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  • 1.
    Asklund, Thomas
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Björ, Ove
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Malmström, Annika
    Blomquist, Erik
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Överlevnanden vid maligna gliom har ökat senaste tio åren. Analys av kvalitetsregisterdata.2012In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 109, no 17-18, p. 875-878Article in journal (Refereed)
    Abstract [en]

    The annual incidence rate of high grade malignant glioma (WHO grade III-IV) in Sweden is approximately 400 patients. The objective for the Swedish National CNS-tumor Group is to lay a foundation for research efforts and facilitate implementation and assessment of therapeutic strategies and health care for this patient group. In the analyses the diagnoses of high grade malignant gliomas are compared for the years 1999-2003, 2004-2006 and 2007-2009 for the Northern Region, the Uppsala Region and the South-east Region of Sweden, a population of 1844 patients. Survival was estimated from Kaplan-Meier survival curves, and a log-rank test was performed to assess whether the survival curves differed. The crude hazard ratio between years of diagnosis was estimated from a Cox regression model. Median survival for all patients 2004-2006 was 10.0 months (95 % confidence interval (CI) 8.9-10.9) compared to 8.1 months 1999-2003 (95 % CI 7.3-8.8). For patients 60-69 years of age almost a doubling of the survival rate has occurred during the last decade. Medan survival has increased from 5.8 months (95 % CI 5.1-7.5) 1999-2003 to 8.5 months (95 % CI 7.0-10.3) for 2004-2006 and to 10.5 months (95 % CI 9.0-12.6) for 2007-2009. Concomitant radiochemotherapy, but also the development of neurosurgical and radiotheraputic techniques and a more active therapeutic attitude, including the older patient groups, have probably contributed to the improved survival rate. A national population based registry, with a close to 100% registration compliance for important diagnostic and outcome parameters is probably an efficient instrument for evaluation of quality measures and implementation of new therapeutic strategies.

  • 2.
    Asklund, Thomas
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Danfors, T
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    PET response and tumor stabilization under erlotinib and bevacizumab treatment of an intracranial lesion non-invasively diagnosed as likely chordoma2011In: Clinical Neuropathology, ISSN 0722-5091, Vol. 30, no 5, p. 242-246Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Chordoma is a rare and a slow-growing tumor originating from the notochord and commonly localized in the skull base. Surgery and occasionally radiotherapy have emerged as the treatments of choice. In the relapsed situations available treatment options are strictly limited; however, recently molecularly targeted agents have been proposed to be of potential beneficial value. THE CASE: A 63-year-old male presenting with seizures and an extradural mass in the left brain hemisphere. An attempt to resect the tumor was followed by severe bradycardia when manipulating with the dura and therefore discontinued. It was considered too hazardous even to take a biopsy specimen. The tumor was considered radiologically and macroscopically as a chordoma. As the tumor progressed after radiotherapy, chemotherapy with erlotinib in combination with cetuximab was initiated. This treatment was interrupted due to progressive disease and toxicity. However, combination treatment with erlotinib and bevacizumab normalized the uptake of [11C]methionine PET signal and resulted in a slight tumor shrinkage on MRI. The patient is still (March 2011) free of symptoms, without cranial nerve deficits or seizures. DISCUSSION: This report shows that erlotinib and bevacizumab in combination may completely quench the transport of the essential amino acid methionine to a treatment refractory intracranial tumor bearing radiological and clinical characteristics of a chordoma. Further studies are necessary to establish this strategy as a treatment option for this indication.

  • 3.
    Asklund, Thomas
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Axelsson, Jan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Bergström, Åsa
    Kasper, Maria
    Ögren, Margareta
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Toftgård, Rune
    Riklund, Katrine Åhlström
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Early and persisting response to vismodegib in a patient with bone metastasizing medulloblastoma2013In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 52, no 4, p. 862-865Article in journal (Refereed)
  • 4.
    Asklund, Thomas
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Kvarnbrink, Samuel
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Holmlund, Camilla
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Wibom, Carl
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Bergenheim, Tommy
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Hedman, Håkan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Synergistic Killing of Glioblastoma Stem-like Cells by Bortezomib and HADC Inhibitors.2012In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 32, no 7, p. 2407-2413Article in journal (Refereed)
    Abstract [en]

    Background: The malignant brain tumour glioblastoma is a devastating disease that remains a therapeutic challenge. Materials and Methods: Effects of combinations of the US Food and Drug Administation (FDA) approved proteasome inhibitor bortezomib and the histone deacetylase (HDAC) inhibitors vorinostat, valproic acid and sodium phenylbutyrate were studied on primary glioblastoma stem cell lines and conventional glioblastoma cell lines. Cell survival, proliferation and death were analyzed by fluorometric microculture cytotoxicity assay (FMCA), propidium iodide labeling and flow cytometry, and cell cloning through limiting dilution and live-cell bright-field microscopy. Results: Bortezomib and the HDAC inhibitors showed synergistic cell killing at clinically relevant drug concentrations, while the conventional cell lines cultured in serum-containing medium were relatively resistant to the same treatments. Conclusion: These findings of synergistic glioblastoma stem cell killing by bortezomib and three different FDA-approved HDAC inhibitors confirm and expand previous observations on co-operative effects between these classes of drugs.

