| 1. |
- Sjöholm, H, et al.
(författare)
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Necrosis of malignant gliomas after intratumoral injection of 201Tl in vivo in the rat
- 1995
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Ingår i: Anti-Cancer Drugs. - 0959-4973. ; 6:1, s. 109-114
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Tidskriftsartikel (refereegranskat)abstract
- Fourteen adult Fischer 344 rats were inoculated in vivo unilaterally in the caudate nucleus in the brain with malignant RG 2 glioma cells. By 3 weeks a tumor with a diameter of 3-6 mm normally develops. Ten animals which survived the repeated periods of anesthesia and thallium (Tl) injections (intratumorally three times of 201Tl, 15-23 days after inoculation) showed a prolonged retention of radioactivity at the site of injection with no uptake in other organs except for the kidneys. Singular circumscribed necroses were found post-mortem at the site of injection, comprising malignant glioma tumor tissue, which in six animals was absent, in three animals was markedly reduced in size compared with controls and in one animal had the expected size. In four animals metastases were found in distant locations in the brain; in three of these cases there was a retention of radioactivity in the tumor. The selective necrotizing effect on the tumor cells is interpreted as mainly due to emission of Auger electrons from intracellularly accumulated 201Tl, giving rise to very high energy deposition in the vicinity of the cell nucleus. The results should also have implications for the treatment of human malignant gliomas.
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| 2. |
- Capala, J, et al.
(författare)
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Boron neutron capture therapy for glioblastoma multiforme : Clinical studies in Sweden
- 2003
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Ingår i: Journal of Neuro-Oncology. - 1573-7373. ; 62:1, s. 135-144
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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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| 3. |
- Munck af Rosenschöld, Per, et al.
(författare)
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Current status of dosimetry at the boron neutron capture therapy facility at Studsvik, Sweden
- 2002
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Ingår i: Research and Development in Neutron Capture Therapy. - 9788832329094 ; , s. 437-441
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Konferensbidrag (refereegranskat)abstract
- The beam was successfully characterized in air and in phantom using various radiation dosimeter:,. The determination of the thermal neutron and photon components of the mixed beam in phantom can be determined with acceptable uncertainties, while the uncertainty of the high-energy neutron component is considerable but of limited clinical significance. The beam intensity is sufficiently high for reasonably short treatment times. A novel approach to in-vivo dosimetry and quality assurance of treatment time in terms of monitor units was introduced in order to comply with national regulations regarding radiation therapy.
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| 4. |
- Persson, Bertil R, et al.
(författare)
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Survival of rats with N29 brain tumours after irradiation with 5 or 15 Gy and immunization with IFN-gamma secreting tumour cells
- 2008
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Ingår i: BioMedical Engineering and Informatics : New Development and the Future - Proceedings of the 1st International Conference on BioMedical Engineering and Informatics, BMEI 2008 - New Development and the Future - Proceedings of the 1st International Conference on BioMedical Engineering and Informatics, BMEI 2008. - 9780769531182 ; 2, s. 243-247
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Konferensbidrag (refereegranskat)abstract
- Intra cerebral tumours were inoculated into the brain of Fischer-344 syngeneic rats. After one week they were treated with either 5 or 15 Gy of Co-60-gamma radiation. The first immunization was given 1 hour before the radiation treatment and then two more times with 14-day intervals. Immunization was performed with 3 x 10(6) radiation sterilized IFN-gamma secreting tumour cells (N29) injected intraperitoneally. Neither radiation therapy with 5 or 15 Gy nor immunization with N29 cells alone had any significant effect on the length of survival of N29 tumour bearing rats. But radiation therapy with 5 Gy combined with immunization with IFN-gamma secreting syngeneic N29 cells resulted in 63 % complete remissions and significantly (p < 0.05) increased survival for the tumour bearing rats. Corresponding combination with 15 Gy RT resulted in 50% complete remissions. There is a possibility of a synergistic effect by optimal combination of radiation therapy and immunization.
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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. |
- 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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| 7. |
- 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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| 8. |
- Ahlstedt, Jonatan, et al.
(författare)
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Growth pattern of experimental glioblastoma
- 2020
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Ingår i: Histology and Histopathology. - 1699-5848. ; 35:8, s. 871-886
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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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| 9. |
- Børresen, Betina, et al.
(författare)
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Evaluation of single-fraction high dose FLASH radiotherapy in a cohort of canine oral cancer patients
- 2023
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Ingår i: Frontiers in Oncology. - 2234-943X. ; 13, s. 1-10
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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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| 10. |
- Ceberg, Crister, et al.
(författare)
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Neutron capture imaging of 10B in tissue specimens
- 1993
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Ingår i: Radiotherapy and Oncology. - 1879-0887. ; 26:2, s. 139-146
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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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