1,526 results on '"Cornelis, M."'
Search Results
2. Immunoglobulin prophylaxis prevents hospital admissions for fever in pediatric acute lymphoblastic leukemia: results of a multicenter randomized trial
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Kirsten A. Thus, Hester A. de Groot-Kruseman, Pauline Winkler-Seinstra, Marta Fiocco, Heidi Segers, Cor van den Bos, Inge M. van der Sluis, Wim J.E. Tissing, Margreet A. Veening, Christian Michel Zwaan, Cornelis M. van Tilburg, Rob Pieters, and Marc Bierings
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Infections lead to substantial morbidity during treatment of acute lymphoblastic leukemia (ALL) in which the adaptive immune system gets severely affected, leading to declining serum immunoglobulin levels. The aim of this trial was to investigate whether intravenous immunoglobulin (IVIG) prophylaxis in pediatric patients with ALL prevents admissions for fever. This randomized controlled trial was a subtrial of the national Dutch multicenter ALL study. Patients aged 1-19 years with medium risk (MR) ALL were randomized into two groups receiving either IVIG prophylaxis (0.7 g/kg IVIG given every three weeks, starting day 22 after diagnosis) or well defined standard of care (control group). Between October 2012 until March 2019, 91 (51%) patients were randomly assigned to IVIG prophylaxis and 86 (49%) to the control arm. In the IVIG prophylaxis group there were 206 admissions for fever versus 271 in the control group (p=0.011). IVIG prophylaxis was not associated with bacteremia. However, IVIG prophylaxis was associated with significantly less admissions for fever with negative blood cultures compared to the control group (N=113 versus 200, p
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- 2024
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3. Class I HDAC inhibition reduces DNA damage repair capacity of MYC-amplified medulloblastoma cells
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Vollmer, Johanna, Ecker, Jonas, Hielscher, Thomas, Valinciute, Gintvile, Ridinger, Johannes, Jamaladdin, Nora, Peterziel, Heike, van Tilburg, Cornelis M., Oehme, Ina, Witt, Olaf, and Milde, Till
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- 2023
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4. LOGGIC/FIREFLY-2: a phase 3, randomized trial of tovorafenib vs. chemotherapy in pediatric and young adult patients with newly diagnosed low-grade glioma harboring an activating RAF alteration
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Cornelis M. van Tilburg, Lindsay B. Kilburn, Sébastien Perreault, Rene Schmidt, Amedeo A. Azizi, Ofelia Cruz-Martínez, Michal Zápotocký, Katrin Scheinemann, Antoinette Y. N. Schouten-van Meeteren, Astrid Sehested, Enrico Opocher, Pablo Hernáiz Driever, Shivaram Avula, David S. Ziegler, David Capper, Arend Koch, Felix Sahm, Jiaheng Qiu, Li-Pen Tsao, Samuel C. Blackman, Peter Manley, Till Milde, Ruth Witt, David T. W. Jones, Darren Hargrave, and Olaf Witt
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Chemotherapy ,First-line ,Pediatric low-grade glioma ,pLGG ,Tovorafenib ,Child ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Pediatric low-grade glioma (pLGG) is essentially a single pathway disease, with most tumors driven by genomic alterations affecting the mitogen-activated protein kinase/ERK (MAPK) pathway, predominantly KIAA1549::BRAF fusions and BRAF V600E mutations. This makes pLGG an ideal candidate for MAPK pathway-targeted treatments. The type I BRAF inhibitor, dabrafenib, in combination with the MEK inhibitor, trametinib, has been approved by the United States Food and Drug Administration for the systemic treatment of BRAF V600E-mutated pLGG. However, this combination is not approved for the treatment of patients with tumors harboring BRAF fusions as type I RAF inhibitors are ineffective in this setting and may paradoxically enhance tumor growth. The type II RAF inhibitor, tovorafenib (formerly DAY101, TAK-580, MLN2480), has shown promising activity and good tolerability in patients with BRAF-altered pLGG in the phase 2 FIREFLY-1 study, with an objective response rate (ORR) per Response Assessment in Neuro-Oncology high-grade glioma (RANO-HGG) criteria of 67%. Tumor response was independent of histologic subtype, BRAF alteration type (fusion vs. mutation), number of prior lines of therapy, and prior MAPK-pathway inhibitor use. Methods LOGGIC/FIREFLY-2 is a two-arm, randomized, open-label, multicenter, global, phase 3 trial to evaluate the efficacy, safety, and tolerability of tovorafenib monotherapy vs. current standard of care (SoC) chemotherapy in patients
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- 2024
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5. Imaging findings for response evaluation of ductal carcinoma in situ in breast cancer patients treated with neoadjuvant systemic therapy: a systematic review and meta-analysis
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Ploumen, Roxanne A. W., de Mooij, Cornelis M., Gommers, Suzanne, Keymeulen, Kristien B. M. I., Smidt, Marjolein L., and van Nijnatten, Thiemo J. A.
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- 2023
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6. MAPK inhibitor sensitivity scores predict sensitivity driven by the immune infiltration in pediatric low-grade gliomas
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Sigaud, Romain, Albert, Thomas K., Hess, Caroline, Hielscher, Thomas, Winkler, Nadine, Kocher, Daniela, Walter, Carolin, Münter, Daniel, Selt, Florian, Usta, Diren, Ecker, Jonas, Brentrup, Angela, Hasselblatt, Martin, Thomas, Christian, Varghese, Julian, Capper, David, Thomale, Ulrich W., Hernáiz Driever, Pablo, Simon, Michèle, Horn, Svea, Herz, Nina Annika, Koch, Arend, Sahm, Felix, Hamelmann, Stefan, Faria-Andrade, Augusto, Jabado, Nada, Schuhmann, Martin U., Schouten-van Meeteren, Antoinette Y. N., Hoving, Eelco, Brummer, Tilman, van Tilburg, Cornelis M., Pfister, Stefan M., Witt, Olaf, Jones, David T. W., Kerl, Kornelius, and Milde, Till
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- 2023
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7. The influence of receptor expression and clinical subtypes on baseline [18F]FDG uptake in breast cancer: systematic review and meta-analysis
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de Mooij, Cornelis M., Ploumen, Roxanne A. W., Nelemans, Patty J., Mottaghy, Felix M., Smidt, Marjolein L., and van Nijnatten, Thiemo J. A.
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- 2023
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8. Implementing data on targeted therapy from the INFORM registry platform for children with relapsed cancer in Sweden
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Sofia Wallin, Ingrid Øra, Gabriela Prochazka, Johanna Sandgren, Caroline Björklund, Gustaf Ljungman, Hartmut Vogt, Torben Ek, Cornelis M. van Tilburg, and Anna Nilsson
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pediatric oncology ,pediatric cancer ,precision medicine ,molecular diagnostic techniques ,molecular targeted therapy ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
BackgroundAdvances in treatment of childhood malignancies have improved overall cure rates to 80%. Nevertheless, cancer is still the most common cause of childhood mortality in Sweden. The prognosis is particularly poor for relapse of high-risk malignancies. In the international INFORM registry, tumor tissue from patients with relapsed, refractory, or progressive pediatric cancer as well as from very-high risk primary tumors is biologically characterized using next-generation sequencing to identify possible therapeutic targets. We analyzed data from Swedish children included in the INFORM registry concerning patient characteristics, survival, sequencing results and whether targeted treatment was administered to the children based on the molecular findings.MethodsA registry-based descriptive analysis of 184 patients included in the INFORM registry in Sweden during 2016–2021.ResultsThe most common diagnoses were soft tissue and bone sarcomas followed by high grade gliomas [including diffuse intrinsic pontine glioma (DIPG)]. Complete molecular analysis was successful for 203/212 samples originating from 184 patients. In 88% of the samples, at least one actionable target was identified. Highly prioritized targets, according to a preset scale, were identified in 48 (24%) samples from 40 patients and 24 of these patients received matched targeted treatment but only six children within a clinical trial. No statistically significant benefit in terms of overall survival or progression free survival was observed between children treated with matched targeted treatment compared to all others.ConclusionThis international collaborative study demonstrate feasibility regarding sequencing of pediatric high-risk tumors providing molecular data regarding potential actionable targets to clinicians. For a few individuals the INFORM analysis was of utmost importance and should be regarded as a new standard of care with the potential to guide targeted therapy.
