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  • 1.
    Andisheh, Bahram
    et al.
    Stockholm University, Faculty of Science, Department of Physics.
    Belkic, D.
    Mavroidis, Panayiotis
    Stockholm University, Faculty of Science, Department of Physics.
    Alahverdi, M.
    Lind, B. K.
    Improving the therapeutic ratio in stereotactic radiosurgery: optimizing treatment protocols based on kinetics of repair of sublethal radiation damage2013In: Technology in Cancer Research & Treatment (Trykt), ISSN 1533-0346, E-ISSN 1533-0338, Vol. 12, no 4, p. 349-361Article in journal (Refereed)
    Abstract [en]

    Sublethal damage after radiation exposure may become lethal or be repaired according to repair kinetics. This is a well-established concept in conventional radiotherapy. It also plays an important role in single-dose stereotactic radiotherapy treatments, often called stereotactic radiosurgery, when duration of treatment is extended due to source decay or treatment planning protocol. The purpose of this study is to look into the radiobiological characteristics of normal brain tissue and treatment protocols and find a way to optimize the time course of these protocols. The general problem is nonlinear and can be solved numerically. For numerical optimization of the time course of radiation protocol, a biexponential repair model with slow and fast components was considered. With the clinically imposed constraints of a fixed total dose and total treatment time, three parameters for each fraction (dose-rate, fraction duration, time of each fraction) were simultaneously optimized. A biological optimization can be performed by maximizing the therapeutic difference between tumor control probability and normal tissue complication probability. Specifically, for gamma knife radiosurgery, this approach can be implemented for normal brain tissue or tumor voxels separately in a treatment plan. Differences in repair kinetics of normal tissue and tumors can be used to find clinically optimized protocols. Thus, in addition to considering the physical dose in tumor and normal tissue, we also account for repair of sublethal damage in both these tissues.

  • 2.
    Andisheh, Bahram
    et al.
    Stockholm University, Faculty of Science, Medical Radiation Physics (together with KI).
    Bitaraf, Mohammad Ali
    University of Tehran.
    Mavroidis, Panayiotis
    Stockholm University, Faculty of Science, Medical Radiation Physics (together with KI).
    Brahme, Anders
    Stockholm University, Faculty of Science, Medical Radiation Physics (together with KI).
    Lind, Bengt
    Stockholm University, Faculty of Science, Medical Radiation Physics (together with KI).
    Vascular structure and binomial statistics for response modeling in radiosurgery of cerebral arteriovenous malformations2010In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 55, no 7, p. 2057-2067Article in journal (Refereed)
    Abstract [en]

    Radiation treatment of arteriovenous malformations (AVMs) has a slow and progressive vaso-occlusive effect. Some studies suggested the possible role of vascular structure in this process. A detailed biomathematical model has been used, where the morphological, biophysical and hemodynamic characteristics of intracranial AVM vessels are faithfully reproduced. The effect of radiation on plexiform and fistulous AVM nidus vessels was simulated using this theoretical model. The similarities between vascular and electrical networks were used to construct this biomathematical AVM model and provide an accurate rendering of transnidal and intranidal hemodynamics. The response of different vessels to radiation and their obliteration probability as a function of different angiostructures were simulated and total obliteration was defined as the probability of obliteration of all possible vascular pathways. The dose response of the whole AVM is observed to depend on the vascular structure of the intra-nidus AVM. Furthermore, a plexiform AVM appears to be more prone to obliteration compared with an AVM of the same size but having more arteriovenous fistulas. Finally, a binomial model was introduced, which considers the number of crucial vessels and is able to predict the dose response behavior of AVMs with a complex vascular structure.

  • 3.
    Andisheh, Bahram
    et al.
    Stockholm University, Faculty of Science, Department of Physics.
    Brahme, Anders
    Stockholm University, Faculty of Science, Medical Radiation Physics (together with KI).
    Bitaraf, Mohammad Ali
    Mavroidis, Panayiotis
    Stockholm University, Faculty of Science, Medical Radiation Physics (together with KI).
    Lind, Bengt K
    Stockholm University, Faculty of Science, Medical Radiation Physics (together with KI).
    Clinical and radiobiological advantages of single-dose stereotactic light-ion radiation therapy for large intracranial arteriovenous malformations. Technical note2009In: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 111, no 5, p. 919-926Article in journal (Refereed)
    Abstract [en]

    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 <or= 10 cm(3), whereas treatment with the light ion Li, Be, or C may be more appropriate for larger AVMs. A binomial model based on the effective number of crucial vessels in the AVM may be used quite well to predict AVM obliteration probabilities for both small and large AVMs when therapies involving either photons or light ions are used.

  • 4. Dzintars, Eric
    et al.
    Stathakis, Sotirios
    Mavroidis, Panayiotis
    Stockholm University, Faculty of Science, Department of Physics.
    Sadeghi, Amir
    Papanikolaou, Nikos
    Performance of independent dose calculation in helical tomotherapy: implementation of the mcsim code2012In: Australasian Physical & Engineering Sciences in Medicine, ISSN 0158-9938, Vol. 35, no 4, p. 423-438Article in journal (Refereed)
    Abstract [en]

    Currently, a software-based second check dose calculation for helical tomotherapy (HT) is not available. The goal of this study is to evaluate the dose calculation accuracy of the in-house software using EGS4/MCSIM Monte Carlo environment against the treatment planning system calculations. In-house software was used to convert HT treatment plan information into a non-helical format. The MCSIM dose calculation code was evaluated by comparing point dose calculations and dose profiles against those from the HT treatment plan. Fifteen patients, representing five treatment sites, were used in this comparison. Point dose calculations between the HT treatment planning system and the EGS4/MCSIM Monte Carlo environment had percent difference values below 5 % for the majority of this study. Vertical and horizontal planar profiles also had percent difference values below 5 % for the majority of this study. Down sampling was seen to improve speed without much loss of accuracy. EGS4/MCSIM Monte Carlo environment showed good agreement with point dose measurements, compared to the HT treatment plans. Vertical and horizontal profiles also showed good agreement. Significant time saving may be obtained by down-sampling beam projections. The dose calculation accuracy of the in-house software using the MCSIM code against the treatment planning system calculations was evaluated. By comparing point doses and dose profiles, the EGS4/MCSIM Monte Carlo environment was seen to provide an accurate independent dose calculation.

