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2. High Prevalence of Chromosomal Rearrangements and LINE Retrotranspositions Detected in Formalin-Fixed, Paraffin-Embedded Colorectal Cancer Tissue

Author

Rubio-Alarcón, Carmen, Stelloo, Ellen, Vessies, Daan C.L., van 't Erve, Iris, Mekkes, Nienke J., Swennenhuis, Joost, Lakbir, Soufyan, van Bree, Elisabeth J., Tijssen, Marianne, Delis-van Diemen, Pien, Lanfermeijer, Mirthe, Linders, Theodora, van den Broek, Daan, Punt, Cornelis J.A., Heringa, Jaap, Meijer, Gerrit A., Abeln, Sanne, Feitsma, Harma, and Fijneman, Remond J.A.

Published
2024
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4. Author Correction: High- or low-dose preoperative ipilimumab plus nivolumab in stage III urothelial cancer: the phase 1B NABUCCO trial

Author

van Dorp, Jeroen, Pipinikas, Christodoulos, Suelmann, Britt B. M., Mehra, Niven, van Dijk, Nick, Marsico, Giovanni, van Montfoort, Maurits L., Hackinger, Sophie, Braaf, Linde M., Amarante, Tauanne, van Steenis, Charlaine, McLay, Kirsten, Daletzakis, Antonios, van den Broek, Daan, van de Kamp, Maaike W., Hendricksen, Kees, de Feijter, Jeantine M., Boellaard, Thierry N., Meijer, Richard P., van der Heijden, Antoine G., Rosenfeld, Nitzan, van Rhijn, Bas W. G., Jones, Greg, and van der Heijden, Michiel S.

Published
2024
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5. High- or low-dose preoperative ipilimumab plus nivolumab in stage III urothelial cancer: the phase 1B NABUCCO trial

Author

van Dorp, Jeroen, Pipinikas, Christodoulos, Suelmann, Britt B. M., Mehra, Niven, van Dijk, Nick, Marsico, Giovanni, van Montfoort, Maurits L., Hackinger, Sophie, Braaf, Linde M., Amarante, Tauanne, van Steenis, Charlaine, McLay, Kirsten, Daletzakis, Antonios, van den Broek, Daan, van de Kamp, Maaike W., Hendricksen, Kees, de Feijter, Jeantine M., Boellaard, Thierry N., Meijer, Richard P., van der Heijden, Antoine G., Rosenfeld, Nitzan, van Rhijn, Bas W. G., Jones, Greg, and van der Heijden, Michiel S.

Published
2023
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8. A scenario‐drafting study to explore potential future implementation pathways of circulating tumor DNA testing in oncology.

Author

Kramer, Astrid, Rubio‐Alarcón, Carmen, van den Broek, Daan, Vessies, Daan C. L., van't Erve, Iris, Meijer, Gerrit A., Vink, Geraldine R., Schuuring, Ed, Fijneman, Remond J. A., Coupé, Veerle M. H., and Retèl, Valesca P.

Abstract

Circulating tumor DNA (ctDNA) detection has multiple promising applications in oncology, but the road toward implementation in clinical practice is unclear. We aimed to support the implementation process by exploring potential future pathways of ctDNA testing. To do so, we studied four ctDNA‐testing applications in two cancer types and elicited opinions from 30 ctDNA experts in the Netherlands. Our results showed that the current available evidence differed per application and cancer type. Tumor profiling and monitoring treatment response were found most likely to be implemented in non‐small cell lung cancer (NSCLC) within 5 years. For colorectal cancer, applications of ctDNA testing were found to be at an early stage in the implementation process. Demonstrating clinical utility was found a key aspect for successful implementation, but there was no consensus regarding the evidence requirements. The next step toward implementation is to define how clinical utility of biomarkers should be evaluated. Finally, these data indicate that specific challenges for each clinical application and tumor type should be appropriately addressed in a deliberative process involving all stakeholders to ensure implementation of ctDNA testing and timely access for patients. [ABSTRACT FROM AUTHOR]

Published
2024
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10. External Quality Assessment on Molecular Tumor Profiling with Circulating Tumor DNA-Based Methodologies Routinely Used in Clinical Pathology within the COIN Consortium

Author

Pathologie Pathologen staf, Cancer, van der Leest, Paul, Rozendal, Pim, Hinrichs, John, van Noesel, Carel J M, Zwaenepoel, Karen, Deiman, Birgit, Huijsmans, Cornelis J J, van Eijk, Ronald, Speel, Ernst Jan M, van Haastert, Rick J, Ligtenberg, Marjolijn J L, van Schaik, Ron H N, Jansen, Maurice P H M, Dubbink, Hendrikus J, de Leng, Wendy W, Leers, Mathie P G, Tamminga, Menno, van den Broek, Daan, van Kempen, Léon C, Schuuring, Ed, Pathologie Pathologen staf, Cancer, van der Leest, Paul, Rozendal, Pim, Hinrichs, John, van Noesel, Carel J M, Zwaenepoel, Karen, Deiman, Birgit, Huijsmans, Cornelis J J, van Eijk, Ronald, Speel, Ernst Jan M, van Haastert, Rick J, Ligtenberg, Marjolijn J L, van Schaik, Ron H N, Jansen, Maurice P H M, Dubbink, Hendrikus J, de Leng, Wendy W, Leers, Mathie P G, Tamminga, Menno, van den Broek, Daan, van Kempen, Léon C, and Schuuring, Ed

Published
2024

11. Early evaluation of the effectiveness and cost-effectiveness of ctDNA-guided selection for adjuvant chemotherapy in stage II colon cancer

Author

Unit Opleiding Aios, Cancer, Onderzoek Medische Oncologie, MS Medische Oncologie, Kramer, Astrid, Greuter, Marjolein J E, Schraa, Suzanna J, Vink, Geraldine R, Phallen, Jillian, Velculescu, Victor E, Meijer, Gerrit A, van den Broek, Daan, Koopman, Miriam, Roodhart, Jeanine M L, Fijneman, Remond J A, Retèl, Valesca P, Coupé, Veerle M H, Unit Opleiding Aios, Cancer, Onderzoek Medische Oncologie, MS Medische Oncologie, Kramer, Astrid, Greuter, Marjolein J E, Schraa, Suzanna J, Vink, Geraldine R, Phallen, Jillian, Velculescu, Victor E, Meijer, Gerrit A, van den Broek, Daan, Koopman, Miriam, Roodhart, Jeanine M L, Fijneman, Remond J A, Retèl, Valesca P, and Coupé, Veerle M H

Published
2024

12. A phase 2 trial combining afatinib with cetuximab in patients with EGFR exon 20 insertion–positive non–small cell lung cancer

Author

van Veggel, Bianca A.M.H., van der Wekken, Anthonie J., Paats, Marthe S., Hendriks, Lizza E.L., Hashemi, Sayed M.S., Daletzakis, Antonios, van den Broek, Daan, Bosch, Linda J.W., Monkhorst, Kim, Smit, Egbert F., de Langen, Adrianus J., van Veggel, Bianca A.M.H., van der Wekken, Anthonie J., Paats, Marthe S., Hendriks, Lizza E.L., Hashemi, Sayed M.S., Daletzakis, Antonios, van den Broek, Daan, Bosch, Linda J.W., Monkhorst, Kim, Smit, Egbert F., and de Langen, Adrianus J.

Abstract

Background: Epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins) mutations are the third most common EGFR mutations in patients with non–small cell lung cancer (NSCLC) and are associated with primary resistance to EGFR tyrosine kinase inhibitors (TKIs). There is evidence of activity of combining EGFR TKIs with monoclonal antibodies. This study reports on the efficacy and safety of afatinib in combination with cetuximab. Methods: In this single-arm phase 2 trial, patients with advanced NSCLC harboring an EGFR ex20ins mutation were treated with afatinib 40 mg once daily in combination with cetuximab 500 mg/m2 every 2 weeks. The primary end point was disease control rate (DCR) at 18 weeks of treatment. Results: Thirty-seven patients started treatment, with a median age of 65 years (range, 40–80 years), 78% female, and 95% White. The study achieved its primary end point with a DCR of 54% at 18 weeks, an overall response rate (ORR) of 43%, and a 32% confirmed ORR. Best responses were partial (n = 16), stable (n = 16), progressive disease (n = 2), or not evaluable (n = 3). Median progression-free survival was 5.5 months (95% CI, 3.7–8.3 months) and median overall survival was 16.8 months (95% CI, 10.7–25.8 months). The most common treatment-related adverse events (TRAEs) were diarrhea (70%), rash (65%), dry skin (59%), paronychia (54%), and erythema (43%). Grade 3 TRAEs were reported in 54% of all patients. Conclusions: Combination treatment with afatinib and cetuximab demonstrated antitumor activity with a DCR of 54% at 18 weeks and a 32% confirmed ORR. Toxicity was significant, although manageable, after dose reduction.