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- 2024
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9. MAPK inhibitor sensitivity scores predict sensitivity driven by the immune infiltration in pediatric low-grade gliomas
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Romain Sigaud, Thomas K. Albert, Caroline Hess, Thomas Hielscher, Nadine Winkler, Daniela Kocher, Carolin Walter, Daniel Münter, Florian Selt, Diren Usta, Jonas Ecker, Angela Brentrup, Martin Hasselblatt, Christian Thomas, Julian Varghese, David Capper, Ulrich W. Thomale, Pablo Hernáiz Driever, Michèle Simon, Svea Horn, Nina Annika Herz, Arend Koch, Felix Sahm, Stefan Hamelmann, Augusto Faria-Andrade, Nada Jabado, Martin U. Schuhmann, Antoinette Y. N. Schouten-van Meeteren, Eelco Hoving, Tilman Brummer, Cornelis M. van Tilburg, Stefan M. Pfister, Olaf Witt, David T. W. Jones, Kornelius Kerl, and Till Milde
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Science - Abstract
Abstract Pediatric low-grade gliomas (pLGG) show heterogeneous responses to MAPK inhibitors (MAPKi) in clinical trials. Thus, more complex stratification biomarkers are needed to identify patients likely to benefit from MAPKi therapy. Here, we identify MAPK-related genes enriched in MAPKi-sensitive cell lines using the GDSC dataset and apply them to calculate class-specific MAPKi sensitivity scores (MSSs) via single-sample gene set enrichment analysis. The MSSs discriminate MAPKi-sensitive and non-sensitive cells in the GDSC dataset and significantly correlate with response to MAPKi in an independent PDX dataset. The MSSs discern gliomas with varying MAPK alterations and are higher in pLGG compared to other pediatric CNS tumors. Heterogenous MSSs within pLGGs with the same MAPK alteration identify proportions of potentially sensitive patients. The MEKi MSS predicts treatment response in a small set of pLGG patients treated with trametinib. High MSSs correlate with a higher immune cell infiltration, with high expression in the microglia compartment in single-cell RNA sequencing data, while low MSSs correlate with low immune infiltration and increased neuronal score. The MSSs represent predictive tools for the stratification of pLGG patients and should be prospectively validated in clinical trials. Our data supports a role for microglia in the response to MAPKi.
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- 2023
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10. The influence of receptor expression and clinical subtypes on baseline [18F]FDG uptake in breast cancer: systematic review and meta-analysis
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Cornelis M. de Mooij, Roxanne A. W. Ploumen, Patty J. Nelemans, Felix M. Mottaghy, Marjolein L. Smidt, and Thiemo J. A. van Nijnatten
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Breast cancer ,Immunohistochemistry ,Clinical subtypes ,[18F]FDG PET ,Systematic review ,Meta-analyses ,Medical physics. Medical radiology. Nuclear medicine ,R895-920 - Abstract
Abstract Background To quantify the relationship between [18F]FDG uptake of the primary tumour measured by PET-imaging with immunohistochemical (IHC) expression of ER, PR, HER2, Ki-67, and clinical subtypes based on these markers in breast cancer patients. Methods PubMed and Embase were searched for studies that compared SUVmax between breast cancer patients negative and positive for IHC expression of ER, PR, HER2, Ki-67, and clinical subtypes based on these markers. Two reviewers independently screened the studies and extracted the data. Standardized mean differences (SMD) and 95% confidence intervals (CIs) were estimated by using DerSimonian-Laird random-effects models. P values less than or equal to 5% indicated statistically significant results. Results Fifty studies were included in the final analysis. SUVmax is significantly higher in ER-negative (31 studies, SMD 0.66, 0.56–0.77, P
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- 2023
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11. Efficient modeling of wave generation and propagation in a semi-enclosed estuary
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Crosby, Sean C., Nederhoff, Cornelis M., VanArendonk, Nathan, and Grossman, Eric E.
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- 2023
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12. Larotrectinib in patients with TRK fusion-positive solid tumours: a pooled analysis of three phase 1/2 clinical trials
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Hong, David S, DuBois, Steven G, Kummar, Shivaani, Farago, Anna F, Albert, Catherine M, Rohrberg, Kristoffer S, van Tilburg, Cornelis M, Nagasubramanian, Ramamoorthy, Berlin, Jordan D, Federman, Noah, Mascarenhas, Leo, Geoerger, Birgit, Dowlati, Afshin, Pappo, Alberto S, Bielack, Stefan, Doz, François, McDermott, Ray, Patel, Jyoti D, Schilder, Russell J, Tahara, Makoto, Pfister, Stefan M, Witt, Olaf, Ladanyi, Marc, Rudzinski, Erin R, Nanda, Shivani, Childs, Barrett H, Laetsch, Theodore W, Hyman, David M, and Drilon, Alexander
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Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Clinical Trials and Supportive Activities ,Clinical Research ,Cancer ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Good Health and Well Being ,Adolescent ,Adult ,Aged ,Aged ,80 and over ,Child ,Child ,Preschool ,Female ,Humans ,Infant ,Infant ,Newborn ,Male ,Middle Aged ,Neoplasms ,Proteins ,Pyrazoles ,Pyrimidines ,Young Adult ,Oncology & Carcinogenesis ,Oncology and carcinogenesis - Abstract
BackgroundThe selective TRK inhibitor larotrectinib was approved for paediatric and adult patients with advanced TRK fusion-positive solid tumours based on a primary analysis set of 55 patients. The aim of our analysis was to explore the efficacy and long-term safety of larotrectinib in a larger population of patients with TRK fusion-positive solid tumours.MethodsPatients were enrolled and treated in a phase 1 adult, a phase 1/2 paediatric, or a phase 2 adolescent and adult trial. Some eligibility criteria differed between these studies. For this pooled analysis, eligible patients were aged 1 month or older, with a locally advanced or metastatic non-CNS primary, TRK fusion-positive solid tumour, who had received standard therapy previously if available. This analysis set includes the 55 patients on which approval of larotrectinib was based. Larotrectinib was administered orally (capsule or liquid formulation), on a continuous 28-day schedule, to adults mostly at a dose of 100 mg twice daily, and to paediatric patients mostly at a dose of 100 mg/m2 (maximum of 100 mg) twice daily. The primary endpoint was objective response as assessed by local investigators in an intention-to-treat analysis. Contributing trials are registered with ClinicalTrials.gov, NCT02122913 (active not recruiting), NCT02637687 (recruiting), and NCT02576431 (recruiting).FindingsBetween May 1, 2014, and Feb 19, 2019, 159 patients with TRK fusion-positive cancer were enrolled and treated with larotrectinib. Ages ranged from less than 1 month to 84 years. The proportion of patients with an objective response according to investigator assessment was 121 (79%, 95% CI 72-85) of 153 evaluable patients, with 24 (16%) having complete responses. In a safety population of 260 patients treated regardless of TRK fusion status, the most common grade 3 or 4 larotrectinib-related adverse events were increased alanine aminotransferase (eight [3%] of 260 patients), anaemia (six, 2%), and decreased neutrophil count (five [2%]). The most common larotrectinib-related serious adverse events were increased alanine aminotransferase (two [
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- 2020
13. Energy Poverty (Re)Invented? Concept and Regulatory Gaps in the EU Amidst the Decarbonisation Process
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Kottari, M., Cornelis, M., Rubio-Bellido, Carlos, editor, and Solis-Guzman, Jaime, editor
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- 2022
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14. Drug sensitivity profiling of 3D tumor tissue cultures in the pediatric precision oncology program INFORM
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Heike Peterziel, Nora Jamaladdin, Dina ElHarouni, Xenia F. Gerloff, Sonja Herter, Petra Fiesel, Yannick Berker, Mirjam Blattner-Johnson, Kathrin Schramm, Barbara C. Jones, David Reuss, Laura Turunen, Aileen Friedenauer, Tim Holland-Letz, Martin Sill, Lena Weiser, Christopher Previti, Gnanaprakash Balasubramanian, Nicolas U. Gerber, Johannes Gojo, Caroline Hutter, Ingrid Øra, Olli Lohi, Antonis Kattamis, Bram de Wilde, Frank Westermann, Stephan Tippelt, Norbert Graf, Michaela Nathrath, Monika Sparber-Sauer, Astrid Sehested, Christof M. Kramm, Uta Dirksen, Olli Kallioniemi, Stefan M. Pfister, Cornelis M. van Tilburg, David T. W. Jones, Jani Saarela, Vilja Pietiäinen, Natalie Jäger, Matthias Schlesner, Annette Kopp-Schneider, Sina Oppermann, Till Milde, Olaf Witt, and Ina Oehme
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract The international precision oncology program INFORM enrolls relapsed/refractory pediatric cancer patients for comprehensive molecular analysis. We report a two-year pilot study implementing ex vivo drug sensitivity profiling (DSP) using a library of 75–78 clinically relevant drugs. We included 132 viable tumor samples from 35 pediatric oncology centers in seven countries. DSP was conducted on multicellular fresh tumor tissue spheroid cultures in 384-well plates with an overall mean processing time of three weeks. In 89 cases (67%), sufficient viable tissue was received; 69 (78%) passed internal quality controls. The DSP results matched the identified molecular targets, including BRAF, ALK, MET, and TP53 status. Drug vulnerabilities were identified in 80% of cases lacking actionable (very) high-evidence molecular events, adding value to the molecular data. Striking parallels between clinical courses and the DSP results were observed in selected patients. Overall, DSP in clinical real-time is feasible in international multicenter precision oncology programs.