  • 5.
    Asklund, Thomas
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Kvarnbrink, Samuel
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Holmlund, Camilla
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Wibom, Carl
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Bergenheim, Tommy
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Hedman, Håkan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Synergistic killing of Glioblastoma Stem-like cells by Bortezomib and HDAC Inhibitors2012In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 32, no 7 ; Special Issue, p. 2407-2413Article in journal (Refereed)
    Abstract [en]

    Background: The malignant brain tumour glioblastoma is a devastating disease that remains a therapeutic challenge. Materials and Methods: Effects of combinations of the US Food and Drug Administation (FDA) approved proteasome inhibitor bortezomib and the histone deacetylase (HDAC) inhibitors vorinostat, valproic acid and sodium phenylbutyrate were studied on primary glioblastoma stem cell lines and conventional glioblastoma cell lines. Cell survival, proliferation and death were analyzed by fluorometric microculture cytotoxicity assay (FMCA), propidium iodide labeling and flow cytometry, and cell cloning through limiting dilution and live-cell bright-field microscopy. Results: Bortezomib and the HDAC inhibitors showed synergistic cell killing at clinically relevant drug concentrations, while the conventional cell lines cultured in serum-containing medium were relatively resistant to the same treatments. Conclusion: These findings of synergistic glioblastoma stem cell killing by bortezomib and three different FDA-approved HDAC inhibitors confirm and expand previous observations on co-operative effects between these classes of drugs.

  • 6.
    Asklund, Thomas
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Malmstrom, Annika
    Björ, Ove
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Blomquist, Erik
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Considerable improvement in survival for patients aged 60-84 years with high grade malignant gliomas - Data from the Swedish Brain Tumour Population-based Registry2013In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 52, no 5, p. 1043-1046Article in journal (Refereed)
  • 7.
    Asklund, Thomas
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Malmström, Annika
    Bergqvist, Michael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Björ, Ove
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Brain tumors in Sweden: Data from a population-based registry 1999-20122015In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 54, no 3, p. 377-384Article in journal (Refereed)
    Abstract [en]

    Background. The Swedish brain tumor registry has, since it was launched in 1999, provided significant amounts of data on histopathological diagnoses and on important aspects of surgical and medical management of these patients. The purpose is mainly quality control, but also as a resource for research.

    Methods. Three Swedish healthcare regions, constituting 40% of the Swedish population, have had an almost complete registration. The following parameters are registered: diagnosis according to SNOMED/WHO classification, symptoms, performance status, pre- and postoperative radiology, tumor size and localization, extent of surgery and occurrence of postoperative complications, postoperative treatment, such as radiotherapy and/or chemotherapy, other treatments, complications and toxicity, occurrence of reoperation/s, participation in clinical trials, multidisciplinary conferences and availability of a contact nurse.

    Results. Surgical radicality has been essentially constant, whereas the use of early (within 72 hours) postoperative CT and MRI has increased, especially for high-grade glioma, which is a reflection of quality of surgery. Survival of patients with high-grade glioma has increased, especially in the age group 60-69. Patients aged 18-39 years had a five-year survival of 40%. Waiting times for the pathological report has been slightly prolonged. Geographical differences do exist for some of the variables.

    Conclusion. Population-based registration is valuable for assessment of clinical management, which could have impact on patient care. As a result of short survival and/or the propensity to affect cognitive functions this patient group has considerable difficulties to make their voices heard in society. We therefore believe that a report like the present one can contribute to the spread of knowledge and increase the awareness for this patient group among caregivers and policy makers.

