A5029982164- Glioma Diagnosis and Treatment
- Radiopharmaceutical Chemistry and Applications
- Medical Imaging Techniques and Applications
- Brain Metastases and Treatment
- Radiomics and Machine Learning in Medical Imaging
- Cancer, Hypoxia, and Metabolism
- Fibroblast Growth Factor Research
- Chromatin Remodeling and Cancer
- Advanced Breast Cancer Therapies
- Cancer Immunotherapy and Biomarkers
- Peptidase Inhibition and Analysis
- HER2/EGFR in Cancer Research
- Cancer Genomics and Diagnostics
- Sarcoma Diagnosis and Treatment
- Monoclonal and Polyclonal Antibodies Research
- Drug Transport and Resistance Mechanisms
- Cancer Treatment and Pharmacology
- MRI in cancer diagnosis
- Neuroscience and Neuropharmacology Research
- Prostate Cancer Treatment and Research
- Palliative Care and End-of-Life Issues
- Melanoma and MAPK Pathways
- Colorectal Cancer Treatments and Studies
- Receptor Mechanisms and Signaling
- Advanced MRI Techniques and Applications
University Medical Center Utrecht
2016-2025
Utrecht University
2012-2024
Ghent University
2014-2024
Erasmus University Rotterdam
2023
Erasmus MC
2005-2023
Ghent University Hospital
2011-2022
Heidelberg University
2012-2022
University Hospital Heidelberg
2012-2022
SBOH
2022
Cancer Genomics Centre
2017-2021
Abstract Although BRAF inhibitor monotherapy yields response rates >50% in BRAFV600-mutant melanoma, only approximately 5% of patients with BRAFV600E colorectal cancer respond. Preclinical studies suggest that the lack efficacy is due to adaptive feedback reactivation MAPK signaling, often mediated by EGFR. This clinical trial evaluated and EGFR inhibition dabrafenib (D) + panitumumab (P) ± MEK trametinib (T) achieve greater suppression improved 142 cancer. Confirmed for D+P, D+T+P,...
Abstract 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 immune checkpoint inhibitor nivolumab (NIVO) or placebo (PBO) in methylated MGMT promoter (NCT02667587). Methods Patients (N = 716) were 1:1 NIVO [(240 mg every 2 weeks × 8, then 480 4 weeks) (60 Gy over 6 (75 mg/m2 once daily during RT,...
To assess the outcome of prostate cancer (PCa) patients diagnosed with oligometastatic disease at recurrence and treated stereotactic body radiotherapy (SBRT).Non-castrate up to 3 synchronous metastases (bone and/or lymph nodes) on positron emission tomography - computed tomography, following biochemical after local curative treatment, were (repeated) SBRT a dose 50 Gy in 10 fractions or 30 fractions. Androgen deprivation therapy-free survival (ADT-FS) defined as time interval between first...
Abstract Background Depatuxizumab mafodotin (Depatux-M) is a tumor-specific antibody–drug conjugate consisting of an antibody (ABT-806) directed against activated epidermal growth factor receptor (EGFR) and the toxin monomethylauristatin-F. We investigated Depatux-M in combination with temozolomide or as single agent randomized controlled phase II trial recurrent EGFR amplified glioblastoma. Methods Eligible were patients centrally confirmed glioblastoma at first recurrence after...
Abstract BRAFV600E alterations are prevalent across multiple tumors. Here we present final efficacy and safety results of a phase 2 basket trial dabrafenib (BRAF kinase inhibitor) plus trametinib (MEK in eight cohorts patients with -mutated advanced rare cancers: anaplastic thyroid carcinoma ( n = 36), biliary tract cancer 43), gastrointestinal stromal tumor 1), adenocarcinoma the small intestine 3), low-grade glioma 13), high-grade 45), hairy cell leukemia 55) myeloma 19). The primary...
Abstract 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 depatuxizumab mafodotin (depatux-m), an antibody–drug conjugate comprised a monoclonal antibody that binds activated EGFR (overexpressed wild-type EGFRvIII-mutant) linked to microtubule-inhibitor toxin in EGFR-amp GBMs. Methods In this phase III trial, adults with centrally confirmed,...
Activated microglia are involved in the immune response of multiple sclerosis (MS). The peripheral benzodiazepine receptor (PBR) is expressed on and up‐regulated after neuronal injury. [ 11 C]PK11195 a positron emission tomography (PET) radioligand for PBR. objective present study was to investigate imaging MS patients its additional value over magnetic resonance (MRI) concerning immuno‐pathophysiological process. Seven healthy 22 subjects were included. Semiquantitative uptake values...
Accurate sizing of nanoparticles in biological media is important for drug delivery and biomedical imaging applications since size directly influences the nanoparticle processing nanotoxicity vivo. Using fluorescence single particle tracking we have succeeded first time following aggregation real undiluted whole blood. We demonstrate that, by using a suitable surface functionalization, blood circulation prevented to large extent.
