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  • 1.
    Andreassen, Björn
    et al.
    Stockholm University, Faculty of Science, Department of Physics.
    Strååt, Sara Janek
    Stockholm University, Faculty of Science, Department of Physics.
    Holmberg, Rickard
    Stockholm University, Faculty of Science, Department of Physics.
    Näfstadius, Peder
    Brahme, Anders
    Stockholm University, Faculty of Science, Department of Physics.
    Fast IMRT with narrow high energy scanned photon beams2011In: Medical physics (Lancaster), ISSN 0094-2405, Vol. 38, no 8, p. 4774-4784Article in journal (Refereed)
    Abstract [en]

    Purpose: Since the first publications on intensity modulated radiation therapy (IMRT) in the early 1980s almost all efforts have been focused on fairly time consuming dynamic or segmental multileaf collimation. With narrow fast scanned photon beams, the flexibility and accuracy in beam shaping increases, not least in combination with fast penumbra trimming multileaf collimators. Previously, experiments have been performed with full range targets, generating a broad bremsstrahlung beam, in combination with multileaf collimators or material compensators. In the present publication, the first measurements with fast narrow high energy (50 MV) scanned photon beams are presented indicating an interesting performance increase even though some of the hardware used were suboptimal. Methods: Inverse therapy planning was used to calculate optimal scanning patterns to generate dose distributions with interesting properties for fast IMRT. To fully utilize the dose distributional advantages with scanned beams, it is necessary to use narrow high energy beams from a thin bremsstrahlung target and a powerful purging magnet capable of deflecting the transmitted electron beam away from the generated photons onto a dedicated electron collector. During the present measurements the scanning system, purging magnet, and electron collimator in the treatment head of the MM50 racetrack accelerator was used with 3-6 mm thick bremsstrahlung targets of beryllium. The dose distributions were measured with diodes in water and with EDR2 film in PMMA. Monte Carlo simulations with GEANT4 were used to study the influence of the electrons transmitted through the target on the photon pencil beam kernel. Results: The full width at half-maximum (FWHM) of the scanned photon beam was 34 mm measured at isocenter, below 9.5 cm of water, 1 m from the 3 mm Be bremsstrahlung target. To generate a homogeneous dose distribution in a 10 x 10 cm(2) field, the authors used a spot matrix of 100 equal intensity beam spots resulting in a uniformity of collimated 80%-20% penumbra of 9 mm at a primary electron energy of 50 MeV. For the more complex cardioid shaped dose distribution, they used 270 spots, which at a pulse repetition frequency of 200 Hz is completed every 1.36 s. Conclusions: The present measurements indicate that the use of narrow scanned photon beams is a flexible and fast method to deliver advanced intensity modulated beams. Fast scanned photon IMRT should, therefore, be a very interesting modality in the delivery of biologically optimized radiation therapy with the possibility for in vivo treatment verification with PET-CT imaging.

  • 2.
    Benmakhlouf, Hamza
    et al.
    Stockholm University, Faculty of Science, Department of Physics. Karolinska Institutet, Sweden.
    Sempau, Josep
    Andreo, Pedro
    Stockholm University, Faculty of Science, Department of Physics. Karolinska Institutet, Sweden.
    Output correction factors for nine small field detectors in 6 MV radiation therapy photon beams: A PENELOPE Monte Carlo study2014In: Medical physics (Lancaster), ISSN 0094-2405, Vol. 41, no 4, p. 041711-Article in journal (Refereed)
    Abstract [en]

