Astrid Weyerbrock - Profile on Academia.edu (original) (raw)

Papers by Astrid Weyerbrock

Research paper thumbnail of Clinical benefit from resection of recurrent glioblastomas: results of a multicenter study including 503 patients with recurrent glioblastomas undergoing surgical resection

Neuro-oncology, Jan 4, 2015

While standards for the treatment of newly diagnosed glioblastomas exist, therapeutic regimens fo... more While standards for the treatment of newly diagnosed glioblastomas exist, therapeutic regimens for tumor recurrence remain mostly individualized. The role of a surgical resection of recurrent glioblastomas remains largely unclear at present. This study aimed to assess the effect of repeated resection of recurrent glioblastomas on patient survival. In a multicenter retrospective-design study, patients with primary glioblastomas undergoing repeat resections for recurrent tumors were evaluated for factors affecting survival. Age, Karnofsky performance status (KPS), extent of resection (EOR), tumor location, and complications were assessed. Five hundred and three patients (initially diagnosed between 2006 and 2010) undergoing resections for recurrent glioblastoma at 20 institutions were included in the study. The patients' median overall survival after initial diagnosis was 25.0 months and 11.9 months after first re-resection. The following parameters were found to influence surviva...

Research paper thumbnail of Early-stage penile carcinoma metastasizing to brain: Case report and literature review

Urology, 2005

Early-stage penile squamous cell carcinoma with subsequent distant metastases is rare. We report ... more Early-stage penile squamous cell carcinoma with subsequent distant metastases is rare. We report a case of a 35-year-old man with Stage pT1pN0 penile squamous cell carcinoma who underwent circumcision and bilateral inguinal lymphadenectomy. Further in the disease course, the patient developed metastases in the kidney, adrenal gland, retroperitoneal lymph nodes, lung, and brain. He underwent multiple resections, whole brain radiotherapy,

Research paper thumbnail of Gene transfer technologies for malignant gliomas

Gene transfer technologies for malignant gliomas

Current Opinion in Oncology, 1999

Research paper thumbnail of Cytokine production during sleep and wakefulness and its relationship to cortisol in healthy humans

Cytokine production during sleep and wakefulness and its relationship to cortisol in healthy humans

Neuropsychobiology

A growing body of evidence indicates that cytokines, especially interleukin-1 beta, are involved ... more A growing body of evidence indicates that cytokines, especially interleukin-1 beta, are involved in the regulation of sleep and wakefulness. The aim of the present pilot study was to investigate the relationship between interleukin-1 beta (IL-1 beta) and gamma-interferon (gamma-IFN) production and the regulation of sleep and wakefulness. Four healthy male volunteers were investigated. After one adaptation night, beginning at 8 a.m. in the morning, the EEG was recorded by means of a mobile long-term EEG and blood samples were drawn every 45 min for the analysis of IL-1 beta, gamma-IFN and cortisol for 24 h. For the analysis of cytokines whole blood cultures were established. After 48 h of incubation in the presence of endotoxin Salmonella typhimurium, IL-1 beta and gamma-IFN levels were measured in the culture supernatants using specific immunodetection assays. Methods of stochastic time series analysis were adopted to evaluate the biochemical data. Our results show the capability of cultured blood cells to produce cytokines upon endotoxin challenge to be at a maximum around the time of sleep onset and during the first hours of sleep, declining during the night to a minimum level in the morning hours. The opposite was observed for cortisol. The analysis of autocorrelation functions gives evidence of a 24-hour rhythm of cortisol and cytokines. The results indicate that the cytokines IL-1 beta and gamma-IFN may play a role in sleep regulation.

Research paper thumbnail of Gliomas: quo vadis

Research paper thumbnail of Early identification of individuals at high risk for cerebral infarction after aneurysmal subarachnoid hemorrhage: the BEHAVIOR score

Early identification of individuals at high risk for cerebral infarction after aneurysmal subarachnoid hemorrhage: the BEHAVIOR score