This study reports on the encapsulation efficiency of proteins in dextran sulfate/poly-L-arginine-based microcapsules, fabricated via layer-by-layer assembly (LbL). For this purpose, radiolabeled are entrapped CaCO(3) microparticles, followed by LbL coating cores and subsequent dissolving using EDTA. To allow to improve protein we studied all steps preparation microcapsules where loss load might occur. The turns out be strongly dependent both charge molecular weight as well number...
Summary Background This open-label, first-in-human, phase 1 study evaluated AMG 232, an oral selective MDM2 inhibitor in patients with TP53 wild-type (P53WT), advanced solid tumors or multiple myeloma (MM). Methods In the dose escalation ( n = 39), P53WT refractory enrolled to receive once-daily 232 (15, 30, 60, 120, 240, 480, and 960 mg) for seven days every 3 weeks (Q3W). expansion 68), -amplified (well-differentiated de-differentiated liposarcomas [WDLPS DDLPS], glioblastoma multiforme...
Abstract Aims Methylation profiling (MP) is increasingly incorporated in the diagnostic process of central nervous system (CNS) tumours at our centres The Netherlands and Scandinavia. We aimed to identify benefits challenges MP as a support tool for CNS tumour diagnostics. Methods About 502 samples were analysed using (850 k) MP. Profiles matched with DKFZ/Heidelberg Tumour Classifier. For each case, final pathological diagnosis was compared before Results In 54.4% (273/502) all cases,...
This phase I/IIa study (NCT02737475) evaluated the safety and activity of BMS-986178, a fully human OX40 agonist IgG1 mAb, ± nivolumab and/or ipilimumab in patients with advanced solid tumors.Patients (with non-small cell lung, renal cell, bladder, other cancers) received BMS-986178 (20-320 mg) (240-480 (1-3 mg/kg). The primary endpoint was safety. Additional endpoints included immunogenicity, pharmacodynamics, pharmacokinetics, antitumor per RECIST version 1.1.Twenty monotherapy, 145...
FGFR genomic alterations (amplification, mutations, and/or fusions) occur in ∼8% of gliomas, particularly FGFR1 and FGFR3. We conducted a multicenter open-label, single-arm, phase II study selective FGFR1-3 inhibitor, infigratinib (BGJ398), patients with FGFR-altered recurrent gliomas.Adults recurrent/progressive gliomas harboring received oral 125 mg on days 1 to 21 28-day cycles. The primary endpoint was investigator-assessed 6-month progression-free survival (PFS) rate by Response...
Abstract Background Standard treatment for patients with newly diagnosed glioblastoma includes surgery, radiotherapy (RT), and temozolomide (TMZ) chemotherapy (TMZ/RT→TMZ). The proteasome has long been considered a promising therapeutic target because of its role as central biological hub in tumor cells. Marizomib is novel pan-proteasome inhibitor that crosses the blood–brain barrier. Methods European Organisation Research Treatment Cancer 1709/Canadian Trials Group CE.8 was multicenter,...
Objective: The objectives of the present study were to assess brain atrophy in multiple sclerosis (MS) patients during different disease stages and investigate by PET [ 11 C]PK11195, a marker microglial activation, relationship between inflammation, clinically relevant measures. Methods: Eight healthy subjects 22 MS included. Semiquantitative C]PK11195 uptake values, with normalization on cortical grey matter, measured for magnetic resonance imaging T 2 - 1 -lesions normal appearing white...
Abstract Background Palliative systematic treatment offers uncertain and often limited benefits, the burden can be high. Hence, decisions require shared decision making (SDM). This trial examined independent combined effect of an oncologist training a patient communication aid on SDM. Methods In this multicenter randomized controlled with four parallel arms (2016–2018), oncologists (n = 31) were to receive SDM skills or not. The consisted reader, two group sessions, booster session,...
Abstract Purpose: This phase I, dose-escalation study investigated the recommended dose for expansion (RDE) of siremadlin, a p53–MDM2 inhibitor, in patients with wild-type TP53 advanced solid or hematologic cancers. Patients and Methods: Initial dosing regimens were: 1A (day 1; 21-day cycle; 12.5–350 mg) 2A (days 1–14; 28-day 1–20 mg). Alternative included 1B 1 8; cycle) 2C 1–7; cycle). The primary endpoint was incidence dose-limiting toxicities (DLT) during cycle 1. Results: Overall, 115...
Abstract Purpose: The influence of the transcriptional and immunologic context mutations on therapeutic outcomes with targeted therapy in cancer has not been well defined. BRAF V600E–mutant (BM) colorectal comprises two main subtypes, BM1 BM2. We sought to determine impact BM subtype, as distinct biological features those response BRAF/MEK/EGFR inhibition patients cancer. Patients Methods: Paired fresh tumor biopsies were acquired at baseline day 15 treatment from all consenting enrolled a...