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1. Potential added value of combined DPYD/DPD genotyping and phenotyping to prevent severe toxicity in patients with a DPYD variant and decreased dihydropyrimidine dehydrogenase enzyme activity

Author

Ockeloen, C.W., Raaijmakers, A., Hijmans-van der Vegt, M., Bierau, J., Vos-Geelen, J. de, Willemsen, A.E.C.A.B., Bosch, B.J. van den, Coenen, M.J.H., Ockeloen, C.W., Raaijmakers, A., Hijmans-van der Vegt, M., Bierau, J., Vos-Geelen, J. de, Willemsen, A.E.C.A.B., Bosch, B.J. van den, and Coenen, M.J.H.

Abstract

Item does not contain fulltext, OBJECTIVE: To investigate if dihydropyrimidine dehydrogenase phenotyping has added value when combined with DPYD genotyping in predicting fluoropyrimidine-related toxicity. METHODS: Retrospective cohort study in which treatment and toxicity data were collected of 228 patients genotyped for four DPYD variants and phenotyped using an ex vivo peripheral blood mononuclear cell assay. RESULTS: Severe toxicity occurred in 25% of patients with a variant and normal dihydropyrimidine dehydrogenase activity, in 21% of patients without a variant and with decreased dihydropyrimidine dehydrogenase activity, and in 29% of patients without a variant and with normal dihydropyrimidine dehydrogenase activity (controls). The majority of patients with a variant or a decreased dihydropyrimidine dehydrogenase activity received an initial dose reduction (68% and 53% vs 19% in controls) and had a lower mean dose intensity (75% and 81% vs 91% in controls). Fifty percent of patients with a variant and decreased enzyme activity experienced severe toxicity, despite the lowest initial dose and whole treatment dose intensity. They also experienced more grade 4/5 toxicities. CONCLUSIONS: Our results indicate that a combined genotype-phenotype approach could be useful to identify patients at increased risk for fluoropyrimidine-associated toxicity (e.g. patients with a variant and decreased dihydropyrimidine dehydrogenase activity). Because the group sizes are too small to demonstrate statistically significant differences, this warrants further research in a prospective study in a larger cohort.

Published
2023

2. The effect of a reduced dose of enzalutamide on fatigue and cognition

Author

Overbeek, J.K., Boerrigter, E., Benoist, G.E., Somford, D.M., Hamberg, P., Tol, J., Scholtes, B., Willemsen, A.E.C.A.B., Buffart, L.M., Kessels, R.P.C., Mehra, N., Oort, I.M. van, Erp, P.H. van, Overbeek, J.K., Boerrigter, E., Benoist, G.E., Somford, D.M., Hamberg, P., Tol, J., Scholtes, B., Willemsen, A.E.C.A.B., Buffart, L.M., Kessels, R.P.C., Mehra, N., Oort, I.M. van, and Erp, P.H. van

Abstract

Item does not contain fulltext

Published
2023

4. Correction: Protocol of the Healthy Brain Study: An accessible resource for understanding the human brain and how it dynamically and individually operates in its bio-social context

