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3. Next generation sequencing of high-grade adult-type diffuse glioma in the Netherlands: interlaboratory variation in the primary diagnostic and recurrent setting

Author

van Opijnen, Mark P., Broekman, Marike L. D., Cuppen, Edwin, Dubbink, Hendrikus J., ter Elst, Arja, van Eijk, Ronald, Mühlebner, Angelika, Jansen, Casper, van der Geize, Robert, Speel, Ernst-Jan M., Groenen, Patricia J. T. A., de Vos, Filip Y. F., Wesseling, Pieter, de Leng, Wendy W. J., and Maas, Sybren L. N.

Published
2024
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4. Dabrafenib plus trametinib in BRAFV600E-mutated rare cancers: the phase 2 ROAR trial

Author

Subbiah, Vivek, Kreitman, Robert J., Wainberg, Zev A., Gazzah, Anas, Lassen, Ulrik, Stein, Alexander, Wen, Patrick Y., Dietrich, Sascha, de Jonge, Maja J. A., Blay, Jean-Yves, Italiano, Antoine, Yonemori, Kan, Cho, Daniel C., de Vos, Filip Y. F. L., Moreau, Philippe, Fernandez, Elena Elez, Schellens, Jan H. M., Zielinski, Christoph C., Redhu, Suman, Boran, Aislyn, Passos, Vanessa Q., Ilankumaran, Palanichamy, and Bang, Yung-Jue

Published
2023
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5. Dabrafenib plus trametinib in patients with BRAFV600E-mutant low-grade and high-grade glioma (ROAR): a multicentre, open-label, single-arm, phase 2, basket trial

Author

Wen, Patrick Y, Stein, Alexander, van den Bent, Martin, De Greve, Jacques, Wick, Antje, de Vos, Filip Y F L, von Bubnoff, Nikolas, van Linde, Myra E, Lai, Albert, Prager, Gerald W, Campone, Mario, Fasolo, Angelica, Lopez-Martin, Jose A, Kim, Tae Min, Mason, Warren P, Hofheinz, Ralf-Dieter, Blay, Jean-Yves, Cho, Daniel C, Gazzah, Anas, Pouessel, Damien, Yachnin, Jeffrey, Boran, Aislyn, Burgess, Paul, Ilankumaran, Palanichamy, Gasal, Eduard, and Subbiah, Vivek

Published
2022
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7. Study protocol of the GLOW study: maximising treatment options for recurrent glioblastoma patients by whole genome sequencing-based diagnostics—a prospective multicenter cohort study

Author

van Opijnen, Mark P., Broekman, Marike L. D., de Vos, Filip Y. F., Cuppen, Edwin, van der Hoeven, Jacobus J. M., van Linde, Myra E., Compter, Annette, Beerepoot, Laurens V., van den Bent, Martin J., Vos, Maaike J., Fiebrich, Helle-Brit, Koekkoek, Johan A. F., Hoeben, Ann, Kho, Kuan H., Driessen, Chantal M. L., Jeltema, Hanne-Rinck, Robe, Pierre A. J. T., and Maas, Sybren L. N.

Published
2022
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10. Baseline and on Treatment Biodistribution Variability of 18F-FLT Uptake in Patients With Advanced Melanoma: Brief Communication

Author

MS Medische Oncologie, Brain, Cancer, van der Hiel, Bernies, Aalbersberg, Else A, van den Eertwegh, Alfons J M, Fischer, Jitha, Boellaard, Ronald, de Vos, Filip Y F L, Boers-Sonderen, Marye J, Stokkel, Marcel P M, de Wit-van der Veen, Linda J, Haanen, John B A G, MS Medische Oncologie, Brain, Cancer, van der Hiel, Bernies, Aalbersberg, Else A, van den Eertwegh, Alfons J M, Fischer, Jitha, Boellaard, Ronald, de Vos, Filip Y F L, Boers-Sonderen, Marye J, Stokkel, Marcel P M, de Wit-van der Veen, Linda J, and Haanen, John B A G

Published
2024

12. The role of molecular biomarkers in recurrent glioblastoma trials: an assessment of the current trial landscape of genome-driven oncology

Author

MS Medische Oncologie, Brain, Cancer, CMM Groep Van Mil, van Opijnen, Mark P, de Vos, Filip Y F, Cuppen, Edwin, Geurts, Marjolein, Maas, Sybren L N, Broekman, Marike L D, MS Medische Oncologie, Brain, Cancer, CMM Groep Van Mil, van Opijnen, Mark P, de Vos, Filip Y F, Cuppen, Edwin, Geurts, Marjolein, Maas, Sybren L N, and Broekman, Marike L D

Published
2024

13. Maximizing treatment opportunities: assessing protocol waivers' impact on safety and outcome in the Drug Rediscovery Protocol

Author

MS Medische Oncologie, Brain, Cancer, van Berge Henegouwen, Jade M, Zeverijn, Laurien J, Geurts, Birgit S, Hoes, Louisa R, van der Wijngaart, Hanneke, van der Noort, Vincent, Huitema, Alwin D R, De Vos, Filip Y F, Grünberg, Katrien, Bloemendal, Haiko J, Verheul, Henk M W, Voest, Emile E, Gelderblom, Hans, MS Medische Oncologie, Brain, Cancer, van Berge Henegouwen, Jade M, Zeverijn, Laurien J, Geurts, Birgit S, Hoes, Louisa R, van der Wijngaart, Hanneke, van der Noort, Vincent, Huitema, Alwin D R, De Vos, Filip Y F, Grünberg, Katrien, Bloemendal, Haiko J, Verheul, Henk M W, Voest, Emile E, and Gelderblom, Hans