Journal of Cerebral Blood Flow & Metabolism, 2015

Cerebral infarction (CI) is a crucial complication of aneurysmal subarachnoid hemorrhage (SAH) as... more Cerebral infarction (CI) is a crucial complication of aneurysmal subarachnoid hemorrhage (SAH) associated with poor clinical outcome. We aimed at developing an early risk score for CI based on clinical characteristics available at the onset of SAH. Out of a database containing 632 consecutive patients with SAH admitted to our institution from January 2005 to December 2012, computed tomography (CT) scans up to day 42 after ictus were evaluated for CIs. Different parameters from admission up to aneurysm treatment were collected with subsequent construction of a risk score. Seven clinical characteristics were independently associated with CI and included in the Risk score (BEHAVIOR Score, 0 to 11 points): Blood on CT scan according to Fisher grade ⩾3 (1 point), Elderly patients (age ⩾55 years, 1 point), Hunt&Hess grade ⩾4 (1 point), Acute hydrocephalus requiring external liquor drainage (1 point), Vasospasm on initial angiogram (3 points), Intracranial pressure elevation >20 mm Hg (3 points), and treatment of multiple aneurysms ('Overtreatment', 1 point). The BEHAVIOR score showed high diagnostic accuracy with respect to the absolute risk for CI (area under curve=0.806, P<0.0001) and prediction of poor clinical outcome at discharge (P<0.0001) and after 6 months (P=0.0002). Further validation in other SAH cohorts is recommended.Journal of Cerebral Blood Flow & Metabolism advance online publication, 29 April 2015; doi:10.1038/jcbfm.2015.81.

Research paper thumbnail of Freiburg neuropathology case conference: tumor of the cerebellum with mild, gyriform enhancement in a 19-year-old patient

Freiburg neuropathology case conference: tumor of the cerebellum with mild, gyriform enhancement in a 19-year-old patient

Clinical neuroradiology, 2014

Research paper thumbnail of TERT promoter mutations and telomere length in adult malignant gliomas and recurrences

Oncotarget, Jan 12, 2015

In this report on 303 gliomas we show the highest frequency of TERT promoter mutations in gliobas... more In this report on 303 gliomas we show the highest frequency of TERT promoter mutations in gliobastomas (80%) followed by oligodendrogliomas (70%) and astrocytomas (39%). We observed positive association between TERT promoter and IDH mutations in oligodendroglial tumors (OR = 26.3; 95% CI 2.5-250.2) and inverse association in primary glioblastomas (OR = 0.13; 95% CI 0.03-0.58). Tumors with TERT promoter mutations compared to those without showed increased TERT transcription; we also showed difference in the transcription levels due to the two main mutations. Tumors with TERT promoter mutations had shorter telomeres than those without. The patients with only TERT promoter mutations showed worst survival (median survival 14.6 months) and patients with both IDH and TERT promoter mutations showed best survival (246.5 months). In patients with astrocytoma, the TERT promoter mutations only associated with poor survival (P < 0.0001); IDH mutations and 1p/19q deletions associated with inc...

Research paper thumbnail of Whole brain irradiation with hippocampal sparing and dose escalation on multiple brain metastases : Local tumour control and survival

Whole brain irradiation with hippocampal sparing and dose escalation on multiple brain metastases : Local tumour control and survival

Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al], Jan 16, 2015

Hippocampal-avoidance whole brain radiotherapy (HA-WBRT) for multiple brain metastases may preven... more Hippocampal-avoidance whole brain radiotherapy (HA-WBRT) for multiple brain metastases may prevent treatment-related cognitive decline, compared to standard WBRT. Additionally, simultaneous integrated boost (SIB) on individual metastases may further improve the outcome. Here, we present initial data concerning local tumour control (LTC), intracranial progression-free survival (PFS), overall survival (OS), toxicity and safety for this new irradiation technique. Twenty patients, enrolled between 2011 and 2013, were treated with HA-WBRT (30 Gy in 12 fractions, D98 % to hippocampus ≤ 9 Gy) and a SIB (51 Gy) on multiple (2-13) metastases using a volumetric modulated arc therapy (VMAT) approach based on 2-4 arcs. Metastases were evaluated bidimensionally along the two largest diameters in contrast-enhanced three-dimensional T1-weighed MRI. Median follow-up was 40 weeks. The median time to progression of boosted metastases has not been reached yet, corresponding to a LTC rate of 73 %. Medi...

Research paper thumbnail of Freiburg neuropathology case conference: multiple small ring-enhancing lesions in a 75-year-old patient

Clinical neuroradiology, 2014

Research paper thumbnail of Freiburg neuropathology case conference: widespread mass lesions after resection of a glioblastoma multiforme

Freiburg neuropathology case conference: widespread mass lesions after resection of a glioblastoma multiforme

Clinical neuroradiology, 2012

Research paper thumbnail of Freiburg neuropathology case conference: a diffusely infiltrating lesion

Freiburg neuropathology case conference: a diffusely infiltrating lesion

Clinical neuroradiology, 2010

Research paper thumbnail of Interdisciplinary pain therapy: an innovative therapeutic but pre-DRG Economical Center of Medical Excellence