Author

Fernandez, G., Aarts, E., Akkerman, A., Altgassen, A.M., Bartels, R.H.M.A., Beckers, D.G.J., Bevelander, K.E., Bijleveld, E., Blaney Davidson, E.N., Boleij, A., Bralten, J.B., Cillessen, A.H.N., Claassen, J.A., Cools, R., Cornelissen, I.M.M., Dresler, M., Eijsvogels, T.M.H., Faber, M., Figner, B., Fritsche, M., Füllbrunn, S.C., Gayet, S., Gelder, M.M.H.J. van, Gerven, M.A.J. van, Geurts, S.A.E., Greven, C.U., Groefsema, M.M., Haak, K.V., Hagoort, P., Hartman, Y.A.W., Heijden, B.I.J.M. van der, Hermans, E., Heuvelmans, V.R., Hintz, F., Hollander, J.W. den, Hulsman, A.M., Idesis, S.A., Jaeger, Martin, Janse, E., Janzing, J.G., Kessels, R.P.C., Kleijn, W.P.E. de, Klein, M., Klumpers, F., Kohn, N., Korzilius, H.P.L.M., Krahmer, B., Lange, F.P. de, Leeuwen, J.M.C. van, Liu, H., Luijten, M., Manders, P., Manevska, K., Marques, J.P., Matthews, J., McQueen, J.M., Medendorp, W.P., Melis, R.J., Meyer, A.S., Oosterman, J.M., Overbeek, L.I.H., Peelen, M.V., Popma, J.A.M., Postma, G.J., Roelofs, K., Rossenberg, Y.G.T. van, Schaap, G.J., Scheepers, P.T., Selen, L.P.J., Starren, M.B.P., Swinkels, D.W., Tendolkar, I., Thijssen, D.H.J., Timmerman, H., Toutounji, R.T., Tuladhar, A.M., Veling, H.P., Verhagen, M., Verkroost, J., Vriezekolk, V., Vrijsen, J.N., Vyrastekova, J., Wal, S.E.I. van der, Willems, R.M., Willemsen, A.E.C.A.B., Fernandez, G., Aarts, E., Akkerman, A., Altgassen, A.M., Bartels, R.H.M.A., Beckers, D.G.J., Bevelander, K.E., Bijleveld, E., Blaney Davidson, E.N., Boleij, A., Bralten, J.B., Cillessen, A.H.N., Claassen, J.A., Cools, R., Cornelissen, I.M.M., Dresler, M., Eijsvogels, T.M.H., Faber, M., Figner, B., Fritsche, M., Füllbrunn, S.C., Gayet, S., Gelder, M.M.H.J. van, Gerven, M.A.J. van, Geurts, S.A.E., Greven, C.U., Groefsema, M.M., Haak, K.V., Hagoort, P., Hartman, Y.A.W., Heijden, B.I.J.M. van der, Hermans, E., Heuvelmans, V.R., Hintz, F., Hollander, J.W. den, Hulsman, A.M., Idesis, S.A., Jaeger, Martin, Janse, E., Janzing, J.G., Kessels, R.P.C., Kleijn, W.P.E. de, Klein, M., Klumpers, F., Kohn, N., Korzilius, H.P.L.M., Krahmer, B., Lange, F.P. de, Leeuwen, J.M.C. van, Liu, H., Luijten, M., Manders, P., Manevska, K., Marques, J.P., Matthews, J., McQueen, J.M., Medendorp, W.P., Melis, R.J., Meyer, A.S., Oosterman, J.M., Overbeek, L.I.H., Peelen, M.V., Popma, J.A.M., Postma, G.J., Roelofs, K., Rossenberg, Y.G.T. van, Schaap, G.J., Scheepers, P.T., Selen, L.P.J., Starren, M.B.P., Swinkels, D.W., Tendolkar, I., Thijssen, D.H.J., Timmerman, H., Toutounji, R.T., Tuladhar, A.M., Veling, H.P., Verhagen, M., Verkroost, J., Vriezekolk, V., Vrijsen, J.N., Vyrastekova, J., Wal, S.E.I. van der, Willems, R.M., and Willemsen, A.E.C.A.B.

Abstract

Contains fulltext : 248974.pdf (Publisher’s version ) (Open Access)

Published
2022

5. Correction: Protocol of the Healthy Brain Study: An accessible resource for understanding the human brain and how it dynamically and individually operates in its bio-social context

