umu.sePublikasjoner
Endre søk
Link to record
Permanent link

Direct link
BETA
Bergström, Per
Publikasjoner (10 av 24) Visa alla publikasjoner
Björkblom, B., Jonsson, P., Tabatabaei, P., Bergström, P., Johansson, M., Asklund, T., . . . Antti, H. (2020). Metabolic response patterns in brain microdialysis fluids and serum during interstitial cisplatin treatment of high-grade glioma. British Journal of Cancer, 122(2), 221-232
Åpne denne publikasjonen i ny fane eller vindu >>Metabolic response patterns in brain microdialysis fluids and serum during interstitial cisplatin treatment of high-grade glioma
Vise andre…
2020 (engelsk)Inngår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 122, nr 2, s. 221-232Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

BACKGROUND: High-grade gliomas are associated with poor prognosis. Tumour heterogeneity and invasiveness create challenges for effective treatment and use of systemically administrated drugs. Furthermore, lack of functional predictive response-assays based on drug efficacy complicates evaluation of early treatment responses.

METHODS: We used microdialysis to deliver cisplatin into the tumour and to monitor levels of metabolic compounds present in the tumour and non-malignant brain tissue adjacent to tumour, before and during treatment. In parallel, we collected serum samples and used multivariate statistics to analyse the metabolic effects.

RESULTS: We found distinct metabolic patterns in the extracellular fluids from tumour compared to non-malignant brain tissue, including high concentrations of a wide range of amino acids, amino acid derivatives and reduced levels of monosaccharides and purine nucleosides. We found that locoregional cisplatin delivery had a strong metabolic effect at the tumour site, resulting in substantial release of glutamic acid, phosphate, and spermidine and a reduction of cysteine levels. In addition, patients with long-time survival displayed different treatment response patterns in both tumour and serum. Longer survival was associated with low tumour levels of lactic acid, glyceric acid, ketoses, creatinine and cysteine. Patients with longer survival displayed lower serum levels of ketohexoses, fatty acid methyl esters, glycerol-3-phosphate and alpha-tocopherol, while elevated phosphate levels were seen in both tumour and serum during treatment.

CONCLUSION: We highlight distinct metabolic patterns associated with high-grade tumour metabolism, and responses to cytotoxic cisplatin treatment.

sted, utgiver, år, opplag, sider
Nature Publishing Group, 2020
HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-167291 (URN)10.1038/s41416-019-0652-x (DOI)000510823600009 ()31819184 (PubMedID)
Forskningsfinansiär
Swedish Cancer SocietySwedish Research Council
Tilgjengelig fra: 2020-01-15 Laget: 2020-01-15 Sist oppdatert: 2020-02-20bibliografisk kontrollert
Tabatabaei, P., Visse, E., Bergström, P., Brännström, T., Siesjö, P. & Bergenheim, A. T. (2017). Radiotherapy induces an immediate inflammatory reaction in malignant glioma: a clinical microdialysis study. Journal of Neuro-Oncology, 131(1), 83-92
Åpne denne publikasjonen i ny fane eller vindu >>Radiotherapy induces an immediate inflammatory reaction in malignant glioma: a clinical microdialysis study
Vise andre…
2017 (engelsk)Inngår i: Journal of Neuro-Oncology, ISSN 0167-594X, E-ISSN 1573-7373, Vol. 131, nr 1, s. 83-92Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