Published
2024

14. Efficacy and Safety of Panitumumab in Patients With RAF/RAS-Wild-Type Glioblastoma:Results From the Drug Rediscovery Protocol

Author

Spiekman, Ilse A. C., Geurts, Birgit S., Zeverijn, Laurien J., de Wit, Gijs F., van der Noort, Vincent, Roepman, Paul, de Leng, Wendy W. J., Jansen, Anne M. L., Kusters, Benno, Beerepoot, Laurens, de Vos, Filip Y. F. L., de Groot, Derk-Jan A., de Groot, Jan Willem B., Hoeben, Ann, Buter, Jan, Gelderblom, Hans A. J., Voest, Emile E., Verheul, Henk M. W., Spiekman, Ilse A. C., Geurts, Birgit S., Zeverijn, Laurien J., de Wit, Gijs F., van der Noort, Vincent, Roepman, Paul, de Leng, Wendy W. J., Jansen, Anne M. L., Kusters, Benno, Beerepoot, Laurens, de Vos, Filip Y. F. L., de Groot, Derk-Jan A., de Groot, Jan Willem B., Hoeben, Ann, Buter, Jan, Gelderblom, Hans A. J., Voest, Emile E., and Verheul, Henk M. W.

Abstract

BACKGROUND: The prognosis of malignant primary high-grade brain tumors, predominantly glioblastomas, is poor despite intensive multimodality treatment options. In more than 50% of patients with glioblastomas, potentially targetable mutations are present, including rearrangements, altered splicing, and/or focal amplifications of epidermal growth factor receptor (EGFR) by signaling through the RAF/RAS pathway. We studied whether treatment with the clinically available anti-EGFR monoclonal antibody panitumumab provides clinical benefit for patients with RAF/RAS-wild-type (wt) glioblastomas in the Drug Rediscovery Protocol (DRUP). METHODS: Patients with progression of treatment refractory RAF/RASwt glioblastoma were included for treatment with panitumumab in DRUP when measurable according to RANO criteria. The primary endpoints of this study are clinical benefit (CB: defined as confirmed objective response [OR] or stable disease [SD] ≥ 16 weeks) and safety. Patients were enrolled using a Simon-like 2-stage model, with 8 patients in stage 1 and up to 24 patients in stage 2 if at least 1 in 8 patients had CB in stage 1. RESULTS: Between 03-2018 and 02-2022, 24 evaluable patients were treated. CB was observed in 5 patients (21%), including 2 patients with partial response (8.3%) and 3 patients with SD ≥ 16 weeks (12.5%). After median follow-up of 15 months, median progression-free survival and overall survival were 1.7 months (95% CI 1.6-2.1 months) and 4.5 months (95% CI 2.9-8.6 months), respectively. No unexpected toxicities were observed. CONCLUSIONS: Panitumumab treatment provides limited CB in patients with recurrent RAF/RASwt glioblastoma precluding further development of this therapeutic strategy.

Published
2024

15. Efficacy and Safety of Panitumumab in Patients With RAF/RAS-Wild-Type Glioblastoma: Results From the Drug Rediscovery Protocol

Author

Pathologie Pathologen staf, Cancer, Pathologie Moleculair, MS Medische Oncologie, Brain, Spiekman, Ilse A C, Geurts, Birgit S, Zeverijn, Laurien J, de Wit, Gijs F, van der Noort, Vincent, Roepman, Paul, de Leng, Wendy W J, Jansen, Anne M L, Kusters, Benno, Beerepoot, Laurens V, de Vos, Filip Y F L, de Groot, Derk-Jan A, de Groot, Jan Willem B, Hoeben, Ann, Buter, Jan, Gelderblom, Hans A J, Voest, Emile E, Verheul, Henk M W, Pathologie Pathologen staf, Cancer, Pathologie Moleculair, MS Medische Oncologie, Brain, Spiekman, Ilse A C, Geurts, Birgit S, Zeverijn, Laurien J, de Wit, Gijs F, van der Noort, Vincent, Roepman, Paul, de Leng, Wendy W J, Jansen, Anne M L, Kusters, Benno, Beerepoot, Laurens V, de Vos, Filip Y F L, de Groot, Derk-Jan A, de Groot, Jan Willem B, Hoeben, Ann, Buter, Jan, Gelderblom, Hans A J, Voest, Emile E, and Verheul, Henk M W

Published
2024

16. Potential Adverse Outcomes of Shared Decision Making about Palliative Cancer Treatment: A Secondary Analysis of a Randomized Trial

Author

MS Medische Oncologie, Brain, Cancer, van de Water, Loïs F, Bos-van den Hoek, Danique W, Kuijper, Steven C, van Laarhoven, Hanneke W M, Creemers, Geert-Jan, Dohmen, Serge E, Fiebrich, Helle-Brit, Ottevanger, Petronella B, Sommeijer, Dirkje W, de Vos, Filip Y F, Smets, Ellen M A, Henselmans, Inge, MS Medische Oncologie, Brain, Cancer, van de Water, Loïs F, Bos-van den Hoek, Danique W, Kuijper, Steven C, van Laarhoven, Hanneke W M, Creemers, Geert-Jan, Dohmen, Serge E, Fiebrich, Helle-Brit, Ottevanger, Petronella B, Sommeijer, Dirkje W, de Vos, Filip Y F, Smets, Ellen M A, and Henselmans, Inge

Published
2024

17. The Predictive Value of FDG PET/CT for Determining Progression-Free Survival in Advanced Stage III-IV BRAF-Mutated Melanoma Patients Treated With Targeted Therapy-What Can Be Learned From Progression?