Author

Healthy Brain Study consortium, ., Aarts, E., Akkerman, A., Altgassen, A.M., Bartels, R.H.M.A., Beckers, D.G.J., Bevelander, K.E., Bijleveld, E., Blaney Davidson, E.N., Boleij, A., Bralten, J.B., Cillessen, A.H.N., Claassen, J.A., Cools, R., Cornelissen, I.M.M., Dresler, M., Eijsvogels, T.M.H., Faber, M., Figner, B., Fernandez, G., Fritsche, M., Füllbrunn, S.C., Gayet, S., Gelder, M.M.H.J. van, Gerven, M.A.J. van, Geurts, S.A.E., Greven, C.U., Groefsema, M.M., Haak, K.V., Hagoort, P., Hartman, Y.A.W., Heijden, B.I.J.M. van der, Hermans, E.J., Heuvelmans, V.R., Hintz, F., Hollander, J.W. den, Hulsman, A.M., Idesis, S.A., Jaeger, Martin, Janse, E., Janzing, J.G., Kessels, R.P.C., Karremans, J.C.T.M., Kleijn, W.P.E. de, Klein, M., Klumpers, F., Kohn, N., Korzilius, H.P.L.M., Krahmer, B., Lange, F.P. de, Leeuwen, J.M.C. van, Liu, H., Luijten, M., Manders, P., Manevska, K., Marques, J.P., Matthews, J., McQueen, J.M., Medendorp, W.P., Melis, R.J.F., Meyer, A.S., Oosterman, J.M., Overbeek, L.I.H., Peelen, M.V., Popma, J.A.M., Postma, G.J., Roelofs, K., Rossenberg, Y.G.T. van, Schaap, G.J., Scheepers, P.T., Selen, L.P.J., Starren, M.B.P., Swinkels, D.W., Tendolkar, I., Thijssen, D.H.J., Timmerman, H., Toutounji, R.T., Tuladhar, A.M., Veling, H.P., Verhagen, M., Verkroost, J., Vriezekolk, V., Vrijsen, J.N., Vyrastekova, J., Wal, S.E.I. van der, Willems, R.M., Willemsen, A.E.C.A.B., Healthy Brain Study consortium, ., Aarts, E., Akkerman, A., Altgassen, A.M., Bartels, R.H.M.A., Beckers, D.G.J., Bevelander, K.E., Bijleveld, E., Blaney Davidson, E.N., Boleij, A., Bralten, J.B., Cillessen, A.H.N., Claassen, J.A., Cools, R., Cornelissen, I.M.M., Dresler, M., Eijsvogels, T.M.H., Faber, M., Figner, B., Fernandez, G., Fritsche, M., Füllbrunn, S.C., Gayet, S., Gelder, M.M.H.J. van, Gerven, M.A.J. van, Geurts, S.A.E., Greven, C.U., Groefsema, M.M., Haak, K.V., Hagoort, P., Hartman, Y.A.W., Heijden, B.I.J.M. van der, Hermans, E.J., Heuvelmans, V.R., Hintz, F., Hollander, J.W. den, Hulsman, A.M., Idesis, S.A., Jaeger, Martin, Janse, E., Janzing, J.G., Kessels, R.P.C., Karremans, J.C.T.M., Kleijn, W.P.E. de, Klein, M., Klumpers, F., Kohn, N., Korzilius, H.P.L.M., Krahmer, B., Lange, F.P. de, Leeuwen, J.M.C. van, Liu, H., Luijten, M., Manders, P., Manevska, K., Marques, J.P., Matthews, J., McQueen, J.M., Medendorp, W.P., Melis, R.J.F., Meyer, A.S., Oosterman, J.M., Overbeek, L.I.H., Peelen, M.V., Popma, J.A.M., Postma, G.J., Roelofs, K., Rossenberg, Y.G.T. van, Schaap, G.J., Scheepers, P.T., Selen, L.P.J., Starren, M.B.P., Swinkels, D.W., Tendolkar, I., Thijssen, D.H.J., Timmerman, H., Toutounji, R.T., Tuladhar, A.M., Veling, H.P., Verhagen, M., Verkroost, J., Vriezekolk, V., Vrijsen, J.N., Vyrastekova, J., Wal, S.E.I. van der, Willems, R.M., and Willemsen, A.E.C.A.B.

