| 1. |
- Edvardsson, Anneli, et al.
(författare)
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Motion induced interplay effects for VMAT radiotherapy
- 2018
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Ingår i: Physics in Medicine and Biology. - : IOP Publishing. - 0031-9155 .- 1361-6560. ; 63:8
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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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| 2. |
- Edvardsson, Anneli, et al.
(författare)
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Verification of motion induced thread effect during tomotherapy using gel dosimetry
- 2015
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Ingår i: 8th International Conference on 3D Radiation Dosimetry (IC3DDOSE). - : IOP Publishing. - 1742-6596 .- 1742-6588. ; 573, s. 012048-012048
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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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| 3. |
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| 4. |
- Adrian, Gabriel, et al.
(författare)
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Rescue Effect Inherited in Colony Formation Assays Affects Radiation Response
- 2018
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Ingår i: Radiation Research. - 0033-7587. ; 189:1, s. 44-52
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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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| 5. |
- Adrian, Gabriel, et al.
(författare)
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The FLASH effect depends on oxygen concentration
- 2019
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Ingår i: British Journal of Radiology. - : British Institute of Radiology. - 1748-880X .- 0007-1285. ; 93:1106
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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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| 6. |
- AHLSTEDT, JONATAN, et al.
(författare)
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Effect of Blockade of Indoleamine 2, 3-dioxygenase in Conjunction with Single Fraction Irradiation in Rat Glioma
- 2015
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Ingår i: Jacobs journal of radiation oncology. - 2376-9424. ; 2:3
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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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| 7. |
- Benedek, Hunor, et al.
(författare)
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The effect of prostate motion during hypofractionated radiotherapy can be reduced by using flattening filter free beams
- 2018
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Ingår i: Physics and imaging in radiation oncology. - : Elsevier BV. - 2405-6316. ; 6, s. 66-70
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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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| 8. |
- Chakwizira, Arthur, et al.
(författare)
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Mathematical modelling of the synergistic combination of radiotherapy and indoleamine-2,3-dioxygenase (IDO) inhibitory immunotherapy against glioblastoma
- 2018
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Ingår i: British Journal of Radiology. - : British Institute of Radiology. - 0007-1285 .- 1748-880X. ; 91:1087
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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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| 9. |
- Lempart, Michael, et al.
(författare)
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Modifying a clinical linear accelerator for delivery of ultra-high dose rate irradiation
- 2019
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Ingår i: Radiotherapy and Oncology. - : Elsevier BV. - 0167-8140. ; 139, s. 40-45
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The purpose of this study was to modify a clinical linear accelerator, making it capable of electron beam ultra-high dose rate (FLASH) irradiation. Modifications had to be quick, reversible, and without interfering with clinical treatments. Methods: Performed modifications: (1) reduced distance with three setup positions, (2) adjusted/optimized gun current, modulator charge rate and beam steering values for a high dose rate, (3) delivery was controlled with a microcontroller on an electron pulse level, and (4) moving the primary and/or secondary scattering foils from the beam path. Results: The variation in dose for a five-pulse delivery was measured to be 1% (using a diode, 4% using film) during 10 minutes after a warm-up procedure, later increasing to 7% (11% using film). A FLASH irradiation dose rate was reached at the cross-hair foil, MLC, and wedge position, with ≥30, ≥80, and ≥300 Gy/s, respectively. Moving the scattering foils resulted in an increased output of ≥120, ≥250, and ≥1000 Gy/s, at the three positions. The beam flatness was 5% at the cross-hair position for a 20 × 20 and a 10 × 10 cm2 area, with and without both scattering foils in the beam. The beam flatness was 10% at the wedge position for a 6 and 2.5 cm diametric area, with and without the scattering foils in the beam path. Conclusions: A clinical accelerator was modified to produce ultra-high dose rates, high enough for FLASH irradiation. Future work aims to fine-tune the dose delivery, using the on-board transmission chamber signal and adjusting the dose-per-pulse.
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| 10. |
- Mondlane, Gracinda, 1987-
(författare)
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Comparative study of Radiation Therapy of Targets in the Upper Abdomen with Photon- or Scanned Proton-beams
- 2017
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Recently, there has been an increase in the number of proton beam therapy (PBT) centers operating worldwide. For certain cases, proton beams have been shown to provide dosimetric and radiobiological advantages when used for cancer treatment, compared to the regular photon-beam based treatments. Under ideal circumstances, the dose given to the tissues surrounding a target can be reduced with PBT. The risk for side effects following treatment is then expected to decrease. Until present, mainly stationary targets, e.g. targets in the brain, have been treated with PBT. There is currently a growing interest to treat also target volumes in other parts of the body with PBT. However, there are sources of uncertainties, which must be more carefully considered when PBT is used, especially for PBT carried out with scanned proton beams. PBT is more sensitive to anatomical changes, e.g. organ motion or a variable gas content in the intestines, which requires that special precautions are taken prior to treating new tumour sites. In photon beam radiotherapy (RT) of moving targets, the main consequence of organ motion is the loss of sharpness of the dose gradients (dose smearing). When scanned proton beams are used, dose deformation caused by the fluctuations in the proton beam range, due to varying tissue heterogeneities (e.g., the ribs moving in and out of the beam path) and the so-called interplay effect, can be expected to impact the dose distributions in addition to the dose smearing. The dosimetric uncertainties, if not accounted for, may cause the planned and accurately calculated dose distribution to be distorted, compromising the main goal of RT of achieving the maximal local disease control while accepting certain risks for normal tissue complications.Currently there is a lack of clinical follow-up data regarding the outcome of PBT for different tumour sites, in particular for extra-cranial tumour sites in moving organs. On the other hand, the use of photon beams for this kind of cancer treatment is well-stablished. A treatment planning comparison between RT carried out with photons and with protons may provide guidelines for when PBT could be more suitable. New clinical applications of particle beams in cancer therapy can also be transferred from photon-beam treatments, for which there is a vast clinical experience. The evaluation of the different uncertainties influencing RT of different tumour sites carried out with photon- and with proton-beams, will hopefully create an understanding for the feasibility of treating cancers with scanned proton beams instead of photon beams. The comparison of two distinct RT modalities is normally performed by studying the dosimetric values obtained from the dose volume histograms (DVH). However, in dosimetric evaluations, the outcome of the treatments in terms of local disease control and healthy tissue toxicity are not estimated. In this regard, radiobiological models can be an indispensable tool for the prediction of the outcome of cancer treatments performed with different types of ionising radiation. In this thesis, different factors that should be taken into consideration in PBT, for treatments influenced by organ motion and density heterogeneities, were studied and their importance quantified.This thesis consists of three published articles (Articles I, II and III). In these reports, the dosimetric and biological evaluations of photon-beam and scanned proton-beam RT were performed and the results obtained were compared. The studies were made for two tumour sites influenced by organ motion and density changes, gastric cancer (GC) and liver metastases. For the GC cases, the impact of changes in tissue density, resulting from variable gas content (which can be observed inter-fractionally), was also studied. In this thesis, both conventional fractionations (implemented in the planning for GC treatments) and hypofractionated regimens (implemented in the planning for the liver metastases cases) were considered. In this work, it was found that proton therapy provided the possibility to reduce the irradiations of the normal tissue located near the target volumes, compared to photon beam RT. However, the effects of density changes were found to be more pronounced in the plans for PBT. Furthermore, with proton beams, the reduction of the integral dose given to the OARs resulted in reduced risks of treatment-induced secondary malignancies.
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