Interstitial photodynamic therapy for newly diagnosed glioblastoma.

Purpose: Innovative, efficient treatments are desperately needed for people with glioblastoma (GBM).

Methods: Sixteen patients (median age 65.8 years) with newly diagnosed, small-sized, not safely resectable supratentorial GBM underwent interstitial photodynamic therapy (iPDT) as upfront eradicating local therapy followed by standard chemoradiation.

The value of stereotactic biopsy of primary and recurrent brain metastases in the era of precision medicine.

Background: Brain metastases (BM) represent the most frequent intracranial tumors with increasing incidence. Many primary tumors are currently treated in protocols that incorporate targeted therapies either upfront or for progressive metastatic disease. Hence, molecular markers are gaining increasing importance in the diagnostic framework of BM.

Limited efficacy of temozolomide alone for astrocytoma, IDH-mutant, CNS WHO grades 2 or 3.

Purpose: The role of temozolomide chemotherapy alone in isocitrate dehydrogenase (IDH)-mutant astrocytomas has not been conclusively determined. Radiotherapy might be superior to temozolomide. Recent studies have linked temozolomide with induction of hypermutation and poor clinical course in some IDH-mutant gliomas.

Diagnostic Yield and Complication Rate of Stereotactic Biopsies in Precision Medicine of Gliomas.

Background: An integrated diagnosis consisting of histology and molecular markers is the basis of the current WHO classification system of gliomas. In patients with suspected newly diagnosed or recurrent glioma, stereotactic biopsy is an alternative in cases in which microsurgical resection is deemed to not be safely feasible or indicated. In this retrospective study, we aimed to analyze both the diagnostic yield and the safety of a standardized biopsy technique.

Molecular diagnostics helps to identify distinct subgroups of spinal astrocytomas.

Primary spinal cord astrocytomas are rare, hence few data exist about the prognostic significance of molecular markers. Here we analyze a panel of molecular alterations in association with the clinical course. Histology and genome sequencing was performed in 26 spinal astrocytomas operated upon between 2000 and 2020.

PCV chemotherapy alone for WHO grade 2 oligodendroglioma: prolonged disease control with low risk of malignant progression.

Introduction: The role of chemotherapy alone in newly diagnosed WHO grade 2 oligodendroglioma after biopsy, incomplete or gross total resection remains controversial. We here analyze the clinical outcome of four patient cohorts being treated with either procarbazine, CCNU and vincristine (PCV) or temozolomide (TMZ) after biopsy, resection only, or wait-and-scan after biopsy.

Methods: Patients (n = 142) with molecularly defined oligodendroglioma (WHO 2016) were assigned to four cohorts: W&S, wait-and-scan after stereotactic biopsy (n = 59); RES, surgical resection only (n = 27); TMZ, temozolomide after biopsy (n = 26) or PCV (n = 30) after biopsy.

Interstitial Photodynamic Therapy Using 5-ALA for Malignant Glioma Recurrences.

Interstitial photodynamic therapy (iPDT) using 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX) as a cytotoxic photosensitizer could be a feasible treatment option for malignant gliomas. In a monocentric cohort of consecutive patients treated between 2006 and 2018, a risk profile analysis of salvage iPDT for local malignant glioma recurrences and associated outcome measures are presented here. It was considered indicated in patients with circumscribed biopsy-proven malignant glioma recurrences after standard therapy, if not deemed eligible for safe complete resection.

Past medical history of tumors other than meningioma is a negative prognostic factor for tumor recurrence in meningiomas WHO grade I.

Background: Prognostic markers for meningioma recurrence are needed to guide patient management. Apart from rare hereditary syndromes, the impact of a previous unrelated tumor disease on meningioma recurrence has not been described before.

Methods: We retrospectively searched our database for patients with meningioma WHO grade I and complete resection provided between 2002 and 2016.

Intraspinal epidermoid and dermoid cysts-tumor resection with multimodal intraoperative neurophysiological monitoring and long-term outcome.

Background: Intraspinal epidermoid/dermoid cysts are very rare, benign tumors arising from pathological displacement of epidermal cells into the spinal canal. Literature data about the long-term outcome after microsurgical resection with multimodal intraoperative neurophysiological monitoring (IONM) are lacking. We analyzed one of the largest case series with special regard to intraoperative characteristics and long-term outcome after IONM-aided surgery.

