| 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. |
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| 3. |
- Edvardsson, Anneli, et al.
(författare)
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Robustness and dosimetric verification of hippocampal-sparing craniospinal pencil beam scanning proton plans for pediatric medulloblastoma
- 2024
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Ingår i: Physics and Imaging in Radiation Oncology. - : Elsevier. - 2405-6316. ; 29
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Tidskriftsartikel (refereegranskat)abstract
- Background and PurposeHippocampal-sparing (HS) is a method that can potentially reduce late cognitive complications for pediatric medulloblastoma (MB) patients treated with craniospinal proton therapy (PT). The aim of this study was to investigate robustness and dosimetric plan verification of pencil beam scanning HS PT.Materials and MethodsHS and non-HS PT plans for the whole brain part of craniospinal treatment were created for 15 pediatric MB patients. A robust evaluation of the plans was performed. Plans were recalculated in a water phantom and measured field-by-field using an ion chamber detector at depths corresponding to the central part of hippocampi. All HS and non-HS fields were measured with the standard resolution of the detector and in addition 16 HS fields were measured with high resolution. Measured and planned dose distributions were compared using gamma evaluation.ResultsThe median mean hippocampus dose was reduced from 22.9 Gy (RBE) to 8.9 Gy (RBE), while keeping CTV V95% above 95 % for all nominal HS plans. HS plans were relatively robust regarding hippocampus mean dose, however, less robust regarding target coverage and maximum dose compared to non-HS plans. For standard resolution measurements, median pass rates were 99.7 % for HS and 99.5 % for non-HS plans (p < 0.001). For high-resolution measurements, median pass rates were 100 % in the hippocampus region and 98.2 % in the surrounding region.ConclusionsA substantial reduction of dose in the hippocampus region appeared feasible. Dosimetric accuracy of HS plans was comparable to non-HS plans and agreed well with planned dose distribution in the hippocampus region.
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| 4. |
- Ek, Hanna, et al.
(författare)
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Transitioning from conventional photon therapy to proton therapy for primary brain tumors
- 2023
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Ingår i: Acta oncologica (Stockholm, Sweden). - 1651-226X. ; 62:4, s. 391-399
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Proton radiation therapy (PT) has become a treatment option alongside photon therapy (XRT) for lower-grade gliomas (LGG). In this single-institution retrospective study, we investigate the patient characteristics and treatment outcomes, including pseudo-progression (PsP), for LGG patients selected for PT. Method: Adult patients with grade 2–3 glioma consecutively treated with radiotherapy (RT) from May 2012 to December 2019 were retrospectively included in this cohort study. Tumor characteristics and treatment data were collected. The groups treated with PT and XRT were compared regarding treatment characteristics, side effects, occurrence of PsP, and survival outcomes. PsP was defined as new or growing lesions followed by either decrease or stabilization during a 12 month-period with no treatment. Results: Out of 143 patients meeting the inclusion criteria, 44 were treated with PT, 98 with XRT and one with mixed PT + XRT. The patients receiving PT were younger, had a lower tumor grade, more oligodendrogliomas and received a lower mean brain and brainstem dose. PsP was observed in 21 out of 126 patients, with no difference between XRT and PT (p =.38). The rate of fatigue in immediate connection to RT (zero to three months after) was higher for XRT than for PT (p =.016). The PT patients had a significantly better PFS and OS than the XRT patients (p =.025 and.035), but in multivariate analysis radiation modality was non-significant. Higher average dose to both brain and brainstem was associated with inferior PFS and OS (p <.001). Median follow-up time were 69 months and 26 months for XRT and PT patients, respectively. Conclusion: Contrary to previous studies, there was no difference in risk of PsP for XRT and PT. PT was associated with lower rates of fatigue <3 months after RT. The superior survival outcomes for PT indicates that the patients with the best prognosis were referred to PT.
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| 5. |
- Gram, D., et al.