  • 5. Dzintars, Erik
    et al.
    Papanikolaou, Nikos
    Mavroidis, Panayiotis
    Stockholm University, Faculty of Science, Department of Physics. Karolinska Institute, Sweden.
    Sadeghi, Amir
    Stathakis, Sotirios
    Application of an independent dose calculation software for estimating the impact of inter-fractional setup shifts in Helical Tomotherapy treatments2013In: Physica medica (Testo stampato), ISSN 1120-1797, E-ISSN 1724-191X, Vol. 29, no 6, p. 615-623Article in journal (Refereed)
    Abstract [en]

    The purpose of this study is to validate the capability of in-house independent point dose calculation software to be used as a second check for Helical Tomotherapy treatment plans. The software performed its calculations in homogenous conditions (using the Cheese phantom, which is a cylindrical phantom with radius 15 cm and length 18 cm) using a factor-based algorithm. Fifty patients, who were treated for pelvic (10), prostate (14), lung (10), head 82 neck (12) and brain (4) cancers, were used. Based on the individual patient kVCT images and the pretreatment MVCT images for each treatment fraction, the corresponding daily patient setup shifts in the IEC-X, IEC-Y, and IEC-Z directions were registered. For each patient, the registered fractional setup shifts were grouped into systematic and random shifts. The average systematic dosimetric variations showed small dose deviation for the different cancer types (1.0%-3.0%) compared to the planned dose. Of the fifty patients, only three had percent differences larger than 5%. The average random dosimetric variations showed relatively small dose deviations (0.2%-1.1%) compared to the planned dose. None of the patients had percent differences larger than 5%. By examining the individual fractions of each patient, it is observed that only in 31 out of 1358 fractions the percent differences exceeded the border of 5%. These results indicate that the overall dosimetric impact from systematic and random variations is small and that the software is a capable platform for independent point dose validation for the Helical Tomotherapy modality. (C) 2012 Associazione Italiana di Fisica Medica.

  • 6. Giantsoudi, D.
    et al.
    Baltas, D.
    Karabis, A.
    Mavroidis, Panayiotis
    Stockholm University, Faculty of Science, Department of Physics. Karolinska Institutet.
    Zamboglou, N.
    Tselis, N.
    Shi, C.
    Papanikolaou, N.
    A gEUD-based inverse planning technique for HDR prostate brachytherapy: Feasibility study2013In: Medical physics (Lancaster), ISSN 0094-2405, Vol. 40, no 4, p. 041704-Article in journal (Refereed)
    Abstract [en]

    Purpose: The purpose of this work was to study the feasibility of a new inverse planning technique based on the generalized equivalent uniform dose for image-guided high dose rate (HDR) prostate cancer brachytherapy in comparison to conventional dose-volume based optimization. Methods: The quality of 12 clinical HDR brachytherapy implants for prostate utilizing HIPO (Hybrid Inverse Planning Optimization) is compared with alternative plans, which were produced through inverse planning using the generalized equivalent uniform dose (gEUD). All the common dose-volume indices for the prostate and the organs at risk were considered together with radiobiological measures. The clinical effectiveness of the different dose distributions was investigated by comparing dose volume histogram and gEUD evaluators. Results: Our results demonstrate the feasibility of gEUD-based inverse planning in HDR brachytherapy implants for prostate. A statistically significant decrease in D-10 or/and final gEUD values for the organs at risk (urethra, bladder, and rectum) was found while improving dose homogeneity or dose conformity of the target volume. Conclusions: Following the promising results of gEUD-based optimization in intensity modulated radiation therapy treatment optimization, as reported in the literature, the implementation of a similar model in HDR brachytherapy treatment plan optimization is suggested by this study. The potential of improved sparing of organs at risk was shown for various gEUD-based optimization parameter protocols, which indicates the ability of this method to adapt to the user's preferences.

  • 7. Knaup, Courtney
    et al.
    Mavroidis, Panayiotis
    Stockholm University, Faculty of Science, Department of Physics.
    Esquivel, Carlos
    Stathakis, Sotirios
    Swanson, Gregory
    Baltas, Dimos
    Papanikolaou, Nikos
    Investigating the dosimetric and tumor control consequences of prostate seed loss and migration2012In: Medical physics (Lancaster), ISSN 0094-2405, Vol. 39, no 6, p. 3291-3298Article in journal (Refereed)
    Abstract [en]

    Purpose: Low dose-rate brachytherapy is commonly used to treat prostate cancer. However, once implanted, the seeds are vulnerable to loss and movement. The goal of this work is to investigate the dosimetric and radiobiological effects of the types of seed loss and migration commonly seen in prostate brachytherapy. Methods: Five patients were used in this study. For each patient three treatment plans were created using Iodine-125, Palladium-103, and Cesium-131 seeds. The three seeds that were closest to the urethra were identified and modeled as the seeds lost through the urethra. The three seeds closest to the exterior of prostatic capsule were identified and modeled as those lost from the prostate periphery. The seed locations and organ contours were exported from Prowess and used by in-house software to perform the dosimetric and radiobiological evaluation. Seed loss was simulated by simultaneously removing 1, 2, or 3 seeds near the urethra 0, 2, or 4 days after the implant or removing seeds near the exterior of the prostate 14, 21, or 28 days after the implant. Results: Loss of one, two or three seeds through the urethra results in a D-90 reduction of 2%, 5%, and 7% loss, respectively. Due to delayed loss of peripheral seeds, the dosimetric effects are less severe than for loss through the urethra. However, while the dose reduction is modest for multiple lost seeds, the reduction in tumor control probability was minimal. Conclusions: The goal of this work was to investigate the dosimetric and radiobiological effects of the types of seed loss and migration commonly seen in prostate brachytherapy. The results presented show that loss of multiple seeds can cause a substantial reduction of D-90 coverage. However, for the patients in this study the dose reduction was not seen to reduce tumor control probability. (C) 2012 American Association of Physicists in Medicine.