Abstract

Contains fulltext : 248974.pdf (Publisher’s version ) (Open Access)

Published
2022

6. Protocol of the Healthy Brain Study: An accessible resource for understanding the human brain and how it dynamically and individually operates in its bio-social context

Author

Fernandez, G., Aarts, E., Akkerman, A., Altgassen, A.M., Bartels, R.H.M.A., Beckers, D.G.J., Bevelander, K.E., Bijleveld, E., Blaney Davidson, E.N., Boleij, A., Bralten, J.B., Cillessen, A.H.N., Claassen, J.A., Cools, R., Cornelissen, I.M.M., Dresler, M., Eijsvogels, T.M.H., Faber, M., Figner, B., Fritsche, M., Füllbrunn, S.C., Gayet, S., Gelder, M.M.H.J. van, Gerven, M.A.J. van, Geurts, S.A.E., Greven, C.U., Groefsema, M.M., Haak, K.V., Hagoort, P., Hartman, Y.A.W., Heijden, B.I.J.M. van der, Hermans, E., Heuvelmans, V.R., Hintz, F., Hollander, J.W. den, Hulsman, A.M., Idesis, S.A., Jaeger, Martin, Janse, E., Janzing, J.G., Kessels, R.P.C., Kleijn, W.P.E. de, Klein, M., Klumpers, F., Kohn, N., Korzilius, H.P.L.M., Krahmer, B., Lange, F.P. de, Leeuwen, J.M.C. van, Liu, H., Luijten, M., Manders, P., Manevska, K., Marques, J.P., Matthews, J., McQueen, J.M., Medendorp, W.P., Melis, R.J., Meyer, A.S., Oosterman, J.M., Overbeek, L.I.H., Peelen, M.V., Popma, J.A.M., Postma, G.J., Roelofs, K., Rossenberg, Y.G.T. van, Schaap, G.J., Scheepers, P.T., Selen, L.P.J., Starren, M.B.P., Swinkels, D.W., Tendolkar, I., Thijssen, D.H.J., Timmerman, H., Toutounji, R.T., Tuladhar, A.M., Veling, H.P., Verhagen, M., Verkroost, J., Vriezekolk, V., Vrijsen, J.N., Vyrastekova, J., Wal, S.E.I. van der, Willems, R.M., Willemsen, A.E.C.A.B., Fernandez, G., Aarts, E., Akkerman, A., Altgassen, A.M., Bartels, R.H.M.A., Beckers, D.G.J., Bevelander, K.E., Bijleveld, E., Blaney Davidson, E.N., Boleij, A., Bralten, J.B., Cillessen, A.H.N., Claassen, J.A., Cools, R., Cornelissen, I.M.M., Dresler, M., Eijsvogels, T.M.H., Faber, M., Figner, B., Fritsche, M., Füllbrunn, S.C., Gayet, S., Gelder, M.M.H.J. van, Gerven, M.A.J. van, Geurts, S.A.E., Greven, C.U., Groefsema, M.M., Haak, K.V., Hagoort, P., Hartman, Y.A.W., Heijden, B.I.J.M. van der, Hermans, E., Heuvelmans, V.R., Hintz, F., Hollander, J.W. den, Hulsman, A.M., Idesis, S.A., Jaeger, Martin, Janse, E., Janzing, J.G., Kessels, R.P.C., Kleijn, W.P.E. de, Klein, M., Klumpers, F., Kohn, N., Korzilius, H.P.L.M., Krahmer, B., Lange, F.P. de, Leeuwen, J.M.C. van, Liu, H., Luijten, M., Manders, P., Manevska, K., Marques, J.P., Matthews, J., McQueen, J.M., Medendorp, W.P., Melis, R.J., Meyer, A.S., Oosterman, J.M., Overbeek, L.I.H., Peelen, M.V., Popma, J.A.M., Postma, G.J., Roelofs, K., Rossenberg, Y.G.T. van, Schaap, G.J., Scheepers, P.T., Selen, L.P.J., Starren, M.B.P., Swinkels, D.W., Tendolkar, I., Thijssen, D.H.J., Timmerman, H., Toutounji, R.T., Tuladhar, A.M., Veling, H.P., Verhagen, M., Verkroost, J., Vriezekolk, V., Vrijsen, J.N., Vyrastekova, J., Wal, S.E.I. van der, Willems, R.M., and Willemsen, A.E.C.A.B.

