| 1. |
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| 2. |
- Murari, A., et al.
(författare)
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A control oriented strategy of disruption prediction to avoid the configuration collapse of tokamak reactors
- 2024
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Ingår i: Nature Communications. - 2041-1723 .- 2041-1723. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- The objective of thermonuclear fusion consists of producing electricity from the coalescence of light nuclei in high temperature plasmas. The most promising route to fusion envisages the confinement of such plasmas with magnetic fields, whose most studied configuration is the tokamak. Disruptions are catastrophic collapses affecting all tokamak devices and one of the main potential showstoppers on the route to a commercial reactor. In this work we report how, deploying innovative analysis methods on thousands of JET experiments covering the isotopic compositions from hydrogen to full tritium and including the major D-T campaign, the nature of the various forms of collapse is investigated in all phases of the discharges. An original approach to proximity detection has been developed, which allows determining both the probability of and the time interval remaining before an incoming disruption, with adaptive, from scratch, real time compatible techniques. The results indicate that physics based prediction and control tools can be developed, to deploy realistic strategies of disruption avoidance and prevention, meeting the requirements of the next generation of devices.
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| 3. |
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| 4. |
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| 5. |
- Alterbeck, Max, et al.
(författare)
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Designing and Implementing a Population-based Organised Prostate Cancer Testing Programme.
- 2022
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Ingår i: European urology focus. - : Elsevier BV. - 2405-4569. ; 8:6, s. 1568-1574
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Tidskriftsartikel (refereegranskat)abstract
- European guidelines recommend that well-informed men at elevated risk of having prostate cancer (PCa) should be offered prostate-specific antigen (PSA) testing with risk-stratified follow-up. The Swedish National Board of Health and Welfare recommends against screening for PCa but supports regional implementation of organised prostate cancer testing (OPT).To report the process for designing and implementing OPT programmes.Population-based OPT programmes in two Swedish regions, designed to include men aged between 50 and 74 yr, launched in September 2020 for 50-yr-old men.The number of men invited, the participation rate, and the numbers of magnetic resonance imaging (MRI) scans, urological visits, and biopsies from September 2020 to June 2021 were recorded.Two Swedish regions co-designed an OPT programme with a risk-stratified diagnostic algorithm based on prostate-specific antigen (PSA), PSA density, MRI findings, and age. An automated administrative system was developed on a nationwide web-based platform. Invitation letters and test results are automatically generated and sent out by post. Men with PSA ≥3ng/ml, a suspicious MRI lesion, and/or PSA density ≥0.15ng/ml/cm3 are referred for a prostate biopsy. Test results are registered for quality control and research. By June 2021, a total of 16515 men were invited, of whom 6309 (38%) participated; 147 had an MRI scan and 39 underwent prostate biopsy. The OPT framework, algorithm, and diagnostic pathways have been working well.We designed and implemented a framework for OPT with a high grade of automation. The framework and organisational experiences may be of value for others who plan a programme for early detection of PCa.We describe the implementation of an organised testing programme for early detection of prostate cancer in two Swedish regions. This model is the first of its kind and may serve as a template for similar programmes.
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| 6. |
- Bhardwaj, R. D., et al.
(författare)
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Neocortical neurogenesis in humans is restricted to development.
- 2006
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 103:33, s. 12564-8
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Tidskriftsartikel (refereegranskat)abstract
- Stem cells generate neurons in discrete regions in the postnatal mammalian brain. However, the extent of neurogenesis in the adult human brain has been difficult to establish. We have taken advantage of the integration of (14)C, generated by nuclear bomb tests during the Cold War, in DNA to establish the age of neurons in the major areas of the human cerebral neocortex. Together with the analysis of the neocortex from patients who received BrdU, which integrates in the DNA of dividing cells, our results demonstrate that, whereas nonneuronal cells turn over, neurons in the human cerebral neocortex are not generated in adulthood at detectable levels but are generated perinatally.
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| 7. |
- Boström, Martina, et al.
(författare)
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A role for endothelial cells in radiation-induced inflammation
- 2018
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Ingår i: International Journal of Radiation Biology. - : Informa UK Limited. - 0955-3002 .- 1362-3095. ; 94:3, s. 259-271
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To unravel the role of the vasculature in radiation-induced brain tissue damage.Materials and methods: Postnatal day 14 mice received a single dose of 10Gy cranial irradiation and were sacrificed 6h, 24h or 7 days post-irradiation. Endothelial cells were isolated from the hippocampus and cerebellum using fluorescence-activated cell sorting, followed by cell cycle analysis and gene expression profiling.Results: Flow cytometric analysis revealed that irradiation increased the percentage of endothelial cells, relative to the whole cell population in both the hippocampus and the cerebellum. This change in cell distribution indicates that other cell types are more susceptible to irradiation-induced cell death, compared to endothelial cells. This was supported by data showing that genes involved in endothelial cell-specific apoptosis (e.g. Smpd1) were not induced at any time point investigated but that genes involved in cell-cycle arrest (e.g. Cdkn1a) were upregulated at all investigated time points, indicating endothelial cell repair. Inflammation-related genes, on the other hand, were strongly induced, such as Ccl2, Ccl11 and Il6.Conclusions: We conclude that endothelial cells are relatively resistant to ionizing radiation but that they play an active, hitherto unknown, role in the inflammatory response after irradiation. In the current study, this was shown in both the hippocampus, where neurogenesis and extensive cell death after irradiation occurs, and in the cerebellum, where neurogenesis no longer occurs at this developmental age.
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| 8. |
- Boström, Martina, et al.
(författare)
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Chronic disturbance in the thalamus following cranial irradiation to the developing mouse brain
- 2019
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Better survival rates among pediatric brain tumor patients have resulted in an increased awareness of late side effects that commonly appear following cancer treatment. Radiation-induced changes in hippocampus and white matter are well described, but do not explain the full range of neurological late effects in childhood cancer survivors. The aim of this study was to investigate thalamus following cranial irradiation (CIR) to the developing brain. At postnatal day 14, male mice pups received a single dose of 8Gy CIR. Cellular effects in thalamus were assessed using immunohistochemistry 4 months after CIR. Interestingly, the density of neurons decreased with 35% (p=0.0431) and the density of astrocytes increased with 44% (p=0.011). To investigate thalamic astrocytes, S100β+ cells were isolated by fluorescence-activated cell sorting and genetically profiled using next-generation sequencing. The phenotypical characterization indicated a disrupted function, such as downregulated microtubules' function, higher metabolic activity, immature phenotype and degraded ECM. The current study provides novel insight into that thalamus, just like hippocampus and white matter, is severely affected by CIR. This knowledge is of importance to understand the late effects seen in pediatric brain tumor survivors and can be used to give them the best suitable care.
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| 9. |
- Bull, Cecilia, 1977, et al.
(författare)
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A novel mouse model of radiation-induced cancer survivorship diseases of the gut
- 2017
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Ingår i: American journal of physiology. Gastrointestinal and liver physiology. - : American Physiological Society. - 1522-1547 .- 0193-1857. ; 313:5, s. G456-G466
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Tidskriftsartikel (refereegranskat)abstract
- A deeper understanding of the radiation-induced pathophysiological processes that develop in the gut is imperative to prevent, alleviate, or eliminate cancer survivorship diseases after radiotherapy to the pelvic area. Most rodent models of high-dose gastrointestinal radiation injury are limited by high mortality. We therefore established a model that allows for the delivering of radiation in fractions at high doses while maintaining long-term survival. Adult male C57/BL6 mice were exposed to small-field irradiation, restricted to 1.5 cm of the colorectum using a linear accelerator. Each mouse received 6 or 8 Gy, two times daily in 12-h intervals in two, three, or four fractions. Acute cell death was examined at 4.5 h postirradiation and histological changes at 6 wk postirradiation. Another group was given four fractions of 8 Gy and followed over time for development of visible symptoms. Irradiation caused immediate cell death, mainly limited to the colorectum. At 6 wk postirradiation, several crypts displayed signs of radiation-induced degeneration. The degenerating crypts were seen alongside crypts that appeared perfectly healthy. Crypt survival was reduced after the fourth fraction regardless of dose, whereas the number of macrophages increased. Angiogenesis was induced, likely as a compensatory mechanism for hypoxia. Four months postirradiation, mice began to show radiation-induced symptoms, and histological examination revealed an extensive crypt loss and fibrosis. Our model is uniquely suitable for studying the long-term trajectory and underlying mechanisms of radiation-induced gastrointestinal injury. NEW & NOTEWORTHY A novel mouse model for studying the long-term trajectory of radiation-induced gut injury. The method allows for the use of high doses and multiple fractions, with minor impact on animal health for at least 3 mo. Crypt loss and a slow progression of fibrosis is observed. Crypt degeneration is a process restricted to isolated crypts. Crypt degeneration is presented as a convenient proxy endpoint for long-term radiation-induced gut injury.