    Purpose: To determine detector-specific output correction factors, k(Qclin,Qmsr)(fclin,fmsr) in 6 MV small photon beams for air and liquid ionization chambers, silicon diodes, and diamond detectors from two manufacturers. Methods: Field output factors, defined according to the international formalism published by Alfonso et al. [Med. Phys. 35, 5179-5186 (2008)], relate the dosimetry of small photon beams to that of the machine-specific reference field; they include a correction to measured ratios of detector readings, conventionally used as output factors in broad beams. Output correction factors were calculated with the PENELOPE Monte Carlo (MC) system with a statistical uncertainty (type-A) of 0.15% or lower. The geometries of the detectors were coded using blueprints provided by the manufacturers, and phase-space files for field sizes between 0.5 x 0.5 cm(2) and 10 x 10 cm(2) from a Varian Clinac iX 6 MV linac used as sources. The output correction factors were determined scoring the absorbed dose within a detector and to a small water volume in the absence of the detector, both at a depth of 10 cm, for each small field and for the reference beam of 10 x 10 cm(2). Results: The Monte Carlo calculated output correction factors for the liquid ionization chamber and the diamond detector were within about +/- 1% of unity even for the smallest field sizes. Corrections were found to be significant for small air ionization chambers due to their cavity dimensions, as expected. The correction factors for silicon diodes varied with the detector type (shielded or un-shielded), confirming the findings by other authors; different corrections for the detectors from the two manufacturers were obtained. The differences in the calculated factors for the various detectors were analyzed thoroughly and whenever possible the results were compared to published data, often calculated for different accelerators and using the EGSnrc MC system. The differences were used to estimate a type-B uncertainty for the correction factors. Together with the type-A uncertainty from the Monte Carlo calculations, an estimation of the combined standard uncertainty was made, assigned to the mean correction factors from various estimates. Conclusions: The present work provides a consistent and specific set of data for the output correction factors of a broad set of detectors in a Varian Clinac iX 6 MV accelerator and contributes to improving the understanding of the physics of small photon beams. The correction factors cannot in general be neglected for any detector and, as expected, their magnitude increases with decreasing field size. Due to the reduced number of clinical accelerator types currently available, it is suggested that detector output correction factors be given specifically for linac models and field sizes, rather than for a beam quality specifier that necessarily varies with the accelerator type and field size due to the different electron spot dimensions and photon collimation systems used by each accelerator model. (C) 2014 American Association of Physicists in Medicine.

  • 3.
    Dasu, Alexandru
    et al.
    Linköping University, Sweden.
    Toma-Dasu, Iuliana
    Stockholm University, Faculty of Science, Department of Physics. Karolinska Institutet, Sweden.
    Impact of variable RBE on proton fractionation2013In: Medical physics (Lancaster), ISSN 0094-2405, Vol. 40, no 1, article id 011705Article in journal (Refereed)
    Abstract [en]

    Purpose: To explore the impact of variable proton RBE on dose fractionation for clinically-relevant situations. A generic RBE=1.1 is generally used for isoeffect calculations, while experimental studies showed that proton RBE varies with tissue type, dose and LET.

    Material and methods: An analytical expression for the LET and α/β dependence of the LQ model has been used for proton simulations in parallel with the assumption of a generic RBE=1.1. Calculations have been performed for ranges of LET values and fractionation sensitivities to describe clinically-relevant cases, like the treatment of H&N and prostate tumors. Isoeffect calculations were compared with predictions from a generic RBE value and reported clinical results.

    Results: The generic RBE=1.1 appears to be a reasonable estimate for the proton RBE of rapidly growing tissues irradiated with low LET radiation. However, the use of a variable RBE predicts larger differences for tissues with low α/β (both tumor and normal) and at low doses per fraction. In some situations these differences may appear in contrast to the findings from photon studies highlighting the importance of accurate accounting for the radiobiological effectiveness of protons. Furthermore, the use of variable RBE leads to closer predictions to clinical results.

    Conclusions: The LET dependence of the RBE has a strong impact on the predicted effectiveness of fractionated proton radiotherapy. The magnitude of the effect is modulated by the fractionation sensitivity and the fractional dose indicating the need for accurate analyses both in the target and around it. Care should therefore be employed for changing clinical fractionation patterns or when analyzing results from clinical studies for this type of radiation.

