A5076579541- Glioma Diagnosis and Treatment
- Radiomics and Machine Learning in Medical Imaging
- Brain Metastases and Treatment
- MRI in cancer diagnosis
- Epigenetics and DNA Methylation
- Cancer Genomics and Diagnostics
- MicroRNA in disease regulation
- Cancer-related molecular mechanisms research
- Histone Deacetylase Inhibitors Research
- Ferroptosis and cancer prognosis
- Chronic Myeloid Leukemia Treatments
- Computational Drug Discovery Methods
- Neuroblastoma Research and Treatments
- Circular RNAs in diseases
- Brain Tumor Detection and Classification
- Advanced Electron Microscopy Techniques and Applications
- Meningioma and schwannoma management
- Vascular Malformations Diagnosis and Treatment
- Microtubule and mitosis dynamics
- Ocular Oncology and Treatments
- Cancer, Hypoxia, and Metabolism
- Drug Transport and Resistance Mechanisms
- Renal and related cancers
- Statistical Methods in Clinical Trials
- Biosimilars and Bioanalytical Methods
Erasmus MC Cancer Institute
2020-2024
Erasmus MC
2019-2024
Erasmus University Rotterdam
2019-2024
Yale University
2024
European Medicines Agency
2023
The Consortium to Inform Molecular and Practical Approaches CNS Tumor Taxonomy (cIMPACT-NOW) has recommended that isocitrate dehydrogenase 1 2 wildtype (IDH1/2wt) diffuse lower-grade gliomas (LGGs) World Health Organization (WHO) grade II or III present with (i) a telomerase reverse transcriptase promoter mutation (pTERTmt), and/or (ii) gain of chromosome 7 combined loss 10, (iii) epidermal growth factor receptor (EGFR) amplification should be reclassified as astrocytic glioma, IDH1/2...
Abstract Purpose: In a post hoc analysis of the CATNON trial (NCT00626990), we explored whether adding temozolomide to radiotherapy improves outcome in patients with IDH1/2 wildtype (wt) anaplastic astrocytomas molecular features glioblastoma [redesignated as glioblastoma, isocitrate dehydrogenase–wildtype (IDH-wt) 2021 World Health Organization (WHO) classification central nervous system tumors]. Patients and Methods: From randomized phase III study examining addition adjuvant concurrent...
Survival in patients with IDH1/2-mutant (mt) anaplastic astrocytomas is highly variable. We have used the prospective phase 3 CATNON trial to identify molecular factors related outcome IDH1/2mt astrocytoma patients.The randomized 751 adult newly diagnosed 1p/19q non-codeleted glioma 59.4 Gy radiotherapy +/- concurrent and/or adjuvant temozolomide. The presence of necrosis microvascular proliferation was scored at central pathology review. Infinium MethylationEPIC BeadChip arrays were for...
Abstract Somatic mutations in the isocitrate dehydrogenase genes IDH1 and IDH2 occur at high frequency several tumour types. Even though these are confined to distinct hotspots, we show that gliomas only type with an exceptionally percentage of R132H mutations. Patients harbouring mutated tumours have lower levels genome-wide DNA-methylation, associated increased gene expression, compared other IDH1/2 (“non-R132H mutations”). This reduced methylation is seen multiple types thus appears...
Abstract BACKGROUND The 1st interim analysis of the CATNON trial showed benefit from adjuvant (adj) temozolomide (TMZ) on overall survival (OS) but remained inconclusive about concurrent (conc) TMZ. A 2nd was planned after 356 events. MATERIAL AND METHODS 2x2 factorial design phase III randomized 751 adult patients with newly diagnosed non-codeleted anaplastic glioma to either 59.4 Gy radiotherapy (RT) alone; same RT concTMZ; and 12 cycles adjTMZ or both concTMZ (doi:...
Gliomas with IDH1/2 mutations without 1p19q codeletion have been identified as the distinct diagnostic entity of IDH mutant astrocytoma (IDHmut astrocytoma). Homozygous deletion Cyclin-dependent kinase 4 inhibitor A/B (CDKN2A/B) has recently incorporated in grading these tumors. The question whether histologic parameters still contribute to prognostic information on top molecular classification, remains unanswered. Here we evaluated consensus for providing additional value IDHmut astrocytomas.
Abstract Background IDH1/2 wildtype (IDHwt) glioma WHO grade 2 and 3 patients with pTERT mutation and/or EGFR amplification + 7/−10 chromosome gain/loss have a similar overall survival time as IDHwt glioblastoma patients, are both considered according to the 2021 classification. However, differences in seizure onset been observed. This study aimed compare course of epilepsy subtypes. Methods We analyzed data an existing cohort including histologically lower-grade molecular glioblastoma-like...
1 Abstract To study the evolutionary processes that drive malignant progression of IDH-mutant astrocytomas, we performed multi-omics on a large cohort matched initial and recurrent tumor samples. The overlay genetic, epigenetic, transcriptomic proteomic data, combined with single-cell analysis, have identified overlapping features associated progression. These are derived from three molecular mechanisms provide rationale underlying biology malignancy: cell-cycling, cell (de-)differentiation...
