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Sökning: WFRF:(Ceberg Crister)

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1.
  • Ceberg, Sofie, et al. (författare)
  • Evaluation of breathing interplay effects during VMAT by using 3D gel measurements
  • 2013
  • Ingår i: 7th International Conference on 3D Radiation Dosimetry (IC3DDose). - : IOP Publishing. - 1742-6588 .- 1742-6596. ; 444, s. 012098-012098
  • Konferensbidrag (refereegranskat)abstract
    • Respiratory motion during dynamic radiotherapy may affect the absorbed dose distribution both by dose-reducing smoothing and by more complicated interplay effects. In this study we present a novel method to determine the relative importance of these two effects. For the two dynamic deliveries studied in this work, the expected target dose reduction due to the smoothing effect was estimated by measurements convolved by the motion function. Remaining absorbed dose differences were attributed to interplay effects between the motion of the gel phantom and the movement of the modulating MLC leaves during modulated arc radiotherapy. The total dosimetric effect due to breathing motion and dynamic MLC motion during VMAT delivery resulted in an average of about 4% target dose reduction. Comparing with only the smoothing effect, the average difference was decreased to around 1%, and the remaining distribution was attributed to interplay effects. Although the interplay effects were small compared to the smoothing effect, the standard deviations of 1.4-2.3% (1SD) were larger than the narrow distribution for repeated stationary measurement with a standard deviation between 0.5-0.9% (1SD).
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2.
  • Ceberg, Sofie, et al. (författare)
  • Modelling the dynamic dose response of an nMAG polymer gel dosimeter.
  • 2012
  • Ingår i: Physics in Medicine and Biology. - : IOP Publishing. - 1361-6560 .- 0031-9155. ; 57:15, s. 4845-4853
  • Tidskriftsartikel (refereegranskat)abstract
    • Gel dosimetry measures the absorbed radiation dose with high spatial resolution in 3D. However, recently published data show that the response of metacrylic-based polymer gels depends on the segmented delivery pattern, which could potentially be a considerable disadvantage for measurements of modern dynamic radiotherapy techniques. The aim of this study is to design a dynamic compartment model for the response of a gel dosimeter, exposed to an arbitrary irradiation pattern (segmented delivery and intensity modulation), in order to evaluate the associated effects on absorbed dose measurements. The model is based on the separation of the protons affecting the magnetic resonance signal (i.e. the R2 value) into six compartments, described by a set of differential equations. The model is used to calculate R2 values for a number of different segmented delivery patterns between 0-4 Gy over 1-33 fractions. Very good agreement is found between calculated and measured R2 values, with an average difference of 0.3 ± 1.1% (1 SD). The model is also used to predict the behaviour of a gel dosimeter exposed to irradiation according to typical IMRT, VMAT and respiratory gating scenarios. The calculated R2 values are approximately independent of the segmented delivery, given that the same total dose is delivered during the same total time. It is concluded that this study helps to improve the theoretical understanding of the dependence of metacrylic-based polymer gel response to segmented radiation delivery.
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3.
  • Edvardsson, Anneli, et al. (författare)
  • Motion induced interplay effects for VMAT radiotherapy
  • 2018
  • Ingår i: Physics in Medicine and Biology. - : IOP Publishing. - 0031-9155 .- 1361-6560. ; 63:8
  • Tidskriftsartikel (refereegranskat)abstract
    • The purpose of this study was to develop a method to simulate breathing motion induced interplay effects for volumetric modulated arc therapy (VMAT), to verify the proposed method with measurements, and to use the method to investigate how interplay effects vary with different patient-and machine specific parameters. VMAT treatment plans were created on a virtual phantom in a treatment planning system (TPS). Interplay effects were simulated by dividing each plan into smaller sub-arcs using an in-house developed software and shifting the isocenter for each sub-arc to simulate a sin(6) breathing motion in the superior-inferior direction. The simulations were performed for both flattening-filter (FF) and flattening-filter free (FFF) plans and for different breathing amplitudes, period times, initial breathing phases, dose levels, plan complexities, CTV sizes, and collimator angles. The resulting sub-arcs were calculated in the TPS, generating a dose distribution including the effects of motion. The interplay effects were separated from dose blurring and the relative dose differences to 2% and 98% of the CTV volume (Delta D-98% and Delta D-2%) were calculated. To verify the simulation method, measurements were carried out, both static and during motion, using a quasi-3D phantom and a motion platform. The results of the verification measurements during motion were comparable to the results of the static measurements. Considerable interplay effects were observed for individual fractions, with the minimum Delta D-98% and maximum Delta D-2% being - 16.7% and 16.2%, respectively. The extent of interplay effects was larger for FFF compared to FF and generally increased for higher breathing amplitudes, larger period times, lower dose levels, and more complex treatment plans. Also, the interplay effects varied considerably with the initial breathing phase, and larger variations were observed for smaller CTV sizes. In conclusion, a method to simulate motion induced interplay effects was developed and verified with measurements, which allowed for a large number of treatment scenarios to be investigated. The simulations showed large interplay effects for individual fractions and that the extent of interplay effects varied with the breathing pattern, FFF/FF, dose level, CTV size, collimator angle, and the complexity of the treatment plan.
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4.
  • Edvardsson, Anneli, et al. (författare)
  • Verification of motion induced thread effect during tomotherapy using gel dosimetry
  • 2015
  • Ingår i: 8th International Conference on 3D Radiation Dosimetry (IC3DDOSE). - : IOP Publishing. - 1742-6596 .- 1742-6588. ; 573, s. 012048-012048
  • Konferensbidrag (refereegranskat)abstract
    • The purpose of the study was to evaluate how breathing motion during tomotherapy (Accuray, CA, USA) treatment affects the absorbed dose distribution. The experiments were carried out using gel dosimetry and a motion device simulating respiratory-like motion (HexaMotion, ScandiDos, Uppsala, Sweden). Normoxic polyacrylamide gels (nPAG) were irradiated, both during respiratory-like motion and in a static mode. To be able to investigate interplay effects the static absorbed dose distribution was convolved with the motion function and differences between the dynamic and convolved static absorbed dose distributions were interpreted as interplay effects. The expected dose blurring was present and the interplay effects formed a spiral pattern in the lower dose volume. This was expected since the motion induced affects the preset pitch and the theoretically predicted thread effect may emerge. In this study, the motion induced thread effect was experimentally verified for the first time.
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6.
  • Haraldsson, André, et al. (författare)
  • Surface-guided tomotherapy improves positioning and reduces treatment time : A retrospective analysis of 16 835 treatment fractions
  • 2020
  • Ingår i: Journal of Applied Clinical Medical Physics. - : Wiley. - 1526-9914. ; 21:8, s. 139-148
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: In this study, we have quantified the setup deviation and time gain when using fast surface scanning for daily setup/positioning with weekly megavoltage computed tomography (MVCT) and compared it to daily MVCT. Methods: A total of 16 835 treatment fractions were analyzed, treated, and positioned using our TomoTherapy HD (Accuray Inc., Madison, USA) installed with a Sentinel optical surface scanning system (C-RAD Positioning AB, Uppsala, Sweden). Patients were positioned using in-room lasers, surface scanning and MVCT for the first three fractions. For the remaining fractions, in-room laser was used for setup followed by daily surface scanning with MVCT once weekly. The three-dimensional (3D) setup correction for surface scanning was evaluated from the registration between MVCT and the planning CT. The setup correction vector for the in-room lasers was assessed from the surface scanning and the MVCT to planning CT registration. The imaging time was evaluated as the time from imaging start to beam-on. Results: We analyzed 894 TomoTherapy treatment plans from 2012 to 2018. Of all the treatment fractions performed with surface scanning, 90 % of the residual errors were within 2.3 mm for CNS (N = 284), 2.9 mm for H&N (N = 254), 8.7 mm for thorax (N = 144) and 10.9 for abdomen (N = 134) patients. The difference in residual error between surface scanning and positioning with in-room lasers was significant (P < 0.005) for all sites. The imaging time was assessed as total imaging time per treatment plan, modality, and treatment site and found that surface scanning significantly reduced patient on-couch time compared to MVCT for all treatment sites (P < 0.005). Conclusions: The results indicate that daily surface scanning with weekly MVCT can be used with the current target margins for H&N, CNS, and thorax, with reduced imaging time.
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7.
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8.
