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Your search keyword '"Van Den Heuvel, M. P."' showing total 132 results
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132 results on '"Van Den Heuvel, M. P."'

5. Immune checkpoint inhibitors for patients with advanced lung cancer and oncogenic driver alterations: results from the IMMUNOTARGET registry

Author

Mazieres, J, Drilon, A, Lusque, A, Mhanna, L, Cortot, AB, Mezquita, L, Thai, AA, Mascaux, C, Couraud, S, Veillon, R, Van den Heuvel, M, Neal, J, Peled, N, Früh, M, Ng, TL, Gounant, V, Popat, S, Diebold, J, Sabari, J, Zhu, VW, Rothschild, SI, Bironzo, P, Martinez-Marti, A, Curioni-Fontecedro, A, Rosell, R, Lattuca-Truc, M, Wiesweg, M, Besse, B, Solomon, B, Barlesi, F, Schouten, RD, Wakelee, H, Camidge, DR, Zalcman, G, Novello, S, Ou, SI, Milia, J, and Gautschi, O

Subjects
Lung, Cancer, Clinical Research, Clinical Trials and Supportive Activities, Lung Cancer, Development of treatments and therapeutic interventions, 5.1 Pharmaceuticals, Good Health and Well Being, Adult, Aged, Aged, 80 and over, Antineoplastic Agents, Immunological, Antineoplastic Combined Chemotherapy Protocols, B7-H1 Antigen, Biomarkers, Tumor, Carcinoma, Non-Small-Cell Lung, Female, Humans, Lung Neoplasms, Male, Middle Aged, Mutation, Oncogenes, Programmed Cell Death 1 Receptor, Progression-Free Survival, Registries, Response Evaluation Criteria in Solid Tumors, Retrospective Studies, immunotherapy, lung cancer, oncogenic addiction, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

BackgroundAnti-PD1/PD-L1 directed immune checkpoint inhibitors (ICI) are widely used to treat patients with advanced non-small-cell lung cancer (NSCLC). The activity of ICI across NSCLC harboring oncogenic alterations is poorly characterized. The aim of our study was to address the efficacy of ICI in the context of oncogenic addiction.Patients and methodsWe conducted a retrospective study for patients receiving ICI monotherapy for advanced NSCLC with at least one oncogenic driver alteration. Anonymized data were evaluated for clinicopathologic characteristics and outcomes for ICI therapy: best response (RECIST 1.1), progression-free survival (PFS), and overall survival (OS) from ICI initiation. The primary end point was PFS under ICI. Secondary end points were best response (RECIST 1.1) and OS from ICI initiation.ResultsWe studied 551 patients treated in 24 centers from 10 countries. The molecular alterations involved KRAS (n = 271), EGFR (n = 125), BRAF (n = 43), MET (n = 36), HER2 (n = 29), ALK (n = 23), RET (n = 16), ROS1 (n = 7), and multiple drivers (n = 1). Median age was 60 years, gender ratio was 1 : 1, never/former/current smokers were 28%/51%/21%, respectively, and the majority of tumors were adenocarcinoma. The objective response rate by driver alteration was: KRAS = 26%, BRAF = 24%, ROS1 = 17%, MET = 16%, EGFR = 12%, HER2 = 7%, RET = 6%, and ALK = 0%. In the entire cohort, median PFS was 2.8 months, OS 13.3 months, and the best response rate 19%. In a subgroup analysis, median PFS (in months) was 2.1 for EGFR, 3.2 for KRAS, 2.5 for ALK, 3.1 for BRAF, 2.5 for HER2, 2.1 for RET, and 3.4 for MET. In certain subgroups, PFS was positively associated with PD-L1 expression (KRAS, EGFR) and with smoking status (BRAF, HER2).Conclusions: ICI induced regression in some tumors with actionable driver alterations, but clinical activity was lower compared with the KRAS group and the lack of response in the ALK group was notable. Patients with actionable tumor alterations should receive targeted therapies and chemotherapy before considering immunotherapy as a single agent.

Published
2019

8. Abundant pleiotropy across neuroimaging modalities identified through a multivariate genome-wide association study

Author

Tissink, E P, Shadrin, A A, van der Meer, D, Parker, N, Hindley, G, Roelfs, D, Frei, O, Fan, C C, Nagel, M, Nærland, T, Budisteanu, M, Djurovic, S, Westlye, L T, van den Heuvel, M P, Posthuma, D, Kaufmann, T, Dale, A M, Andreassen, O A, Tissink, E P, Shadrin, A A, van der Meer, D, Parker, N, Hindley, G, Roelfs, D, Frei, O, Fan, C C, Nagel, M, Nærland, T, Budisteanu, M, Djurovic, S, Westlye, L T, van den Heuvel, M P, Posthuma, D, Kaufmann, T, Dale, A M, and Andreassen, O A

Abstract

Genetic pleiotropy is abundant across spatially distributed brain characteristics derived from one neuroimaging modality (e.g. structural, functional or diffusion magnetic resonance imaging [MRI]). A better understanding of pleiotropy across modalities could inform us on the integration of brain function, micro- and macrostructure. Here we show extensive genetic overlap across neuroimaging modalities at a locus and gene level in the UK Biobank (N = 34,029) and ABCD Study (N = 8607). When jointly analysing phenotypes derived from structural, functional and diffusion MRI in a genome-wide association study (GWAS) with the Multivariate Omnibus Statistical Test (MOSTest), we boost the discovery of loci and genes beyond previously identified effects for each modality individually. Cross-modality genes are involved in fundamental biological processes and predominantly expressed during prenatal brain development. We additionally boost prediction of psychiatric disorders by conditioning independent GWAS on our multimodal multivariate GWAS. These findings shed light on the shared genetic mechanisms underlying variation in brain morphology, functional connectivity, and tissue composition.