Author

MS Medische Oncologie, Brain, Cancer, van der Hiel, Bernies, Aalbersberg, Else A, van den Eertwegh, Alfons J M, de Wit-van der Veen, Linda J, Stokkel, Marcel P M, Lopez-Yurda, Marta, Boellaard, Ronald, Kapiteijn, Ellen W, Hospers, Geke A P, Aarts, Maureen J B, de Vos, Filip Y F L, Boers-Sonderen, Marye J, van der Veldt, Astrid A M, de Groot, Jan Willem B, Haanen, John B A G, MS Medische Oncologie, Brain, Cancer, van der Hiel, Bernies, Aalbersberg, Else A, van den Eertwegh, Alfons J M, de Wit-van der Veen, Linda J, Stokkel, Marcel P M, Lopez-Yurda, Marta, Boellaard, Ronald, Kapiteijn, Ellen W, Hospers, Geke A P, Aarts, Maureen J B, de Vos, Filip Y F L, Boers-Sonderen, Marye J, van der Veldt, Astrid A M, de Groot, Jan Willem B, and Haanen, John B A G

Published
2024

18. Next generation sequencing of high-grade adult-type diffuse glioma in the Netherlands: interlaboratory variation in the primary diagnostic and recurrent setting

Author

CMM Groep Van Mil, Pathologie Pathologen staf, Brain, Cancer, MS Medische Oncologie, Pathologie Groep Van Diest, van Opijnen, Mark P, Broekman, Marike L D, Cuppen, Edwin, Dubbink, Hendrikus J, Ter Elst, Arja, van Eijk, Ronald, Mühlebner, Angelika, Jansen, Casper, van der Geize, Robert, Speel, Ernst-Jan M, Groenen, Patricia J T A, de Vos, Filip Y F, Wesseling, Pieter, de Leng, Wendy W J, Maas, Sybren L N, CMM Groep Van Mil, Pathologie Pathologen staf, Brain, Cancer, MS Medische Oncologie, Pathologie Groep Van Diest, van Opijnen, Mark P, Broekman, Marike L D, Cuppen, Edwin, Dubbink, Hendrikus J, Ter Elst, Arja, van Eijk, Ronald, Mühlebner, Angelika, Jansen, Casper, van der Geize, Robert, Speel, Ernst-Jan M, Groenen, Patricia J T A, de Vos, Filip Y F, Wesseling, Pieter, de Leng, Wendy W J, and Maas, Sybren L N

Published
2024

19. Focused Ultrasound-Enhanced Liquid Biopsy: A Promising Diagnostic Tool for Brain Tumor Patients

Author

ZL Neuro-Oncologie Medisch, Researchgr. Beeldg. Moleculaire Interv., Cancer, MS Medische Oncologie, Brain, Neurologen, Bakker, Akke, Ixkes, Anna E, Venugopal, Hema, Ries, Mario G, Lak, Nathalie S M, de Vos, Filip Y F L, van Vuurden, Dannis G, Snijders, Tom J, ZL Neuro-Oncologie Medisch, Researchgr. Beeldg. Moleculaire Interv., Cancer, MS Medische Oncologie, Brain, Neurologen, Bakker, Akke, Ixkes, Anna E, Venugopal, Hema, Ries, Mario G, Lak, Nathalie S M, de Vos, Filip Y F L, van Vuurden, Dannis G, and Snijders, Tom J

Published
2024

20. Phase 1 study of the pan-HER inhibitor dacomitinib plus the MEK1/2 inhibitor PD-0325901 in patients with KRAS-mutation-positive colorectal, non-small-cell lung and pancreatic cancer

Author

van Geel, Robin M. J. M., van Brummelen, Emilie M. J., Eskens, Ferry A. L. M., Huijberts, Sanne C. F. A., de Vos, Filip Y. F. L., Lolkema, Martijn P. J. K., Devriese, Lot A., Opdam, Frans L., Marchetti, Serena, Steeghs, Neeltje, Monkhorst, Kim, Thijssen, Bas, Rosing, Hilde, Huitema, Alwin D. R., Beijnen, Jos H., Bernards, René, and Schellens, Jan H. M.

Published
2020
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23. Bevacizumab and temozolomide in patients with first recurrence of WHO grade II and III glioma, without 1p/19q co-deletion (TAVAREC): a randomised controlled phase 2 EORTC trial

Author

van den Bent, Martin J, Klein, Martin, Smits, Marion, Reijneveld, Jaap C, French, Pim J, Clement, Paul, de Vos, Filip Y F, Wick, Antje, Mulholland, Paul J, Taphoorn, Martin J B, Lewis, Joanne, Weller, Michael, Chinot, Olivier L, Kros, Johan M, de Heer, Iris, Verschuere, Tina, Coens, Corneel, Golfinopoulos, Vassilis, Gorlia, Thierry, and Idbaih, Ahmed

Published
2018
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25. Potential Adverse Outcomes of Shared Decision Making about Palliative Cancer Treatment: A Secondary Analysis of a Randomized Trial

Author

van de Water, Loïs F., primary, Bos–van den Hoek, Danique W., additional, Kuijper, Steven C., additional, van Laarhoven, Hanneke W. M., additional, Creemers, Geert-Jan, additional, Dohmen, Serge E., additional, Fiebrich, Helle-Brit, additional, Ottevanger, Petronella B., additional, Sommeijer, Dirkje W., additional, de Vos, Filip Y. F., additional, Smets, Ellen M. A., additional, and Henselmans, Inge, additional

Published
2023
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26. Focused Ultrasound-Enhanced Liquid Biopsy: A Promising Diagnostic Tool for Brain Tumor Patients.