  • Mannerberg, Annika, et al. (författare)
  • Surface guided electron FLASH radiotherapy for canine cancer patients
  • 2023
  • Ingår i: Medical Physics. - 0094-2405. ; 50:7, s. 4047-4054
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundDuring recent years FLASH radiotherapy (FLASH-RT) has shown promising results in radiation oncology, with the potential to spare normal tissue while maintaining the antitumor effects. The high speed of the FLASH-RT delivery increases the need for fast and precise motion monitoring to avoid underdosing the target. Surface guided radiotherapy (SGRT) uses surface imaging (SI) to render a 3D surface of the patient. SI provides real-time motion monitoring and has a large scanning field of view, covering off-isocentric positions. However, SI has so far only been used for human patients with conventional setup and treatment.PurposeThe aim of this study was to investigate the performance of SI as a motion management tool during electron FLASH-RT of canine cancer patients.MethodsTo evaluate the SI system's ability to render surfaces of fur, three fur-like blankets in white, grey, and black were used to imitate the surface of canine patients and the camera settings were optimized for each blanket. Phantom measurements using the fur blankets were carried out, simulating respiratory motion and sudden shift. Respiratory motion was simulated using the QUASAR Respiratory Motion Phantom with the fur blankets placed on the phantom platform, which moved 10 mm vertically with a simulated respiratory period of 4 s. Sudden motion was simulated with an in-house developed phantom, consisting of a platform which was moved vertically in a stepwise motion at a chosen frequency. For sudden measurements, 1, 2, 3, 4, 5, 6, 7, and 10 Hz were measured. All measurements were both carried out at the conventional source-to-surface distance (SSD) of 100 cm, and in the locally used FLASH-RT setup at SSD = 70 cm. The capability of the SI system to reproduce the simulated motion and the sampling time were evaluated. As an initial step towards clinical implementation, the feasibility of SI for surface guided FLASH-RT was evaluated for 11 canine cancer patients.ResultsThe SI camera was capable of rendering surfaces for all blankets. The deviation between simulated and measured mean peak-to-peak breathing amplitude was within 0.6 mm for all blankets. The sampling time was generally higher for the black fur than for the white and grey fur, for the measurement of both respiratory and sudden motion. The SI system could measure sudden motion within 62.5 ms and detect motion with a frequency of 10 Hz. The feasibility study of the canine patients showed that the SI system could be an important tool to ensure patient safety. By using this system we could ensure and document that 10 out of 11 canine patients had a total vector offset from the reference setup position ConclusionsWe have shown that SI can be used for surface guided FLASH-RT of canine patients. The SI system is currently not fast enough to interrupt a FLASH-RT beam while irradiating but with the short sampling time sudden motion can be detected. The beam can therefore be held just prior to irradiation, preventing treatment errors such as underdosing the target.
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9.
  • Nordström, Fredrik, et al. (författare)
  • 3D geometric gel dosimetry verification of intraprostatic fiducial guided hypofractionated radiotherapy of prostate cancer
  • 2010
  • Ingår i: Journal of Physics: Conference Series. - : IOP Publishing. - 1742-6596. ; 250, s. 287-291
  • Konferensbidrag (refereegranskat)abstract
    • This pre-study is aimed to investigate the feasibility of a normoxic polyacrylamide gel (nPAG) dosimeter with implanted gold fiducials to evaluate the geometric precision, including setup correction strategies, in the delivery of hypofractionated treatments. For this purpose a phantom consisting of three parts was constructed: (1) the patient simulating volume, providing realistic scatter conditions and weight, (2) a bottle containing the active dosimetric volume and (3) the gold fiducials and the fiducial support structure. A 6.1 Gy prostate IMRT treatment was delivered to the phantom using the sliding-window technique. The phantom was positioned prior to the treatment using the implanted fiducials and kV on-board imaging. An overlay of the 95% isosurface of the TPS calculated dose distribution and the measured dose distribution using gel showed good agreement. The clinical target volume (CTV) was well centred inside the 95% isodose surface of the measured volume. It was shown for the evaluated case that the use of on-board imaging and integrated setup correction tools could be used to compensate for a deliberately introduced offset in CTV position. The study showed that MRI based nPAG gel dosimetry can be used to verify setup correction procedures using implanted gold fiducials.
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10.
  • Adrian, Gabriel, et al. (författare)
  • Cancer Cells Can Exhibit a Sparing FLASH Effect at Low Doses Under Normoxic In Vitro-Conditions
  • 2021
  • Ingår i: Frontiers in Oncology. - : Frontiers Media SA. - 2234-943X. ; 11
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Irradiation with ultra-high dose rate (FLASH) has been shown to spare normal tissue without hampering tumor control in several in vivo studies. Few cell lines have been investigated in vitro, and previous results are inconsistent. Assuming that oxygen depletion accounts for the FLASH sparing effect, no sparing should appear for cells irradiated with low doses in normoxia. Methods: Seven cancer cell lines (MDA-MB-231, MCF7, WiDr, LU-HNSCC4, HeLa [early passage and subclone]) and normal lung fibroblasts (MRC-5) were irradiated with doses ranging from 0 to 12 Gy using FLASH (≥800 Gy/s) or conventional dose rates (CONV, 14 Gy/min), with a 10 MeV electron beam from a clinical linear accelerator. Surviving fraction (SF) was determined with clonogenic assays. Three cell lines were further studied for radiation-induced DNA-damage foci using a 53BP1-marker and for cell cycle synchronization after irradiation. Results: A tendency of increased survival following FLASH compared with CONV was suggested for all cell lines, with significant differences for 4/7 cell lines. The magnitude of the FLASH-sparing expressed as a dose-modifying factor at SF=0.1 was around 1.1 for 6/7 cell lines and around 1.3 for the HeLasubclone. Similar cell cycle distributions and 53BP1-foci numbers were found comparing FLASH to CONV. Conclusion: We have found a FLASH effect appearing at low doses under normoxic conditions for several cell lines in vitro. The magnitude of the FLASH effect differed between the cell lines, suggesting inherited biological susceptibilities for FLASH irradiation.
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11.
  • Adrian, Gabriel, et al. (författare)
  • Rescue Effect Inherited in Colony Formation Assays Affects Radiation Response
  • 2018
  • Ingår i: Radiation Research. - 0033-7587. ; 189:1, s. 44-52
  • Tidskriftsartikel (refereegranskat)abstract
    • It is well known that nonirradiated cells can exhibit radiation damage (bystander effect), and recent findings have shown that nonirradiated cells may help protect irradiated cells (rescue effect). These findings call into question the traditional view of radiation response: cells cannot be envisioned as isolated units. Here, we investigated traditional colony formation assays to determine if they also comprise cellular communication affecting the radiation response, using colony formation assays with varying numbers of cells, modulated beam irradiation and media transfer. Our findings showed that surviving fraction gradually increased with increasing number of irradiated cells. Specifically, for DU-145 human prostate cancer cells, surviving fraction increased 1.9-to-4.1-fold after 5-12 Gy irradiation; and for MM576 human melanoma cells, surviving fraction increased 1.9-fold after 5 Gy irradiation. Furthermore, increased surviving fraction was evident after modulated beam irradiation, where irradiated cells could communicate with nonirradiated cells. Media from dense cell culture also increased surviving fraction. The results suggest that traditional colony formation assays comprise unavoidable cellular communication affecting radiation outcome and the shape of the survival curve. We also propose that the increased in-field surviving fraction after modulated beam irradiation is due to the same effect.
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12.
  • Adrian, Gabriel, et al. (författare)
  • The FLASH effect depends on oxygen concentration
  • 2019
  • Ingår i: British Journal of Radiology. - : British Institute of Radiology. - 1748-880X .- 0007-1285. ; 93:1106
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Recent in vivo results have shown prominent tissue sparing effect of radiotherapy with ultra-high dose rates (FLASH) compared to conventional dose rates (CONV). Oxygen depletion has been proposed as the underlying mechanism, but in vitro data to support this have been lacking. The aim of the current study was to compare FLASH to CONV irradiation under different oxygen concentrations in vitro. METHODS: Prostate cancer cells were irradiated at different oxygen concentrations (relative partial pressure ranging between 1.6 and 20%) with a 10 MeV electron beam at a dose rate of either 600 Gy/s (FLASH) or 14 Gy/min (CONV), using a modified clinical linear accelerator. We evaluated the surviving fraction of cells using clonogenic assays after irradiation with doses ranging from 0 to 25 Gy. RESULTS: Under normoxic conditions, no differences between FLASH and CONV irradiation were found. For hypoxic cells (1.6%), the radiation response was similar up to a dose of about 5-10 Gy, above which increased survival was shown for FLASH compared to CONV irradiation. The increased survival was shown to be significant at 18 Gy, and the effect was shown to depend on oxygen concentration. CONCLUSION: The in vitro FLASH effect depends on oxygen concentration. Further studies to characterize and optimize the use of FLASH in order to widen the therapeutic window are indicated. ADVANCES IN KNOWLEDGE: This paper shows in vitro evidence for the role of oxygen concentration underlying the difference between FLASH and CONV irradiation.
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13.
