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Blomquist, Erik
Publications (10 of 24) Show all publications
Fahlström, M., Fransson, S., Blomquist, E., Nyholm, T. & Larsson, E.-M. (2018). Dynamic Contrast-Enhanced Magnetic Resonance Imaging May Act as a Biomarker for Vascular Damage in Normal Appearing Brain Tissue after Radiotherapy in Patients with Glioblastoma. Acta Radiologica Open, 7(11)
Open this publication in new window or tab >>Dynamic Contrast-Enhanced Magnetic Resonance Imaging May Act as a Biomarker for Vascular Damage in Normal Appearing Brain Tissue after Radiotherapy in Patients with Glioblastoma
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2018 (English)In: Acta Radiologica Open, ISSN 2058-4601, Vol. 7, no 11Article in journal (Refereed) Published
Abstract [en]

Background: Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a promising perfusion method and may be useful in evaluating radiation-induced changes in normal-appearing brain tissue.

Purpose: To assess whether radiotherapy induces changes in vascular permeability (Ktrans) and the fractional volume of the extravascular extracellular space (Ve) derived from DCE-MRI in normal-appearing brain tissue and possible relationships to radiation dose given.

Material and Methods: Seventeen patients with glioblastoma treated with radiotherapy and chemotherapy were included; five were excluded because of inconsistencies in the radiotherapy protocol or early drop-out. DCE-MRI, contrast-enhanced three-dimensional (3D) T1-weighted (T1W) images and T2-weighted fluid attenuated inversion recovery (T2-FLAIR) images were acquired before and on average 3.3, 30.6, 101.6, and 185.7 days after radiotherapy. Pre-radiotherapy CE T1W and T2-FLAIR images were segmented into white and gray matter, excluding all non-healthy tissue. Ktrans and Ve were calculated using the extended Kety model with the Parker population-based arterial input function. Six radiation dose regions were created for each tissue type, based on each patient's computed tomography-based dose plan. Mean Ktrans and Ve were calculated over each dose region and tissue type.

Results: Global Ktrans and Ve demonstrated mostly non-significant changes with mean values higher for post-radiotherapy examinations in both gray and white matter compared to pre-radiotherapy. No relationship to radiation dose was found.

Conclusion: Additional studies are needed to validate if Ktrans and Ve derived from DCE-MRI may act as potential biomarkers for acute and early-delayed radiation-induced vascular damages. No dose-response relationship was found.

National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-346813 (URN)10.1177/2058460118808811 (DOI)000450106500001 ()30542625 (PubMedID)
Funder
Swedish Cancer Society
Available from: 2018-03-21 Created: 2018-03-21 Last updated: 2019-01-07Bibliographically approved
Fahlström, M., Blomquist, E., Nyholm, T. & Larsson, E.-M. (2018). Perfusion Magnetic Resonance Imaging Changes in Normal Appearing Brain Tissue after Radiotherapy in Glioblastoma Patients may Confound Longitudinal Evaluation of Treatment Response. Radiology and Oncology, 52(2), 143-151
Open this publication in new window or tab >>Perfusion Magnetic Resonance Imaging Changes in Normal Appearing Brain Tissue after Radiotherapy in Glioblastoma Patients may Confound Longitudinal Evaluation of Treatment Response
2018 (English)In: Radiology and Oncology, ISSN 1318-2099, E-ISSN 1581-3207, Vol. 52, no 2, p. 143-151Article in journal (Refereed) Published
Abstract [en]

Background: The aim of this study was assess acute and early delayed radiation-induced changes in normal-appearing brain tissue perfusion as measured with perfusion magnetic resonance imaging (MRI) and the dependence of these changes on the fractionated radiotherapy (FRT) dose level.

Patients and methods: Seventeen patients with glioma WHO grade III-IV treated with FRT were included in this prospective study, seven were excluded because of inconsistent FRT protocol or missing examinations. Dynamic susceptibility contrast MRI and contrast-enhanced 3D-T1-weighted (3D-T1w) images were acquired prior to and in average (standard deviation): 3.1 (3.3), 34.4 (9.5) and 103.3 (12.9) days after FRT. Pre-FRT 3D-T1w images were segmented into white- and grey matter. Cerebral blood volume (CBV) and cerebral blood flow (CBF) maps were calculated and co-registered patient-wise to pre-FRT 3D-T1w images. Seven radiation dose regions were created for each tissue type: 0-5 Gy, 5-10 Gy, 10-20 Gy, 20-30 Gy, 30-40 Gy, 40-50 Gy and 50-60 Gy. Mean CBV and CBF were calculated in each dose region and normalised (nCBV and nCBF) to the mean CBV and CBF in 0-5 Gy white- and grey matter reference regions, respectively.