  • 4.
    Dasu, Alexandru
    et al.
    Norrland University Hospital, Sweden.
    Toma-Dasu, Iuliana
    Stockholm University, Faculty of Science, Medical Radiation Physics (together with KI).
    Vascular oxygen content and the tissue oxygenation - A theoretical analysis2008In: Medical physics (Lancaster), ISSN 0094-2405, Vol. 35, no 2, p. 539-545Article in journal (Refereed)
    Abstract [en]

    Several methods exist for evaluating tumor oxygenation as hypoxia is an important prognostic factor for cancer patients. They use different measuring principles that highlight various aspects of oxygenation. The results could be empirically correlated, but it has been suspected that there could be discordances in some cases. This study describes an analysis of the relationship between vascular and tissue oxygenations. Theoretical simulation has been employed to characterize tissue oxygenations for a broad range of distributions of intervessel distances and vascular oxygenations. The results were evaluated with respect to the implications for practical measurements of tissue oxygenations. The findings showed that although the tissue oxygenation is deterministically related to vascular oxygenation, the relationship between them is not unequivocal. Variability also exists between the fractions of values below the sensitivity thresholds of various measurement methods which in turn could be reflected in the power of correlations between results from different methods or in the selection of patients for prognostic studies. The study has also identified potential difficulties that may be encountered at the quantitative evaluation of the results from oxygenation measurements. These could improve the understanding of oxygenation measurements and the interpretation of comparisons between results from various measurement methods.

  • 5. Giantsoudi, D.
    et al.
    Baltas, D.
    Karabis, A.
    Mavroidis, Panayiotis
    Stockholm University, Faculty of Science, Department of Physics. University of Texas Health Sciences Center, United States; Karolinska Institutet, Sweden.
    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.

  • 6.
    Kempe, Johanna
    et al.
    Stockholm University, Faculty of Science, Medical Radiation Physics (together with KI).
    Brahme, Anders
    Stockholm University, Faculty of Science, Medical Radiation Physics (together with KI).
    Energy-range relation and mean energy variation in therapeutic particle beams2008In: Medical physics (Lancaster), ISSN 0094-2405, Vol. 35, no 1, p. 159-170Article in journal (Refereed)
    Abstract [en]

    Analytical expressions for the mean energy and range of therapeutic light ion beams and low- and high-energy electrons have been derived, based on the energy dependence of their respective stopping powers. The new mean energy and range relations are power-law expressions relevant for light ion radiation therapy, and are based on measured practical ranges or known tabulated stopping powers and ranges for the relevant incident particle energies. A practical extrapolated range, Rp, for light ions was defined, similar to that of electrons, which is very closely related to the extrapolated range of the primary ions. A universal energy-range relation for light ions and electrons that is valid for all material mixtures and compounds has been developed. The new relation can be expressed in terms of the range for protons and alpha particles, and is found to agree closely with experimental data in low atomic number media and when the difference in the mean ionization energy is low. The variation of the mean energy with depth and the new energy-range relation are useful for accurate stopping power and mass scattering power calculations, as well as for general particle transport and dosimetry applications.

  • 7.
    Kjellsson Lindblom, Emely
    et al.
    Stockholm University, Faculty of Science, Department of Physics.
    Ureba, Ana
    Stockholm University, Faculty of Science, Department of Physics.
    Dasu, Alexandru
    Wersäll, Peter
    Even, Aniek J. G.
    van Elmpt, Wouter
    Lambin, Philippe
    Toma-Dasu, Iuliana
    Stockholm University, Faculty of Science, Department of Physics. Karolinska Institutet, Sweden.
    Impact of SBRT fractionation in hypoxia dose painting - accounting for heterogeneous and dynamic tumour oxygenation2019In: Medical physics (Lancaster), ISSN 0094-2405, Vol. 46, no 5, p. 2512-2521Article in journal (Refereed)
    Abstract [en]

    Purpose

    Tumor hypoxia, often found in nonsmall cell lung cancer (NSCLC), implies an increased resistance to radiotherapy. Pretreatment assessment of tumor oxygenation is, therefore, warranted in these patients, as functional imaging of hypoxia could be used as a basis for dose painting. This study aimed at investigating the feasibility of using a method for calculating the dose required in hypoxic subvolumes segmented on 18F‐HX4 positron emission tomography (PET) imaging of NSCLC.

