8 results on '"Steeghs N"'
Search Results
2. Molecular Tumor Boards : Current Practice and Future Needs
- Author
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van der Velden, D. L., van Herpen, C. M.L., van Laarhoven, H. W.M., Smit, E. F., Groen, H. J.M., Willems, S. M., Nederlof, P. M., Langenberg, M. H.G., Cuppen, E., Sleijfer, S., Steeghs, N., Voest, E. E., van der Velden, D. L., van Herpen, C. M.L., van Laarhoven, H. W.M., Smit, E. F., Groen, H. J.M., Willems, S. M., Nederlof, P. M., Langenberg, M. H.G., Cuppen, E., Sleijfer, S., Steeghs, N., and Voest, E. E.
- Published
- 2017
3. Molecular Tumor Boards: Current Practice and Future Needs
- Author
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Pathologie Pathologen staf, Cancer, MS Medische Oncologie, CMM, van der Velden, D. L., van Herpen, C. M.L., van Laarhoven, H. W.M., Smit, E. F., Groen, H. J.M., Willems, S. M., Nederlof, P. M., Langenberg, M. H.G., Cuppen, E., Sleijfer, S., Steeghs, N., Voest, E. E., Pathologie Pathologen staf, Cancer, MS Medische Oncologie, CMM, van der Velden, D. L., van Herpen, C. M.L., van Laarhoven, H. W.M., Smit, E. F., Groen, H. J.M., Willems, S. M., Nederlof, P. M., Langenberg, M. H.G., Cuppen, E., Sleijfer, S., Steeghs, N., and Voest, E. E.
- Published
- 2017
4. The time to progression ratio : A new individualized volumetric parameter for the early detection of clinical benefit of targeted therapies
- Author
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Cirkel, G. A., Weeber, F., Bins, S., Gadellaa-van Hooijdonk, C. G M, van Werkhoven, E., Willems, S. M., van Stralen, M., Veldhuis, W. B., Ubink, I., Steeghs, N., de Jonge, M. J., Langenberg, M. H G, Schellens, J. H M, Sleijfer, S., Lolkema, M. P., Voest, Emile E., Cirkel, G. A., Weeber, F., Bins, S., Gadellaa-van Hooijdonk, C. G M, van Werkhoven, E., Willems, S. M., van Stralen, M., Veldhuis, W. B., Ubink, I., Steeghs, N., de Jonge, M. J., Langenberg, M. H G, Schellens, J. H M, Sleijfer, S., Lolkema, M. P., and Voest, Emile E.
- Published
- 2016
5. The time to progression ratio: A new individualized volumetric parameter for the early detection of clinical benefit of targeted therapies
- Author
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Divisie Beeld & Oncologie, Trialsecretariaat Medische Oncologie, Unit Opleiding Aios, Cancer, Externen Med. Onco, Radiotherapie, Pathologie patiënten zorg, Other research (not in main researchprogram), Researchgr. Beeldg. Moleculaire Interv., MS Radiologie, Circulatory Health, Verpleegafd Vaatchirurgie D4 Oost, MS CGO, MS Medische Oncologie, Cirkel, G. A., Weeber, F., Bins, S., Gadellaa-van Hooijdonk, C. G M, van Werkhoven, E., Willems, S. M., van Stralen, M., Veldhuis, W. B., Ubink, I., Steeghs, N., de Jonge, M. J., Langenberg, M. H G, Schellens, J. H M, Sleijfer, S., Lolkema, M. P., Voest, Emile E., Divisie Beeld & Oncologie, Trialsecretariaat Medische Oncologie, Unit Opleiding Aios, Cancer, Externen Med. Onco, Radiotherapie, Pathologie patiënten zorg, Other research (not in main researchprogram), Researchgr. Beeldg. Moleculaire Interv., MS Radiologie, Circulatory Health, Verpleegafd Vaatchirurgie D4 Oost, MS CGO, MS Medische Oncologie, Cirkel, G. A., Weeber, F., Bins, S., Gadellaa-van Hooijdonk, C. G M, van Werkhoven, E., Willems, S. M., van Stralen, M., Veldhuis, W. B., Ubink, I., Steeghs, N., de Jonge, M. J., Langenberg, M. H G, Schellens, J. H M, Sleijfer, S., Lolkema, M. P., and Voest, Emile E.
