| 51. |
- Fukuda, Aya, et al.
(författare)
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Progenitor cell injury after irradiation to the developing brain can be modulated by mild hypothermia or hyperthermia
- 2005
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Ingår i: J Neurochem. ; 94:6, s. 1604-19
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Tidskriftsartikel (refereegranskat)abstract
- Ionizing radiation induced acute cell death in the dentate gyrus subgranular zone (SGZ) and the subventricular zone (SVZ). Hypomyelination was also observed. The effects of mild hypothermia and hyperthermia for 4 h after irradiation (IR) were studied in postnatal day 9 rats. One hemisphere was irradiated with a single dose of 8 Gy and animals were randomized to normothermia (rectal temperature 36 degrees C for 4 h), hypothermia (32 degrees C for 4 h) or hyperthermia (39 degrees C for 4 h). Cellular injury, e.g. chromatin condensation and nitrotyrosine formation, appeared to proceed faster when the body temperature was higher. Caspase-3 activation was more pronounced in the hyperthermia group and nuclear translocation of p53 was less pronounced in the hypothermia group 6 h after IR. In the SVZ the loss of nestin-positive progenitors was more pronounced (48%) and the size was smaller (45%) in the hyperthermia group 7 days post-IR. Myelination was not different after hypo- or hyperthermia. This is the first report to demonstrate that hypothermia may be beneficial and that hyperthermia may aggravate the adverse side-effects after radiation therapy to the developing brain.
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| 52. |
- Fukuda, Hirotsugu, et al.
(författare)
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Irradiation-induced progenitor cell death in the developing brain is resistant to erythropoietin treatment and caspase inhibition
- 2004
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Ingår i: Cell Death Differ. - Univ Gothenburg, Dept Physiol, Perinatal Ctr, SE-40530 Gothenburg, Sweden. Osaka Univ, Sch Med, Dept Obstet & Gynecol, Suita, Osaka 5650871, Japan. Zhengzhou Univ, Affiliated Hosp 3, Dept Pediat, Zhengzhou 450052, Peoples R China. Uppsala Univ, Dept Neurosci, SE-75123 Uppsala, Sweden. Sahlgrens Univ Hosp, Dept Radiat Phys, SE-41345 Gothenburg, Sweden. H Lundbeck & Co AS, Mol Dis Biol, DK-2500 Copenhagen, Denmark. Sahlgrens Univ Hosp, Dept Oncol, SE-41345 Gothenburg, Sweden. Queen Silvia Childrens Hosp, Dept Pediat, SE-41685 Gothenburg, Sweden. : NATURE PUBLISHING GROUP. - 1350-9047 .- 1476-5403. ; 11:11, s. 1166-78
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Tidskriftsartikel (refereegranskat)abstract
- One hemisphere of postnatal day 8 (P8) rats or P10 mice was irradiated with a single dose of 4-12 Gy, and animals were killed from 2 h to 8 weeks after irradiation (IR). In the subventricular zone (SVZ) and the granular cell layer (GCL) of the dentate gyrus, harboring neural and other progenitor cells, nitrosylation and p53 peaked 2-12 h after IR, followed by markers for active caspase-3, apoptosis-inducing factor and TUNEL (6-24 h). Ki67-positive (proliferating) cells had disappeared by 12 h and partly reappeared by 7 days post-IR. The SVZ and GCL areas decreased approximately 50% 7 days after IR. The development of white matter was hampered, resulting in 50-70% less myelin basic protein staining. Pretreatment with erythropoietin did not confer protection against IR. Caspase inhibition by overexpression of XIAP prevented caspase-9 and caspase-3 activation but not cell death, presumably because of increased caspase-independent cell death.
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| 53. |
- Gasic, D., et al.