Interdisciplinary pain therapy: an innovative therapeutic but pre-DRG Economical Center of Medical Excellence

Zentralblatt für Neurochirurgie, 2006

After the implementation of the G-DRG system in Germany, doubts arose whether and how interdiscip... more After the implementation of the G-DRG system in Germany, doubts arose whether and how interdisciplinary pain therapy centers should be restructured to remain profitable and maintain medical excellence for patients with a long ordeal of malaise. To reveal structural deficits, we performed a detailed economic analysis of all patients treated at an interdisciplinary pain therapy center of a German University hospital in 2004. 3,672 patients were treated: 2,163 outpatients, 753 at the daycare clinic, 619 as consults and 132 inpatients. The costs for personnel were euro 736,645, consumables euro 105,061, and infrastructure euro 277,762. We calculated fixed costs of euro 236, and consumables of euro 24 per patient. The costs for surgery were euro 1,595, and for a neuroradiological examination euro 245 per patient. Overall treatment costs were euro 319 per patient. We calculated an overall loss of euro 476,752 or euro 109.19 per patient. Outpatients caused a total loss of euro 456,665.83 o...

Research paper thumbnail of Active bleeding from ruptured cerebral aneurysms during diagnostic angiography: emergency treatment

AJNR. American journal of neuroradiology

Despite new developments in the treatment of cerebral aneurysms, recurrent hemorrhage of an aneur... more Despite new developments in the treatment of cerebral aneurysms, recurrent hemorrhage of an aneurysm is the most feared complication of subarachnoid bleeding. The prognosis of patients with early reruptured aneurysms is discouraging. A rerupture of an aneurysm with active bleeding is extremely rare, and the mechanisms involved remain unclear. We report the management of active bleeding of reruptured aneurysms during diagnostic angiography. In two patients, emergency treatment of the active hemorrhage was performed by means of neurosurgical intervention and by an endovascular approach in one other case. The causes and management of reruptured aneurysms with active bleeding are also discussed within the context of a review of the literature.

Research paper thumbnail of Selective opening of the blood-tumor barrier by a nitric oxide donor and long-term survival in rats with C6 gliomas

Selective opening of the blood-tumor barrier by a nitric oxide donor and long-term survival in rats with C6 gliomas

Journal of neurosurgery, 2003

The response of brain tumors to systemic chemotherapy is limited by the blood-tumor barrier (BTB)... more The response of brain tumors to systemic chemotherapy is limited by the blood-tumor barrier (BTB). Nitric oxide (NO) has been implicated in the regulation of vascular permeability and blood flow. The authors evaluated the effects of exogenous NO, which was released from a short-acting NO donor (Proli/NO), and those of NO metabolites on the capillary permeability of tumors and normal brain tissue by using quantitative autoradiography in a C6 glioma model in rats. The Proli/NO was infused at a wide dose range (10(-2) to 10(-12) M) either intravenously or into the internal carotid artery (ICA) and demonstrated substantial tumor-selective increases in blood-brain barrier (BBB) permeability in response to various-sized tracers ([14C]aminoisobutyric acid, [14C]sucrose, [14C]dextran). Internal carotid artery or intravenous administration of sodium nitrite had a comparable effect on BTB permeability. The NO effect on microvascular permeability could be obtained without causing hemodynamic s...

Research paper thumbnail of Lack of evidence for PlGF mediating the tumor resistance after anti-angiogenic therapy in malignant gliomas

Journal of Neuro-Oncology, 2014

Placenta growth factor (PlGF) is a member of vascular endothelial growth factor family which can ... more Placenta growth factor (PlGF) is a member of vascular endothelial growth factor family which can promote cancer growth by various mechanisms. Placenta growth factor is upregulated in many neoplastic diseases and serum levels of PlGF are increased in cancer patients following anti-angiogenic therapy. However, its role in glioma growth is yet not fully elucidated. In this study we analyzed the expression of PlGF mRNA using real time PCR in human gliomas of different WHO grades. Placenta growth factor mRNA levels were highly variable and did not correlate with WHO grades, arguing against a significant role in glioma progression. The highest PlGF expression was observed in anaplastic astrocytomas whereas grade II astrocytomas and glioblastomas displayed lower levels of expression. Immunohistochemical analysis showed that PlGF was expressed by inflammatory and endothelial cells in addition to tumor cells. Placenta growth factor mRNA expression in 12 matched glioblastoma samples before and after therapy, including bevacizumab and cilengitide treatment was largely unaffected by the aforementioned treatment modalities. In vitro, the exposure of VEGFR-1 expressing glioma cells to bevacizumab did not increase the expression levels of PlGF mRNA. In summary, our results do not support the hypothesis that PlGF plays a major role in the resistance of gliomas after anti-angiogenic therapy.