The knowledge of response to radiation in the immuno-microenvironment of high grade gliomas is sparse. In vitro results have indicated an inflammatory response of myeloid cells after irradiation. Therefore, microdialysis was used to verify whether this is operative in tumor tissue and brain adjacent to tumor (BAT) after clinical radiotherapy of patients with high grade glioma. Stereotactic biopsies and implantation of microdialysis catheters in tumor tissue and BAT were performed in eleven patients with high-grade glioma. The patients were given daily radiation fractions of 2-3.4 Gy. Microdialysis samples were collected before radiotherapy and during the first five days of radiation. Cytokines, glucose metabolites, glutamate and glycerol were analyzed. Immunohistochemistry was performed to detect macrophages (CD68) and monocytes (CD163) as well as IL-6, IL-8 and MCP-1. A significant increase of IL-8, MCP-1 and MIP-1a were detected in tumor tissue already after the first dose of radiation and increased further during 5 days of radiation. IL-6 did also increase but after five fractions of radiation. In BAT, the cytokine response was modest with significant increase of IL-8 after third dose of radiation. We found a positive correlation between baseline IL-8 and IL-6 microdialysis levels in tumor tissue and survival. Glucose metabolites or glycerol and glutamate did not change during radiation. In all tumors staining for macrophages was demonstrated. IL-6 was found in viable tumor cells while MCP-1 was demonstrated in macrophages or tumor matrix. Our findings suggest that radiation induces a rapid enhancement of the prevailing inflammation in high-grade glioma tissue. The microdialysis technique is feasible for this type of study and could be used to monitor metabolic changes after different interventions.

sted, utgiver, år, opplag, sider
Springer, 2017
Emneord
Cytokine, Glioblastoma, Radiotherapy, Microdialysis, Inflammation
HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-131132 (URN)10.1007/s11060-016-2271-1 (DOI)000393065400010 ()27664151 (PubMedID)
Tilgjengelig fra: 2017-02-06 Laget: 2017-02-06 Sist oppdatert: 2019-05-09bibliografisk kontrollert
Mörén, L., Wibom, C., Bergström, P., Johansson, M., Antti, H. & Bergenheim, A. T. (2016). Characterization of the serum metabolome following radiation treatment in patients with high-grade gliomas. Radiation Oncology, 11, Article ID 51.
Åpne denne publikasjonen i ny fane eller vindu >>Characterization of the serum metabolome following radiation treatment in patients with high-grade gliomas
Vise andre…
2016 (engelsk)Inngår i: Radiation Oncology, ISSN 1748-717X, E-ISSN 1748-717X, Vol. 11, artikkel-id 51Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Background: Glioblastomas progress rapidly making response evaluation using MRI insufficient since treatment effects are not detectable until months after initiation of treatment. Thus, there is a strong need for supplementary biomarkers that could provide reliable and early assessment of treatment efficacy. Analysis of alterations in the metabolome may be a source for identification of new biomarker patterns harboring predictive information. Ideally, the biomarkers should be found within an easily accessible compartment such as the blood. Method: Using gas-chromatographic-time-of-flight-mass spectroscopy we have analyzed serum samples from 11 patients with glioblastoma during the initial phase of radiotherapy. Fasting serum samples were collected at admittance, on the same day as, but before first treatment and in the morning after the second and fifth dose of radiation. The acquired data was analyzed and evaluated by chemometrics based bioinformatics methods. Our findings were compared and discussed in relation to previous data from microdialysis in tumor tissue, i.e. the extracellular compartment, from the same patients. Results: We found a significant change in metabolite pattern in serum comparing samples taken before radiotherapy to samples taken during early radiotherapy. In all, 68 metabolites were lowered in concentration following treatment while 16 metabolites were elevated in concentration. All detected and identified amino acids and fatty acids together with myo-inositol, creatinine, and urea were among the metabolites that decreased in concentration during treatment, while citric acid was among the metabolites that increased in concentration. Furthermore, when comparing results from the serum analysis with findings in tumor extracellular fluid we found a common change in metabolite patterns in both compartments on an individual patient level. On an individual metabolite level similar changes in ornithine, tyrosine and urea were detected. However, in serum, glutamine and glutamate were lowered after treatment while being elevated in the tumor extracellular fluid. Conclusion: Cross-validated multivariate statistical models verified that the serum metabolome was significantly changed in relation to radiation in a similar pattern to earlier findings in tumor tissue. However, all individual changes in tissue did not translate into changes in serum. Our study indicates that serum metabolomics could be of value to investigate as a potential marker for assessing early response to radiotherapy in malignant glioma.

