first-order kinetics of the disappearance of DSBs has been assumed to be 10 min. Experimental sources of errors and their influence on experimental results are analyzed. Some experimental situations may lead to serious misinterpretation data. The differential decreases in fractions released (amounts of DNA) as often followed in pulsed-field gel electrophoresis depend on run conditions, background and level of DSB induction and are a function of time itself--a time function that is unrelated to the half-life of DSBs. It is shown that, using the decrease of a measured amount of DNA, one may obtain practically any value for the half-life time.

Animals↗
PubMed1994

Randomly distributed DNA double-strand breaks as measured by pulsed field gel electrophoresis: a series of explanatory calculations.

The aim of this article is to characterize expressions of relevance to the interpretation of pulsed field gel electrophoresis (PFGE) experiments where randomly distributed double-strand breaks (DSBs) are detected as smears of DNA fragments. Specifically, equations for conversion of percentages of fragments in defined size ranges to DSBs were derived. Several models have been used, one of which is based on theoretically fragmented DNA from the fission yeast Schizosaccharomyces pombe, which has three PFGE separable chromosomes.

Chromosomes, Fungal↗
PubMed1994

An analytical solution for the dynamic control of multileaf collimators.

All current optimization techniques in radiation therapy benefit from the use of strongly non-uniform radiation beams. The most flexible way of generating these fields under real time control is by elementary beam scanning and/or dynamic multileaf collimation. In this work general analytical expressions are derived for the required motion of the collimator leaves to achieve a desired energy fluence distribution or collimator opening density in the patient in the shortest possible time. By simplification of the general expressions the equations of motion have been derived for both the shrinking field and the curtain shutter techniques with the associated approximations clearly quantified. The mechanical limitations on leaf motion, caused by the finite velocity and acceleration, are taken into account. It is shown that almost any desired energy fluence distribution can be created even when the limitations on velocity and acceleration are considered. The basic rule with the curtain shutter technique is that when the energy fluence gradient along the direction of motion of the leaves is positive, the leading leaf should move at maximum speed and the lagging leaf should modulate the field. In regions where the gradient is negative the lagging leaf should instead move at full speed and the leading leaf should modulate the field. The overall treatment time is then proportional to the total increment in energy fluence or opening density between consecutive minima and maxima. For energy fluence profiles with numerous high peaks the treatment time may therefore increase considerably over that for conventional uniform dose delivery. However, in general the treatment time is prolonged by a factor of about two compared to a traditional uniform treatment. Obviously the method developed here for multileaf collimators is also suitable for simple block collimators since it can be used to deliver arbitrary regular or irregular 'dynamic wedge' profiles along the direction of motion of the collimator blocks.

Humans↗
PubMed1993

Optimal radiation beam profiles considering uncertainties in beam patient alignment.

The often large uncertainties that exist in beam patient alignment during radiation therapy may require modification of the incident beams to ensure an optimal delivered dose distribution to the target volume. This problem becomes increasingly severe when the required dose distribution of the incident beams becomes more heterogeneous. A simple analytical formula is derived for the case when the fraction number is high, and the desired relative dose variations are small. This formula adjusts the fluence distribution of the incident beam so that the resultant dose distribution will be as close as possible to the desired one considering the uncertainties in beam patient alignment. When sharp dose gradients are important, for instance at the border of the target volume, the problem is much more difficult. It is shown here that, if the tumor is surrounded by organs at risk, it is generally best to open up the field by about one standard deviation of the positional uncertainty--that is sigma/2 on each side of the target volume. In principle it is simultaneously desirable to increase the prescribed dose by a few per cent compared to the case where the positional uncertainty is negligible, in order to compensate for the rounded shoulders of the delivered dose distribution. When the tissues surrounding the tumor no longer are dose limiting even larger increases in field size may be advantageous. For more critical clinical situations the positional uncertainty may even limit the success of radiotherapy. In such cases one generally wants to create a steeper dose distribution than the underlying random Gaussian displacement process allows. The problem is then best handled by quantifying the treatment outcome under the influence of the stochastic process of patient misalignment. Either the coincidence with the desired dose distribution, or the expectation value of the probability of achieving complication-free tumor control is maximized under the influence of this stochastic process. It is shown that the most advantageous treatment is to apply beams that are either considerably widened or slightly widened and over flattened near the field edges for small and large fraction numbers respectively.

Dose-Response Relationship, Radiation↗
PubMed1992

Tumour and normal tissue responses to fractionated non-uniform dose delivery.