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| 10. |
- Curtis, Maurice A, et al.
(författare)
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Human neuroblasts migrate to the olfactory bulb via a lateral ventricular extension.
- 2007
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Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 315:5816, s. 1243-9
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Tidskriftsartikel (refereegranskat)abstract
- The rostral migratory stream (RMS) is the main pathway by which newly born subventricular zone cells reach the olfactory bulb (OB) in rodents. However, the RMS in the adult human brain has been elusive. We demonstrate the presence of a human RMS, which is unexpectedly organized around a lateral ventricular extension reaching the OB, and illustrate the neuroblasts in it. The RMS ensheathing the lateral olfactory ventricular extension, as seen by magnetic resonance imaging, cell-specific markers, and electron microscopy, contains progenitor cells with migratory characteristics and cells that incorporate 5-bromo-2'-deoxyuridine and become mature neurons in the OB.
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| 11. |
- Eriksson, Peter S, 1959, et al.
(författare)
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Neurogenesis in the adult human hippocampus
- 1998
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Ingår i: Nat Med. - 1078-8956. ; 4:11, s. 1313-7
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Tidskriftsartikel (refereegranskat)abstract
- The genesis of new cells, including neurons, in the adult human brain has not yet been demonstrated. This study was undertaken to investigate whether neurogenesis occurs in the adult human brain, in regions previously identified as neurogenic in adult rodents and monkeys. Human brain tissue was obtained postmortem from patients who had been treated with the thymidine analog, bromodeoxyuridine (BrdU), that labels DNA during the S phase. Using immunofluorescent labeling for BrdU and for one of the neuronal markers, NeuN, calbindin or neuron specific enolase (NSE), we demonstrate that new neurons, as defined by these markers, are generated from dividing progenitor cells in the dentate gyrus of adult humans. Our results further indicate that the human hippocampus retains its ability to generate neurons throughout life.
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| 12. |
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| 13. |
- Kalm, Marie, 1981, et al.
(författare)
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Serum concentrations of the axonal injury marker neurofilament light protein are not influenced by blood-brain barrier permeability
- 2017
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Ingår i: Brain Research. - : Elsevier BV. - 0006-8993. ; 1668, s. 12-19
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Tidskriftsartikel (refereegranskat)abstract
- A blood biomarker to monitor individual susceptibility to neuronal injury from cranial radiotherapy could potentially help to individualize radiation treatment and thereby reduce the incidence and severity of late effects. An important feature of such a blood biomarker is that its concentration is not confounded by varying degrees of release from the brain into the blood across the blood-brain barrier (BBB). In this study, we investigated serum neurofilament light protein (NFL) concentrations in 21-day old mice following a single dose of cranial irradiation (8 Gy). Cranial irradiation resulted in acute cell injury measured as a 12.9-fold increase in caspase activity 6 h after irradiation; activation of inflammation measured by levels of CCL2 and increased BBB permeability measured by C-14-sucrose concentration ratios in brain and cerebrospinal fluid (CSF). Serum levels of NFL peaked at 6 h after both anesthesia and cranial irradiation, but no timely correlation of serum NFL concentration with BBB permeability was found. Further, three groups of patients with different degrees of BBB impairment (measured as the CSF/serum albumin ratio) were investigated. There was no correlation between serum NFL concentration and CSF/serum albumin ratio (r = 0.139, p = 0.3513), however a strong correlation was found for NFL concentration in serum and NFL concentration in CSF (r = 0.6303, p < 0.0001). In conclusion, serum NFL appears to be a reliable blood biomarker for neuronal injury, and its concentration is not confounded by BBB permeability. (C) 2017 Elsevier B.V. All rights reserved.
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| 14. |
- Naylor, Andrew Stuart, 1977, et al.
(författare)
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Voluntary running rescues adult hippocampal neurogenesis after irradiation of the young mouse brain.
- 2008
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 105:38, s. 14632-7
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Tidskriftsartikel (refereegranskat)abstract
- Cranial radiation therapy is commonly used in the treatment of childhood cancers. It is associated with cognitive impairments tentatively linked to the hippocampus, a neurogenic region of the brain important in memory function and learning. Hippocampal neurogenesis is positively regulated by voluntary exercise, which is also known to improve hippocampal-dependent cognitive functions. In this work, we irradiated the brains of C57/BL6 mice on postnatal day 9 and evaluated both the acute effects of irradiation and the effects of voluntary running on hippocampal neurogenesis and behavior 3 months after irradiation. Voluntary running significantly restored precursor cell and neurogenesis levels after a clinically relevant, moderate dose of irradiation. We also found that irradiation perturbed the structural integration of immature neurons in the hippocampus and that this was reversed by voluntary exercise. Furthermore, irradiation-induced behavior alterations observed in the open-field test were ameliorated. Together, these results clearly demonstrate the usefulness of physical exercise for functional and structural recovery from radiation-induced injury to the juvenile brain, and they suggest that exercise should be evaluated in rehabilitation therapy of childhood cancer survivors.
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| 15. |
- Smith, Frida, 1973, et al.
(författare)
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Exploring the meaning, role and experiences of a patient-led social innovation for people affected by cancer: a new collaborative care model complementing traditional cancer rehabilitation in Sweden
- 2021
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Ingår i: BMJ open quality. - : BMJ. - 2399-6641. ; 10:4
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Tidskriftsartikel (refereegranskat)abstract
- Objective Kraftens Hus is the first support centre in Sweden designed by and for people affected by cancer, including patients, family, friends, staff members and local community representatives (collectively 'stakeholders'). The purpose of this study was to explore the meaning, role and experiences of Kraftens Hus stakeholders using a patient and public involved methodology. Methods To understand and map the experiences of visitors to Kraftens Hus, we applied concept mapping (CM), a mixed methods approach where data are collected and analysed in four structured steps designed to capture the diverse perspectives of multiple stakeholders. Qualitative interviews with relevant stakeholders supplemented the CM findings. Results The final concept map contained six clusters of ideas. Within the clusters, there was a recurring theme that cancer-affected people value accessible and long-term psychosocial support (PSS). The intended emotional, social and practical needs identified in a previous design process seem to have been addressed and appreciated by Kraftens Hus visitors. Conclusion Kraftens Hus is an example of a new patient-led social innovation based on a life-event perspective and integration of resources from different sectors in society. By focusing on life, not the disease, the care continuum expands, and long-term PSS is provided alongside cancer treatment. The evaluation confirms that PSS should focus on health and well-being in the broadest sense.
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| 16. |
- Zhu, Changlian, 1964, et al.
(författare)
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X chromosome-linked inhibitor of apoptosis protein reduces oxidative stress after cerebral irradiation or hypoxia-ischemia through up-regulation of mitochondrial antioxidants.
- 2007
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Ingår i: The European journal of neuroscience. - : Wiley. - 1460-9568 .- 0953-816X. ; 26:12, s. 3402-10
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Tidskriftsartikel (refereegranskat)abstract
- We demonstrate that X chromosome-linked inhibitor of apoptosis protein (XIAP) counteracts oxidative stress in two essentially different disease-related models of brain injury, hypoxia-ischemia and irradiation, as judged by lower expression of nitrotyrosine (5-fold) and 4-hydroxy-2-nonenal (10-fold) in XIAP-overexpressing compared with wild-type mice. XIAP overexpression induced up-regulation of at least three antioxidants residing in mitochondria, superoxide dismutase 2, thioredoxin 2 and lysine oxoglutarate reductase. Cytochrome c release from mitochondria was reduced in XIAP-overexpressing mice. Hence, in addition to blocking caspases, XIAP can regulate reactive oxygen species in the brain, at least partly through up-regulation of mitochondrial antioxidants. XIAP-induced prevention of oxidative stress was not secondary to tissue protection because although XIAP overexpression provides tissue protection after hypoxia-ischemia, it does not prevent tissue loss after irradiation. This is a previously unknown role of XIAP and may provide the basis for development of novel protective strategies for both acute and chronic neurodegenerative diseases, where oxidative stress is an integral component of the injury mechanisms involved.