(författare)
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Retrospective estimation of heart and lung doses in pediatric patients treated with spinal irradiation
- 2018
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Ingår i: Radiotherapy and Oncology. - : Elsevier BV. - 0167-8140. ; 128:2, s. 209-213
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: The purpose of this study was to investigate whether treatment information from medical records can be used to estimate radiation doses to heart and lungs retrospectively in pediatric patients receiving spinal irradiation with conventional posterior fields. Material and methods: An algorithm for retrospective dosimetry in children treated with spinal irradiation was developed in a cohort of 21 pediatric patients with available CT-scans and treatment plans. We developed a multivariable linear regression model with explanatory variables identifiable in case note review for retrospective estimation of minimum, maximum, mean and V-10%-V-80% doses to the heart and lungs. Doses were estimated for both linear accelerator (Linac) and Co-60 radiation therapy modalities. Results: Age and spinal field width were identified as statistically significant predictors of heart and lung doses in multivariable analyses (p < 0.01 in all models). Models showed excellent predictive performance with R-2 = 0.70 for mean heart dose and 0.79 for mean lung dose, for Linac plans. In leave-one-out cross-validation analysis the average difference between predicted and actual mean heart dose was 6.7% and 7.6% of the prescription dose for Linac and Co-60 plans, respectively, and 5.2% and 4.9% for mean lung dose. Due to the small sample size and large inter-patient variation in heart and lung dose, prospective studies validating these findings are highly warranted. Conclusions: The models presented here provide retrospective estimates of heart and lung doses for historical cohorts of pediatric patients, thus facilitating studies of long-term adverse effects of radiation. (C) 2018 Elsevier B.V. All rights reserved.
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| 54. |
- Glimelius, B., et al.
(författare)
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Number of patients potentially eligible for proton therapy
- 2005
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Ingår i: Acta Oncol. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 44:8, s. 836-49
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Tidskriftsartikel (refereegranskat)abstract
- A group of Swedish radiation oncologists and hospital physicists have estimated the number of patients in Sweden suitable for proton beam therapy in a facility where one of the principal aims is to facilitate randomized and other studies in which the advantage of protons can be shown and the magnitude of the differences compared with optimally administered conventional radiation treatment, also including intensity-modulated radiation therapy (IMRT) and brachytherapy, can be shown. The estimations have been based on current statistics of tumour incidence in Sweden, number of patients potentially eligible for radiation treatment, scientific support from clinical trials and model dose planning studies and knowledge of the dose-response relations of different tumours together with information on normal tissue complication rates. In Sweden, it is assessed that between 2200 and 2500 patients annually are eligible for proton beam therapy, and that for these patients the potential therapeutic benefit is so great as to justify the additional expense of proton therapy. This constitutes between 14-15% of all irradiated patients annually.
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| 55. |
- 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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| 56. |
- Gram, D., 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. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 62:2, s. 134-140
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Tidskriftsartikel (refereegranskat)abstract
- Background and purposeHippocampus 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 methodsFor 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.ResultsThe median mean dose to the hippocampus could be reduced from 31.3 Gy(RBE) to 7.3 Gy(RBE) (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 Gy(RBE) 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.ConclusionsWe 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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| 57. |
- 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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| 58. |
- Gurjar, Mrugaja, 1997, et al.
(författare)
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Automated data extraction tool (DET) for external applications in radiotherapy.
- 2023
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Ingår i: Technical innovations & patient support in radiation oncology. - : Elsevier BV. - 2405-6324. ; 25
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Tidskriftsartikel (refereegranskat)abstract
- Oncological Information Systems (OIS) manage information in radiotherapy (RT) departments. Due to database structure limitations, stored information can rarely be directly used except for vendor-specific purposes. Our aim is to enable the use of such data in various external applications by creating a tool for automatic data extraction, cleaning and formatting.We used OIS data from a nine-linac RT department in Sweden (70weeks, 2015-16). Extracted data included patients' referrals and appointments with details for RT sub-tasks. The data extraction tool to prepare the data for external use was built in C# programming language. It used excel-automation queries to remove unassigned/duplicated values, substitute missing data and perform application-specific calculations. Descriptive statistics were used to verify the output with the manually prepared dataset from the corresponding time period.From the initial raw data, 2030 (51%)/907 (23%) patients had known curative and palliative treatment intent for 84 different cancer diagnoses. After removal of incomplete entries, 373 (10%) patients had unknown treatment intents which were substituted based on the known curative/palliative ratio. Automatically- and manuallyprepared datasets differed<1% for Mould, Treatment planning, Quality assurance and±5% for Fractions and Magnetic resonance imaging with overestimations in 80/140 (57%) entries by the tool.We successfully implemented a software tool to prepare ready-to-use OIS datasets for external applications. Our evaluations showed overall results close to the manually-prepared dataset. The time taken to prepare the dataset using our automated strategy can reduce the time for manual preparation from weeks to seconds.