  • 8. Lavdas, Eleftherios
    et al.
    Mavroidis, Panayiotis
    Stockholm University, Faculty of Science, Department of Physics.
    Hatzigeorgiou, Vasiliki
    Roka, Violeta
    Arikidis, Nikos
    Oikonomou, Georgia
    Andrianopoulos, Konstantinos
    Notaras, Ioannis
    Elimination of motion and pulsation artifacts using BLADE sequences in knee MR imaging2012In: Magnetic Resonance Imaging, ISSN 0730-725X, E-ISSN 1873-5894, Vol. 30, no 8, p. 1099-1110Article in journal (Refereed)
    Abstract [en]

    The purpose of this study is to evaluate the ability of proton density (PD)-BLADE sequences in reducing or even eliminating motion and pulsatile flow artifacts in knee magnetic resonance imaging examinations. Eighty consecutive patients, who had been routinely scanned for knee examination, participated in the study. The following pairs of sequences with and without BLADE were compared: (a) PD turbo spin echo (TSE) sagittal (SAG) fat saturation (FS) in 35 patients, (b) PD TSE coronal (CUR) FS in 19 patients, (c) T2 TSE axial in 13 patients and (d) PD TSE SAG in 13 patients. Both qualitative and quantitative analyses were performed based on the signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and relative contrast (ReCon) measures of normal anatomic structures. The qualitative analysis was performed by experienced radiologists. Also, the presence of image motion and pulsation artifacts was evaluated. Based on the results of the SNR, CRN and ReCon for the different sequences and anatomical structures, the BLADE sequences were significantly superior in 19 cases, whereas the corresponding conventional sequences were significantly superior in only 6 cases. BLADE sequences eliminated motion artifacts in all the cases. However, motion artifacts were shown in (a) six PD TSE SAG FS, (b) three PD TSE CUR FS, (c) three PD TSE SAG and (d) two T2 TSE axial conventional sequences. In our results, it was found that, in PD FS sequences (sagittal and coronal), the differences between the BLADE and conventional sequences regarding the elimination of motion and pulsatile flow artifacts were statistically significant. In all the comparisons, the PD FS BLADE sequences (coronal and sagittal) were significantly superior to the corresponding conventional sequences regarding the classification of their image quality. In conclusion, this technique appears to be capable to potentially eliminate motion and pulsatile flow artifacts in MR images.

  • 9. Lavdas, Eleftherios
    et al.
    Mavroidis, Panayiotis
    Stockholm University, Faculty of Science, Department of Physics. Karolinska Institutet.
    Kostopoulos, Spiros
    Glotsos, Dimitrios
    Roka, Violeta
    Koutsiaris, Aristotle G.
    Batsikas, Georgios
    Sakkas, Georgios K.
    Tsagkalis, Antonios
    Notaras, Ioannis
    Stathakis, Sotirios
    Papanikolaou, Nikos
    Vassiou, Katerina
    Elimination of motion, pulsatile flow and cross-talk artifacts using blade sequences in lumbar spine MR imaging2013In: Magnetic Resonance Imaging, ISSN 0730-725X, E-ISSN 1873-5894, Vol. 31, no 6, p. 882-890Article in journal (Refereed)
    Abstract [en]

    The purpose of this study is to evaluate the ability of T2 turbo spin echo (TSE) axial and sagittal BLADE sequences in reducing or even eliminating motion, pulsatile flow and cross-talk artifacts in lumbar spine MRI examinations. Forty four patients, who had routinely undergone a lumbar spine examination, participated in the study. The following pairs of sequences with and without BLADE were compared: a) 12 TSE Sagittal (SAG) in thirty two cases, and b) 12 TSE Axial (AX) also in thirty two cases. Both quantitative and qualitative analyses were performed based on measurements in different normal anatomical structures and examination of seven characteristics, respectively. The qualitative analysis was performed by experienced radiologists. Also, the presence of image motion, pulsatile flow and cross-talk artifacts was evaluated. Based on the results of the qualitative analysis for the different sequences and anatomical structures, the BLADE sequences were found to be significantly superior to the conventional ones in all the cases. The BLADE sequences eliminated the motion artifacts in all the cases. In our results, it was found that in the examined sequences (sagittal and axial) the differences between the BLADE and conventional sequences regarding the elimination of motion, pulsatile flow and cross-talk artifacts were statistically significant. In all the comparisons, the 12 TSE BLADE sequences were significantly superior to the corresponding conventional sequences regarding the classification of their image quality. In conclusion, this technique appears to be capable of potentially eliminating motion, pulsatile flow and cross-talk artifacts in lumbar spine MR images and producing high quality images in collaborative and non-collaborative patients.

  • 10. Lavdas, Eleftherios
    et al.
    Mavroidis, Panayiotis
    Stockholm University, Faculty of Science, Department of Physics.
    Kostopoulos, Spiros
    Glotsos, Dimitrios
    Roka, Violeta
    Topalzikis, Theofilos
    Bakas, Athanasios
    Oikonomou, Georgia
    Papanikolaou, Nikos
    Batsikas, Georgios
    Kaffes, Ioannis
    Kechagias, Dimitrios
    Improvement of image quality using BLADE sequences in brain MR imaging2013In: Magnetic Resonance Imaging, ISSN 0730-725X, E-ISSN 1873-5894, Vol. 31, no 2, p. 189-200Article in journal (Refereed)
    Abstract [en]

    The purpose of this study is to compare two types of sequences in brain magnetic resonance (MR) examinations of uncooperative and cooperative patients. For each group of patients, the pairs of sequences that were compared were two T2-weighted (T2-W) fluid attenuated inversion recovery sequences with different k-space trajectories (conventional Cartesian and BLADE) and two T2-TSE weighted with different k-space trajectories (conventional Cartesian and BLADE). Twenty-three consecutive uncooperative patients and 44 cooperative patients, who routinely underwent brain MR imaging examination, participated in the study. Both qualitative and quantitative analyses were performed based on the signal-to-noise ratio, contrast-to-noise ratio (CNR), and relative contrast (ReCon) measures of normal anatomic structures. The qualitative analysis was performed by experienced radiologists. Also, the presence of motion, other (e.g., Gibbs, susceptibility artifacts, phase encoding from vessels) artifacts and pulsatile flow artifacts was evaluated. In the uncooperative group of patients, BLADE sequences were superior to the corresponding conventional sequences in all the cases. Furthermore, the differences were found to be statistically significant in almost all the cases. In the cooperative group of patients, BLADE sequences were superior to the conventional sequences with the differences of the CNR and ReCon values in nine cases being statistically significant. Furthermore, BLADE sequences eliminated motion and other artifacts and T2 FLAIR BLADE sequences eliminated pulsatile flow artifacts. BLADE sequences (T2-TSE and T2 FLAIR) should be used in brain MR examinations of uncooperative patients. In cooperative patients, T2-TSE BLADE sequences may be used as part of the routine protocol and orbital examinations. T2 FLAIR BLADE sequences may be used optionally in examinations of AVM, orbits, haemorrhages, ventricular lesions, lesions in the frontal lobe, periventricular lesions, lesions in regions close to artifacts and lesions in posterior fossa.