  • AHLSTEDT, JONATAN, et al. (författare)
  • Effect of Blockade of Indoleamine 2, 3-dioxygenase in Conjunction with Single Fraction Irradiation in Rat Glioma
  • 2015
  • Ingår i: Jacobs journal of radiation oncology. - 2376-9424. ; 2:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Glioblastoma (GBM), or WHO Astrocytoma grade IV, is the most common primary brain tumour in adults. GBM is shown to escape host immune surveillance through many paths, of which expression of indoleamine 2,3-dioxygenase (IDO), leading to induction and accumulation of regulatory T-cells in the tumour microenvironment, has been shown to be of importance. 1-Methyl tryptophan (1-MT) is an inhibitor of IDO that has been shown to have a positive effect on survival in experimental models of GBM. In this study, we evaluate the effect of combined single-fraction irradiation of 8 Gy with 1-MT treatment in Fischer rats carrying the RG2 glioma model. We also investigate expression of IDO in the RG2 model before and after irradiation. Thirty-three Fischer 344 rats received intracranial inoculations of RG2 tumour cells, and were treated with either intraperito-neal 1-MT, 8 Gy single-fraction radiotherapy, or a combination of the two. Survival in the combined treatment group (29 days ± 0.75) was significantly better than controls (20 ± 0.99, p=0.015) and radiation only (17 ± 2.75, p=0.014). Survival was also better with combined treatment compared to 1-MT only but the difference was non-significant (18 ± 0.28, p=0.215).Our results add to the growing base of evidence suggesting 1-methyl-tryptophan is an attractive candidate for clinical investi-gation in patients carrying highly malignant astrocytoma, especially in combination with radiation treatment, even in singular fraction settings.
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14.
  • Ahlstedt, Jonatan, et al. (författare)
  • Growth pattern of experimental glioblastoma
  • 2020
  • Ingår i: Histology and Histopathology. - 1699-5848. ; 35:8, s. 871-886
  • Tidskriftsartikel (refereegranskat)abstract
    • Glioblastoma multiforme (GBM) is an aggressive primary brain malignancy with a very poor prognosis. Researchers employ animal models to develop potential therapies. It is important that these models have clinical relevance. This means that old models, propagated for decades in cultures, should be questioned. Parameters to be evaluated include whether animals are immune competent or not, the infiltrative growth pattern of the tumor, tumor volume resulting in symptoms and growth rate.We here describe the growth pattern of an experimental glioblastoma model in detail with GFP positive glioblastoma cells in fully immune competent animalsand study tumor growth rate and tumor mass as a function of time from inoculation.We were able to correlate findings made with classical immunohistochemistry and MR findings. The tumor growth rate was fitted by a Gompertz function. The model predicted the time until onset of symptoms for 5000 inoculated cells to 18.7±0.4 days, and the tumor mass at days 10 and 14, which are commonly used as the start of treatment in therapeutic studies, were 5.97±0.62 mg and 29.1±3.0 mg, respectively.We want to raise the question regarding the clinical relevance of the outline of glioblastoma experiments, where treatment is ofteninitiated at a very early stage. The approach presented here could potentially be modified to gain information also from other tumor models.
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15.
  • Ahlstedt, Jonatan, et al. (författare)
  • Increased effect of two-fraction radiotherapy in conjunction with IDO1 inhibition in experimental glioblastoma
  • 2020
  • Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 15:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives The aim of the study was to investigate therapeutic efficacy of single-or two-fraction radiotherapy in conjunction with IDO1-inhibition in a syngeneic rat glioblastoma model. IDO is known to cause immunosuppression through breakdown of tryptophan in the tumor microenvironment. Methods Gene expression analyses of IDO in glioblastoma were performed with data from publicly available datasets. Fractionation studies were done on animals to evaluate tumor size, immune cell infiltration of tumors and serum profile on day 18 after tumor inoculation. Survival analyses were done with animals carrying intracranial glioblastomas comparing twofraction radiotherapy+IDO1-inhibition to controls. IDO inhibition was achieved by administration of 1-methyl tryptophan (1-MT), and radiotherapy (RT) was delivered in doses of 8Gy. Results The expression of IDO1 was increased on gene level in glioblastoma stem cells. Tumor size was significantly reduced in animals treated with 1-MT+RTx 2 (both long and short intervals, i.e. 7 and 4 days between the treatments) as compared to control animals, animals treated with only 1-MT or animals treated with 1-MT+RTx1. Serum levels of IL-1A were significantly altered in all treated animals as compared to control animals. Survival was significantly increased in the animals treated with 1-MT+RTx2 (7-day interval) compared to control animals. Conclusions Addition of two-fraction RT to IDO1 inhibition with 1-MT significantly reduced tumor size in animals with glioblastoma. Survival was significantly increased in animals treated with twofractioned RT+1-MT as compared to untreated controls increased significantly. Advances in knowledge The currently used combination of only two fractions of radiotherapy and immune therapy is a promising area of research, increasing efficacy compared to single fraction irradiation, while potentially lowering radiation side effects compared to radiation in current clinical practice.
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16.
  • Andersson, Jonas, 1975-, et al. (författare)
  • Artificial intelligence and the medical physics profession-A Swedish perspective
  • 2021
  • Ingår i: Physica Medica-European Journal of Medical Physics. - : Elsevier BV. - 1120-1797 .- 1724-191X. ; 88, s. 218-225
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: There is a continuous and dynamic discussion on artificial intelligence (AI) in present-day society. AI is expected to impact on healthcare processes and could contribute to a more sustainable use of resources allocated to healthcare in the future. The aim for this work was to establish a foundation for a Swedish perspective on the potential effect of AI on the medical physics profession. Materials and methods: We designed a survey to gauge viewpoints regarding AI in the Swedish medical physics community. Based on the survey results and present-day situation in Sweden, a SWOT analysis was performed on the implications of AI for the medical physics profession. Results: Out of 411 survey recipients, 163 responded (40%). The Swedish medical physicists with a professional license believed (90%) that AI would change the practice of medical physics but did not foresee (81%) that AI would pose a risk to their practice and career. The respondents were largely positive to the inclusion of AI in educational programmes. According to self-assessment, the respondents' knowledge of and workplace preparedness for AI was generally low. Conclusions: From the survey and SWOT analysis we conclude that AI will change the medical physics profession and that there are opportunities for the profession associated with the adoption of AI in healthcare. To overcome the weakness of limited AI knowledge, potentially threatening the role of medical physicists, and build upon the strong position in Swedish healthcare, medical physics education and training should include learning objectives on AI.
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17.
  • Benedek, Hunor, et al. (författare)
  • The effect of prostate motion during hypofractionated radiotherapy can be reduced by using flattening filter free beams
  • 2018
  • Ingår i: Physics and imaging in radiation oncology. - : Elsevier BV. - 2405-6316. ; 6, s. 66-70
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and purpose: Hypofractionated radiotherapy of prostate cancer reduces the overall treatment time but increases the per-fraction beam-on time due to the higher fraction doses. This increased fraction treatment time results in a larger uncertainty of the prostate position. The purpose of this study was to investigate the effect of prostate motion during flattening filter free (FFF) Volumetric Modulated Arc Therapy (VMAT) in ultrahypofractionation of prostate cancer radiotherapy with preserved plan quality compared to conventional flattened beams.Materials and methods: Nine prostate patients from the Scandinavian HYPO-RT-PC trial were re-planned using VMAT technique with both conventional and flattening filter free beams. Two fractionation schedules were used, one hypofractionated (42.7 Gy in 7 fractions), and one conventional (78.0 Gy in 39 fractions). Pre-treatment verification measurements were performed on all plans and the treatment time was recorded. Measurements with simulated prostate motion were performed for the plans with the longest treatment times. Results: All the 10FFF plans fulfilled the clinical gamma pass rate, 90% (3%, 2 mm), during all simulated prostate motion trajectories. The 10MV plans only fulfilled the clinical pass rate for three of the trajectories. The mean beam-on-time for the hypofractionated plans were reduced from 2.3 min to 1.0 min when using 10FFF compared to 10MV. No clinically relevant differences in dose distribution were identified when comparing the plans with different beam qualities. Conclusion: Flattening-filter free VMAT reduces treatment times, limiting the dosimetric effect of organ motion for ultrahypofractionated prostate cancer with preserved plan quality.
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18.
  • Bjärngard, Bengt E, et al. (författare)
  • Quality control of measured x-ray beam data
  • 1997
  • Ingår i: Medical Physics. - : Wiley. - 0094-2405. ; 24:9, s. 1441-1444
  • Tidskriftsartikel (refereegranskat)abstract
    • The purpose of this study was to examine whether the quality of measured x-ray beam data can be judged from how well the data agree with a semiempirical formula. Tissue-phantom ratios (TPR) and output factors for several accelerators in the energy range 4-25 MV were fitted to the formula, separating the dose contributions from primary and phantom-scattered photons. The former was described by exponential attenuation in water, with beam hardening, and the latter by the scatter-to-primary dose ratio using two parameters related to the probability and the directional distribution of the scattered photons. Electron disequilibrium was not considered. Two approaches were evaluated. In one, the attenuation and hardening coefficients were determined from measurements in a narrow-beam geometry; in the other, they were extracted by the fitting procedure. Measured and fitted data agreed within +/- 2% in both cases. The differences were randomly distributed and had a standard deviation of typically 0.7%. Singular points with errors were easily identified. Systematic errors were revealed by increased standard deviation. However, when the attenuation was derived by the fitting algorithm, the attenuation coefficient deviated significantly from the experimental value. It is concluded that the semiempirical formula can serve to evaluate and verify beam data measured in water and that the physically most accurate description requires that the attenuation and hardening coefficients be determined in a narrow-beam geometry. The attenuation coefficient is an excellent measure of both the primary and the scatter dose component, i.e., of beam quality.