Author

Bakker, Akke, Ixkes, Anna E., Venugopal, Hema, Ries, Mario G., Lak, Nathalie S. M., de Vos, Filip Y. F. L., van Vuurden, Dannis G., and Snijders, Tom J.

Subjects
MEDICAL information storage & retrieval systems, GLIOMAS, RESEARCH funding, BLOOD-brain barrier, BODY fluid examination, CANCER patients, MINIMALLY invasive procedures, ULTRASONIC imaging, MEDLINE, SYSTEMATIC reviews, ONLINE information services, BRAIN tumors, BIOMARKERS
Abstract

Simple Summary: Diagnosing brain tumors using minimally invasive methods, such as a liquid biopsy, is challenging due to the blood–brain barrier (BBB). The BBB blocks tumor biomarkers from entering the bloodstream. However, a technique called focused ultrasound with microbubbles (FUS-BBBO) can temporarily open the BBB, thereby potentially increasing the tumor biomarkers in the bloodstream. This systematic review collected data on FUS-BBBO-enhanced liquid biopsy for primary brain tumors. The review included five animal studies and two human studies. Animal studies have shown that biomarker levels were higher in groups subjected to FUS-BBBO compared to control groups. Clinical studies involving 14 patients also showed increased biomarker levels after FUS-BBBO treatment. It is worth noting that using stable cavitation during FUS-BBBO appeared promising for liquid biopsy. Overall, this technique has the potential to improve brain tumor diagnosis and disease monitoring. However, further investigation is necessary to ensure its safe and effective use in the clinical setting. The performance of minimally invasive molecular diagnostic tools in brain tumors, such as liquid biopsy, has so far been limited by the blood–brain barrier (BBB). The BBB hinders the release of brain tumor biomarkers into the bloodstream. The use of focused ultrasound in conjunction with microbubbles has been shown to temporarily open the BBB (FUS-BBBO). This may enhance blood-based tumor biomarker levels. This systematic review provides an overview of the data regarding FUS-BBBO-enhanced liquid biopsy for primary brain tumors. A systematic search was conducted in PubMed and Embase databases with key terms "brain tumors", "liquid biopsy", "FUS" and their synonyms, in accordance with PRISMA statement guidelines. Five preclinical and two clinical studies were included. Preclinical studies utilized mouse, rat and porcine glioma models. Biomarker levels were found to be higher in sonicated groups compared to control groups. Both stable and inertial microbubble cavitation increased biomarker levels, whereas only inertial cavitation induced microhemorrhages. In clinical studies involving 14 patients with high-grade brain tumors, biomarker levels were increased after FUS-BBBO with stable cavitation. In conclusion, FUS-BBBO-enhanced liquid biopsy using stable cavitation shows diagnostic potential for primary brain tumors. Further research is imperative before integrating FUS-BBBO for liquid biopsy enhancement into clinical practice. [ABSTRACT FROM AUTHOR]

Published
2024
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30. Pharmacokinetic Effects and Safety of Olaparib Administered with Endocrine Therapy: A Phase I Study in Patients with Advanced Solid Tumours

Author

Plummer, Ruth, Verheul, Henk M., De Vos, Filip Y. F. L., Leunen, Karin, Molife, L. Rhoda, Rolfo, Christian, Grundtvig-Sørensen, Peter, De Grève, Jacques, Rottey, Sylvie, Jerusalem, Guy, Italiano, Antoine, Spicer, James, Dirix, Luc, Goessl, Carsten, Birkett, Joseph, Spencer, Stuart, Learoyd, Maria, Bailey, Christopher, and Dean, Emma

Published
2018
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32. Prognostic Significance of DNA Methylation Profiles at MRI Enhancing Tumor Recurrence

Author

Draaisma, Kaspar, Tesileanu, C Mircea S, de Heer, Iris, Klein, Martin, Smits, Marion, Reijneveld, Jaap C, Clement, Paul M, de Vos, Filip Y F, Wick, Antje, Mulholland, Paul J, Taphoorn, Martin J B, Weller, Michael, Chinot, Olivier L, Kros, Johan M, Verschuere, Tina, Coens, Corneel, Golfinopoulos, Vassilis, Gorlia, Thierry, Idbaih, Ahmed, Robe, Pierre A, van den Bent, Martin J, French, Pim J, Medical psychology, Neurology, CCA - Imaging and biomarkers, CCA - Cancer Treatment and quality of life, Radiology & Nuclear Medicine, Pathology, University of Zurich, and French, Pim J

Subjects
Cancer Research, Brain Neoplasms, Homozygote, 610 Medicine & health, Glioma, DNA Methylation, Prognosis, Magnetic Resonance Imaging, Isocitrate Dehydrogenase, 10040 Clinic for Neurology, DNA Repair Enzymes, Oncology, SDG 3 - Good Health and Well-being, Mutation, Humans, 2730 Oncology, 1306 Cancer Research, Neoplasm Recurrence, Local, DNA Modification Methylases, Sequence Deletion
Abstract