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- 2022
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15. Molecular diagnostics enables detection of actionable targets: the Pediatric Targeted Therapy 2.0 registry
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Ecker, Jonas, Selt, Florian, Sturm, Dominik, Sill, Martin, Korshunov, Andrey, Hirsch, Steffen, Capper, David, Dikow, Nicola, Sutter, Christian, Müller, Carina, Sigaud, Romain, Eggert, Angelika, Simon, Thorsten, Niehues, Tim, von Deimling, Andreas, Pajtler, Kristian W., van Tilburg, Cornelis M., Jones, David T.W., Sahm, Felix, Pfister, Stefan M., Witt, Olaf, and Milde, Till
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- 2023
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16. Resistance, rebound, and recurrence regrowth patterns in pediatric low-grade glioma treated by MAPK inhibition: A modified Delphi approach to build international consensus-based definitions—International Pediatric Low-Grade Glioma Coalition
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O’Hare, Patricia, primary, Cooney, Tabitha, additional, de Blank, Peter, additional, Gutmann, David H, additional, Kieran, Mark, additional, Milde, Till, additional, Fangusaro, Jason, additional, Fisher, Michael, additional, Avula, Shivaram, additional, Packer, Roger, additional, Fukuoka, Kohei, additional, Mankad, Kshitij, additional, Mueller, Sabine, additional, Waanders, Angela J, additional, Opocher, Enrico, additional, Bouffet, Eric, additional, Raabe, Eric, additional, Werle, Natacha Entz, additional, Azizi, Amedeo A, additional, Robison, Nathan J, additional, Hernáiz Driever, Pablo, additional, Russo, Mark, additional, Schouten, Netteke, additional, van Tilburg, Cornelis M, additional, Sehested, Astrid, additional, Grill, Jacques, additional, Bandopadhayay, Pratiti, additional, Kilday, John-Paul, additional, Witt, Olaf, additional, Ashley, David M, additional, Ertl-Wagner, Birgit Betina, additional, Tabori, Uri, additional, and Hargrave, Darren R, additional
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- 2024
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17. Modeling Extreme Water Levels in the Salish Sea: The Importance of Including Remote Sea Level Anomalies for Application in Hydrodynamic Simulations
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Eric E. Grossman, Babak Tehranirad, Cornelis M. Nederhoff, Sean C. Crosby, Andrew W. Stevens, Nathan R. Van Arendonk, Daniel J. Nowacki, Li H. Erikson, and Patrick L. Barnard
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extreme water levels ,sea level anomalies ,storm surge ,hydrodynamic modeling ,climate change impacts ,Salish Sea ,Hydraulic engineering ,TC1-978 ,Water supply for domestic and industrial purposes ,TD201-500 - Abstract
Extreme water-level recurrence estimates for a complex estuary using a high-resolution 2D model and a new method for estimating remotely generated sea level anomalies (SLAs) at the model boundary have been developed. The hydrodynamic model accurately resolves the dominant physical processes contributing to extreme water levels across the Washington State waters of the Salish Sea, including the relative contribution of remote SLA and other non-tidal residual processes that drive extreme water levels above the predicted tide. The model’s predictions have errors of less than 15 cm (2 = 0.76). The hydrodynamic model simulations using the remote SLA predictor compared well with simulations using the widely used data-assimilative global ocean model HYCOM SLA data (root mean square difference of 5.5 cm). Extreme water-level recurrence estimates with and without remote SLA show that remote forcing accounts for 50–60% of the total water level anomaly observed along Salish Sea shorelines. The resulting model simulations across decadal timescales provide estimates of extreme water level recurrence across the Salish Sea, capturing climate variability important to long-term coastal hazard planning. This approach has widespread applications for other complex estuarine systems.
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- 2023
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18. Drug sensitivity profiling of 3D tumor tissue cultures in the pediatric precision oncology program INFORM
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Peterziel, Heike, Jamaladdin, Nora, ElHarouni, Dina, Gerloff, Xenia F., Herter, Sonja, Fiesel, Petra, Berker, Yannick, Blattner-Johnson, Mirjam, Schramm, Kathrin, Jones, Barbara C., Reuss, David, Turunen, Laura, Friedenauer, Aileen, Holland-Letz, Tim, Sill, Martin, Weiser, Lena, Previti, Christopher, Balasubramanian, Gnanaprakash, Gerber, Nicolas U., Gojo, Johannes, Hutter, Caroline, Øra, Ingrid, Lohi, Olli, Kattamis, Antonis, de Wilde, Bram, Westermann, Frank, Tippelt, Stephan, Graf, Norbert, Nathrath, Michaela, Sparber-Sauer, Monika, Sehested, Astrid, Kramm, Christof M., Dirksen, Uta, Kallioniemi, Olli, Pfister, Stefan M., van Tilburg, Cornelis M., Jones, David T. W., Saarela, Jani, Pietiäinen, Vilja, Jäger, Natalie, Schlesner, Matthias, Kopp-Schneider, Annette, Oppermann, Sina, Milde, Till, Witt, Olaf, and Oehme, Ina
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- 2022
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19. Präzisionsonkologie und Phase-I/II-Netzwerke in der Kinderkrebsmedizin
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Nesper-Brock, Martina, Metzler, Markus, Reinhardt, Dirk, Rutkowski, Stefan, Thorwarth, Anne, van Tilburg, Cornelis M., Pfister, Stefan M., Schrappe, Martin, and Witt, Olaf
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- 2021
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20. Value of 18F-FDG PET/CT for predicting axillary pathologic complete response following neoadjuvant systemic therapy in breast cancer patients: emphasis on breast cancer subtype
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Cornelis M. de Mooij, Cristina Mitea, Felix M. Mottaghy, Marjolein L. Smidt, and Thiemo J. A. van Nijnatten
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Positron emission tomography/computed tomography ,Neoadjuvant systemic therapy ,Breast cancer ,Axillary lymph node metastases ,Response prediction ,Medical physics. Medical radiology. Nuclear medicine ,R895-920 - Abstract
Abstract Background Neoadjuvant systemic therapy (NST) is a widely accepted initial treatment modality that can lead to pathologic downstaging of the axillary disease burden in breast cancer patients. Axillary response as well as baseline 18F-fluorodeoxyglucose (18F-FDG) uptake on positron emission tomography with computed tomography (PET/CT) differ between breast cancer subtypes. The value of baseline 18F-FDG PET/CT in predicting axillary response to NST is not yet established, possibly since breast cancer subtype was not taken into account. The purpose of this study was to investigate the value of baseline 18F-FDG PET/CT in predicting axillary response to NST with a specific emphasis on subtype. Methods PET-parameters derived from the primary tumor as well as the most FDG-avid axillary lymph node were measured on baseline 18F-FDG PET/CT. Overall imaging findings were compared with the gold standard of histopathology of the axillary surgery specimen. Analyses for ER-positive/HER2-negative were performed separately from HER2-positive and TN patients. In addition, separate analyses for clinically node-positive patients were performed. Results Sixty-six patients with 69 primary tumors were included in this study. Thirty-three axillae contained ER-positive/HER2-negative, 16 HER2-positive, and 20 TN breast cancer. No significant difference in PET-parameters between patients with axillary residual disease and axillary pathologic complete response were found for ER-positive/HER2-negative breast cancer. In the combined HER2-positive/TN subgroup, the SUVmax was significantly lower in patients without residual axillary disease in both the entire cohort and in patients with clinically node-positive disease. In this combined subgroup, a cut-off of 4.89 SUVmax measured on the most FDG-avid axillary lymph node could predict residual axillary disease with a sensitivity, specificity, PPV, and NPV of 90%, 69%, 53%, and 95%, respectively. Conclusions Predicting axillary response following NST with baseline 18F-FDG PET/CT can be performed when focusing on breast cancer subtypes. The easily computed PET-parameter SUVmax can predict axillary response in HER2-positive and TN breast cancer. This study adds to the accumulating evidence that studies investigating the value of 18F-FDG PET/CT in breast cancer should always take subtypes into account.