  • 8.
    Asklund, Thomas
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Nyholm, Tufve
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Garpebring, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Hauksson, Jon
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Brynolfsson, Patrik
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Karlsson, Mikael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Evaluation of advanced MR techniques for development of early biomarkers for treatment efficacy in malignant brain tumors2010Conference paper (Refereed)
  • 9.
    Asklund, Thomas
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Sandström, Maria
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Shahidi, Saeed
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Durable stabilization of three chordoma cases by bevacizumab and erlotinib2014In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 53, no 7, p. 980-984Article in journal (Refereed)
  • 10.
    Brynolfsson, Patrik
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Löfstedt, Tommy
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Asklund, Thomas
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Nyholm, Tufve
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Garpebring, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Gray-level invariant Haralick texture features2018In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 127, p. S279-S280Article in journal (Other academic)
  • 11.
    Brynolfsson, Patrik
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Nilsson, David
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Hauksson, Jon
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Karlsson, Mikael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Garpebring, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Birgander, Richard
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Trygg, Johan
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Nyholm, Tufve
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Asklund, Thomas
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    ADC texture-An imaging biomarker for high-grade glioma?2014In: Medical physics (Lancaster), ISSN 0094-2405, Vol. 41, no 10, p. 101903-Article in journal (Refereed)
    Abstract [en]

    Purpose:

    Survival for high-grade gliomas is poor, at least partly explained by intratumoral heterogeneity contributing to treatment resistance. Radiological evaluation of treatment response is in most cases limited to assessment of tumor size months after the initiation of therapy. Diffusion-weighted magnetic resonance imaging (MRI) and its estimate of the apparent diffusion coefficient (ADC) has been widely investigated, as it reflects tumor cellularity and proliferation. The aim of this study was to investigate texture analysis of ADC images in conjunction with multivariate image analysis as a means for identification of pretreatment imaging biomarkers.

    Methods:

    Twenty-three consecutive high-grade glioma patients were treated with radiotherapy (2 Gy/60 Gy) with concomitant and adjuvant temozolomide. ADC maps and T1-weighted anatomical images with and without contrast enhancement were collected prior to treatment, and (residual) tumor contrast enhancement was delineated. A gray-level co-occurrence matrix analysis was performed on the ADC maps in a cuboid encapsulating the tumor in coronal, sagittal, and transversal planes, giving a total of 60 textural descriptors for each tumor. In addition, similar examinations and analyses were performed at day 1, week 2, and week 6 into treatment. Principal component analysis (PCA) was applied to reduce dimensionality of the data, and the five largest components (scores) were used in subsequent analyses. MRI assessment three months after completion of radiochemotherapy was used for classifying tumor progression or regression.

    Results:

    The score scatter plots revealed that the first, third, and fifth components of the pretreatment examinations exhibited a pattern that strongly correlated to survival. Two groups could be identified: one with a median survival after diagnosis of 1099 days and one with 345 days, p = 0.0001.

    Conclusions:

    By combining PCA and texture analysis, ADC texture characteristics were identified, which seems to hold pretreatment prognostic information, independent of known prognostic factors such as age, stage, and surgical procedure. These findings encourage further studies with a larger patient cohort. (C) 2014 Author(s).

  • 12.
    Brynolfsson, Patrik
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Nilsson, David
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Torheim, Turid
    Asklund, Thomas
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Thellenberg Karlsson, Camilla
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Trygg, Johan
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Nyholm, Tufve
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Garpebring, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Haralick texture features from apparent diffusion coefficient (ADC) MRI images depend on imaging and pre-processing parameters2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 4041Article in journal (Refereed)
    Abstract [en]

    In recent years, texture analysis of medical images has become increasingly popular in studies investigating diagnosis, classification and treatment response assessment of cancerous disease. Despite numerous applications in oncology and medical imaging in general, there is no consensus regarding texture analysis workflow, or reporting of parameter settings crucial for replication of results. The aim of this study was to assess how sensitive Haralick texture features of apparent diffusion coefficient (ADC) MR images are to changes in five parameters related to image acquisition and pre-processing: noise, resolution, how the ADC map is constructed, the choice of quantization method, and the number of gray levels in the quantized image. We found that noise, resolution, choice of quantization method and the number of gray levels in the quantized images had a significant influence on most texture features, and that the effect size varied between different features. Different methods for constructing the ADC maps did not have an impact on any texture feature. Based on our results, we recommend using images with similar resolutions and noise levels, using one quantization method, and the same number of gray levels in all quantized images, to make meaningful comparisons of texture feature results between different subjects.