Purpose: Despite recent advances in the molecular characterization of gliomas, it remains unclear which patients benefit most from which second-line treatments. The TAVAREC trial was a randomized, open-label phase II trial assessing the benefit of the addition of the angiogenesis inhibitor bevacizumab to treatment with temozolomide in patients with a first enhancing recurrence of World Health Organization grade 2 or 3 glioma without 1p/19q codeletion. We evaluated the prognostic significance of genome-wide DNA methylation profiles and copy-number variations on the TAVAREC trial samples. Experimental Design: Isocitrate dehydrogenase (IDH) mutation status was determined via Sanger sequencing and IHC. DNA methylation analysis was performed using the MethylationEPIC BeadChip (Illumina) from which 1p/19q codeletion, MGMT promoter methylation (MGMT-STP27), and homozygous deletion of CDKN2A/B were determined. DNA methylation classes were determined according to classifiers developed in Heidelberg and The Cancer Genome Atlas (TCGA; “Heidelberg” and “TCGA” classifier respectively). Results: DNA methylation profiles of 122 samples were successfully determined. As expected, most samples were IDH-mutant (89/122) and MGMT promotor methylated (89/122). Methylation classes were prognostic for time to progression. However, Heidelberg methylation classes determined at time of diagnosis were no longer prognostic following enhancing recurrence of the tumor. In contrast, TCGA methylation classes of primary samples remained prognostic also following enhancing recurrence. Homozygous deletions in CDKN2A/B were found in 10 of 87 IDH-mutated samples and were prognostically unfavorable at recurrence. Conclusions: DNA methylome Heidelberg classification at time of diagnosis is no longer of prognostic value at the time of enhancing recurrence. CDKN2A/B deletion status was predictive of survival from progression of IDH-mutated tumors.

Published
2022
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33. Dabrafenib plus trametinib in BRAFV600E-mutated rare cancers:the phase 2 ROAR trial

Author

Subbiah, Vivek, Kreitman, Robert J., Wainberg, Zev A, Gazzah, Anas, Lassen, Ulrik, Stein, Alexander, Wen, Patrick Y, Dietrich, Sascha, de Jonge, Maja J A, Blay, Jean-Yves, Italiano, Antoine, Yonemori, Kan, Cho, Daniel C., de Vos, Filip Y. F. L., Moreau, Philippe, Fernandez, Elena Elez, Schellens, Jan H M, Zielinski, Christoph C., Redhu, Suman, Boran, Aislyn, Passos, Vanessa Q., Ilankumaran, Palanichamy, Bang, Yung-Jue, Subbiah, Vivek, Kreitman, Robert J., Wainberg, Zev A, Gazzah, Anas, Lassen, Ulrik, Stein, Alexander, Wen, Patrick Y, Dietrich, Sascha, de Jonge, Maja J A, Blay, Jean-Yves, Italiano, Antoine, Yonemori, Kan, Cho, Daniel C., de Vos, Filip Y. F. L., Moreau, Philippe, Fernandez, Elena Elez, Schellens, Jan H M, Zielinski, Christoph C., Redhu, Suman, Boran, Aislyn, Passos, Vanessa Q., Ilankumaran, Palanichamy, and Bang, Yung-Jue

Abstract

BRAFV600E alterations are prevalent across multiple tumors. Here we present final efficacy and safety results of a phase 2 basket trial of dabrafenib (BRAF kinase inhibitor) plus trametinib (MEK inhibitor) in eight cohorts of patients with BRAFV600E-mutated advanced rare cancers: anaplastic thyroid carcinoma (n = 36), biliary tract cancer (n = 43), gastrointestinal stromal tumor (n = 1), adenocarcinoma of the small intestine (n = 3), low-grade glioma (n = 13), high-grade glioma (n = 45), hairy cell leukemia (n = 55) and multiple myeloma (n = 19). The primary endpoint of investigator-assessed overall response rate in these cohorts was 56%, 53%, 0%, 67%, 54%, 33%, 89% and 50%, respectively. Secondary endpoints were median duration of response (DoR), progression-free survival (PFS), overall survival (OS) and safety. Median DoR was 14.4 months, 8.9 months, not reached, 7.7 months, not reached, 31.2 months, not reached and 11.1 months, respectively. Median PFS was 6.7 months, 9.0 months, not reached, not evaluable, 9.5 months, 5.5 months, not evaluable and 6.3 months, respectively. Median OS was 14.5 months, 13.5 months, not reached, 21.8 months, not evaluable, 17.6 months, not evaluable and 33.9 months, respectively. The most frequent (≥20% of patients) treatment-related adverse events were pyrexia (40.8%), fatigue (25.7%), chills (25.7%), nausea (23.8%) and rash (20.4%). The encouraging tumor-agnostic activity of dabrafenib plus trametinib suggests that this could be a promising treatment approach for some patients with BRAFV600E-mutated advanced rare cancers. ClinicalTrials.gov registration: NCT02034110.