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- 2021
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21. Influence of the gut and airway microbiome on asthma development and disease
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Smulders, Tamar, primary, Van Der Schee, Marc P., additional, Maitland‐Van Der Zee, Anke H., additional, Dikkers, Frederik G., additional, and Van Drunen, Cornelis M., additional
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- 2024
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22. Gene regulatory network landscape of Group 3/4 medulloblastoma
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Joshi, Piyush, primary, Stelzer, Tamina, additional, Okonechnikov, Konstantin, additional, Sarropoulos, Ioannis, additional, Sepp, Mari, additional, Pour-Jamnani, Mischan V., additional, Rademacher, Anne, additional, Yamada-Saito, Tetsuya, additional, Schneider, Céline, additional, Schmidt, Julia, additional, Schäfer, Philipp, additional, Leiss, Kevin, additional, Bortolomeazzi, Michele, additional, Mallm, Jan-Philipp, additional, da Silva, Patricia B.G., additional, Statz, Britta, additional, Wittmann, Andrea, additional, Schramm, Kathrin, additional, Blattner-Johnson, Mirjam, additional, Fiesel, Petra, additional, Jones, Barbara, additional, Milde, Till, additional, Pajtler, Kristian, additional, van Tilburg, Cornelis M., additional, Witt, Olaf, additional, Rippe, Karsten, additional, Korshunov, Andrey, additional, Jones, David T.W., additional, Hovestadt, Volker, additional, Northcott, Paul A., additional, Thongjuea, Supat, additional, Jäger, Natalie, additional, Kaessmann, Henrik, additional, Pfister, Stefan M., additional, and Kutscher, Lena M., additional
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- 2024
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23. Implementing data on targeted therapy from the INFORM registry platform for children with relapsed cancer in Sweden
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Wallin, Sofia, primary, Øra, Ingrid, additional, Prochazka, Gabriela, additional, Sandgren, Johanna, additional, Björklund, Caroline, additional, Ljungman, Gustaf, additional, Vogt, Hartmut, additional, Ek, Torben, additional, van Tilburg, Cornelis M., additional, and Nilsson, Anna, additional
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- 2024
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24. Radiation-induced gliomas represent H3-/IDH-wild type pediatric gliomas with recurrent PDGFRA amplification and loss of CDKN2A/B
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Maximilian Y. Deng, Dominik Sturm, Elke Pfaff, Martin Sill, Damian Stichel, Gnana Prakash Balasubramanian, Stephan Tippelt, Christof Kramm, Andrew M. Donson, Adam L. Green, Chris Jones, Jens Schittenhelm, Martin Ebinger, Martin U. Schuhmann, Barbara C. Jones, Cornelis M. van Tilburg, Andrea Wittmann, Andrey Golanov, Marina Ryzhova, Jonas Ecker, Till Milde, Olaf Witt, Felix Sahm, David Reuss, David Sumerauer, Josef Zamecnik, Andrey Korshunov, Andreas von Deimling, Stefan M. Pfister, and David T. W. Jones
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Science - Abstract
Radiation-induced gliomas (RIGs) have been reported in patients after treatment with cranial irradiation for various primary malignancies but their origin are still unclear. Here, the authors define the genomic, epigenetic and transcriptional landscape of 32 RIGs cases.
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- 2021
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25. Precision Medicine for More Oxygen (P4O2)—Study Design and First Results of the Long COVID-19 Extension
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Nadia Baalbaki, Jelle M. Blankestijn, Mahmoud I. Abdel-Aziz, Jan de Backer, Somayeh Bazdar, Inés Beekers, Rosanne J. H. C. G. Beijers, Joop P. van den Bergh, Lizan D. Bloemsma, Harm Jan Bogaard, Job J. M. H. van Bragt, Vera van den Brink, Jean Paul Charbonnier, Merel E. B. Cornelissen, Yennece Dagelet, Elin Haf Davies, Anne M. van der Does, George S. Downward, Cornelis M. van Drunen, Debbie Gach, J. J. Miranda Geelhoed, Jorrit Glastra, Kornel Golebski, Irene H. Heijink, Judith C. S. Holtjer, Sebastiaan Holverda, Laura Houweling, John J. L. Jacobs, Renée Jonker, Renate Kos, Ramon C. J. Langen, Ivo van der Lee, Asabi Leliveld, Firdaus A. A. Mohamed Hoesein, Anne H. Neerincx, Lieke Noij, Johan Olsson, Marianne van de Pol, Simon D. Pouwels, Emiel Rolink, Michael Rutgers, Havva Șahin, Daphne Schaminee, Annemie M. W. J. Schols, Lisanne Schuurman, Gitte Slingers, Olie Smeenk, Brigitte Sondermeijer, Paul J. Skipp, Marisca Tamarit, Inge Verkouter, Roel Vermeulen, Rianne de Vries, Els J. M. Weersink, Marco van de Werken, Yolanda de Wit-van Wijck, Stewart Young, Esther J. Nossent, and Anke H. Maitland-van der Zee
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precision medicine ,long COVID ,infectious disease ,prospective observational cohort study ,Medicine - Abstract
Introduction: The coronavirus disease 2019 (COVID-19) pandemic has led to the death of almost 7 million people, however, with a cumulative incidence of 0.76 billion, most people survive COVID-19. Several studies indicate that the acute phase of COVID-19 may be followed by persistent symptoms including fatigue, dyspnea, headache, musculoskeletal symptoms, and pulmonary functional-and radiological abnormalities. However, the impact of COVID-19 on long-term health outcomes remains to be elucidated. Aims: The Precision Medicine for more Oxygen (P4O2) consortium COVID-19 extension aims to identify long COVID patients that are at risk for developing chronic lung disease and furthermore, to identify treatable traits and innovative personalized therapeutic strategies for prevention and treatment. This study aims to describe the study design and first results of the P4O2 COVID-19 cohort. Methods: The P4O2 COVID-19 study is a prospective multicenter cohort study that includes nested personalized counseling intervention trial. Patients, aged 40–65 years, were recruited from outpatient post-COVID clinics from five hospitals in The Netherlands. During study visits at 3–6 and 12–18 months post-COVID-19, data from medical records, pulmonary function tests, chest computed tomography scans and biological samples were collected and questionnaires were administered. Furthermore, exposome data was collected at the patient’s home and state-of-the-art imaging techniques as well as multi-omics analyses will be performed on collected data. Results: 95 long COVID patients were enrolled between May 2021 and September 2022. The current study showed persistence of clinical symptoms and signs of pulmonary function test/radiological abnormalities in post-COVID patients at 3–6 months post-COVID. The most commonly reported symptoms included respiratory symptoms (78.9%), neurological symptoms (68.4%) and fatigue (67.4%). Female sex and infection with the Delta, compared with the Beta, SARS-CoV-2 variant were significantly associated with more persisting symptom categories. Conclusions: The P4O2 COVID-19 study contributes to our understanding of the long-term health impacts of COVID-19. Furthermore, P4O2 COVID-19 can lead to the identification of different phenotypes of long COVID patients, for example those that are at risk for developing chronic lung disease. Understanding the mechanisms behind the different phenotypes and identifying these patients at an early stage can help to develop and optimize prevention and treatment strategies.
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- 2023
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26. Child Abuse, Misdiagnosed by an Expertise Center: Part I—Medico-Social Aspects
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Marianne Vlaming, Pieter J. J. Sauer, Emile P. F. Janssen, Peter J. van Koppen, Cornelis M. A. Bruijninckx, Marga W. M. Akkerman-Zaalberg van Zelst, H. A. Martino Neumann, and Martin J. C. van Gemert
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infant bruises and rib fractures ,Dutch expertise center for child abuse ,diagnostic error ,misdiagnosed child abuse ,medical and social aspects ,foster care placement ,Pediatrics ,RJ1-570 - Abstract
Child abuse is a dangerous situation for an infant. Professionals need to weigh the risk of failing to act when children are seriously harmed against the serious harm done by carrying out safeguarding interventions. In severe cases, foster care might be advisable. The negative effects for the child’s psychosocial development requires that such placement must be based on very solid evidence. Our aim is to identify why Dutch parents whose child may have a medical condition that could mimic symptoms of child abuse have a significant chance of being erroneously convicted and losing custody of their child. As a method, we describe and analyze the following case. An Armenian-Dutch newborn (uncomplicated term vaginal delivery), starting at two weeks after birth, developed small bruises on varying body locations. At two months, a Well-Baby Clinic physician referred the girl to a university hospital, mentioning that there were no reasons to suspect child abuse and that her Armenian grandmother easily bruised as well. However, before consultation by a pediatrician of the hospital-located Expertise Center for Child Abuse, the parents were suspected of child abuse. Based on the expertise center’s protocols, skeletal X-rays were made, which showed three healed, asymptomatic rib fractures, while invalid statistics suggested, incorrectly, a 10–100 times more likely non-accidental than accidental cause of the symptoms (discussed in Part II of this series). The expertise enter physician ignored any argument that could show parental innocence, including the positive parent-child relationship reported by the Well-Baby Clinic and the general practitioner. The girl and her older brother were placed in a family foster home and then in a secret home. The case radically resolved when a large bruise also developed there, and an independent tissue disease specialist diagnosed a hereditary connective tissue disorder in the mother, implying that the girl’s bruises and rib fractures could well be disease-related. In conclusion, if child abuse is suspected, and foster care placement considered, the patient and the parents should be thoroughly investigated by an independent experienced pediatrician together with an experienced pediatric clinical psychologist or psychotherapist to produce an independent opinion. Children deserve this extra safeguard before being separated from their parents.