  • 13.
    Garpebring, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Brynolfsson, Patrik
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Yu, Jun
    Sveriges lantbruksuniversitet, Centre of Biostochastiscs.
    Wirestam, Ronnie
    Lunds universitet, Medicinsk strålningsfysik.
    Johansson, Adam
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Asklund, Thomas
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Karlsson, Mikael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Uncertainty estimation in dynamic contrast-enhanced MRI2013In: Magnetic Resonance in Medicine, ISSN 0740-3194, E-ISSN 1522-2594, Vol. 69, no 4, p. 992-1002Article in journal (Refereed)
    Abstract [en]

    Using dynamic contrast-enhanced MRI (DCE-MRI), it is possible to estimate pharmacokinetic (PK) parameters that convey information about physiological properties, e.g., in tumors. In DCE-MRI, errors propagate in a nontrivial way to the PK parameters. We propose a method based on multivariate linear error propagation to calculate uncertainty maps for the PK parameters. Uncertainties in the PK parameters were investigated for the modified Kety model. The method was evaluated with Monte Carlo simulations and exemplified with in vivo brain tumor data. PK parameter uncertainties due to noise in dynamic data were accurately estimated. Noise with standard deviation up to 15% in the baseline signal and the baseline T1 map gave estimated uncertainties in good agreement with the Monte Carlo simulations. Good agreement was also found for up to 15% errors in the arterial input function amplitude. The method was less accurate for errors in the bolus arrival time with disagreements of 23%, 32%, and 29% for Ktrans, ve, and vp, respectively, when the standard deviation of the bolus arrival time error was 5.3 s. In conclusion, the proposed method provides efficient means for calculation of uncertainty maps, and it was applicable to a wide range of sources of uncertainty.

  • 14.
    Garpebring, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Brynolfsson, Patrik
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Yu, Jun
    Wirestam, Ronnie
    Radiofysik, Lunds Universitet.
    Johansson, Adam
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Thomas, Asklund
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Karlsson, Mikael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Uncertainty Maps in Dynamic Contrast-Enhanced MRI2012Conference paper (Refereed)
  • 15.
    Garpebring, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Brynolfsson, Patrik
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Yu, Jun
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
    Wirestam, Ronnie
    Radiofysik, Lunds Universitet.
    Johansson, Adam
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Thomas, Asklund
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Karlsson, Mikael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Uncertainty Maps in Dynamic Contrast-Enhanced MRI2012Conference paper (Refereed)
  • 16.
    Garpebring, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Wirestam, Ronnie
    Yu, Jun
    SLU, Centre of Biostochastics.
    Asklund, Thomas
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Karlsson, Mikael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Phase-based arterial input functions in humans applied to dynamic contrast-enhanced MRI: potential usefulness and limitations2011In: Magnetic Resonance Materials in Physics, Biology and Medicine, ISSN 0968-5243, E-ISSN 1352-8661, Vol. 24, no 4, p. 233-245Article in journal (Refereed)
    Abstract [en]

    Object: Phase-based arterial input functions (AIFs) provide a promising alternative to standard magnitude-based AIFs, for example, because inflow effects are avoided. The usefulness of phase-based AIFs in clinical dynamic contrast-enhanced MRI (DCE-MRI) was investigated, and relevant pitfalls and sources of uncertainty were identified.

    Materials and methods: AIFs were registered from eight human subjects on, in total, 21 occasions. AIF quality was evaluated by comparing AIFs from right and left internal carotid arteries and by assessing the reliability of blood plasma volume estimates.

    Results: Phase-based AIFs yielded an average bolus peak of 3.9 mM and a residual concentration of 0.37 mM after 3 min, (0.033 mmol/kg contrast agent injection). The average blood plasma volume was 2.7% when using the AIF peak in the estimation, but was significantly different (p < 0.0001) and less physiologically reasonable when based on the AIF tail concentration. Motion-induced phase shifts and accumulation of contrast agent in background tissue regions were identified as main sources of uncertainty.

    Conclusions: Phase-based AIFs are a feasible alternative to magnitude AIFs, but sources of errors exist, making quantification difficult, especially of the AIF tail. Improvement of the technique is feasible and also required for the phase-based AIF approach to reach its full potential.

  • 17.
    Henriksson, Roger
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Asklund, Thomas
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Poulsen, Hans Skovgaard
    Radiumhemmet, Karolinska Hospital, Stockholm, Sweden; Department of Oncology, Finsencenter, University Hospital, 9 Blegdamsvej, 2100 Copenhagen, Denmark.
    Impact of therapy on quality of life, neurocognitive function and their correlates in glioblastoma multiforme: a review2011In: Journal of Neuro-Oncology, ISSN 0167-594X, E-ISSN 1573-7373, Vol. 104, no 3, p. 639-646Article, review/survey (Refereed)
    Abstract [en]

    The maintenance of quality of life (QoL) in patients with high-grade glioma is an important endpoint during treatment, particularly in those with glioblastoma multiforme (GBM) given its dismal prognosis despite limited advances in standard therapy. It has proven difficult to identify new therapies that extend survival in patients with recurrent GBM, so one of the primary aims of new therapies is to reduce morbidity, restore or preserve neurologic functions, and the capacity to perform daily activities. Apart from temozolomide, cytotoxic chemotherapeutic agents do not appear to significantly impact response or survival, but produce toxicity that is likely to negatively impact QoL. New biological agents, such as bevacizumab, can induce a clinically meaningful proportion of durable responses among patients with recurrent GBM with an acceptable safety profile. Emerging evidence suggests that bevacizumab produces an improvement or preservation of neurocognitive function in GBM patients, suggestive of QoL improvement, in most poor-prognosis patients who would otherwise be expected to show a sudden and rapid deterioration in QoL.