Published
2023

34. Practice variation in re-resection for recurrent glioblastoma: A nationwide survey among Dutch neuro-oncology specialists

Author

MS Medische Oncologie, Cancer, Neurologen, Brain, MS Radiotherapie, Circulatory Health, van Opijnen, Mark P, de Vos, Filip Y F, Nabuurs, Rob J A, Snijders, Tom J, Nandoe Tewarie, Rishi D S, Taal, Walter, Verhoeff, Joost J C, van der Hoeven, Jacobus J M, Broekman, Marike L D, MS Medische Oncologie, Cancer, Neurologen, Brain, MS Radiotherapie, Circulatory Health, van Opijnen, Mark P, de Vos, Filip Y F, Nabuurs, Rob J A, Snijders, Tom J, Nandoe Tewarie, Rishi D S, Taal, Walter, Verhoeff, Joost J C, van der Hoeven, Jacobus J M, and Broekman, Marike L D

Published
2023

35. Limited clinical activity of palbociclib and ribociclib monotherapy in advanced cancers with cyclin D-CDK4/6 pathway alterations in the Dutch DRUP and Australian MoST trials

Author

Palliatieve Zorg, Pathologie Moleculair, Pathologie Pathologen staf, Cancer, MS Medische Oncologie, Externen Med. Onco, Zeverijn, Laurien J, Looze, Eleonora J, Thavaneswaran, Subotheni, van Berge Henegouwen, J Maxime, Simes, Robert J, Hoes, Louisa R, Sjoquist, Katrin M, van der Wijngaart, Hanneke, Sebastian, Lucille, Geurts, Birgit S, Lee, Chee K, de Wit, Gijsbrecht F, Espinoza, David, Roepman, Paul, Lin, Frank P, Jansen, Anne M L, de Leng, Wendy W J, van der Noort, Vincent, Leek, Lindsay V M, de Vos, Filip Y F L, van Herpen, Carla M L, Gelderblom, Hans, Verheul, Henk M W, Thomas, David M, Voest, Emile E, Palliatieve Zorg, Pathologie Moleculair, Pathologie Pathologen staf, Cancer, MS Medische Oncologie, Externen Med. Onco, Zeverijn, Laurien J, Looze, Eleonora J, Thavaneswaran, Subotheni, van Berge Henegouwen, J Maxime, Simes, Robert J, Hoes, Louisa R, Sjoquist, Katrin M, van der Wijngaart, Hanneke, Sebastian, Lucille, Geurts, Birgit S, Lee, Chee K, de Wit, Gijsbrecht F, Espinoza, David, Roepman, Paul, Lin, Frank P, Jansen, Anne M L, de Leng, Wendy W J, van der Noort, Vincent, Leek, Lindsay V M, de Vos, Filip Y F L, van Herpen, Carla M L, Gelderblom, Hans, Verheul, Henk M W, Thomas, David M, and Voest, Emile E

Published
2023

36. Prevalence and Predictors of Physician-Patient Discordance in Prognostic Perceptions in Advanced Cancer

Author

MS Medische Oncologie, Cancer, van der Velden, Naomi Cornelia Anna, Han, Paul K J, van Laarhoven, Hanneke W M, de Vos, Filip Y F L, Hendriks, Lizza E L, Burgers, Sjaak A, Dingemans, Anne-Marie C, van Haarst, Jan Maarten W, Dits, Joyce, Smets, Ellen M A, Henselmans, Inge, MS Medische Oncologie, Cancer, van der Velden, Naomi Cornelia Anna, Han, Paul K J, van Laarhoven, Hanneke W M, de Vos, Filip Y F L, Hendriks, Lizza E L, Burgers, Sjaak A, Dingemans, Anne-Marie C, van Haarst, Jan Maarten W, Dits, Joyce, Smets, Ellen M A, and Henselmans, Inge

Published
2023

37. Dabrafenib plus trametinib in BRAFV600E-mutated rare cancers: the phase 2 ROAR trial

Author

MS Medische Oncologie, Cancer, Subbiah, Vivek, Kreitman, Robert J, Wainberg, Zev A, Gazzah, Anas, Lassen, Ulrik, Stein, Alexander, Wen, Patrick Y, Dietrich, Sascha, de Jonge, Maja J A, Blay, Jean-Yves, Italiano, Antoine, Yonemori, Kan, Cho, Daniel C, de Vos, Filip Y F L, Moreau, Philippe, Fernandez, Elena Elez, Schellens, Jan H M, Zielinski, Christoph C, Redhu, Suman, Boran, Aislyn, Passos, Vanessa Q, Ilankumaran, Palanichamy, Bang, Yung-Jue, MS Medische Oncologie, Cancer, Subbiah, Vivek, Kreitman, Robert J, Wainberg, Zev A, Gazzah, Anas, Lassen, Ulrik, Stein, Alexander, Wen, Patrick Y, Dietrich, Sascha, de Jonge, Maja J A, Blay, Jean-Yves, Italiano, Antoine, Yonemori, Kan, Cho, Daniel C, de Vos, Filip Y F L, Moreau, Philippe, Fernandez, Elena Elez, Schellens, Jan H M, Zielinski, Christoph C, Redhu, Suman, Boran, Aislyn, Passos, Vanessa Q, Ilankumaran, Palanichamy, and Bang, Yung-Jue