Abstract

Contains fulltext : 242453.pdf (Publisher’s version ) (Open Access), The endeavor to understand the human brain has seen more progress in the last few decades than in the previous two millennia. Still, our understanding of how the human brain relates to behavior in the real world and how this link is modulated by biological, social, and environmental factors is limited. To address this, we designed the Healthy Brain Study (HBS), an interdisciplinary, longitudinal, cohort study based on multidimensional, dynamic assessments in both the laboratory and the real world. Here, we describe the rationale and design of the currently ongoing HBS. The HBS is examining a population-based sample of 1,000 healthy participants (age 30-39) who are thoroughly studied across an entire year. Data are collected through cognitive, affective, behavioral, and physiological testing, neuroimaging, bio-sampling, questionnaires, ecological momentary assessment, and real-world assessments using wearable devices. These data will become an accessible resource for the scientific community enabling the next step in understanding the human brain and how it dynamically and individually operates in its bio-social context. An access procedure to the collected data and bio-samples is in place and published on https://www.healthybrainstudy.nl/en/data-and-methods. https://www.trialregister.nl/trial/7955

Published
2021

7. Baseline effector cells predict response and NKT cells predict pulmonary toxicity in advanced breast cancer patients treated with everolimus and exemestane

Author

Willemsen, A.E.C.A.B., He, X., Cranenbroek, B. van, Jong, P.C. de, Boer, M den, Joosten, I., Koenen, H.J.P.M., Herpen, C.M.L. van, Gerritsen, W.R., Willemsen, A.E.C.A.B., He, X., Cranenbroek, B. van, Jong, P.C. de, Boer, M den, Joosten, I., Koenen, H.J.P.M., Herpen, C.M.L. van, and Gerritsen, W.R.

Abstract

Contains fulltext : 232015.pdf (Publisher’s version ) (Open Access), BACKGROUND: The mTOR inhibitor everolimus used in cancer has immune-modulating effects, potentially contributing to an antitumor response but also leading to pulmonary toxicity. We studied the association of immunological cell subsets with antitumor response and pulmonary toxicity in breast cancer patients treated with everolimus plus exemestane. METHODS: In this exploratory analysis, peripheral blood mononuclear cells (PBMCs) were collected at baseline and 14, 35, 60, and 90 days after start of treatment, and at the moment of pulmonary toxicity. The percentage and absolute number of T-cells, B-cells, NK-cells, monocytes and numerous subtypes were measured in peripheral blood using flow cytometric analysis and were compared using a (paired) t-test. RESULTS: From 20 patients, a total of 89 samples were collected. At baseline, responders versus non-responders had 0.86% versus 0.32% CD4+ effector cells (CD45RA+CD27-) (p = 0.1266) and non-response could be predicted with 0.71 sensitivity and 0.82 specificity. Patients who developed pulmonary toxicity compared to patients without pulmonary toxicity had relatively more NKT-cells at baseline (6.0% versus 1.3%, p = 0.0068, 59 k versus 12 k * 10(9)/l, p = 0.0081) and at the moment of toxicity (5.2% versus 1.2%, p = 0.0106 and 47 k versus 16 k * 10(9)/l, p = 0.0466). Baseline percentage NKT cells predicted pulmonary toxicity with 0.78 sensitivity and 1.0 specificity. CONCLUSIONS: Our results suggest that baseline CD4+ effector cells may be predictive of antitumor responses and baseline NKT cells may be predictive of pulmonary toxicity. These results warrant further validation.

Published
2021

8. Optimizing everolimus treatment in advanced breast cancer patients

Author

Willemsen, A.E.C.A.B., Gerritsen, W.R., Herpen, C.M.L. van, Erp, P.H. van, Tol, J., and Radboud University Nijmegen

Subjects
Radboud Institute for Health Sciences, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], Urological cancers [Radboudumc 15]
Abstract

Contains fulltext : 222328.pdf (Publisher’s version ) (Open Access) Radboud University, 12 oktober 2020 Promotores : Gerritsen, W.R., Herpen, C.M.L. van Co-promotores : Erp, P.H. van, Tol, J.