    Methods

    Positron emission tomography imaging data based on the hypoxia tracer 18F‐HX4 of 19 NSCLC patients were included in the study. Normalized tracer uptake was converted to oxygen partial pressure (pO2) and hypoxic target volumes (HTVs) were segmented using a threshold of 10 mmHg. Uniform doses required to overcome the hypoxic resistance in the target volumes were calculated based on a previously proposed method taking into account the effect of interfraction reoxygenation, for fractionation schedules ranging from extremely hypofractionated stereotactic body radiotherapy (SBRT) to conventionally fractionated radiotherapy.

    Results

    Gross target volumes ranged between 6.2 and 859.6 cm3, and the hypoxic fraction < 10 mmHg between 1.2% and 72.4%. The calculated doses for overcoming the resistance of cells in the HTVs were comparable to those currently prescribed in clinical practice as well as those previously tested in feasibility studies on dose escalation in NSCLC. Depending on the size of the HTV and the distribution of pO2, HTV doses were calculated as 43.6–48.4 Gy for a three‐fraction schedule, 51.7–57.6 Gy for five fractions, and 59.5–66.4 Gy for eight fractions. For patients in whom the HTV pO2 distribution was more favorable, a lower dose was required despite a bigger volume. Tumor control probability was lower for single‐fraction schedules, while higher levels of tumor control probability were found for schedules employing several fractions.

    Conclusions

    The method to account for heterogeneous and dynamic hypoxia in target volume segmentation and dose prescription based on 18F‐HX4‐PET imaging appears feasible in NSCLC patients. The distribution of oxygen partial pressure within HTV could impact the required prescribed dose more than the size of the volume.

  • 8. 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.

  • 9. Liamsuwan, Thiansin
    et al.
    Hultqvist, Martha
    Stockholm University, Faculty of Science, Department of Physics.
    Lindborg, Lennart
    Uehara, Shuzo
    Nikjoo, Hooshang
    Microdosimetry of proton and carbon ions2014In: Medical physics (Lancaster), ISSN 0094-2405, Vol. 41, no 8, p. 239-250Article in journal (Refereed)
    Abstract [en]

    Purpose: To investigate microdosimetry properties of 160 MeV/u protons and 290 MeV/u C-12 ion beams in small volumes of diameters 10-100 nm. Methods: Energy distributions of primary particles and nuclear fragments in the beams were calculated from simulations with the general purpose code SHIELD-HIT, while energy depositions by monoenergetic ions in nanometer volumes were obtained from the event-by-event Monte Carlo track structure ion code PITS99 coupled with the electron track structure code KURBUC. Results: The results are presented for frequencies of energy depositions in cylindrical targets of diameters 10-100 nm, dose distributions (y) over bar (D) in lineal energy y, and dose-mean lineal energies YD For monoenergetic ions, the hp was found to increase with an increasing target size for high-linear energy transfer (LET) ions, but decrease with an increasing target size for low-LET ions. Compared to the depth dose profile of the ion beams, the maximum of the hp depth profile for the 160 MeV proton beam was located at similar to 0.5 cm behind the Bragg peak maximum, while the PD peak of the 290 MeV/u C-12 beam coincided well with the peak of the absorbed dose profile. Differences between the (y) over bar (D) and dose-averaged linear energy transfer (LETD) were large in the proton beam for both target volumes studied, and in the C-12 beam for the 10 nm diameter cylindrical volumes. The (y) over bar (D) determined for 100 run diameter cylindrical volumes in the C-12 beam was approximately equal to the LETD. The contributions from secondary particles to the (y) over bar (D) of the beams are presented, including the contributions from secondary protons in the proton beam and from fragments with atomic number Z = 1-6 in the C-12 beam. Conclusions: The present investigation provides an insight into differences in energy depositions in subcellular-size volumes when irradiated by proton and carbon ion beams. The results are useful for characterizing ion beams of practical importance for biophysical modeling of radiation-induced DNA damage response and repair in the depth profiles of protons and carbon ions used in radiotherapy.