Microscopic brain invasion in meningiomas previously classified as WHO grade I is not associated with patient outcome.

Purpose: For meningiomas, the 2016 revision of the WHO classification introduced brain invasion per se as a sufficient condition to classify as grade II. We analyzed whether meningiomas previously graded as WHO grade I differ in prognosis depending on the presence of microscopic brain invasion.

Methods: A consecutive series of patients with intracranial meningioma WHO grade I (± brain invasion) at two neurosurgical departments was analyzed retrospectively.

Long-term outcome in orbital meningiomas: progression-free survival after targeted resection combined with early or postponed postoperative radiotherapy.

Objective: In meningiomas involving the orbit and optic canal, surgery is the mainstay of therapy. However, radical resection is often limited to avoid functional damage, so multidisciplinary treatment concepts are implemented. Data on the timing and value of early postoperative radiotherapy (PORT) are scarce.

Dynamic 18F-FET PET is a powerful imaging biomarker in gadolinium-negative gliomas.

Background: We aimed to elucidate the place of dynamic O-(2-[18F]-fluoroethyl)-L-tyrosine (18F-FET) PET in prognostic models of gadolinium (Gd)-negative gliomas.

Methods: In 98 patients with Gd-negative gliomas undergoing 18F-FET PET guided biopsy, time activity curves (TACs) of each tumor were qualitatively categorized as either increasing or decreasing. Additionally, post-hoc quantitative analyses were done using minimal time-to-peak (TTPmin) measurements.

Iodine-125 brachytherapy as upfront and salvage treatment for brain metastases : A comparative analysis.

Background: Outcome and toxicity profiles of salvage stereotactic ablative radiation strategies for recurrent pre-irradiated brain metastases are poorly defined. This study compared risk-benefit profiles of upfront and salvage iodine-125 brachytherapy (SBT) for small brain metastases. As the applied SBT treatment algorithm required histologic proof of metastatic brain disease in all patients, we additionally aimed to elucidate the value of biopsy before SBT.

Early treatment of complex located pediatric low-grade gliomas using iodine-125 brachytherapy alone or in combination with microsurgery.

To analyze efficacy, functional outcome, and treatment toxicity of low-dose rate I-125 brachytherapy (SBT) alone or in combination with best safe resection (in case of larger tumor volumes) as first-line treatment for pediatric low-grade gliomas (PLGGs) not suitable for complete resection. Consecutively treated (2000-2014) complex located circumscribed WHO grade I/II PLGGs were included. For small tumors (≤4 cm in diameter) SBT alone was performed; for larger tumors best safe resection and subsequent SBT was chosen.

Dynamic 18F-FET PET in suspected WHO grade II gliomas defines distinct biological subgroups with different clinical courses.

In suspected grade II gliomas, three distinct patterns of time-activity curves (TAC) on O-(2-[(18)F]fluoroethyl)-1-tyrosine ((18)F-FET) positron emission tomography (PET) have been delineated (i) increasing TAC homogeneously throughout the tumor, and decreasing TAC, (ii) either homogeneously throughout the tumor or (iii) only focally within otherwise increasing TAC patterns. Increasing TAC was associated with low-grade histology and decreasing TAC with high-grade histology. This prospective study analyzed whether these patterns correlate with distinct biological tumor subtypes and differential outcome.

Predictive chromosomal clusters of synchronous and metachronous brain metastases in clear cell renal cell carcinoma.

Synchronous (early) and metachronous (late) brain metastasis (BM) events of sporadic clear cell renal cell carcinoma (ccRCC) (n = 148) were retrospectively analyzed using comparative genomic hybridization (CGH). Using oncogenetic tree models and cluster analyses, chromosomal imbalances related to recurrence-free survival until BM (RFS-BM) were analyzed. Losses at 9p and 9q appeared to be hallmarks of metachronous BM events, whereas an absence of detectable chromosomal changes at 3p was often associated with synchronous BM events.

Molecular stereotactic biopsy technique improves diagnostic accuracy and enables personalized treatment strategies in glioma patients.