Results: Regional and global nCBV and nCBF in white- and grey matter decreased after FRT, followed by a tendency to recover. The response of nCBV and nCBF was dose-dependent in white matter but not in grey matter.

Conclusions: Our data suggest that radiation-induced perfusion changes occur in normal-appearing brain tissue after FRT. This can cause an overestimation of relative tumour perfusion using dynamic susceptibility contrast MRI, and can thus confound tumour treatment evaluation.

Keywords
malignant gliomas, normal-appearing brain tissue, perfusion MRI, radiation-induced changes
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-356784 (URN)10.2478/raon-2018-0022 (DOI)000433103400004 ()30018517 (PubMedID)
Funder
Swedish Cancer Society
Available from: 2018-08-07 Created: 2018-08-07 Last updated: 2018-08-20Bibliographically approved
Vlachogiannis, P., Gudjonsson, O., Montelius, A., Grusell, E., Isacsson, U., Nilsson, K. & Blomquist, E. (2017). Hypofractionated high-energy proton-beam irradiation is an alternative treatment for WHO grade I meningiomas. Acta Neurochirurgica, 159(12), 2391-2400
Open this publication in new window or tab >>Hypofractionated high-energy proton-beam irradiation is an alternative treatment for WHO grade I meningiomas
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2017 (English)In: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 159, no 12, p. 2391-2400Article in journal (Refereed) Published
Abstract [en]

Radiation treatment is commonly employed in the treatment of meningiomas. The aim of this study was to evaluate the effectiveness and safety of hypofractionated high-energy proton therapy as adjuvant or primary treatment for WHO grade I meningiomas. A total of 170 patients who received irradiation with protons for grade I meningiomas between 1994 and 2007 were included in the study. The majority of the tumours were located at the skull base (n = 155). Eighty-four patients were treated post subtotal resection, 42 at tumour relapse and 44 with upfront radiotherapy after diagnosis based on the typical radiological image. Irradiation was given in a hypofractionated fashion (3-8 fractions, usually 5 or 6 Gy) with a mean dose of 21.9 Gy (range, 14-46 Gy). All patients were planned for follow-up with clinical controls and magnetic resonance imaging scans at 6 months and 1, 2, 3, 5, 7 and 10 years after treatment. The median follow-up time was 84 months. Age, gender, tumour location, Simpson resection grade and target volume were assessed as possible prognostic factors for post-irradiation tumour progression and radiation related complications. The actuarial 5- and 10-year progression-free survival rates were 93% and 85% respectively. Overall mortality rate was 13.5%, while disease-specific mortality was 1.7% (3/170 patients). Older patients and patients with tumours located in the middle cranial fossa had a lower risk for tumour progression. Radiation-related complications were seen in 16 patients (9.4%), with pituitary insufficiency being the most common. Tumour location in the anterior cranial fossa was the only factor that significantly increased the risk of complications. Hypofractionated proton-beam radiation therapy may be used particularly in the treatment of larger World Health Organisation grade I meningiomas not amenable to total surgical resection. Treatment is associated with high rates of long-term tumour growth control and acceptable risk for complications.

Keywords
Meningioma, Benign meningioma, Proton beam irradiation, Hypofractionation
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-342199 (URN)10.1007/s00701-017-3352-4 (DOI)000415354800024 ()29064038 (PubMedID)
Available from: 2018-02-20 Created: 2018-02-20 Last updated: 2018-02-20Bibliographically approved
Ryttlefors, M., Danfors, T., Latini, F., Montelius, A., Blomquist, E. & Gudjonsson, O. (2016). Long-term evaluation of the effect of hypofractionated high-energy proton treatment of benign meningiomas by means of (11)C-L-methionine positron emission tomography. European Journal of Nuclear Medicine and Molecular Imaging, 43(8), 1432-1443
Open this publication in new window or tab >>Long-term evaluation of the effect of hypofractionated high-energy proton treatment of benign meningiomas by means of (11)C-L-methionine positron emission tomography
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2016 (English)In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 43, no 8, p. 1432-1443Article in journal (Refereed) Published
Abstract [en]

PURPOSE: To determine if (11)C-L-methionine PET is a useful tool in the evaluation of the long-term effect of proton beam treatment in patients with meningioma remnant.