Published
2023

38. Depatuxizumab-mafodotin in EGFR-amplified newly diagnosed glioblastoma: a phase III randomized clinical trial

Author

MS Medische Oncologie, Cancer, Lassman, Andrew B, Pugh, Stephanie L, Wang, Tony J C, Aldape, Kenneth, Gan, Hui K, Preusser, Matthias, Vogelbaum, Michael A, Sulman, Erik P, Won, Minhee, Zhang, Peixin, Moazami, Golnaz, Macsai, Marian S, Gilbert, Mark R, Bain, Earle E, Blot, Vincent, Ansell, Peter J, Samanta, Suvajit, Kundu, Madan G, Armstrong, Terri S, Wefel, Jeffrey S, Seidel, Clemens, de Vos, Filip Y, Hsu, Sigmund, Cardona, Andrés F, Lombardi, Giuseppe, Bentsion, Dmitry, Peterson, Richard A, Gedye, Craig, Bourg, Véronique, Wick, Antje, Curran, Walter J, Mehta, Minesh P, MS Medische Oncologie, Cancer, Lassman, Andrew B, Pugh, Stephanie L, Wang, Tony J C, Aldape, Kenneth, Gan, Hui K, Preusser, Matthias, Vogelbaum, Michael A, Sulman, Erik P, Won, Minhee, Zhang, Peixin, Moazami, Golnaz, Macsai, Marian S, Gilbert, Mark R, Bain, Earle E, Blot, Vincent, Ansell, Peter J, Samanta, Suvajit, Kundu, Madan G, Armstrong, Terri S, Wefel, Jeffrey S, Seidel, Clemens, de Vos, Filip Y, Hsu, Sigmund, Cardona, Andrés F, Lombardi, Giuseppe, Bentsion, Dmitry, Peterson, Richard A, Gedye, Craig, Bourg, Véronique, Wick, Antje, Curran, Walter J, and Mehta, Minesh P

Published
2023

40. Potential Adverse Outcomes of Shared Decision Making about Palliative Cancer Treatment: A Secondary Analysis of a Randomized Trial.

Author

van de Water, Loïs F., Bos–van den Hoek, Danique W., Kuijper, Steven C., van Laarhoven, Hanneke W. M., Creemers, Geert-Jan, Dohmen, Serge E., Fiebrich, Helle-Brit, Ottevanger, Petronella B., Sommeijer, Dirkje W., de Vos, Filip Y. F., Smets, Ellen M. A., and Henselmans, Inge

Abstract

Background: While shared decision making (SDM) is advocated for ethical reasons and beneficial outcomes, SDM might also negatively affect patients with incurable cancer. The current study explored whether SDM, and an oncologist training in SDM, are associated with adverse outcomes (i.e., patient anxiety, tension, helplessness/hopelessness, decisional uncertainty, and reduced fighting spirit). Design: A secondary analysis of a randomized clinical trial investigating the effects of SDM interventions in the context of advanced cancer. The relations between observed SDM (OPTION12), specific SDM elements (4SDM), oncologist SDM training, and adverse outcomes were analyzed. We modeled adverse outcomes as a multivariate phenomenon, followed by univariate regressions if significant. Results: In total, 194 patients consulted by 31 oncologists were included. In a multivariate analysis, observed SDM and adverse outcomes were significantly related. More specifically, more observed SDM in the consultation was related to patients reporting more tension (P = 0.002) and more decisional uncertainty (P = 0.004) at 1 wk after the consultation. The SDM element "informing about the options" was especially found to be related to adverse outcomes, specifically to more helplessness/hopelessness (P = 0.002) and more tension (P = 0.016) at 1 wk after the consultation. Whether the patient consulted an oncologist who had received SDM training or not was not significantly related to adverse outcomes. No relations with long-term adverse outcomes were found. Conclusions: It is important for oncologists to realize that for some patients, SDM may temporarily be associated with negative emotions. Further research is needed to untangle which, when, and how adverse outcomes might occur and whether and how burden may be minimized for patients. Highlights: Observed shared decision making was related to more tension and uncertainty postconsultation in advanced cancer patients However, training oncologists in SDM did not affect adverse outcomes. Further research is needed to untangle which, when, and how adverse outcomes might occur and how burden may be minimized [ABSTRACT FROM AUTHOR]

Published
2024
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41. Prevalence and Predictors of Physician-Patient Discordance in Prognostic Perceptions in Advanced Cancer

Author

van der Velden, Naomi Cornelia Anna, primary, Han, Paul K J, additional, van Laarhoven, Hanneke W M, additional, de Vos, Filip Y F L, additional, Hendriks, Lizza E L, additional, Burgers, Sjaak A, additional, Dingemans, Anne-Marie C, additional, van Haarst, Jan Maarten W, additional, Dits, Joyce, additional, Smets, Ellen M A, additional, and Henselmans, Inge, additional

Published
2023
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44. Health-Related Quality of Life Results from the Randomized Phase Ii Tavarec Trial on Temozolomide With or Without Bevacizumab in 1p/19q Intact First Recurrence Who Grade 2 and 3 Glioma (Eortc 26091)

Author

Reijneveld, Jaap C., primary, Machingura, Abigirl, additional, Coens, Corneel, additional, Taphoorn, Martin J. B., additional, Taal, Walter, additional, Clement, Paul M., additional, Idbaih, Ahmed, additional, de Vos, Filip Y. F., additional, Klein, Martin, additional, Wick, Wolfgang, additional, Mulholland, Paul J., additional, Lewis, Joanne, additional, Golfinopoulos, Vassilis, additional, Ghislain, Irina, additional, Bottomley, Andrew, additional, van den Bent, Martin, additional, and Group, EORTC Brain Tumor, additional

Published
2023
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46. Single-agent bevacizumab or lomustine versus a combination of bevacizumab plus lomustine in patients with recurrent glioblastoma (BELOB trial): a randomised controlled phase 2 trial

Author

Taal, Walter, Oosterkamp, Hendrika M, Walenkamp, Annemiek M E, Dubbink, Hendrikus J, Beerepoot, Laurens V, Hanse, Monique C J, Buter, Jan, Honkoop, Aafke H, Boerman, Dolf, de Vos, Filip Y F, Dinjens, Winand N M, Enting, Roelien H, Taphoorn, Martin J B, van den Berkmortel, Franchette W P J, Jansen, Rob L H, Brandsma, Dieta, Bromberg, Jacoline E C, van Heuvel, Irene, Vernhout, René M, van der Holt, Bronno, and van den Bent, Martin J

Published
2014
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48. Limited clinical activity of palbociclib and ribociclib monotherapy in advanced cancers with cyclin D‐CDK4/6 pathway alterations in the Dutch DRUP and Australian MoST trials.