  • 11. Lavdas, Eleftherios
    et al.
    Mavroidis, Panayiotis
    Stockholm University, Faculty of Science, Department of Physics.
    Roka, Violeta
    Arikidis, Nikolaos
    Arvanitis, Dimitrios L.
    Fezoulidis, Ioannis V.
    Vassiou, Katerina
    A method for limiting pitfalls in the production of enhancement kinetic curves in 3T dynamic magnetic resonance mammography2012In: Journal of Thoracic Disease, ISSN 2072-1439, Vol. 4, no 4, p. 358-367Article in journal (Refereed)
    Abstract [en]

    Purpose: The aim of the present study is to investigate means for the reduction or even elimination of enhancement kinetic curve errors due to breast motion in order to avoid pitfalls and to increase the sensitivity and specificity of the method. Methods: 115 women underwent breast Magnetic Resonance Imaging (MRI). All patients were properly immobilized in a dedicated bilateral phased array coil. A magnetic resonance unit 3-Tesla (Signa, GE Healthcare) was used. The following sequences were applied: (I) axial T2-TSE, (II) axial STIR and (III) Vibrant axial T1-weighted fat saturation (six phases). Kinetic curves were derived semi-automatically using the software of the system and manually by positioning the regions of interest (ROI) from stable reference points in all the phases. Results: 376 abnormalities in 115 patients were investigated. In 81 (21.5%) cases, a change of the enhancement kinetic curve type was found when the two different methods were used. In cases of large fatty breasts, a change of the enhancement kinetic curve type in 13 lesions was found. In cases of small and dense breasts, only in 4 lesions the kinetic curve type changed, whereas in cases of small and fatty breasts, the kinetic curve type changed in 64 lesions (50 were observed in left breasts and 14 in right breasts). Conclusions: The derivation of enhancement kinetic curves should be performed by controlling and verifying that the ROIs lay at the same location of the lesion in all the phases of the dynamic study.

  • 12. Lavdas, Eleftherios
    et al.
    Mavroidis, Panayiotis
    Stockholm University, Faculty of Science, Department of Physics.
    Topaltzikis, Theofilos
    Slatinopoulos, Vasileios
    Roka, Violeta
    Vlachopoulou, Anna
    Papanikolaou, Nikos
    Stathakis, Sotirios
    Kapsalaki, Eftichia
    Batsikas, Georgios
    Comparison of BLADE and conventional T2-TSE sequences for the sagittal visualization of the cervical spinal cord in multiple sclerosis patients - A case report2013In: Magnetic Resonance Imaging, ISSN 0730-725X, E-ISSN 1873-5894, Vol. 31, no 10, p. 1766-1770Article in journal (Refereed)
    Abstract [en]

    The purpose of this study is to report the significant differences found in the identification of lesions in cervical spinal cord of two patients with multiple sclerosis when using the BLADE T2-TSE and BLADE T2-TIRM sequences as opposed to the conventional T2-TSE and T2-TIRM sequences for sagittal acquisition at 1.5 T. In both patients, one more lesion was identified with the BLADE sequences than with the conventional ones. Consequently, we suggest the use of BLADE T2-TSE and BLADE T2-TIRM sequences in place of conventional ones for sagittal examination of the cervical spinal cord of multiple sclerosis patients. The advantages of TIRM to reveal the pathology of the cervical spinal cord and the advantage of BLADE sequences to improve image quality should be combined in a sequence that could be ideal for cervical spinal cord examinations.

  • 13.
    Mavroidis, Panayiotis
    et al.
    Stockholm University, Faculty of Science, Department of Physics.
    Ferreira, Brigida Costa
    Lopes, Maria do Carmo
    Response-probability volume histograms and iso-probability of response charts in treatment plan evaluation2011In: Medical physics (Lancaster), ISSN 0094-2405, Vol. 38, no 5, p. 2382-2397Article in journal (Refereed)
    Abstract [en]

    Purpose: This study aims at demonstrating a new method for treatment plan evaluation and comparison based on the radiobiological response of individual voxels. This is performed by applying them on three different cancer types and treatment plans of different conformalities. Furthermore, their usefulness is examined in conjunction with traditionally applied radiobiological and dosimetric treatment plan evaluation criteria. Methods: Three different cancer types (head and neck, breast and prostate) were selected to quantify the benefits of the proposed treatment plan evaluation method. In each case, conventional conformal radiotherapy (CRT) and intensity modulated radiotherapy (IMRT) treatment configurations were planned. Iso-probability of response charts was produced by calculating the response probability in every voxel using the linear-quadratic-Poisson model and the dose-response parameters of the corresponding structure to which this voxel belongs. The overall probabilities of target and normal tissue responses were calculated using the Poisson and the relative seriality models, respectively. The 3D dose distribution converted to a 2 Gy fractionation, D(2GY) and iso-BED distributions are also shown and compared with the proposed methodology. Response-probability volume histograms (RVH) were derived and compared with common dose volume histograms (DVH). The different dose distributions were also compared using the complication-free tumor control probability, P(+), the biologically effective uniform dose, (sic), and common dosimetric criteria. Results: 3D Iso-probability of response distributions is very useful for plan evaluation since their visual information focuses on the doses that are likely to have a larger clinical effect in that particular organ. The graphical display becomes independent of the prescription dose highlighting the local radiation therapy effect in each voxel without the loss of important spatial information. For example, due to the exponential nature of the Poisson distribution, cold spots in the target volumes or hot spots in the normal tissues are much easier to be identified. Response-volume histograms, as DVH, can also be derived and used for plan comparison. RVH are advantageous since by incorporating the radiobiological properties of each voxel they summarize the 3D distribution into 2D without the loss of relevant information. Thus, more clinically relevant radiobiological objectives and constraints could be defined and used in treatment planning optimization. These measures become increasingly important when dose distributions need to be designed according to the microscopic biological properties of tumor and normal tissues. Conclusions: The proposed methods do not aim to replace quantifiers like the probabilities of total tissue response, which ultimately are the quantities of interest to evaluate treatment success. However, iso-probability of response charts and response-probability volume histograms illustrates more clearly the difference in effectiveness between different treatment plans than the information provided by alternative dosimetric data. The use of 3D iso-probability of response distributions could serve as a good descriptor of the effectiveness of a dose distribution indicating primarily the regions in a tissue that dominate its response.