Research paper thumbnail of Freiburg Neuropathology Case Conference: an Intramedullary Mass Lesion in a Child

Freiburg Neuropathology Case Conference: an Intramedullary Mass Lesion in a Child

Clinical Neuroradiology, 2010

Research paper thumbnail of Cilengitide combined with standard treatment for patients with newly diagnosed glioblastoma with methylated MGMT promoter (CENTRIC EORTC 26071-22072 study): a multicentre, randomised, open-label, phase 3 trial

The Lancet. Oncology, 2014

Cilengitide is a selective αvβ3 and αvβ5 integrin inhibitor. Data from phase 2 trials suggest tha... more Cilengitide is a selective αvβ3 and αvβ5 integrin inhibitor. Data from phase 2 trials suggest that it has antitumour activity as a single agent in recurrent glioblastoma and in combination with standard temozolomide chemoradiotherapy in newly diagnosed glioblastoma (particularly in tumours with methylated MGMT promoter). We aimed to assess cilengitide combined with temozolomide chemoradiotherapy in patients with newly diagnosed glioblastoma with methylated MGMT promoter. In this multicentre, open-label, phase 3 study, we investigated the efficacy of cilengitide in patients from 146 study sites in 25 countries. Eligible patients (newly diagnosed, histologically proven supratentorial glioblastoma, methylated MGMT promoter, and age ≥18 years) were stratified for prognostic Radiation Therapy Oncology Group recursive partitioning analysis class and geographic region and centrally randomised in a 1:1 ratio with interactive voice response system to receive temozolomide chemoradiotherapy wi...

Research paper thumbnail of Aneurysmal and Non-Aneurysmal SAH – Is Initial Computed Tomography Predictive?

Aneurysmal and Non-Aneurysmal SAH – Is Initial Computed Tomography Predictive?

RöFo - Fortschritte auf dem Gebiet der Röntgenstrahlen und der bildgebenden Verfahren, 2009

Diagnostic workup in patients with angiographically negative subarachnoid hemorrhage (SAH) remain... more Diagnostic workup in patients with angiographically negative subarachnoid hemorrhage (SAH) remains controversial. We discuss the relevance of bleeding patterns on CT as they pertain to the prediction of angiographic results. We compared bleeding patterns on 112 CTs of patients with non-aneurysmal subarachnoid hemorrhage (non-ASAH) and 104 CTs of patients with aneurysmal SAH (ASAH) taken within 48 hours according to a CT-based grading system (Type 0 - 4). Bleeding patterns differed between ASAH and non-ASAH patients (p &lt; 0.0001). Non-ASAH patients had no or prepontine blood (type 0 + 1) in 40% of cases, extension into the medial (type 2) or lateral (type 3) Sylvian fissure in 60% of cases and no intracerebral hemorrhage (type 4). All type 0 and 1 patients had negative initial and repeat angiographies. A CT classification of bleeding patterns helps to predict angiographic results. Digital subtraction angiography (DSA) should remain the gold standard as it allows detection non-aneurysmal bleeding sources at low-risk. Repeat angiography may be omitted in the case of type 0 and 1 bleeding if a complete, high quality DSA was obtained initially.

Research paper thumbnail of Delayed cell death associated with mitotic catastrophe in γ-irradiated stem-like glioma cells

Radiation Oncology, 2011

Background and Purpose: Stem-like tumor cells are regarded as highly resistant to ionizing radiat... more Background and Purpose: Stem-like tumor cells are regarded as highly resistant to ionizing radiation (IR). Previous studies have focused on apoptosis early after irradiation, and the apoptosis resistance observed has been attributed to reduced DNA damage or enhanced DNA repair compared to non-stem tumor cells. Here, early and late radioresponse of patient-derived stem-like glioma cells (SLGCs) and differentiated cells directly derived from them were examined for cell death mode and the influence of stem cell-specific growth factors. Materials and methods: Primary SLGCs were propagated in serum-free medium with the stem-cell mitogens epidermal growth factor (EGF) and fibroblast growth factor-2 (FGF-2). Differentiation was induced by serumcontaining medium without EGF and FGF. Radiation sensitivity was evaluated by assessing proliferation, clonogenic survival, apoptosis, and mitotic catastrophe. DNA damage-associated γH2AX as well as p53 and p21 expression were determined by Western blots.