(författare)
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Residual positioning errors and uncertainties for pediatric craniospinal irradiation and the impact of image guidance
- 2020
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Ingår i: Radiation Oncology. - : Springer Science and Business Media LLC. - 1748-717X. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Optimal alignment is of utmost importance when treating pediatric patients with craniospinal irradiation (CSI), especially with regards to field junctions and multiple isocenters and techniques applying high dose gradients. Here, we investigated the setup errors and uncertainties for pediatric CSI using different setup verification protocols. Methods A total of 38 pediatric patients treated with CSI were identified for whom treatment records and setup images were available. The setup images were registered retrospectively to the reference image using an automated tool and matching on bony anatomy, subsequently, the impact of different correction protocols was simulated. Results For an action-level (AL)-protocol and a non-action level (NAL)-protocol, the translational residual setup error can be as large as 24 mm for an individual patient during a single fraction, and the rotational error as large as 6.1 degrees. With daily IGRT, the maximum setup errors were reduced to 1 mm translational and 5.4 degrees rotational versus 1 mm translational and 2.4 degrees rotational for 3- and 6- degrees of freedom (DoF) couch shifts, respectively. With a daily 6-DoF IGRT protocol for a wide field junction irradiation technique, the residual positioning uncertainty was below 1 mm and 1 degrees for translational and rotational directions, respectively. The largest rotational uncertainty was found for the patients' roll even though this was the least common type of rotational error, while the largest translational uncertainty was found in the patients' anterior-posterior-axis. Conclusions These results allow for informed margin calculation and robust optimization of treatments. Daily IGRT is the superior choice for setup of pediatric patients treated with CSI, although centers that do not have this option could use the results presented here to improve their margins and uncertainty estimates for a more accurate treatment alignment.
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| 6. |
- Gram, Daniel, et al.
(författare)
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The risk of radiation-induced neurocognitive impairment and the impact of sparing the hippocampus during pediatric proton cranial irradiation
- 2023
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Ingår i: Acta Oncologica. - 0284-186X. ; 62:2, s. 134-140
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: Hippocampus is a central component for neurocognitive function and memory. We investigated the predicted risk of neurocognitive impairment of craniospinal irradiation (CSI) and the deliverability and effects of hippocampal sparing. The risk estimates were derived from published NTCP models. Specifically, we leveraged the estimated benefit of reduced neurocognitive impairment with the risk of reduced tumor control. Material and methods: For this dose planning study, a total of 504 hippocampal sparing intensity modulated proton therapy (HS-IMPT) plans were generated for 24 pediatric patients whom had previously received CSI. Plans were evaluated with respect to target coverage and homogeneity index to target volumes, maximum and mean dose to OARs. Paired t-tests were used to compare hippocampal mean doses and normal tissue complication probability estimates. Results: The median mean dose to the hippocampus could be reduced from 31.3 GyRBE to 7.3 GyRBE (p <.001), though 20% of these plans were not considered clinically acceptable as they failed one or more acceptance criterion. Reducing the median mean hippocampus dose to 10.6 GyRBE was possible with all plans considered as clinically acceptable treatment plans. By sparing the hippocampus to the lowest dose level, the risk estimation of neurocognitive impairment could be reduced from 89.6%, 62.1% and 51.1% to 41.0% (p <.001), 20.1% (p <.001) and 29.9% (p <.001) for task efficiency, organization and memory, respectively. Estimated tumor control probability was not adversely affected by HS-IMPT, ranging from 78.5 to 80.5% for all plans. Conclusions: We present estimates of potential clinical benefit in terms of neurocognitive impairment and demonstrate the possibility of considerably reducing neurocognitive adverse effects, minimally compromising target coverage locally using HS-IMPT.
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| 7. |
- 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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| 8. |
- Lempart, Michael, et al.
(författare)
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A deeply supervised convolutional neural network ensemble for multilabel segmentation of pelvic OARs
- 2021
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Ingår i: Radiotherapy and Oncology. - 1879-0887. ; 161:Suppl 1, s. 1417-1418
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Accurate delineation of organs at risk (OAR) is a crucial step in radiation therapy (RT) treatment planning but is a manual and time-consuming process. Deep learning-based methods have shown promising results for medical image segmentation and can be used to accelerate this task. Nevertheless, it is rarely applied to complex structures found in the pelvis region, where manual segmentation can be difficult, costly and is not always feasible. The aim of this study was to train and validate a model, based on a modified U-Net architecture, for automated and improved multilabel segmentation of 10 pelvic OAR structures (total bone marrow, lower pelvis bone marrow, iliac bone marrow, lumosacral bone marrow, bowel cavity, bowel, small bowel, large bowel, rectum, and bladder).