Accurate grading of IDH-mutant gliomas defines patient prognosis and guides the treatment path. Histological is however difficult and, apart from CDKN2A/B homozygous deletions in astrocytomas, there are no other objective molecular markers used for grading. Experimental Design: RNA-sequencing was conducted on primary astrocytomas (n=138) included prospective CATNON trial, which performed to assess prognostic effect adjuvant concurrent temozolomide. We integrated RNA sequencing data with...
The survival outcome of glioblastomas lacking necrosis vascular proliferations is controversial, especially in with only an isolated TERT promoter mutation. Limited evidence suggests a favorable for these patients, which challenges the concept proposed CNS5 classification glioblastoma. In this study we assessed impact on lack or glioblastoma, and investigated mutations. Although clinical presentation different, did not find glioblastoma patients high grade histological features
Abstract Purpose: Despite recent advances in the molecular characterization of gliomas, it remains unclear which patients benefit most from second-line treatments. The TAVAREC trial was a randomized, open-label phase II assessing addition angiogenesis inhibitor bevacizumab to treatment with temozolomide first enhancing recurrence World Health Organization grade 2 or 3 glioma without 1p/19q codeletion. We evaluated prognostic significance genome-wide DNA methylation profiles and copy-number...
Abstract Asciminib is an allosteric high-affinity tyrosine kinase inhibitor (TKI) of the BCR-ABL1 protein kinase. This translated from Philadelphia chromosome in chronic myeloid leukemia (CML). Marketing authorization for asciminib was granted on August 25, 2022 by European Commission. The approved indication patients with chromosome-positive CML phase which have previously been treated at least 2 TKIs. Clinical efficacy and safety were evaluated open-label, randomized, III ASCEMBL study....
The European Medicines Agency (EMA) offers guidance and support to pharmaceutical companies through bilateral discussions called business pipeline meetings (BPMs). An analysis of BPMs in oncology over a 5-year period was conducted identify common topics recurring queries. documents all available at the EMA regarding field from January 1, 2018, Decemer 31, 2022, were reviewed. For every query, main category assigned, case multiple relevant topics, secondary appointed too. queries, follow-up...
<title>Abstract</title> To study the evolutionary processes that drive malignant progression of IDH-mutant astrocytomas, we performed multi-omics on a large cohort matched initial and recurrent tumor samples. The overlay genetic, epigenetic, transcriptomic proteomic data, combined with single-cell analysis, have identified overlapping features associated progression. These are derived from three molecular mechanisms provide rationale underlying biology malignancy: cell-cycling, cell...
Abstract BACKGROUND Recently, isocitrate dehydrogenase wildtype (IDHwt) lower grade gliomas (LGGs) that have a telomerase reverse transcriptase (TERT) promoter mutation and/or gain of chromosome 7 combined with loss 10 epidermal growth factor receptor amplification been reclassified as IDHwt astrocytomas molecular features glioblastoma, WHO IV (‘astrocytomas IDHwt, IV’). Survival these tumors meeting the criteria is less well studied. The objective this study to compare overall survival (OS)...
Abstract BACKGROUND The phase III CATNON trial randomized 751 adult patients with newly diagnosed 1p/19q non-codeleted anaplastic glioma to 59.4 Gy radiotherapy +/- concurrent and/or adjuvant TMZ. Here, we present the molecular analysis of IDH1/2wt subgroup, and associations between characteristics patient outcomes. METHODS CNV data MGMT promoter methylation status were assessed from EPIC array data. IDH1/2 H3F3A mutation determined a tailored next-generation sequencing panel TERT using...
Abstract BACKGROUND Uncontrolled studies have suggested that methylation-based epigenetic subtypes can be used for prognostication of glioma. We the prospective randomized CATNON trial to validate clinical relevance these subtypes. METHODS The phase III 751 adult patients with newly diagnosed 1p/19q non-codeleted anaplastic glioma 59.4 Gy radiotherapy +/- concurrent and/or adjuvant TMZ. CNV data and methylation were derived from Infinium MethylationEPIC arrays. Epigenetic subtyping risk...
<div>AbstractPurpose:<p>Despite recent advances in the molecular characterization of gliomas, it remains unclear which patients benefit most from second-line treatments. The TAVAREC trial was a randomized, open-label phase II assessing addition angiogenesis inhibitor bevacizumab to treatment with temozolomide first enhancing recurrence World Health Organization grade 2 or 3 glioma without 1p/19q codeletion. We evaluated prognostic significance genome-wide DNA methylation profiles...
Supplementary Figure from Prognostic Significance of DNA Methylation Profiles at MRI Enhancing Tumor Recurrence: a Report the EORTC 26091 TAVAREC Trial
Supplementary Data from Prognostic Significance of DNA Methylation Profiles at MRI Enhancing Tumor Recurrence: a Report the EORTC 26091 TAVAREC Trial
<div>AbstractPurpose:<p>Despite recent advances in the molecular characterization of gliomas, it remains unclear which patients benefit most from second-line treatments. The TAVAREC trial was a randomized, open-label phase II assessing addition angiogenesis inhibitor bevacizumab to treatment with temozolomide first enhancing recurrence World Health Organization grade 2 or 3 glioma without 1p/19q codeletion. We evaluated prognostic significance genome-wide DNA methylation profiles...