Published
2024

13. Early evaluation of the effectiveness and cost-effectiveness of ctDNA-guided selection for adjuvant chemotherapy in stage II colon cancer

Author

Kramer, Astrid, Greuter, Marjolein J.E., Schraa, Suzanna J., Vink, Geraldine R., Phallen, Jillian, Velculescu, Victor E., Meijer, Gerrit A., van den Broek, Daan, Koopman, Miriam, Roodhart, Jeanine M.L., Fijneman, Remond J.A., Retèl, Valesca P., Coupé, Veerle M.H., Kramer, Astrid, Greuter, Marjolein J.E., Schraa, Suzanna J., Vink, Geraldine R., Phallen, Jillian, Velculescu, Victor E., Meijer, Gerrit A., van den Broek, Daan, Koopman, Miriam, Roodhart, Jeanine M.L., Fijneman, Remond J.A., Retèl, Valesca P., and Coupé, Veerle M.H.

Abstract

Background: Current patient selection for adjuvant chemotherapy (ACT) after curative surgery for stage II colon cancer (CC) is suboptimal, causing overtreatment of high-risk patients and undertreatment of low-risk patients. Postoperative circulating tumor DNA (ctDNA) could improve patient selection for ACT. Objectives: We conducted an early model-based evaluation of the (cost-)effectiveness of ctDNA-guided selection for ACT in stage II CC in the Netherlands to assess the conditions for cost-effective implementation. Methods: A validated Markov model, simulating 1000 stage II CC patients from diagnosis to death, was supplemented with ctDNA data. Five ACT selection strategies were evaluated: the current guideline (pT4, pMMR), ctDNA-only, and three strategies that combined ctDNA status with pT4 and pMMR status in different ways. For each strategy, the costs, life years, quality-adjusted life years (QALYs), recurrences, and CC deaths were estimated. Sensitivity analyses were performed to assess the impact of the costs of ctDNA testing, strategy adherence, ctDNA as a predictive biomarker, and ctDNA test performance. Results: Model predictions showed that compared to current guidelines, the ctDNA-only strategy was less effective (+2.2% recurrences, −0.016 QALYs), while the combination strategies were more effective (−3.6% recurrences, +0.038 QALYs). The combination strategies were not cost-effective, since the incremental cost-effectiveness ratio was €67,413 per QALY, exceeding the willingness-to-pay threshold of €50,000 per QALY. Sensitivity analyses showed that the combination strategies would be cost-effective if the ctDNA test costs were lower than €1500, or if ctDNA status was predictive of treatment response, or if the ctDNA test performance improved substantially. Conclusion: Adding ctDNA to current high-risk clinicopathological features (pT4 and pMMR) can improve patient selection for ACT and can also potentially be cost-effective. Future studies should investi

Published
2024

14. Author Correction: High- or low-dose preoperative ipilimumab plus nivolumab in stage III urothelial cancer: the phase 1B NABUCCO trial (Nature Medicine, (2023), 29, 3, (588-592), 10.1038/s41591-022-02199-y)

Author

Cancer, MS Medische Oncologie, MS Urologische Oncologie, van Dorp, Jeroen, Pipinikas, Christodoulos, Suelmann, Britt B M, Mehra, Niven, van Dijk, Nick, Marsico, Giovanni, van Montfoort, Maurits L, Hackinger, Sophie, Braaf, Linde M, Amarante, Tauanne, van Steenis, Charlaine, McLay, Kirsten, Daletzakis, Antonios, van den Broek, Daan, van de Kamp, Maaike W, Hendricksen, Kees, de Feijter, Jeantine M, Boellaard, Thierry N, Meijer, Richard P, van der Heijden, Antoine G, Rosenfeld, Nitzan, van Rhijn, Bas W G, Jones, Greg, van der Heijden, Michiel S, Cancer, MS Medische Oncologie, MS Urologische Oncologie, van Dorp, Jeroen, Pipinikas, Christodoulos, Suelmann, Britt B M, Mehra, Niven, van Dijk, Nick, Marsico, Giovanni, van Montfoort, Maurits L, Hackinger, Sophie, Braaf, Linde M, Amarante, Tauanne, van Steenis, Charlaine, McLay, Kirsten, Daletzakis, Antonios, van den Broek, Daan, van de Kamp, Maaike W, Hendricksen, Kees, de Feijter, Jeantine M, Boellaard, Thierry N, Meijer, Richard P, van der Heijden, Antoine G, Rosenfeld, Nitzan, van Rhijn, Bas W G, Jones, Greg, and van der Heijden, Michiel S

Published
2024

15. External Quality Assessment on Molecular Tumor Profiling with Circulating Tumor DNA-Based Methodologies Routinely Used in Clinical Pathology within the COIN Consortium

Author

van der Leest, Paul, Rozendal, Pim, Hinrichs, John, van Noesel, Carel J.M., Zwaenepoel, Karen, Deiman, Birgit, Huijsmans, Cornelis J.J., van Eijk, Ronald, Speel, Ernst Jan M., van Haastert, Rick J., Ligtenberg, Marjolijn J.L., van Schaik, Ron H.N., Jansen, Maurice P.H.M., Dubbink, Hendrikus J., de Leng, Wendy W., Leers, Mathie P.G., Tamminga, Menno, van den Broek, Daan, van Kempen, Leon C., Schuuring, Ed, van der Leest, Paul, Rozendal, Pim, Hinrichs, John, van Noesel, Carel J.M., Zwaenepoel, Karen, Deiman, Birgit, Huijsmans, Cornelis J.J., van Eijk, Ronald, Speel, Ernst Jan M., van Haastert, Rick J., Ligtenberg, Marjolijn J.L., van Schaik, Ron H.N., Jansen, Maurice P.H.M., Dubbink, Hendrikus J., de Leng, Wendy W., Leers, Mathie P.G., Tamminga, Menno, van den Broek, Daan, van Kempen, Leon C., and Schuuring, Ed

Abstract

Background: Identification of tumor-derived variants in circulating tumor DNA (ctDNA) has potential as a sensitive and reliable surrogate for tumor tissue-based routine diagnostic testing. However, variations in pre(analytical) procedures affect the efficiency of ctDNA recovery. Here, an external quality assessment (EQA) was performed to determine the performance of ctDNA mutation detection work flows that are used in current diagnostic settings across laboratories within the Dutch COIN consortium (ctDNA on the road to implementation in The Netherlands). Methods: Aliquots of 3 high-volume diagnostic leukapheresis (DLA) plasma samples and 3 artificial reference plasma samples with predetermined mutations were distributed among 16 Dutch laboratories. Participating laboratories were requested to perform ctDNA analysis for BRAF exon 15, EGFR exon 18-21, and KRAS exon 2-3 using their regular circulating cell-free DNA (ccfDNA) analysis work flow. Laboratories were assessed based on adherence to the study protocol, overall detection rate, and overall genotyping performance. Results: A broad range of preanalytical conditions (e.g., plasma volume, elution volume, and extraction methods) and analytical methodologies (e.g., droplet digital PCR [ddPCR], small-panel PCR assays, and next-generation sequencing [NGS]) were used. Six laboratories (38%) had a performance score of >0.90; all other laboratories scored between 0.26 and 0.80. Although 13 laboratories (81%) reached a 100% overall detection rate, the therapeutically relevant EGFR p.(S752_I759del) (69%), EGFR p.(N771_H773dup) (50%), and KRAS p.(G12C) (48%) mutations were frequently not genotyped accurately. Conclusions: Divergent (pre)analytical protocols could lead to discrepant clinical outcomes when using the same plasma samples. Standardization of (pre)analytical work flows can facilitate the implementation of reproducible liquid biopsy testing in the clinical routine.

Published
2024

16. Design, validation and performance of aspartate aminotransferase- and lactate dehydrogenase-reporting algorithms for haemolysed specimens including correction within quality specifications.