  • 10.
    Mavroidis, Panayiotis
    et al.
    Stockholm University, Faculty of Science, Department of Physics. Karolinska Institutet, Sweden.
    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.

  • 11.
    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.

  • 12.
    Mavroidis, Panayiotis
    et al.
    Stockholm University, Faculty of Science, Medical Radiation Physics (together with KI).
    Komisopoulos, Georgios
    Lind, Bengt K
    Papanikolaou, Nikos
    Interpretation of the dosimetric results of three uniformity regularization methods in terms of expected treatment outcome.2008In: Medical physics (Lancaster), ISSN 0094-2405, Vol. 35, no 11, p. 5009-18Article in journal (Refereed)
    Abstract [en]

    In IMRT treatment plan optimization there are various methods that try to regularize the variation of dose nonuniformity using purely dosimetric measures. However, although these methods can help in finding a good dose distribution, they do not provide any information regarding the expected treatment outcome. When a treatment plan optimization is performed using biological measures, the final goal should be some indication about the expected tumor control or normal tissue complications, which is the primary goal of treatment planning (the association of treatment configurations and dose prescription with the treatment outcome). In this study, this issue is analyzed distinguishing the dose-oriented treatment plan optimization from the response-oriented optimization. Three different dose distributions were obtained by using a dose-based optimization technique, an EUD-based optimization without applying any technique for regularizing the nonuniformity of the dose distribution, and an EUD-based optimization using a variational regularization technique, which controls dose nonuniformity. The clinical effectiveness of the three dose distributions was investigated by calculating the response probabilities of the tumors and organs-at-risk (OARs) involved in two head and neck and prostate cancer cases. The radiobiological models used are the linear-quadratic-Poisson and the Relative Seriality models. Furthermore, the complication-free tumor control probability and the biologically effective uniform dose (D) were used for treatment plan evaluation and comparison. The radiobiological comparison shows that the EUD-based optimization using L-curve regularization gives better results than the EUD-based optimization without regularization and dose-based optimization in both clinical cases. Concluding, it appears that the applied dose nonuniformity regularization technique is expected to improve the effectiveness of the optimized IMRT dose distributions. However, more patient cases are needed to validate the statistical significance of the results and conclusions presented in this paper.

  • 13. 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]

  • 14. 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.

  • 15. Tsubouchi, Toshiro
    et al.
    Henry, Thomas
    Stockholm University, Faculty of Science, Department of Physics.
    Ureba, Ana
    Stockholm University, Faculty of Science, Department of Physics.
    Valdman, Alexander
    Bassler, Niels
    Stockholm University, Faculty of Science, Department of Physics.
    Siegbahn, Albert
    Stockholm University, Faculty of Science, Department of Physics.
    Quantitative evaluation of potential irradiation geometries for carbon-ion beam grid therapy2018In: Medical physics (Lancaster), ISSN 0094-2405, Vol. 45, no 3, p. 1210-1221Article in journal (Refereed)
    Abstract [en]

    Purpose: Radiotherapy using grids containing cm-wide beam elements has been carried out sporadically for more than a century. During the past two decades, preclinical research on radiotherapy with grids containing small beam elements, 25 m-0.7 mm wide, has been performed. Grid therapy with larger beam elements is technically easier to implement, but the normal tissue tolerance to the treatment is decreasing. In this work, a new approach in grid therapy, based on irradiations with grids containing narrow carbon-ion beam elements was evaluated dosimetrically. The aim formulated for the suggested treatment was to obtain a uniform target dose combined with well-defined grids in the irradiated normal tissue. The gain, obtained by crossfiring the carbon-ion beam grids over a simulated target volume, was quantitatively evaluated.

    Methods: The dose distributions produced by narrow rectangular carbon-ion beams in a water phantom were simulated with the PHITS Monte Carlo code. The beam-element height was set to 2.0 cm in the simulations, while the widths varied from 0.5 to 10.0 mm. A spread-out Bragg peak (SOBP) was then created for each beam element in the grid, to cover the target volume with dose in the depth direction. The dose distributions produced by the beam-grid irradiations were thereafter constructed by adding the dose profiles simulated for single beam elements. The variation of the valley-to-peak dose ratio (VPDR) with depth in water was thereafter evaluated. The separation of the beam elements inside the grids were determined for different irradiation geometries with a selection criterion.

