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3. Halved contrast medium dose coronary dual-layer CT-angiography – phantom study of tube current and patient characteristics

Author

Researchgr. Systems Radiology, Researchgr. Hart-brein as., Brain, Circulatory Health, MS Radiologie, Cancer, Infection & Immunity, Regenerative Medicine and Stem Cells, Kristiansen, C. H., Tetteroo, P. M., Dobrolinska, M. M., Lauritzen, P. M., Velthuis, B. K., Greuter, M. J.W., Suchá, D., de Jong, P. A., van der Werf, N. R., Researchgr. Systems Radiology, Researchgr. Hart-brein as., Brain, Circulatory Health, MS Radiologie, Cancer, Infection & Immunity, Regenerative Medicine and Stem Cells, Kristiansen, C. H., Tetteroo, P. M., Dobrolinska, M. M., Lauritzen, P. M., Velthuis, B. K., Greuter, M. J.W., Suchá, D., de Jong, P. A., and van der Werf, N. R.

Published
2024

8. A New Scoring Tool to Estimate Post-Treatment Ambulatory Status after Radiotherapy of Metastatic Spinal Cord Compression

Author

Rades, D., primary, Al-Salool, A., additional, Cremers, F., additional, Staackmann, C., additional, Cacicedo, J., additional, Lomidze, D., additional, Segedin, B., additional, Groselj, B., additional, Jankarashvili, N., additional, Moreno, A.J. Conde, additional, Ciervide, R., additional, Kristiansen, C., additional, and Schild, S.E., additional

Published
2022
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10. Surveillance with FDG PET/CT after Completion of Therapy for NSCLC: A Status Update on Inclusion in the SUPE_R Trial

Author

Guldbrandsen, K., Skougaard, K., Rasmussen, T. R., Sørensen, B., Mortensen, L. S., Saghir, Z., Borissova, S., Persson, G., Skuladottir, H., Thisaruban, S., Bødtger, U., Schwaner, S. H., Land, L. H., Gerke, O., Laursen, C. B., Ahlborn, L. B., Pøhl, M., Meyer, C. N., Ehlers, J., Christophersen, M. S., Kristiansen, C., Hilberg, O., Rychwicka-Kielek, B. A., McCulloch, T., and Fischer, B. M.

Published
2022

11. EP01.07-001 Surveillance with FDG PET/CT after Completion of Therapy for NSCLC: A Status Update on Inclusion in the SUPE_R Trial

Author

Guldbrandsen, K., primary, Skougaard, K., additional, Rasmussen, T.R., additional, Sørensen, B., additional, Mortensen, L.S., additional, Saghir, Z., additional, Borissova, S., additional, Persson, G., additional, Skuladottir, H., additional, Thisaruban, S., additional, Bødtger, U., additional, Schwaner, S.H., additional, Land, L.H., additional, Gerke, O., additional, Laursen, C.B., additional, Ahlborn, L.B., additional, Pøhl, M., additional, Meyer, C.N., additional, Ehlers, J., additional, Christophersen, M.S., additional, Kristiansen, C., additional, Hilberg, O., additional, Rychwicka-Kielek, B.A., additional, McCulloch, T., additional, and Fischer, B.M., additional

Published
2022
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13. Thorough design and pre-trial quality assurance (QA) decrease dosimetric impact of delineation and dose planning variability in the STRICTLUNG and STARLUNG trials for stereotactic body radiotherapy (SBRT) of central and ultra-central lung tumours

Author

Hoffmann, L., Persson, G. F., Nygård, L., Nielsen, T. B., Borrisova, S., Gaard-Petersen, F., Josipovic, M., Khalil, A. A., Kjeldsen, R., Knap, M. M., Kristiansen, C., Møller, D. S., Ottosson, W., Sand, H., Thing, R., Pøhl, M., and Schytte, T.

Subjects
Organs at Risk, RISK, PATTERNS-OF-CARE, ORGANS, Lung Neoplasms, Stereotactic body radiotherapy, Radiotherapy Planning, Computer-Assisted, Radiotherapy Dosage, Hematology, ATLAS, Radiosurgery, CANCER, Quality assurance, TOXICITY, Oncology, CLINICAL-PRACTICE, RADIATION-THERAPY, PHASE-II, Humans, Central tumours, HEART, Radiology, Nuclear Medicine and imaging, Radiotherapy, Intensity-Modulated, Lung tumours, Retrospective Studies
Abstract