Author

Colak, Selcuk, Tasdemir, Onur, van der Schaaf, Marianne, Opdam, Frans, van den Noort, Vincent, van den Broek, Daan, and van Rossum, Huub H

Subjects
CORRECTION factors, MEDICAL laboratories, ASPARTIC acid, EXPERIMENTAL design, ALGORITHMS
Abstract

Background: In vitro haemolysis is a major operational challenge for medical laboratories. A new experimental design was used to investigate under what conditions algorithms could be designed to report either quantitative or qualitative aspartate aminotransferase and lactate dehydrogenase results outside the manufacturer's haemolysis specifications. Quantitative corrections were required to meet prespecified quality specifications. Methods: Twenty-five patient samples were used to design reporting algorithms and another 41 patient samples were used to validate the algorithms. Aspartate aminotransferase, lactate dehydrogenase and haemolysis index were determined using a Cobas 6000 analyser (Roche diagnostics, Mannheim, Germany). Correction factors were determined, and the accuracy of the correction was investigated. Reporting algorithms were designed based on (i) the manufacturer's cut-off for the haemolysis index, (ii) corrections within the total allowable error specification and (iii) qualitative reporting based on obtained results. The impact of the reporting algorithms was retrospectively determined by recalculating six months of aspartate aminotransferase and lactate dehydrogenase results. Results: No correction for aspartate aminotransferase/lactate dehydrogenase was possible for results below the upper reference interval limit, while results equal to or greater than the upper reference interval limit could, up to mild haemolysis, be corrected within the total error criterion. All samples generated from the validated patient cohort fulfilled the set criteria. The algorithms allowed reporting 88.5% and 85.9% of otherwise unreported aspartate aminotransferase and lactate dehydrogenase results, respectively. Conclusions: An approach is presented that allows to generate and validate reporting algorithms for aspartate aminotransferase and lactate dehydrogenase compatible with prespecified quality specifications. The designed algorithms resulted in a significant reduction of otherwise unreported aspartate aminotransferase and lactate dehydrogenase results. [ABSTRACT FROM AUTHOR]

Published
2024
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18. External Quality Assessment on Molecular Tumor Profiling with Circulating Tumor DNA-Based Methodologies Routinely Used in Clinical Pathology within the COIN Consortium

Author

van der Leest, Paul, primary, Rozendal, Pim, additional, Hinrichs, John, additional, van Noesel, Carel J M, additional, Zwaenepoel, Karen, additional, Deiman, Birgit, additional, Huijsmans, Cornelis J J, additional, van Eijk, Ronald, additional, Speel, Ernst Jan M, additional, van Haastert, Rick J, additional, Ligtenberg, Marjolijn J L, additional, van Schaik, Ron H N, additional, Jansen, Maurice P H M, additional, Dubbink, Hendrikus J, additional, de Leng, Wendy W, additional, Leers, Mathie P G, additional, Tamminga, Menno, additional, van den Broek, Daan, additional, van Kempen, Léon C, additional, and Schuuring, Ed, additional

Published
2024
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19. Redactioneel.

Author

Budiman, Manneke and van den Broek, Daan

Published
2024

21. Analytical and adaptable initial conditions for dry and moist baroclinic waves in the global hydrostatic model OpenIFS (CY43R3).

Author

Bouvier, Clément, van den Broek, Daan, Ekblom, Madeleine, and Sinclair, Victoria A.

Subjects
*WIND speed, *NUMERICAL weather forecasting, *ZONAL winds, *INVISCID flow, *STANDARD deviations, *WEATHER forecasting, *CYCLONES
Abstract

This article presents a description of an analytical, stable, and flexible initial background state for both dry and moist baroclinic wave simulation on an aquaplanet in order to test the dynamical core of numerical weather prediction models and study the dynamics and evolution of extratropical cyclones. The initial background state is derived from an analytical zonal wind speed field, or jet structure, and the hydrostatic primitive equations for moist adiabatic and frictionless flow in spherical coordinates. A baroclinic wave can develop if a perturbation is added to the zonal wind speed field. This new baroclinic wave configuration has been implemented in the Open Integrated Forecasting System (OpenIFS) CY43R3, a global numerical weather prediction model developed by the European Centre for Medium-Range Weather Forecasts. In total, seven parameters can be used to control the generation of the initial background state and hence the development of the baroclinic waves in the OpenIFS configuration file: the jet's width, the jet's height, the maximum zonal mean wind speed of the jet, the horizontal mean of the surface virtual temperature, the surface relative humidity, the lapse rate, and the surface roughness. Nine dry and nine moist initial background states have been generated to test their stability without perturbations. The meteorological stability of the initial states is investigated by examining the spatial distributions of the equivalent potential temperature, the absolute vorticity, and the Brunt–Väisälä frequency. Moreover, the root mean square error (RMSE) of the zonal wind speed has been computed to assess their numerical stability. Finally, six dry and six moist initial background state have been used with an unbalanced perturbation to ensure that the baroclinic life cycles that develop are physically realistic. The resulting baroclinic wave is shown to be sensitive to the jet's width. This configuration for baroclinic wave simulations will be used to create a large ensemble of baroclinic life cycles to study how extratropical cyclones may evolve in the future. [ABSTRACT FROM AUTHOR]

Published
2024
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22. A scenario‐drafting study to explore potential future implementation pathways of circulating tumor DNA testing in oncology

Author

Kramer, Astrid, primary, Rubio‐Alarcón, Carmen, additional, van den Broek, Daan, additional, Vessies, Daan C. L., additional, van `t Erve, Iris, additional, Meijer, Gerrit A., additional, Vink, Geraldine R., additional, Schuuring, Ed, additional, Fijneman, Remond J.A., additional, Coupé, Veerle M.H., additional, and Retèl, Valesca P., additional

Published
2023
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23. A phase 2 trial combining afatinib with cetuximab in patients with EGFR exon 20 insertion–positive non–small cell lung cancer

Author

van Veggel, Bianca A. M. H., primary, van der Wekken, Anthonie J., additional, Paats, Marthe S., additional, Hendriks, Lizza E. L., additional, Hashemi, Sayed M. S., additional, Daletzakis, Antonios, additional, van den Broek, Daan, additional, Bosch, Linda J. W., additional, Monkhorst, Kim, additional, Smit, Egbert F., additional, and de Langen, Adrianus J., additional

Published
2023
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25. Tumor-educated platelet blood tests for Non-Small Cell Lung Cancer detection and management

Author

Antunes-Ferreira, Mafalda, D’Ambrosi, Silvia, Arkani, Mohammad, Post, Edward, in ‘t Veld, Sjors G. J. G., Ramaker, Jip, Zwaan, Kenn, Kucukguzel, Ece Demirel, Wedekind, Laurine E., Griffioen, Arjan W., Oude Egbrink, Mirjam, Kuijpers, Marijke J. E., van den Broek, Daan, Noske, David P., Hartemink, Koen J., Sabrkhany, Siamack, Bahce, Idris, Sol, Nik, Bogaard, Harm-Jan, Koppers-Lalic, Danijela, Best, Myron G., Wurdinger, Thomas, Neurosurgery, Pulmonary medicine, Medical oncology laboratory, AII - Cancer immunology, CCA - Cancer biology and immunology, CCA - Cancer Treatment and quality of life, ACS - Pulmonary hypertension & thrombosis, CCA - Imaging and biomarkers, and CCA - Cancer immunology

Abstract

Liquid biopsy approaches offer a promising technology for early and minimally invasive cancer detection. Tumor-educated platelets (TEPs) have emerged as a promising liquid biopsy biosource for the detection of various cancer types. In this study, we processed and analyzed the TEPs collected from 466 Non-small Cell Lung Carcinoma (NSCLC) patients and 410 asymptomatic individuals (controls) using the previously established thromboSeq protocol. We developed a novel particle-swarm optimization machine learning algorithm which enabled the selection of an 881 RNA biomarker panel (AUC 0.88). Herein we propose and validate in an independent cohort of samples (n = 558) two approaches for blood samples testing: one with high sensitivity (95% NSCLC detected) and another with high specificity (94% controls detected). Our data explain how TEP-derived spliced RNAs may serve as a biomarker for minimally-invasive clinical blood tests, complement existing imaging tests, and assist the detection and management of lung cancer patients.