Research paper thumbnail of Clinical benefit from resection of recurrent glioblastomas: results of a multicenter study including 503 patients with recurrent glioblastomas undergoing surgical resection

Neuro-oncology, Jan 4, 2015

While standards for the treatment of newly diagnosed glioblastomas exist, therapeutic regimens fo... more While standards for the treatment of newly diagnosed glioblastomas exist, therapeutic regimens for tumor recurrence remain mostly individualized. The role of a surgical resection of recurrent glioblastomas remains largely unclear at present. This study aimed to assess the effect of repeated resection of recurrent glioblastomas on patient survival. In a multicenter retrospective-design study, patients with primary glioblastomas undergoing repeat resections for recurrent tumors were evaluated for factors affecting survival. Age, Karnofsky performance status (KPS), extent of resection (EOR), tumor location, and complications were assessed. Five hundred and three patients (initially diagnosed between 2006 and 2010) undergoing resections for recurrent glioblastoma at 20 institutions were included in the study. The patients' median overall survival after initial diagnosis was 25.0 months and 11.9 months after first re-resection. The following parameters were found to influence surviva...

Research paper thumbnail of Early-stage penile carcinoma metastasizing to brain: Case report and literature review

Urology, 2005

Early-stage penile squamous cell carcinoma with subsequent distant metastases is rare. We report ... more Early-stage penile squamous cell carcinoma with subsequent distant metastases is rare. We report a case of a 35-year-old man with Stage pT1pN0 penile squamous cell carcinoma who underwent circumcision and bilateral inguinal lymphadenectomy. Further in the disease course, the patient developed metastases in the kidney, adrenal gland, retroperitoneal lymph nodes, lung, and brain. He underwent multiple resections, whole brain radiotherapy,

Research paper thumbnail of Gene transfer technologies for malignant gliomas

Gene transfer technologies for malignant gliomas

Current Opinion in Oncology, 1999

Research paper thumbnail of Cytokine production during sleep and wakefulness and its relationship to cortisol in healthy humans

Cytokine production during sleep and wakefulness and its relationship to cortisol in healthy humans

Neuropsychobiology

A growing body of evidence indicates that cytokines, especially interleukin-1 beta, are involved ... more A growing body of evidence indicates that cytokines, especially interleukin-1 beta, are involved in the regulation of sleep and wakefulness. The aim of the present pilot study was to investigate the relationship between interleukin-1 beta (IL-1 beta) and gamma-interferon (gamma-IFN) production and the regulation of sleep and wakefulness. Four healthy male volunteers were investigated. After one adaptation night, beginning at 8 a.m. in the morning, the EEG was recorded by means of a mobile long-term EEG and blood samples were drawn every 45 min for the analysis of IL-1 beta, gamma-IFN and cortisol for 24 h. For the analysis of cytokines whole blood cultures were established. After 48 h of incubation in the presence of endotoxin Salmonella typhimurium, IL-1 beta and gamma-IFN levels were measured in the culture supernatants using specific immunodetection assays. Methods of stochastic time series analysis were adopted to evaluate the biochemical data. Our results show the capability of cultured blood cells to produce cytokines upon endotoxin challenge to be at a maximum around the time of sleep onset and during the first hours of sleep, declining during the night to a minimum level in the morning hours. The opposite was observed for cortisol. The analysis of autocorrelation functions gives evidence of a 24-hour rhythm of cortisol and cytokines. The results indicate that the cytokines IL-1 beta and gamma-IFN may play a role in sleep regulation.

Research paper thumbnail of Gliomas: quo vadis

Research paper thumbnail of Early identification of individuals at high risk for cerebral infarction after aneurysmal subarachnoid hemorrhage: the BEHAVIOR score

Early identification of individuals at high risk for cerebral infarction after aneurysmal subarachnoid hemorrhage: the BEHAVIOR score

