Publications by authors named "Antje Wick"

Background: Diffuse hemispheric glioma, histone 3 (H3) G34-mutant, has been newly defined in the 2021 WHO classification of central nervous system tumors. Here we sought to define the prognostic roles of clinical, neuroimaging, pathological, and molecular features of these tumors.

Methods: We retrospectively assembled a cohort of 114 patients (median age 22 years) with diffuse hemispheric glioma, H3 G34-mutant, CNS WHO grade 4 and profiled the imaging, histological and molecular landscape of their tumors.

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Article Synopsis
  • Primary optic nerve sheath meningiomas (ONSMs) are benign tumors that can cause gradual vision loss, and radiation therapy, particularly proton therapy, is key for treatment as it may improve visual function while minimizing side effects.* -
  • In a study of 32 patients treated with proton beam radiotherapy, results showed a 100% local control rate after 5 years and 84.4% of patients experienced improved or stable vision, despite a 9.4% occurrence of radiation-induced optic neuropathy (RION).* -
  • The findings support proton beam therapy as a safe and effective option for ONSM treatment, though further research is needed to compare its effectiveness against traditional photon radiotherapy.*
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Purpose: There is a lack of evidence regarding how patients with malignant brain tumor and their relatives experience participation in neurooncological clinical trials. Similarly, insights from the perspective of trial staff caring for this group of patients are missing. This study aims to investigate patient, relative and trial staff experiences regarding participation in clinical neurooncological trials.

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Background: While surgical resection remains the primary treatment approach for symptomatic or growing meningiomas, radiotherapy represents an auspicious alternative in patients with meningiomas not safely amenable to surgery. Biopsies are often omitted in light of potential postoperative neurological deficits, resulting in a lack of histological grading and (molecular) risk stratification. In this prospective explorative biomarker study, extracellular vesicles in the bloodstream will be investigated in patients with macroscopic meningiomas to identify a biomarker for molecular risk stratification and disease monitoring.

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Purpose: Surgery for recurrent glioma provides cytoreduction and tissue for molecularly informed treatment. With mostly heavily pretreated patients involved, it is unclear whether the benefits of repeat surgery outweigh its potential risks.

Methods: Patients receiving surgery for recurrent glioma WHO grade 2-4 with the goal of tissue sampling for targeted therapies were analyzed retrospectively.

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Background: Glioblastoma is the most frequent and a particularly malignant primary brain tumor with no efficacy-proven standard therapy for recurrence. It has recently been discovered that excitatory synapses of the AMPA-receptor subtype form between non-malignant brain neurons and tumor cells. This neuron-tumor network connectivity contributed to glioma progression and could be efficiently targeted with the EMA/FDA approved antiepileptic AMPA receptor inhibitor perampanel in preclinical studies.

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Malignant tumors commonly exhibit a reversed pH gradient compared with normal tissue, with a more acidic extracellular pH and an alkaline intracellular pH (pH). In this prospective study, pH values in gliomas were quantified using high-resolution phosphorous 31 (P) spectroscopic MRI at 7.0 T and were used to correlate pH alterations with histopathologic findings.

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Background: Novel radiotherapeutic modalities using carbon ions provide an increased relative biological effectiveness (RBE) compared to photons, delivering a higher biological dose while reducing radiation exposure for adjacent organs. This prospective phase 2 trial investigated bimodal radiotherapy using photons with carbon-ion (C12)-boost in patients with WHO grade 2 meningiomas following subtotal resection (Simpson grade 4 or 5).

Methods: A total of 33 patients were enrolled from July 2012 until July 2020.

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Introduction: Diffuse midline gliomas (DMG) are universally lethal central nervous system tumors that carry almost unanimously the clonal driver mutation histone-3 K27M (H3K27M). The single amino acid substitution of lysine to methionine harbors a neoantigen that is presented in tumor tissue. The long peptide vaccine H3K27M-vac targeting this major histocompatibility complex class II (MHC class II)-restricted neoantigen induces mutation-specific immune responses that suppress the growth of H3K27M flank tumors in an MHC-humanized rodent model.

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Purpose: Multimodal therapies have significantly improved prognosis in glioma. However, in particular radiotherapy may induce long-term neurotoxicity compromising patients' neurocognition and quality of life. The present prospective multicenter study aimed to evaluate associations of multimodal treatment with neurocognition with a particular focus on hippocampal irradiation.

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Purpose: The EORTC-26101 study was a randomized phase II and III clinical trial of bevacizumab in combination with lomustine versus lomustine alone in progressive glioblastoma. Other than for progression-free survival (PFS), there was no benefit from addition of bevacizumab for overall survival (OS). However, molecular data allow for the rare opportunity to assess prognostic biomarkers from primary surgery for their impact in progressive glioblastoma.

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Background: Median survival with glioblastoma remains in the range of 12 months on population levels. Only few patients survive for more than 5 years. Patient and disease features associated with long-term survival remain poorly defined.

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Purpose: Astrocytomas and oligodendrogliomas are mainly diffuse primary brain tumors harboring a diagnostic and prognostically favorable isocitrate dehydrogenase mutation. They are still incurable besides growing molecular knowledge and therapy options. Circumscribed astrocytomas are also discussed here, although they represent a separate entity despite similarities in the nomenclature.

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Background: Approximately 50% of newly diagnosed glioblastomas (GBMs) harbor epidermal growth factor receptor gene amplification (EGFR-amp). Preclinical and early-phase clinical data suggested efficacy of depatuxizumab mafodotin (depatux-m), an antibody-drug conjugate comprised of a monoclonal antibody that binds activated EGFR (overexpressed wild-type and EGFRvIII-mutant) linked to a microtubule-inhibitor toxin in EGFR-amp GBMs.

