Adelheid Wöhrer

Washington University in St. Louis, San Luis, Missouri, United States

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Publications (72)259.31 Total impact

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    ABSTRACT: OBJECT An important prognostic factor for the surgical outcome and recurrence of a pituitary adenoma is its invasiveness into parasellar tissue, particularly into the space of the cavernous sinus (CS). The aims of this study were to reevaluate the existing parasellar classifications using an endoscopic technique and to evaluate the clinical and radiological outcomes associated with each grade. METHODS The authors investigated 137 pituitary macroadenomas classified radiologically at least on one side as Grade 1 or higher (parasellar extension) and correlated the surgical findings using an endoscopic technique, with special reference to the invasiveness of the tumor into the CS. In each case, postoperative MRI was performed to evaluate the gross-total resection (GTR) rate and the rate of endocrinological remission (ER) in functioning adenomas. RESULTS The authors found a 16% rate of CS invasion during surgery for these macroadenomas. Adenomas radiologically classified as Grade 1 were found to be invasive in 1.5%, and the GTR/ER rate was 83%/88%. For Grade 2 adenomas, the rate of invasion was 9.9%, and the GTR/ER rate was 71%/60%. For Grade 3 adenomas, the rate of invasion was 37.9%, and the GTR/ER rate was 75%/33%. When the superior compartment of the CS (Grade 3A) was involved, the authors found a rate of invasion that was lower (p < 0.001) than that when the inferior compartment was involved (Grade 3B). The rate of invasion in Grade 3A adenomas was 26.5% with a GTR/ER rate of 85%/67%, whereas for Grade 3B adenomas, the rate of surgically observed invasion was 70.6% with a GTR/ER rate of 64%/0%. All of the Grade 4 adenomas were invasive, and the GTR/ER rate was 0%. A comparison of microscopic and endoscopic techniques revealed no difference in adenomas with Grade 1 or 4 parasellar extension. In Grade 2 adenomas, however, the CS was found by the endoscopic technique to be invaded in 9.9% and by microscopic evaluation to be invaded in 88% (p < 0.001); in Grade 3 adenomas, the difference was 37.9% versus 86%, respectively (p = 0.002). Grade 4 adenomas had a statistically significant lower rate of GTR than those of all the other grades. In case of ER only, Grade 1 adenomas had a statistically significant higher rate of remission than did Grade 3B and Grade 4 adenomas. CONCLUSIONS The proposed classification proved that with increasing grades, the likelihood of surgically observed invasion rises and the chance of GTR and ER decreases. The direct endoscopic view confirmed the low rate of invasion of Grade 1 adenomas but showed significantly lower rates of invasion in Grade 2 and 3 adenomas than those previously found using the microscopic technique. In cases in which the intracavernous internal carotid artery was encased (Grade 4), all the adenomas were invasive and the GTR/ER rate was 0%/0%. The authors suggest the addition of Grades 3A and 3B to distinguish the strikingly different outcomes of adenomas invading the superior CS compartments and those invading the inferior CS compartments.
