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- Sandstrom, Maria, et al.
(författare)
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A Retrospective Evaluation of Bevacizumab Treatment in Patients with Progressive Malignant Glioma in Northern Sweden
- 2017
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Ingår i: Anticancer Research. - : INT INST ANTICANCER RESEARCH. - 0250-7005 .- 1791-7530. ; 37:4, s. 1869-1874
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Tidskriftsartikel (refereegranskat)abstract
- 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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| 2. |
- Asklund, Thomas, et al.
(författare)
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Brain tumors in Sweden : Data from a population-based registry 1999-2012
- 2015
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Ingår i: Acta Oncologica. - : Informa Healthcare. - 0284-186X .- 1651-226X. ; 54:3, s. 377-384
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 7. |
- Asklund, Thomas, et al.
(författare)
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PET response and tumor stabilization under erlotinib and bevacizumab treatment of an intracranial lesion non-invasively diagnosed as likely chordoma
- 2011
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Ingår i: Clinical Neuropathology. - Deisenhofen : Dustri-Verlag Feistle. - 0722-5091. ; 30:5, s. 242-246
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 8. |
- Asklund, Thomas, et al.
(författare)
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Synergistic Killing of Glioblastoma Stem-like Cells by Bortezomib and HADC Inhibitors.
- 2012
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Ingår i: Anticancer Research. - : International Institute of Anticancer Research. - 0250-7005 .- 1791-7530. ; 32:7, s. 2407-2413
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 9. |
- Asklund, Thomas
(författare)
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Two novel combination therapies of glioblastoma multiforme from a Cx43 perspective : studies of in vitro models
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The group of patients suffering from the malignant brain tumour glioblastoma multiforme (GBM) have a median survival of only about one year. Thus, new treatment strategies are urgently needed. Gap junctions are intercellular channels, permitting intercellular transfer of water soluble substances. They are vital for cellular homesostasis, proliferation and differentiation. Gap junctions are composed of multimeric proteins termed connexins (Cxs), of which Cx43 is the most ubiquitous. Cx43 serves as a tumour suppressor independent of its ability to form gap junctions. Herpes simplex virus thymidine kinase (HSV-tk) mediated suicide gene therapy has shown promising results in preclinical research, but has as yet failed to prove clinical efficacy. Intriguingly, neural progenitor cells (NPCs) have shown tropism for intracranial tumours and could be exploited for improving the delivery of therapeutic genes or gene products. Epigenetic regulators, such as histone deacetylase inhibitors (HDACi) and receptor tyrosine kinase inhibitors (RTKIs), including gefitinib and vandetanib, have recently entered clinical trials. In the present study, primary cultures of GBM cells were established and showed positivity for neuroepithelial markers. Additionally, they were Cx43 positive and functional gap junctions were demonstrated. The bystander effect in the HSV-tk/ganciclovir (HSV-tk/GCV) suicide gene therapy system was attenuated by a specific gap junction inhibitor, AGA, showing that this phenomenon is dependent on gap junction coupling in glioma cells. The HDAC inhibitor 4-phenylbutyrate (4-PB) up regulated Cx43 and enhanced gap junction communication (GJC), a strategy which could have potential for improving efficacy of suicide gene therapy. NPCs exposed to 4-PB also increased Cx43 expression and gap junction formation. This, together with the propensity of NPCs of tracking down tumour cells, could add a new dimension to gene therapy. Cooperative antitumoural effects were evident in combination treatment of 4-PB and the RTKIs gefitinib and vandetanib. These RTKIs showed an up regulating effect on the tumour suppressor Cx43, which could show to be of importance in the downstream effects of RTKIs.
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| 10. |
- Asklund, Thomas, et al.
(författare)
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Överlevnaden vid maligna gliom har ökat senaste tio åren - Analys av kvalitetsregisterdata : [Survival in malignant gliomas has increased the last decade. Analysis of quality data]
- 2012
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Ingår i: Läkartidningen. - : Läkartidningen Förlag. - 0023-7205 .- 1652-7518. ; 109:17-18, s. 875-878
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Tidskriftsartikel (refereegranskat)abstract
- Den årliga incidensen av högmaligna gliom, WHO grad III–IV, i Sverige är ungefär 400.Medianöverlevnaden för höggradiga gliom har ökat från 8,1 månader till 10,0 månader under det senaste decenniet i en oselekterad svensk population.För åldersgruppen 60–69 år har medianöverlevnaden ökat från 5,8 månader till 10,5 månader under denna period, dvs nästan en fördubbling.Utveckling av befintliga behandlingsmetoder, nya behandlingsstrategier och en mer aktiv inställning till terapi har sannolikt bidragit till de beskrivna överlevnadsvinsterna.
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