Published
2020

9. Optimizing everolimus treatment in advanced breast cancer patients

Author

Gerritsen, W.R., Herpen, C.M.L. van, Erp, P.H. van, Tol, J., Willemsen, A.E.C.A.B., Gerritsen, W.R., Herpen, C.M.L. van, Erp, P.H. van, Tol, J., and Willemsen, A.E.C.A.B.

Abstract

Radboud University, 12 oktober 2020, Promotores : Gerritsen, W.R., Herpen, C.M.L. van Co-promotores : Erp, P.H. van, Tol, J., Contains fulltext : 222328.pdf (publisher's version ) (Open Access)

Published
2020

11. Molecular tumour boards and molecular diagnostics for patients with cancer in the Netherlands: experiences, challenges, and aspirations

Author

Willemsen, A.E.C.A.B., Krausz, S., Ligtenberg, M.J.L., Grunberg, K., Groen, H.J.M., Voest, E.E., Cuppen, E., Laarhoven, H.W.M. van, Herpen, C.M.L. van, Willemsen, A.E.C.A.B., Krausz, S., Ligtenberg, M.J.L., Grunberg, K., Groen, H.J.M., Voest, E.E., Cuppen, E., Laarhoven, H.W.M. van, and Herpen, C.M.L. van

Abstract

Contains fulltext : 207194.pdf (Publisher’s version ) (Open Access), Advances in molecular tumour diagnostics and the number of targeted therapies increase rapidly. Molecular tumour boards (MTBs) are designated to interpret these data and provide clinical recommendations. Not all patients with cancer have access to advice of an MTB. We aimed to determine the current status, opportunities, and challenges of the organisation of MTBs in the Netherlands. We interviewed several stakeholders about their experiences with an MTB, using template analysis. Most clinicians and patient representatives underscore the significance of an MTB, because it can stimulate rational treatment options, enrolment in clinical trials, and interdisciplinary knowledge transfer. Health insurance companies and financial managers are concerned about increasing costs. Registries to assess the clinical benefit of MTBs, guidelines on quality control, financial agreements, and logistical resources are lacking. The national organisation of MTBs and a registry of molecular and clinical data are important issues to address.

Published
2019

12. Prospective Study of Drug-induced Interstitial Lung Disease in Advanced Breast Cancer Patients Receiving Everolimus Plus Exemestane

Author

Willemsen, A.E.C.A.B., Tol, Jolien, Erp, N.P. van, Jonker, M.A., Boer, Maaike de, Meek, Bob, Gerritsen, W.R., Grutters, Jan C., Herpen, C.M.L. van, Willemsen, A.E.C.A.B., Tol, Jolien, Erp, N.P. van, Jonker, M.A., Boer, Maaike de, Meek, Bob, Gerritsen, W.R., Grutters, Jan C., and Herpen, C.M.L. van

Abstract

Contains fulltext : 206246.pdf (publisher's version ) (Open Access)

Published
2019

14. Everolimus Exposure and Early Metabolic Response as Predictors of Treatment Outcomes in Breast Cancer Patients Treated with Everolimus and Exemestane

Author

Willemsen, A.E.C.A.B., Geus-Oei, L.F. de, Boer, Maaike de, Tol, J., Kamm, Yvonne, Jong, P.C. de, Jonker, M.A., Aarntzen, E.H.J.G., Gerritsen, W.R., Herpen, C.M.L. van, Erp, N.P. van, Willemsen, A.E.C.A.B., Geus-Oei, L.F. de, Boer, Maaike de, Tol, J., Kamm, Yvonne, Jong, P.C. de, Jonker, M.A., Aarntzen, E.H.J.G., Gerritsen, W.R., Herpen, C.M.L. van, and Erp, N.P. van

Abstract

Item does not contain fulltext

Published
2018

15. Nivolumab-associated Nephrotic Syndrome in a Patient With Renal Cell Carcinoma: A Case Report

Author

Daanen, R.A., Maas, R.J.H., Koornstra, R.H., Steenbergen, E.J., Herpen, C.M.L. van, Willemsen, A.E.C.A.B., Daanen, R.A., Maas, R.J.H., Koornstra, R.H., Steenbergen, E.J., Herpen, C.M.L. van, and Willemsen, A.E.C.A.B.