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| 17. |
- Abel, Edvard, 1970, et al.
(författare)
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Fatigue in Patients With Head and Neck Cancer Treated With Radiation Therapy: A Prospective Study of Patient-Reported Outcomes and Their Association With Radiation Dose to the Cerebellum
- 2022
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Ingår i: Advances in Radiation Oncology. - : Elsevier BV. - 2452-1094. ; 7:5
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Although fatigue is a known side effect in patients with head and neck cancer (HNC) receiving radiation therapy, knowledge regarding long-term fatigue and dose-response relationships to organs at risk is scarce. The aim of this prospective study was to analyze patient-reported fatigue in patients with HNC receiving radiation therapy and to explore any possible association with organ-at-risk doses. Methods and Materials: Patients with HNC referred for curative radiation therapy were eligible for inclusion in the study. To assess patient-reported fatigue, quality of life questionnaires (European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-FA12) were distributed before treatment and 1, 3, 6, 12, 24, and 60 months after the start of treatment. Mean dose (Dmean) and near maximum dose (D2%) of the cerebellum and brain stem were evaluated in relation to baseline-adjusted fatigue scores at 3 months. Results: One hundred twenty-six patients treated with intensity modulated radiation therapy between 2008 and 2010 were available for final analysis. Female sex and age <60 years were associated with higher fatigue at baseline, whereas patients also treated with chemotherapy had reduced physical and emotional fatigue at 6 months. Physical fatigue (QLQ-FA12 scale) increased from baseline up to 3 months (29 vs 59; P < .0001) but showed no difference compared with baseline from 1 to 5 years. Emotional fatigue was significantly lower at 5 years compared with baseline (14 vs 28; P < .0001). Patients with cerebellum Dmean > 3.5 Gy had higher mean physical fatigue scores at 3 months (38 vs 27; P = .036). Conclusions: Although there is a significant increase in fatigue scores for patients with HNC up to 1 year after radiation therapy, this study showed a return to baseline levels at 5 years. A possible association was found between physical fatigue and a higher mean dose to the cerebellum.
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| 18. |
- Abel, Edvard, 1970, et al.
(författare)
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Impact on quality of life of IMRT versus 3-D conformal radiation therapy in head and neck cancer patients: A case control study
- 2017
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Ingår i: Advances in Radiation Oncology. - : Elsevier BV. - 2452-1094. ; 2:3, s. 346-353
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Tidskriftsartikel (refereegranskat)abstract
- Objective The purpose of this study was to prospectively and longitudinally compare the health-related quality of life (HRQOL) outcomes between head and neck (HN) cancer patients treated with parotid-sparing intensity modulated radiation therapy (IMRT) and patients treated with 3-dimensional conventional radiation therapy (3D-CRT). Methods and materials Before and up to 12 months after treatment, HRQOL was recorded in patients with HN cancer who were referred to the Department of Oncology at Sahlgrenska University Hospital for curative IMRT. The study group's HRQOL was compared with a matched group of patients from previous descriptive HRQOL studies treated with 3D-CRT. Both groups' HRQOL was measured by the European Organization for Research and Treatment for Cancer QLQ-C30 and European Organization for Research and Treatment for Cancer QLQ-HN35 at 6 time points in the first year after diagnosis. Results Two hundred and seven patients were included, 111 treated with IMRT and 96 matched controls treated with 3D-CRT. Both groups' HRQOL deteriorated during and after treatment. Just after treatment, worse HRQOL scores were observed in the IMRT group regarding insomnia (38 vs 27; P = .032), appetite loss (64 vs 50; P = .019), senses (54 vs 41; P = .017), and coughing (39 vs 26, P = .009). At 12 months, however, significantly better HRQOL scores were observed in the IMRT group regarding problems with dry mouth (72 vs 62; P = .018), pain (28 vs 20; P = .018), sexuality (37 vs 23; P = .016), social contacts (10 vs 6; P = .026), cognitive functioning (79 vs 87; P = .0057), and financial difficulties (12 vs 20; P = .0019). Conclusions This study further supports the hypothesis that the introduction of IMRT has improved the long-term quality of life of HN cancer patients who have been treated with radiation therapy, but might cause more acute side effects. Longer follow-up is needed to study late complications.
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| 19. |
- Abel, Edvard, 1970, et al.
(författare)
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Long-Term Aspects of Quality of Life in Head and Neck Cancer Patients Treated With Intensity Modulated Radiation Therapy: A 5-Year Longitudinal Follow-up and Comparison with a Normal Population Cohort
- 2020
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Ingår i: Advances in Radiation Oncology. - : Elsevier BV. - 2452-1094. ; 5:1, s. 101-110
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Tidskriftsartikel (refereegranskat)abstract
- © 2019 The Author(s) Purpose: Knowledge of long-term health-related quality of life (HRQOL) in patients with advanced head and neck cancer treated with intensity modulated radiation therapy is scarce. Methods and Materials: HRQOL in 126 patients with advanced head and neck cancer treated with intensity modulated radiation therapy was followed longitudinally from diagnosis to 5 years after treatment with the European Organization for Research and Treatment of Cancer's QLQ-C30, the European Organization for Research and Treatment of Cancer's Head and Neck Cancer Module, and the M.D. Anderson Dysphagia Inventory. The survivors' HRQOL was compared with an age- and sex-matched normal population cohort. Results: At 5 years, 73 of the 95 surviving patients had completed the study. Significant reductions in general pain (29 vs 12), head and neck (HN) pain (22 vs 14), and feeling ill (20 vs 10) were found, and emotional functioning (70 vs 83) and global quality of life (67 vs 74) improved, compared with baseline values. Conversely, dry mouth (19 vs 56), senses (8 vs 27), teeth problems (10 vs 22), opening mouth (19 vs 56), and sticky saliva (15 vs 40) were markedly worse, although significant improvements had occurred over time after treatment. Anderson Dysphagia Inventory scores >80 at 5 years indicated good swallowing function. In a subgroup analysis, dry mouth and senses were significantly better in patients treated with chemoradiotherapy. Comparison to a normal population cohort's HRQOL shows that the study group experienced a wide array of symptoms affecting their quality of life. Conclusions: The results of this large, long-term follow-up study show that a majority of patients report a reasonable quality of life 5 years after treatment and that there seems to be continuous improvement over time. Comparison with a normal population cohort, however, underlines the fact that classical side effects remain, even with improved radiation techniques. Additional emphasis on normal-tissue-sparing radiation therapy is warranted, with close attention devoted to HRQOL outcomes.
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| 20. |
- Adolfsson, Karin, et al.
(författare)
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Referral of patients with cancer to palliative care: Attitudes, practices and work-related experiences among Swedish physicians
- 2022
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Ingår i: European Journal of Cancer Care. - : Hindawi Limited. - 0961-5423 .- 1365-2354. ; 31:6
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Tidskriftsartikel (refereegranskat)abstract
- Objective This study aimed to explore the attitudes, practices and work-related experiences among Swedish physicians regarding the referral process, integration and transition between oncology care and palliative care (PC). Methods A cross-sectional online survey was performed with a study-specific questionnaire in 2016-2017 in south-eastern Sweden. Physicians working with cancer patients within surgical specialties, medical specialties and paediatric oncology participated. Results The vast majority of the 130 participating physicians (99.2%) stated that PC was beneficial for the patient and were positive about early integration of PC (65.5%). Still, only 27.6% of the participants introduced PC at an early stage of non-curable disease. However, paediatric oncologists had a very early introduction of PC in comparison with medical specialties (p = 0.004). Almost 90% of the study population said they wanted to know that the patient had been taken care of by another care facility. Conclusions Despite the physicians' positive attitude towards early integration and referral to PC, they often acted late in the disease trajectory. This late approach can reduce the patient's opportunity of improving quality of life during severe circumstances. There is a need for in-depth knowledge of the physicians' challenges in order to bridge the gap between intentions and actions.
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| 21. |
- Ask, Anders, et al.
(författare)
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The potential of proton beam radiation therapy in head and neck cancer.