    Results: The simulated carbon-ion beams remained narrow down to the depths of the Bragg peaks. With the formulated selection criterion, a beam-element separation which was close to the beam-element width was found optimal for grids containing 3.0-mm-wide beam elements, while a separation which was considerably larger than the beam-element width was found advantageous for grids containing 0.5-mm-wide beam elements. With the single-grid irradiation setup, the VPDRs were close to 1.0 already at a distance of several cm from the target. The valley doses given to the normal tissue at 0.5 cm distance from the target volume could be limited to less than 10% of the mean target dose if a crossfiring setup with four interlaced grids was used.

    Conclusions: The dose distributions produced by grids containing 0.5- and 3.0-mm wide beam elements had characteristics which could be useful for grid therapy. Grids containing mm-wide carbon-ion beam elements could be advantageous due to the technical ease with which these beams can be produced and delivered, despite the reduced threshold doses observed for early and late responding normal tissue for beams of millimeter width, compared to submillimetric beams. The treatment simulations showed that nearly homogeneous dose distributions could be created inside the target volumes, combined with low valley doses in the normal tissue located close to the target volume, if the carbon-ion beam grids were crossfired in an interlaced manner with optimally selected beam-element separations. The formulated selection criterion was found useful for the quantitative evaluation of the dose distributions produced by the different irradiation setups.

  • 16. Wedenberg, Minna
    et al.
    Toma-Dasu, Iuliana
    Stockholm University, Faculty of Science, Department of Physics. Karolinska Institutet, Sweden .
    Disregarding RBE variation in treatment plan comparison may lead to bias in favor of proton plans2014In: Medical physics (Lancaster), ISSN 0094-2405, Vol. 41, no 9, p. 091706-Article in journal (Refereed)
    Abstract [en]

    Purpose: Currently in proton radiation therapy, a constant relative biological effectiveness (RBE) equal to 1.1 is assumed. The purpose of this study is to evaluate the impact of disregarding variations in RBE on the comparison of proton and photon treatment plans.

    Methods: Intensity modulated treatment plans using photons and protons were created for three brain tumor cases with the target situated close to organs at risk. The proton plans were optimized assuming a standard RBE equal to 1.1, and the resulting linear energy transfer (LET) distribution for the plans was calculated. In the plan evaluation, the effect of a variable RBE was studied. The RBE model used considers the RBE variation with dose, LET, and the tissue specific parameter α/β of photons. The plan comparison was based on dose distributions, DVHs and normal tissue complication probabilities (NTCPs).

    Results: Under the assumption of RBE = 1.1, higher doses to the tumor and lower doses to the normal tissues were obtained for the proton plans compared to the photon plans. In contrast, when accounting for RBE variations, the comparison showed lower doses to the tumor and hot spots in organs at risk in the proton plans. These hot spots resulted in higher estimated NTCPs in the proton plans compared to the photon plans.

    Conclusions: Disregarding RBE variations might lead to suboptimal proton plans giving lower effect in the tumor and higher effect in normal tissues than expected. For cases where the target is situated close to structures sensitive to hot spot doses, this trend may lead to bias in favor of proton plans in treatment plan comparisons.

  • 17.
    Ödén, Jakob
    et al.
    Stockholm University, Faculty of Science, Department of Physics. RaySearch Laboratories, Sweden.
    Eriksson, Kjell
    RaySearch Laboratories, Sweden.
    Toma-Dasu, Iuliana
    Stockholm University, Faculty of Science, Department of Physics. Karolinska Institutet, Sweden.
    Inclusion of a variable RBE into proton and photon plan comparison for various fractionation schedules in prostate radiation therapy2017In: Medical physics (Lancaster), ISSN 0094-2405, Vol. 44, no 3, p. 810-822Article in journal (Refereed)
    Abstract [en]

    Purpose: A constant relative biological effectiveness (RBE) of 1.1 is currently used in proton radiation therapy to account for the increased biological effectiveness compared to photon therapy. However, there is increasing evidence that proton RBE vary with the linear energy transfer (LET), the dose per fraction and the type of the tissue. Therefore, this study aims to evaluate the impact of disregarding variations in RBE when comparing proton and photon dose plans for prostate treatments for various fractionation schedules using published RBE models and several α/β assumptions.