Introduction: SBRT of central lung tumours implies significant risk of toxicity. We are initiating two phase II trials prescribing 56 Gy/eight fractions to PTV, allowing for dose escalation of GTV. We prioritize organs at risk (OAR) constraints over target coverage, making the treatment plans very sensitive to OAR delineation variations. The aim of this study is to quantify the dosimetric impact of contouring variations and to provide a thorough description of pre-trial quality assurance to be used in upcoming trials to provide consistent clinical care.& nbsp;Materials and methods: Delineation: Seven physicians delineated OAR in three rounds, with evaluations in-between. For each patient case, seven treatment plans, repeatedly using each of the OAR structure sets from the seven physicians, were made and compared to evaluate the dosimetric effect of delineation variability.& nbsp;Treatment planning: Treatment plans for seven cases were made at six departments in two rounds, with discussion in-between.& nbsp;Results: OAR delineation variation between centres resulted in high variabilities in OAR dose for simulated plans and led to potential overdosage of the lobar bronchus (constraint: D0.03cc < 45 Gy), with maximum doses ranging between 58 Gy (first round), and 50 Gy (third round). For mediastinal tissue, the constraint (D0.03cc < 45 Gy) was violated for the majority of the delineations in all three rounds, with maximum doses of 84 Gy (first round), and 72 Gy (third round). For the treatment planning study, the range of the standard deviation for GTV mean dose was 12.8-18.5 Gy (first round) and 2.8-3.5 Gy (second round).& nbsp;Conclusions: Even small variations in OAR delineation led to high OAR overdosage. The study demonstrates the importance of having extensive QA procedures in place before initiating clinical trials on dose escalation in SBRT. (C) 2022 The Author(s). Published by Elsevier B.V. Radiotherapy and Oncology xxx (2022) xxx-xxx.

Published
2022

15. Thorough design and pre-trial quality assurance (QA) decrease dosimetric impact of delineation and dose planning variability in the STRICTLUNG and STARLUNG trials for stereotactic body radiotherapy (SBRT) of central and ultra-central lung tumours

Author

Hoffmann, L., primary, Persson, G.F., additional, Nygård, L., additional, Nielsen, T.B., additional, Borrisova, S., additional, Gaard-Petersen, F., additional, Josipovic, M., additional, Khalil, A.A., additional, Kjeldsen, R., additional, Knap, M.M., additional, Kristiansen, C., additional, Møller, D.S., additional, Ottosson, W., additional, Sand, H., additional, Thing, R., additional, Pøhl, M., additional, and Schytte, T., additional

Published
2022
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19. MO-0550 Pre-study QA reduces delineation errors and minimize dose to OAR in a central lung tumour SBRT trial

Author

Hoffmann, L., primary, Persson, G.F., additional, Nygård, L., additional, Nielsen, T.B., additional, Borrisova, S., additional, Gaard-Petersen, F., additional, Josipovic, M., additional, Khalil, A.A., additional, Kjeldsen, R., additional, Knap, M.M., additional, Kristiansen, C., additional, Møller, D.S., additional, Ottosson, W., additional, Sand, H., additional, Thing, R., additional, Pøhl, M., additional, and Schytte, T., additional

Published
2022
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22. P10.06 Affiliation to the Labour Market in Denmark for Patients Under 60 Years of Age After Diagnosis and Treatment for ALK-Positive NSCLC

Author

Andersen, J., primary, Johansen, J., additional, Urbanska, E., additional, Meldgaard, P., additional, Hansen, P., additional, Kristiansen, C., additional, Stelmach, M., additional, Santoni-Rugiu, E., additional, Højgaard, B., additional, Jensen, M., additional, Dünweber, C., additional, and Hansen, K., additional

Published
2021
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27. Real word experience with first-line immunotherapy in advanced non-small cell lung cancer patients in a Danish nationwide cohort

Author

Mouritzen, M., Bjoernhart, B., Poehl, M., Ladekarl, M., Vesteghem, C., Boegsted, M., Nielsen, A.W. Moelby, Meldgaard, P., Hansen, K.H., Larsen, J.W.W., Kristiansen, C., Wedervang, K., Bareid-Oestby, A-C., Frank, M.S., Persson, G., Kristensen, E.B., Homann, P.H., and Carus, A.