  • 18.
    Henriksson, Roger
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Johansson, Fredrik
    Johansson, Mikael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Asklund, Thomas
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Blomquist, Erik
    Bergström, Stefan
    Ekman, Simon
    Bergqvist, Michael
    Brain Tumors - Prognostic and Predictive Markers2009In: Histological and Serological Tumor Markers and Gene Expression and Their Clinical Usefulness in Cancers / [ed] Dan Hellberg, Hauppauge: Nova Science Publishers, Inc., 2009, p. 53-75Chapter in book (Refereed)
    Abstract [en]

    This review summarizes the status of prognostic and predictive markers in brain tumors with a focus on the most frequent tumors, gliomas. Brain tumors are a heterogeneous group of different tumors with a huge variation in outcome. Although the most common tumor, high-grade malignant glioma, still has a dismal prognosis, the last years have seen a significant improvement in the management in this tumor as well as in most other brain tumors. Age, tumor grade and KPS are still the most reliable prognostic and predictive variables available for patients with brain tumors. Although chromosome 1p/19q co-deletion and methylation status of the promoter of the MGMT gene (encoding O6-methylguanine-DNA methyl transferase) have been identified as the most promising potential predictors of response to chemotherapy in malignant gliomas, there are as yet no reliable biomarkers for tumour grading or tumour monitoring in the clinical setting.

  • 19. Holgersson, Georg
    et al.
    Bergström, Stefan
    Liv, Per
    Nilsson, Jonas
    Edlund, Per
    Blomberg, Carl
    Nyman, Jan
    Friesland, Signe
    Ekman, Simon
    Asklund, Thomas
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Bergqvist, Michael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Center for Research and Development, Uppsala University, Gävle Hospital, Gävle, Sweden ; Department of Oncology, Gävle Hospital, Gävle, Sweden.
    Effect of Increased Radiotoxicity on Survival of Patients with Non-small Cell Lung Cancer Treated with Curatively Intended Radiotherapy2015In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 35, no 10, p. 5491-5497Article in journal (Refereed)
    Abstract [en]

    Aim: To elucidate the impact of different forms of radiation toxicities (esophagitis, radiation pneumonitis, mucositis and hoarseness), on the survival of patients treated with curatively intended radiotherapy for non-small cell lung cancer (NSCLC).

    Patients and Methods: Data were individually collected retrospectively for all patients diagnosed with NSCLC subjected to curatively intended radiotherapy (>= 50 Gy) in Sweden during the time period 1990 to 2000.

    Results: Esophagitis was the only radiation-induced toxicity with an impact on survival (hazard ratio=0.83, p=0.016). However, in a multivariate model, with clinical-and treatment-related factors taken into consideration, the impact of esophagitis on survival was no longer statistically significant (hazard ratio=0.88, p=0.17).

    Conclusion: The effect on survival seen in univariate analysis may be related to higher radiation dose and to the higher prevalence of chemotherapy in this group. The results do not suggest that the toxicities examined have any detrimental effect on overall survival.

  • 20.
    Johansson, Adam
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Garpebring, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Asklund, Thomas
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Tufve, Nyholm
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    CT substitutes derived from MR images reconstructed with parallel imaging2014In: Medical physics (Lancaster), ISSN 0094-2405, Vol. 41, no 8, p. 474-480Article in journal (Refereed)
    Abstract [en]

    Purpose: Computed tomography (CT) substitute images can be generated from ultrashort echo time (UTE) MRI sequences with radial k-space sampling. These CT substitutes can be used as ordinary CT images for PET attenuation correction and radiotherapy dose calculations. Parallel imaging allows faster acquisition of magnetic resonance (MR) images by exploiting differences in receiver coil element sensitivities. This study investigates whether non-Cartesian parallel imaging reconstruction can be used to improve CT substitutes generated from shorter examination times.