Published
2023
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29. Optimising primary molecular profiling in non-small cell lung cancer

Author

Schouten, Robert Dirk, primary, Schouten, Irene, additional, Schuurbiers, Milou, additional, Van der Noort, Vincent, additional, Damhuis, Ronald, additional, Van der Heijden, Erik, additional, Burgers, Sjaak, additional, Barlo, Nicole, additional, Van Lindert, Anne, additional, Maas, Klaar, additional, Van den Brand, Joop, additional, Smit, Arthur, additional, Van Haarst, Jan-Maarten, additional, Van der Maat, Bas, additional, Schuuring, Ed, additional, Blaauwgeers, Hans, additional, Willems, Stefan, additional, Monkhorst, Kim, additional, Van den Broek, Daan, additional, and Van den Heuvel, Michel, additional

Published
2023
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30. IMPemBra: a phase 2 study comparing pembrolizumab with intermittent/short-term dual MAPK pathway inhibition plus pembrolizumab in patients with melanoma harboring the BRAFV600 mutation

Author

Rozeman, Elisa A, primary, Versluis, Judith M, additional, Sikorska, Karolina, additional, Hoefsmit, Esmée P, additional, Dimitriadis, Petros, additional, Rao, Disha, additional, Lacroix, Ruben, additional, Grijpink-Ongering, Lindsay G, additional, Lopez-Yurda, Marta, additional, Heeres, Birthe C, additional, van de Wiel, Bart A, additional, Flohil, Claudie, additional, Sari, Aysegul, additional, Heijmink, Stijn W T P J, additional, van den Broek, Daan, additional, Broeks, Annegien, additional, de Groot, Jan Willem B, additional, Vollebergh, Marieke A, additional, Wilgenhof, Sofie, additional, van Thienen, Johannes V, additional, Haanen, John B A G, additional, and Blank, Christian U, additional

Published
2023
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31. A phase 2 trial combining afatinib with cetuximab in patients with EGFR exon 20 insertion–positive non–small cell lung cancer.

Author

van Veggel, Bianca A. M. H., van der Wekken, Anthonie J., Paats, Marthe S., Hendriks, Lizza E. L., Hashemi, Sayed M. S., Daletzakis, Antonios, van den Broek, Daan, Bosch, Linda J. W., Monkhorst, Kim, Smit, Egbert F., and de Langen, Adrianus J.

Subjects
NON-small-cell lung carcinoma, CETUXIMAB, AFATINIB, EPIDERMAL growth factor receptors, PROTEIN-tyrosine kinase inhibitors
Abstract

Background: Epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins) mutations are the third most common EGFR mutations in patients with non–small cell lung cancer (NSCLC) and are associated with primary resistance to EGFR tyrosine kinase inhibitors (TKIs). There is evidence of activity of combining EGFR TKIs with monoclonal antibodies. This study reports on the efficacy and safety of afatinib in combination with cetuximab. Methods: In this single‐arm phase 2 trial, patients with advanced NSCLC harboring an EGFR ex20ins mutation were treated with afatinib 40 mg once daily in combination with cetuximab 500 mg/m2 every 2 weeks. The primary end point was disease control rate (DCR) at 18 weeks of treatment. Results: Thirty‐seven patients started treatment, with a median age of 65 years (range, 40–80 years), 78% female, and 95% White. The study achieved its primary end point with a DCR of 54% at 18 weeks, an overall response rate (ORR) of 43%, and a 32% confirmed ORR. Best responses were partial (n = 16), stable (n = 16), progressive disease (n = 2), or not evaluable (n = 3). Median progression‐free survival was 5.5 months (95% CI, 3.7–8.3 months) and median overall survival was 16.8 months (95% CI, 10.7–25.8 months). The most common treatment‐related adverse events (TRAEs) were diarrhea (70%), rash (65%), dry skin (59%), paronychia (54%), and erythema (43%). Grade 3 TRAEs were reported in 54% of all patients. Conclusions: Combination treatment with afatinib and cetuximab demonstrated antitumor activity with a DCR of 54% at 18 weeks and a 32% confirmed ORR. Toxicity was significant, although manageable, after dose reduction. Combination treatment with afatinib and cetuximab in patients with non–small cell lung cancer harboring an EGFR exon 20 insertion mutation demonstrated antitumor activity with a disease control rate of 54% at 18 weeks of treatment and a 32% confirmed overall response rate. [ABSTRACT FROM AUTHOR]

Published
2024
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32. Squamous Cell Carcinoma Antigen in the Follow‐up of Patients With Head and Neck Cancer.

Author

Schepens, Emma J.A., Al‐Mamgani, Abrahim, Karssemakers, Luc H.E., van den Broek, Daan, van den Brekel, Michiel. W.M., and Lopez‐Yurda, Marta

Abstract

Objective: to determine if the tumor marker squamous cell carcinoma antigen (SCC‐Ag) observed over time may contribute to the early detection of recurrence, metastasis, and second primary tumors in the follow‐up of patients with head and neck squamous cell carcinoma (HNSCC). Study Design: A retrospective analysis of patients with HNSCC and at least one SCC‐Ag measurement was conducted. Hazard ratios (HRs) were used to determine the correlation between SCC‐Ag and an event. Setting: patients with HNSCC, treated in the Antoni van Leeuwenhoek Hospital in The Netherlands between 2010 and 2020 were used for the analysis. Methods: Data from 789 patients were used on event‐free survival (EFS) with time‐dependent Cox models. In addition to current (most recent) SCC‐Ag (also dichotomized into high and low as done for clinical practice), average SCC‐Ag and change between SCC‐Ag measurements (delta SCC‐Ag) were considered, using restricted cubic splines to explore nonlinear relationships. Results: Dichotomized SCC‐Ag values (HR = 3.01, 95% confidence interval [CI]: 2.17‐4.18) and the delta SCC‐Ag (HR = 1.15, 95% CI: 1.07‐1.22) predicted EFS better than models using the cumulative average or current value of SCC‐Ag, also after adjusting for tumor site, stage, age, and gender. A strong association was observed when using delta SCC‐Ag as a linear predictor in the subgroup of oropharynx patients (HR = 4.88, 95% CI: 2.71‐8.79). Conclusion: Dichotomized and delta SCC‐Ag values can be important markers for EFS, during the follow‐up of patients treated for HNSCC. These results were more evident in patients with oropharyngeal cancer. [ABSTRACT FROM AUTHOR]

Published
2024
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33. Blood platelet RNA profiles do not enable for nivolumab response prediction at baseline in patients with non-small cell lung cancer.

Author

Muller, Mirte, Best, Myron G., van der Noort, Vincent, Hiltermann, T. Jeroen N., Niemeijer, Anna-Larissa N., Post, Edward, Sol, Nik, In 't Veld, Sjors G.J.G., Nogarede, Tineke, Visser, Lisanne, Schouten, Robert D., van den Broek, Daan, Hummelink, Karlijn, Monkhorst, Kim, de Langen, Adrianus J., Schuuring, Ed, Smit, Egbert F., Groen, Harry J.M., Wurdinger, Thomas, and van den Heuvel, Michel M.

Subjects
NON-small-cell lung carcinoma, BLOOD platelets, NIVOLUMAB, RNA, SUPPORT vector machines
Abstract

BACKGROUND: Anti-PD-(L)1 immunotherapy has emerged as a promising treatment approach for non-small cell lung cancer (NSCLC), though the response rates remain low. Pre-treatment response prediction may improve patient allocation for immunotherapy. Blood platelets act as active immune-like cells, thereby constraining T-cell activity, propagating cancer metastasis, and adjusting their spliced mRNA content. OBJECTIVE: We investigated whether platelet RNA profiles before start of nivolumab anti-PD1 immunotherapy may predict treatment responses. METHODS: We performed RNA-sequencing of platelet RNA samples isolated from stage III-IV NSCLC patients before treatment with nivolumab. Treatment response was scored by the RECIST-criteria. Data were analyzed using a predefined thromboSeq analysis including a particle-swarm-enhanced support vector machine (PSO/SVM) classification algorithm. RESULTS: We collected and processed a 286-samples cohort, separated into a training/evaluation and validation series and subjected those to training of the PSO/SVM-classification algorithm. We observed only low classification accuracy in the 107-samples validation series (area under the curve (AUC) training series: 0.73 (95% -CI: 0.63–0.84, n = 88 samples), AUC evaluation series: 0.64 (95% -CI: 0.51–0.76, n = 91 samples), AUC validation series: 0.58 (95% -CI: 0.45–0.70, n = 107 samples)), employing a five-RNAs biomarker panel. CONCLUSIONS: We concluded that platelet RNA may have minimally discriminative capacity for anti-PD1 nivolumab response prediction, with which the current methodology is insufficient for diagnostic application. [ABSTRACT FROM AUTHOR]

Published
2024
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35. Abstract 222: High frequency of structural variants in FFPE colorectal cancer tissue detected by targeting selected common fragile site genes and LINE transposable elements

Author

Rubio-Alarcon, Carmen, primary, Stelloo, Ellen, additional, Vessies, Daan C., additional, van ‘t Erve, Iris, additional, Mekkes, Nienke, additional, Swennenhuis, Joost, additional, Lakbir, Soufyan, additional, van Bree, Elise, additional, Tijssen, Marianne, additional, Delis-van Diemen, Pien, additional, Lanfermeijer, Mirthe, additional, Linders, Theodora C., additional, van den Broek, Daan, additional, Punt, Cornelis J., additional, Heringa, Jaap, additional, Meijer, Gerrit A., additional, Abeln, Sanne, additional, Feitsma, Harma, additional, and Fijneman, Remond J., additional

