| 1. |
- 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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| 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. |
- Gjaldbæk, Bolette W., et al.
(författare)
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Long-term toxicity and efficacy of FLASH radiotherapy in dogs with superficial malignant tumors
- 2024
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Ingår i: Frontiers in Oncology. - 2234-943X. ; 14, s. 01-09
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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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| 4. |
- Konradsson, Elise, et al.
(författare)
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Establishment and Initial Experience of Clinical FLASH Radiotherapy in Canine Cancer Patients
- 2021
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Ingår i: Frontiers in Oncology. - : Frontiers Media SA. - 2234-943X. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- FLASH radiotherapy has emerged as a treatment technique with great potential to increase the differential effect between normal tissue toxicity and tumor response compared to conventional radiotherapy. To evaluate the feasibility of FLASH radiotherapy in a relevant clinical setting, we have commenced a feasibility and safety study of FLASH radiotherapy in canine cancer patients with spontaneous superficial solid tumors or microscopic residual disease, using the electron beam of our modified clinical linear accelerator. The setup for FLASH radiotherapy was established using a short electron applicator with a nominal source-to-surface distance of 70 cm and custom-made Cerrobend blocks for collimation. The beam was characterized by measuring dose profiles and depth dose curves for various field sizes. Ten canine cancer patients were included in this initial study; seven patients with nine solid superficial tumors and three patients with microscopic disease. The administered dose ranged from 15 to 35 Gy. To ensure correct delivery of the prescribed dose, film measurements were performed prior to and during treatment, and a Farmer-type ion-chamber was used for monitoring. Treatments were found to be feasible, with partial response, complete response or stable disease recorded in 11/13 irradiated tumors. Adverse events observed at follow-up ranging from 3-6 months were mild and consisted of local alopecia, leukotricia, dry desquamation, mild erythema or swelling. One patient receiving a 35 Gy dose to the nasal planum, had a grade 3 skin adverse event. Dosimetric procedures, safety and an efficient clincal workflow for FLASH radiotherapy was established. The experience from this initial study will be used as a basis for a veterinary phase I/II clinical trial with more specific patient inclusion selection, and subsequently for human trials.
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| 5. |
- 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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| 6. |
- Munck af Rosenschöld, Per, et al.
(författare)
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Prompt gamma tomography during BNCT – a feasibility study
- 2006
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Ingår i: Journal of Instrumentation. - 1748-0221. ; 1
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Tidskriftsartikel (refereegranskat)abstract
- The success of clinical boron neutron capture therapy (BNCT) lies in the ability to manage the radiobiological effect on the tumour and healthy tissue, and thus, accurate dosimetry measurements is pertinent for each individual patient. In the present work we investigate the possibility of performing online prompt gamma tomography (PGT) during BNCT. A prototype detector system was constructed, which is in principle a pin-hole collimator with a HPGe crystal to be mounted on a C-bow device, with shielding of lithium-plastic and lead. The detector system was used to measure on a phantom placed in an epithermal neutron beam and on a 137Cs-source. The possibility of tomographic reconstruction using the detector system was tested on a phantom filled with a 131I-solution with a smaller sphere inserted containing a higher specific activity (ratio 10:1). The detector system was possible to operate up to about 6 × 108 cm-2 s-1 thermal neutron fluence at the peak in the phantom, at which time it was saturated. A 478 keV boron-peak was visible in the measured spectra but the signal-to-noise-ratio was rather low. No post-irradiation damage or neutron activation was detectable. A tomographic reconstruction of the phantom filled with 131I-solutions was performed using an algorithm developed in house and based on the MLEM method. The image quality is fairly good and the results provide a clear indication that the detector system can be used to obtain data that enables tomographic reconstruction. A spatial resolution of the detector system of about 2 cm was obtained from both the measurement on the 137Cs-source and the 131I-phantom. In conclusion, the presented feasibility study on a prototype PGT system is encouraging further studies specifically directed at improving the signal-to-noise-ratio in measurements in epithermal neutron beams.
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| 7. |
- Munck af Rosenschöld, Per, et al.