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19.
  • Bjärngard, Bengt E, et al. (författare)
  • Tissue-phantom ratios from percentage depth doses
  • 1996
  • Ingår i: Medical Physics. - : Wiley. - 0094-2405. ; 23:5, s. 629-634
  • Tidskriftsartikel (refereegranskat)abstract
    • When converting fractional (percentage) depth doses to tissue-phantom ratios, one must use a factor that accounts for the different source-to-point distances. Two minor correction factors are also involved. One is the ratio of total to primary dose at the two different distances from the source, for the same depth and field size. This factor is usually ignored. It was determined experimentally that this can introduce up to 1.5% error at 6 MV. The second correction factor reflects differences related to scattered photons and electrons at the depth of normalization in the two geometries. This correction is accounted for in published conversion procedures. It was found to be less than 1% provided the normalization depth is sufficient for electron equilibrium, which occurs first well beyond the depth of maximum dose. One may avoid electron-equilibrium problems by using an interim normalization depth that provides electron equilibrium with some margin, renormalizing to a shallower depth if desired. With this precaution, the accuracy when measured fractional depth doses were converted to tissue-phantom ratios was comparable to that of directly measured tissue-phantom ratios even when the correction factors were ignored.
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20.
  • Børresen, Betina, et al. (författare)
  • Evaluation of single-fraction high dose FLASH radiotherapy in a cohort of canine oral cancer patients
  • 2023
  • Ingår i: Frontiers in Oncology. - 2234-943X. ; 13, s. 1-10
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: FLASH radiotherapy (RT) is a novel method for delivering ionizingradiation, which has been shown in preclinical studies to have a normal tissuesparing effect and to maintain anticancer efficacy as compared to conventionalRT. Treatment of head and neck tumors with conventional RT is commonlyassociated with severe toxicity, hence the normal tissue sparing effect of FLASHRT potentially makes it especially advantageous for treating oral tumors. In thiswork, the objective was to study the adverse effects of dogs with spontaneousoral tumors treated with FLASH RT.Methods: Privately-owned dogs with macroscopic malignant tumors of the oralcavity were treated with a single fraction of ≥30Gy electron FLASH RT andsubsequently followed for 12 months. A modified conventional linear acceleratorwas used to deliver the FLASH RT.Results: Eleven dogs were enrolled in this prospective study. High grade adverseeffects were common, especially if bone was included in the treatment field. Fourout of six dogs, who had bone in their treatment field and lived at least 5 monthsafter RT, developed osteoradionecrosis at 3-12 months post treatment. Thetreatment was overall effective with 8/11 complete clinical responses and 3/11partial responses.Conclusion: This study shows that single-fraction high dose FLASH RT wasgenerally effective in this mixed group of malignant oral tumors, but the risk ofosteoradionecrosis is a serious clinical concern. It is possible that the risk ofosteonecrosis can be mitigated through fractionation and improved doseconformity, which needs to be addressed before moving forward with clinicaltrials in human cancer patients.
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21.
  • Capala, J, et al. (författare)
  • Boron neutron capture therapy for glioblastoma multiforme : Clinical studies in Sweden
  • 2003
  • Ingår i: Journal of Neuro-Oncology. - 1573-7373. ; 62:1, s. 135-144
  • Tidskriftsartikel (refereegranskat)abstract
    • A boron neutron capture therapy (BNCT) facility has been constructed at Studsvik, Sweden. It includes two filter/moderator configurations. One of the resulting neutron beams has been optimized for clinical irradiations with a filter/moderator system that allows easy variation of the neutron spectrum from the thermal to the epithermal energy range. The other beam has been designed to produce a large uniform field of thermal neutrons for radio-biological research. Scientific operations of the Studsvik BNCT project are overseen by the Scientific Advisory Board comprised of representatives of major universities in Sweden. Furthermore, special task groups for clinical and preclinical studies have been formed to facilitate collaboration with academia. The clinical Phase II trials for glioblastoma are sponsored by the Swedish National Neuro-Oncology Group and, presently, involve a protocol for BNCT treatment of glioblastoma patients who have not received any therapy other than surgery. In this protocol, p-boronophenylalanine (BPA), administered as a 6-h intravenous infusion, is used as the boron delivery agent. As of January 2002, 17 patients were treated. The 6-h infusion of 900 mg BPA/kg body weight was shown to be safe and resulted in the average blood-boron concentration of 24 μg/g (range: 15-32 μg/g) at the time of irradiation (approximately 2-3 h post-infusion). Peak and average weighted radiation doses to the brain were in the ranges of 8.0-15.5 Gy(W) and 3.3-6.1 Gy(W), respectively. So far, no severe BNCT-related acute toxicities have been observed. Due to the short follow-up time, it is too early to evaluate the efficacy of these studies.
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22.
  • Ceberg, Crister, et al. (författare)
  • A comparative study on the pharmacokinetics and biodistribution of boronated porphyrin (BOPP) and sulfhydryl boron hydride (BSH) in the RG2 rat glioma model
  • 1995
  • Ingår i: Journal of Neurosurgery. - 0022-3085. ; 83:1, s. 86-92
  • Tidskriftsartikel (refereegranskat)abstract
    • Boron neutron capture therapy is a treatment modality for cancer that depends on the specific uptake of boron by the tumor cells. The infiltrative growth of malignant gliomas requires that boron reach and accumulate in migrating cells outside the margin of the tumor; thus, it is important that the biodistribution of new boron compounds is also studied in the surrounding healthy brain tissue. This study is undertaken in the present work, in which the biodistribution and pharmacokinetics of sulfhydryl boron hydride (BSH) and boronated porphyrin (BOPP) in the RG2 rat glioma model are investigated. This model mimics the characteristics of human glioma with cells migrating into the surrounding brain. The animals were infused intravenously with either BSH (25 micrograms or 175 micrograms of boron per gram of body weight) or BOPP (12 micrograms of boron per gram body weight). For the low dose of BSH, the maximum tumor-boron content was 8 ppm at approximately 9 hours after the infusion with a tumor-to-blood ratio of 0.6. At the higher dose, the corresponding figures were 15 ppm after 12 hours with a tumor-to-blood ratio of 0.5. For BOPP, a tumor-boron concentration of 81 ppm was achieved 24 hours after the infusion and sustained in that range for at least 72 hours. The tumor-to-blood ratio at 24 hours was slightly above 6, but continued to increase as the blood was cleared. These results indicate that both compounds are spread into the normal brain tissue following the same pathways as the migrating tumor cells and in this way can be taken up even in distant tumor cell foci.
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23.
  • Ceberg, Crister, et al. (författare)
  • A new method for quantification of image distortion due to pile-up in scintillation cameras
  • 1991
  • Ingår i: European Journal Of Nuclear Medicine. - 1432-105X. ; 18:12, s. 959-963
  • Tidskriftsartikel (refereegranskat)abstract
    • Characterization of the count-rate performance of scintillation cameras should include not only the specification of count losses. At high count rates, there is also an image distortion due to the mispositioning of pile-up events. In this paper a simple and clinically relevant procedure to quantify this distortion is presented. The images of a square uniform technetium-99m phantom at high and low count rates are used. The fraction of the total counts being correctly positioned is determined as the peripheral count density divided by the total average count density. This ratio, corrected for the camera non-uniformity at low count rates, is called the 'positioning ability'. According to the National Electrical Manufacturers' Association (NEMA), the 'system count rate performance with scatter' should be reported as the measured count rate giving 20% count losses. In this paper it is suggested that this measure be complemented by a measure of the fraction correct positioned events at this count rate. This fraction, the 'high count rate positioning ability', can be easily and accurately measured using our method. The method has been tested on two different scintillation cameras. For one of them the high count rate positioning ability was determined as 91% at a measured count rate of 30,000 s-1 with 20% count losses. For the other camera, the corresponding figures were 88% at 59,000 s-1 and close to 100% at 38,000 s-1, before and after the installation of a new pile-up rejection circuit, respectively.
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24.
  • Ceberg, Crister (författare)
  • A note on the interpretation of the gamma evaluation index
  • 2013
  • Ingår i: 7th International Conference on 3D Radiation Dosimetry (IC3DDose). - : IOP Publishing. - 1742-6596 .- 1742-6588. ; 444, s. 012082-012082
  • Konferensbidrag (refereegranskat)abstract
    • The gamma evaluation method has become the gold standard for the comparison between measured and calculated absorbed dose distributions. However, test criteria and failure rate tolerance levels have hitherto normally been based on empirical evidence, rather than rigorous statistical analysis. In this work, it is proposed that the gamma-evaluation method could be reinterpreted such that the absorbed dose difference and distance-to-agreement criteria are replaced by the standard deviations of the associated uncertainties. By comparison between absorbed dose calculations and simulated measurements for clinically realistic test cases in 1D and 2D, it is then shown that the resulting squared gamma distribution follows a chi-squared distribution with one degree of freedom. This result can be used to test the statistical significance of measured deviations, and to determine proper failure rate tolerance levels in clinical radiotherapy quality control.