sted, utgiver, år, opplag, sider
BioMed Central, 2016
Emneord
Glioblastoma, Radiation therapy, Treatment response, Metabolomics, Chemometrics
HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-119631 (URN)10.1186/s13014-016-0626-6 (DOI)000373185900001 ()27039175 (PubMedID)
Tilgjengelig fra: 2016-05-20 Laget: 2016-04-25 Sist oppdatert: 2018-06-07bibliografisk kontrollert
Lindvall, P., Grayson, D., Bergström, P. & Bergenheim, A. T. (2015). Hypofractionated stereotactic radiotherapy in medium-sized to large arteriovenous malformations. Journal of clinical neuroscience, 22(6), 955-958
Åpne denne publikasjonen i ny fane eller vindu >>Hypofractionated stereotactic radiotherapy in medium-sized to large arteriovenous malformations
2015 (engelsk)Inngår i: Journal of clinical neuroscience, ISSN 0967-5868, E-ISSN 1532-2653, Vol. 22, nr 6, s. 955-958Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

We have reviewed treatment results in terms of obliteration and complications in 24 patients with medium to large sized cerebral arteriovenous malformations (AVMs) (mean volume 18.5 +/- 8.9 cm(3); range: 10-42) treated with hypofractionated stereotactic radiotherapy (HSRT). AVMs are congenital lesions associated with a high morbidity and mortality. Radiosurgery is one option for treatment. However, in larger AVMs with volumes exceeding 10 cm(3) obliteration rates are less favourable and radiation induced complications more frequent. For larger AVMs, volume-staged radiosurgery is one option while another option may be the use of HSRT. Patients were treated with 6-7 Gy in five fractions to a total dose of 30-35 Gy (mean total dose 32.9 +/- 1.6 Gy [standard error of the mean]). Sixteen patients (69.6%) showed obliteration after a mean time of 35.2 +/- 14.8 months (range: 24-60). Only one patient (4.2%) experienced symptomatic radionecrosis. Our treatment with HSRT seems safe and efficient for treatment of medium to large sized AVMs. Treatment results seem to be in line with volume-staged radiosurgery and may be an alternative for AVMs not suitable for single fraction radiosurgery.

Emneord
Arteriovenous malformations, Linear accelerator, Radiosurgery, Treatment results
HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-106122 (URN)10.1016/j.jocn.2014.12.015 (DOI)000355050300006 ()25827867 (PubMedID)
Tilgjengelig fra: 2015-07-14 Laget: 2015-07-09 Sist oppdatert: 2018-06-07bibliografisk kontrollert
Kristensen, I., Agrup, M., Bergström, P., Engellau, J., Haugen, H., Martinsson, U., . . . Nilsson, P. (2014). Assessment of volume segmentation in radiotherapy of adolescents: a treatment planning study by the Swedish Workgroup for Paediatric Radiotherapy. Acta Oncologica, 53(1), 126-133
Åpne denne publikasjonen i ny fane eller vindu >>Assessment of volume segmentation in radiotherapy of adolescents: a treatment planning study by the Swedish Workgroup for Paediatric Radiotherapy
Vise andre…
2014 (engelsk)Inngår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 53, nr 1, s. 126-133Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Background and purpose. The variability in target delineation for similar cases between centres treating paediatric and adolescent patients, and the apparent differences in interpretation of radiotherapy guidelines in the treatment protocols encouraged us to perform a dummy-run study as a part of our quality assurance work. The aim was to identify and quantify differences in the segmentation of target volumes and organs at risk (OARs) and to analyse the treatment plans and dose distributions. Materials and methods. Four patient cases were selected: Wilm's tumour, Hodgkin's disease, rhabdomyosarcoma of the prostate and chordoma of the skull base. The five participating centres received the same patient-related material. They introduced the cases in their treatment planning system, delineated target volumes and OARs and created treatment plans. Dose-volume histograms were retrieved for relevant structures and volumes and dose metrics were derived and compared, e. g. target volumes and their concordance, dose homogeneity index (HI), treated and irradiated volumes, remaining volume at risk and relevant V x and D x values. Results. We found significant differences in target segmentation in the majority of the cases. The planning target volumes (PTVs) varied two-to four-fold and conformity indices were in the range of 0.3-0.6. This resulted in large variations in dose distributions to OARs as well as in treated and irradiated volumes even though the treatment plans showed good conformity to the PTVs. Potential reasons for the differences in target delineation were analysed. Conclusion. Considerations of the growing child and difficulties in interpretation of the radiotherapy information in the treatment protocols were identified as reasons for the variation. As a result, clarified translated detailed radiotherapy guidelines for paediatric/adolescent patients have been recognised as a way to reduce this variation.