METHODS: Included in the study were 19 patients (4 men, 15 women) with intracranial meningioma remnants who received hypofractionated high-energy proton beam treatment. Patients were examined with (11)C-L-methionine PET and MRI prior to treatment and after 6 months, and 1, 2, 3, 5, 7 and 10 years. Temporal changes in methionine uptake ratio, meningioma volume, meningioma regrowth and clinical symptoms throughout the follow-up period were evaluated.

RESULTS: In 17 patients the tumour volume was unchanged throughout the follow-up. The methionine uptake ratio on PET decreased over the years in most patients. In two patients the tumour remnant showed progression on MRI. In these patients, prior to the volume increase on MRI, the methionine uptake ratio increased. One patient experienced transient clinical symptoms and showed radiological evidence of a radiation-induced reaction close to the irradiated field.

CONCLUSION: Proton beam treatment is a safe and effective treatment for achieving long-term growth arrest in meningioma remnants. Follow-up with (11)C-L-methionine PET may be a valuable adjunct to, but not a replacement for, standard radiological follow-up.

Keywords
Meningioma; Proton beam treatment; Stereotactic irradiation; C-11-L-Methionine; Positron emission tomography
National Category
Cancer and Oncology Surgery Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-291472 (URN)10.1007/s00259-016-3310-z (DOI)000378005000007 ()26819102 (PubMedID)
Available from: 2016-05-02 Created: 2016-05-02 Last updated: 2017-11-30Bibliographically approved
Blomquist, E., Ronne Engström, E., Borota, L., Gál, G., Nilsson, K., Lewén, A., . . . Enblad, P. (2016). Positive correlation between occlusion rate and nidus size of proton beam treated brain arteriovenous malformations (AVMs). Acta Oncologica, 55(1), 105-112
Open this publication in new window or tab >>Positive correlation between occlusion rate and nidus size of proton beam treated brain arteriovenous malformations (AVMs)
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2016 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 55, no 1, p. 105-112Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Proton beam radiotherapy of arteriovenous malformations (AVM) in the brain has been performed in Uppsala since 1991. An earlier study based on the first 26 patients concluded that proton beam can be used for treating large and medium sized AVMs that were considered difficult to treat with photons due to the risk of side effects. In the present study we analyzed the result from treating the subsequent 65 patients.

MATERIAL AND METHODS: A retrospective review of the patients' medical records, treatment protocols and radiological results was done. Information about gender, age, presenting symptoms, clinical course, the size of AVM nidus and rate of occlusion was collected. Outcome parameters were the occlusion of the AVM, clinical outcome and side effects.

RESULTS: The rate of total occlusion was overall 68%. For target volume 0-2cm(3) it was 77%, for 3-10 cm(3) 80%, for 11-15 cm(3) 50% and for 16-51 cm(3) 20%. Those with total regress of the AVM had significantly smaller target volumes (p < 0.009) higher fraction dose (p < 0.001) as well as total dose (p < 0.004) compared to the rest. The target volume was an independent predictor of total occlusion (p = 0.03). There was no difference between those with and without total occlusion regarding mean age, gender distribution or symptoms at diagnosis. Forty-one patients developed a mild radiation-induced brain edema and this was more common in those that had total occlusion of the AVM. Two patients had brain hemorrhages after treatment. One of these had no effect and the other only partial occlusion from proton beams. Two thirds of those presenting with seizures reported an improved seizure situation after treatment.

CONCLUSION: Our observations agree with earlier results and show that proton beam irradiation is a treatment alternative for brain AVMs since it has a high occlusion rate even in larger AVMs.

National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-254040 (URN)10.3109/0284186X.2015.1043023 (DOI)000367007700015 ()25972265 (PubMedID)
Available from: 2015-06-04 Created: 2015-06-04 Last updated: 2017-12-04Bibliographically approved
Sooman, L., Ekman, S., Tsakonas, G., Jaiswal, A., Navani, S., Edqvist, P.-H., . . . Lennartsson, J. (2014). PTPN6 expression is epigenetically regulated and influences survival and response to chemotherapy in high-grade gliomas. Tumor Biology, 35(5), 4479-4488
Open this publication in new window or tab >>PTPN6 expression is epigenetically regulated and influences survival and response to chemotherapy in high-grade gliomas
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2014 (English)In: Tumor Biology, ISSN 1010-4283, E-ISSN 1423-0380, Vol. 35, no 5, p. 4479-4488Article in journal (Refereed) Published
Abstract [en]

Background: The prognosis of high-grade glioma patients is poor and the tumors are characterized by resistance to therapy. The aims of this study were to analyze the prognostic value of the expression of the protein tyrosine phosphatase, non-receptor type 6 (PTPN6, also referred to as SHP1) in high-grade glioma patients and the epigenetic regulation of the expression of PTPN6 and the role of its expression in chemotherapy resistance in glioma-derived cells.