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25.
  • Ceberg, Crister, et al. (författare)
  • A stochastic model for subcellular dosimetry in boron neutron capture therapy
  • 1995
  • Ingår i: Physics in Medicine and Biology. - : IOP Publishing. - 1361-6560 .- 0031-9155. ; 40:11, s. 1819-1830
  • Tidskriftsartikel (refereegranskat)abstract
    • The therapeutic effectiveness of boron neutron capture therapy is highly dependent on the microscopic distribution of the administered boron compound. Two boron compounds with different uptake mechanisms in the tumour cells may thus cause effects of different degrees even if the macroscopic boron concentrations in the tumour tissue are the same. This difference is normally expressed quantitatively by the so-called relative local efficiency (RLE). In this work, a stochastic model for the subcellular dosimetry has been developed. This model can be used to calculate the probability for an energy deposition above a certain threshold level in the cell nucleus due to a single neutron capture reaction. If a threshold cell-kill function is assumed, and if the dose is low enough that multiple energy depositions are rare, the model can also be applied to calculations of the survival probability for a cell population. Subcellular boron distributions in rats carrying RG 2 rat gliomas were measured by subcellular fractionation after administration of two different boron compounds: a sulphydryl boron hydride (BSH) and a boronated porphyrin (BOPP). Based on these data, the RLE factors were then calculated for these compounds using the stochastic model.
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26.
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27.
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28.
  • Ceberg, Crister, et al. (författare)
  • Enhanced boron uptake in RG 2 rat gliomas by electropermeabilization in vivo--a new possibility in boron neutron capture therapy
  • 1994
  • Ingår i: Anti-Cancer Drugs. - 0959-4973. ; 5:4, s. 463-466
  • Tidskriftsartikel (refereegranskat)abstract
    • Accumulation of boron in tumor tissue is an indispensable requirement for boron neutron capture therapy and it is important that the uptake is as high as possible. In this work we have studied the influence of electropermeabilization in vivo on the uptake of boron in normal and RG 2 glioma bearing Fischer 344 rats. Two different boron compounds, a sulfhydryl boron hydride (BSH) and a boronated porphyrin (BOPP), have been investigated. The rats were infused intravenously during 5 min with 175 micrograms BSH/g body weight or 12 micrograms BOPP/g body weight. Two electrodes were placed 5 mm apart in the brain and electropermeabilization was performed with eight square 400 V pulses at 4 and 7 min after the end of the infusion. After 6 h the animals were killed, and the boron content in the tumors and the surrounding brain was measured with neutron-activated autoradiography. In electropermeabilized healthy animals the BOPP uptake was low and limited to the electrode lesions, whereas BSH was spread extensively throughout the hemisphere. Rats with gliomas showed doubled (BOPP) to 10-fold (BSH) uptake of boron in the tumor when electropermeabilization was performed as compared with untreated animals. We conclude that electropermeabilization in the future may provide an interesting possibility to increase the uptake of certain boron compounds before neutron capture therapy.
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29.
  • Ceberg, Crister, et al. (författare)
  • Neutron capture imaging of 10B in tissue specimens
  • 1993
  • Ingår i: Radiotherapy and Oncology. - 1879-0887. ; 26:2, s. 139-146
  • Tidskriftsartikel (refereegranskat)abstract
    • Boron Neutron Capture Therapy (BNCT) is an attractive concept for radiation treatment of malignant tumours. The patients receive a 10B-carrying compound with selective uptake in tumour cells, after which they are irradiated with epithermal neutrons. Theoretically, the tumour cells are killed by the high-LET particles produces in 10B(n, alpha)7Li reactions inside or close to the cell nucleus, while healthy brain cells with no boron uptake will be spared. In practice, a successful BNCT depends on the actual boron-distribution in the tissue, and consequently a new boron-compound aimed for BNCT must undergo detailed bio-distribution studies before clinical trials. In experimental work there is accordingly a great need for methods for quantitative bio-distribution measurements in tissue samples. In this paper we present an improved technique for neutron activated autoradiography providing quantitative boron images of freeze-sectioned tissue specimens from highly malignant rat brain gliomas. Particular attention has been paid to the correlation with the morphology of the specimens and to the altered self-absorption properties due to freeze-drying. A self-absorption correction factor for tumour tissue has been experimentally determined.
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30.
  • Ceberg, Crister, et al. (författare)
  • Performance of sulfhydryl boron hydride in patients with grade III and IV astrocytoma: a basis for boron neutron capture therapy
  • 1995
  • Ingår i: Journal of Neurosurgery. - 0022-3085. ; 83:1, s. 79-85
  • Tidskriftsartikel (refereegranskat)abstract
    • This study investigated the rationale of boron neutron capture therapy (BNCT) for the treatment of Grade III and IV astrocytoma. The European Community joint research program on BNCT plans to use sulfhydryl boron hydride (BSH) in clinical trials. The work presented here, examines the performance of BSH in eight patients with Grade III and IV astrocytoma using a measurement technique which precisely correlates the boron uptake with the histology of the tumor and the peritumoral brain. Astrocytomas are exceptionally heterogeneous and spread migrating tumor cells into the surrounding brain. The patients were infused with 50 mg BSH per kilogram of body weight at 12, 18, 24 or 48 hours before surgery. At the time of operation, specimens were obtained of the tumor, skin, muscle, dura, blood, urine, and, when surgically possible, the brain adjacent to tumor. In three patients the intracellular boron distribution was investigated by subcellular fractionation. The blood clearance was biphasic with half-lives of 0.6 and 8.2 hours. After 3 days, approximately 70% of the dose injected was excreted in the urine. The maximum boron concentration in the tumor was 20 ppm, 12 hours after the infusion. The tumor-to-blood ratios ranged between 0.2 and 1.4, with the highest values after 18 to 24 hours. In the brain specimens the boron concentration never exceeded 1 ppm. This work confirms a selective uptake of boron in the tumor compared to the surrounding brain and that boron, to some extent, is incorporated in the tumor cells.
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31.
  • Ceberg, Crister, et al. (författare)
  • Photon activation therapy of RG2 glioma carrying Fischer rats using stable thallium and monochromatic synchrotron radiation.
  • 2012
  • Ingår i: Physics in Medicine and Biology. - : IOP Publishing. - 1361-6560 .- 0031-9155. ; 57:24, s. 8377-8391
  • Tidskriftsartikel (refereegranskat)abstract
    • 75 RG2 glioma-carrying Fischer rats were treated by photon activation therapy (PAT) with monochromatic synchrotron radiation and stable thallium. Three groups were treated with thallium in combination with radiation at different energy; immediately below and above the thallium K-edge, and at 50 keV. Three control groups were given irradiation only, thallium only, or no treatment at all. For animals receiving thallium in combination with radiation to 15 Gy at 50 keV, the median survival time was 30 days, which was 67% longer than for the untreated controls (p = 0.0020) and 36% longer than for the group treated with radiation alone (not significant). Treatment with thallium and radiation at the higher energy levels were not effective at the given absorbed dose and thallium concentration. In the groups treated at 50 keV and above the K-edge, several animals exhibited extensive and sometimes contra-lateral edema, neuronal death and frank tissue necrosis. No such marked changes were seen in the other groups. The results were discussed with reference to Monte Carlo calculated electron energy spectra and dose enhancement factors.
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32.
  • Ceberg, Crister, et al. (författare)
  • Prediction of stopping-power ratios in flattening-filter free beams.
  • 2010
  • Ingår i: Medical Physics. - : Wiley. - 0094-2405. ; 37:3, s. 1164-1168
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: In recent years, there has been an increasing interest in flattening-filter free (FFF) beams. However, since the removal of the flattening filter will affect both the mean and the variance of the energy spectrum, current beam-quality specifiers may not be adequate for reference dosimetry in such beams. The purpose of this work was to investigate an alternative, more general beam-quality specifier. METHODS: The beam-quality specifier used in this work was a combination of the kerma-weighted mean and the coefficient of variation of the linear attenuation coefficient in water. These parameters can in theory be determined from narrow-beam transmission measurements using a miniphantom "in-air," which is a measurement condition well suited also to small and nonstandard fields. The relation between the Spencer-Attix stopping-power ratios and this novel beam-quality specifier was described by a simple polynomial. For reference, the authors used Monte Carlo calculated spectra and stopping-power data for nine different beams, with and without flattening filter. RESULTS: The polynomial coefficients were obtained by least-squares optimization. For all beams included in this investigation, the average of the differences between the predicted and the Monte Carlo calculated stopping-power ratios was 0.02 +/- 0.17% (1 SD) (including TomoTherapy and CyberKnife example beams). CONCLUSIONS: An alternative dual-parameter beam-quality specifier was investigated. The evaluation suggests that it can be used successfully to predict stopping-power ratios in FFF as well as conventional beams, regardless of filtration.