- 2005
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Ingår i: Acta oncologica (Stockholm, Sweden). - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 44:8, s. 876-80
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Tidskriftsartikel (refereegranskat)abstract
- A group of Swedish oncologists and hospital physicists have estimated the number of patients in Sweden suitable for proton beam therapy. The estimations have been based on current statistics of tumour incidence, 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 and normal tissues. In head and neck cancer, including thyroid cancer, it is assessed that at least 300 patients annually will gain sufficiently from proton beam therapy, both to improve tumour control and to decrease toxicity to compensate for the increased treatment costs using protons.
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| 22. |
- Barlind, Anna, 1978, et al.
(författare)
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Decreased cytogenesis in the granule cell layer of the hippocampus and impaired place learning after irradiation of the young mouse brain evaluated using the IntelliCage platform.
- 2010
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Ingår i: Experimental brain research. - : Springer Science and Business Media LLC. - 1432-1106 .- 0014-4819. ; 201:4, s. 781-787
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Tidskriftsartikel (refereegranskat)abstract
- Radiation therapy is used to treat malignant tumors in the brain and central nervous system involvement of leukemia and lymphomas in children. However, ionizing radiation causes a number of adverse long-term side effects in the brain, including cognitive impairment. Hippocampal neurogenesis is important for place learning and has been shown to be decreased by irradiation (IR) in rats and mice. In the present study, 10-day-old male mice received 6-Gy IR to the brain on postnatal day 10. We used BrdU labeling of the granule cell layer (GCL) of the hippocampus to evaluate cell proliferation and survival. An unbiased, automated platform for monitoring of behavior in a group housing environment (IntelliCage) was used to evaluate place learning 2 months after IR. We show that cranial IR impaired place learning and reduced BrdU labeling by 50% in the GCL. Cranial IR also reduced whole body weight gain 5%. We conclude that this experimental paradigm provides a novel and time-saving model to detect differences in place learning in mice subjected to IR. This method of detecting behavioral differences can be used for further studies of adverse effects of IR on hippocampal neurogenesis and possible new strategies to ameliorate the negative effects of IR on cognition.
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| 23. |
- Barlind, Anna, 1978, et al.
(författare)
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The growth hormone secretagogue hexarelin increases cell proliferation in neurogenic regions of the mouse hippocampus.
- 2010
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Ingår i: Growth hormone & IGF research. - : Elsevier BV. - 1532-2238 .- 1096-6374. ; 20:1, s. 49-54
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Radiation therapy (RT) to the brain is often used in the treatment of children with different types of malignant diseases affecting the brain. However, RT in childhood may also have severe side effects including impaired brain maturation and intellectual development. For childhood cancer survivors these adverse effects of RT can cause lifelong disability and suffering. Therefore, there is an unmet need to limit late effects after RT. Precursor cells in the subgranular zone of the dentate gyrus (DG) in the hippocampus are particularly sensitive to irradiation (IR). This may be of significance as newly generated neurons in the DG are important for memory and learning. GH secretagogues (GHS) have previously been shown to promote neurogenesis and to have neuroprotective effects. In addition, several parts of the brain, including the hippocampus, have been shown to express the GHS receptor 1a (GHS-R1a). The aim of this study was to evaluate the potential effect of the GHS hexarelin on proliferation and survival of progenitor cells in the hippocampus after brain IR in a mouse model. DESIGN: In the present study, 10-day-old male mice received 6Gy cranial IR. Non-irradiated sham animals were used as controls. We treated one group of irradiated and one sham group with hexarelin (100mug/kg/day) for 28days and used immunohistochemical labeling of bromo-deoxy uridine (BrdU) and phospho-histone H3 of the granular cell layer of the DG to evaluate proliferation and cell survival after IR at postnatal day ten. RESULTS: Our results show that hexarelin significantly increased the number of BrdU-positive cells in the granule cell layer by approximately 50% compared to controls. CONCLUSION: The increased number of BrdU-positive cells in the granule cell layer suggests a partial restoration in the pool of proliferating cells by hexarelin after IR.
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| 24. |
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| 25. |
- Björk-Eriksson, Thomas, 1960, et al.
(författare)
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Discrimination of human tumor radioresponsiveness using low-dose rate irradiation
- 1998
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Ingår i: Int J Radiat Oncol Biol Phys. - 0360-3016. ; 42:5, s. 1147-53
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Evaluation of the theoretical and practical value of using low-dose rate (LDR) irradiation to increase the resolution of radiosensitivity testing of primary human tumors using clonogenic assays. METHODS AND MATERIALS: Fourteen human tumor cell lines were assessed for surviving fraction at 2-8 Gy (SF2-SF8) using low-dose rate irradiation and a clonogenic assay. Further data were collected from the literature for 64 low-dose rate irradiation survival curves from human tumor cell lines. The data were grouped into five different radioresponsiveness categories (A-E). An analysis was made of the ability of the graded survival levels to discriminate between the different radioresponse groups and compared with previous analyses for high-dose rate SF2. Fifteen human cervical carcinoma specimens were analysed for SF2 and SF3.5 following high- and low-dose rate irradiation. RESULTS: Low-dose rate irradiation increased the spread of tumor cell line radiosensitivity data and the ability to discriminate between radioresponse groups was greater at low than at high-dose rates. Using low-dose rate irradiation on primary tumor specimens and a soft agar clonogenic assay decreased the success rate in obtaining data. The latter dropped from 70% for high-dose rate SF2 to 51% for low-dose rate SF3.5. CONCLUSIONS: The work on cell lines illustrates that low-dose rate irradiation does improve the ability of clonogenic radiosensitivity measurements to discriminate between tumors of different radioresponsiveness groups. However, using low-dose rate irradiation on primary human tumors with a soft agar clonogenic assay was not practical because of reducing the success rate for obtaining data for radiosensitivity measurements.
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| 26. |
- Björk-Eriksson, Thomas, 1960, et al.
(författare)
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Fewer problems with dry nasal mucous membranes following local use of sesame oil
- 2000
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Ingår i: Rhinology. - 0300-0729. ; 38:4, s. 200-3
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Tidskriftsartikel (refereegranskat)abstract
- Many people experience problems with a dry nasal mucous membrane, often without wondering why. Their noses itch and burn and dried mucus collects there. These problems are exacerbated during the winter, in air-conditioned environments and after nasal irradiation. Twenty patients experiencing problems with dryness of the nose were selected from outpatient clinics, together with twenty patients who had previously undergone nasal irradiation. During the first five days no treatment was administered. For the following twenty days the patients sprayed sesame oil into each nostril three times a day. For the last five days no treatment was given. When both groups received treatment and sprayed sesame oil (Nozoil) in their noses, the nasal problems decreased significantly. The greatest effect is exerted on dryness. The side effects from using this oil are few in number and mild.
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| 27. |
- Björk-Eriksson, Thomas, 1960, et al.
(författare)
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Mortality Among Pediatric Patients With Acute Lymphoblastic Leukemia in Sweden From 1988 to 2017
- 2022
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Ingår i: JAMA network open. - : American Medical Association (AMA). - 2574-3805. ; 5:11
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Acute lymphoblastic leukemia (ALL) constitutes 20% to 30% of all pediatric cancers. The 5-year overall survival among pediatric patients with ALL in high-income countries such as Sweden is currently more than 90%, but long-term unselected nationwide mortality data and mortality data in relation to the general population are lacking. Objective: To compare mortality between pediatric patients with ALL and the general population during a 30-year period in Sweden and to assess the incidence of ALL in Sweden. Design, Setting, and Participants: This cohort study included pediatric patients (aged <18 years) with a morphologically verified ALL diagnosis in the Swedish Cancer Register and/or at least 2 ALL diagnoses in the Swedish National Patient Register between January 1, 1988, and December 31, 2017. Data were cross-linked to the Swedish Cause of Death Register. Data were analyzed from May 2019 to January 2022. Main Outcomes and Measures: The main outcomes were mortality among patients with ALL compared with that in the general population and mortality in different subgroups within the cohort. Standardized mortality ratios (SMRs) were calculated using the general Swedish population as a reference. Within-cohort survival analyses were performed. Results: A total of 2397 patients (1354 [56%] male; mean [SD] age at diagnosis, 6.1 [4.7] years) were included in the study. The mean (SD) incidence of pediatric ALL during the study period was 4.11 (0.60) cases per 100 000 persons per year (females, 3.68 [0.65] cases per 100 000 persons per year; males, 4.52 [0.81] cases per 100 000 persons per year; P<.001). The observed number of deaths among pediatric patients with ALL was 409 vs the 9.5 deaths expected in the general population, resulting in an overall SMR of 43.1 (95% CI, 39.0-47.5); females had a higher SMR than males (57.8 [95% CI, 49.5-67.2] vs 34.5 [95% CI, 32.0-41.4]; P<.001). Analysis within the cohort showed a continued decrease in survival throughout the 30-year follow-up. The association between calendar year of ALL diagnosis, corresponding with different ALL treatment protocols, and mortality showed the lowest survival for the 1988-1991 group and the highest for the 2008-2017 group (χ2=20.3; P<.001). Conclusions and Relevance: In this cohort study, a consistently high SMR was seen among pediatric patients with ALL. Within the ALL cohort, survival evolved to a similar extent as in the young general population of Sweden. Furthermore, survival among patients with ALL decreased throughout the whole follow-up period without any trend difference after the 5-year follow-up time point. The changes in ALL treatment protocols were associated with overall improved absolute survival over time.