    Methods: Photon and proton dose plans were created for three generic prostate cancer cases. Three BED3Gy equivalent schedules were studied, 78, 57.2 and 42.8 Gy in 39, 15 and 7 fractions, respectively. The proton plans were optimized assuming a constant RBE of 1.1. By using the Monte Carlo calculated dose-averaged LET (LETd) distribution and assuming α/β values on voxel level, three variable RBE models were applied to the proton dose plans. The impact of the variable RBE was studied in the plan comparison, which was based on the dose distribution, DVHs and normal tissue complication probabilities (NTCP) for the rectum. Subsequently, the physical proton dose was re-optimized for each proton plan based on the LETd distribution, to achieve a homogeneous RBE weighted target dose when applying a specific RBE model and still fulfil the clinical goals for the rectum and bladder.

    Results: All the photon and proton plans assuming RBE=1.1 met the clinical goals with similar target coverage. The proton plans fulfilled the robustness criteria in terms of range and setup uncertainty. Applying the variable RBE models generally resulted in higher target doses and rectum NTCP compared to the photon plans. The increase was most pronounced for the fractionation dose of 2 Gy(RBE) whereas it was of less magnitude and more dependent on model and α/β assumption for the hypofractionated schedules. The re-optimized proton plans proved to be robust and showed similar target coverage and doses to the organs at risk as the proton plans optimized with a constant RBE.

    Conclusions: Model predicted RBE values may differ substantially from 1.1. This is most pronounced for fractionation doses of around 2 Gy(RBE) with higher doses to the target and the OARs, whereas the effect seems to be of less importance for the hypofractionated schedules. This could result in misleading conclusions when comparing proton plans to photon plans. By accounting for a variable RBE in the optimization process, robust and clinically acceptable dose plans, with the potential of lowering rectal NTCP, may be generated by re-optimizing the physical dose. However, the direction and magnitude of the changes in the physical proton dose to the prostate are dependent on RBE model and α/β assumptions and should therefore be used conservatively.

  • 18.
    Ödén, Jakob
    et al.
    Stockholm University, Faculty of Science, Department of Physics. RaySearch Laboratories AB, Sweden.
    Toma-Dasu, Iuliana
    Stockholm University, Faculty of Science, Department of Physics. Karolinska Institutet, Sweden.
    Witt Nyström, Petra
    The Skandion Clinic, Sweden.
    Traneus, Erik
    RaySearch Laboratories AB, Sweden.
    Dasu, Alexandru
    The Skandion Clinic, Sweden.
    Spatial correlation of linear energy transfer and relative biological effectiveness with treatment related toxicities following proton therapy for intracranial tumors2019In: Medical physics (Lancaster), ISSN 0094-2405Article in journal (Refereed)
    Abstract [en]

    Purpose: The enhanced relative biological effectiveness (RBE) at the end of the proton range might increase the risk of radiation-induced toxicities. This is of special concern for intracranial treatments where several critical organs at risk (OARs) surround the tumor.  In the light of this, a retrospective analysis of dose-averaged linear energy transfer (LETd) and RBE-weighted dose (DRBE) distributions was conducted for three clinical cases with suspected treatment related toxicities following intracranial proton therapy. Alternative treatment strategies aiming to reduce toxicity risks are also presented.