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33.
  • Ceberg, Crister, et al. (författare)
  • The effects of divergence and nonuniformity on the x-ray pencil-beam dose kernel
  • 1996
  • Ingår i: Medical Physics. - : Wiley. - 0094-2405. ; 23:9, s. 1531-1535
  • Tidskriftsartikel (refereegranskat)abstract
    • The scattered-photon part of pencil-beam dose kernels for high-energy x-ray beams can be derived experimentally by differentiating the broad-beam scatter-to-primary dose ratio as a function of radius. Formally, this requires a uniform and parallel beam, and the procedure is complicated by the nonideal, actual beam conditions: the primary dose profile is not uniform, the beam quality is not constant, and the distance to the source is not infinite. The experimentally determined scatter-to-primary ratios can be corrected for these effects before they are differentiated to give the pencil-beam kernels. The correction factors were calculated and shown to reach as much as 5% of the true scatter-to-primary ratio. The effect on the pencil beam was evaluated and corrected pencil beams were determined.
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34.
  • Chakwizira, Arthur, et al. (författare)
  • Mathematical modelling of the synergistic combination of radiotherapy and indoleamine-2,3-dioxygenase (IDO) inhibitory immunotherapy against glioblastoma
  • 2018
  • Ingår i: British Journal of Radiology. - : British Institute of Radiology. - 0007-1285 .- 1748-880X. ; 91:1087
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Recent research has shown that combining radiotherapy and immunotherapy can counteract the ability of cancer to evade and suppress the native immune system. To optimise the synergy of the combined therapies, factors such as radiation dose and fractionation must be considered, alongside numerous parameters resulting from the complexity of cancer-immune system interactions. It is instructive to use mathematical models to tackle this problem. Methods: In this work, we adapted a model primarily to describe the synergistic effect between single-fraction radiotherapy and immunotherapy (1-methyl tryptophan) observed in previous experiments with glioblastoma-carrying rats. We also showed how the model can be used to generate hypotheses on the outcome of other treatment fractionation schemes. Results: The model successfully reproduced the results of the experiments. Moreover, it provided support for the hypothesis that, for a given biologically effective dose, the efficacy of the combination therapy and the synergy between the two therapies are favoured by the administration of radiotherapy in a hypofractionated regime. Furthermore, for a double-fraction irradiation regimen, the synergy is favoured by a short time interval between the treatment fractions. Conclusion: It was concluded that the model could be fitted to reproduce the experimental data well within its uncertainties. It was also demonstrated that the fitted model can be used to form hypotheses to be validated by further pre-clinical experiments. Advances in knowledge: The results of this work support the hypothesis that the synergetic action of combined radiotherapy and immunotherapy is favoured by using a hypofractionated radiation treatment regimen, given over a short time interval.
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35.
  • Cheng, Chee-Wai, et al. (författare)
  • Dosimetric comparison of treatment planning systems in irradiation of breast with tangential fields
  • 1997
  • Ingår i: International Journal of Radiation Oncology, Biology, Physics. - 0360-3016. ; 38:4, s. 835-842
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: The objectives of this study are: (1) to investigate the dosimetric differences of the different treatment planning systems (TPS) in breast irradiation with tangential fields, and (2) to study the effect of beam characteristics on dose distributions in tangential breast irradiation with 6 MV linear accelerators from different manufacturers. METHODS AND MATERIALS: Nine commercial and two university-based TPS are evaluated in this study. The computed tomographic scan of three representative patients, labeled as "small", "medium" and "large" based on their respective chest wall separations in the central axis plane (CAX) were used. For each patient, the tangential fields were set up in each TPS. The CAX distribution was optimized separately with lung correction, for each TPS based on the same set of optimization conditions. The isodose distributions in two other off-axis planes, one 6 cm cephalic and the other 6 cm caudal to the CAX plane were also computed. To investigate the effect of beam characteristics on dose distributions, a three-dimensional TPS was used to calculate the isodose distributions for three different linear accelerators, the Varian Clinac 6/100, the Siemens MD2 and the Philips SL/7 for the three patients. In addition, dose distributions obtained with 6 MV X-rays from two different accelerators, the Varian Clinac 6/100 and the Varian 2100C, were compared. RESULTS: For all TPS, the dose distributions in all three planes agreed qualitatively to within +/- 5% for the "small" and the "medium" patients. For the "large" patient, all TPS agreed to within +/- 4% on the CAX plane. The isodose distributions in the caudal plane differed by +/- 5% among all TPS. In the cephalic plane in which the patient separation is much larger than that in the CAX plane, six TPS correctly calculated the dose distribution showing a cold spot in the center of the breast contour. The other five TPS showed that the center of the breast received adequate dose. Isodose distributions for 6 MV X-rays from three different accelerators differed by about +/- 3% for the "small" patient and more than +/- 5% for the "large" patient. For two different 6 MV machines of the same manufacturer, the isodose distribution agreed to within +/- 2% for all three planes for the "large" patient. CONCLUSION: The differences observed among the various TPS in this study were within +/- 5% for both the "small" and the "medium" patients while doses at the hot spot exhibit a larger variation. The large discrepancy observed in the off-axis plane for the "large" patient is largely due to the inability of most TPS to incorporate the collimator angles in the dose calculation. Only six systems involved agreed to within +/- 5% for all three patients in all calculation planes. The difference in dose distributions obtained with three accelerators from different manufacturers is probably due to the difference in beam profiles. On the other hand, the 6 MV X-rays from two different models of linear accelerators from the same manufacturer have similar beam characteristics and the dose distributions are within +/- 2% of each other throughout the breast volume. In general, multi-institutional breast treatment data can be compared within a +/- 5% accuracy.
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36.
  • Dalaryd, Mårten, et al. (författare)
  • A Monte Carlo study of a flattening filter-free linear accelerator verified with measurements.
  • 2010
  • Ingår i: Physics in Medicine and Biology. - : IOP Publishing. - 1361-6560 .- 0031-9155. ; 55:23, s. 7333-7344
  • Tidskriftsartikel (refereegranskat)abstract
    • A Monte Carlo model of an Elekta Precise linear accelerator has been built and verified by measured data for a 6 and 10 MV photon beam running with and without a flattening filter in the beam line. In this study the flattening filter was replaced with a 6 mm thick copper plate, provided by the linac vendor, in order to stabilize the beam. Several studies have shown that removal of the filter improves some properties of the photon beam, which could be beneficial for radiotherapy treatments. The investigated characteristics of this new beam included output, spectra, mean energy, half value layer and the origin of scattered photons. The results showed an increased dose output per initial electron at the central axis of 1.76 and 2.66 for the 6 and 10 MV beams, respectively. The number of scattered photons from the accelerator head was reduced by (31.7 ± 0.03)% (1 SD) for the 6 MV beam and (47.6 ± 0.02)% for the 10 MV beam. The photon energy spectrum of the unflattened beam was softer compared to a conventional beam and did not vary significantly with the off-axis distance, even for the largest field size (0-20 cm off-axis).
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37.
  • Dalaryd, Mårten, et al. (författare)
  • Combining tissue-phantom ratios to provide a beam-quality specifier for flattening filter free photon beams.
  • 2014
  • Ingår i: Medical Physics. - : Wiley. - 0094-2405. ; 41:11
  • Tidskriftsartikel (refereegranskat)abstract
    • There are currently several commercially available radiotherapy treatment units without a flattening filter in the beam line. Unflattened photon beams have an energy and lateral fluence distribution that is different from conventional beams and, thus, their attenuation properties differ. As a consequence, for flattening filter free (FFF) beams, the relationship between the beam-quality specifier TPR20,10 and the Spencer-Attix restricted water-to-air mass collision stopping-power ratios, L̄/ρair (water), may have to be refined in order to be used with equivalent accuracy as for beams with a flattening filter. The purpose of this work was twofold. First, to study the relationship between TPR20,10 and L̄/ρair (water) for FFF beams, where the flattening filter has been replaced by a metal plate as in most clinical FFF beams. Second, to investigate the potential of increasing the accuracy in determining L̄/ρair (water) by adding another beam-quality metric, TPR10,5. The relationship between L̄/ρair (water) and %dd(10)x for beams with and without a flattening filter was also included in this study.
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38.