Abstract

Item does not contain fulltext, INTRODUCTION: Immune checkpoint inhibitors have taken an important place in the treatment of different types of malignancies. These drugs are known to have specific immune-mediated adverse events. We describe a case of severe nephrotic syndrome secondary to treatment with nivolumab in a patient with renal cell carcinoma. CASE PRESENTATION: A 62-year-old man was treated with nivolumab for papillary renal cell carcinoma type 2 for 8 weeks when he was admitted to the hospital with a severe nephrotic syndrome and acute kidney injury. Renal biopsy showed focal segmental glomerulosclerosis. Treatment with high-dose corticosteroids had insufficient effect, but the addition of mycophenolate mofetil resulted in remission of the nephrotic syndrome and recovery of renal function. Proteinuria subsequently relapsed during corticosteroid tapering. CONCLUSIONS: The time course in this patient strongly suggests that the nephrotic syndrome occurred as an adverse drug reaction to nivolumab treatment. If during nivolumab treatment renal insufficiency, hypoalbuminemia, or proteinuria develops, further analysis for a possible nephrotic syndrome is warranted for early detection and treatment of this life-threatening complication.

Published
2017

16. [Choosing wisely when prescribing statins]

Author

Willemsen, A.E.C.A.B., Bredie, S.J.H., Lobo, C.M., Vlugt, M.J. van der, and Kramers, C.

Subjects
Other Research Radboud Institute for Health Sciences [Radboudumc 0], Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], nutritional and metabolic diseases, lipids (amino acids, peptides, and proteins), cardiovascular diseases, Healthcare improvement science Radboud Institute for Health Sciences [Radboudumc 18], Rare cancers Radboud Institute for Health Sciences [Radboudumc 9]
Abstract

Item does not contain fulltext The Dutch campaign 'Verstandig kiezen', based on the American programme 'Choosing wisely', aims to improve quality in healthcare, with attention to cost control. The 'Choosing wisely'-based programme can be applied in the choice of a statin. Atorvastatin and rosuvastatin are regarded as equal choices in various guidelines regarding cardiovascular risk management. Generic atorvastatin is available, and is approximately 25 times cheaper than rosuvastatin in almost equipotent doses. Rosuvastatin provides a greater LDL reduction than atorvastatin. Patient LDL targets can usually be achieved with atorvastatin, and rosuvastatin is not needed. At group level, there are no relevant differences in adverse-events profile between both statins. Atorvastatin and rosuvastatin do have different pharmacokinetic interactions. When changing medication, good provision of information is a prerequisite for patient satisfaction and compliance. We advise use of atorvastatin instead of rosuvastatin as drug of choice when the LDL target is not reached using simvastatin. However, under specific conditions, rosuvastatin should be the treatment of choice. Efficacy and adverse effects should then be evaluated at individual patient level.

Published
2015

17. Effect of food and acid-reducing agents on the absorption of oral targeted therapies in solid tumors

Author

Willemsen, A.E.C.A.B., Lubberman, F.J.E., Tol, J., Gerritsen, W.R., Herpen, C.M.L. van, Erp, N. van, Willemsen, A.E.C.A.B., Lubberman, F.J.E., Tol, J., Gerritsen, W.R., Herpen, C.M.L. van, and Erp, N. van

Abstract

Contains fulltext : 172414.pdf (publisher's version ) (Closed access), Oral targeted therapies represent an increasingly important group of drugs within modern oncology. With the shift from intravenously to orally administered drugs, drug absorption is a newly introduced factor in drug disposition. The process of absorption can have a large effect on inter- and intrasubject variability in drug exposure and thereby potentially treatment benefit or the severity of toxicities. The intake of oral targeted therapies with food and concomitant use of acid-reducing agents (ARAs) can significantly affect drug absorption. The size and direction of the effect of food and ARAs on drug absorption varies among drugs as a result of different chemical characteristics. Therefore, an awareness and understanding of these effects for each drug is essential to optimize patient outcomes.