Material and methods: PTPN6 expression was analyzed with immunohistochemistry in 89 high-grade glioma patients. Correlation between PTPN6 expression and overall survival was analyzed with Kaplan-Meier univariate analysis and Cox regression multivariate analysis. Differences in drug sensitivity to a panel of 16 chemotherapeutic drugs between PTPN6 overexpressing clones and control clones were analyzed in vitro with the fluorometric microculture cytotoxicity assay. Cell cycle analysis was done with Krishan staining and flow cytometry. Apoptosis was analyzed with a cell death detection ELISA kit as well as cleaved caspase-3 and caspase-9 Western blotting. Autophagy was analyzed with LC3B Western blotting. Methylation of the PTPN6 promoter was analyzed with bisulfite-Pyrosequencing and demethylation of PTPN6 was done with decitabine treatment.

Results: PTPN6 expression correlated in univariate analysis to poor survival for anaplastic glioma patients (p=0.026). In glioma-derived cell lines, overexpression of PTPN6 caused increased resistance (p<0.05) to the chemotherapeutic drugs bortezomib, cisplatin and melphalan. PTPN6 expression did not affect bortezomib-induced cell cycle arrest, apoptosis or autophagy. Low PTPN6 promoter methylation correlated to protein expression and the protein expression was increased upon demethylation in glioma-derived cells.

Conclusion: PTPN6 expression may be a factor contributing to poor survival for anaplastic glioma patients and in glioma-derived cells its expression is epigenetically regulated and influences the response to chemotherapy.

Keywords
high-grade glioma, PTPN6, SHP1, survival, chemotherapy, methylation
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-214761 (URN)10.1007/s13277-013-1590-5 (DOI)000335759800063 ()
Available from: 2014-01-09 Created: 2014-01-09 Last updated: 2018-01-11Bibliographically approved
Reizenstein, J. A., Holmberg, L., Bergqvist, M., Linder, A., Ekman, S., Lödén, B., . . . Bergström, S. N. (2014). Time trends in T3 to T4 laryngeal cancer: a population-based long-term analysis. Head and Neck, 36(12), 1727-1731
Open this publication in new window or tab >>Time trends in T3 to T4 laryngeal cancer: a population-based long-term analysis
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2014 (English)In: Head and Neck, ISSN 1043-3074, E-ISSN 1097-0347, Vol. 36, no 12, p. 1727-1731Article in journal (Refereed) Published
Abstract [en]

Background:

A decline in laryngectomies and survival in laryngeal cancer has been reported, especially among advanced tumors.

Methods:

Out of 1058 patients with laryngeal cancer diagnosed 1978-2007 in the Uppsala-Örebro-region in Sweden 263 T3-4 tumors treated with curative intent were studied retrospectively. Two time periods were defined, 1978-1992 and 1993-2007.

Results:

Glottic tumors decreased constituting 68.6% of cases 1978-1992 and 47.9% 1993-2007. Laryngectomy was performed in 38.8% and in 34.5% in the corresponding time periods. The use of laryngectomy was not strongly prognostic. A decline in overall survival over time could only be identified for the first year of follow-up. Chemotherapy was only used in a minority of cases.

Conclusion:

The marked decrease of glottic site may mark a shift in etiology. Laryngectomy was not strongly associated with improved survival. The absence of improved survival calls for intensified research.

National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-216387 (URN)10.1002/hed.23524 (DOI)000344801200013 ()24166872 (PubMedID)
Available from: 2014-01-21 Created: 2014-01-21 Last updated: 2017-12-06Bibliographically approved
Asklund, T., Malmstrom, A., Bjor, O., Blomquist, E. & Henriksson, R. (2013). Considerable improvement in survival for patients aged 60-84 years with high grade malignant gliomas: Data from the Swedish Brain Tumour Population-based Registry [Letter to the editor]. Acta Oncologica, 52(5), 1043-1046
Open this publication in new window or tab >>Considerable improvement in survival for patients aged 60-84 years with high grade malignant gliomas: Data from the Swedish Brain Tumour Population-based Registry
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2013 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 52, no 5, p. 1043-1046Article in journal, Letter (Refereed) Published
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-201937 (URN)10.3109/0284186X.2012.754993 (DOI)000318655300023 ()
Available from: 2013-06-18 Created: 2013-06-18 Last updated: 2017-12-06Bibliographically approved
Fredriksson, F., Nordborg, C., Hallén, T. & Blomquist, E. (2013). Haemangiopericytoma presenting with acute intracerebral haemorrhage: a case report and literature review. Acta Oncologica, 52(4), 753-758
Open this publication in new window or tab >>Haemangiopericytoma presenting with acute intracerebral haemorrhage: a case report and literature review
2013 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 52, no 4, p. 753-758Article, review/survey (Refereed) Published
Abstract [en]

Background.