Background: In gliomas molecular biomarkers are increasingly gaining diagnostic, prognostic and predictive significance. Determination of biomarker status after biopsy is important as not all patients are eligible for open tumor resection. We developed and validated prospectively (6/10-12/11) a protocol allowing for both reliable determination of multiple biomarkers and representative histological diagnoses from small-sized biopsies.

Protoporphyrin IX fluorescence and photobleaching during interstitial photodynamic therapy of malignant gliomas for early treatment prognosis.

Background And Objective: Interstitial photodynamic therapy (iPDT) of non-resectable recurrent glioblastoma using 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) has shown a promising outcome. It remained unclear, however, to what extent inter- and intra-tumoural differences of PpIX concentrations influence the efficacy of iPDT. In the current pilot study, we analysed PpIX concentrations quantitatively and assessed PpIX induced fluorescence and photobleaching intraoperatively.

In human glioblastomas transcript elongation by alternative polyadenylation and miRNA targeting is a potent mechanism of MGMT silencing.

Favorable outcome after chemotherapy of glioblastomas cannot unequivocally be linked to promoter hypermethylation of the O6-methylguanine-DNA methyltransferase (MGMT) gene encoding a DNA repair enzyme associated with resistance to alkylating agents. This indicates that molecular mechanisms determining MGMT expression have not yet been fully elucidated. We here show that glioblastomas are capable to downregulate MGMT expression independently of promoter methylation by elongation of the 3'-UTR of the mRNA, rendering the alternatively polyadenylated transcript susceptible to miRNA-mediated suppression.

Prediction of oligodendroglial histology and LOH 1p/19q using dynamic [(18)F]FET-PET imaging in intracranial WHO grade II and III gliomas.

Oligodendroglial components (OC) and loss of heterozygosity on chromosomes 1p and 19q (LOH 1p/19q) are associated with better outcome in patients with glioma. We aimed to assess the fitness of [(18)F]fluoroethyltyrosine positron-emission-tomography (FET-PET) for noninvasively identifying these important prognostic/predictive factors. One hundred forty-four patients with MRI-suspected WHO grade II and III glioma underwent FET-PET scans prior to histological diagnosis.

The amyloid precursor protein (APP) family members are key players in S-adenosylmethionine formation by MAT2A and modify BACE1 and PSEN1 gene expression-relevance for Alzheimer's disease.

Central hallmark of Alzheimer's disease are senile plaques mainly composed of β-amyloid, which is a cleavage product of the amyloid precursor protein (APP). The physiological function of APP and its family members APLP1 and APLP2 is poorly understood. In order to fill this gap, we established a cell-culture based model with simultaneous knockdown of all members of the family.

Intramedullary pilomyxoid astrocytoma with intracerebral metastasis exhibiting oligoden-droglioma-like features.

Intramedullary glioma are rare and their biological behaviour can differ from their cerebral counterparts. Pilomyxoid astrocytoma (PMA, WHO grade II), predominantly occur in the hypothalamic/chiasmatic region of infants and children. The few reported cases of pediatric intramedullary PMA displayed a particularly aggressive behavior.

Human high temperature requirement serine protease A1 (HTRA1) degrades tau protein aggregates.

Protective proteases are key elements of protein quality control pathways that are up-regulated, for example, under various protein folding stresses. These proteases are employed to prevent the accumulation and aggregation of misfolded proteins that can impose severe damage to cells. The high temperature requirement A (HtrA) family of serine proteases has evolved to perform important aspects of ATP-independent protein quality control.

Spinocerebellar ataxia type 1 (SCA1): new pathoanatomical and clinico-pathological insights.

Aims: Spinocerebellar ataxia type 1 (SCA1) represents the first molecular genetically characterized autosomal dominantly inherited cerebellar ataxia and is assigned to the CAG-repeat or polyglutamine diseases. Owing to limited knowledge about SCA1 neuropathology, appropriate pathoanatomical correlates of a large variety of SCA1 disease symptoms are missing and the neuropathological basis for further morphological and experimental SCA1 studies is still fragmentary.

Methods: In the present study, we investigated for the first time serial tissue sections through the complete brains of clinically diagnosed and genetically confirmed SCA1 patients.