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| 28. |
- Björk-Eriksson, Thomas, 1960, et al.
(författare)
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Potential impact on tumor control and organ preservation with cisplatin and 5-fluorouracil for patients with advanced tumors of the paranasal sinuses and nasal fossa. A prospective pilot study
- 1992
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Ingår i: Cancer. - 0008-543X. ; 70:11, s. 2615-20
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Tidskriftsartikel (refereegranskat)abstract
- METHODS. Twelve patients with advanced epithelial nonadenocarcinoma of the paranasal sinuses and nasal fossa were treated with three cycles of cisplatin (100 mg/m2, day 1) and 5-fluorouracil (1000 mg/m2/24 hours on days 1-5 by continuous infusion), followed by preoperative external radiation therapy of 48 Gy and limited surgery, clearing the paranasal sinuses and nasal fossa. RESULTS. After chemotherapy, 11 of 12 patients were free of the previous symptoms of disease. Clinical response rates were different, however, with an overall response rate of approximately 70% with no complete responses. Histopathologic analysis of resected specimens showed no vital tumor in eight patients, minimal microscopic disease in three patients, and infiltrating tumor in one patient. Local control was achieved in 11 of 12 patients. Ten patients are alive with no evidence of disease (mean follow-up, 27 months). Surgical mutilation was avoided, with no functional or cosmetic loss. CONCLUSIONS. The results of this small pilot study seem to indicate a high chemosensitivity of carcinomas of the paranasal sinuses and nasal fossa, which, in this study, has meant significant relief of symptoms and an unusually high rate of local control (90%) without mutilation.
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| 29. |
- Björk-Eriksson, Thomas, 1960, et al.
(författare)
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The immunohistochemical expression of DNA-PKCS and Ku (p70/p80) in head and neck cancers: relationships with radiosensitivity
- 1999
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Ingår i: Int J Radiat Oncol Biol Phys. - 0360-3016. ; 45:4, s. 1005-10
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The DNA-PK complex is one of the major pathways by which mammalian cells respond to DNA double-strand breaks induced by ionizing radiation. This study evaluated the relationship between the immunohistochemical expression of the individual components of DNA-PK and cellular radiosensitivity in head and neck cancers. METHODS AND MATERIALS: Biopsies from patients with previously untreated squamous cell carcinomas of the head and neck were assessed for inherent tumor radiosensitivity measured as the surviving fraction at 2 Gy (SF2) using a soft agar clonogenic assay. Paraffin-embedded tumor material from 64 successfully grown specimens was immunohistochemically stained for expression of DNA-PKcs and Ku (p70/p80). The same tumor material was previously analyzed for the immunohistochemical expression of p53. RESULTS: A significant correlation was found between the degree of expression of DNA-PKcs and Ku (p70/p80) (r = 0.55, p<0.001). There were no overall significant differences in the levels of expression of DNA-PKcs and Ku (p70/p80) in tumors from patients of either sex, different sites, histologies, and stages. No relationship was found between SF2 and the expression of either DNA-PKcs (r = 0.22, p = 0.081) or Ku (p70/p80) (r = 0.064, p = 0.62). Comparison with previous immunohistochemical characterization showed no significant correlations between the expression levels of p53 and either DNA-PKcs (r = 0.093, p = 0.46) or Ku (p70/p80) (r = -0.17, p = 0.17). CONCLUSIONS: This study suggests that determining the immunohistochemical expression of DNA-PK in head and neck cancers from multiple sites does not have a role as a predictive assay of tumor in vitro radiosensitivity.
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| 30. |
- Björk-Eriksson, Thomas, 1960, et al.
(författare)
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The in vitro radiosensitivity of human head and neck cancers
- 1998
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Ingår i: Br J Cancer. - 0007-0920. ; 77:12, s. 2371-5
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Tidskriftsartikel (refereegranskat)abstract
- A study was made of the intrinsic radiosensitivity of 140 biopsy and surgical specimens of malignant head and neck tumours of different histologies. Using a soft-agar clonogenic assay, the material was assessed for the ability to grow in culture (colony-forming efficiency; CFE) and inherent tumour radiosensitivity (surviving fraction at 2 Gy, SF2). The success rate for obtaining growth was 74% (104/140) with a mean CFE of 0.093% (median 0.031) and a range of 0.002-1.3%. SF2 was obtained for 88 of 140 specimens, representing a success rate of 63% with a mean SF2 of 0.48 (median 0.43) and a range of 0.10-1.00. There were no significant differences in radiosensitivity between different sites of the head and neck region. There were no significant relationships between SF2 and disease stage, nodal status, tumour grade, patient age, primary tumour growth pattern and CFE. The results were compared with those for other tumour types previously analysed with the same assay. The distribution of the SF2 values for the head and neck tumours was similar to that for 145 cervix carcinomas and there was no significant difference in mean radiosensitivity between the two tumour types. Also, there was no significant difference in radiosensitivity between head and neck tumours and either breast or colorectal cancers. However, a group of eight lymphomas was significantly more radiosensitive. These results confirm the feasibility of carrying out radiosensitivity measurements using a soft-agar clonogenic assay on head and neck tumours. In addition, the work has shown that radiosensitivity is independent of many clinical parameters and that the mean value is similar to that reported for cervix carcinomas.
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| 31. |
- Björk-Eriksson, Thomas, 1960, et al.
(författare)
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The lack of correlation between proliferation (Ki-67, PCNA, LI, Tpot), p53 expression and radiosensitivity for head and neck cancers
- 1999
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Ingår i: Br J Cancer. - 0007-0920. ; 80:9, s. 1400-4
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Tidskriftsartikel (refereegranskat)abstract
- A study was made of the relationship between measurements of radiosensitivity versus proliferation and p53 status in head and neck cancers. Inherent tumour radiosensitivity was assessed as surviving fraction at 2 Gy (SF2) using a clonogenic soft agar assay (n = 77). The results were compared to data on proliferation obtained by both flow cytometry (labelling index (LI), the potential doubling time (Tpot) n = 55) and immunohistochemistry (Ki-67 and PCNA; n = 68), together with immunohistochemical p53 expression (n = 68). There were no overall significant differences in the median values of the various parameters analysed for the different sites within the head and neck region, disease stages, grades of tumour differentiation or nodal states. A subgroup analysis showed that oropharyngeal (n = 22) versus oral cavity (n = 35) tumours were more radiosensitive (P = 0.056) and had a higher Ki-67 index (P = 0.001). Node-positive tumours had higher LI (P = 0.021) and a trend towards lower Tpot (P = 0.067) values than node-negative ones. No correlations were seen between SF2 and any of the parameters studied. The long-standing dogma of an increased radiosensitivity of rapidly proliferating cells in contrast to slowly proliferating cells was not confirmed. The study shows that parallel measurements of different biological markers can be obtained for a large number of patients with head and neck cancers. The independence of the various parameters studied suggests that there may be potential for their combined use as prognostic factors for the outcome of radiotherapy.
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| 32. |
- Björk-Eriksson, Thomas, 1960, et al.
(författare)
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The potential of proton beam radiation for palliation and reirradiation.