Published
2023
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36. Correction To: Tumour-educated platelets for breast cancer detection: biological and technical insights (British Journal of Cancer, (2023), 128, 8, (1572-1581), 10.1038/s41416-023-02174-5)

Author

Liefaard, Marte C. (author), Moore, Kat S. (author), Mulder, Lennart (author), van den Broek, Daan (author), Wesseling, Jelle (author), Sonke, Gabe S. (author), Wessels, L.F.A. (author), Rookus, Matti (author), Lips, Esther H. (author), Liefaard, Marte C. (author), Moore, Kat S. (author), Mulder, Lennart (author), van den Broek, Daan (author), Wesseling, Jelle (author), Sonke, Gabe S. (author), Wessels, L.F.A. (author), Rookus, Matti (author), and Lips, Esther H. (author)

Abstract

In this article the data availability statement was incorrectly given. “EGAS0000100682” should have been “EGAS00001006821”. The correct statement as follows. The datasets generated during and/or analysed during the current study are deposited at the European Genome-phenome Archive (EGA) under the accession numbers EGAS00001006821 and EGAD00001009790. The original article has been corrected., Pattern Recognition and Bioinformatics

Published
2023
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37. Tumour-educated platelets for breast cancer detection: biological and technical insights

Author

Liefaard, Marte C. (author), Moore, Kat S. (author), Mulder, Lennart (author), van den Broek, Daan (author), Wesseling, Jelle (author), Sonke, Gabe S. (author), Wessels, L.F.A. (author), Rookus, Matti (author), Lips, Esther H. (author), Liefaard, Marte C. (author), Moore, Kat S. (author), Mulder, Lennart (author), van den Broek, Daan (author), Wesseling, Jelle (author), Sonke, Gabe S. (author), Wessels, L.F.A. (author), Rookus, Matti (author), and Lips, Esther H. (author)

Abstract

Background: Studies have shown that blood platelets contain tumour-specific mRNA profiles tumour-educated platelets (TEPs). Here, we aim to train a TEP-based breast cancer detection classifier. Methods: Platelet mRNA was sequenced from 266 women with stage I–IV breast cancer and 212 female controls from 6 hospitals. A particle swarm optimised support vector machine (PSO-SVM) and an elastic net-based classifier (EN) were trained on 71% of the study population. Classifier performance was evaluated in the remainder (29%) of the population, followed by validation in an independent set (37 cases and 36 controls). Potential confounding was assessed in post hoc analyses. Results: Both classifiers reached an area under the curve (AUC) of 0.85 upon internal validation. Reproducibility in the independent validation set was poor with an AUC of 0.55 and 0.54 for the PSO-SVM and EN classifier, respectively. Post hoc analyses indicated that 19% of the variance in gene expression was associated with hospital. Genes related to platelet activity were differentially expressed between hospitals. Conclusions: We could not validate two TEP-based breast cancer classifiers in an independent validation cohort. The TEP protocol is sensitive to within-protocol variation and revision might be necessary before TEPs can be reconsidered for breast cancer detection., correction: the data availability statement was incorrectly given. “EGAS0000100682” should have been “EGAS00001006821”. The original article has been corrected (the pdf file has been changed now), Pattern Recognition and Bioinformatics

Published
2023
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38. High- or low-dose preoperative ipilimumab plus nivolumab in stage III urothelial cancer: the phase 1B NABUCCO trial

Author

Cancer, MS Medische Oncologie, MS Urologische Oncologie, van Dorp, Jeroen, Pipinikas, Christodoulos, Suelmann, Britt B.M., Mehra, Niven, van Dijk, Nick, Marsico, Giovanni, van Montfoort, Maurits L., Hackinger, Sophie, Braaf, Linde M., Amarante, Tauanne, van Steenis, Charlaine, McLay, Kirsten, Daletzakis, Antonios, van den Broek, Daan, van de Kamp, Maaike W., Hendricksen, Kees, de Feijter, Jeantine M., Boellaard, Thierry N., Meijer, Richard P., van der Heijden, Toine G., Rosenfeld, Nitzan, van Rhijn, Bas W.G., Jones, Greg, van der Heijden, Michiel S., Cancer, MS Medische Oncologie, MS Urologische Oncologie, van Dorp, Jeroen, Pipinikas, Christodoulos, Suelmann, Britt B.M., Mehra, Niven, van Dijk, Nick, Marsico, Giovanni, van Montfoort, Maurits L., Hackinger, Sophie, Braaf, Linde M., Amarante, Tauanne, van Steenis, Charlaine, McLay, Kirsten, Daletzakis, Antonios, van den Broek, Daan, van de Kamp, Maaike W., Hendricksen, Kees, de Feijter, Jeantine M., Boellaard, Thierry N., Meijer, Richard P., van der Heijden, Toine G., Rosenfeld, Nitzan, van Rhijn, Bas W.G., Jones, Greg, and van der Heijden, Michiel S.

Published
2023

40. Abstract A020: Structural variants in the pathogenesis of colorectal cancer: The elephant in the room

Author

van Bree, Elise, primary, Alarcón, Carmen Rubio, additional, Lakbir, Soufyan, additional, Stelloo, Ellen, additional, Buranelli, Caterina, additional, Hondema, Amber, additional, van 't Erve, Iris, additional, Vessies, Daan, additional, Delis-van Diemen, Pien, additional, Tijssen, Marianne, additional, Bolijn, Anne, additional, Lanfermeijer, Mirthe, additional, Linders, Dorothe, additional, Swennenhuis, Joost, additional, van den Broek, Daan, additional, Heringa, Jaap, additional, Meijer, Gerrit, additional, Carvalho, Beatriz, additional, Feitsma, Harma, additional, Abeln, Sanne, additional, and Fijneman, Remond J. A., additional

Published
2022
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41. PP48 A Micro-Costing Study For Circulating Tumor DNA testing In Oncology

Author

Kramer, Astrid, primary, Schuuring, Ed, additional, Vessies, Daan, additional, van der Leest, Paul, additional, Geerlings, Maartje, additional, Rozendal, Pim, additional, Lanfermeijer, Mirthe, additional, Linders, Theodora, additional, van Kempen, Léon, additional, Fijneman, Remond, additional, Ligtenberg, Marjolijn, additional, Meijer, Gerrit, additional, van den Broek, Daan, additional, Retèl, Valesca, additional, and Coupé, Veerle, additional

Published
2022
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42. Analytical and adaptable initial conditions for moist baroclinic waves in a global hydrostatic model.

Author

Bouvier, Clément, van den Broek, Daan, Ekblom, Madeleine, and Sinclair, Victoria A.

Subjects
TROPICAL cyclones, WIND speed, NUMERICAL weather forecasting, ZONAL winds, INVISCID flow, ADIABATIC flow, HUMIDITY
Abstract

This article presents a description of an analytical, stable and flexible initial background state for moist baroclinic wave simulation on an aquaplanet in order to test dynamical core of numerical weather prediction models and study the dynamics and evolution of extra-tropical cyclones. The initial background state is derived from an analytical zonal wind speed field, or jet structure, and the hydrostatic primitive equations for moist adiabatic and frictionless flow in spherical coordinates. A baroclinic wave can develop only if a unbalanced perturbation is added to the zonal wind speed field. The implementation of this baroclinic wave simulation have been done on the Open Integrated Forecasting System (OpenIFS) cy43r3, a global numerical weather prediction model developed by the European Centre for Medium-range Weather Forecasts. In total, seven parameters can be used to control the generation of the initial background state and hence the development of the baroclinic waves in the OpenIFS configuration file: the jet's width, the jet's height, the maximum zonal mean wind speed of the jet, the horizontal mean of the surface virtual temperature, the surface relative humidity, the lapse rate and the surface roughness. Nine dry and nine moist initial background states have been generated to test their stability without perturbations. The meteorological stability of the initial state is investigated by examining the spatial distributions of the equivalent potential temperature, the absolute vorticity and the Brunt-Väisälä frequency. Moreover, the Root-Mean-Squared-Error (RMSE) of the zonal wind speed has been computed to assess their numerical stability. Finally, six of these moist initial initial background state have been used with an unbalanced perturbation to ensure that the baroclinic lifecycles developing are physically realistic. The resulting baroclinic wave is shown to be sensitive to the jet's width. This configuration for baroclinic wave simulations will be used to create large baroclinic lifecycles ensemble to study how extra-tropical cyclones may evolve in the future. [ABSTRACT FROM AUTHOR]

Published
2023
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43. Smeltende herinneringen in het koloniale antropoceen: Posthumanistisch geheugen aan de Nova Zembla-expeditie in het ijs van Spitsbergen en de roman Waarachtige beschrijvingen uit de permafrost (2022).