    Methods: The authors used gridding as well as two non-Cartesian parallel imaging reconstruction methods, SPIRiT and CG-SENSE, to reconstruct radial UTE and gradient echo (GE) data into images of the head for 23 patients. For each patient, images were reconstructed from the full dataset and from a number of subsampled datasets. The subsampled datasets simulated shorter acquisition times by containing fewer radial k-space spokes (1000, 2000, 3000, 5000, and 10 000 spokes) than the full dataset (30 000 spokes). For each combination of patient, reconstruction method, and number of spokes, the reconstructed UTE and GE images were used to generate a CT substitute. Each CT substitute image was compared to a real CT image of the same patient.

    Results: The mean absolute deviation between the CT number in CT substitute and CT decreased when using SPIRiT as compared to gridding reconstruction. However, the reduction was small and the CT substitute algorithm was insensitive to moderate subsampling (≥5000 spokes) regardless of reconstruction method. For more severe subsampling (≤3000 spokes), corresponding to acquisition times less than aminute long, the CT substitute quality was deteriorated for all reconstructionmethods but SPIRiT gave a reduction in the mean absolute deviation of down to 25 Hounsfield units compared to gridding.

    Conclusions: SPIRiT marginally improved the CT substitute quality for a given number of radial spokes as compared to gridding. However, the increased reconstruction time of non-Cartesian parallel imaging reconstruction is difficult to motivate from this improvement. Because the CT substitute algorithm was insensitive to moderate subsampling, data for a CT substitute could be collected in as little as minute and reconstructed with gridding without deteriorating the CT substitute quality.

  • 21.
    Johansson, Adam
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Garpebring, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Karlsson, Mikael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Asklund, Thomas
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Nyholm, Tufve
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Improved quality of computed tomography substitute derived from magnetic resonance (MR) data by incorporation of spatial information: potential application for MR-only radiotherapy and attenuation correction in positron emission tomography2013In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 52, no 7, p. 1369-1373Article in journal (Refereed)
    Abstract [en]

    Background: Estimation of computed tomography (CT) equivalent data, i.e. a substitute CT (s-CT), from magnetic resonance (MR) images is a prerequisite both for attenuation correction of positron emission tomography (PET) data acquired with a PET/MR scanner and for dose calculations in an MR-only radiotherapy workflow. It has previously been shown that it is possible to estimate Hounsfield numbers based on MR image intensities, using ultra short echo-time imaging and Gaussian mixture regression (GMR). In the present pilot study we investigate the possibility to also include spatial information in the GMR, with the aim to improve the quality of the s-CT. Material and methods: MR and CT data for nine patients were used in the present study. For each patient, GMR models were created from the other eight patients, including either both UTE image intensities and spatial information on a voxel by voxel level, or only UTE image intensities. The models were used to create s-CT images for each respective patient. Results: The inclusion of spatial information in the GMR model improved the accuracy of the estimated s-CT. The improvement was most pronounced in smaller, complicated anatomical regions as the inner ear and post-nasal cavities. Conclusions: This pilot study shows that inclusion of spatial information in GMR models to convert MR data to CT equivalent images is feasible. The accuracy of the s-CT is improved and the spatial information could make it possible to create a general model for the conversion applicable to the whole body.

  • 22.
    Johansson, Adam
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Karlsson, Mikael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Yu, Jun
    SLU, Centre of Biostochastics.
    Asklund, Thomas
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Nyholm, Tufve
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Voxel-wise uncertainty in CT substitute derived from MRI2012In: Medical physics (Lancaster), ISSN 0094-2405, Vol. 39, no 6, p. 3283-3290Article in journal (Refereed)
    Abstract [en]

    Purpose: In an earlier work, we demonstrated that substitutes for CT images can be derived from MR images using ultrashort echo time (UTE) sequences, conventional T2 weighted sequences, and Gaussian mixture regression (GMR). In this study, we extend this work by analyzing the uncertainties associated with the GMR model and the information contributions from the individual imaging sequences.

    Methods: An analytical expression for the voxel-wise conditional expected absolute deviation (EAD) in substitute CT (s-CT) images was derived. The expression depends only on MR images and can thus be calculated along with each s-CT image. The uncertainty measure was evaluated by comparing the EAD to the true mean absolute prediction deviation (MAPD) between the s-CT and CT images for 14 patients. Further, the influence of the different MR images included in the GMR model on the generated s-CTs was investigated by removing one or more images and evaluating the MAPD for a spectrum of predicted radiological densities.

    Results: The largest EAD was predicted at air-soft tissue and bone-soft tissue interfaces. The EAD agreed with the MAPD in both these regions and in regions with lower EADs, such as the brain. Two of the MR images included in the GMR model were found to be mutually redundant for the purpose of s-CT generation.

    Conclusions: The presented uncertainty estimation method accurately predicts the voxel-wise MAPD in s-CT images. Also, the non-UTE sequence previously used in the model was found to be redundant.