- 2005
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Ingår i: Acta oncologica (Stockholm, Sweden). - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 44:8, s. 918-20
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Tidskriftsartikel (refereegranskat)abstract
- A group of Swedish oncologists and hospital physicists have estimated the number of patients in Sweden suitable for proton beam therapy. The estimations have been based on current statistics of tumour incidence, 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 and normal tissues. If an estimated 1% of the palliative treatments can be administered by protons with substantial benefits to the patient, almost 100 patients per year in Sweden would be eligible. It is further estimated that around 150 patients per year in need of reirradiation would benefit from radiation with protons compared to photons.
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| 33. |
- Björk-Eriksson, Thomas, 1960, et al.
(författare)
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The potential of proton beam radiation therapy in breast cancer.
- 2005
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Ingår i: Acta oncologica (Stockholm, Sweden). - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 44:8, s. 884-9
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Tidskriftsartikel (refereegranskat)abstract
- A group of Swedish oncologists and hospital physicists have estimated the number of patients in Sweden suitable for proton beam therapy. The estimations have been based on current statistics of tumour incidence, 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 and normal tissues. In primary breast cancer, it is estimated that about 300 of the annually 3 425 irradiated patients can potentially be candidates for proton beam therapy to reduce late toxicity, mainly from the heart and lungs.
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| 34. |
- Björk-Eriksson, Thomas, 1960, et al.
(författare)
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The potential of proton beam therapy in paediatric cancer.
- 2005
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Ingår i: Acta oncologica (Stockholm, Sweden). - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 44:8, s. 871-5
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Tidskriftsartikel (refereegranskat)abstract
- A group of Swedish oncologists and hospital physicists have estimated the number of patients in Sweden suitable for proton beam therapy. The estimations have been based on current statistics of tumour incidence, 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 and normal tissues. It is estimated that in paediatric cancers, proton beams are of potential importance in 80-100 children annually in Sweden. About 20 of the patients have medulloblastoma. The main purpose is to reduce late sequelae, but these are also increased chances to avoid myelosupression during e.g. concomitant chemo-radiation and to further intensify the chemotherapy.
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| 35. |
- Björk-Eriksson, Thomas, 1960, et al.
(författare)
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The potentials of proton beam radiation therapy in malignant lymphoma, thymoma and sarcoma.
- 2005
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Ingår i: Acta oncologica (Stockholm, Sweden). - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 44:8, s. 913-7
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Tidskriftsartikel (refereegranskat)abstract
- A group of Swedish oncologists and hospital physicists have estimated the number of patients in Sweden suitable for proton beam therapy. The estimations have been based on current statistics of tumour incidence, 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 and normal tissues. Besides sarcomas of the base of skull, which are classical sites for proton beam therapy, it is estimated that about 40 patients yearly in Sweden with sarcomas at other sites are candidates for proton beam therapy. About 20 patients each with malignant lymphomas, chiefly in the mediastinum, and thymomas are also candidates to decrease doses to surrounding heart and lungs.
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| 36. |
- Björk-Eriksson, Thomas, 1960, et al.
(författare)
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Tumor radiosensitivity (SF2) is a prognostic factor for local control in head and neck cancers
- 2000
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Ingår i: Int J Radiat Oncol Biol Phys. - 0360-3016. ; 46:1, s. 13-9
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To evaluate prospectively the prognostic value of SF2 for local control and survival in patients undergoing radiation therapy for head and neck cancers. METHODS AND MATERIALS: Following informed consent tumor specimens were obtained from 156 patients with primary carcinomas of the head and neck region. The specimens were assessed for the ability to grow in vitro (colony forming efficiency, CFE) and inherent radiosensitivity measured as the surviving fraction at 2 Gy (SF2) using a soft-agar clonogenic assay. Patients were treated mainly with neoadjuvant chemotherapy plus radiation therapy usually as a combination of accelerated external beam and interstitial radiotherapy. The probabilities of local control and survival were analyzed by univariate, bivariate and Cox multivariate analyses. RESULTS: Successful growth was achieved in 110/156 specimens and SF2 values were obtained from 99/156. Eighty four out of these patients underwent radical treatment. The median SF2 value for the 84 tumors was 0.40. At a mean follow-up time of 25 months (range 7-65) the median SF2 value of tumors from 14 patients who developed local recurrence was 0.53, which was significantly higher than the median of 0.38 for tumors from 70 patients without local recurrence (p = 0.015). Tumor SF2 was a significant prognostic factor for local control (p = 0.036), but not for overall survival (p = 0.20). Tumor SF2 was an independent prognostic factor for local control within bivariate and Cox multivariate analyses. CONCLUSIONS: This study has shown that tumor radiosensitivity measured as SF2 is a significant prognostic factor for local control in head and neck cancers.
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| 37. |
- Blomstrand, Malin, 1974, et al.
(författare)
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Different reactions to irradiation in the juvenile and adult hippocampus
- 2014
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Ingår i: International Journal of Radiation Biology. - : Informa UK Limited. - 0955-3002 .- 1362-3095. ; 90:9, s. 807-815
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Cranial radiotherapy is an important tool in the cure of primary brain tumors. Unfortunately, it is associated with late-appearing toxicity to the normal brain tissue, including cognitive impairment, particularly in children. The underlying mechanisms are not fully understood but involve changes in hippocampal neurogenesis. Recent studies report essentially different responses in the juvenile and the adult brain after irradiation, but this has never been verified in a comparative study. Materials and methods: We subjected juvenile (9-day-old) and adult (6-month-old) male rats to a single dose of 6 Gray (Gy) whole brain irradiation and euthanized them 6 hours, 7 days or 4 weeks later. Hippocampal lysates were analyzed for caspase-3 activity (apoptosis) and the expression of cytokines, chemokines and growth factors. Four weeks after irradiation, the number of microglia (expressing ionized calcium-binding adapter molecule 1, Iba-1), activated microglia (expressing cluster of differentiation 68 [CD68]), bromodeoxyuridine (BrdU) incorporation and granule cell layer (GCL) volume were assessed. Results: The major findings were (i) higher baseline BrdU incorporation (cell proliferation) in juvenile than in adult controls, which explains the increased susceptibility to irradiation and higher level of acute cell death (caspase activity) in juvenile rats, leading to impaired growth and subsequently a smaller dentate gyrus volume 4 weeks after irradiation, (ii) more activated (CD68-positive) microglia in adult compared to juvenile rats, regardless of irradiation, and (iii) differently expressed cytokines and chemokines after cranial irradiation in the juvenile compared to the adult rat hippocampus, indicating a more pro-inflammatory response in adult brains. Conclusion: We found essentially diverse irradiation reactions in the juvenile compared to the adult hippocampus, indicating different mechanisms involved in degeneration and regeneration after injury. Strategies to ameliorate the cognitive deficits after cranial radiotherapy should therefore likely be adapted to the developmental level of the brain.
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| 38. |
- Blomstrand, Malin, et al.
(författare)
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Estimated clinical benefit of protecting neurogenesis in the developing brain during radiation therapy for pediatric medulloblastoma.
- 2012
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Ingår i: Neuro-Oncology. - : Oxford University Press (OUP). - 1523-5866 .- 1522-8517. ; 14:7, s. 882-889
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Tidskriftsartikel (refereegranskat)abstract
- We sought to assess the feasibility and estimate the benefit of sparing the neurogenic niches when irradiating the brain of pediatric patients with medulloblastoma (MB) based on clinical outcome data. Pediatric MB survivors experience a high risk of neurocognitive adverse effects, often attributed to the whole-brain irradiation that is part of standard management. Neurogenesis is very sensitive to radiation, and limiting the radiation dose to the hippocampus and the subventricular zone (SVZ) may preserve neurocognitive function. Radiotherapy plans were created using 4 techniques: standard opposing fields, intensity-modulated radiotherapy (IMRT), intensity-modulated arc therapy (IMAT), and intensity-modulated proton therapy (IMPT). Mean dose to the hippocampus and SVZ (mean for both sites) could be limited to 88.3% (range, 83.6%-91.0%), 77.1% (range, 71.5%-81.3%), and 42.3% (range, 26.6%-51.2%) with IMAT, IMRT, and IMPT, respectively, while maintaining at least 95% of the prescribed dose in 95% of the whole-brain target volume. Estimated risks for developing memory impairment after a prescribed dose of 23.4 Gy were 47% (95% confidence interval [CI], 21%-69%), 44% (95% CI, 21%-65%), 41% (95% CI, 22%-60%), and 33% (95% CI, 23%-44%) with opposing fields, IMAT, IMRT, and IMPT, respectively. Neurogenic niche sparing during cranial irradiation of pediatric patients with MB is feasible and is estimated to lower the risks of long-term neurocognitive sequelae. Greatest sparing is achieved with intensity-modulated proton therapy, thus making this an attractive option to be tested in a prospective clinical trial.