Journal of Cerebral Blood Flow & Metabolism, 2015

Cerebral infarction (CI) is a crucial complication of aneurysmal subarachnoid hemorrhage (SAH) as... more Cerebral infarction (CI) is a crucial complication of aneurysmal subarachnoid hemorrhage (SAH) associated with poor clinical outcome. We aimed at developing an early risk score for CI based on clinical characteristics available at the onset of SAH. Out of a database containing 632 consecutive patients with SAH admitted to our institution from January 2005 to December 2012, computed tomography (CT) scans up to day 42 after ictus were evaluated for CIs. Different parameters from admission up to aneurysm treatment were collected with subsequent construction of a risk score. Seven clinical characteristics were independently associated with CI and included in the Risk score (BEHAVIOR Score, 0 to 11 points): Blood on CT scan according to Fisher grade ⩾3 (1 point), Elderly patients (age ⩾55 years, 1 point), Hunt&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;Hess grade ⩾4 (1 point), Acute hydrocephalus requiring external liquor drainage (1 point), Vasospasm on initial angiogram (3 points), Intracranial pressure elevation &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;20 mm Hg (3 points), and treatment of multiple aneurysms (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;Overtreatment&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;, 1 point). The BEHAVIOR score showed high diagnostic accuracy with respect to the absolute risk for CI (area under curve=0.806, P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.0001) and prediction of poor clinical outcome at discharge (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.0001) and after 6 months (P=0.0002). Further validation in other SAH cohorts is recommended.Journal of Cerebral Blood Flow &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp; Metabolism advance online publication, 29 April 2015; doi:10.1038/jcbfm.2015.81.

Research paper thumbnail of Freiburg neuropathology case conference: tumor of the cerebellum with mild, gyriform enhancement in a 19-year-old patient

Freiburg neuropathology case conference: tumor of the cerebellum with mild, gyriform enhancement in a 19-year-old patient

Clinical neuroradiology, 2014

Research paper thumbnail of TERT promoter mutations and telomere length in adult malignant gliomas and recurrences

Oncotarget, Jan 12, 2015

In this report on 303 gliomas we show the highest frequency of TERT promoter mutations in gliobas... more In this report on 303 gliomas we show the highest frequency of TERT promoter mutations in gliobastomas (80%) followed by oligodendrogliomas (70%) and astrocytomas (39%). We observed positive association between TERT promoter and IDH mutations in oligodendroglial tumors (OR = 26.3; 95% CI 2.5-250.2) and inverse association in primary glioblastomas (OR = 0.13; 95% CI 0.03-0.58). Tumors with TERT promoter mutations compared to those without showed increased TERT transcription; we also showed difference in the transcription levels due to the two main mutations. Tumors with TERT promoter mutations had shorter telomeres than those without. The patients with only TERT promoter mutations showed worst survival (median survival 14.6 months) and patients with both IDH and TERT promoter mutations showed best survival (246.5 months). In patients with astrocytoma, the TERT promoter mutations only associated with poor survival (P < 0.0001); IDH mutations and 1p/19q deletions associated with inc...

Research paper thumbnail of Whole brain irradiation with hippocampal sparing and dose escalation on multiple brain metastases : Local tumour control and survival

Whole brain irradiation with hippocampal sparing and dose escalation on multiple brain metastases : Local tumour control and survival

Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al], Jan 16, 2015

Hippocampal-avoidance whole brain radiotherapy (HA-WBRT) for multiple brain metastases may preven... more Hippocampal-avoidance whole brain radiotherapy (HA-WBRT) for multiple brain metastases may prevent treatment-related cognitive decline, compared to standard WBRT. Additionally, simultaneous integrated boost (SIB) on individual metastases may further improve the outcome. Here, we present initial data concerning local tumour control (LTC), intracranial progression-free survival (PFS), overall survival (OS), toxicity and safety for this new irradiation technique. Twenty patients, enrolled between 2011 and 2013, were treated with HA-WBRT (30 Gy in 12 fractions, D98 % to hippocampus ≤ 9 Gy) and a SIB (51 Gy) on multiple (2-13) metastases using a volumetric modulated arc therapy (VMAT) approach based on 2-4 arcs. Metastases were evaluated bidimensionally along the two largest diameters in contrast-enhanced three-dimensional T1-weighed MRI. Median follow-up was 40 weeks. The median time to progression of boosted metastases has not been reached yet, corresponding to a LTC rate of 73 %. Medi...

Research paper thumbnail of Freiburg neuropathology case conference: multiple small ring-enhancing lesions in a 75-year-old patient

Clinical neuroradiology, 2014

Research paper thumbnail of Freiburg neuropathology case conference: widespread mass lesions after resection of a glioblastoma multiforme

Freiburg neuropathology case conference: widespread mass lesions after resection of a glioblastoma multiforme

Clinical neuroradiology, 2012

Research paper thumbnail of Freiburg neuropathology case conference: a diffusely infiltrating lesion

Freiburg neuropathology case conference: a diffusely infiltrating lesion

Clinical neuroradiology, 2010

Research paper thumbnail of Interdisciplinary pain therapy: an innovative therapeutic but pre-DRG Economical Center of Medical Excellence