  • Ericsson-Szecsenyi, Rebecka, et al. (författare)
  • Robustness Assessment of Images From a 0.35T Scanner of an Integrated MRI-Linac : Characterization of Radiomics Features in Phantom and Patient Data
  • 2022
  • Ingår i: Technology in Cancer Research and Treatment. - : SAGE Publications. - 1533-0346 .- 1533-0338. ; 21
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: Radiomics entails the extraction of quantitative imaging biomarkers (or radiomics features) hypothesized to provide additional pathophysiological and/or clinical information compared to qualitative visual observation and interpretation. This retrospective study explores the variability of radiomics features extracted from images acquired with the 0.35 T scanner of an integrated MRI-Linac. We hypothesized we would be able to identify features with high repeatability and reproducibility over various imaging conditions using phantom and patient imaging studies. We also compared findings from the literature relevant to our results. Methods: Eleven scans of a Magphan® RT phantom over 13 months and 11 scans of a ViewRay Daily QA phantom over 11 days constituted the phantom data. Patient datasets included 50 images from ten anonymized stereotactic body radiation therapy (SBRT) pancreatic cancer patients (50 Gy in 5 fractions). A True Fast Imaging with Steady-State Free Precession (TRUFI) pulse sequence was selected, using a voxel resolution of 1.5 mm × 1.5 mm × 1.5 mm and 1.5 mm × 1.5 mm × 3.0 mm for phantom and patient data, respectively. A total of 1087 shape-based, first, second, and higher order features were extracted followed by robustness analysis. Robustness was assessed with the Coefficient of Variation (CoV < 5%). Results: We identified 130 robust features across the datasets. Robust features were found within each category, except for 2 second-order sub-groups, namely, Gray Level Size Zone Matrix (GLSZM) and Neighborhood Gray Tone Difference Matrix (NGTDM). Additionally, several robust features agreed with findings from other stability assessments or predictive performance studies in the literature. Conclusion: We verified the stability of the 0.35 T scanner of an integrated MRI-Linac for longitudinal radiomics phantom studies and identified robust features over various imaging conditions. We conclude that phantom measurements can be used to identify robust radiomics features. More stability assessment research is warranted.
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39.
  • Gabel, D, et al. (författare)
  • Pharmacokinetics of Na2B12H11SH (BSH) in patients with malignant brain tumours as prerequisite for a phase I clinical trial of boron neutron capture
  • 1997
  • Ingår i: Acta Neurochirurgica. - 0001-6268. ; 139:7, s. 606-612
  • Tidskriftsartikel (refereegranskat)abstract
    • The disposition of Na2B12H11SH (BSH) in patients with malignant glioma has been investigated, in preparation for a Phase I clinical trial of boron neutron capture therapy. BSH was found to possess a linear disposition over the dosage interval investigated (up to 75 mg/kg). A bi-phasic blood pharmacokinetics was observed. Tumour-to-blood ratios showed variations between patients between 0.08 and 5.1. The data allow the definition of amount of BSH and timing of infusion for a Phase I clinical trial protocol.
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40.
  • Gjaldbæk, Bolette W., et al. (författare)
  • Long-term toxicity and efficacy of FLASH radiotherapy in dogs with superficial malignant tumors
  • 2024
  • Ingår i: Frontiers in Oncology. - 2234-943X. ; 14, s. 01-09
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: FLASH radiotherapy (RT) has emerged as a promising modality, demonstrating both a normal tissue sparing effect and anticancer efficacy. We have previously reported on the safety and efficacy of single fraction FLASH RT in the treatment of oral tumors in canine cancer patients, showing tumor response but also a risk of radiation-induced severe late adverse effects (osteoradionecrosis) for doses ≥35 Gy. Accordingly, the objective in this study was to investigate if single fraction high dose FLASH RT is safe for treating non-oral tumors. Methods: Privately-owned dogs with superficial tumors or microscopic residual disease were included. Treatment was generally delivered as a single fraction of 15-35 Gy 10 MeV electron FLASH RT, although two dogs were re-irradiated at a later timepoint. Follow-up visits were conducted up to 12 months post-treatment to evaluate treatment efficiency and adverse effects. Results: Fourteen dogs with 16 tumors were included, of which nine tumors were treated for gross disease whilst seven tumors were treated post-surgery for microscopic residual disease. Four treatment sites treated with 35 Gy had ulceration post irradiation, which was graded as severe adverse effect. Only mild adverse effects were observed for the remaining treatment sites. None of the patients with microscopic disease experienced recurrence (0/7), and all patients with macroscopic disease showed either a complete (5/9) or a partial response (4/9). Five dogs were euthanized due to clinical disease progression. Discussion: Our study demonstrates that single fraction high dose FLASH RT is generally safe, with few severe adverse effects, particularly in areas less susceptible to radiation-induced damage. In addition, our study indicates that FLASH has anti-tumor efficacy in a clinical setting. No osteoradionecrosis was observed in this study, although other types of high-grade adverse effects including ulcer-formations were observed for the highest delivered dose (35 Gy). Overall, we conclude that osteoradionecrosis following single fraction, high dose FLASH does not appear to be a general problem for non-oral tumor locations. Also, as has been shown previously for oral tumors, 30 Gy appeared to be the maximum safe dose to deliver with single fraction FLASH RT.
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41.
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42.
  • Johnsson, Stefan, et al. (författare)
  • Off-axis primary-dose measurements using a mini-phantom
  • 1997
  • Ingår i: Medical Physics. - : Wiley. - 0094-2405. ; 24:5, s. 763-767
  • Tidskriftsartikel (refereegranskat)abstract
    • The characterization of the incident photon beam is usually divided into its dependence on collimator setting (head-scatter factor) and off-axis position (primary off-axis ratio). These parameters are normally measured "in air" with a build-up cap thick enough to generate full dose build-up at the depth of dose maximum. In order to prevent any influence from contaminating electrons, it has been recommended that head-scatter measurements are carried out using a mini-phantom rather than a conventional build-up cap. Due to the volume of the mini-phantom, the effects from attenuation and scatter are not negligible. In relative head-scatter measurements these effects cancel and the head scatter is thus a good representation of the variation of the incident photon beam with collimator setting. However, in off-axis measurements, attenuation and scatter conditions vary due to beam softening and do not cancel in the calculation of the primary off-axis ratio. The purpose of the present work was to estimate the effects from attenuation and phantom scatter in order to determine their influence on primary off-axis ratio measurements. We have characterized the off-axis beam-softening effect by means of narrow-beam transmission measurements to obtain the effective attenuation coefficient as a function of off-axis position. We then used a semi-analytical expression for the phantom-scatter calculation that depends solely on this attenuation coefficient. The derived formalism for relative "in air" measurements using a mini-phantom is clear and consistent, which enables the user to separately calculate the effects from scatter and attenuation. For the investigated beam qualities, 6 and 18 MV, our results indicate that the effects from attenuation and scatter in the mini-phantom nearly cancel (the combined effect is less than 1%) within 12.5 cm from the central beam axis. Thus, no correction is needed when the primary off-axis ratio is measured with a mini-phantom.
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43.
  • Johnsson, Stefan, et al. (författare)
  • On beam quality and stopping power ratios for high-energy x-rays
  • 2000
  • Ingår i: Physics in Medicine and Biology. - : IOP Publishing. - 1361-6560 .- 0031-9155. ; 45:10, s. 2733-2745
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this work is to quantitatively compare two commonly used beam quality indices, IPR(20/10) and %dd(10)x, with respect to their ability to predict stopping power ratios (water to air), s(w,air), for high-energy x-rays. In particular, effects due to a varied amount of filtration of the photon beam will be studied. A new method for characterizing beam quality is also presented, where the information we strive to obtain is the moments of the spectral distribution. We will show how the moments enter into a general description of the transmission curve and that it is possible to correlate the moments to s(w,air) with a unique and simple relationship. Comparisons with TPR(20/10) and %dd(10), show that the moments are well suited for beam quality specification in terms of choosing the correct s(w,air).
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44.
  • Johnsson, Stefan, et al. (författare)
  • Transmission measurements in air using the ESTRO mini-phantom
  • 1999
  • Ingår i: Physics in Medicine and Biology. - 1361-6560. ; 44:10, s. 2445-2450
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this work is to study the possibility of using the ESTRO mini-phantom for transmission measurements of primary kerma in water at a point free in air. We discuss in-air measurements in general, with special attention given to in-air equivalent measurements using a water equivalent mini-phantom. The study includes four different photon energies (4, 6, 10 and 18 MV), where scoring of dose and primary kerma inside a mini-phantom in narrow beam geometry is performed with the Monte Carlo code EGS4. The results reveal that relative measurements (i.e. with and without a water absorber present) at 10 cm depth in a mini-phantom do not represent the variation of primary kerma in water at a point free in air (deviations as large as 7% at 4 MV are observed). Minimum deviations are obtained at depths somewhat larger than the depth of dose maximum. The observed deviations are due to a considerable beam hardening in the water absorber, which changes the amount of attenuation and scatter inside the mini-phantom.
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45.
  • Khazaei, Somayeh, et al. (författare)
  • Research Paper Impact of combining vitamin C with radiation therapy in human breast cancer : Does it matter?