Published
2016

18. Positron emission tomography response criteria in solid tumours criteria for quantitative analysis of [(18)F]-fluorodeoxyglucose positron emission tomography with integrated computed tomography for treatment response assessment in metastasised solid tumours: All that glitters is not gold

Author

Willemsen, A.E.C.A.B., Vlenterie, M., Herpen, C.M.L. van, Erp, N. van, Graaf, W.T.A. van der, Geus-Oei, L.F. de, Oyen, W.J., Willemsen, A.E.C.A.B., Vlenterie, M., Herpen, C.M.L. van, Erp, N. van, Graaf, W.T.A. van der, Geus-Oei, L.F. de, and Oyen, W.J.

Abstract

Item does not contain fulltext, For solid tumours, quantitative analysis of [(18)F]-fluorodeoxyglucose positron emission tomography with integrated computed tomography potentially can have significant value in early response assessment and thereby discrimination between responders and non-responders at an early stage of treatment. Standardised strategies for this analysis have been proposed, and the positron emission tomography response criteria in solid tumours (PERCIST) criteria can be regarded as the current standard to perform quantitative analysis in a research setting, yet is not implemented in daily practice. However, several exceptions and limitations limit the feasibility of PERCIST criteria. In this article, we point out dilemmas that arise when applying proposed criteria like PERCIST on an expansive set of patients with metastasised solid tumours. Clinicians and scientists should be aware of these limitations to prevent that methodological issues impede successful introduction of research data into clinical practice. Therefore, to deliver on the high potential of quantitative imaging, consensus should be reached on a standardised, feasible and clinically useful analysis methodology. This methodology should be applicable in the majority of patients, tumour types and treatments.

Published
2016

21. Experimental treatment of NRAS-mutated neurocutaneous melanocytosis with MEK162, a MEK-inhibitor

Author

Kusters-vandevelde, H.V., Willemsen, A.E.C.A.B., Groenen, P.J.T.A., Kusters, B., Lammens, M.M., Wesseling, P., Djafarihamedani, M., Rijntjes, J., Delye, H.H., Willemsen, M.A., Herpen, C.M.L. van, Blokx, W.A.M., Kusters-vandevelde, H.V., Willemsen, A.E.C.A.B., Groenen, P.J.T.A., Kusters, B., Lammens, M.M., Wesseling, P., Djafarihamedani, M., Rijntjes, J., Delye, H.H., Willemsen, M.A., Herpen, C.M.L. van, and Blokx, W.A.M.

Abstract

Contains fulltext : 137997.pdf (publisher's version ) (Open Access), Neurocutaneous melanosis (NCM) is a rare congenital disorder characterized by the association of large and/or multiple congenital melanocytic nevi (CMN) of the skin with melanocytic lesions of the leptomeninges, including melanocytosis. Leptomeningeal melanocytosis carries a poor prognosis once neurological symptoms develop. Despite surgery, which is often not radical, few other treatment options exist. Recently, it was demonstrated that early embryonic, post-zygotic somatic mutations in the NRAS gene are implicated in the pathogenesis of NCM.In this report, we present a 13-year-old boy with NCM and progressive symptomatic leptomeningeal melanocytosis. A somatic NRASQ61K mutation was present in both CMN as well as the melanocytosis. Despite repeated surgery, the patient showed clinical progression. Therefore, treatment with MEK162, a MEK inhibitor, was started on compassionate use base. The patient died only five days later, i.e. too early to expect a clinical effect of MEK162 therapy. We therefore studied the effect of MEK162 at the protein level in the leptomeningeal tumor by immunohistochemical and Western Blot analyses using Ki67 and pERK antibodies. We observed lower MIB-1 expression and lower pERK expression in the post-treatment samples compared to pre-treatment, suggesting a potential effect of MEK inhibiting therapy. Further studies are needed to determine whether MEK inhibitors can effectively target NRAS-mutated symptomatic NCM, a rare but potentially fatal disease.

Published
2014

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