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| 59. |
- Hallqvist, Andreas, 1973, et al.
(författare)
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Accelerated hyperfractionated radiotherapy and concomitant chemotherapy in small cell lung cancer limited-disease. Dose response, feasibility and outcome for patients treated in western Sweden, 1998-2004.
- 2007
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Ingår i: Pubmed. - : Informa UK Limited. - 0284-186X. ; , s. 1-6
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Tidskriftsartikel (refereegranskat)abstract
- Addition of thoracic radiation therapy (TRT) to chemotherapy (CHT) can increase overall survival in patients with small cell lung cancer limited-disease (SCLC-LD). Accelerated fractionation and early concurrent platinum-based CHT, in combination with prophylactic cranial irradiation, represent up-front treatment for this group of patients. Optimised and tailored local and systemic treatment is important. These concepts were applied when a new regional treatment programme was designed at Sahlgrenska University Hospital in 1997. The planned treatment consisted of six courses of CHT (carboplatin/etoposide) + TRT+/-prophylactic cranial irradiation (PCI). Standard TRT was prescribed as 1.5 Gy BID to a total of 60 Gy during 4 weeks, starting concomitantly with the second or third course of CHT. However, patients with large tumour burdens, poor general condition and/or poor lung function received 45 Gy, 1.5 Gy BID, during 3 weeks. PCI in 15 fractions to a total dose of 30 Gy was administered to all patients with complete remission (CR) and "good" partial remission (PR) at response evaluation. Eighty consecutive patients were treated between January 1998 and December 2004. Forty-six patients were given 60 Gy and 34 patients 45 Gy. Acute toxicity occurred as esophagitis grade III (RTOG/EORTC) in 16% and as pneumonitis grade I-II in10%. There were no differences in toxicity between the two groups. Three- and five-year overall survival was 25% and 16%, respectively. Median survival was 20.8 months with no significant difference between the two groups. In conclusion, TRT with a total dose of 60 or 45 Gy is feasible with comparable toxicity and no difference in local control or survival. Distant metastasis is the main cause of death in this disease; the future challenge is thus further improvement of the systemic therapy combined with optimised local TRT.
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| 60. |
- Hedman, Mattias, et al.
(författare)
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Comparison of predicted and clinical response to radiotherapy: a radiobiology modelling study.
- 2009
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Ingår i: Acta oncologica (Stockholm, Sweden). - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 48:4, s. 584-90
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: A model to predict clinical outcome after radiation therapy would be a valuable aid in the effort of developing more tailored treatment regimes for different patients. In this work we evaluate the clinical utility of a model that incorporates the following individually measured radiobiology parameters: intrinsic radiosensitivity, proliferation and number of clonogenic cells. The hypothesis underlying the study was that the incorporation of individually measured tumour parameters in a model would increase its reliability in predicting treatment outcome compared with the use of average population derived data. MATERIAL AND METHODS: Forty-six patients with head and neck tumours were analyzed, the majority of whom received both external beam radiotherapy and brachytherapy. Eighteen patients received external beam treatment alone and statistical analyses were carried out on this subgroup. RESULTS: Four of the 18 patients had a >95% calculated probability of cure and none developed a local recurrence resulting in a negative predictive value of 100% (compared with 67% for population-derived data). The sensitivity of the model in predicting local recurrence was 75% (compared with 38% for population-derived data). Using a model that incorporated individually measured radiobiology data, there was a statistically significant difference in local control levels for patients with >95% and <5% predicted probability of local control (chi(2), p = 0.04). DISCUSSION: This study suggests, therefore, that incorporation of measured biological data within a radiobiological model improves its ability to predict radiation therapy outcome compared with the use of population-derived data.
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