  • 14.
    Mavroidis, Panayiotis
    et al.
    Stockholm University, Faculty of Science, Department of Physics. Department of Radiation Oncology, University of Texas Health Sciences Center at San Antonio, Texas.
    Ferreira, Brigida Costa
    Papanikolaou, Nikos
    Lopes, Maria do Carmo
    Analysis of fractionation correction methodologies for multiple phase treatment plans in radiation therapy2013In: Medical physics (Lancaster), ISSN 0094-2405, Vol. 40, no 3, p. 031715-Article in journal (Refereed)
    Abstract [en]

    Purpose: Radiation therapy is often delivered by multiple sequential treatment plans. For an accurate radiobiological evaluation of the overall treatment, fractionation corrections to each dose distribution must be applied before summing the three-dimensional dose matrix of each plan since the simpler approach of performing the fractionation correction to the total dose-volume histograms, obtained by the arithmetical sum of the different plans, becomes inaccurate for more heterogeneous dose patterns. In this study, the differences between these two fractionation correction methods, named here as exact (corrected before) and approximate (after summation), respectively, are assessed for different cancer types. Methods: Prostate, breast, and head and neck (HN) tumor patients were selected to quantify the differences between two fractionation correction methods (the exact vs the approximate). For each cancer type, two different treatment plans were developed using uniform (CRT) and intensity modulated beams (IMRT), respectively. The responses of the target and normal tissue were calculated using the Poisson linear-quadratic-time model and the relative seriality model, respectively. All treatments were radiobiologically evaluated and compared using the complication-free tumor control probability (P+), the biologically effective uniform dose ((D) double under bar) together with common dosimetric criteria. Results: For the prostate cancer patient, an underestimation of around 14%-15% in P+ was obtained when the fractionation correction was applied after summation compared to the exact approach due to significant biological and dosimetric variations obtained between the two fractionation correction methods in the involved lymph nodes. For the breast cancer patient, an underestimation of around 3%-4% in the maximum dose in the heart was obtained. Despite the dosimetric differences in this organ, no significant variations were obtained in treatment outcome. For the HN tumor patient, an underestimation of about 5% in treatment outcome was obtained for the CRT plan as a result of an underestimation of the planning target volume control probability by about 10%. An underestimation of about 6% in the complication probability of the right parotid was also obtained. For all the other organs at risk, dosimetric differences of up to 4% were obtained but with no significant impact in the expected clinical outcome. However, for the IMRT plan, an overestimation in P+ of 4.3% was obtained mainly due to an underestimation of the complication probability of the left and right parotids (2.9% and 5.8%, respectively). Conclusions: The use of the exact fractionation correction method, which is applying fractionation correction on the separate dose distributions of a multiple phase treatment before their summation was found to have a significant expected clinical impact. For regions of interest that are irradiated with very heterogeneous dose distributions and significantly different doses per fraction in the different treatment phases, the exact fractionation correction method needs to be applied since a significant underestimation of the true patient outcome can be introduced otherwise.

  • 15.
    Mavroidis, Panayiotis
    et al.
    Stockholm University, Faculty of Science, Department of Physics. Karolinska Institute, Sweden.
    Milickovic, Natasa
    Cruz, Wilbert F.
    Tselis, Nikolaos
    Karabis, Andreas
    Stathakis, Sotirios
    Papanikolaou, Nikos
    Zamboglou, Nikolaos
    Baltas, Dimos
    Comparison of Different Fractionation Schedules Toward a Single Fraction in High-Dose-Rate Brachytherapy as Monotherapy for Low-Risk Prostate Cancer Using 3-Dimensional Radiobiological Models2014In: International Journal of Radiation Oncology, Biology, Physics, ISSN 0360-3016, E-ISSN 1879-355X, Vol. 88, no 1, p. 216-223Article in journal (Refereed)
    Abstract [en]

    Purpose: The aim of the present study was the investigation of different fractionation schemes to estimate their clinical impact. For this purpose, widely applied radiobiological models and dosimetric measures were used to associate their results with clinical findings. Methods and Materials: The dose distributions of 12 clinical high-dose-rate brachytherapy implants for prostate were evaluated in relation to different fractionation schemes. The fractionation schemes compared were: (1) 1 fraction of 20 Gy; (2) 2 fractions of 14 Gy; (3) 3 fractions of 11 Gy; and (4) 4 fractions of 9.5 Gy. The clinical effectiveness of the different fractionation schemes was estimated through the complication-free tumor control probability (P (+)), the biologically effective uniform dose, and the generalized equivalent uniform dose index. Results: For the different fractionation schemes, the tumor control probabilities were 98.5% in 1 x 20 Gy, 98.6% in 2 x 14 Gy, 97.5% in 3 x 11 Gy, and 97.8% in 4 x 9.5 Gy. The corresponding P+ values were 88.8% in 1 x 20 Gy, 83.9% in 2 x 14 Gy, 86.0% in 3 x 11 Gy, and 82.3% in 4 x 9.5 Gy. With use of the fractionation scheme 4 x 9.5 Gy as reference, the isoeffective schemes regarding tumor control for 1, 2, and 3 fractions were 1 x 19.68 Gy, 2 x 13.75 Gy, and 3 x 11.05 Gy. The optimum fractionation schemes for 1, 2, 3, and 4 fractions were 1 x 19.16 Gy with a P+ of 91.8%, 2 x 13.2 Gy with a P+ of 89.6%, 3 x 10.6 Gy with a P+ of 88.4%, and 4 x 9.02 Gy with a P+ of 86.9%. Conclusions: Among the fractionation schemes 1 (+) 20 Gy, 2 (+) 14 Gy, 3 x 11 Gy, and 4 x 9.5 Gy, the first scheme was more effective in terms of P+. After performance of a radiobiological optimization, it was shown that a single fraction of 19.2 to 19.7 Gy (average 19.5 Gy) should produce at least the same benefit as that given by the 4 x 9.5 Gy scheme, and it should reduce the expected total complication probability by approximately 40% to 55%.