Published
2024

13. A low-dimensional cognitive-network space in Alzheimer’s disease and frontotemporal dementia

Author

Pini, L., de Lange, S. C., Pizzini, F. B., Boscolo Galazzo, I., Manenti, R., Cotelli, Maria, Galluzzi, S., Cotelli, M. S., Corbetta, M., van den Heuvel, M. P., Pievani, M., Cotelli M., Pini, L., de Lange, S. C., Pizzini, F. B., Boscolo Galazzo, I., Manenti, R., Cotelli, Maria, Galluzzi, S., Cotelli, M. S., Corbetta, M., van den Heuvel, M. P., Pievani, M., and Cotelli M.

Abstract

Background: Alzheimer’s disease (AD) and frontotemporal dementia (FTD) show network dysfunctions linked with cognitive deficits. Within this framework, network abnormalities between AD and FTD show both convergent and divergent patterns. However, these functional patterns are far from being established and their relevance to cognitive processes remains to be elucidated. Methods: We investigated the relationship between cognition and functional connectivity of major cognitive networks in these diseases. Twenty-three bvFTD (age: 71±10), 22 AD (age: 72±6), and 20 controls (age: 72±6) underwent cognitive evaluation and resting-state functional MRI. Principal component analysis was used to describe cognitive variance across participants. Brain network connectivity was estimated with connectome analysis. Connectivity matrices were created assessing correlations between parcels within each functional network. The following cognitive networks were considered: default mode (DMN), dorsal attention (DAN), ventral attention (VAN), and frontoparietal (FPN) networks. The relationship between cognition and connectivity was assessed using a bootstrapping correlation and interaction analyses. Results: Three principal cognitive components explained more than 80% of the cognitive variance: the first component (cogPC1) loaded on memory, the second component (cogPC2) loaded on emotion and language, and the third component (cogPC3) loaded on the visuo-spatial and attentional domains. Compared to HC, AD and bvFTD showed impairment in all cogPCs (p<0.002), and bvFTD scored worse than AD in cogPC2 (p=0.031). At the network level, the DMN showed a significant association in the whole group with cogPC1 and cogPC2 and the VAN with cogPC2. By contrast, DAN and FPN showed a divergent pattern between diagnosis and connectivity for cogPC2. We confirmed these results by means of a multivariate analysis (canonical correlation). Conclusions: A low-dimensional representation can account for a large

Published
2022

26. Functional architecture of the human brain

Author

Onderzoeksgroep 6, Child Health, Brain, Zalesky, Andrew, Keilholz, Shella D, van den Heuvel, M P, Onderzoeksgroep 6, Child Health, Brain, Zalesky, Andrew, Keilholz, Shella D, and van den Heuvel, M P

Published
2017

32. Anatomical and Functional Brain Network Architecture in Schizophrenia

Author

UMC Utrecht, AIOS Psychiatrie, Brain, Onderzoeksgroep 6, Child Health, Abel, Ted, Nickl-Jockschat, Thomas, Collin, G., van den Heuvel, M. P., UMC Utrecht, AIOS Psychiatrie, Brain, Onderzoeksgroep 6, Child Health, Abel, Ted, Nickl-Jockschat, Thomas, Collin, G., and van den Heuvel, M. P.

Published
2016

33. Connectomics-based structural network alterations in obsessive-compulsive disorder

Author

Onderzoeksgroep 6, Projectafdeling ALS, Brain, Child Health, Reess, T. J., Rus, O. G., Schmidt, R., De Reus, M. A., Zaudig, M., Wagner, G., Zimmer, C., Van Den Heuvel, M. P., Koch, K., Onderzoeksgroep 6, Projectafdeling ALS, Brain, Child Health, Reess, T. J., Rus, O. G., Schmidt, R., De Reus, M. A., Zaudig, M., Wagner, G., Zimmer, C., Van Den Heuvel, M. P., and Koch, K.

Published
2016

34. Connectome organization is related to longitudinal changes in general functioning, symptoms and IQ in chronic schizophrenia

Author

AIOS Psychiatrie, Onderzoeksgroep 1, Brain, Affectieve & Psychotische Med., Onderzoeksgroep 6, Collin, G., de Nijs, J., Hulshoff Pol, H. E., Cahn, W., van den Heuvel, M. P., AIOS Psychiatrie, Onderzoeksgroep 1, Brain, Affectieve & Psychotische Med., Onderzoeksgroep 6, Collin, G., de Nijs, J., Hulshoff Pol, H. E., Cahn, W., and van den Heuvel, M. P.

Published
2016

41. Affected connectivity organization of the reward system structure in obesity

Author

Onderzoeksgroep 6, Brain, Marqués-Iturria, I., Scholtens, L. H., Garolera, M., Pueyo, R., García-García, I., González-Tartiere, P., Segura, B., Junqué, C., Sender-Palacios, M. J., Vernet-Vernet, M., Sánchez-Garre, C., de Reus, M. A., Jurado, M. A., van den Heuvel, M. P., Onderzoeksgroep 6, Brain, Marqués-Iturria, I., Scholtens, L. H., Garolera, M., Pueyo, R., García-García, I., González-Tartiere, P., Segura, B., Junqué, C., Sender-Palacios, M. J., Vernet-Vernet, M., Sánchez-Garre, C., de Reus, M. A., Jurado, M. A., and van den Heuvel, M. P.

Published
2015

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