| 1. |
- Mannerberg, Annika, et al.
(författare)
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Surface guided electron FLASH radiotherapy for canine cancer patients
- 2023
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Ingår i: Medical Physics. - 0094-2405. ; 50:7, s. 4047-4054
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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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| 2. |
- 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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| 3. |
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| 4. |
- Haraldsson, André, et al.
(författare)
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Surface-guided tomotherapy improves positioning and reduces treatment time : A retrospective analysis of 16 835 treatment fractions
- 2020
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Ingår i: Journal of Applied Clinical Medical Physics. - : Wiley. - 1526-9914. ; 21:8, s. 139-148
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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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| 5. |
- Andersson, Jonas, 1975-, et al.
(författare)
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Artificial intelligence and the medical physics profession-A Swedish perspective
- 2021
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Ingår i: Physica Medica-European Journal of Medical Physics. - : Elsevier BV. - 1120-1797 .- 1724-191X. ; 88, s. 218-225
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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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| 6. |
- Mondlane, Gracinda, 1987-
(författare)
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Radiation therapy of upper gastrointestinal cancers with scanned proton beams : A treatment planning study
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Proton beam therapy (PBT), using scanned beams, is an emerging modality used for the treatment of cancer. The clinical advantages of PBT, compared to commonly used photon beam therapy, have been demonstrated in different studies. However, the techniques used for planning and delivering treatments with photon beams have gradually been improved over the years. With the introduction of PBT in the clinic, guidelines to select patients to photon- or proton-beam therapy are indispensable.A simple approach used for selecting patients for PBT is based on the patient age. The paediatric patient group is considered to be the most radiosensitive and, therefore, in larger need of RT techniques that provide improved sparing of the organs at risk (OARs). With the increasing number of cancer clinics with access to PBT, combined with the constant clinical need of reducing the frequency of acute and late toxicities, there has been an increased use of PBT also for adult patients. At present, there is only limited clinical follow-up data available regarding the outcome of PBT for different tumour sites, in particular for extra-cranial tumours. The use of photon beams for such cancer treatments is, on the other hand, well-established. Therefore, the expected benefit of using proton beams in cancer therapy can be translated from the results obtained in the clinical experience attained from photon-beam treatments. The evaluation of the different uncertainties influencing the radiotherapy (RT) of different tumour sites carried out with photon- or proton-beams, will also create an improved understanding of the feasibility of treating cancer with scanned proton beams instead of with photon beams. The comparison of two distinct RT modalities is normally performed by studying the calculated dose distributions superimposed on the patient CT images and by evaluating the dosimetric values obtained from the dose volume histograms (DVHs). The dosimetric evaluation can be complemented with treatment outcome predictions in terms of local disease control and normal tissue toxicity. 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. These estimates can in turn be used in the decision process for selecting patients for treatments with a specific RT modality.This thesis consists of five articles. In these studies, treatment plans for RT with scanned proton-beams have been prepared and compared with clinical plans used for photon-beam based RT. For this purpose, dosimetric and biological-model based evaluations of these plans were performed. These studies were carried out for two distinct upper gastrointestinal (GI) cancers, namely, gastric cancer (GC) and liver metastases. RT treatments with both conventional fractionation schemes (implemented in the planning for the GC treatments) and hypofractionated regimens (implemented in the planning for the liver metastases cases) were considered. For the GC cases, the impact of changes in tissue density, resulting from a variable gas content (which can be observed inter-fractionally), was investigated. Proton therapy was found to provide the possibility to reduce the doses given to normal tissues surrounding the target volumes, compared to photon RT. This dose reduction with PBT resulted in reduced risks for both treatment-induced normal tissue toxicities and secondary malignancies. The impact of the introduced density changes on the dose distributions were found to be more pronounced for the PBT plans, if plan robustness approaches were disregarded. The findings presented in this thesis can be of clinical importance in the selection process between different RT modalities.
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| 7. |
- Salford, Leif, et al.
(författare)
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A new brain tumour therapy combining bleomycin with in vivo electropermeabilization
- 1993
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Ingår i: Biochemical and Biophysical Research Communications. - : Elsevier BV. - 1090-2104 .- 0006-291X. ; 194:2, s. 938-943
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Tidskriftsartikel (refereegranskat)abstract
- The potentials of in vivo electropermeabilization in combination with bleomycin in brain tumor treatment have been explored. In the brain of normal Fischer 344 rats, 2 electrodes were placed 5 mm apart. Electropermeabilization was performed with 8 to 12 exponential 400 V pulses with a time constant of 325 microseconds. Some animals were given bleomycin i.v., 1mg/kg b.w., 4 minutes before electric pulses delivery. No adverse effects were recorded during the observation of the animals during the following month. The effect of bleomycin and electropermeabilization upon tumour growth was studied in rats with glioma cells (RG2) implanted in the head of the right caudate nucleus. Treatment was given at different time intervals after the implantation of tumor cells and the effect upon survival was studied. Bleomycin alone did not prolong the survival of the animals. On the contrary, bleomycin plus electropermeabilization on the 10th, 11th or 12th day after inoculation increased the survival time to almost double that of untreated animals. We conclude that this treatment may be of value in brain tumour therapy.
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| 8. |
- Adrian, Gabriel, et al.
(författare)
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Cancer Cells Can Exhibit a Sparing FLASH Effect at Low Doses Under Normoxic In Vitro-Conditions
- 2021
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Ingår i: Frontiers in Oncology. - : Frontiers Media SA. - 2234-943X. ; 11
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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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| 9. |
- 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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| 10. |
- 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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