  • 16.
    Mavroidis, Panayiotis
    et al.
    Stockholm University, Faculty of Science, Department of Physics.
    Shi, C.
    Plataniotis, G. A.
    Delichas, M. G.
    Costa Ferreira, B.
    Rodriguez, S.
    Lind, B. K.
    Stockholm University, Faculty of Science, Department of Physics.
    Papanikolaou, N.
    Comparison of the helical tomotherapy against the multileaf collimator-based intensity-modulated radiotherapy and 3D conformal radiation modalities in lung cancer radiotherapy2011In: British Journal of Radiology, ISSN 0007-1285, E-ISSN 1748-880X, Vol. 84, no 998, p. 161-172Article in journal (Refereed)
    Abstract [en]

    Objectives: The aim of this study was to compare three-dimensional (3D) conformal radiotherapy and the two different forms of IMRT in lung cancer radiotherapy. Methods: Cases of four lung cancer patients were investigated by developing a 3D conformal treatment plan, a linac MLC-based step-and-shoot IMRT plan and an HT plan for each case. With the use of the complication-free tumour control probability (P(+)) index and the uniform dose concept as the common prescription point of the plans, the different treatment plans were compared based on radiobiological measures. Results: The applied plan evaluation method shows the MLC-based IMRT and the HT treatment plans are almost equivalent over the clinically useful dose prescription range; however, the 3D conformal plan inferior. At the optimal dose levels, the 3D conformal treatment plans give an average P(+) of 48.1% for a effective uniform dose to the internal target volume (ITV) of 62.4 Gy, whereas the corresponding MLC-based IMRT treatment plans are more effective by an average Delta P(+) of 27.0% for a D effective uniform dose of 16.3 Gy. Similarly, the HT treatment plans are more effective than the 3D-conformal plans by an average Delta P(+) of 23.8% for a Delta effective uniform dose of 11.6 Gy. Conclusion: A radiobiological treatment plan evaluation can provide a closer association of the delivered treatment with the clinical outcome by taking into account the dose-response relations of the irradiated tumours and normal tissues. The use of P - effective uniform dose diagrams can complement the traditional tools of evaluation to compare and effectively evaluate different treatment plans.

  • 17.
    Mavroidis, Panayiotis
    et al.
    Stockholm University, Faculty of Science, Department of Physics.
    Su, F-C
    Giantsoudi, D.
    Stathakis, S.
    Komisopoulos, G.
    Shi, C.
    Swanson, G.
    Papanikolaou, N.
    Radiobiological and Dosimetric Analysis of Daily Megavoltage CT Registration on Adaptive Radiotherapy with Helical Tomotherapy2011In: Technology in Cancer Research & Treatment (Trykt), ISSN 1533-0346, E-ISSN 1533-0338, Vol. 10, no 1, p. 1-13Article in journal (Refereed)
    Abstract [en]

    Pre-treatment patient repositioning in highly conformal image-guided radiation therapy modalities is a prerequisite for reducing setup uncertainties. In Helical Tomotherapy (HT) treatment, a megavoltage CT (MVCT) image is usually acquired to evaluate daily changes in the patient's internal anatomy and setup position. This MVCT image is subsequently compared to the kilovoltage CT (kVCT) study that was used for dosimetric planning, by applying a registration process. This study aims at investigating the expected effect of patient setup correction using the Hi-Art tomotherapy system by employing radiobiological measures such as the biologically effective uniform dose (<(D)double over bar>) and the complication-free tumor control probability (P.). A new module of the Tomotherapy software (Tomo Therapy, Inc, Madison, WI) called Planned Adaptive is employed in this study. In this process the delivered dose can be calculated by using the sinogram for each delivered fraction and the registered MVCT image set that corresponds to the patient's position and anatomical distribution for that fraction. In this study, patients treated for lung, pancreas and prostate carcinomas are evaluated by this method. For each cancer type, a Helical Tomotherapy plan was developed. In each cancer case, two dose distributions were calculated using the MVCT image sets before and after the patient setup correction. The fractional dose distributions were added and renormalized to the total number of fractions planned. The dosimetric and radiobiological differences of the dose distributions with and without patient setup correction were calculated. By using common statistical measures of the dose distributions and the P, and <(D)double over bar> concepts and plotting the tissue response probabilities vs. <(D)double over bar> a more comprehensive comparison was performed based on radiobiological measures. For the lung cancer case, at the clinically prescribed dose levels of the dose distributions, with and without patient setup correction, the complication-free tumor control probabilities, P. are 48.5% and 48.9% for a <(D)double over bar>(ITV) of 53.3 Gy. The respective total control probabilities, P(B) are 56.3% and 56.5%, whereas the corresponding total complication probabilities, P(I) are 7.9% and 7.5%. For the pancreas cancer case, at the prescribed dose levels of the two dose distributions, the P. values are 53.7% and 45.7% for a <(D)double over bar>(ITV) of 54.7 Gy and 53.8 Gy, respectively. The respective PB values are 53.7% and 45.8%, whereas the corresponding P, values are similar to 0.0% and 0.1%. For the prostate cancer case, at the prescribed dose levels of the two dose distributions, the P. values are 10.9% for a <(D)double over bar>(ITV) of 75.2 Gy and 11.9% for a D(ITV) of 75.4 Gy, respectively. The respective PB values are 14.5% and 15.3%, whereas the corresponding P, values are 3.6% and 3.4%. Our analysis showed that the very good daily patient setup and dose delivery were very close to the intended ones. With the exception of the pancreas cancer case, the deviations observed between the dose distributions with and without patient setup correction were within +/- 2% in terms of P(+). In the radiobiologically optimized dose distributions, the role of patient setup correction using MVCT images could appear to be more important than in the cases of dosimetrically optimized treatment plans were the individual tissue radiosensitivities are not precisely considered.

  • 18. Milickovic, Natasa
    et al.
    Mavroidis, Panayiotis
    Stockholm University, Faculty of Science, Department of Physics.
    Tselis, Nikolaos
    Nikolova, Iliyana
    Katsilieri, Zaira
    Kefala, Vasiliki
    Zamboglou, Nikolaos
    Baltas, Dimos
    4D analysis of influence of patient movement and anatomy alteration on the quality of 3D U/S-based prostate HDR brachytherapy treatment delivery2011In: Medical physics (Lancaster), ISSN 0094-2405, Vol. 38, no 9, p. 4982-4993Article in journal (Refereed)
    Abstract [en]