The dose-volume response of tumours and normal tissues is discussed in terms of 'parallelity' and 'seriality'. The volume dependence of the radiation response of a tumour depends primarily on the eradication of all its clonogenic cells and the tumour has a parallel organization. The response of heterogeneous tumours is examined, and it is shown that a small resistant clonogen population may cause a low dose-response gradient, gamma. Injury to normal tissue is a much more complex and gradual process. It depends on earlier effects induced long before depletion of stem cells or differentiated cells that in addition may have a complex structural and functional organization. The volume dependence of the dose-response relation of normal tissues is therefore described here by a new parameter, the 'relative seriality', s, of the infrastructure of the organ. The model is compared with clinical and experimental data on normal tissue response, and shows good agreement both with regard to the shape of dose-response relation and the volume dependence of the isoeffect dose. For example, the spinal cord has a high and the lung a low 'relative seriality', which is reasonable with regard to the organization of these tissues. The response of tumours and normal tissues to non-uniform dose delivery is quantified for fractionated therapy using the linear quadratic cell survival parameters alpha and beta. The steepness, gamma, and the 50% response dose, D50, of the dose-response relationship are derived both for a constant dose per fraction and a constant number of dose fractions.

Dose-Response Relationship, Radiation↗
PubMed1992

An algorithm for maximizing the probability of complication-free tumour control in radiation therapy.

New radiobiological models are used to describe tumour and normal tissue reactions and to account for their dependence on the irradiated volume and inhomogeneities of the delivered dose distribution and cell sensitivity. The probability of accomplishing complication-free tumour control is maximized by an iterative algorithm. The algorithm is demonstrated by applying it to a one-dimensional (1D) tumour model but also to a more clinically relevant 2D case. The new algorithm is n-dimensional so it could simultaneously optimize the dose delivery in a 3D volume and in principle also select the ideal beam orientations, beam modalities (photons, electrons, neutrons, etc) and optimal spectral distributions of the corresponding modalities. To make calculation time reasonable, 2D-3D problems are most practical, and suitable beam orientations are preselected by the choice of irradiation kernel. The energy deposition kernel should therefore be selected in order to avoid irradiation through organs at risk. Clinically established dose response parameters for the tissues of interest are used to make the optimization as relevant as possible to the clinical problems at hand. The algorithm can be used even with a poorly selected kernel because it will always, as far as possible, avoid irradiating organs at risk. The generated dose distribution will be optimal with respect to the spatial distribution and assumed radiobiological properties of the tumour and normal tissues at risk for the kernel chosen. More specifically the probability of achieving tumour control without fatal complications in normal tissues is maximized. In the clinical examples a reduced tumour dose is seen at the border to sensitive organs at risk, but instead an increased dose just inside the tumour border is generated. The increased tumour dose has the effect that the dose fall-off is as steep as possible at the border to organs at risk.

Algorithms↗
PubMed1990

Experimental verification of an algorithm for inverse radiation therapy planning.

In inverse radiotherapy planning, the traditional dose planning sequence is reversed. This makes it possible to calculate the optimal incident beam profiles required to produce the desired dose distribution in the target volume by solving an integral equation with an iterative algorithm. The major advantage, compared with conventional treatment planning, is that the trial and error part is avoided, and replaced by a deterministic calculation of the optimal treatment plan. In the present paper this algorithm is briefly described and compared with experimental results and an analytical inversion formula which is valid for a cylindrical geometry. The experiments were performed with non-homogeneous beams shaped with compensators designed using the algorithm. The agreement between the experimental results and the predictions of the algorithm are quite good, generally within about 5%. The differences are caused by discretization noise due to the finite resolution of the calculation matrix, imperfections in the experimental situation, and by the assumption of spatial invariant dose distribution kernels.

Algorithms↗
PubMed1988

Shaping of arbitrary dose distributions by dynamic multileaf collimation.

Traditionally, the shaping of non-uniform dose distributions has been performed by using wedges or compensating filters. The advent of high resolution multileaf collimators may largely eliminate the need for material attenuators for modification of the beam. This is achieved by a new technique for the shaping of arbitrary dose distributions by dynamic motion of the collimator leaves. By employing narrow elementary slit beams that correspond to the smallest possible opening of the multileaf collimator, the optimal density of such slit beams, i.e. opening density, can be determined automatically using a newly developed inversion algorithm. The present method has two major advantages (1) internal structures in the field can be created, controlled solely by steering the collimator leaves, (2) the opening density determined by the algorithm never gives rise to underdosage: this is important from a radiobiological point of view.

Humans↗