(författare)
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Quality assurance of patient dosimetry in boron neutron capture therapy
- 2004
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 43:4, s. 404-411
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Tidskriftsartikel (refereegranskat)abstract
- The verification of the correctness of planned and executed treatments is imperative for safety in radiotherapy. The purpose of the present work is to describe and evaluate the quality assurance (QA) procedures for patient dosimetry implemented at the boron neutron capture therapy (BNCT) facility at Studsvik, Sweden. The dosimetric complexity of the mixed neutron-photon field during BNCT suggests a careful verification of routine procedures, specifically the treatment planning calculations. In the present study, two methods for QA of patient dosimetry are presented. The first is executed prior to radiotherapy and involves an independent check of the planned absorbed dose to be delivered to a point in the patient for each treatment field. The second QA procedure involves in vivo dosimetry measurements using posttreatment activation analysis. Absorbed dose conversion factors taking the difference in material composition and geometry of the patient and the PMMA phantom used for reference dosimetry were determined using the Monte Carlo method. The agreement of the QA procedure prior to radiotherapy reveals an acceptably small deviation for 60 treatment fields of ±4.2% (1 SD), while the in vivo dosimetry method presented may benefit from improvements, as the deviations observed were quite substantial (±12%, 1 SD), and were unlikely to be due to actual errors in the clinical dosimetry.
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| 8. |
- Persson, Bertil R, et al.
(författare)
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“Abscopal” Effect of Radiation Therapy Combined with Immune-Therapy Using IFN-γ Gene Transfected Syngeneic Tumor Cells, in Rats with Bilateral Implanted N29 Tumors
- 2011
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Ingår i: ISRN Immunology. - : Hindawi Limited. - 2090-5645 .- 2090-5653. ; 2011
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Tidskriftsartikel (refereegranskat)abstract
- The tumor growth rate response was studied on N29 rat glioma tumor cells subcutaneously implanted on both hind legs of Fischer-344 rats. At around 30 days after inoculation, RT was given with 60Co gamma radiation with 4 daily fractions of 5 Gy only to the right-lateral tumors. At days 26, 42, and 54 after inoculation, immunization was performed with irradiated syngeneic IFNγ-gene transfected cells. Tumor growth rate (TGR % per day) of the right-lateral irradiated tumor was significantly decreased (P<0.01) after RT alone and with the combination of RT and immunization. But immunization alone gave no significant decrease of the TGR but significantly increased time of survival. The TGR of the unirradiated left-lateral tumors was significantly decreased (P<0.02) only in the group of rats treated with RT alone. It is apparent that tumor cells killed by the radiation mediate suppression of tumor cells outside the target area. This effect is called the abscopal effect.
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| 9. |
- Persson, Bertil R, et al.
(författare)
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Radiation immunomodulatory gene tumor therapy of rats with intracerebral glioma tumors.
- 2010
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Ingår i: Radiation Research. - 0033-7587. ; 173:4, s. 433-440
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Tidskriftsartikel (refereegranskat)abstract
- Single-fraction radiation therapy with 5 or 15 Gy (60)Co gamma radiation was combined with intraperitoneal injections of syngeneic interferon gamma (IFN-gamma)-transfected cells in rats with intracerebral N29 or N32 glioma tumors at days 7, 21 and 35 after inoculation. For intracerebral N29 tumors, single-fraction radiation therapy with 5 or 15 Gy had no significant effect on the survival time. Immunization with IFN-gamma-transfected N29 cells significantly increased the survival time by 61%. Single-fraction radiation therapy with 5 Gy combined with immunization increased the survival time significantly by 87% and complete remissions by 75% while with 15 Gy the survival time increased 45% with 38% complete remissions. For intracerebral N32 tumors, single-fraction radiation therapy with 15 Gy increased the survival time significantly by 20%. Immunization by itself had no significant effect with IFN-gamma-transfected N32 cells, but combined with 15 Gy single-fraction radiation therapy it increased survival time significantly by 40%, although there were no complete remissions. Based on these findings, we suggest a new therapeutic regimen for malignant glioma using single-fraction radiation therapy with a target absorbed dose of the order of 5-10 Gy combined with clinically verified immunotherapy.
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| 10. |
- 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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