Abstract

BackgroundImmune checkpoint inhibitors (ICIs) have become a cornerstone in the treatment of advanced non-small cell lung cancer (NSCLC). In the pivotal Keynote-024 study with highly selected patients, pembrolizumab improved survival compared with platinum-based chemotherapy (CT) in patients with a PD-L1 tumor proportion score ≥50% (median overall survival (mOS) 26.3 months and 1-year survival 70%) and treatment-related adverse events were less frequent compared to CT. Recent real-world studies show comparable results with the exception of patients with poor performance status (PS).MethodsData were collected retrospectively from consecutive patients treated in first-line with ICI from March 2017 to October 2018 in a nationwide oncology study. Clinical data included gender, age, smoking status, ECOG PS, TNM stage, histology, metastatic sites, comorbidity and reasons for treatment cessation and adverse events that caused hospitalization or death. Overall survival was assessed using Kaplan-Meier estimates and the association to clinical features determined by a multivariate Cox’s proportional hazards regression model.ResultsA total of 578 stage III-IV NSCLC patients were included. Median age was 69.8 years (range 45 – 88) and 43% were male. Tumors were predominantly adenocarcinomas (71%), and 82% of patients had stage IV disease. At baseline metastases to the brain, bones, and liver were observed in 7%, 28% and 11% of patients, respectively. Fifteen percent of patients had PS ≥2. Median OS was 19.6 months (95%CI 16.6-23.6), and estimated 1-year survival was 63.7%. In the multivariate analysis, patients with PS ≥2 (HR 1.7; 95%CI 1.2-2.3; P=0.002), bone metastases (HR 1.8; 95%CI 1.4-2.4; P=0.00) and liver metastases (HR 1.5; 95%CI 1.1-2.2; P=0.02) had a significantly worse prognosis. Age ≥75 years, sex, smoking status, histology, and Charlson Comorbidity Index Score were not significantly associated with OS.ConclusionsA slightly poorer mOS and 1-year survival of real-world NSCLC patients compared to randomized trials was explained primarily by treatment of patients with PS ≥2 and metastases to the liver and bones. Age ≥75 years was not associated with a poor outcome.

Published
2020

29. 1334P Real word experience with first-line immunotherapy in advanced non-small cell lung cancer patients in a Danish nationwide cohort

Author

Mouritzen, M., primary, Bjoernhart, B., additional, Poehl, M., additional, Ladekarl, M., additional, Vesteghem, C., additional, Boegsted, M., additional, Nielsen, A.W. Moelby, additional, Meldgaard, P., additional, Hansen, K.H., additional, Larsen, J.W.W., additional, Kristiansen, C., additional, Wedervang, K., additional, Bareid-Oestby, A-C., additional, Frank, M.S., additional, Persson, G., additional, Kristensen, E.B., additional, Homann, P.H., additional, and Carus, A., additional

Published
2020
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32. Neuropathy-related mutations alter the membrane binding properties of the human myelin protein P0 cytoplasmic tail

Author

Raasakka, A. (Arne), Ruskamo, S. (Salla), Barker, R. (Robert), Krokengen, O. C. (Oda C.), Vatne, G. H. (Guro H.), Kristiansen, C. K. (Cecilie K.), Hallin, E. I. (Erik I.), Skoda, M. W. (Maximilian W. A.), Bergmann, U. (Ulrich), Wacklin-Knecht, H. (Hanna), Jones, N. C. (Nykola C.), Hoffmann, S. V. (Søren V.), Kursula, P. (Petri), Raasakka, A. (Arne), Ruskamo, S. (Salla), Barker, R. (Robert), Krokengen, O. C. (Oda C.), Vatne, G. H. (Guro H.), Kristiansen, C. K. (Cecilie K.), Hallin, E. I. (Erik I.), Skoda, M. W. (Maximilian W. A.), Bergmann, U. (Ulrich), Wacklin-Knecht, H. (Hanna), Jones, N. C. (Nykola C.), Hoffmann, S. V. (Søren V.), and Kursula, P. (Petri)

Abstract

Schwann cells myelinate selected axons in the peripheral nervous system (PNS) and contribute to fast saltatory conduction via the formation of compact myelin, in which water is excluded from between tightly adhered lipid bilayers. Peripheral neuropathies, such as Charcot-Marie-Tooth disease (CMT) and Dejerine-Sottas syndrome (DSS), are incurable demyelinating conditions that result in pain, decrease in muscle mass, and functional impairment. Many Schwann cell proteins, which are directly involved in the stability of compact myelin or its development, are subject to mutations linked to these neuropathies. The most abundant PNS myelin protein is protein zero (P0); point mutations in this transmembrane protein cause CMT subtype 1B and DSS. P0 tethers apposing lipid bilayers together through its extracellular immunoglobulin-like domain. Additionally, P0 contains a cytoplasmic tail (P0ct), which is membrane-associated and contributes to the physical properties of the lipid membrane. Six CMT- and DSS-associated missense mutations have been reported in P0ct. We generated recombinant disease mutant variants of P0ct and characterized them using biophysical methods. Compared to wild-type P0ct, some mutants have negligible differences in function and folding, while others highlight functionally important amino acids within P0ct. For example, the D224Y variant of P0ct induced tight membrane multilayer stacking. Our results show a putative molecular basis for the hypermyelinating phenotype observed in patients with this particular mutation and provide overall information on the effects of disease-linked mutations in a flexible, membrane-binding protein segment. Using neutron reflectometry, we additionally show that P0ct embeds deep into a lipid bilayer, explaining the observed effects of P0ct on the physical properties of the membrane.