    Journal of Neurosurgery 02/2015; 122(4):1-9. DOI:10.3171/2014.12.JNS141083 · 3.23 Impact Factor
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    ABSTRACT: OBJECT Surgery of suspected low-grade gliomas (LGGs) poses a special challenge for neurosurgeons due to their diffusely infiltrative growth and histopathological heterogeneity. Consequently, neuronavigation with multimodality imaging data, such as structural and metabolic data, fiber tracking, and 3D brain visualization, has been proposed to optimize surgery. However, currently no standardized protocol has been established for multimodality imaging data in modern glioma surgery. The aim of this study was therefore to define a specific protocol for multimodality imaging and navigation for suspected LGG. METHODS Fifty-one patients who underwent surgery for a diffusely infiltrating glioma with nonsignificant contrast enhancement on MRI and available multimodality imaging data were included. In the first 40 patients with glioma, the authors retrospectively reviewed the imaging data, including structural MRI (contrast-enhanced T1-weighted, T2-weighted, and FLAIR sequences), metabolic images derived from PET, or MR spectroscopy chemical shift imaging, fiber tracking, and 3D brain surface/vessel visualization, to define standardized image settings and specific indications for each imaging modality. The feasibility and surgical relevance of this new protocol was subsequently prospectively investigated during surgery with the assistance of an advanced electromagnetic navigation system in the remaining 11 patients. Furthermore, specific surgical outcome parameters, including the extent of resection, histological analysis of the metabolic hotspot, presence of a new postoperative neurological deficit, and intraoperative accuracy of 3D brain visualization models, were assessed in each of these patients. RESULTS After reviewing these first 40 cases of glioma, the authors defined a specific protocol with standardized image settings and specific indications that allows for optimal and simultaneous visualization of structural and metabolic data, fiber tracking, and 3D brain visualization. This new protocol was feasible and was estimated to be surgically relevant during navigation-guided surgery in all 11 patients. According to the authors' predefined surgical outcome parameters, they observed a complete resection in all resectable gliomas (n = 5) by using contour visualization with T2-weighted or FLAIR images. Additionally, tumor tissue derived from the metabolic hotspot showed the presence of malignant tissue in all WHO Grade III or IV gliomas (n = 5). Moreover, no permanent postoperative neurological deficits occurred in any of these patients, and fiber tracking and/or intraoperative monitoring were applied during surgery in the vast majority of cases (n = 10). Furthermore, the authors found a significant intraoperative topographical correlation of 3D brain surface and vessel models with gyral anatomy and superficial vessels. Finally, real-time navigation with multimodality imaging data using the advanced electromagnetic navigation system was found to be useful for precise guidance to surgical targets, such as the tumor margin or the metabolic hotspot. CONCLUSIONS In this study, the authors defined a specific protocol for multimodality imaging data in suspected LGGs, and they propose the application of this new protocol for advanced navigation-guided procedures optimally in conjunction with continuous electromagnetic instrument tracking to optimize glioma surgery.
    Neurosurgical FOCUS 01/2015; 38(1):E4. DOI:10.3171/2014.10.FOCUS14597 · 2.14 Impact Factor
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    Adelheid Woehrer, Gabor G Kovacs
    Clinical neuropathology 01/2015; 34(1):4-5. DOI:10.5414/NP300847 · 1.31 Impact Factor
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    ABSTRACT: The Brain Tumor Epidemiology Consortium (BTEC) is an open scientific forum, which fosters the development of multi-center, international and inter-disciplinary collaborations. BTEC aims to develop a better understanding of the etiology, outcomes, and prevention of brain tumors ( The 15th annual Brain Tumor Epidemiology Consortium Meeting, hosted by the Austrian Societies of Neuropathology and Neuro-oncology, was held on September 9 - 11, 2014 in Vienna, Austria. The meeting focused on the central role of brain tumor epidemiology within multidisciplinary neuro-oncology. Knowledge of disease incidence, outcomes, as well as risk factors is fundamental to all fields involved in research and treatment of patients with brain tumors; thus, epidemiology constitutes an important link between disciplines, indeed the very hub. This was reflected by the scientific program, which included various sessions linking brain tumor epidemiology with clinical neuro-oncology, tissue-based research, and cancer registration. Renowned experts from Europe and the United States contributed their personal perspectives stimulating further group discussions. Several concrete action plans evolved for the group to move forward until next year's meeting, which will be held at the Mayo Clinic at Rochester, MN, USA.
    Clinical neuropathology 01/2015; 34(1):40-46. DOI:10.5414/NP300846 · 1.31 Impact Factor
  • Adelheid Woehrer, Luc Bauchet, Jill S Barnholtz-Sloan
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    ABSTRACT: Glioblastoma is the most common malignant brain tumor in adults and carries a particularly poor prognosis. Since 2005, state-of-the-art therapy consists of maximal well tolerated surgical resection followed by combined radiotherapy and chemotherapy with temozolomide. Over the past decade, further advances have been achieved in various disciplines, most prominently including antiangiogenic treatment with bevacizumab. Still, whether these therapeutic innovations have translated to the general population remains unclear.