Interdisciplinary pain therapy: an innovative therapeutic but pre-DRG Economical Center of Medical Excellence

Zentralblatt für Neurochirurgie, 2006

After the implementation of the G-DRG system in Germany, doubts arose whether and how interdiscip... more After the implementation of the G-DRG system in Germany, doubts arose whether and how interdisciplinary pain therapy centers should be restructured to remain profitable and maintain medical excellence for patients with a long ordeal of malaise. To reveal structural deficits, we performed a detailed economic analysis of all patients treated at an interdisciplinary pain therapy center of a German University hospital in 2004. 3,672 patients were treated: 2,163 outpatients, 753 at the daycare clinic, 619 as consults and 132 inpatients. The costs for personnel were euro 736,645, consumables euro 105,061, and infrastructure euro 277,762. We calculated fixed costs of euro 236, and consumables of euro 24 per patient. The costs for surgery were euro 1,595, and for a neuroradiological examination euro 245 per patient. Overall treatment costs were euro 319 per patient. We calculated an overall loss of euro 476,752 or euro 109.19 per patient. Outpatients caused a total loss of euro 456,665.83 o...

Research paper thumbnail of Active bleeding from ruptured cerebral aneurysms during diagnostic angiography: emergency treatment

AJNR. American journal of neuroradiology

Despite new developments in the treatment of cerebral aneurysms, recurrent hemorrhage of an aneur... more Despite new developments in the treatment of cerebral aneurysms, recurrent hemorrhage of an aneurysm is the most feared complication of subarachnoid bleeding. The prognosis of patients with early reruptured aneurysms is discouraging. A rerupture of an aneurysm with active bleeding is extremely rare, and the mechanisms involved remain unclear. We report the management of active bleeding of reruptured aneurysms during diagnostic angiography. In two patients, emergency treatment of the active hemorrhage was performed by means of neurosurgical intervention and by an endovascular approach in one other case. The causes and management of reruptured aneurysms with active bleeding are also discussed within the context of a review of the literature.

Research paper thumbnail of Selective opening of the blood-tumor barrier by a nitric oxide donor and long-term survival in rats with C6 gliomas

Selective opening of the blood-tumor barrier by a nitric oxide donor and long-term survival in rats with C6 gliomas

Journal of neurosurgery, 2003

The response of brain tumors to systemic chemotherapy is limited by the blood-tumor barrier (BTB)... more The response of brain tumors to systemic chemotherapy is limited by the blood-tumor barrier (BTB). Nitric oxide (NO) has been implicated in the regulation of vascular permeability and blood flow. The authors evaluated the effects of exogenous NO, which was released from a short-acting NO donor (Proli/NO), and those of NO metabolites on the capillary permeability of tumors and normal brain tissue by using quantitative autoradiography in a C6 glioma model in rats. The Proli/NO was infused at a wide dose range (10(-2) to 10(-12) M) either intravenously or into the internal carotid artery (ICA) and demonstrated substantial tumor-selective increases in blood-brain barrier (BBB) permeability in response to various-sized tracers ([14C]aminoisobutyric acid, [14C]sucrose, [14C]dextran). Internal carotid artery or intravenous administration of sodium nitrite had a comparable effect on BTB permeability. The NO effect on microvascular permeability could be obtained without causing hemodynamic s...

Research paper thumbnail of Lack of evidence for PlGF mediating the tumor resistance after anti-angiogenic therapy in malignant gliomas

Journal of Neuro-Oncology, 2014

Placenta growth factor (PlGF) is a member of vascular endothelial growth factor family which can ... more Placenta growth factor (PlGF) is a member of vascular endothelial growth factor family which can promote cancer growth by various mechanisms. Placenta growth factor is upregulated in many neoplastic diseases and serum levels of PlGF are increased in cancer patients following anti-angiogenic therapy. However, its role in glioma growth is yet not fully elucidated. In this study we analyzed the expression of PlGF mRNA using real time PCR in human gliomas of different WHO grades. Placenta growth factor mRNA levels were highly variable and did not correlate with WHO grades, arguing against a significant role in glioma progression. The highest PlGF expression was observed in anaplastic astrocytomas whereas grade II astrocytomas and glioblastomas displayed lower levels of expression. Immunohistochemical analysis showed that PlGF was expressed by inflammatory and endothelial cells in addition to tumor cells. Placenta growth factor mRNA expression in 12 matched glioblastoma samples before and after therapy, including bevacizumab and cilengitide treatment was largely unaffected by the aforementioned treatment modalities. In vitro, the exposure of VEGFR-1 expressing glioma cells to bevacizumab did not increase the expression levels of PlGF mRNA. In summary, our results do not support the hypothesis that PlGF plays a major role in the resistance of gliomas after anti-angiogenic therapy.