Author

van den Broek, Daan

Abstract

Copyright of Vooys is the property of Stichting Tijdschrift Vooys and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Published
2023

45. Detection and localization of early- and late-stage cancers using platelet RNA

Author

In ’t Veld, Sjors G.J.G., primary, Arkani, Mohammad, additional, Post, Edward, additional, Antunes-Ferreira, Mafalda, additional, D’Ambrosi, Silvia, additional, Vessies, Daan C.L., additional, Vermunt, Lisa, additional, Vancura, Adrienne, additional, Muller, Mirte, additional, Niemeijer, Anna-Larissa N., additional, Tannous, Jihane, additional, Meijer, Laura L., additional, Le Large, Tessa Y.S., additional, Mantini, Giulia, additional, Wondergem, Niels E., additional, Heinhuis, Kimberley M., additional, van Wilpe, Sandra, additional, Smits, A. Josien, additional, Drees, Esther E.E., additional, Roos, Eva, additional, Leurs, Cyra E., additional, Tjon Kon Fat, Lee-Ann, additional, van der Lelij, Ewoud J., additional, Dwarshuis, Govert, additional, Kamphuis, Maarten J., additional, Visser, Lisanne E., additional, Harting, Romee, additional, Gregory, Annemijn, additional, Schweiger, Markus W., additional, Wedekind, Laurine E., additional, Ramaker, Jip, additional, Zwaan, Kenn, additional, Verschueren, Heleen, additional, Bahce, Idris, additional, de Langen, Adrianus J., additional, Smit, Egbert F., additional, van den Heuvel, Michel M., additional, Hartemink, Koen J., additional, Kuijpers, Marijke J.E., additional, oude Egbrink, Mirjam G.A., additional, Griffioen, Arjan W., additional, Rossel, Rafael, additional, Hiltermann, T. Jeroen N., additional, Lee-Lewandrowski, Elizabeth, additional, Lewandrowski, Kent B., additional, De Witt Hamer, Philip C., additional, Kouwenhoven, Mathilde, additional, Reijneveld, Jaap C., additional, Leenders, William P.J., additional, Hoeben, Ann, additional, Verdonck-de Leeuw, Irma M., additional, Leemans, C. René, additional, Baatenburg de Jong, Robert J., additional, Terhaard, Chris H.J., additional, Takes, Robert P., additional, Langendijk, Johannes A., additional, de Jager, Saskia C., additional, Kraaijeveld, Adriaan O., additional, Pasterkamp, Gerard, additional, Smits, Minke, additional, Schalken, Jack A., additional, Łapińska-Szumczyk, Sylwia, additional, Łojkowska, Anna, additional, Żaczek, Anna J., additional, Lokhorst, Henk, additional, van de Donk, Niels W.C.J., additional, Nijhof, Inger, additional, Prins, Henk-Jan, additional, Zijlstra, Josée M., additional, Idema, Sander, additional, Baayen, Johannes C., additional, Teunissen, Charlotte E., additional, Killestein, Joep, additional, Besselink, Marc G., additional, Brammen, Lindsay, additional, Bachleitner-Hofmann, Thomas, additional, Mateen, Farrah, additional, Plukker, John T.M., additional, Heger, Michal, additional, de Mast, Quirijn, additional, Lisman, Ton, additional, Pegtel, D. Michiel, additional, Bogaard, Harm-Jan, additional, Jassem, Jacek, additional, Supernat, Anna, additional, Mehra, Niven, additional, Gerritsen, Winald, additional, de Kroon, Cornelis D., additional, Lok, Christianne A.R., additional, Piek, Jurgen M.J., additional, Steeghs, Neeltje, additional, van Houdt, Winan J., additional, Brakenhoff, Ruud H., additional, Sonke, Gabe S., additional, Verheul, Henk M., additional, Giovannetti, Elisa, additional, Kazemier, Geert, additional, Sabrkhany, Siamack, additional, Schuuring, Ed, additional, Sistermans, Erik A., additional, Wolthuis, Rob, additional, Meijers-Heijboer, Hanne, additional, Dorsman, Josephine, additional, Oudejans, Cees, additional, Ylstra, Bauke, additional, Westerman, Bart A., additional, van den Broek, Daan, additional, Koppers-Lalic, Danijela, additional, Wesseling, Pieter, additional, Nilsson, R. Jonas A., additional, Vandertop, W. Peter, additional, Noske, David P., additional, Tannous, Bakhos A., additional, Sol, Nik, additional, Best, Myron G., additional, and Wurdinger, Thomas, additional

Published
2022
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46. Detection and localization of early- and late-stage cancers using platelet RNA

Author

In ’t Veld, Sjors G.J.G., Arkani, Mohammad, Post, Edward, Antunes-Ferreira, Mafalda, D'Ambrosi, Silvia, Vessies, Daan C.L., Vermunt, Lisa, Vancura, Adrienne, Muller, Mirte, Niemeijer, Anna Larissa N., Tannous, Jihane, Meijer, Laura L., Le Large, Tessa Y.S., Mantini, Giulia, Wondergem, Niels E., Heinhuis, Kimberley M., van Wilpe, Sandra, Smits, A. Josien, Drees, Esther E.E., Roos, Eva, Leurs, Cyra E., Tjon Kon Fat, Lee Ann, van der Lelij, Ewoud J., Dwarshuis, Govert, Kamphuis, Maarten J., Visser, Lisanne E., Harting, Romee, Gregory, Annemijn, Schweiger, Markus W., Wedekind, Laurine E., Ramaker, Jip, Zwaan, Kenn, Verschueren, Heleen, Bahce, Idris, de Langen, Adrianus J., Smit, Egbert F., van den Heuvel, Michel M., Hartemink, Koen J., Kuijpers, Marijke J.E., oude Egbrink, Mirjam G.A., Griffioen, Arjan W., Rossel, Rafael, Hiltermann, T. Jeroen N., Lee-Lewandrowski, Elizabeth, Lewandrowski, Kent B., De Witt Hamer, Philip C., Kouwenhoven, Mathilde, Reijneveld, Jaap C., Leenders, William P.J., Hoeben, Ann, Verdonck-de Leeuw, Irma M., Leemans, C. René, Baatenburg de Jong, Robert J., Terhaard, Chris H.J., Takes, Robert P., Langendijk, Johannes A., de Jager, Saskia C., Kraaijeveld, Adriaan O., Pasterkamp, Gerard, Smits, Minke, Schalken, Jack A., Łapińska-Szumczyk, Sylwia, Łojkowska, Anna, Żaczek, Anna J., Lokhorst, Henk, van de Donk, Niels W.C.J., Nijhof, Inger, Prins, Henk Jan, Zijlstra, Josée M., Idema, Sander, Baayen, Johannes C., Teunissen, Charlotte E., Killestein, Joep, Besselink, Marc G., Brammen, Lindsay, Bachleitner-Hofmann, Thomas, Mateen, Farrah, Plukker, John T.M., Heger, Michal, de Mast, Quirijn, Lisman, Ton, Pegtel, D. Michiel, Bogaard, Harm Jan, Jassem, Jacek, Supernat, Anna, Mehra, Niven, Gerritsen, Winald, de Kroon, Cornelis D., Lok, Christianne A.R., Piek, Jurgen M.J., Steeghs, Neeltje, van Houdt, Winan J., Brakenhoff, Ruud H., Sonke, Gabe S., Verheul, Henk M., Giovannetti, Elisa, Kazemier, Geert, Sabrkhany, Siamack, Schuuring, Ed, Sistermans, Erik A., Wolthuis, Rob, Meijers-Heijboer, Hanne, Dorsman, Josephine, Oudejans, Cees, Ylstra, Bauke, Westerman, Bart A., van den Broek, Daan, Koppers-Lalic, Danijela, Wesseling, Pieter, Nilsson, R. Jonas A., Vandertop, W. Peter, Noske, David P., Tannous, Bakhos A., Sol, Nik, Best, Myron G., Wurdinger, Thomas, In ’t Veld, Sjors G.J.G., Arkani, Mohammad, Post, Edward, Antunes-Ferreira, Mafalda, D'Ambrosi, Silvia, Vessies, Daan C.L., Vermunt, Lisa, Vancura, Adrienne, Muller, Mirte, Niemeijer, Anna Larissa N., Tannous, Jihane, Meijer, Laura L., Le Large, Tessa Y.S., Mantini, Giulia, Wondergem, Niels E., Heinhuis, Kimberley M., van Wilpe, Sandra, Smits, A. Josien, Drees, Esther E.E., Roos, Eva, Leurs, Cyra E., Tjon Kon Fat, Lee Ann, van der Lelij, Ewoud J., Dwarshuis, Govert, Kamphuis, Maarten J., Visser, Lisanne E., Harting, Romee, Gregory, Annemijn, Schweiger, Markus W., Wedekind, Laurine E., Ramaker, Jip, Zwaan, Kenn, Verschueren, Heleen, Bahce, Idris, de Langen, Adrianus J., Smit, Egbert F., van den Heuvel, Michel M., Hartemink, Koen J., Kuijpers, Marijke J.E., oude Egbrink, Mirjam G.A., Griffioen, Arjan W., Rossel, Rafael, Hiltermann, T. Jeroen N., Lee-Lewandrowski, Elizabeth, Lewandrowski, Kent B., De Witt Hamer, Philip C., Kouwenhoven, Mathilde, Reijneveld, Jaap C., Leenders, William P.J., Hoeben, Ann, Verdonck-de Leeuw, Irma M., Leemans, C. René, Baatenburg de Jong, Robert J., Terhaard, Chris H.J., Takes, Robert P., Langendijk, Johannes A., de Jager, Saskia C., Kraaijeveld, Adriaan O., Pasterkamp, Gerard, Smits, Minke, Schalken, Jack A., Łapińska-Szumczyk, Sylwia, Łojkowska, Anna, Żaczek, Anna J., Lokhorst, Henk, van de Donk, Niels W.C.J., Nijhof, Inger, Prins, Henk Jan, Zijlstra, Josée M., Idema, Sander, Baayen, Johannes C., Teunissen, Charlotte E., Killestein, Joep, Besselink, Marc G., Brammen, Lindsay, Bachleitner-Hofmann, Thomas, Mateen, Farrah, Plukker, John T.M., Heger, Michal, de Mast, Quirijn, Lisman, Ton, Pegtel, D. Michiel, Bogaard, Harm Jan, Jassem, Jacek, Supernat, Anna, Mehra, Niven, Gerritsen, Winald, de Kroon, Cornelis D., Lok, Christianne A.R., Piek, Jurgen M.J., Steeghs, Neeltje, van Houdt, Winan J., Brakenhoff, Ruud H., Sonke, Gabe S., Verheul, Henk M., Giovannetti, Elisa, Kazemier, Geert, Sabrkhany, Siamack, Schuuring, Ed, Sistermans, Erik A., Wolthuis, Rob, Meijers-Heijboer, Hanne, Dorsman, Josephine, Oudejans, Cees, Ylstra, Bauke, Westerman, Bart A., van den Broek, Daan, Koppers-Lalic, Danijela, Wesseling, Pieter, Nilsson, R. Jonas A., Vandertop, W. Peter, Noske, David P., Tannous, Bakhos A., Sol, Nik, Best, Myron G., and Wurdinger, Thomas