    Methods: The clinical single-field optimized (SFO) plans were recalculated for 81 error scenarios with a Monte Carlo dose engine. The fractionation DRBE was 1.8 Gy (RBE) in 28 or 30 fractions assuming a constant RBE of 1.1. Two LETd- and α/β-dependent variable RBE models were used for evaluation, including a sensitivity analysis of the α/β parameter. Resulting distributions of DRBE and LETd were analyzed together with normal tissue complication probabilities (NTCPs). Subsequently, four multi-field optimized (MFO) plans, with an additional beam and/or objectives penalizing protons stopping in OARs, were created to investigate the potential reduction of LETd, DRBE and NTCP.

    Results: The two variable RBE models agreed well and predicted average RBE values around 1.3 in the toxicity volumes, resulting in increased near-maximum DRBE of 7-11 Gy (RBE) compared to RBE=1.1 in the nominal scenario. The corresponding NTCP estimates increased from 0.8%, 0.0% and 3.7% (RBE=1.1) to 15.5%, 1.8% and 45.7% (Wedenberg RBE model) for the three patients, respectively. The MFO plans generally allowed for LETd, DRBE and NTCP reductions in OARs, without compromising the target dose. Compared to the clinical SFO plans, the maximum reduction of the near-maximum LETd was 56%, 63% and 72% in the OAR exhibiting the toxicity for the three patients, respectively.

    Conclusions: Although a direct causality between RBE and toxicity cannot be established here, high LETd and DRBE correlated spatially with the observed toxicities, whereas setup and range uncertainties had a minor impact. Individual factors, which might affect the patient-specific radiosensitivity, were however not included in these calculations. The MFO plans using both an additional beam and proton track-end objectives allowed the largest reductions in LETd, DRBE and NTCP, and might be future tools for similar cases.

  • 19.
    Ödén, Jakob
    et al.
    Stockholm University, Faculty of Science, Department of Physics. Karolinska Institutet, Sweden.
    Zimmerman, Jens
    Bujila, Robert
    Nowik, Patrik
    Poludniowski, Gavin
    Technical Note: On the calculation of stopping-power ratio for stoichiometric calibration in proton therapy2015In: Medical physics (Lancaster), ISSN 0094-2405, Vol. 42, no 9, p. 5252-5257Article in journal (Refereed)
    Abstract [en]

    Purpose: The quantitative effects of assumptions made in the calculation of stopping-power ratios (SPRs) are investigated, for stoichiometric CT calibration in proton therapy. The assumptions investigated include the use of the Bethe formula without correction terms, Bragg additivity, the choice of I-value for water, and the data source for elemental I-values. Methods: The predictions of the Bethe formula for SPR (no correction terms) were validated against more sophisticated calculations using the SRIM software package for 72 human tissues. A stoichiometric calibration was then performed at our hospital. SPR was calculated for the human tissues using either the assumption of simple Bragg additivity or the Seltzer-Berger rule (as used in ICRU Reports 37 and 49). In each case, the calculation was performed twice: First, by assuming the I-value of water was an experimentally based value of 78 eV (value proposed in Errata and Addenda for ICRU Report 73) and second, by recalculating the I-value theoretically. The discrepancy between predictions using ICRU elemental I-values and the commonly used tables of Janni was also investigated. Results: Errors due to neglecting the correction terms to the Bethe formula were calculated at less than 0.1% for biological tissues. Discrepancies greater than 1%, however, were estimated due to departures from simple Bragg additivity when a fixed I-value for water was imposed. When the I-value for water was calculated in a consistent manner to that for tissue, this disagreement was substantially reduced. The difference between SPR predictions when using Janni's or ICRU tables for I-values was up to 1.6%. Experimental data used for materials of relevance to proton therapy suggest that the ICRU-derived values provide somewhat more accurate results (root-mean-square-error: 0.8% versus 1.6%). Conclusions: The conclusions from this study are that (1) the Bethe formula can be safely used for SPR calculations without correction terms; (2) simple Bragg additivity can be reasonably assumed for compound materials; (3) if simple Bragg additivity is assumed, then the I-value for water should be calculated in a consistent manner to that of the tissue of interest (rather than using an experimentally derived value); (4) the ICRU Report 37 I-values may provide a better agreement with experiment than Janni's tables. (C) 2015 American Association of Physicists in Medicine.

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