    Current Opinion in Neurology 12/2014; 27(6):666-674. DOI:10.1097/WCO.0000000000000144 · 5.73 Impact Factor
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    ABSTRACT: Primary central nervous system lymphoma (PCNSL) is a rare and malignant tumour type. Established treatment approaches include high-dose methotrexate (HD-MTX) -based chemotherapy and whole-brain radiotherapy (WBRT). WBRT is associated with significant neurotoxicity and autologous haematopoietic stem cell transplantation (ASCT) has been proposed as an alternative treatment – either in the 1st line setting after HD-MTX based chemotherapy or as salvage treatment for relapsed/refractory PCNSL. We here report our single centre experience with five PCNSL patients, who had achieved an objective response after a high-dose methotrexate based induction therapy and consecutively received a high-dose chemotherapy, consisting of carmustine and thiotepa, followed by ASCT. We also provide a literature review on ASCL for PCNSL. Our data, with three out of five patients in continuous complete remission and four out of five patients alive after a median follow-up time of 8 months, as well as previously published results, show that ASCT is a safe treatment option that is able to induce tumour remissions in patients with PCNSL. However, controlled trials are needed to compare the long-term efficacy and tolerability of ASCT with other treatment approaches and also to establish the optimal sequence of treatment regimens in PCNSL patients.This article is protected by copyright. All rights reserved.
    European Journal Of Haematology 12/2014; 95(1). DOI:10.1111/ejh.12482 · 2.41 Impact Factor
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    ABSTRACT: Background: For its numerous abilities including sedation, we have been using thalidomide (TH) as the 'last therapeutic option' in patients with advanced gliomas. We noticed that a small subgroup, i.e. patients with secondary glioblastoma (GBM, whose GBM has evolved over several months or years from a less malignant glioma), survived for prolonged periods. Therefore, we retrospectively evaluated the outcomes of patients with secondary GBM treated with TH at our centre. Patients and Methods: Starting in the year 2000, we have studied 23 patients (13 females, 10 males, with a median age of 31.5 years) with secondary GBM who have received palliative treatment with TH 100 mg at bedtime. All patients had previously undergone radiotherapy and received at least 1 and up to 5 regimens of chemotherapy. Results: The median duration of TH administration was 4.0 months (range 0.8-32). The median duration of overall survival after the start of TH therapy was 18.3 months (range 0.8-57). Eleven patients with secondary GBM survived longer than 1 year. Symptomatic improvement was most prominent in the restoration of a normal sleep pattern. Conclusion: The palliative effects of TH, especially the normalization of a sleep pattern, were highly valued by patients and families. The prolongation of survival of patients with secondary GBM has not been reported previously. © 2014 S. Karger AG, Basel.
    Oncology 11/2014; 88(3):173-179. DOI:10.1159/000368903 · 2.61 Impact Factor
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    ABSTRACT: Immune checkpoint inhibitors targeting programmed cell death 1 (PD1) or its ligand (PD-L1) showed activity in several cancer types.
    Neuro-Oncology 10/2014; DOI:10.1093/neuonc/nou307 · 5.29 Impact Factor
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    ABSTRACT: Metastases to the central nervous system (CNS) are common in several cancer types. For most primary tumors that commonly metastasize to the CNS, molecular biomarker analyses are recommended in the clinical setting for selection of appropriate targeted therapies. Therapeutic efficacy of some of these agents has been documented in patients with brain metastases, and molecular testing of CNS metastases should be considered in the clinical setting. Here, we summarize the clinically relevant biomarker tests that should be considered in neurosurgical specimens based on the current recommendations of the European Society of Medical Oncology (ESMO) or the National Comprehensive Cancer Network (NCCN) for the most relevant primary tumor types: lung cancer (EGFR mutations, ALK rearrangement, BRAF mutations), breast cancer (HER2 amplification, steroid receptor overexpression), melanoma (BRAF mutations), and colorectal cancer (RAS mutations). Furthermore, we discuss emerging therapeutic targets including novel oncogenic alterations (ROS1 rearrangements, FGFR1 amplifications, CMET amplifications, and others) and molecular features of the tumor microenvironment (including immune-checkpoint molecules such as CTLA4 and PD-1/PD-L1). We also discuss the potential role of advanced biomarker tests such as next-generation sequencing and "liquid biopsies" for patients with CNS metastases.