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- 2023
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27. Prediction of Primary Tumour and Axillary Lymph Node Response to Neoadjuvant Chemo(Targeted) Therapy with Dedicated Breast [18F]FDG PET/MRI in Breast Cancer
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Cornelis M. de Mooij, Thiemo J. A. van Nijnatten, Briete Goorts, Loes F. S. Kooreman, Isabel W. M. Raymakers, Silke P. L. van Meijl, Maaike de Boer, Kristien B. M. I. Keymeulen, Joachim E. Wildberger, Felix M. Mottaghy, Marc B. I. Lobbes, and Marjolein L. Smidt
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breast neoplasms ,fluorodeoxyglucose F18 ,positron emission tomography ,magnetic resonance imaging ,neoadjuvant therapy ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Background: The aim of this study was to investigate whether sequential hybrid [18F]FDG PET/MRI can predict the final pathologic response to neoadjuvant chemo(targeted) therapy (NCT) in breast cancer. Methods: Sequential [18F]FDG PET/MRI was performed before, halfway through and after NCT, followed by surgery. Qualitative response evaluation was assessed after NCT. Quantitatively, the SUVmax obtained by [18F]FDG PET and signal enhancement ratio (SER) obtained by MRI were determined sequentially on the primary tumour. For the response of axillary lymph node metastases (ALNMs), SUVmax was determined sequentially on the most [18F]FDG-avid ALN. ROC curves were generated to determine the optimal cut-off values for the absolute and percentage change in quantitative variables in predicting response. Diagnostic performance in predicting primary tumour response was assessed with AUC. Similar analyses were performed in clinically node-positive (cN+) patients for ALNM response. Results: Forty-one breast cancer patients with forty-two primary tumours and twenty-six cases of pathologically proven cN+ disease were prospectively included. Pathologic complete response (pCR) of the primary tumour occurred in 16 patients and pCR of the ALNMs in 14 cN+ patients. The AUC of the qualitative evaluation after NCT was 0.71 for primary tumours and 0.54 for ALNM responses. For primary tumour response, combining the percentage decrease in SUVmax and SER halfway through NCT achieved an AUC of 0.78. The AUC for ALNM response prediction increased to 0.92 by combining the absolute and the percentage decrease in SUVmax halfway through NCT. Conclusions: Qualitative PET/MRI after NCT can predict the final pathologic primary tumour response, but not the ALNM response. Combining quantitative variables halfway through NCT can improve the diagnostic accuracy for final pathologic ALNM response prediction.
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- 2023
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28. Compressed Prostate Cancer Cells Decrease Osteoclast Activity While Enhancing Osteoblast Activity In Vitro
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Victor J. B. van Santen, Behrouz Zandieh Doulabi, Cornelis M. Semeins, Jolanda M. A. Hogervorst, Cornelia Bratengeier, and Astrid D. Bakker
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bone metastasis ,bone remodeling ,epithelial-to-mesenchymal transition ,pressure ,adipose tissue-derived mesenchymal stromal cell ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Once prostate cancer cells metastasize to bone, they perceive approximately 2 kPa compression. We hypothesize that 2 kPa compression stimulates the epithelial-to-mesenchymal transition (EMT) of prostate cancer cells and alters their production of paracrine signals to affect osteoclast and osteoblast behavior. Human DU145 prostate cancer cells were subjected to 2 kPa compression for 2 days. Compression decreased expression of 2 epithelial genes, 5 out of 13 mesenchymal genes, and increased 2 mesenchymal genes by DU145 cells, as quantified by qPCR. Conditioned medium (CM) of DU145 cells was added to human monocytes that were stimulated to differentiate into osteoclasts for 21 days. CM from compressed DU145 cells decreased osteoclast resorptive activity by 38% but did not affect osteoclast size and number compared to CM from non-compressed cells. CM was also added to human adipose stromal cells, grown in osteogenic medium. CM of compressed DU145 cells increased bone nodule production (Alizarin Red) by osteoblasts from four out of six donors. Compression did not affect IL6 or TNF-α production by PC DU145 cells. Our data suggest that compression affects EMT-related gene expression in DU145 cells, and alters their production of paracrine signals to decrease osteoclast resorptive activity while increasing mineralization by osteoblasts is donor dependent. This observation gives further insight in the altered behavior of PC cells upon mechanical stimuli, which could provide novel leads for therapies, preventing bone metastases.
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- 2023
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29. Diagnostik und Therapie von Tumoren mit NTRK-Genfusionen
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Stenzinger, Albrecht, van Tilburg, Cornelis M., Tabatabai, Ghazaleh, Länger, Florian, Graf, Norbert, Griesinger, Frank, Heukamp, Lukas C., Hummel, Michael, Klingebiel, Thomas, Hettmer, Simone, Vokuhl, Christian, Merkelbach-Bruse, Sabine, Overkamp, Friedrich, Reichardt, Peter, Scheer, Monika, Weichert, Wilko, Westphalen, C. Benedikt, Bokemeyer, Carsten, Ivanyi, Philipp, Loges, Sonja, Schirmacher, Peter, Wörmann, Bernhard, Bielack, Stefan, and Seufferlein, Thomas T. W.
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- 2021
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30. Novel loci associated with usual sleep duration: the CHARGE Consortium Genome-Wide Association Study
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Gottlieb, DJ, Hek, K, Chen, T-H, Watson, NF, Eiriksdottir, G, Byrne, EM, Cornelis, M, Warby, SC, Bandinelli, S, Cherkas, L, Evans, DS, Grabe, HJ, Lahti, J, Li, M, Lehtimäki, T, Lumley, T, Marciante, KD, Pérusse, L, Psaty, BM, Robbins, J, Tranah, GJ, Vink, JM, Wilk, JB, Stafford, JM, Bellis, C, Biffar, R, Bouchard, C, Cade, B, Curhan, GC, Eriksson, JG, Ewert, R, Ferrucci, L, Fülöp, T, Gehrman, PR, Goodloe, R, Harris, TB, Heath, AC, Hernandez, D, Hofman, A, Hottenga, J-J, Hunter, DJ, Jensen, MK, Johnson, AD, Kähönen, M, Kao, L, Kraft, P, Larkin, EK, Lauderdale, DS, Luik, AI, Medici, M, Montgomery, GW, Palotie, A, Patel, SR, Pistis, G, Porcu, E, Quaye, L, Raitakari, O, Redline, S, Rimm, EB, Rotter, JI, Smith, AV, Spector, TD, Teumer, A, Uitterlinden, AG, Vohl, M-C, Widen, E, Willemsen, G, Young, T, Zhang, X, Liu, Y, Blangero, J, Boomsma, DI, Gudnason, V, Hu, F, Mangino, M, Martin, NG, O'Connor, GT, Stone, KL, Tanaka, T, Viikari, J, Gharib, SA, Punjabi, NM, Räikkönen, K, Völzke, H, Mignot, E, and Tiemeier, H
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Biomedical and Clinical Sciences ,Clinical Sciences ,Mental Health ,Sleep Research ,Clinical Research ,Brain Disorders ,Genetics ,Human Genome ,2.1 Biological and endogenous factors ,Aetiology ,Good Health and Well Being ,Adult ,Black or African American ,Aged ,Dyssomnias ,Female ,Genetic Association Studies ,Genome-Wide Association Study ,Humans ,Male ,Middle Aged ,Polymorphism ,Single Nucleotide ,Self Report ,Sleep ,White People ,Biological Sciences ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Psychiatry ,Clinical sciences ,Biological psychology ,Clinical and health psychology - Abstract
Usual sleep duration is a heritable trait correlated with psychiatric morbidity, cardiometabolic disease and mortality, although little is known about the genetic variants influencing this trait. A genome-wide association study (GWAS) of usual sleep duration was conducted using 18 population-based cohorts totaling 47 180 individuals of European ancestry. Genome-wide significant association was identified at two loci. The strongest is located on chromosome 2, in an intergenic region 35- to 80-kb upstream from the thyroid-specific transcription factor PAX8 (lowest P=1.1 × 10(-9)). This finding was replicated in an African-American sample of 4771 individuals (lowest P=9.3 × 10(-4)). The strongest combined association was at rs1823125 (P=1.5 × 10(-10), minor allele frequency 0.26 in the discovery sample, 0.12 in the replication sample), with each copy of the minor allele associated with a sleep duration 3.1 min longer per night. The alleles associated with longer sleep duration were associated in previous GWAS with a more favorable metabolic profile and a lower risk of attention deficit hyperactivity disorder. Understanding the mechanisms underlying these associations may help elucidate biological mechanisms influencing sleep duration and its association with psychiatric, metabolic and cardiovascular disease.