sted, utgiver, år, opplag, sider
Informa Healthcare, 2014
HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-85620 (URN)10.3109/0284186X.2013.782104 (DOI)000328945500018 ()
Tilgjengelig fra: 2014-02-10 Laget: 2014-02-07 Sist oppdatert: 2018-06-08bibliografisk kontrollert
Nyholm, T., Jonsson, J., Söderström, K., Bergström, P., Carlberg, A., Frykholm, G., . . . Zackrisson, B. (2013). Variability in prostate and seminal vesicle delineations defined on magnetic resonance images, a multi-observer, -center and -sequence study. Radiation Oncology, 8, 126
Åpne denne publikasjonen i ny fane eller vindu >>Variability in prostate and seminal vesicle delineations defined on magnetic resonance images, a multi-observer, -center and -sequence study
Vise andre…
2013 (engelsk)Inngår i: Radiation Oncology, ISSN 1748-717X, E-ISSN 1748-717X, Vol. 8, s. 126-Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Background: The use of magnetic resonance (MR) imaging as a part of preparation for radiotherapy is increasing. For delineation of the prostate several publications have shown decreased delineation variability using MR compared to computed tomography (CT). The purpose of the present work was to investigate the intra- and inter-physician delineation variability for prostate and seminal vesicles, and to investigate the influence of different MR sequence settings used clinically at the five centers participating in the study.

Methods: MR series from five centers, each providing five patients, were used. Two physicians from each center delineated the prostate and the seminal vesicles on each of the 25 image sets. The variability between the delineations was analyzed with respect to overall, intra-and inter-physician variability, and dependence between variability and origin of the MR images, i.e. the MR sequence used to acquire the data.

Results: The intra-physician variability in different directions was between 1.3 - 1.9 mm and 3 - 4 mm for the prostate and seminal vesicles respectively (1 std). The inter-physician variability for different directions were between 0.7 - 1.7 mm and approximately equal for the prostate and seminal vesicles. Large differences in variability were observed for individual patients, and also for individual imaging sequences used at the different centers. There was however no indication of decreased variability with higher field strength.

Conclusion: The overall delineation variability is larger for the seminal vesicles compared to the prostate, due to a larger intra-physician variability. The imaging sequence appears to have a large influence on the variability, even for different variants of the T2-weighted spin-echo based sequences, which were used by all centers in the study.

sted, utgiver, år, opplag, sider
BioMed Central, 2013
Emneord
Prostate, Seminal-vesicles, Delineation, Magnetic resonance imaging, Radiotherapy, Variability
HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-78454 (URN)10.1186/1748-717X-8-126 (DOI)000320268700001 ()
Tilgjengelig fra: 2013-07-23 Laget: 2013-07-22 Sist oppdatert: 2018-06-08bibliografisk kontrollert
Wibom, C., Surowiec, I., Mörén, L., Bergström, P., Johansson, M., Antti, H. & Bergenheim, A. T. (2010). Metabolomic patterns in glioblastoma and changes during radiotherapy: a clinical microdialysis study. Journal of Proteome Research, 9(6), 2909-2919
Åpne denne publikasjonen i ny fane eller vindu >>Metabolomic patterns in glioblastoma and changes during radiotherapy: a clinical microdialysis study
Vise andre…
2010 (engelsk)Inngår i: Journal of Proteome Research, ISSN 1535-3893, E-ISSN 1535-3907, Vol. 9, nr 6, s. 2909-2919Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