- Published
- 2016
6. Phase Ib/II Study of the Efficacy and Safety of Binimetinib (MEK162) Plus Panitumumab for Mutant or Wild-Type RAS Metastatic Colorectal Cancer.
- Author
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Van Cutsem E, Yaeger R, Delord JP, Tabernero J, Siu LL, Ducreux M, Siena S, Elez E, Kasper S, Zander T, Steeghs N, Murphy D, Edwards M, and Wainberg ZA
- Subjects
- Humans, Panitumumab adverse effects, Benzimidazoles adverse effects, ErbB Receptors genetics, ErbB Receptors therapeutic use, Antineoplastic Combined Chemotherapy Protocols adverse effects, Proto-Oncogene Proteins p21(ras) genetics, Colorectal Neoplasms drug therapy, Colorectal Neoplasms genetics, Colorectal Neoplasms pathology, Colonic Neoplasms drug therapy, Rectal Neoplasms drug therapy
- Abstract
Introduction: Activating RAS gene mutations occur in approximately 55% of patients with metastatic colorectal cancer (mCRC) and are associated with poorer clinical outcomes due to epidermal growth factor receptor (EGFR) blockade resistance. Combined EGFR and mitogen-activated protein kinase (MEK) inhibition may extend response to EGFR inhibition and overcome acquired resistance. This phase Ib/II dose escalation trial evaluated the safety and activity of dual inhibition with binimetinib (MEK1/2 inhibitor) and panitumumab (EGFR inhibitor [EGFRi]) in patients with RAS mutant or BRAF wild type (WT)/RAS WT mCRC., Methods: Phase Ib dose escalation started with binimetinib 45 mg twice daily plus panitumumab 6 mg/kg administered every 2 weeks. In the phase II study, patients with measurable mCRC were enrolled into 4 groups based on previous anti-EGFR monoclonal antibody therapy and RAS mutational status., Results: No patients in the phase Ib portion (n = 10) had a response; 70% of patients had stable disease. In the phase II portion (n = 43), overall response rate (ORR, confirmed) was 2.3% with one partial response in the RAS WT group, DCR was 30.2%, and median progression-free survival was 1.8 months (95%CI, 1.6-3.3). All patients experienced ≥1 adverse event, with the most common being diarrhea (71.7%), vomiting (52.8%), nausea (50.9%), fatigue (49.1%), dermatitis acneiform (43.4%), and rash (41.5%). Most patients required treatment interruption or dose reduction due to difficulties tolerating treatment., Conclusions: The combination of binimetinib and panitumumab had substantial toxicity and limited clinical activity for patients with mutant or WT RAS mCRC, independent of EGFRi treatment history (Trial registration: NCT01927341)., (© The Author(s) 2023. Published by Oxford University Press.)
- Published
- 2023
- Full Text
- View/download PDF
7. Phase I Study of Afatinib and Selumetinib in Patients with KRAS-Mutated Colorectal, Non-Small Cell Lung, and Pancreatic Cancer.
- Author
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van Brummelen EMJ, Huijberts S, van Herpen C, Desar I, Opdam F, van Geel R, Marchetti S, Steeghs N, Monkhorst K, Thijssen B, Rosing H, Huitema A, Beijnen J, Bernards R, and Schellens J
- Subjects
- Afatinib therapeutic use, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Benzimidazoles, Humans, Lung, Mutation, Phosphatidylinositol 3-Kinases, Protein Kinase Inhibitors adverse effects, Proto-Oncogene Proteins p21(ras) genetics, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Non-Small-Cell Lung genetics, Colorectal Neoplasms drug therapy, Colorectal Neoplasms genetics, Lung Neoplasms drug therapy, Lung Neoplasms genetics, Pancreatic Neoplasms drug therapy
- Abstract
Lessons Learned: Afatinib and selumetinib can be combined in continuous and intermittent dosing schedules, albeit at lower doses than approved for monotherapy. Maximum tolerated dose for continuous and intermittent schedules is afatinib 20 mg once daily and selumetinib 25 mg b.i.d. Because the anticancer activity was limited, further development of this combination is not recommended until better biomarkers for response and resistance are defined., Background: Antitumor effects of MEK inhibitors are limited in KRAS-mutated tumors because of feedback activation of upstream epidermal growth factor receptors, which reactivates the MAPK and the phosphoinositide 3-kinase-AKT pathway. Therefore, this phase I trial was initiated with the pan-HER inhibitor afatinib plus the MEK inhibitor selumetinib in patients with KRAS mutant, PIK3CA wild-type tumors., Methods: Afatinib and selumetinib were administered according to a 3+3 design in continuous and intermittent schedules. The primary objective was safety, and the secondary objective was clinical efficacy., Results: Twenty-six patients were enrolled with colorectal cancer (n = 19), non-small cell lung cancer (NSCLC) (n = 6), and pancreatic cancer (n = 1). Dose-limiting toxicities occurred in six patients, including grade 3 diarrhea, dehydration, decreased appetite, nausea, vomiting, and mucositis. The recommended phase II dose (RP2D) was 20 mg afatinib once daily (QD) and 25 mg selumetinib b.i.d. (21 days on/7 days off) for continuous afatinib dosing and for intermittent dosing with both drugs 5 days on/2 days off. Efficacy was limited with disease stabilization for 221 days in a patient with NSCLC as best response., Conclusion: Afatinib and selumetinib can be combined in continuous and intermittent schedules in patients with KRAS mutant tumors. Although target engagement was observed, the clinical efficacy was limited., (© AlphaMed Press; the data published online to support this summary are the property of the authors.)
