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  • 51.
    Toma-Daşu, Iuliana
    et al.
    Umeå University.
    Daşu, Alexandru
    Umeå University.
    Karlsson, Mikael
    Umeå University.
    Theoretical simulation of tumour hypoxia measurements2006In: Advances in Experimental Medicine and Biology, ISSN 0065-2598, E-ISSN 2214-8019, Vol. 578, no 12, p. 369-374Article in journal (Refereed)
    Abstract [en]

    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.

  • 52.
    Toma-Daşu, Iuliana
    et al.
    Umeå University.
    Daşu, Alexandru
    Umeå University.
    Waites, Anthony
    Umeå University.
    Denekamp, Juliana
    Umeå University.
    Computer simulation of oxygen microelectrode measurements in tissues2003In: Advances in Experimental Medicine and Biology, ISSN 0065-2598, E-ISSN 2214-8019, Vol. 510, p. 157-161Article in journal (Refereed)
  • 53.
    Toma-Daşu, Iuliana
    et al.
    Umeå University.
    Daşu, Alexandru
    Umeå University.
    Waites, Anthony
    Umeå University.
    Denekamp, Juliana
    Umeå University.
    Fowler, Jack F
    University of Wisconsin Hospital, USA.
    Theoretical simulation of oxygen tension measurement in the tissue using a microelectrode: II. Simulated measurements in tissues2002In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 64, no 1, p. 109-118Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE: The objectives of this study were to make a computer simulation of tissues with different vascular structures and to simulate measurements of oxygen tension using an Eppendorf-like electrode in these tissues and to compare the response to radiation of the tissues with the real oxygen distributions (called input distribution) with the response to radiation of the tissues in which the oxygen distribution is given by the results of the simulated measurements (called output distribution).

    MATERIALS AND METHODS: The structure of various tissues and the measurements of oxygen tension using a microelectrode were simulated using a computer program. The mathematical model used combines the description of a gradient of tissue oxygenation and the electrode absorption process.

    RESULTS: We have compared the oxygen distributions resulting from diffusion (input) with those obtained from a simulation of measurements (output) for various tissues in the same points. Because the electrode measurement is an averaging process, the calculated oxygen distributions are different from the expected ones and the extreme high and low values are not detected. We have then calculated the survival curves describing the response to radiation if there is a small fraction of truly hypoxic cells (expected values) or a large fraction of cells at intermediate values (observed results) in order to determine the differences between them.

    CONCLUSIONS: The results of our study show that oxygen electrode measurements do not give the true distribution of pO(2) values in the tissue. However, our results do not contradict the numerous empirical correlations between the Eppendorf measurements of tumour oxygenation and the outcome of treatments. Measurement results will be misleading for modelling purposes since they do not reflect the actual distributions of oxygen tensions in the measured tissue. Decisions based on such modelling could be very dangerous, especially with respect to the clinical response of tumours to new treatments.

  • 54.
    Toma-Daşu, Iuliana
    et al.
    Stockholm University and Karolinska Institutet.
    Uhrdin, Johan
    RaySearch Laboratories AB, Stockholm.
    Daşu, Alexandru
    Umeå University.
    Brahme, Anders
    Karolinska Institutet.
    Therapy optimization based on non-linear uptake of PET tracers versus "linear dose painting"2009In: IFMBE Proceedings, Vol. 25/I, p. 221-224Article in journal (Refereed)
    Abstract [en]