We employed stereotactic microdialysis to sample extracellular fluid intracranially from glioblastoma patients, before and during the first five days of conventional radiotherapy treatment. Microdialysis catheters were implanted in the contrast enhancing tumor as well as in the brain adjacent to tumor (BAT). Reference samples were collected subcutaneously from the patients' abdomen. The samples were analyzed by gas chromatography-time-of-flight mass spectrometry (GC-TOF MS), and the acquired data was processed by hierarchical multivariate curve resolution (H-MCR) and analyzed with orthogonal partial least-squares (OPLS). To enable detection of treatment-induced alterations, the data was processed by individual treatment over time (ITOT) normalization. One-hundred fifty-one metabolites were reliably detected, of which 67 were identified. We found distinct metabolic differences between the intracranially collected samples from tumor and the BAT region. There was also a marked difference between the intracranially and the subcutaneously collected samples. Furthermore, we observed systematic metabolic changes induced by radiotherapy treatment among both tumor and BAT samples. The metabolite patterns affected by treatment were different between tumor and BAT, both containing highly discriminating information, ROC values of 0.896 and 0.821, respectively. Our findings contribute to increased molecular knowledge of basic glioblastoma pathophysiology and point to the possibility of detecting metabolic marker patterns associated to early treatment response.

sted, utgiver, år, opplag, sider
American Chemical Society (ACS), 2010
Emneord
chemometrics, gas chromatography-mass spectrometry, glioblastoma, metabolomics, predictive metabolomics, radiotherapy, treatment response
HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-25668 (URN)10.1021/pr901088r (DOI)000278243300011 ()20302353 (PubMedID)
Tilgjengelig fra: 2009-08-27 Laget: 2009-08-27 Sist oppdatert: 2018-06-08bibliografisk kontrollert
Lindvall, P., Bergström, P., Blomquist, M. & Bergenheim, A. T. (2010). Radiation schedules in relation to obliteration and complications in hypofractionated conformal stereotactic radiotherapy of arteriovenous malformations. Stereotactic and Functional Neurosurgery, 88(1), 24-28
Åpne denne publikasjonen i ny fane eller vindu >>Radiation schedules in relation to obliteration and complications in hypofractionated conformal stereotactic radiotherapy of arteriovenous malformations
2010 (engelsk)Inngår i: Stereotactic and Functional Neurosurgery, ISSN 1011-6125, E-ISSN 1423-0372, Vol. 88, nr 1, s. 24-28Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

AIMS: The purpose of this investigation was to assess the obliteration rate and complications following different radiation schedules of hypofractionated conformal stereotactic radiotherapy for cerebral arteriovenous malformations (AVMs). METHODS: Twenty-five patients were treated with 35 Gy in 5 fractions, whereas 31 patients were treated with 30-32.5 Gy (mean: 31.6 +/- 0.23 Gy) in 5 fractions. A complete angiographic follow-up is available for 40 patients. RESULTS: Thirty-seven out of 40 patients (92.5%) have so far shown obliteration of their AVMs after a mean time of 3.2 +/- 0.26 years (range: 2-8 years). The mean AVM volume in these patients was 8.2 +/- 1.0 cm(3) (range: 1.5-29 cm(3)). There was a higher rate of obliteration (88%) in patients treated with 35 Gy compared to those treated with < 35 Gy (78%), even if this was not statistically significant. There was a significantly shorter time to obliteration in patients treated with 35 Gy. All patients who experienced symptomatic radionecrosis belonged to the group treated with 35 Gy. CONCLUSION: A radiation schedule of 35 Gy in 5 fractions may be more effective than a radiation schedule of <35 (30-32.5) Gy in obliterating AVMs. This may, however, be at the price of an increased risk of symptomatic radionecrosis.