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- 2015
31. INFORM2 NivEnt: The first trial of the INFORM2 biomarker driven phase I/II trial series: the combination of nivolumab and entinostat in children and adolescents with refractory high-risk malignancies
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Cornelis M. van Tilburg, Ruth Witt, Melanie Heiss, Kristian W. Pajtler, Christoph Plass, Isabel Poschke, Michael Platten, Inga Harting, Oliver Sedlaczek, Angelika Freitag, David Meyrath, Lenka Taylor, Gnana Prakash Balasubramanian, Natalie Jäger, Elke Pfaff, Barbara C. Jones, Till Milde, Stefan M. Pfister, David T. W. Jones, Annette Kopp-Schneider, and Olaf Witt
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Entinostat ,Nivolumab ,Child ,Bayesian design ,Biomarker ,Phase I/II ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Pediatric patients with relapsed or refractory disease represent a population with a desperate medical need. The aim of the INFORM (INdividualized Therapy FOr Relapsed Malignancies in Childhood) program is to translate next generation molecular diagnostics into a biomarker driven treatment strategy. The program consists of two major foundations: the INFORM registry providing a molecular screening platform and the INFORM2 series of biomarker driven phase I/II trials. The INFORM2 NivEnt trial aims to determine the recommended phase 2 dose (RP2D) of the combination treatment of nivolumab and entinostat (phase I) and to evaluate activity and safety (phase II). Methods This is an exploratory non-randomized, open-label, multinational and multicenter seamless phase I/II trial in children and adolescents with relapsed / refractory or progressive high-risk solid tumors and CNS tumors. The phase I is divided in 2 age cohorts: 12–21 years and 6–11 years and follows a 3 + 3 design with two dose levels for entinostat (2 mg/m2 and 4 mg/m2 once per week) and fixed dose nivolumab (3 mg/kg every 2 weeks). Patients entering the trial on RP2D can seamlessly enter phase II which consists of a biomarker defined four group basket trial: high mutational load (group A), high PD-L1 mRNA expression (group B), focal MYC(N) amplification (group C), low mutational load and low PD-L1 mRNA expression and no MYC(N) amplification (group D). A Bayesian adaptive design will be used to early stop cohorts that fail to show evidence of activity. The maximum number of patients is 128. Discussion This trial intends to exploit the immune enhancing effects of entinostat on nivolumab using an innovative biomarker driven approach in order to maximize the chance of detecting signs of activity. It prevents exposure to unnecessary risks by applying the Bayesian adaptive design for early stopping for futility. The adaptive biomarker driven design provides an innovative approach accelerating drug development and reducing exposure to investigational treatments in these vulnerable children at the same time. Trial registration ClinicalTrials.gov, NCT03838042 . Registered on 12 February 2019.
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- 2020
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32. Radiation-induced gliomas represent H3-/IDH-wild type pediatric gliomas with recurrent PDGFRA amplification and loss of CDKN2A/B
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Deng, Maximilian Y., Sturm, Dominik, Pfaff, Elke, Sill, Martin, Stichel, Damian, Balasubramanian, Gnana Prakash, Tippelt, Stephan, Kramm, Christof, Donson, Andrew M., Green, Adam L., Jones, Chris, Schittenhelm, Jens, Ebinger, Martin, Schuhmann, Martin U., Jones, Barbara C., van Tilburg, Cornelis M., Wittmann, Andrea, Golanov, Andrey, Ryzhova, Marina, Ecker, Jonas, Milde, Till, Witt, Olaf, Sahm, Felix, Reuss, David, Sumerauer, David, Zamecnik, Josef, Korshunov, Andrey, von Deimling, Andreas, Pfister, Stefan M., and Jones, David T. W.
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- 2021
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33. Value of 18F-FDG PET/CT for predicting axillary pathologic complete response following neoadjuvant systemic therapy in breast cancer patients: emphasis on breast cancer subtype
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de Mooij, Cornelis M., Mitea, Cristina, Mottaghy, Felix M., Smidt, Marjolein L., and van Nijnatten, Thiemo J. A.
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- 2021
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34. The Social and Local Dimensions of Governance of Energy Poverty: Adaptive Responses to State Remoteness
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Creutzfeldt, N., Gill, C., McPherson, R., and Cornelis, M.
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- 2020
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35. Response to trametinib treatment in progressive pediatric low-grade glioma patients
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Selt, Florian, van Tilburg, Cornelis M., Bison, Brigitte, Sievers, Philipp, Harting, Inga, Ecker, Jonas, Pajtler, Kristian W., Sahm, Felix, Bahr, Annabelle, Simon, Michèle, Jones, David T. W., Well, Lennart, Mautner, Victor-Felix, Capper, David, Hernáiz Driever, Pablo, Gnekow, Astrid, Pfister, Stefan M., Witt, Olaf, and Milde, Till
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- 2020
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36. Biologicals in childhood severe asthma: the European PERMEABLE survey on the status quo
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Elisangela Santos-Valente, Heike Buntrock-Döpke, Rola Abou Taam, Stefania Arasi, Arzu Bakirtas, Jaime Lozano Blasco, Klaus Bønnelykke, Mihai Craiu, Renato Cutrera, Antoine Deschildre, Basil Elnazir, Louise Fleming, Urs Frey, Monika Gappa, Antonio Nieto García, Kirsten Skamstrup Hansen, Laurence Hanssens, Karina Jahnz-Rozyk, Milos Jesenak, Sebastian Kerzel, Matthias V. Kopp, Gerard H. Koppelman, Uros Krivec, Kenneth A. MacLeod, Mika Mäkelä, Erik Melén, Györgyi Mezei, Alexander Moeller, Andre Moreira, Petr Pohunek, Predrag Minić, Niels W.P. Rutjes, Patrick Sammut, Nicolaus Schwerk, Zsolt Szépfalusi, Mirjana Turkalj, Iren Tzotcheva, Alexandru Ulmeanu, Stijn Verhulst, Paraskevi Xepapadaki, Jakob Niggel, Susanne Vijverberg, Anke H. Maitland-van der Zee, Uroš Potočnik, Susanne M. Reinartz, Cornelis M. van Drunen, and Michael Kabesch
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Medicine - Abstract
Introduction Severe asthma is a rare disease in children, for which three biologicals, anti-immunoglobulin E, anti-interleukin-5 and anti-IL4RA antibodies, are available in European countries. While global guidelines exist on who should receive biologicals, knowledge is lacking on how those guidelines are implemented in real life and which unmet needs exist in the field. In this survey, we aimed to investigate the status quo and identify open questions in biological therapy of childhood asthma across Europe. Methods Structured interviews regarding experience with biologicals, regulations on access to the different treatment options, drug selection, therapy success and discontinuation of therapy were performed. Content analysis was used to analyse data. Results We interviewed 37 experts from 25 European countries and Turkey and found a considerable range in the number of children treated with biologicals per centre. All participating countries provide public access to at least one biological. Most countries allow different medical disciplines to prescribe biologicals to children with asthma, and only a few restrict therapy to specialised centres. We observed significant variation in the time point at which treatment success is assessed, in therapy duration and in the success rate of discontinuation. Most participating centres intend to apply a personalised medicine approach in the future to match patients a priori to available biologicals. Conclusion Substantial differences exist in the management of childhood severe asthma across Europe, and the need for further studies on biomarkers supporting selection of biologicals, on criteria to assess therapy response and on how/when to end therapy in stable patients is evident.