  • 23.
    Jonsson, Joakim H.
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Akhtari, Mohammad M.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Karlsson, Magnus G.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Johansson, Adam
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Asklund, Thomas
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Nyholm, Tufve
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Accuracy of inverse treatment planning on substitute CT images derived from MR data for brain lesions2015In: Radiation Oncology, ISSN 1748-717X, E-ISSN 1748-717X, Vol. 10, article id 13Article in journal (Refereed)
    Abstract [en]

    Background: In this pilot study we evaluated the performance of a substitute CT (s-CT) image derived from MR data of the brain, as a basis for optimization of intensity modulated rotational therapy, final dose calculation and derivation of reference images for patient positioning. Methods: S-CT images were created using a Gaussian mixture regression model on five patients previously treated with radiotherapy. Optimizations were compared using D-max, D-min, D-median and D-mean measures for the target volume and relevant risk structures. Final dose calculations were compared using gamma index with 1%/1 mm and 3%/3 mm acceptance criteria. 3D geometric evaluation was conducted using the DICE similarity coefficient for bony structures. 2D geometric comparison of digitally reconstructed radiographs (DRRs) was performed by manual delineation of relevant structures on the s-CT DRR that were transferred to the CT DRR and compared by visual inspection. Results: Differences for the target volumes in optimization comparisons were small in general, e.g. a mean difference in both D-min and D-max within similar to 0.3%. For the final dose calculation gamma evaluations, 100% of the voxels passed the 1%/1 mm criterion within the PTV. Within the entire external volume between 99.4% and 100% of the voxels passed the 3%/3 mm criterion. In the 3D geometric comparison, the DICE index varied between approximately 0.8-0.9, depending on the position in the skull. In the 2D DRR comparisons, no appreciable visual differences were found. Conclusions: Even though the present work involves a limited number of patients, the results provide a strong indication that optimization and dose calculation based on s-CT data is accurate regarding both geometry and dosimetry.

  • 24.
    Jonsson, Joakim
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Johansson, Adam
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Söderström, Karin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Asklund, Thomas
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Nyholm, Tufve
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Treatment planning of intracranial targets on MRI derived substitute CT data2013In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 108, no 1, p. 118-122Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The use of magnetic resonance imaging (MRI) as a complement to computed tomography (CT) in the target definition procedure for radiotherapy is increasing. To eliminate systematic uncertainties due to image registration, a workflow based entirely on MRI may be preferable. In the present pilot study, we investigate dose calculation accuracy for automatically generated substitute CT (s-CT) images of the head based on MRI. We also produce digitally reconstructed radiographs (DRRs) from s-CT data to evaluate the feasibility of patient positioning based on MR images. METHODS AND MATERIALS: Five patients were included in the study. The dose calculation was performed on CT, s-CT, s-CT data without inhomogeneity correction and bulk density assigned MRI images. Evaluation of the results was performed using point dose and dose volume histogram (DVH) comparisons, and gamma index evaluation. RESULTS: The results demonstrate that the s-CT images improves the dose calculation accuracy compared to the method of non-inhomogeneity corrected dose calculations (mean improvement 2.0 percentage points) and that it performs almost identically to the method of bulk density assignment. The s-CT based DRRs appear to be adequate for patient positioning of intra-cranial targets, although further investigation is needed on this subject. CONCLUSIONS: The s-CT method is very fast and yields data that can be used for treatment planning without sacrificing accuracy.

  • 25.
    Kesek, Milos
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Nyholm, Tufve
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Asklund, Thomas
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Radiotherapy and pacemaker: 80 Gy to target close to the device may be feasible.2012In: Europace, ISSN 1099-5129, E-ISSN 1532-2092, Vol. 14, no 11, p. 1595-Article in journal (Refereed)
  • 26.
    Larsson, Anne
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Johansson, Adam
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Axelsson, Jan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Nyholm, Tufve
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Asklund, Thomas
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Karlsson, Mikael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Evaluation of an attenuation correction method for PET/MR imaging of the head based on substitute CT images2013In: Magnetic Resonance Materials in Physics, Biology and Medicine, ISSN 0968-5243, E-ISSN 1352-8661, Vol. 26, no 1, p. 127-136Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to evaluate MR-based attenuation correction of PET emission data of the head, based on a previously described technique that calculates substitute CT (sCT) images from a set of MR images. Images from eight patients, examined with F-18-FLT PET/CT and MRI, were included. sCT images were calculated and co-registered to the corresponding CT images, and transferred to the PET/CT scanner for reconstruction. The new reconstructions were then compared with the originals. The effect of replacing bone with soft tissue in the sCT-images was also evaluated. The average relative difference between the sCT-corrected PET images and the CT-corrected PET images was 1.6 % for the head and 1.9 % for the brain. The average standard deviations of the relative differences within the head were relatively high, at 13.2 %, primarily because of large differences in the nasal septa region. For the brain, the average standard deviation was lower, 4.1 %. The global average difference in the head when replacing bone with soft tissue was 11 %. The method presented here has a high rate of accuracy, but high-precision quantitative imaging of the nasal septa region is not possible at the moment.