- Published
- 2021
- Full Text
- View/download PDF
8. Implementation of a Multicenter Biobanking Collaboration for Next-Generation Sequencing-Based Biomarker Discovery Based on Fresh Frozen Pretreatment Tumor Tissue Biopsies.
- Author
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Bins S, Cirkel GA, Gadellaa-Van Hooijdonk CG, Weeber F, Numan IJ, Bruggink AH, van Diest PJ, Willems SM, Veldhuis WB, van den Heuvel MM, de Knegt RJ, Koudijs MJ, van Werkhoven E, Mathijssen RH, Cuppen E, Sleijfer S, Schellens JH, Voest EE, Langenberg MH, de Jonge MJ, Steeghs N, and Lolkema MP
- Subjects
- Adult, Aged, Female, Humans, Image-Guided Biopsy, Male, Middle Aged, Neoplasms pathology, Netherlands, Biological Specimen Banks, Biomarkers, Tumor genetics, High-Throughput Nucleotide Sequencing, Neoplasms genetics
- Abstract
Background: The discovery of novel biomarkers that predict treatment response in advanced cancer patients requires acquisition of high-quality tumor samples. As cancer evolves over time, tissue is ideally obtained before the start of each treatment. Preferably, samples are freshly frozen to allow analysis by next-generation DNA/RNA sequencing (NGS) but also for making other emerging systematic techniques such as proteomics and metabolomics possible. Here, we describe the first 469 image-guided biopsies collected in a large collaboration in The Netherlands (Center for Personalized Cancer Treatment) and show the utility of these specimens for NGS analysis., Patients and Methods: Image-guided tumor biopsies were performed in advanced cancer patients. Samples were fresh frozen, vital tumor cellularity was estimated, and DNA was isolated after macrodissection of tumor-rich areas. Safety of the image-guided biopsy procedures was assessed by reporting of serious adverse events within 14 days after the biopsy procedure., Results: Biopsy procedures were generally well tolerated. Major complications occurred in 2.1%, most frequently consisting of pain. In 7.3% of the percutaneous lung biopsies, pneumothorax requiring drainage occurred. The majority of samples (81%) contained a vital tumor percentage of at least 30%, from which at least 500 ng DNA could be isolated in 91%. Given our preset criteria, 74% of samples were of sufficient quality for biomarker discovery. The NGS results in this cohort were in line with those in other groups., Conclusion: Image-guided biopsy procedures for biomarker discovery to enable personalized cancer treatment are safe and feasible and yield a highly valuable biobank. The Oncologist 2017;22:33-40Implications for Practice: This study shows that it is safe to perform image-guided biopsy procedures to obtain fresh frozen tumor samples and that it is feasible to use these biopsies for biomarker discovery purposes in a Dutch multicenter collaboration. From the majority of the samples, sufficient DNA could be yielded to perform next-generation sequencing. These results indicate that the way is paved for consortia to prospectively collect fresh frozen tumor tissue., (© AlphaMed Press 2016.)
- Published
- 2017
- Full Text
- View/download PDF
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