Emneord
Arteriovenous malformations, stereotactic radiotherapy, fractionation, linear particle accelerator
Identifikatorer
urn:nbn:se:umu:diva-35296 (URN)10.1159/000260076 (DOI)19940546 (PubMedID)
Tilgjengelig fra: 2010-08-11 Laget: 2010-08-11 Sist oppdatert: 2018-06-08bibliografisk kontrollert
Lindvall, P., Bergström, P., Löfroth, P.-O. & Bergenheim, A. T. (2009). A comparison between surgical resection in combination with WBRT or hypofractionated stereotactic irradiation in the treatment of solitary brain metastases.. Acta Neurochirurgica, 151(9), 1053-1059
Åpne denne publikasjonen i ny fane eller vindu >>A comparison between surgical resection in combination with WBRT or hypofractionated stereotactic irradiation in the treatment of solitary brain metastases.
2009 (engelsk)Inngår i: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 151, nr 9, s. 1053-1059Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

BACKGROUND: The standard treatment of solitary brain metastases previously has been tumour resection in combination with whole-brain radiation therapy (WBRT). Stereotactic radiotherapy has emerged as a non-invasive treatment option especially for small brain metastases. We now report our results on resection + WBRT or hypofractionated stereotactic irradiation (HCSRT) in the treatment of solitary brain metastases. METHODS: Between 1993 and 2004 patients with metastatic cancer and solitary brain metastases were selected for surgical resection + WBRT or HCSRT alone at the Umeå University Hospital. Fifty-nine patients were treated with surgical resection + WBRT (34 male, 25 female, mean age 63.3 years). Forty-seven patients were treated with HCSRT alone (15 male, 32 female, mean age 64.9 years). FINDINGS: In patients followed radiologically, 28% treated with resection + WBRT showed a local recurrence after a median time of 8.0 months, whereas there was a lack of local control in 16% in the HCSRT group after a median time of 3.0 months. There was a significantly longer survival time for patients treated with resection + WBRT (median 7.9, mean 12.9 months) compared to HCSRT (median 5.0, mean 7.6 months). Even in patients with a tumour volume <10 cc, there was a significantly longer survival in favour of resection + WBRT (median 8.4, mean 17.4 months) compared to HCSRT (median 5.0, mean 7.9 months). CONCLUSION: This retrospective and non-randomised study indicates that surgical resection in combination with WBRT may be an option even for small brain metastases suitable for treatment with HCSRT. Since survival and local control following resection + WBRT was at least as favourable as compared to HCSRT alone, tumour location and expected neurological outcome may be the strongest aspect when selecting treatment modality.

Emneord
Cerebral metastases, surgical resection, stereotactic irradiation, whole-brain radiation therapy, hypofractionation
HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-25811 (URN)10.1007/s00701-009-0325-2 (DOI)19390775 (PubMedID)
Tilgjengelig fra: 2009-09-03 Laget: 2009-09-03 Sist oppdatert: 2019-11-19bibliografisk kontrollert
Henriksson, R., Bergström, P., Johansson, M. & Sandström, M. (2009). Enigma of a rapid introduction of antiangiogenic therapy with bevacizumab in glioblastoma: a new era in the treatment of malignant brain tumours?. Acta Oncologica, 48(1), 6-8
Åpne denne publikasjonen i ny fane eller vindu >>Enigma of a rapid introduction of antiangiogenic therapy with bevacizumab in glioblastoma: a new era in the treatment of malignant brain tumours?
2009 (engelsk)Inngår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 48, nr 1, s. 6-8Artikkel i tidsskrift, Editorial material (Annet vitenskapelig) Published
sted, utgiver, år, opplag, sider
Oslo: Taylor & Francis, 2009
Emneord
glioma, temozolomide, angiogenesis, combination, multiforme, inhibitor
HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-11500 (URN)10.1080/02841860802468112 (DOI)000261847600001 ()18932097 (PubMedID)
Tilgjengelig fra: 2009-01-13 Laget: 2009-01-13 Sist oppdatert: 2019-05-15bibliografisk kontrollert
Organisasjoner