    Acta Neuropathologica 10/2014; DOI:10.1007/s00401-014-1350-7 · 9.78 Impact Factor
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    ABSTRACT: Objective To identify the prevalence of MRI features of Binswanger's disease (BD), specifically MRI with diffuse white matter lesions and scattered multiple lacunes (BD-MRI), and to describe neurological features and pathological outcomes of a community-based cohort study.Methods Of 697 participants (all 75 years old), 503 completed neurological examinations at baseline and were followed-up every 30 months thereafter with MRIs, the mini-mental state examination (MMSE) and the Unified Parkinson Disease Rating Scale-Motor Section (UPDRSM). Data from participants with BD-MRI were compared with those from participants with predominant white matter lesions (WML-MRI), scattered multiple lacunes (ML-MRI), or normal MRIs.ResultsFourteen BD-MRI patients (2.8%) were detected at baseline. The mean MMSE scores in the BD-MRI, WML-MRI, ML-MRI, and normal MRIs groups were 26.4, 28.2, 28.4, and 28.5, respectively, and the mean UPDRSM scores were 9.1, 1.3, 3.1, and 1.7, respectively. At the 30-month follow-up, mortality rates in the normal MRIs, WML-MRI and ML-MRI were 4%, 9.1%, and 22.2%, respectively, and follow-up MRIs were available for 80%, 82%, and 61% of the participants, respectively. In the BD-MRI, however, five patients were deceased, and only five follow-up individual MRIs were available (33.3%). Autopsies were performed on six of eight BD-MRI brains, and these brains fulfilled the pathological criteria for BD independent of Alzheimer disease pathology. All these six individuals also showed systemic atherosclerosis and renal arterio-arteriolosclerosis.InterpretationThe BD-MRI participants had poor prognoses and showed pure BD pathology with advanced systemic vascular disease. BD-MRI appears to be a predictor of vascular neurocognitive impairment.
    10/2014; DOI:10.1002/acn3.123
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    ABSTRACT: BackgroundCMET represents an emerging therapy target for monoclonal antibodies and tyrosine kinase inhibitors in non-small cell lung cancer (NSCLC).Methods We investigated CMET gene amplification status by fluorescence in-situ hybridization (FISH) and CMET protein expression by immunohistochemistry in a large series of 209 NSCLC brain metastases (BM; 165 adenocarcinoma, 20 squamous cell carcinoma, 11 adenosquamous carcinomas, 11 large cell carcinomas and 2 large cell neuroendocrine carcinomas) and correlated our results to clinic-pathological parameters and molecular data from previous studies.ResultsWe found CMET gene amplification in 36/167 (21.6%) and CMET protein expression in 87/196 (44.4%) of evaluable BM. There was a strong correlation between the presence of CMET gene amplification and CMET protein expression (p<0.001, Chi square test). Furthermore, presence of CMET amplification correlated positively with presence of ALK amplifications (p=0.039, Chi square test) and high HIF1 alpha index (p=0.013, Mann Whitney U-test). Neither CMET expression nor CMET gene amplification status correlated with patient outcome parameters or known prognostic factors.ConclusionsCMET overexpression and CMET amplification are commonly found in NSCLC BM and may represent a promising therapeutic target.This article is protected by copyright. All rights reserved.
    Histopathology 07/2014; 65(5). DOI:10.1111/his.12475 · 3.30 Impact Factor
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    ABSTRACT: Using conventional MRI methods, the differentiation of primary cerebral lymphomas (PCNSL) and other primary brain tumors, such as glioblastomas, is difficult due to overlapping imaging characteristics. This study was designed to discriminate tumor entities using normalized vascular intratumoral signal intensity values (nVITS) obtained from pulsed arterial spin labeling (PASL), combined with intratumoral susceptibility signals (ITSS) from susceptibility-weighted imaging (SWI). Thirty consecutive patients with glioblastoma (n = 22) and PCNSL (n = 8), histologically classified according to the WHO brain tumor classification, were included. MRIs were acquired on a 3 T scanner, and included PASL and SWI sequences. nVITS was defined by the signal intensity ratio between the tumor and the contralateral normal brain tissue, as obtained by PASL images. ITSS was determined as intratumoral low signal intensity structures detected on SWI sequences and were divided into four different grades. Potential differences in the nVITS and ITSS between glioblastomas and PCNSLs were revealed using statistical testing. To determine sensitivity, specificity, and diagnostic accuracy, as well as an optimum cut-off value for the differentiation of PCNSL and glioblastoma, a receiver operating characteristic analysis was used. We found that nVITS (p = 0.011) and ITSS (p = 0.001) values were significantly higher in glioblastoma than in PCNSL. The optimal cut-off value for nVITS was 1.41 and 1.5 for ITSS, with a sensitivity, specificity, and accuracy of more than 95%. These findings indicate that nVITS values have a comparable diagnostic accuracy to ITSS values in differentiating glioblastoma and PCNSL, offering a completely non-invasive and fast assessment of tumoral vascularity in a clinical setting.
