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- Børresen, Betina, et al.
(author)
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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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In: Frontiers in Oncology. - 2234-943X. ; 13, s. 1-10
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Journal article (peer-reviewed)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. |
- Konradsson, Elise, et al.
(author)
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Establishment and Initial Experience of Clinical FLASH Radiotherapy in Canine Cancer Patients
- 2021
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In: Frontiers in Oncology. - : Frontiers Media SA. - 2234-943X. ; 11
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Journal article (peer-reviewed)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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| 3. |
- Mannerberg, Annika, et al.
(author)
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Surface guided electron FLASH radiotherapy for canine cancer patients
- 2023
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In: Medical Physics. - 0094-2405. ; 50:7, s. 4047-4054
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Journal article (peer-reviewed)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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