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| 39. |
- Blomstrand, Malin, 1974, et al.
(författare)
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No clinically relevant effect on cognitive outcomes after low-dose radiation to the infant brain: A population-based cohort study in Sweden
- 2014
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 53:9, s. 1143-1150
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Tidskriftsartikel (refereegranskat)abstract
- While the detrimental effects of cranial radiotherapy on the developing brain are well known, the effects on cognitive performance of low doses of ionizing radiation is less studied. We performed a population-based cohort study to determine whether low doses of ionizing radiation to the brain in infancy affects cognitive function later in life. Further we hypothesized that the dose to the hippocampus predicts cognitive late side effects better than the anterior or the posterior brain doses. Material and methods. During 1950 - 1960 3860 boys were treated with radiation in Sweden for cutaneous hemangiomas before the age of 18 months. Of these, 3030 were analyzed for military test scores at the age of 18 years and 2559 for the highest obtained educational level. Results. Logical, spatial and technical test scores were not affected by increasing irradiation doses. The verbal test scores displayed a significant trend for decreasing scores with increasing doses to the hippocampus (p = 0.005). However, the absolute mean difference between the zero dose and the highest dose category (median 680 mGy) was very small, only 0.64 stanine points, and the significance was dependent on the highest dose category, containing few subjects. The educational level was not affected by brain irradiation. Overall, the hippocampal dose was a better predictor of late cognitive side effects than the doses to the anterior or the posterior brain. In conclusion, there was no decrease in logical, spatial and technical verbal or global test scores after ionizing radiation doses up to 250 mGy, but a subtle decrease in verbal test scores if the highest dose category was included (median 680 mGy). However, the clinical relevance of this decline in the highest dose group is questionable, since we could not find any effect on the highest obtained educational level.
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| 40. |
- Brodin, N Patrik, et al.
(författare)
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Hippocampal sparing radiotherapy for pediatric medulloblastoma: impact of treatment margins and treatment technique.
- 2014
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Ingår i: Neuro-oncology. - : Oxford University Press (OUP). - 1523-5866 .- 1522-8517. ; 16:4, s. 594-602
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundWe investigated how varying the treatment margin and applying hippocampal sparing and proton therapy impact the risk of neurocognitive impairment in pediatric medulloblastoma patients compared with current standard 3D conformal radiotherapy.MethodsWe included 17 pediatric medulloblastoma patients to represent the variability in tumor location relative to the hippocampal region. Treatment plans were generated using 3D conformal radiotherapy, hippocampal sparing intensity-modulated radiotherapy, and spot-scanned proton therapy, using 3 different treatment margins for the conformal tumor boost. Neurocognitive impairment risk was estimated based on dose-response models from pediatric CNS malignancy survivors and compared among different margins and treatment techniques.ResultsMean hippocampal dose and corresponding risk of cognitive impairment were decreased with decreasing treatment margins (P < .05). The largest risk reduction, however, was seen when applying hippocampal sparing proton therapy-the estimated risk of impaired task efficiency (95% confidence interval) was 92% (66%-98%), 81% (51%-95%), and 50% (30%-70%) for 3D conformal radiotherapy, intensity-modulated radiotherapy, and proton therapy, respectively, for the smallest boost margin and 98% (78%-100%), 90% (60%-98%), and 70% (39%-90%) if boosting the whole posterior fossa. Also, the distance between the closest point of the planning target volume and the center of the hippocampus can be used to predict mean hippocampal dose for a given treatment technique.ConclusionsWe estimate a considerable clinical benefit of hippocampal sparing radiotherapy. In choosing treatment margins, the tradeoff between margin size and risk of neurocognitive impairment quantified here should be considered.
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| 41. |
- Brodin, N. Patrik, et al.
(författare)
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Life years lost-comparing potentially fatal late complications after radiotherapy for pediatric medulloblastoma on a common scale
- 2012
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Ingår i: Cancer. - : Wiley. - 1097-0142 .- 0008-543X. ; 118:21, s. 5432-5440
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The authors developed a framework for estimating and comparing the risks of various long-term complications on a common scale and applied it to 3 different techniques for craniospinal irradiation in patients with pediatric medulloblastoma. METHODS: Radiation dose-response parameters related to excess hazard ratios for secondary breast, lung, stomach, and thyroid cancer; heart failure, and myocardial infarction were derived from large published clinical series. Combined with age-specific and sex-specific hazards in the US general population, the dose-response analysis yielded excess hazards of complications for a cancer survivor as a function of attained age. After adjusting for competing risks of death, life years lost (LYL) were estimated based on excess hazard and prognosis of a complication for 3-dimensional conformal radiotherapy (3D CRT), volumetric modulated arc therapy (VMAT), and intensity-modulated proton therapy (IMPT). RESULTS: Lung cancer contributed most to the estimated LYL, followed by myocardial infarction, and stomach cancer. The estimates of breast or thyroid cancer incidence were higher than those for lung and stomach cancer incidence, but LYL were lower because of the relatively good prognosis. Estimated LYL ranged between 1.90 years for 3D CRT to 0.28 years for IMPT. In a paired comparison, IMPT was associated with significantly fewer LYL than both photon techniques. CONCLUSIONS: Estimating the risk of late complications is associated with considerable uncertainty, but including prognosis and attained age at an event to obtain the more informative LYL estimate added relatively little to this uncertainty. Cancer 2012. (c) 2012 American Cancer Society.
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| 42. |
- Brodin, N. Patrik, et al.
(författare)
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Modeling freedom from progression for standard-risk medulloblastoma : A mathematical tumor control model with multiple modes of failure
- 2013
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Ingår i: International Journal of Radiation Oncology, Biology, Physics. - : Elsevier BV. - 0360-3016. ; 87:2, s. 422-429
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Tidskriftsartikel (refereegranskat)abstract
- Purpose As pediatric medulloblastoma (MB) is a relatively rare disease, it is important to extract the maximum information from trials and cohort studies. Here, a framework was developed for modeling tumor control with multiple modes of failure and time-to-progression for standard-risk MB, using published pattern of failure data. Methods and Materials Outcome data for standard-risk MB published after 1990 with pattern of relapse information were used to fit a tumor control dose-response model addressing failures in both the high-dose boost volume and the elective craniospinal volume. Estimates of 5-year event-free survival from 2 large randomized MB trials were used to model the time-to-progression distribution. Uncertainty in freedom from progression (FFP) was estimated by Monte Carlo sampling over the statistical uncertainty in input data. Results The estimated 5-year FFP (95% confidence intervals [CI]) for craniospinal doses of 15, 18, 24, and 36 Gy while maintaining 54 Gy to the posterior fossa was 77% (95% CI, 70%-81%), 78% (95% CI, 73%-81%), 79% (95% CI, 76%-82%), and 80% (95% CI, 77%-84%) respectively. The uncertainty in FFP was considerably larger for craniospinal doses below 18 Gy, reflecting the lack of data in the lower dose range. Conclusions Estimates of tumor control and time-to-progression for standard-risk MB provides a data-driven setting for hypothesis generation or power calculations for prospective trials, taking the uncertainties into account. The presented methods can also be applied to incorporate further risk-stratification for example based on molecular biomarkers, when the necessary data become available.
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| 43. |
- Brodin, N Patrik, et al.
(författare)
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Radiobiological risk estimates of adverse events and secondary cancer for proton and photon radiation therapy of pediatric medulloblastoma.