Published
2019

41. Molecular mechanisms of Charcot-Marie-Tooth neuropathy linked to mutations in human myelin protein P2

Author

Ruskamo, S. (Salla), Nieminen, T. (Tuomo), Kristiansen, C. K. (Cecilie K.), Vatne, G. H. (Guro H.), Baumann, A. (Anne), Hallin, E. I. (Erik I.), Raasakka, A. (Arne), Joensuu, P. (Päivi), Bergmann, U. (Ulrich), Vattulainen, I. (Ilpo), Kursula, P. (Petri), Ruskamo, S. (Salla), Nieminen, T. (Tuomo), Kristiansen, C. K. (Cecilie K.), Vatne, G. H. (Guro H.), Baumann, A. (Anne), Hallin, E. I. (Erik I.), Raasakka, A. (Arne), Joensuu, P. (Päivi), Bergmann, U. (Ulrich), Vattulainen, I. (Ilpo), and Kursula, P. (Petri)

Abstract

Charcot-Marie-Tooth (CMT) disease is one of the most common inherited neuropathies. Recently, three CMT1-associated point mutations (I43N, T51P, and I52T) were discovered in the abundant peripheral myelin protein P2. These mutations trigger abnormal myelin structure, leading to reduced nerve conduction velocity, muscle weakness, and distal limb atrophy. P2 is a myelin-specific protein expressed by Schwann cells that binds to fatty acids and membranes, contributing to peripheral myelin lipid homeostasis. We studied the molecular basis of the P2 patient mutations. None of the CMT1-associated mutations alter the overall folding of P2 in the crystal state. P2 disease variants show increased aggregation tendency and remarkably reduced stability, T51P being most severe. In addition, P2 disease mutations affect protein dynamics. Both fatty acid binding by P2 and the kinetics of its membrane interactions are affected by the mutations. Experiments and simulations suggest opening of the β barrel in T51P, possibly representing a general mechanism in fatty acid-binding proteins. Our findings demonstrate that altered biophysical properties and functional dynamics of P2 may cause myelin defects in CMT1 patients. At the molecular level, a few malformed hydrogen bonds lead to structural instability and misregulation of conformational changes related to ligand exchange and membrane binding.

Published
2017

50. PET/CT and histopathologic response to preoperative chemoradiation therapy in locally advanced rectal cancer

Author

Kristiansen, C., Loft, A., Berthelsen, Anne Kiil, Graff, J., Lindebjerg, J., Bisgaard, C., Jakobsen, A., Kristiansen, C., Loft, A., Berthelsen, Anne Kiil, Graff, J., Lindebjerg, J., Bisgaard, C., and Jakobsen, A.

Abstract

PURPOSE: The objective of this study was to investigate the possibility of using positron emission tomography/computer tomography to predict the histopathologic response in locally advanced rectal cancer treated with preoperative chemoradiation. METHODS: The study included 30 patients with locally advanced rectal adenocarcinoma treated with a combination of radiotherapy and concurrent Uftoral (uracil, tegafur) and leucovorine. All patients were evaluated by positron emission tomography/computer tomography scan seven weeks after end of chemoradiation, and the results were compared to histopathologic tumor regression as the "standard." The pathologic response was quantified by tumor regression grade. RESULTS: Positron emission tomography/computer tomography correctly identified six of eight patients (specificity 75 percent) with complete pathologic response. However, the sensitivity of positron emission tomography/computer tomography was only 45 percent and the accuracy 53 percent. The positive and negative predictive values were 83 and 33 percent, respectively. CONCLUSIONS: We conclude that positron emission tomography/computer tomography performed seven weeks after the end of chemoradiation is not able to predict the histopathologic response in locally advanced rectal cancer. There is an obvious need for other complementary methods especially with respect to the low sensitivity of positron emission tomography/computer tomography Udgivelsesdato: 2008/1

Published
2008

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