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| 9. |
- Lempart, Michael, et al.
(författare)
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Pelvic U-Net : multi-label semantic segmentation of pelvic organs at risk for radiation therapy anal cancer patients using a deeply supervised shuffle attention convolutional neural network
- 2022
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Ingår i: Radiation Oncology. - : Springer Science and Business Media LLC. - 1748-717X. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Delineation of organs at risk (OAR) for anal cancer radiation therapy treatment planning is a manual and time-consuming process. Deep learning-based methods can accelerate and partially automate this task. The aim of this study was to develop and evaluate a deep learning model for automated and improved segmentations of OAR in the pelvic region. Methods: A 3D, deeply supervised U-Net architecture with shuffle attention, referred to as Pelvic U-Net, was trained on 143 computed tomography (CT) volumes, to segment OAR in the pelvic region, such as total bone marrow, rectum, bladder, and bowel structures. Model predictions were evaluated on an independent test dataset (n = 15) using the Dice similarity coefficient (DSC), the 95th percentile of the Hausdorff distance (HD95), and the mean surface distance (MSD). In addition, three experienced radiation oncologists rated model predictions on a scale between 1–4 (excellent, good, acceptable, not acceptable). Model performance was also evaluated with respect to segmentation time, by comparing complete manual delineation time against model prediction time without and with manual correction of the predictions. Furthermore, dosimetric implications to treatment plans were evaluated using different dose-volume histogram (DVH) indices. Results: Without any manual corrections, mean DSC values of 97%, 87% and 94% were found for total bone marrow, rectum, and bladder. Mean DSC values for bowel cavity, all bowel, small bowel, and large bowel were 95%, 91%, 87% and 81%, respectively. Total bone marrow, bladder, and bowel cavity segmentations derived from our model were rated excellent (89%, 93%, 42%), good (9%, 5%, 42%), or acceptable (2%, 2%, 16%) on average. For almost all the evaluated DVH indices, no significant difference between model predictions and manual delineations was found. Delineation time per patient could be reduced from 40 to 12 min, including manual corrections of model predictions, and to 4 min without corrections. Conclusions: Our Pelvic U-Net led to credible and clinically applicable OAR segmentations and showed improved performance compared to previous studies. Even though manual adjustments were needed for some predicted structures, segmentation time could be reduced by 70% on average. This allows for an accelerated radiation therapy treatment planning workflow for anal cancer patients.
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| 10. |
- Lempart, Michael, et al.
(författare)
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Volumetric modulated arc therapy dose prediction and deliverable treatment plan generation for prostate cancer patients using a densely connected deep learning model
- 2021
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Ingår i: Physics and imaging in radiation oncology. - : Elsevier BV. - 2405-6316. ; 19, s. 112-119
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: Radiation therapy treatment planning is a manual, time-consuming task that might be accelerated using machine learning algorithms. In this study, we aimed to evaluate if a triplet-based deep learning model can predict volumetric modulated arc therapy (VMAT) dose distributions for prostate cancer patients. Materials and methods: A modified U-Net was trained on triplets, a combination of three consecutive image slices and corresponding segmentations, from 160 patients, and compared to a baseline U-Net. Dose predictions from 17 test patients were transformed into deliverable treatment plans using a novel planning workflow. Results: The model achieved a mean absolute dose error of 1.3%, 1.9%, 1.0% and ≤ 2.6% for clinical target volume (CTV) CTV_D100%, planning target volume (PTV) PTV_D98%, PTV_D95% and organs at risk (OAR) respectively, when compared to the clinical ground truth (GT) dose distributions. All predicted distributions were successfully transformed into deliverable treatment plans and tested on a phantom, resulting in a passing rate of 100% (global gamma, 3%, 2 mm, 15% cutoff). The dose difference between deliverable treatment plans and GT dose distributions was within 4.4%. The difference between the baseline model and our improved model was statistically significant (p < 0.05) for CVT_D100%, PTV_D98% and PTV_D95%. Conclusion: Triplet-based training improved VMAT dose distribution predictions when compared to 2D. Dose predictions were successfully transformed into deliverable treatment plans using our proposed treatment planning procedure. Our method may automate parts of the workflow for external beam prostate radiation therapy and improve the overall treatment speed and plan quality.
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