    Treatment optimization based on positron emission tomography (PET) images of tumor hypoxia has been proposed as a method to improve the cure rates in radiotherapy through the increased dose delivery to tumor regions with increased radioresistance. One of the major advantages of PET imaging of hypoxia is that it can provide information on both the extent and the spatial distribution of the resistant regions. One of the key issues for the practical implementation of this approach is the accurate conversion of the intensities in the recorded images into radiosensitivity maps that could then be used for dose escalation. The present paper explores the influence of the conversion from uptake to prescribed doses. Transformation functions derived from the uptake properties of the PET tracers were taken into consideration. The results have shown that the available tracers have different uptake properties and therefore they could interpret differently the gradients in the images which in turn would lead to different dose predictions. Best results in terms of dose prescription would therefore be achieved by carefully taking into account the uptake characteristics of the imaged tracers. Linear approximations could lead to unnecessary overestimations of the doses for cases of partial hypoxia in tumors. This highlights the need for more experimental studies of the uptake properties of PET tracers proposed to image tissue hypoxia. These would eventually provide more reliable methods for dose prescription that could be used with optimization algorithms for the successful individualization of radiation therapy.

  • 55.
    Toma-Daşu, Iuliana
    et al.
    Umeå University.
    Waites, Anthony
    Umeå University.
    Daşu, Alexandru
    Umeå University.
    Denekamp, Juliana
    Umeå University.
    Theoretical simulation of oxygen tension measurement in tissues using a microelectrode: I. The response function of the electrode2001In: Physiological Measurement, ISSN 0967-3334, E-ISSN 1361-6579, Vol. 22, no 4, p. 713-725Article in journal (Refereed)
    Abstract [en]

    The aim of this article is to determine the correlation between the actual oxygen distribution in tissues and the distribution of oxygen measured by microelectrodes. This correlation is determined by the response function of the electrode, which depends on the oxygen consumed by the electrode. In tissue it is necessary to consider the gradients resulting from cellular respiration. A computer program has been used to simulate the vascular structure of various tissues and also the measurements of oxygen tension using a polarographic electrode. The electrode absorption process is described using a theoretical model. The gradient of oxygen in tissue is described by a mathematical model that takes into consideration both diffusion and cellular consumption of oxygen. We have compared the results obtained using the response function of the electrode and some simplifications of it. The results of these comparisons show that there are some differences in the 'observed' distributions of the oxygen tension in tissues predicted using different formulae for the electrode response function. Also, there are considerable differences between the input oxygen distribution and the measured values in all cases. All the results of the simulations of the oxygen tension 'observed' by a 12 microm polarographic electrode, using different response functions of the electrode, show that the electrode averages the values from many cells. Care should be taken in using a simplification for the response function of the electrode, especially if the results are going to be used as input values in modelling the tumour response to new treatments and/or as a basis of selecting patients for treatments. A computer simulation of measurement of oxygen tensions in regions of steep pO2 gradients shows that extremely high and extremely low pO2 values will not be detected.

  • 56.
    Ureba, Ana
    et al.
    Medical Radiation Physics, Department of Physics, Stockholm University, Stockholm, Sweden.
    Lindblom, Emely
    Medical Radiation Physics, Department of Physics, Stockholm University, Stockholm, Sweden.
    Dasu, Alexandru
    The Skandion Clinic, Uppsala, Sweden.
    Uhrdin, Johan
    RaySearch Laboratories AB, Stockholm, Sweden.
    Even, Aniek J. G.
    Maastricht University Medical Center, Maastricht, The Netherlands.
    van Elmpt, Wouter
    Maastricht University Medical Center, Maastricht, The Netherlands.
    Lambin, Philippe
    Maastricht University Medical Center, Maastricht, The Netherlands.
    Wersäll, Peter
    Department of Oncology, Karolinska University Hospital, Stockholm, Sweden.
    Toma-Dasu, Iuliana
    Medical Radiation Physics, Department of Physics, Stockholm University, Stockholm, Sweden; Medical Radiation Physics, Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden.
    Non-linear conversion of HX4 uptake for automatic segmentation of hypoxic volumes and dose prescription2018In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 57, no 4, p. 485-490Article in journal (Refereed)
    Abstract [en]

    Background: Tumour hypoxia is associated with increased radioresistance and poor response to radiotherapy. Pre-treatment assessment of tumour oxygenation could therefore give the possibility to tailor the treatment by calculating the required boost dose needed to overcome the increased radioresistance in hypoxic tumours. This study concerned the derivation of a non-linear conversion function between the uptake of the hypoxia-PET tracer 18F-HX4 and oxygen partial pressure (pO2).