Abstract

Cancer patients benefit from early tumor detection since treatment outcomes are more favorable for less advanced cancers. Platelets are involved in cancer progression and are considered a promising biosource for cancer detection, as they alter their RNA content upon local and systemic cues. We show that tumor-educated platelet (TEP) RNA-based blood tests enable the detection of 18 cancer types. With 99% specificity in asymptomatic controls, thromboSeq correctly detected the presence of cancer in two-thirds of 1,096 blood samples from stage I–IV cancer patients and in half of 352 stage I–III tumors. Symptomatic controls, including inflammatory and cardiovascular diseases, and benign tumors had increased false-positive test results with an average specificity of 78%. Moreover, thromboSeq determined the tumor site of origin in five different tumor types correctly in over 80% of the cancer patients. These results highlight the potential properties of TEP-derived RNA panels to supplement current approaches for blood-based cancer screening.

Published
2022

47. Longitudinal nonlinear mixed effects modeling of EGFR mutations in ctDNA as predictor of disease progression in treatment of EGFR-mutant non-small cell lung cancer

Author

Apotheek O&O&O, Cancer, Janssen, Julie M., Verheijen, Remy B., van Duijl, Tirsa T., Lin, Lishi, van den Heuvel, Michel M., Beijnen, Jos H., Steeghs, Neeltje, van den Broek, Daan, Huitema, Alwin D.R., Dorlo, Thomas P.C., Apotheek O&O&O, Cancer, Janssen, Julie M., Verheijen, Remy B., van Duijl, Tirsa T., Lin, Lishi, van den Heuvel, Michel M., Beijnen, Jos H., Steeghs, Neeltje, van den Broek, Daan, Huitema, Alwin D.R., and Dorlo, Thomas P.C.

Published
2022

48. Dutch National Round Robin Trial on Plasma-Derived Circulating Cell-Free DNA Extraction Methods Routinely Used in Clinical Pathology for Molecular Tumor Profiling

Author

van der Leest, Paul, Ketelaar, Emma M., van Noesel, Carel J.M., van den Broek, Daan, van Boerdonk, Robert A.A., Deiman, Birgit, Rifaela, Naomi, van der Geize, Robert, Huijsmans, Cornelis J.J., Speel, Ernst Jan M., Geerlings, Maartje J., van Schaik, Ron H.N., Jansen, Maurice P.H.M., Dane-Vogelaar, Ria, Driehuis, Else, Leers, Mathie P.G., Sidorenkov, Grigory, Tamminga, Menno, van Kempen, Léon C., Schuuring, Ed, van der Leest, Paul, Ketelaar, Emma M., van Noesel, Carel J.M., van den Broek, Daan, van Boerdonk, Robert A.A., Deiman, Birgit, Rifaela, Naomi, van der Geize, Robert, Huijsmans, Cornelis J.J., Speel, Ernst Jan M., Geerlings, Maartje J., van Schaik, Ron H.N., Jansen, Maurice P.H.M., Dane-Vogelaar, Ria, Driehuis, Else, Leers, Mathie P.G., Sidorenkov, Grigory, Tamminga, Menno, van Kempen, Léon C., and Schuuring, Ed

Abstract

BACKGROUND: Efficient recovery of circulating tumor DNA (ctDNA) depends on the quantity and quality of circulating cell-free DNA (ccfDNA). Here, we evaluated whether various ccfDNA extraction methods routinely applied in Dutch laboratories affect ccfDNA yield, ccfDNA integrity, and mutant ctDNA detection, using identical lung cancer patient-derived plasma samples. METHODS: Aliquots of 4 high-volume diagnostic leukapheresis plasma samples and one artificial reference plasma sample with predetermined tumor-derived mutations were distributed among 14 Dutch laboratories. Extractions of ccfDNA were performed according to local routine standard operating procedures and were analyzed at a central reference laboratory for mutant detection and assessment of ccfDNA quantity and integrity. RESULTS: Mutant molecule levels in extracted ccfDNA samples varied considerably between laboratories, but there was no indication of consistent above or below average performance. Compared to silica membrane-based methods, samples extracted with magnetic beads-based kits revealed an overall lower total ccfDNA yield (-29%; P < 0.0001) and recovered fewer mutant molecules (-41%; P < 0.01). The variant allelic frequency and sample integrity were similar. In samples with a higher-than-average total ccfDNA yield, an augmented recovery of mutant molecules was observed. CONCLUSIONS: In the Netherlands, we encountered diversity in preanalytical workflows with potential consequences on mutant ctDNA detection in clinical practice. Silica membrane-based methodologies resulted in the highest total ccfDNA yield and are therefore preferred to detect low copy numbers of relevant mutations. Harmonization of the extraction workflow for accurate quantification and sensitive detection is required to prevent introduction of technical divergence in the preanalytical phase and reduce interlaboratory discrepancies.