  • 27. Malmstrom, A.
    et al.
    Akesson, L.
    Asklund, Thomas
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Kinhult, S.
    Werlenius, K.
    Hesselager, G.
    Hylin, S.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    GENDER DIFFERENCES IN GLIOMA - FINDINGS FROM THE SWEDISH NATIONAL QUALITY REGISTRY FOR PRIMARY BRAIN TUMORS2018In: Neuro-Oncology, ISSN 1522-8517, E-ISSN 1523-5866, Vol. 20, p. 267-267Article in journal (Other academic)
    Abstract [en]

    Background

    An often debated topic in neuro-oncology are the differences in incidence and survival between men and women with glioma. To the Swedish National Quality Registry for Primary Brain Tumors (SNQR) over 90% of all Swedish patients with primary brain tumor have been reported since 1999. We therefore conducted a study of clinical factors in relation to gender in patients registered with high grade glioma using data from the SNQR.

    Methods

    The SNQR was searched for patients diagnosed with high grade glioma from 1999 through 2016 and clinical data were analyzed for gender differences regarding prognostic factors, tumor location and survival.

    Results

    In all 5470 patients were identified, 2268 women and 3202 men, giving a ratio of 1:1.4. We found a survival benefit for women when analyzing the whole time period. While there was no difference in median survival (315 versus 326 days for women versus men), there were significantly more long term survivors among women, with mean survival being 742 versus 628 days (p=0.03). The survival benefit for women was also only present in those being younger than 50 years at diagnosis. We looked at the prognostic factors age, performance status (PS) and surgery in relation to gender. We found that median age for being diagnosed with high grade glioma was significantly higher in women than men (63 versus 62 years, p=0.002) and the ratio of women in relation to men increases with increasing age, the ratios for younger than 50 years being 1:1.5 and over 50 years 1:1.39. A higher fraction of the women are over 60 years when diagnosed compared to men (57% vs 53%, p=0.002). For PS we identified that significantly more women were reported to have PS 3 and for men more PS 0 was registered. For type of surgery we found no gender differences. For tumor location more women had tumors in the frontal and less in the temporal lobe as compared to men.

    Conclusion

    In the Swedish National Quality Registry for Primary Brain Tumors we identified differences in incidence and survival between men and women related to age and also a disparity regarding PS and tumor location. If the cause of these clinical differences is due to molecular background or has other causes warrants further study.

  • 28.
    Rosenlund, L.
    et al.
    Reg Canc Ctr, Stockholm, Sweden.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Asklund, Thomas
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Reg Canc Ctr, Stockholm, Sweden.
    Petersson, L.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
    Developing Patient Reported Outcome Measures (PRO) for Implementation in the Swedish National Quality Register for Primary Brain Tumors2014In: Neuro-Oncology, ISSN 1522-8517, E-ISSN 1523-5866, Vol. 16, no Suppl. 2, p. Meeting Abstract: P15.14-Article in journal (Refereed)
  • 29.
    Sandstrom, Maria
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Laudius, Maria
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Lindqvist, Thomas
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Asklund, Thomas
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Johansson, Mikael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    A Retrospective Evaluation of Bevacizumab Treatment in Patients with Progressive Malignant Glioma in Northern Sweden2017In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 37, no 4, p. 1869-1874Article in journal (Refereed)
    Abstract [en]

    Background/Aim: Overall survival for glioblastoma patients is short. Standard treatment is surgery followed by radiochemotherapy and adjuvant temozolomide. The aim of this study was to evaluate the outcome for all patients with progressive disease treated with bevacizumab-based treatment combinations in the northern region of Sweden. Patients and Methods: This was a single-center retrospective analysis after bevacizumab-based second-line treatment for malignant glioma. All patients treated with bevacizumab, between 2007 and 2011 in our Center were retrospectively evaluated. Results: Progression-free survival after the start of bevacizumab-based treatment was 20 weeks and overall survival was 31 weeks. Treatment was well tolerated, but 9% of patients (n=6) suffered from serious adverse events. In 68% of patients, a >= 25% decrease in contrast enhancement was seen at best response. Conclusion: Results from this retrospective study are comparable with earlier phase-II. studies and motivate randomized trials of bevacizumab-based treatment in the second-line setting.

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