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- 2021
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37. Measurement of the Pitch Exploration Amongst Elite Professional Soccer Players: Official Match Analysis.
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Filipe Manuel Clemente, Adam Owen, Aida Mustapha, Cornelis M. I. (Niels) van der Linden, João Ribeiro, Bruno Mendes, and Jelle Reichert
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- 2018
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38. Measurement of the Pitch Exploration Amongst Elite Professional Soccer Players: Official Match Analysis
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Clemente, Filipe Manuel, Owen, Adam, Mustapha, Aida, van der Linden, Cornelis M. I. (Niels), Ribeiro, João, Mendes, Bruno, Reichert, Jelle, Kacprzyk, Janusz, Series editor, Pal, Nikhil R., Advisory editor, Bello Perez, Rafael, Advisory editor, Corchado, Emilio S., Advisory editor, Hagras, Hani, Advisory editor, Kóczy, László T., Advisory editor, Kreinovich, Vladik, Advisory editor, Lin, Chin-Teng, Advisory editor, Lu, Jie, Advisory editor, Melin, Patricia, Advisory editor, Nedjah, Nadia, Advisory editor, Nguyen, Ngoc Thanh, Advisory editor, Wang, Jun, Advisory editor, Ghazali, Rozaida, editor, Deris, Mustafa Mat, editor, Nawi, Nazri Mohd, editor, and Abawajy, Jemal H., editor
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- 2018
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39. Space-quality data from balloon-borne telescopes: the High Altitude Lensing Observatory (HALO)
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Rhodes, Jason, Dobke, Benjamin, Booth, Jeffrey, Massey, Richard, Liewer, Kurt, Smith, Roger, Amara, Adam, Aldrich, Jack, Berge, Joel, Bezawada, Naidu, Brugarolas, Paul, Clark, Paul, Dubbeldam, Cornelis M., Ellis, Richard, Frenk, Carlos, Gallie, Angus, Heavens, Alan, Henry, David, Jullo, Eric, Kitching, Thomas, Lanzi, James, Lilly, Simon, Lunney, David, Miyazaki, Satoshi, Morris, David, Paine, Christopher, Peacock, John, Pellegrino, Sergio, Pittock, Roger, Pool, Peter, Refregier, Alexandre, Seiffert, Michael, Sharples, Ray, Smith, Alexandra, Stuchlik, David, Taylor, Andy, Teplitz, Harry, Vanderveld, R. Ali, and Wu, James
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Astrophysics - Instrumentation and Methods for Astrophysics ,Astrophysics - Cosmology and Nongalactic Astrophysics - Abstract
We present a method for attaining sub-arcsecond pointing stability during sub- orbital balloon flights, as designed for in the High Altitude Lensing Observatory (HALO) concept. The pointing method presented here has the potential to perform near-space quality optical astronomical imaging at 1-2% of the cost of space-based missions. We also discuss an architecture that can achieve sufficient thermomechanical stability to match the pointing stability. This concept is motivated by advances in the development and testing of Ultra Long Duration Balloon (ULDB) flights which promise to allow observation campaigns lasting more than three months. The design incorporates a multi-stage pointing architecture comprising: a gondola coarse azimuth control system, a multi-axis nested gimbal frame structure with arcsecond stability, a telescope de-rotator to eliminate field rotation, and a fine guidance stage consisting of both a telescope mounted angular rate sensor and guide CCDs in the focal plane to drive a fast-steering mirror. We discuss the results of pointing tests together with a preliminary thermo-mechanical analysis required for sub-arcsecond pointing at high altitude. Possible future applications in the areas of wide-field surveys and exoplanet searches are also discussed., Comment: 26 pages and 7 figures; to appear in Astroparticle Physics
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- 2012
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40. Precision Medicine for Childhood Cancer: Current Limitations and Future Perspectives.
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McCabe, Martin G., Geoerger, Birgit, Chesler, Louis, Hargrave, Darren, Parsons, D. Williams, van Tilburg, Cornelis M., Schleiermacher, Gudrun, Hickman, John A., and George, Sally L.
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CHILDHOOD cancer ,INDIVIDUALIZED medicine - Abstract
Greater collaboration needed to realize potential of molecular profiling initiatives for pediatric cancers. [ABSTRACT FROM AUTHOR]
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- 2024
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41. Outcome of Children and Adolescents With Relapsed/Refractory/Progressive Malignancies Treated With Molecularly Informed Targeted Drugs in the Pediatric Precision Oncology Registry INFORM
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Heipertz, Anna-Elisa, primary, Pajtler, Kristian W., additional, Pfaff, Elke, additional, Schramm, Kathrin, additional, Blattner-Johnson, Mirjam, additional, Milde, Till, additional, Jones, Barbara C., additional, Zuliani, Cecilia, additional, Hutter, Caroline, additional, Lohi, Olli, additional, Kattamis, Antonis, additional, Dachowska-Kalwak, Iwona, additional, Nilsson, Anna, additional, Gerber, Nicolas U., additional, Langenberg, Karin P.S., additional, Goemans, Bianca F., additional, Zwaan, C. Michel, additional, Molenaar, Jan J., additional, Jäger, Natalie, additional, Dirksen, Uta, additional, Witt, Ruth, additional, Pfister, Stefan M., additional, Jones, David T.W., additional, Kopp-Schneider, Annette, additional, Witt, Olaf, additional, and van Tilburg, Cornelis M., additional
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- 2023
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42. IL-1β, IL-23, and TGF-β drive plasticity of human ILC2s towards IL-17-producing ILCs in nasal inflammation
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Korneliusz Golebski, Xavier R. Ros, Maho Nagasawa, Sophie van Tol, Balthasar A. Heesters, Hajar Aglmous, Chantal M. A. Kradolfer, Medya M. Shikhagaie, Sven Seys, P. W. Hellings, Cornelis M. van Drunen, Wytske J. Fokkens, Hergen Spits, and Suzanne M. Bal
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Science - Abstract
Innate lymphoid cells (ILCs) play critical immunological roles including immune surveillance at mucosal sites. Here the authors show that during nasal inflammation pathogen-induced cytokine production guides the differentiation of ILCs.
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- 2019
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43. Safety and efficacy of mTOR inhibitor treatment in patients with tuberous sclerosis complex under 2 years of age – a multicenter retrospective study
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Afshin Saffari, Ines Brösse, Adelheid Wiemer-Kruel, Bernd Wilken, Paula Kreuzaler, Andreas Hahn, Matthias K. Bernhard, Cornelis M. van Tilburg, Georg F. Hoffmann, Matthias Gorenflo, Sven Hethey, Olaf Kaiser, Stefan Kölker, Robert Wagner, Olaf Witt, Andreas Merkenschlager, Andreas Möckel, Timo Roser, Jan-Ulrich Schlump, Antje Serfling, Juliane Spiegler, Till Milde, Andreas Ziegler, and Steffen Syrbe
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Tuberous sclerosis complex ,mTOR inhibitor ,Everolimus ,Children ,Neonates ,Medicine - Abstract
Abstract Background Tuberous sclerosis complex (TSC) is a multisystem disease with prominent neurologic manifestations such as epilepsy, cognitive impairment and autism spectrum disorder. mTOR inhibitors have successfully been used to treat TSC-related manifestations in older children and adults. However, data on their safety and efficacy in infants and young children are scarce. The objective of this study is to assess the utility and safety of mTOR inhibitor treatment in TSC patients under the age of 2 years. Results A total of 17 children (median age at study inclusion 2.4 years, range 0–6; 12 males, 5 females) with TSC who received early mTOR inhibitor therapy were studied. mTOR inhibitor treatment was started at a median age of 5 months (range 0–19 months). Reasons for initiation of treatment were cardiac rhabdomyomas (6 cases), subependymal giant cell astrocytomas (SEGA, 5 cases), combination of cardiac rhabdomyomas and SEGA (1 case), refractory epilepsy (4 cases) and disabling congenital focal lymphedema (1 case). In all cases everolimus was used. Everolimus therapy was overall well tolerated. Adverse events were classified according to the Common Terminology Criteria of Adverse Events (CTCAE, Version 5.0). Grade 1–2 adverse events occurred in 12 patients and included mild transient stomatitis (2 cases), worsening of infantile acne (1 case), increases of serum cholesterol and triglycerides (4 cases), changes in serum phosphate levels (2 cases), increase of cholinesterase (2 cases), transient neutropenia (2 cases), transient anemia (1 case), transient lymphopenia (1 case) and recurrent infections (7 cases). No grade 3–4 adverse events were reported. Treatment is currently continued in 13/17 patients. Benefits were reported in 14/17 patients and included decrease of cardiac rhabdomyoma size and improvement of arrhythmia, decrease of SEGA size, reduction of seizure frequency and regression of congenital focal lymphedema. Despite everolimus therapy, two patients treated for intractable epilepsy are still experiencing seizures and another one treated for SEGA showed no volume reduction. Conclusion This retrospective multicenter study demonstrates that mTOR inhibitor treatment with everolimus is safe in TSC patients under the age of 2 years and shows beneficial effects on cardiac manifestations, SEGA size and early epilepsy.