Methods: In this phase III trial, adults with centrally confirmed, EGFR-amp newly diagnosed GBM were randomized 1:1 to radiotherapy, temozolomide, and depatux-m/placebo.

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Background: Pulmonary fibrosis is a rare, but dangerous side effect of CCNU (lomustine). CCNU is a frequently used chemotherapeutic agent in the setting of recurrent or progressive glioblastoma. At present, CCNU is also administered in patients with newly diagnosed gliomas in combination with temozolomide.

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Introduction: Isocitrate dehydrogenase (IDH) mutations are disease-defining mutations in IDH-mutant astrocytomas and IDH-mutant and 1p/19q-codeleted oligodendrogliomas. In more than 80% of these tumors, point mutations in IDH type 1 (IDH1) lead to expression of the tumor-specific protein IDH1R132H. IDH1R132H harbors a major histocompatibility complex class II (MHCII)-restricted neoantigen that was safely and successfully targeted in a first-in human clinical phase 1 trial evaluating an IDH1R132H 20-mer peptide vaccine (IDH1-vac) in newly diagnosed astrocytomas concomitant to standard of care (SOC).

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Background: Nearly all patients with newly diagnosed glioblastoma experience recurrence following standard-of-care radiotherapy (RT) + temozolomide (TMZ). The purpose of the phase III randomized CheckMate 548 study was to evaluate RT + TMZ combined with the immune checkpoint inhibitor nivolumab (NIVO) or placebo (PBO) in patients with newly diagnosed glioblastoma with methylated MGMT promoter (NCT02667587).

Methods: Patients (N = 716) were randomized 1:1 to NIVO [(240 mg every 2 weeks × 8, then 480 mg every 4 weeks) + RT (60 Gy over 6 weeks) + TMZ (75 mg/m2 once daily during RT, then 150-200 mg/m2 once daily on days 1-5 of every 28-day cycle × 6)] or PBO + RT + TMZ following the same regimen.

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Purpose: Despite recent advances in the molecular characterization of gliomas, it remains unclear which patients benefit most from which second-line treatments. The TAVAREC trial was a randomized, open-label phase II trial assessing the benefit of the addition of the angiogenesis inhibitor bevacizumab to treatment with temozolomide in patients with a first enhancing recurrence of World Health Organization grade 2 or 3 glioma without 1p/19q codeletion. We evaluated the prognostic significance of genome-wide DNA methylation profiles and copy-number variations on the TAVAREC trial samples.

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Background: Effective treatments are needed to improve outcomes for high-grade glioma and low-grade glioma. The activity and safety of dabrafenib plus trametinib were evaluated in adult patients with recurrent or progressive BRAF mutation-positive high-grade glioma and low-grade glioma.

Methods: This study is part of an ongoing open-label, single-arm, phase 2 Rare Oncology Agnostic Research (ROAR) basket trial at 27 community and academic cancer centres in 13 countries (Austria, Belgium, Canada, France, Germany, Italy, Japan, the Netherlands, Norway, South Korea, Spain, Sweden, and the USA).

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Background: Gadolinium-based contrast agents (GBCAs) are widely used to enhance tissue contrast during MRI scans and play a crucial role in the management of patients with cancer. However, studies have shown gadolinium deposition in the brain after repeated GBCA administration with yet unknown clinical significance. We aimed to assess the feasibility and diagnostic value of synthetic post-contrast T1-weighted MRI generated from pre-contrast MRI sequences through deep convolutional neural networks (dCNN) for tumour response assessment in neuro-oncology.

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Tryptophan (Trp)-catabolic enzymes (TCEs) produce metabolites that activate the aryl hydrocarbon receptor (AHR) and promote tumor progression and immunosuppression in glioblastoma. As therapies targeting TCEs or AHR become available, a better understanding of Trp metabolism is required. The combination of LC-MS/MS with chemical isobaric labeling enabled the simultaneous quantitative comparison of Trp and its amino group-bearing metabolites in multiple samples.

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Mutated isocitrate dehydrogenase 1 (IDH1) defines a molecularly distinct subtype of diffuse glioma. The most common IDH1 mutation in gliomas affects codon 132 and encodes IDH1(R132H), which harbours a shared clonal neoepitope that is presented on major histocompatibility complex (MHC) class II. An IDH1(R132H)-specific peptide vaccine (IDH1-vac) induces specific therapeutic T helper cell responses that are effective against IDH1(R132H) tumours in syngeneic MHC-humanized mice.

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Purpose: Patients with glioblastoma (GBM) or brain metastases (MET) and atrial fibrillation (AF) might be at an increased risk of intracranial hemorrhage (ICH) due to anticoagulation (AC). Our aim was to assess this risk.

Methods: Our institution's database (from 2005 to 2017) was screened for patients with GBM or MET and AF with an indication for AC according to their CHADSVASc stroke risk score (≥ 2).

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Purpose: BAY1436032, an inhibitor of mutant isocitrate dehydrogenase 1 (mIDH1), was active against multiple IDH1-R132X solid tumors in preclinical models. This first-in-human study was designed to determine the safety and pharmacokinetics of BAY1436032, and to evaluate its potential pharmacodynamics and antitumor effects.

Patients And Methods: The study comprised of dose escalation and dose expansion cohorts.

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Chimeric antigen receptor (CAR) T cell (CART) therapy has been established as a treatment option for patients with CD19-positive lymphoid malignancies in both the refractory and the relapsed setting. Displaying significant responses in clinical trials, two second-generation CART products directed against CD19, axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel), have been approved and integrated into the clinical routine. However, experimental assay for quantitative monitoring of both of these CART products in treated patients in the open domain are lacking.

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