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Improved dose response modeling for normal tissue damage and therapy optimization
Stockholm University, Faculty of Science, Medical Radiation Physics (together with KI).
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

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.

Place, publisher, year, edition, pages
Stockholm: Medicinsk strålningsfysik (tills m KI) , 2008. , 52 p.
Keyword [en]
Normal tissue complications, radiobiological models, dose-response, volume effect, spinal cord, effective FSU size
Research subject
Medical Radiation Physics
Identifiers
URN: urn:nbn:se:su:diva-7433ISBN: 978-91-7155-584-7 (print)OAI: oai:DiVA.org:su-7433DiVA: diva2:198264
Public defence
2008-04-04, Rolf Lufts Auditorium, Karolinska Universitetssjukhuset, Solna, 09:15
Opponent
Supervisors
Available from: 2008-03-13 Created: 2008-03-13Bibliographically approved
List of papers
1. Variation in radiation sensitivity and repair kinetics in different parts of the spinal cord
Open this publication in new window or tab >>Variation in radiation sensitivity and repair kinetics in different parts of the spinal cord
2008 In: Acta Oncologica, ISSN 1651-226X (electronic) 0284-186X (paper), 1-9 p.Article in journal (Refereed) Published
Identifiers
urn:nbn:se:su:diva-24755 (URN)000257081200013 ()
Note
Part of urn:nbn:se:su:diva-7433Available from: 2008-03-13 Created: 2008-03-13Bibliographically approved
2. The dose response relation for rat spinal cord paralysis analyzed in terms of the effective size of the functional subunit
Open this publication in new window or tab >>The dose response relation for rat spinal cord paralysis analyzed in terms of the effective size of the functional subunit
Manuscript (Other academic)
Identifiers
urn:nbn:se:su:diva-24756 (URN)
Note
Part of urn:nbn:se:su:diva-7433Available from: 2008-03-13 Created: 2008-03-13 Last updated: 2010-01-13Bibliographically approved
3. Comments on ‘Reconsidering the definition of a dose–volume histogram’—dose–mass histogram (DMH) versus dose–volume histogram (DVH) for predicting radiation-induced pneumonitis
Open this publication in new window or tab >>Comments on ‘Reconsidering the definition of a dose–volume histogram’—dose–mass histogram (DMH) versus dose–volume histogram (DVH) for predicting radiation-induced pneumonitis
2006 In: Physics in Medicine and Biology, ISSN 0031-9155 (Print), 1361-6560 (Online), Vol. 51, no 24, L43–L50- p.Article in journal (Refereed) Published
Identifiers
urn:nbn:se:su:diva-24757 (URN)
Note
Part of urn:nbn:se:su:diva-7433Available from: 2008-03-13 Created: 2008-03-13Bibliographically approved
4. Impact of Different Dose-Response Parameters on Biologically Optimized IMRT in Breast Cancer
Open this publication in new window or tab >>Impact of Different Dose-Response Parameters on Biologically Optimized IMRT in Breast Cancer
Show others...
2008 (English)In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 53, no 10, 2733-2752 p.Article in journal (Refereed) Published
Abstract [en]

The full potential of biologically optimized radiation therapy can only be maximized with the prediction of individual patient radiosensitivity prior to treatment. Unfortunately, the available biological parameters, derived from clinical trials, reflect an average radiosensitivity of the examined populations. In the present study, a breast cancer patient of stage I–II with positive lymph nodes was chosen in order to analyse the effect of the variation of individual radiosensitivity on the optimal dose distribution. Thus, deviations from the average biological parameters, describing tumour, heart and lung response, were introduced covering the range of patient radiosensitivity reported in the literature. Two treatment configurations of three and seven biologically optimized intensity-modulated beams were employed. The different dose distributions were analysed using biological and physical parameters such as the complication-free tumour control probability (P+), the biologically effective uniform dose (), dose volume histograms, mean doses, standard deviations, maximum and minimum doses. In the three-beam plan, the difference in P+ between the optimal dose distribution (when the individual patient radiosensitivity is known) and the reference dose distribution, which is optimal for the average patient biology, ranges up to 13.9% when varying the radiosensitivity of the target volume, up to 0.9% when varying the radiosensitivity of the heart and up to 1.3% when varying the radiosensitivity of the lung. Similarly, in the seven-beam plan, the differences in P+ are up to 13.1% for the target, up to 1.6% for the heart and up to 0.9% for the left lung. When the radiosensitivity of the most important tissues in breast cancer radiation therapy was simultaneously changed, the maximum gain in outcome was as high as 7.7%. The impact of the dose–response uncertainties on the treatment outcome was clinically insignificant for the majority of the simulated patients. However, the jump from generalized to individualized radiation therapy may significantly increase the therapeutic window for patients with extreme radio sensitivity or radioresistance, provided that these are identified. Even for radiosensitive patients a simple treatment technique is sufficient to maximize the outcome, since no significant benefits were obtained with a more complex technique using seven intensity-modulated beams portals.

Identifiers
urn:nbn:se:su:diva-24758 (URN)10.1088/0031-9155/53/10/019 (DOI)000256342700019 ()
Note
Part of urn:nbn:se:su:diva-7433Available from: 2008-03-13 Created: 2008-03-13 Last updated: 2017-12-13Bibliographically approved

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