Research paper thumbnail of Freiburg Neuropathology Case Conference: an Intramedullary Mass Lesion in a Child

Freiburg Neuropathology Case Conference: an Intramedullary Mass Lesion in a Child

Clinical Neuroradiology, 2010

Research paper thumbnail of Cilengitide combined with standard treatment for patients with newly diagnosed glioblastoma with methylated MGMT promoter (CENTRIC EORTC 26071-22072 study): a multicentre, randomised, open-label, phase 3 trial

The Lancet. Oncology, 2014

Cilengitide is a selective αvβ3 and αvβ5 integrin inhibitor. Data from phase 2 trials suggest tha... more Cilengitide is a selective αvβ3 and αvβ5 integrin inhibitor. Data from phase 2 trials suggest that it has antitumour activity as a single agent in recurrent glioblastoma and in combination with standard temozolomide chemoradiotherapy in newly diagnosed glioblastoma (particularly in tumours with methylated MGMT promoter). We aimed to assess cilengitide combined with temozolomide chemoradiotherapy in patients with newly diagnosed glioblastoma with methylated MGMT promoter. In this multicentre, open-label, phase 3 study, we investigated the efficacy of cilengitide in patients from 146 study sites in 25 countries. Eligible patients (newly diagnosed, histologically proven supratentorial glioblastoma, methylated MGMT promoter, and age ≥18 years) were stratified for prognostic Radiation Therapy Oncology Group recursive partitioning analysis class and geographic region and centrally randomised in a 1:1 ratio with interactive voice response system to receive temozolomide chemoradiotherapy wi...

Research paper thumbnail of Aneurysmal and Non-Aneurysmal SAH – Is Initial Computed Tomography Predictive?

Aneurysmal and Non-Aneurysmal SAH – Is Initial Computed Tomography Predictive?

RöFo - Fortschritte auf dem Gebiet der Röntgenstrahlen und der bildgebenden Verfahren, 2009

Diagnostic workup in patients with angiographically negative subarachnoid hemorrhage (SAH) remain... more Diagnostic workup in patients with angiographically negative subarachnoid hemorrhage (SAH) remains controversial. We discuss the relevance of bleeding patterns on CT as they pertain to the prediction of angiographic results. We compared bleeding patterns on 112 CTs of patients with non-aneurysmal subarachnoid hemorrhage (non-ASAH) and 104 CTs of patients with aneurysmal SAH (ASAH) taken within 48 hours according to a CT-based grading system (Type 0 - 4). Bleeding patterns differed between ASAH and non-ASAH patients (p &lt; 0.0001). Non-ASAH patients had no or prepontine blood (type 0 + 1) in 40% of cases, extension into the medial (type 2) or lateral (type 3) Sylvian fissure in 60% of cases and no intracerebral hemorrhage (type 4). All type 0 and 1 patients had negative initial and repeat angiographies. A CT classification of bleeding patterns helps to predict angiographic results. Digital subtraction angiography (DSA) should remain the gold standard as it allows detection non-aneurysmal bleeding sources at low-risk. Repeat angiography may be omitted in the case of type 0 and 1 bleeding if a complete, high quality DSA was obtained initially.

Research paper thumbnail of Delayed cell death associated with mitotic catastrophe in γ-irradiated stem-like glioma cells

Radiation Oncology, 2011

Background and Purpose: Stem-like tumor cells are regarded as highly resistant to ionizing radiat... more Background and Purpose: Stem-like tumor cells are regarded as highly resistant to ionizing radiation (IR). Previous studies have focused on apoptosis early after irradiation, and the apoptosis resistance observed has been attributed to reduced DNA damage or enhanced DNA repair compared to non-stem tumor cells. Here, early and late radioresponse of patient-derived stem-like glioma cells (SLGCs) and differentiated cells directly derived from them were examined for cell death mode and the influence of stem cell-specific growth factors. Materials and methods: Primary SLGCs were propagated in serum-free medium with the stem-cell mitogens epidermal growth factor (EGF) and fibroblast growth factor-2 (FGF-2). Differentiation was induced by serumcontaining medium without EGF and FGF. Radiation sensitivity was evaluated by assessing proliferation, clonogenic survival, apoptosis, and mitotic catastrophe. DNA damage-associated γH2AX as well as p53 and p21 expression were determined by Western blots.