    European Journal of Radiology 05/2014; DOI:10.1016/j.ejrad.2014.01.017 · 2.16 Impact Factor
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    ABSTRACT: BRAF V600E mutation and homozygous deletion of CDKN2A (p16) are frequent molecular alterations in pleomorphic xanthoastrocytomas (PXA). We investigated 49 PXAs for clinical, histological and immunohistochemical characteristics related to BRAF mutation status. BRAF mutation was detected by immunohistochemistry/sequencing in 38/49 (78%) tumors. All but one PXA from temporal location harbored a BRAF V600E mutation (23/24; 96%) compared to 10/19 (53%) non-temporal PXAs (p=0.0009). Histological and immunohistochemical analysis demonstrated increased reticulin deposition (76% vs. 27%; p=0.003) and a more frequent expression of CD34 in BRAF mutant PXAs (76% vs. 27%; p=0.003). We further investigated the utility of combined BRAF V600E (VE1) and p16 analysis by immunohistochemisty to delineate PXAs from relevant histological mimics like giant cell glioblastoma. In PXAs 38/49 (78%) were VE1 positive, and 30/49 (61%) had a loss of p16 expression. The combined features (VE1+ / p16 loss) were observed in 25/49 (51%) PXAs but were not observed in giant cell glioblastoma (VE1 0/28, p16 loss 14/28). Together, we demonstrate that temporal location, reticulin deposition and CD34 expression are associated with BRAF mutation in PXA. Combined VE1 positivity and p16 loss represent a frequent immunoprofile of PXA and may therefore constitute an additional diagnostic tool for its differential diagnostics.
    Brain Pathology 04/2014; 24(3):221-9. DOI:10.1111/bpa.12111 · 4.35 Impact Factor
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    Christine Haberler, Adelheid Wöhrer
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    ABSTRACT: Genome-wide molecular approaches have substantially elucidated molecular alterations and pathways involved in the oncogenesis of brain tumors. In gliomas, several molecular biomarkers including IDH mutation, 1p/19q co-deletion, and MGMT promotor methylation status have been introduced into neuropathological practice. Recently, mutations of the ATRX gene have been found in various subtypes and grades of gliomas and were shown to refine the prognosis of malignant gliomas in combination with IDH and 1p/19q status. Mutations of ATRX are associated with loss of nuclear ATRX protein expression, detectable by a commercially available antibody, thus turning ATRX into a promising prognostic candidate biomarker in the routine neuropathological setting.
    Clinical neuropathology 03/2014; 33(2):108-11. DOI:10.5414/NP300758 · 1.31 Impact Factor
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    ABSTRACT: Survival upon diagnosis of brain metastases (BM) in patients with non-small cell lung cancer (NSCLC) is highly variable and established prognostic scores do not include tissue-based parameters. Patients who underwent neurosurgical resection as first-line therapy for newly diagnosed NSCLC BM were included. Microvascular density (MVD), Ki67 tumor cell proliferation index and hypoxia-inducible factor 1 alpha (HIF-1 alpha) index were determined by immunohistochemistry. NSCLC BM specimens from 230 patients (151 male, 79 female; median age 56 years; 199 nonsquamous histology) and 53/230 (23.0 %) matched primary tumor samples were available. Adjuvant whole-brain radiation therapy (WBRT) was given to 153/230 (66.5 %) patients after neurosurgical resection. MVD and HIF-1 alpha indices were significantly higher in BM than in matched primary tumors. In patients treated with adjuvant WBRT, low BM HIF-1 alpha expression was associated with favorable overall survival (OS), while among patients not treated with adjuvant WBRT, BM HIF-1 alpha expression did not correlate with OS. Low diagnosis-specific graded prognostic assessment score (DS-GPA), low Ki67 index, high MVD, low HIF-1 alpha index and administration of adjuvant WBRT were independently associated with favorable OS. Incorporation of tissue-based parameters into the commonly used DS-GPA allowed refined discrimination of prognostic subgroups. Ki67 index, MVD and HIF-1 alpha index have promising prognostic value in BM and should be validated in further studies.