Intracranial haemangiopericytoma (HPC), a rare malignant tumour, should be distinguished from meningioma and solitary fibrous tumour, which have been considered as separate entities since 1993, according to histopathology and clinical characteristics.

Methods.

A PUBMED search for "Intracranial Haemangiopericytoma" yielded 176 articles, where 26 were of particular interest for this review article.

Case report.

Our patient, a 27-year-old man with HPC of grade III according to WHO, presents with an acute intracerebral haematoma, which is extremely rare.

Results.

Surgery (total resection) is the primary treatment. Long-term close clinical and radiological follow-up is crucial due to the high rate of recurrence and tendency for development of metastasis.

Discussion.

The effects of postoperative radiotherapy need further investigation. Besides neurosurgery, radiotherapy should always be considered in both patients with these highly malignant tumours (WHO grade III) and in patients with partial resection or inoperable cases (WHO grade II).

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-187778 (URN)10.3109/0284186X.2012.716163 (DOI)000317239200009 ()22937954 (PubMedID)
Available from: 2012-12-10 Created: 2012-12-10 Last updated: 2017-12-07Bibliographically approved
Sooman, L., Ekman, S., Andersson, C., Kultima, H. G., Isaksson, A., Johansson, F., . . . Gullbo, J. (2013). Synergistic interactions between camptothecin and EGFR or RAC1 inhibitors and between imatinib and Notch signaling or RAC1 inhibitors in glioblastoma cell lines. Cancer Chemotherapy and Pharmacology, 72(2), 329-340
Open this publication in new window or tab >>Synergistic interactions between camptothecin and EGFR or RAC1 inhibitors and between imatinib and Notch signaling or RAC1 inhibitors in glioblastoma cell lines
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2013 (English)In: Cancer Chemotherapy and Pharmacology, ISSN 0344-5704, E-ISSN 1432-0843, Vol. 72, no 2, p. 329-340Article in journal (Refereed) Published
Abstract [en]

The current treatment strategies for glioblastoma have limited health and survival benefits for the patients. A common obstacle in the treatment is chemoresistance. A possible strategy to evade this problem may be to combine chemotherapeutic drugs with agents inhibiting resistance mechanisms. The aim with this study was to identify molecular pathways influencing drug resistance in glioblastoma-derived cells and to evaluate the potential of pharmacological interference with these pathways to identify synergistic drug combinations. Global gene expressions and drug sensitivities to three chemotherapeutic drugs (imatinib, camptothecin and temozolomide) were measured in six human glioblastoma-derived cell lines. Gene expressions that correlated to drug sensitivity or resistance were identified and mapped to specific pathways. Selective inhibitors of these pathways were identified. The effects of six combinations of inhibitors and chemotherapeutic drugs were evaluated in glioblastoma-derived cell lines. Drug combinations with synergistic effects were also evaluated in non-cancerous epithelial cells. Four drug combinations had synergistic effects in at least one of the tested glioblastoma-derived cell lines; camptothecin combined with gefitinib (epidermal growth factor receptor inhibitor) or NSC 23766 (ras-related C3 botulinum toxin substrate 1 inhibitor) and imatinib combined with DAPT (Notch signaling inhibitor) or NSC 23766. Of these, imatinib combined with DAPT or NSC 23766 did not have synergistic effects in non-cancerous epithelial cells. Two drug combinations had at least additive effects in one of the tested glioblastoma-derived cell lines; temozolomide combined with gefitinib or PF-573228 (focal adhesion kinase inhibitor). Four synergistic and two at least additive drug combinations were identified in glioblastoma-derived cells. Pathways targeted by these drug combinations may serve as targets for future drug development with the potential to increase efficacy of currently used/evaluated chemotherapy.

Keywords
Glioblastoma, Synergistic drug combinations, Camptothecin, Imatinib
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-207017 (URN)10.1007/s00280-013-2197-7 (DOI)000322132600006 ()
Available from: 2013-09-10 Created: 2013-09-09 Last updated: 2017-12-06Bibliographically approved
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