  • 2022
  • Ingår i: Oncotarget. - 1949-2553. ; 13:1, s. 439-453
  • Tidskriftsartikel (refereegranskat)abstract
    • Vitamin C may impact the efficiency of radiation therapy (RT) in breast cancer. The effects of RT alone or in combination with vitamin C in SKBR3, MDA-MB-231, and MCF7 cells were compared using clonogenic assay, proliferation assay (MTT), cell cycle analysis, and Western blot. Vitamin C use was assessed in 1803 breast cancer patients 2002–2017 in relation to clinicopathological features and recurrences after RT. Vitamin C combined with RT resulted in non-significant increases in colony formation and minor differences in cell cycle arrest and expression of studied proteins, compared to RT alone. Lower vitamin C doses alone or in combination with RT, resulted in higher proliferation with MTT than higher vitamin C doses in a cell line-dependent manner. Vitamin C use was associated with lower histological grade and BMI but not recurrence risk in RT-treated patients (LogRank P = 0.54). Vitamin C impacted RT efficiency differently depending on breast cancer subtype and vitamin C concentration. Lower doses of vitamin C, achievable with oral administration, might increase breast cancer cell proliferation and decrease radiosensitivity. Despite vitamin C users having less aggressive tumors than non-users, the recurrence risk in RT-treated patients was similar in vitamin C users and non-users.
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46.
  • Knöös, Tommy, et al. (författare)
  • Independent checking of the delivered dose for high-energy X-rays using a hand-held PC
  • 2001
  • Ingår i: Radiotherapy and Oncology. - 1879-0887. ; 58:2, s. 201-208
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and purpose: The requirements on the delivered dose in radical radiation therapy are extremely high. The dose should be within a few percent and also delivered with high accuracy in space. Vendors and users have successfully managed to implement radiation therapy systems, which are able to achieve these demands with high accuracy and reproducibility. These systems include computerized tomography scanners, treatment planning systems, simulators, treatment machines, and record and verify systems. More and more common are also computer networks to assure data integrity when transferring information between the systems. Even if these systems are commissioned and kept under quality assurance programs to maintain their accuracy, errors may be introduced. Especially, the human factor is an uncontrolled parameter that may introduce errors. Thus, unintentional changes or incorrect handling of data may occur during clinical use of the equipment. Having an independent dose calculation system implemented in the daily quality assurance process may assure a high quality of treatments and avoidance of severe errors.Materials and methods: To accomplish this, a system of equations for calculating the absorbed dose to the prescription point from the set-up information, has been compiled into a dose-calculation engine. The model is based on data completely independent of the treatment planning system (TPS). The fundamental parameter in the dose engine is the linear attenuation coefficient for the primary photons. This parameter can readily be determined experimentally. The dose calculation engine has been programmed into a hand-held PC allowing direct calculation of the dose to the prescription point when the first treatment is delivered to the patient.Results and conclusion: The model is validated with measurements and is shown to be within +/-1.0% (1 SD). Comparison against a state-of-the-art TPS shows an average difference of 0.3% with a standard deviation of +/-2.1%. An action level covering 95% of the cases has been chosen, i.e. +/-4.0%. Deviations larger than this are with a high probability due to erroneous handling of the patient set-up data. This system has been implemented into the daily clinical quality control program.
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47.
  •  
48.
  • Konradsson, Elise, et al. (författare)
  • Beam control system and output fine-tuning for safe and precise delivery of FLASH radiotherapy at a clinical linear accelerator
  • 2024
  • Ingår i: Frontiers in Oncology. - 2234-943X. ; 14
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: We have previously adapted a clinical linear accelerator (Elekta Precise, Elekta AB) for ultra-high dose rate (UHDR) electron delivery. To enhance reliability in future clinical FLASH radiotherapy trials, the aim of this study was to introduce and evaluate an upgraded beam control system and beam tuning process for safe and precise UHDR delivery. Materials and Methods: The beam control system is designed to interrupt the beam based on 1) a preset number of monitor units (MUs) measured by a monitor detector, 2) a preset number of pulses measured by a pulse-counting diode, or 3) a preset delivery time. For UHDR delivery, an optocoupler facilitates external control of the accelerator’s thyratron trigger pulses. A beam tuning process was established to maximize the output. We assessed the stability of the delivery, and the independent interruption capabilities of the three systems (monitor detector, pulse counter, and timer). Additionally, we explored a novel approach to enhance dosimetric precision in the delivery by synchronizing the trigger pulse with the charging cycle of the pulse forming network (PFN). Results: Improved beam tuning of gun current and magnetron frequency resulted in average dose rates at the dose maximum at isocenter distance of >160 Gy/s or >200 Gy/s, with or without an external monitor chamber in the beam path, respectively. The delivery showed a good repeatability (standard deviation (SD) in total film dose of 2.2%) and reproducibility (SD in film dose of 2.6%). The estimated variation in DPP resulted in an SD of 1.7%. The output in the initial pulse depended on the PFN delay time. Over the course of 50 measurements employing PFN synchronization, the absolute percentage error between the delivered number of MUs calculated by the monitor detector and the preset MUs was 0.8 ± 0.6% (mean ± SD). Conclusion: We present an upgraded beam control system and beam tuning process for safe and stable UHDR electron delivery of hundreds of Gy/s at isocenter distance at a clinical linac. The system can interrupt the beam based on monitor units and utilize PFN synchronization for improved dosimetric precision in the dose delivery, representing an important advancement toward reliable clinical FLASH trials.
  •  
49.
  • Konradsson, Elise, et al. (författare)
  • Comparable Long-Term Tumor Control for Hypofractionated FLASH Versus Conventional Radiation Therapy in an Immunocompetent Rat Glioma Model
  • 2022
  • Ingår i: Advances in Radiation Oncology. - : Elsevier BV. - 2452-1094. ; 7:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: To ensure a clinical translation of FLASH radiation therapy (FLASH-RT) for a specific tumor type, studies on tumor control and toxicity within the same biological system are needed. In this study, our objective was to evaluate tumor control and toxicity for hypofractionated FLASH-RT and conventional radiation therapy (CONV-RT) in an immunocompetent rat glioma model. Methods and Materials: Fisher 344 rats (N = 68) were inoculated subcutaneously with NS1 glioma cells and randomized into groups (n = 9-10 per group). CONV-RT (∼8 Gy/min) or FLASH-RT (70-90 Gy/s) was administered in 3 fractions of either 8 Gy, 12.5 Gy, or 15 Gy using a 10-MeV electron beam. The maximum tumor diameter was measured weekly, and overall survival was determined until day 100. Long-term tumor control was defined as no evident tumor on day 100. Animals were evaluated for acute dermal side effects at 2 to 5 weeks after completed RT and for late dermal side effects at 3 months after initiation of treatment. Results: Survival was significantly increased in all irradiated groups compared with control animals (P <.001). In general, irradiated tumors started to shrink at 1 week post–completed RT. In 40% (23 of 58) of the irradiated animals, long-term tumor control was achieved. Radiation-induced skin toxic effects were mild and consisted of hair loss, erythema, and dry desquamation. No severe toxic effect was observed. There was no significant difference between FLASH-RT and CONV-RT in overall survival, acute side effects, or late side effects for any of the dose levels. Conclusions: This study shows that hypofractionated FLASH-RT results in long-term tumor control rates similar to those of CONV-RT for the treatment of large subcutaneous glioblastomas in immunocompetent rats. Neither treatment technique induced severe skin toxic effects. Consequently, no significant difference in toxicity could be resolved, suggesting that higher doses may be required to detect a FLASH sparing of skin.
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50.
  • Konradsson, Elise, et al. (författare)
  • Correction for Ion Recombination in a Built-in Monitor Chamber of a Clinical Linear Accelerator at Ultra-High Dose Rates
  • 2020
  • Ingår i: Radiation Research. - 0033-7587. ; 194:6, s. 580-586
  • Tidskriftsartikel (refereegranskat)abstract
    • In the novel and promising radiotherapy technique known as FLASH, ultra-high dose-rate electron beams are used. As a step towards clinical trials, dosimetric advances will be required for accurate dose delivery of FLASH. The purpose of this study was to determine whether a built-in transmission chamber of a clinical linear accelerator can be used as a real-Time dosimeter to monitor the delivery of ultra-high-dose-rate electron beams. This was done by modeling the drop-in ion-collection efficiency of the chamber with increasing dose-per-pulse values, so that the ion recombination effect could be considered. The raw transmission chamber signal was extracted from the linear accelerator and its response was measured using radiochromic film at different dose rates/dose-per-pulse values, at a source-To-surface distance of 100 cm. An increase of the polarizing voltage, applied over the transmission chamber, by a factor of 2 and 3, improved the ion-collection efficiency, with corresponding increased efficiency at the highest dose-per-pulse values by a factor 1.4 and 2.2, respectively. The drop-in ion-collection efficiency with increasing dose-per-pulse was accurately modeled using a logistic function fitted to the transmission chamber data. The performance of the model was compared to that of the general theoretical Boag models of ion recombination in ionization chambers. The logistic model was subsequently used to correct for ion recombination at dose rates ranging from conventional to ultra-high, making the transmission chamber useful as a real-Time monitor for the dose delivery of FLASH electron beams in a clinical setup.
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