    Purpose: Modern HDR brachytherapy treatment for prostate cancer based on the 3D ultrasound (U/S) plays increasingly important role. The purpose of this study is to investigate possible patient movement and anatomy alteration between the clinical image set acquisition, made after the needle implantation, and the patient irradiation and their influence on the quality of treatment. Methods: The authors used 3D U/S image sets and the corresponding treatment plans based on a 4D-treatment planning procedure: plans of 25 patients are obtained right after the needle implantation (clinical plan is based on this 3D image set) and just before and after the treatment delivery. The authors notice the slight decrease of treatment quality with increase of time gap between the clinical image set acquisition and the patient irradiation. 4D analysis of dose-volume-histograms (DVHs) for prostate: CTV1 - PTV, and urethra, rectum, and bladder as organs at risk (OARs) and conformity index (COIN) is presented, demonstrating the effect of prostate, OARs, and needles displacement. Results: The authors show that in the case that the patient body movement/anatomy alteration takes place, this results in modification of DVHs and radiobiological parameters, hence the plan quality. The observed average displacement of needles (1 mm) and of prostate (0.57 mm) is quite small as compared with the average displacement noted in several other reports [A. A. Martinez et al., Int. J. Radiat. Oncol., Biol., Phys. 49(1), 61-69 (2001); S. J. Damore et al., Int. J. Radiat. Oncol., Biol., Phys. 46(5), 1205-1211 (2000); P. J. Hoskin et al., Radiotherm. Oncol. 68(3), 285-288 (2003); E. Mullokandov et al., Int. J. Radiat. Oncol., Biol., Phys. 58(4), 1063-1071 (2004)] in the literature. Conclusions: Although the decrease of quality of dosimetric and radiobiological parameters occurs, this does not cause clinically unacceptable changes to the 3D dose distribution, according to our clinical protocol. (C) 2011 American Association of Physicists in Medicine. [DOI: 10.1118/1.3618735]

  • 19. Roland, Teboh
    et al.
    Tryggestad, Erik
    Mavroidis, Panayiotis
    Stockholm University, Faculty of Science, Department of Physics.
    Hales, Russell
    Papanikolaou, Nikos
    The radiobiological P+ index for pretreatment plan assessment with emphasis on four-dimensional radiotherapy modalities2012In: Medical physics (Lancaster), ISSN 0094-2405, Vol. 39, no 10, p. 6420-6430Article in journal (Refereed)
    Abstract [en]

    Purpose: Radiation treatment modalities will continue to emerge that promise better clinical outcomes albeit technologically challenging to implement. An important question facing the radiotherapy community then is the need to justify the added technological effort for the clinical return. Mobile tumor radiotherapy is a typical example, where 4D tumor tracking radiotherapy (4DTRT) has been proposed over the simpler conventional modality for better results. The modality choice per patient can depend on a wide variety of factors. In this work, we studied the complication-free tumor control probability (P+) index, which combines the physical complexity of the treatment plan with the radiobiological characteristics of the clinical case at hand and therefore found to be useful in evaluating different treatment techniques and estimating the expected clinical effectiveness of different radiation modalities. Methods: 4DCT volumes of 18 previously treated lung cancer patients with tumor motion and size ranging from 2 mm to 15 mm and from 4 cc to 462 cc, respectively, were used. For each patient, 4D treatment plans were generated to extract the 4D dose distributions, which were subsequently used with clinically derived radiobiological parameters to compute the P+ index per modality. Results: The authors observed, on average, a statistically significant increase in P+ of 3.4% +/- 3.8% (p < 0.003) in favor of 4DTRT. There was high variability among the patients with a < 0.5% up to 13.4% improvement in P+. Conclusions: The observed variability in the improvement of the clinical effectiveness suggests that the relative benefit of tracking should be evaluated on a per patient basis. Most importantly, this variability could be effectively captured in the computed P+. The index can thus be useful to discriminate and hence point out the need for a complex modality like 4DTRT over another. Besides tumor mobility, a wide range of other factors, e.g., size, location, fractionation, etc., can affect the relative benefits. Application of the P+ objective is a simple and effective way to combine these factors in the evaluation of a treatment plan.

  • 20. Stathakis, Sotirios
    et al.
    Mavroidis, Panayiotis
    Stockholm University, Faculty of Science, Department of Physics. Karolinska Institute, Sweden.
    Shi, Chengyu
    Xu, Jun
    Kauweloa, Kevin I.
    Narayanasamy, Ganesh
    Papanikolaou, Niko
    gamma(+) index: A new evaluation parameter for quantitative quality assurance2014In: Computer Methods and Programs in Biomedicine, ISSN 0169-2607, E-ISSN 1872-7565, Vol. 114, no 1Article in journal (Refereed)
    Abstract [en]

    Purpose: The accuracy dose delivery and the evaluation of differences between calculated and delivered dose distributions, has been studied by several groups. The aim of this investigation is to extend the gamma index by including radiobiological information and to propose a new index that we will here forth refer to as the gamma plus (gamma(+)). Further more, to validate the robustness of this new index in performing a quality control analysis of an IMRT treatment plan using pure radiobiological measures such as the biologically effective uniform dose ((D) over bar) and complication-free tumor control probability (P+). Material and methods: A new quality assurance index, the (gamma(+)), is proposed based on the theoretical concept of gamma index presented by Low et al. (1998). In this study, the dose difference, including the radiobiological dose information (biological effective dose, BED) is used instead of just the physical dose difference when performing the gamma(+) calculation. An in-house software was developed to compare different dose distributions based on the gamma(+) concept. A test pattern for a two-dimensional dose comparison was built using the in-house software platform. The gamma(+) index was tested using planar dose distributions (exported from the treatment planning system) and delivered (film) dose distributions acquired in a solid water phantom using a test pattern and a theoretical clinical case. Furthermore, a lung cancer case for a patient treated with IMRT was also selected for the analysis. The respective planar dose distributions from the treatment plan and the film were compared based on the gamma(+) index and were evaluated using the radiobiological measures of P+ and (D) over bar. Results: The results for the test pattern analysis indicate that the gamma(+) index distributions differ from those of the gamma index since the former considers radiobiological parameters that may affect treatment outcome. For the theoretical clinical case, it is observed that the gamma(+) index varies for different treatment parameters (e.g. dose per fraction). The dose area histogram (DAH) from the plan and film dose distributions are associated with P+ values of 50.8% and 49.0%, for a (D) over bar to the target of 54.0 Gy and 53.3 Gy, respectively. Conclusion: The gamma(+) index shows advantageous properties in the quantitative evaluation of dose delivery and quality control of IMRT treatments because it includes information about the expected responses and radiobiological doses of the individual tissues.