Published
2022

49. Detection and localization of early- and late-stage cancers using platelet RNA

Author

Pharmaceutics, Sub Membrane Biochemistry & Biophysics, Afd Pharmaceutics, In ’t Veld, Sjors G.J.G., Arkani, Mohammad, Post, Edward, Antunes-Ferreira, Mafalda, D'Ambrosi, Silvia, Vessies, Daan C.L., Vermunt, Lisa, Vancura, Adrienne, Muller, Mirte, Niemeijer, Anna Larissa N., Tannous, Jihane, Meijer, Laura L., Le Large, Tessa Y.S., Mantini, Giulia, Wondergem, Niels E., Heinhuis, Kimberley M., van Wilpe, Sandra, Smits, A. Josien, Drees, Esther E.E., Roos, Eva, Leurs, Cyra E., Tjon Kon Fat, Lee Ann, van der Lelij, Ewoud J., Dwarshuis, Govert, Kamphuis, Maarten J., Visser, Lisanne E., Harting, Romee, Gregory, Annemijn, Schweiger, Markus W., Wedekind, Laurine E., Ramaker, Jip, Zwaan, Kenn, Verschueren, Heleen, Bahce, Idris, de Langen, Adrianus J., Smit, Egbert F., van den Heuvel, Michel M., Hartemink, Koen J., Kuijpers, Marijke J.E., oude Egbrink, Mirjam G.A., Griffioen, Arjan W., Rossel, Rafael, Hiltermann, T. Jeroen N., Lee-Lewandrowski, Elizabeth, Lewandrowski, Kent B., De Witt Hamer, Philip C., Kouwenhoven, Mathilde, Reijneveld, Jaap C., Leenders, William P.J., Hoeben, Ann, Verdonck-de Leeuw, Irma M., Leemans, C. René, Baatenburg de Jong, Robert J., Terhaard, Chris H.J., Takes, Robert P., Langendijk, Johannes A., de Jager, Saskia C., Kraaijeveld, Adriaan O., Pasterkamp, Gerard, Smits, Minke, Schalken, Jack A., Łapińska-Szumczyk, Sylwia, Łojkowska, Anna, Żaczek, Anna J., Lokhorst, Henk, van de Donk, Niels W.C.J., Nijhof, Inger, Prins, Henk Jan, Zijlstra, Josée M., Idema, Sander, Baayen, Johannes C., Teunissen, Charlotte E., Killestein, Joep, Besselink, Marc G., Brammen, Lindsay, Bachleitner-Hofmann, Thomas, Mateen, Farrah, Plukker, John T.M., Heger, Michal, de Mast, Quirijn, Lisman, Ton, Pegtel, D. Michiel, Bogaard, Harm Jan, Jassem, Jacek, Supernat, Anna, Mehra, Niven, Gerritsen, Winald, de Kroon, Cornelis D., Lok, Christianne A.R., Piek, Jurgen M.J., Steeghs, Neeltje, van Houdt, Winan J., Brakenhoff, Ruud H., Sonke, Gabe S., Verheul, Henk M., Giovannetti, Elisa, Kazemier, Geert, Sabrkhany, Siamack, Schuuring, Ed, Sistermans, Erik A., Wolthuis, Rob, Meijers-Heijboer, Hanne, Dorsman, Josephine, Oudejans, Cees, Ylstra, Bauke, Westerman, Bart A., van den Broek, Daan, Koppers-Lalic, Danijela, Wesseling, Pieter, Nilsson, R. Jonas A., Vandertop, W. Peter, Noske, David P., Tannous, Bakhos A., Sol, Nik, Best, Myron G., Wurdinger, Thomas, Pharmaceutics, Sub Membrane Biochemistry & Biophysics, Afd Pharmaceutics, In ’t Veld, Sjors G.J.G., Arkani, Mohammad, Post, Edward, Antunes-Ferreira, Mafalda, D'Ambrosi, Silvia, Vessies, Daan C.L., Vermunt, Lisa, Vancura, Adrienne, Muller, Mirte, Niemeijer, Anna Larissa N., Tannous, Jihane, Meijer, Laura L., Le Large, Tessa Y.S., Mantini, Giulia, Wondergem, Niels E., Heinhuis, Kimberley M., van Wilpe, Sandra, Smits, A. Josien, Drees, Esther E.E., Roos, Eva, Leurs, Cyra E., Tjon Kon Fat, Lee Ann, van der Lelij, Ewoud J., Dwarshuis, Govert, Kamphuis, Maarten J., Visser, Lisanne E., Harting, Romee, Gregory, Annemijn, Schweiger, Markus W., Wedekind, Laurine E., Ramaker, Jip, Zwaan, Kenn, Verschueren, Heleen, Bahce, Idris, de Langen, Adrianus J., Smit, Egbert F., van den Heuvel, Michel M., Hartemink, Koen J., Kuijpers, Marijke J.E., oude Egbrink, Mirjam G.A., Griffioen, Arjan W., Rossel, Rafael, Hiltermann, T. Jeroen N., Lee-Lewandrowski, Elizabeth, Lewandrowski, Kent B., De Witt Hamer, Philip C., Kouwenhoven, Mathilde, Reijneveld, Jaap C., Leenders, William P.J., Hoeben, Ann, Verdonck-de Leeuw, Irma M., Leemans, C. René, Baatenburg de Jong, Robert J., Terhaard, Chris H.J., Takes, Robert P., Langendijk, Johannes A., de Jager, Saskia C., Kraaijeveld, Adriaan O., Pasterkamp, Gerard, Smits, Minke, Schalken, Jack A., Łapińska-Szumczyk, Sylwia, Łojkowska, Anna, Żaczek, Anna J., Lokhorst, Henk, van de Donk, Niels W.C.J., Nijhof, Inger, Prins, Henk Jan, Zijlstra, Josée M., Idema, Sander, Baayen, Johannes C., Teunissen, Charlotte E., Killestein, Joep, Besselink, Marc G., Brammen, Lindsay, Bachleitner-Hofmann, Thomas, Mateen, Farrah, Plukker, John T.M., Heger, Michal, de Mast, Quirijn, Lisman, Ton, Pegtel, D. Michiel, Bogaard, Harm Jan, Jassem, Jacek, Supernat, Anna, Mehra, Niven, Gerritsen, Winald, de Kroon, Cornelis D., Lok, Christianne A.R., Piek, Jurgen M.J., Steeghs, Neeltje, van Houdt, Winan J., Brakenhoff, Ruud H., Sonke, Gabe S., Verheul, Henk M., Giovannetti, Elisa, Kazemier, Geert, Sabrkhany, Siamack, Schuuring, Ed, Sistermans, Erik A., Wolthuis, Rob, Meijers-Heijboer, Hanne, Dorsman, Josephine, Oudejans, Cees, Ylstra, Bauke, Westerman, Bart A., van den Broek, Daan, Koppers-Lalic, Danijela, Wesseling, Pieter, Nilsson, R. Jonas A., Vandertop, W. Peter, Noske, David P., Tannous, Bakhos A., Sol, Nik, Best, Myron G., and Wurdinger, Thomas

Published
2022

50. Longitudinal nonlinear mixed effects modeling of EGFR mutations in ctDNA as predictor of disease progression in treatment of EGFR-mutant non-small cell lung cancer.

Author

Janssen, Julie M, Verheijen, Remy B, van Duijl, Tirsa T, Lin, Lishi, van den Heuvel, Michel M, Beijnen, Jos H, Steeghs, Neeltje, van den Broek, Daan, Huitema, Alwin D R, Dorlo, Thomas P. C., Janssen, Julie M, Verheijen, Remy B, van Duijl, Tirsa T, Lin, Lishi, van den Heuvel, Michel M, Beijnen, Jos H, Steeghs, Neeltje, van den Broek, Daan, Huitema, Alwin D R, and Dorlo, Thomas P. C.

Abstract

Correlations between increasing concentrations of circulating tumor DNA (ctDNA) in plasma and disease progression have been shown. A nonlinear mixed effects model to describe the dynamics of epidermal growth factor receptor (EGFR) ctDNA data from patients with non-small cell lung cancer (NSCLC) combined with a parametric survival model were developed to evaluate the ability of these modeling techniques to describe ctDNA data. Repeated ctDNA measurements on L858R, exon19del, and T790M mutants were available from 54 patients with EGFR mutated NSCLC treated with erlotinib or gefitinib. Different dynamic models were tested to describe the longitudinal ctDNA concentrations of the driver and resistance mutations. Subsequently, a parametric time-to-event model for progression-free survival (PFS) was developed. Predicted L858R, exon19del, and T790M concentrations were used to evaluate their value as predictor for disease progression. The ctDNA dynamics were best described by a model consisting of a zero-order increase and first-order elimination (19.7/day, 95% confidence interval [CI] 14.9-23.6/day) of ctDNA concentrations. In addition, time-dependent development of resistance (5.0 × 10-4 , 95% CI 2.0 × 10-4 -7.0 × 10-4 /day) was included in the final model. Relative change in L858R and exon19del concentrations from baseline was identified as most significant predictor of disease progression (p = 0.001). The dynamic model for L858R, exon19del, and T790M concentrations in ctDNA and time-to-event model adequately described the observed concentrations and PFS data in our clinical cohort. In addition, it was shown that nonlinear mixed effects modeling is a valuable method for the analysis of longitudinal and heterogeneous biomarker datasets obtained from clinical practice.

Published
2022
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