- 2011
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Ingår i: Acta oncologica (Stockholm, Sweden). - 1651-226X. ; 50:6, s. 806-16
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Introduction. The aim of this model study was to estimate and compare the risk of radiation-induced adverse late effects in pediatric patients with medulloblastoma (MB) treated with either three-dimensional conformal radiotherapy (3D CRT), inversely-optimized arc therapy (RapidArc(®) (RA)) or spot-scanned intensity-modulated proton therapy (IMPT). The aim was also to find dose-volume toxicity parameters relevant to children undergoing RT to be used in the inverse planning of RA and IMPT, and to use in the risk estimations. Material and methods. Treatment plans were created for all three techniques on 10 pediatric patients that have been treated with craniospinal irradiation (CSI) at our institution in 2007-2009. Plans were generated for two prescription CSI doses, 23.4 Gy and 36 Gy. Risk estimates were based on childhood cancer survivor data when available and secondary cancer (SC) risks were estimated as a function of age at exposure and attained age according to the organ-equivalent dose (OED) concept. Results. Estimates of SC risk was higher for the RA plans and differentiable from the estimates for 3D CRT at attained ages above 40 years. The risk of developing heart failure, hearing loss, hypothyroidism and xerostomia was highest for the 3D CRT plans. The risks of all adverse effects were estimated as lowest for the IMPT plans, even when including secondary neutron (SN) irradiation with high values of the neutron radiation weighting factors (WR(neutron)). Conclusions. When comparing RA and 3D CRT treatment for pediatric MB it is a matter of comparing higher SC risk against higher risks of non-cancer adverse events. Considering time until onset of the different complications is necessary to fully assess patient benefit in such a comparison. The IMPT plans, including SN dose contribution, compared favorably to the photon techniques in terms of all radiobiological risk estimates.
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| 46. |
- 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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| 47. |
- Ekholm, S. E., et al.
(författare)
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MRI staging using gadodiamide for soft-tissue tumors of the head and neck region. Results from a phase II trial and a 5-year clinical follow-up
- 2001
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Ingår i: Eur J Radiol. - 0720-048X. ; 39:3, s. 168-75
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Tidskriftsartikel (refereegranskat)abstract
- In order to document the safety, tolerability and efficacy of gadodiamide outside CNS, an open, non-drug comparative study was performed in patients with tumors of the head and neck region. Fifty adult patients were included and 48 patients received the contrast medium. The examinations were performed on a 1.5 T imager using transverse, non-enhanced T1- and PD-/T2-weighted conventional spin-echo sequences, followed by a contrast-enhanced transverse T1-weighted sequence. Post-contrast images provided more diagnostic information compared to unenhanced images in 33 of 48 patients (69%). This information was of significant help in four and of moderate help in 14 cases. Post-contrast images compared to non-enhanced T1-weighted showed improvement in lesion delineation for 29 of the 43 patients where a lesion was observed. Only in two patients was the diagnostic information lower post-contrast. A comparison between all pre-contrast images versus contrast medium enhanced showed post-contrast images to give more diagnostic information in 14 and less in nine patients. No patient experienced discomfort in relation to gadodiamide injection. Only one adverse event occurred which was described as thirst, being of moderate intensity. The 5-year clinical outcome was analyzed and compared with the pre-operative staging. The case-books of all patients were reviewed and in 44 patients all information could be found. Of those, 18 were still alive, one with active disease (AAD) and 17 with no evidence of disease (NED). Two of those four patients, where information was incomplete, showed NED and two had died. This trial showed that contrast-enhancement using gadodiamide for evaluation of soft tissue tumors in the head and neck region was safe and provided statistically significant more diagnostic information compared with unenhanced images. MRI, when compared with palpation/inspection, changed tumor staging in approximately 30% of all cases.
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| 48. |
- Fernström, Erik, et al.
(författare)
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Results of preoperative chemoradiotherapy for patients with advanced cancer of the nasal cavity and paranasal sinuses.
- 2017
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Ingår i: Acta oto-laryngologica. - : Informa UK Limited. - 1651-2251 .- 0001-6489. ; 137:12, s. 1292-1300
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Tidskriftsartikel (refereegranskat)abstract
- Curative treatment of nasal cavity and paranasal sinus cancer is challenging due to the proximity to critical anatomical structures. The purpose of this study was to analyze the impact of trimodality therapy with preoperative chemotherapy and reduced-dose radiotherapy followed by organ-preserving surgery for treating patients with nasal cavity and paranasal sinus cancer.This retrospective study included all 156 patients diagnosed with sinonasal cancer in western Sweden between 1986 and 2009. We determined the treatment selection pattern and treatment outcomes for 79 patients treated with preoperative chemoradiotherapy.Squamous cell carcinoma was the most common histology. The five-year overall survival was 54%, and 85% of these patients had T3 or T4 tumors. The five-year cumulative incidence rate of local recurrence was 32%. The five-year overall survival in patients with squamous cell carcinoma and adenocarcinoma was 45% and 76%, respectively. The median preoperative radiation dose was 48Gy. Orbital exenteration was performed in 7% of patients.Preoperative chemoradiotherapy may be beneficial for patients with advanced sinonasal cancer when primary radical surgery is challenging. Survival outcomes were comparable to outcomes reported in the literature despite conservative surgery and relatively low radiation doses in patients with locally advanced tumors.
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| 49. |
- Flejmer, Anna M.
(författare)
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Radiation burden from modern radiation therapy techniques including proton therapy for breast cancer treatment - clinical implications
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The purpose of this thesis was to study the clinical implications of modern radiotherapy techniques for breast cancer treatment. This was investigated in several individual studies.Study I investigated the implications of using the analytical anisotropic algorithm (AAA) from the perspective of clinical recommendations for breast cancer radiotherapy. Pencil beam convolution plans of 40 breast cancer patients were recalculated with AAA. The latter plans had a significantly worse coverage of the planning target volume (PTV) with the 93% isodose, higher maximum dose in hotspots, higher volumes of the ipsilateral lung receiving doses below 25 Gy and smaller volumes with doses above 25 Gy. AAA also predicted lower doses to the heart.Study II investigated the implications of using the irregular surface compensator (ISC), an electronic compensation algorithm, in comparison to three‐dimensional conformal radiotherapy (3D‐CRT) for breast cancer treatment. Ten breast cancer patients were planned with both techniques. The ISC technique led to better coverage of the clinical target volume of the tumour bed (CTV‐T) and PTV in almost all patients with significant improvement in homogeneity.Study III investigated the feasibility of using scanning pencil beam proton therapy for regional and loco‐regional breast cancer with comparison of ISC photon planning. Ten patients were included in the study, all with dose heterogeneity in the target and/or hotspots in the normal tissues outside the PTV. The proton plans showed comparable or better CTV‐T and PTV coverage, with large reductions in the mean doses to the heart and the ipsilateral lung.Study IV investigated the added value of enhanced inspiration gating (EIG) for proton therapy. Twenty patients were planned on CT datasets acquired during EIG and freebreathing (FB) using photon 3D‐CRT and scanning proton therapy. Proton spot scanning has a high potential to reduce the irradiation of organs‐at‐risk for most patients, beyond what could be achieved with EIG and photon therapy, especially in terms of mean doses to the heart and the left anterior descending artery.Study V investigated the impact of physiological breathing motion during proton radiotherapy for breast cancer. Twelve thoracic patients were planned on CT datasets during breath‐hold at inhalation phase and breath‐hold at exhalation phase. Between inhalation and exhalation phase there were very small differences in dose delivered to the target and cardiovascular structures, with very small clinical implication.The results of these studies showed the potential of various radiotherapy techniques to improve the quality of life for breast cancer patients by limiting the dose burden for normal tissues.
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| 50. |
- Fukuda, A., et al.
(författare)
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Age-dependent sensitivity of the developing brain to irradiation is correlated with the number and vulnerability of progenitor cells
- 2005
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Ingår i: J Neurochem. ; 92:3, s. 569-84
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Tidskriftsartikel (refereegranskat)abstract
- In a newly established model of unilateral, irradiation (IR)-induced injury we compared the outcome after IR to the immature and juvenile brain, using rats at postnatal days 9 or 23, respectively. We demonstrate that (i) the immature brains contained more progenitors in the subventricular zone (SVZ) and subgranular zone (SGZ) compared with the juvenile brains; (ii) cellular injury, as judged by activation of caspase 3 and p53, as well as nitrotyrosine formation, was more pronounced in the SVZ and SGZ in the immature brains 6 h after IR; (iii) the number of progenitor and immature cells in the SVZ and SGZ decreased 6 h and 7 days post-IR, corresponding to acute and subacute effects in humans, respectively, these effects were more pronounced in immature brains; (iv) myelination was impaired after IR at both ages, and much more pronounced after IR to immature brains; (v) the IR-induced changes remained significant for at least 10 weeks, corresponding to late effects in humans, and were most pronounced after IR to immature brains. It appears that IR induces both an acute loss of progenitors through apoptosis and a perturbed microenvironment incompatible with normal proliferation and differentiation, and that this is more pronounced in the immature brain.
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