    Material and methods: Building on previous experience with FMISO including experimental data on tracer uptake and pO2, tracer-specific model parameters were derived for converting the normalised HX4-uptake at the optimal imaging time point to pO2. The conversion function was implemented in a Python-based computational platform utilising the scripting and the registration modules of the treatment planning system RayStation. Subsequently, the conversion function was applied to determine the pO2 in eight non-small-cell lung cancer (NSCLC) patients imaged with HX4-PET before the start of radiotherapy. Automatic segmentation of hypoxic target volumes (HTVs) was then performed using thresholds around 10 mmHg. The HTVs were compared to sub-volumes segmented based on a tumour-to-blood ratio (TBR) of 1.4 using the aortic arch as the reference oxygenated region. The boost dose required to achieve 95% local control was then calculated based on the calibrated levels of hypoxia, assuming inter-fraction reoxygenation due to changes in acute hypoxia but no overall improvement of the oxygenation status.

    Results: Using the developed conversion tool, HTVs could be obtained using pO2 a threshold of 10 mmHg which were in agreement with the TBR segmentation. The dose levels required to the HTVs to achieve local control were feasible, being around 70–80 Gy in 24 fractions.

    Conclusions: Non-linear conversion of tracer uptake to pO2 in NSCLC imaged with HX4-PET allows a quantitative determination of the dose-boost needed to achieve a high probability of local control.

  • 57.
    Ödén, Jakob
    et al.
    Stockholm University and RaySearch Laboratories AB, Stockholm, Sweden.
    Toma-Dasu, Iuliana
    Stockholm University and Karolinska Institutet, Stockholm, Sweden.
    Eriksson, Kjell
    RaySearch Laboratories AB, Stockholm, Sweden.
    Flejmer, Anna M.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Dasu, Alexandru
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. The Skandion Clinic, Uppsala, Sweden.
    The influence of breathing motion and a variable relative biological effectiveness in proton therapy of left-sided breast cancer2017In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 56, no 11, p. 1428-1436Article in journal (Refereed)
    Abstract [en]

    Background: Proton breast radiotherapy has been suggested to improve target coverage as well as reduce cardiopulmonary and integral dose compared with photon therapy. This study aims to assess this potential when accounting for breathing motion and a variable relative biological effectiveness (RBE).

    Methods: Photon and robustly optimized proton plans were generated to deliver 50 Gy (RBE) in 25 fractions (RBE=1.1) to the CTV (whole left breast) for 12 patients. The plan evaluation was performed using the constant RBE and a variable RBE model. Robustness against breathing motion, setup, range and RBE uncertainties was analyzed using CT data obtained at free-breathing, breath-hold-at-inhalation and breath-hold-at-exhalation.

    Results: All photon and proton plans (RBE=1.1) met the clinical goals. The variable RBE model predicted an average RBE of 1.18 for the CTVs (range 1.14–1.21) and even higher RBEs in organs at risk (OARs). However, the dosimetric impact of this latter aspect was minor due to low OAR doses. The normal tissue complication probability (NTCP) for the lungs was low for all patients (<1%), and similar for photons and protons. The proton plans were generally considered robust for all patients. However, in the most extreme scenarios, the lowest dose received by 98% of the CTV dropped from 96 to 99% of the prescribed dose to around 92–94% for both protons and photons. Including RBE uncertainties in the robustness analysis resulted in substantially higher worst-case OAR doses.

    Conclusions: Breathing motion seems to have a minor effect on the plan quality for breast cancer. The variable RBE might impact the potential benefit of protons, but could probably be neglected in most cases where the physical OAR doses are low. However, to be able to identify outlier cases at risk for high OAR doses, the biological evaluation of proton plans taking into account the variable RBE is recommended.

12 51 - 57 of 57
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