    Strahlentherapie und Onkologie 02/2014; DOI:10.1007/s00066-014-0639-8 · 2.73 Impact Factor
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    Josef Finsterer, Madleine Melichart, Adelheid Wöhrer
    Archives of Medical Science 02/2014; 10(1):200-2. DOI:10.5114/aoms.2014.40747 · 1.89 Impact Factor
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    ABSTRACT: Loss of consciousness may be due to neurological or cardiac involvement in mitochondrial disease, and is often difficult to attribute to either cause, as in the following case. A 67-year-old man with hypertension, diabetes, elevated serum creatine kinase, glaucoma, optic atrophy, and vertigo had experienced recurrent losses of consciousness since 63 years of age. Diagnostic work-up revealed paroxysmal supraventricular arrhythmias, hyperlipidemia, steatosis hepatis, renal insufficiency, polyneuropathy, first-degree atrio-ventricular block, orthostasis, and cataract. From the age of 66 years, he developed tonic-clonic seizures. Electrocardiography loop recording showed some losses of consciousness as associated with supraventricular tachycardias and others with epileptic activity or arterial hypotension. Neurological investigations and muscle biopsy were indicative of mitochondrial disease with multisystem involvement. Losses of consciousness disappeared after catheter ablation and treatment with levetiracetam. Recurrent loss of consciousness in mitochondrial disease may not only be due to arrhythmias but also seizure activity, or autonomic neuropathy. Arrhythmias, seizures, and polyneuropathy may have a common underlying cause affecting various tissues.
    Journal of Cardiovascular Medicine 02/2014; 15(2). DOI:10.2459/JCM.0b013e328365c0e0 · 1.51 Impact Factor
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    ABSTRACT: Atypical teratoid rhabdoid tumors (ATRTs) are recently defined highly aggressive embryonal central nervous system tumors with a poor prognosis and no definitive guidelines for treatment. We report on the importance of an initial correct diagnosis and disease-specific therapy on outcome in 22 consecutive patients and propose a new treatment strategy. From 1992 to 2012, nine patients initially diagnosed correctly as ATRT (cohort A, median age 24 months) were treated according to an intensive multimodal regimen (MUV-ATRT) consisting of three 9-week courses of a dose-dense regimen including doxorubicin, cyclophosphamide, vincristine, ifosfamide, cisplatin, etoposide, and methotrexate augmented with intrathecal therapy, followed by high-dose chemotherapy (HDCT) and completed with local radiotherapy. Thirteen patients were treated differently (cohort B, median age 30 months) most of whom according to protocols in use for their respective diagnoses. As of July 2013, 5-year overall survival (OS) and event-free survival (EFS) for all 22 consecutive patients was 56.3 ± 11.3% and 52.9 ± 11.0%, respectively. For MUV-ATRT regimen-treated patients (cohort A) 5-year OS was 100% and EFS was 88.9 ± 10.5%. For patients treated differently (cohort B) 5-year OS and EFS were 28.8 ± 13.1%. All nine MUV-ATRT regimen-treated patients are alive for a median of 76 months (range: 16–197), eight in first complete remission. Our results compare favorably to previously published data. The drug combination and sequence used in the proposed MUV-ATRT regimen appear to be efficacious in preventing early relapses also in young children with M1–M3 stage disease allowing postponement of radiotherapy until after HDCT.