  • 21.
    Tzikas, A.
    et al.
    Stockholm University, Faculty of Science, Department of Physics.
    Karaiskos, P.
    Papanikolaou, N.
    Sandilos, P.
    Koutsouveli, E.
    Lavdas, E.
    Scarleas, C.
    Dardoufas, K.
    Lind, B. K.
    Stockholm University, Faculty of Science, Department of Physics.
    Mavroidis, P.
    Stockholm University, Faculty of Science, Department of Physics.
    Investigating the Clinical Aspects of Using CT vs. CT-MRI Images During Organ Delineation and Treatment Planning in Prostate Cancer Radiotherapy2011In: Technology in Cancer Research & Treatment (Trykt), ISSN 1533-0346, E-ISSN 1533-0338, Vol. 10, no 3, p. 231-242Article in journal (Refereed)
    Abstract [en]

    In order to apply highly conformal dose distributions, which are characterized by steep dose fall-offs, it is necessary to know the exact target location and extension. This study aims at evaluating the impact of using combined CT-MRI images in organ delineation compared to using CT images alone, on the clinical results. For 10 prostate cancer patients, the respective CT and MRI images at treatment position were acquired. The CTV was delineated using the CT and MRI images, separately, whereas bladder and rectum were delineated using the CT images alone. Based on the CT and MRI images, two CTVs were produced for each patient. The mutual information algorithm was used in the fusion of the two image sets. In this way, the structures drawn on the MRI images were transferred to the CT images in order to produce the treatment plans. For each set of structures of each patient, IMRT and 3D-CRT treatment plans were produced. The individual treatment plans were compared using the biologically effective uniform dose (D) and the complication-free tumor control probability (R) concepts together with the DVHs of the targets and organs at risk and common dosimetric criteria. For the IMRT treatment, at the optimum dose level of the average CT and CT-MRI delineated CTV dose distributions, the P. values are 74.7% in both cases for a D(CTV) of 91.5 Gy and 92.1 Gy, respectively. The respective average total control probabilities, P(B) are 90.0% and 90.2%, whereas the corresponding average total complication probabilities, P, are 15.3% and 15.4%. Similarly, for the 3D-CRT treatment, the average P. values are 42.5% and 46.7%, respectively for a D(CTV) of 86.4 Gy and 86.7 Gy, respectively. The respective average PB values are 80.0% and 80.6%, whereas the corresponding average P values are 37.4% and 33.8%, respectively. For both radiation modalities, the improvement mainly stems from the better sparing of rectum. According to these results, the expected clinical effectiveness of IMRT can be increased by a maximum Delta P, of around 0.9%, whereas of 3D-CRT by about 4.2% when combined CT-MRI delineation is performed instead of using CT images alone. It is apparent that in both IMRT and 3D-CRT radiation modalities, the better knowledge of the CTV extension improved the produced dose distribution. It is shown that the CTV is irradiated more effectively, while the complication probabilities of bladder and rectum, which is the principal organs at risk, are lower in the CT-MRI based treatment plans.

  • 22.
    Tzikas, Athanasios
    et al.
    Stockholm University, Faculty of Science, Department of Physics.
    Komisopoulos, Georgios
    Ferreira, Brigida Costa
    Hyodynmaa, Simo
    Axelsson, Sofie
    Stockholm University, Faculty of Science, Department of Physics.
    Papanikolaou, Nikos
    Lavdas, Eleftherios
    Lind, Bengt K.
    Stockholm University, Faculty of Science, Department of Physics.
    Mavroidis, Panayiotis
    Stockholm University, Faculty of Science, Department of Physics.
    Radiobiological Evaluation of Breast Cancer Radiotherapy Accounting for the Effects of Patient Positioning and Breathing in Dose Delivery. A Meta Analysis2013In: Technology in Cancer Research & Treatment (Trykt), ISSN 1533-0346, E-ISSN 1533-0338, Vol. 12, no 1, p. 31-44Article in journal (Refereed)
    Abstract [en]

    In breast cancer radiotherapy, significant discrepancies in dose delivery can contribute to underdosage of the tumor or overdosage of normal tissue, which is potentially related to a reduction of local tumor control and an increase of side effects. To study the impact of these factors in breast cancer radiotherapy, a meta analysis of the clinical data reported by Mavroidis et al. (2002) in Acta Oncol (41:471-85), showing the patient setup and breathing uncertainties characterizing three different irradiation techniques, were employed. The uncertainties in dose delivery are simulated based on fifteen breast cancer patients (5 mastectomized, 5 resected with negative node involvement (R) and 5 resected with positive node involvement (R+)), who were treated by three different irradiation techniques, respectively. The positioning and breathing effects were taken into consideration in the determination of the real dose distributions delivered to the CTV and lung in each patient. The combined frequency distributions of the positioning and breathing distributions were obtained by convolution. For each patient the effectiveness of the dose distribution applied is calculated by the Poisson and relative seriality models and a set of parameters that describe the dose-response relations of the target and lung. The three representative radiation techniques are compared based on radiobiological measures by using the complication-free tumor control probability, P+ and the biologically effective uniform dose, E, concepts. For the Mastectomy case, the average P+ values of the planned and delivered dose distributions are 93.8% for a (sic)(CTV) of 51.8 Gy and 85.0% for a (sic)(CTV) of 50.3 Gy, respectively. The respective total control probabilities, P-B values are 94.8% and 92.5%, whereas the corresponding total complication probabilities, P-I values are 0.9% and 7.4%. For the R- case, the average P+ values are 89.4% for a (sic)(CTV) of 48.9 Gy and 88.6% for a (sic)(CTV) of 49.0 Gy, respectively. The respective PB values are 89.8% and 89.9%, whereas the corresponding PI values are 0.4% and 1.2%. For the R+ case, the average P+ values are 86.1% for a (sic)(CTV) of 49.2 Gy and 85.5% for a (sic)(CTV) of 49.1 Gy, respectively. The respective PB values are 90.2% and 90.1%, whereas the corresponding P-I values are 4.1% and 4.6%. The combined effects of positioning uncertainties and breathing can introduce a significant deviation between the planned and delivered dose distributions in lung in breast cancer radiotherapy. The positioning and breathing uncertainties do not affect much the dose distribution to the CTV. The simulated delivered dose distributions show larger lung complication probabilities than the treatment plans. This means that in clinical practice the true expected complications are underestimated. Radiation pneumonitis of Grade 1-2 is more frequent and any radiotherapy optimization should use this as a more clinically relevant endpoint.

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