Author

Zeverijn, Laurien J., Looze, Eleonora J., Thavaneswaran, Subotheni, van Berge Henegouwen, J. Maxime, Simes, Robert J., Hoes, Louisa R., Sjoquist, Katrin M., van der Wijngaart, Hanneke, Sebastian, Lucille, Geurts, Birgit S., Lee, Chee K., de Wit, Gijsbrecht F., Espinoza, David, Roepman, Paul, Lin, Frank P., Jansen, Anne M. L., de Leng, Wendy W. J., van der Noort, Vincent, Leek, Lindsay V. M., and de Vos, Filip Y. F. L.

Subjects
CYCLINS, CYCLIN-dependent kinase inhibitors, CANCER patients, PROGRESSION-free survival, CYCLIN-dependent kinases
Abstract

The Dutch Drug Rediscovery Protocol (DRUP) and the Australian Cancer Molecular Screening and Therapeutic (MoST) Program are similar nonrandomized, multidrug, pan‐cancer trial platforms that aim to identify signals of clinical activity of molecularly matched targeted therapies or immunotherapies outside their approved indications. Here, we report results for advanced or metastatic cancer patients with tumors harboring cyclin D‐CDK4/6 pathway alterations treated with CDK4/6 inhibitors palbociclib or ribociclib. We included adult patients that had therapy‐refractory solid malignancies with the following alterations: amplifications of CDK4, CDK6, CCND1, CCND2 or CCND3, or complete loss of CDKN2A or SMARCA4. Within MoST, all patients were treated with palbociclib, whereas in DRUP, palbociclib and ribociclib were assigned to different cohorts (defined by tumor type and alteration). The primary endpoint for this combined analysis was clinical benefit, defined as confirmed objective response or stable disease ≥16 weeks. We treated 139 patients with a broad variety of tumor types; 116 with palbociclib and 23 with ribociclib. In 112 evaluable patients, the objective response rate was 0% and clinical benefit rate at 16 weeks was 15%. Median progression‐free survival was 4 months (95% CI: 3‐5 months), and median overall survival 5 months (95% CI: 4‐6 months). In conclusion, only limited clinical activity of palbociclib and ribociclib monotherapy in patients with pretreated cancers harboring cyclin D‐CDK4/6 pathway alterations was observed. Our findings indicate that monotherapy use of palbociclib or ribociclib is not recommended and that merging data of two similar precision oncology trials is feasible. [ABSTRACT FROM AUTHOR]

Published
2023
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49. Cancer patients' trust as a motivator to seek a second opinion and its effects on trust.

Author

Hillen, Marij A., Smets, Ellen M. A., M. Stouthard, Jacqueline, de Vos, Filip Y. F., and Lehmann, Vicky

Subjects
MOTIVATION (Psychology), PHYSICIAN-patient relations, RESEARCH methodology, SELF-evaluation, CANCER patients, MEDICAL referrals, COMMUNICATION, SOUND recordings, DESCRIPTIVE statistics, TRUST, LONGITUDINAL method, ONCOLOGISTS
Abstract

Cancer patients may seek a second opinion (SO) driven by reduced trust in their own providers. Their trust may be diminished or reinforced through the SO. This study aimed to assess (1) what proportion of patients seek SOs motivated by lacking trust and how trust changes over time; (2) whether patients' trust differs by the outcome of the SO (i.e. similar/different opinion); and (3) how communication during the SO affects trust. A longitudinal mixed methods study including self-report assessments before (T0), immediately following (T1), and two months after the SO (T2). SO consultations (N = 62) were audio recorded, and patient-oncologist communication about the referring oncologist was coded. Patient-reported motives and their trust in referring oncologists. Reduced trust motivated 21% of patients to seek a SO. Most patients criticised their referring oncologist. Consulting oncologists generally defended their colleagues, but such affirmation was unrelated to patients' subsequent trust. Over time, trust did not change substantially. Yet, it was restored in patients motivated by impaired trust, and remained low for patients receiving a different medical outcome. Patients need support to more constructively discuss their treatment relationship. Oncologists need support in providing independent SOs without harming trust relations. [ABSTRACT FROM AUTHOR]

Published
2023
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50. A dose escalating phase I study of GLPG0187, a broad spectrum integrin receptor antagonist, in adult patients with progressive high-grade glioma and other advanced solid malignancies

Author

Cirkel, Geert A., Kerklaan, Bojana Milojkovic, Vanhoutte, Frédéric, der Aa, Annegret Van, Lorenzon, Giocondo, Namour, Florence, Pujuguet, Philippe, Darquenne, Sophie, de Vos, Filip Y. F., Snijders, Tom J., Voest, Emile E., Schellens, Jan H. M., and Lolkema, Martijn P.

Published
2016
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