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- 2019
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44. Performance of polygenic scores for predicting phobic anxiety
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Glymour, Medellena, Walter, S, Glymour, MM, Koenen, K, Liang, L, Tchetgen, EJ, Cornelis, M, Chang, SC, Rimm, E, Kawachi, I, and Kubzansky, LD
- Abstract
Context: Anxiety disorders are common, with a lifetime prevalence of 20% in the U.S., and are responsible for substantial burdens of disability, missed work days and health care utilization. To date, no causal genetic variants have been identified for anxi
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- 2013
45. An audit of radiation doses received by paediatric patients undergoing computed tomography investigations at academic hospitals in South Africa
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Cornelis M. van der Merwe and Nasreen Mahomed
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radiation dose ,computed tomography (ct) ,paediatric patients ,diagnostic reference level (drl) ,computed tomography dose indexvolume (ctdivolume) ,Medical physics. Medical radiology. Nuclear medicine ,R895-920 - Abstract
Background: Diagnostic reference levels (DRLs) are a crucial element of auditing radiation doses in paediatric computed tomography (CT). Currently, there are no national paediatric CT DRLs in South Africa. Objectives: The aim of this article was to establish local paediatric DRLs for CT examinations at two academic hospitals and to compare paediatric CT radiation output levels with established DRLs in the developed and developing world. Method: Computed Tomography Dose Indexvolume (CTDIvol) and dose length product (DLP) values were collected from CT examinations performed at two university hospitals for patients aged 0–15 years, during 01 November 2016–30 April 2017. The 75th percentile of the data distribution was calculated for each CT examination type and age group, further categorised into routine working hours and after-hours for both hospitals and statistically compared. Results: Of the 1031 CT examinations performed, CT brain examination was the most common (755/1031; 72.23%). DLP values were increased in the after-hours categories compared to regular working hours at both hospitals. The largest increase was in the 0–1 year age group (150.56%). With the exception of CT Chest and CT abdomen in the 0–1 year age group, the CTDIvol and DLP values compared favourably to international standards. Conclusion: Most of the calculated DRLs are acceptable and internationally comparable. This likely indicates effective reduction techniques and protocols. Computed tomography body examination protocols for 0–1 year patients should be reviewed. Strategies should be implemented to limit higher doses in after-hours examinations.
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- 2020
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46. Limitations of Weight Velocity Analysis by Commercial Computer Program Growth Analyser Viewer Edition
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van Gemert, Martin J. C., Bruijninckx, Cornelis M. A., van Leeuwen, Ton G., Neumann, H. A. Martino, and Sauer, Pieter J. J.
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- 2019
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47. Informed Conditioning on Clinical Covariates Increases Power in Case-Control Association Studies
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Pasaniuc, Bogdan, Zaitlen, Noah, Lindström, S, Cornelis, M, Genovese, G, Pollack, S, Barton, A, Bickeböller, H, Bowden, DW, and Eyre, S
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Genetic case-control association studies often include data on clinical covariates, such as body mass index (BMI), smoking status, or age, that may modify the underlying genetic risk of case or control samples. For example, in type 2 diabetes, odds ratios
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- 2012
48. Mechanical Loading Differentially Affects Osteocytes in Fibulae from Lactating Mice Compared to Osteocytes in Virgin Mice: Possible Role for Lacuna Size
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Hemmatian, Haniyeh, Jalali, Rozita, Semeins, Cornelis M., Hogervorst, Jolanda M. A., van Lenthe, G. Harry, Klein-Nulend, Jenneke, and Bakker, Astrid D.
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- 2018
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49. NTRK Alterations in Pediatric High-Risk Malignancies Identified Through European Clinical Sequencing Programs Constitute Promising Drug Targets
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Pfaff, Elke, Adam de Beaumais, Tiphaine, Marchais, Antonin, van Tilburg, Cornelis M., Blattner-Johnson, Mirjam, Dirksen, Uta, Øra, Ingrid, Geoerger, Birgit, Schleiermacher, Gudrun, Pfister, Stefan M., Witt, Stefan M., Jones, David T. W., and Vassal, Gilles
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- 2021
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50. Implementation of paediatric precision oncology into clinical practice: The Individualized Therapies for Children with cancer program ‘iTHER’
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Langenberg, Karin P.S., Meister, Michael T., Bakhuizen, Jette J., Boer, Judith M., van Eijkelenburg, Natasha K.A., Hulleman, Esther, Ilan, Uri, Looze, Eleonora J., Dierselhuis, Miranda P., van der Lugt, Jasper, Breunis, Willemijn, Schild, Linda G., Ober, Kimberley, van Hooff, Sander R., Scheijde-Vermeulen, Marijn A., Hiemcke-Jiwa, Laura S., Flucke, Uta E., Kranendonk, Mariette E.G., Wesseling, Pieter, Sonneveld, Edwin, Punt, Simone, Boltjes, Arjan, van Dijk, Freerk, Verwiel, Eugene T.P., Volckmann, Richard, Hehir-Kwa, Jayne Y., Kester, Lennart A., Koudijs, Marco M.J., Waanders, Esme, Holstege, Frank C.P., Vormoor, H. Josef, Hoving, Eelco W., van Noesel, Max M., Pieters, Rob, Kool, Marcel, Stumpf, Miriam, Blattner-Johnson, Mirjam, Balasubramanian, Gnana P., Van Tilburg, Cornelis M., Jones, Barbara C., Jones, David T.W., Witt, Olaf, Pfister, Stefan M., Jongmans, Marjolijn C.J., Kuiper, Roland P., de Krijger, Ronald R., Wijnen, Marc H.W., den Boer, Monique L., Zwaan, C. Michel, Kemmeren, Patrick, Koster, Jan, Tops, Bastiaan B.J., Goemans, Bianca F., Molenaar, Jan J., Dep Scheikunde, Afd Pharmaceutics, Pharmaceutics, Dep Scheikunde, Afd Pharmaceutics, Pharmaceutics, Center of Experimental and Molecular Medicine, Oncogenomics, and CCA - Cancer Treatment and Quality of Life
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Cancer Research ,Adolescent ,Molecular biology ,Precision medicine ,High-Throughput Nucleotide Sequencing ,Medical Oncology ,Hereditary ,Oncology ,Neoplasms ,Mutation ,Exome Sequencing ,Next-generation sequencing ,Humans ,Molecular targeted therapy ,Prospective Studies ,Child ,Cancer - Abstract
iTHER is a Dutch prospective national precision oncology program aiming to define tumour molecular profiles in children and adolescents with primary very high-risk, relapsed, or refractory paediatric tumours. Between April 2017 and April 2021, 302 samples from 253 patients were included. Comprehensive molecular profiling including low-coverage whole genome sequencing (lcWGS), whole exome sequencing (WES), RNA sequencing (RNA-seq), Affymetrix, and/or 850k methylation profiling was successfully performed for 226 samples with at least 20% tumour content. Germline pathogenic variants were identified in 16% of patients (35/219), of which 22 variants were judged causative for a cancer predisposition syndrome. At least one somatic alteration was detected in 204 (90.3%), and 185 (81.9%) were considered druggable, with clinical priority very high (6.1%), high (21.3%), moderate (26.0%), intermediate (36.1%), and borderline (10.5%) priority. iTHER led to revision or refinement of diagnosis in 8 patients (3.5%). Temporal heterogeneity was observed in paired samples of 15 patients, indicating the value of sequential analyses. Of 137 patients with follow-up beyond twelve months, 21 molecularly matched treatments were applied in 19 patients (13.9%), with clinical benefit in few. Most relevant barriers to not applying targeted therapies included poor performance status, as well as limited access to drugs within clinical trial. iTHER demonstrates the feasibility of comprehensive molecular profiling across all ages, tumour types and stages in paediatric cancers, informing of diagnostic, prognostic, and targetable alterations as well as reportable germline variants. Therefore, WES and RNA-seq is nowadays standard clinical care at the Princess Máxima Center for all children with cancer, including patients at primary diagnosis. Improved access to innovative treatments within biology-driven combination trials is required to ultimately improve survival.
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- 2022
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