    Cancer Medicine 02/2014; 3(1). DOI:10.1002/cam4.161
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    ABSTRACT: Object Subtotal resection (STR) of spinal tumors can result in tumor recurrence. Currently, no clinically reliable marker is available for intraoperative visualization of spinal tumor tissue. Protoporphyrin IX (PpIX) fluorescence induced by 5-aminolevulinic acid (5-ALA) is capable of visualizing malignant gliomas. Fluorescence-guided resections of malignant cerebral gliomas using 5-ALA have resulted in an increased rate of complete tumor removal. Recently, the application of 5-ALA has also been described in the first cases of spinal tumors. Therefore, the aim of this observational study was to systematically investigate 5-ALA-induced fluorescence characteristics in different spinal tumor entities. Methods Three hours before the induction of anesthesia, 5-ALA was administered to patients with different intra- and extradural spinal tumors. In all patients a neurosurgical resection or biopsy of the spinal tumor was performed under conventional white-light microscopy. During each surgery, the presence of PpIX fluorescence was additionally assessed using a modified neurosurgical microscope. At the end of an assumed gross-total resection (GTR) under white-light microscopy, a final inspection of the surgical cavity of fluorescing intramedullary tumors was performed to look for any remaining fluorescing foci. Histopathological tumor diagnosis was established according to the current WHO classification. Results Fifty-two patients with 55 spinal tumors were included in this study. Resection was performed in 50 of 55 cases, whereas 5 of 55 cases underwent biopsy. Gross-total resection was achieved in 37 cases, STR in 5, and partial resection in 8 cases. Protoporphyrin IX fluorescence was visible in 30 (55%) of 55 cases, but not in 25 (45%) of 55 cases. Positive PpIX fluorescence was mainly detected in ependymomas (12 of 12), meningiomas (12 of 12), hemangiopericytomas (3 of 3), and in drop metastases of primary CNS tumors (2 of 2). In contrast, none of the neurinomas (8 of 8), carcinoma metastases (5 of 5), and primary spinal gliomas (3 of 3; 1 pilocytic astrocytoma, 1 WHO Grade II astrocytoma, 1 WHO Grade III anaplastic oligoastrocytoma) revealed PpIX fluorescence. It is notable that residual fluorescing tumor foci were detected and subsequently resected in 4 of 8 intramedullary ependymomas despite assumed GTR under white-light microscopy. Conclusions In this study, 5-ALA-PpIX fluorescence was observed in spinal tumors, especially ependymomas, meningiomas, hemangiopericytomas, and drop metastases of primary CNS tumors. In cases of intramedullary tumors, 5-ALA-induced PpIX fluorescence is a useful tool for the detection of potential residual tumor foci.
    Neurosurgical FOCUS 02/2014; 36(2):E11. DOI:10.3171/2013.12.FOCUS13485 · 2.14 Impact Factor
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    ABSTRACT: Therapeutic options for patients with pretreated advanced high-grade glioma (HGG) are limited. Sorafenib, a small molecule with multiple potential beneficial actions, appears particularly promising. We reviewed the outcomes of 30 patients with recurrent or progressive HGG treated with sorafenib within a named patient program. Overall, 16 patients suffered from recurrent or progressive glioblastoma multiforme and 14 patients had grade 3 gliomas. All but four patients had previously undergone surgical debulking; all but one patient had received previous standard multimodal treatment; and 18 patients (60%) had received more than one line of chemotherapy, in median three. Progression-free survival (PFS), defined as the time from initiation of sorafenib to treatment discontinuation because of tumor progression or death, was selected as the endpoint. The use of sorafenib resulted in a median PFS of 3 months [95% confidence interval (CI) 1.9-4.1 months] in patients with glioblastoma and of 3.1 months (95% CI 1.4-4.8 months) in patients with other HGG. The PFS-6 for the whole cohort was 23%. Sixteen patients reported adverse events, mostly moderate, with hypertension as the most frequently reported toxicity (seven patients). One patient died of cerebral bleeding (grade 5 toxicity). The overall survival after initiation of sorafenib was 6 months (95% CI 3.9-8.0 months) for patients with glioblastoma multiforme and 10 months (95% CI 3.1-16.9 months) for patients with HGG. In this retrospective analysis of heavily pretreated patients with HGG, sorafenib monotherapy was associated with tumor stabilization in a small subset of patients. The risk-benefit ratio was acceptable in the context of an apparent clinical benefit in patients with a fatal disease.
    Anti-cancer drugs 01/2014; DOI:10.1097/CAD.0000000000000077 · 1.89 Impact Factor

Publication Stats

784 Citations
259.31 Total Impact Points


  • 2015
    • Washington University in St. Louis
      • Division of Hematology and oncology
      San Luis, Missouri, United States
  • 2008–2015
    • Medical University of Vienna
      • Universitätsklinik für Neurochirurgie
      Wien, Vienna, Austria
  • 2014
    • French Institute of Health and Medical Research
      Lutetia Parisorum, Île-de-France, France
  • 2012
    • Ludwig Boltzmann Institute for Cancer Research
      Wien, Vienna, Austria