31 results on '"Menke-van der Houven van Oordt, C. Willemien"'
Search Results
2. Validation of simplified uptake measures against dynamic Patlak Ki for quantification of lesional 89Zr-Immuno-PET antibody uptake
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Wijngaarden, Jessica E., Huisman, Marc C., Jauw, Yvonne W. S., van Dongen, Guus A. M. S., Greuter, Henri N. J. M., Schuit, Robert C., Cleveland, Matthew, Gootjes, Elske C., Vugts, Daniëlle J., Menke-van der Houven van Oordt, C. Willemien, and Boellaard, Ronald
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- 2023
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3. Impact of EDP-M on survival of patients with metastatic adrenocortical carcinoma: A population-based study
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Debets, Pien, Dreijerink, Koen M.A., Engelsman, Anton, Dahele, Max, Haak, Harm R., Steenaard, Rebecca V., Kapiteijn, Ellen, Corssmit, Eleonora, and Menke–van der Houven van Oordt, C. Willemien
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- 2024
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4. Changes in breast cancer treatment during the COVID-19 pandemic: a Dutch population-based study
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Eijkelboom, Anouk H., de Munck, Linda, Menke-van der Houven van Oordt, C. Willemien, Broeders, Mireille J. M., van den Bongard, Desiree H. J. G., Strobbe, Luc J. A., Mureau, Marc A. M., Lobbes, Marc B. I., Westenend, Pieter J., Koppert, Linetta B., Jager, Agnes, Siemerink, Ester J. M., Wesseling, Jelle, Verkooijen, Helena M., Vrancken Peeters, Marie-Jeanne T. F. D., Smidt, Marjolein L., Tjan-Heijnen, Vivianne C. G., and Siesling, Sabine
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- 2023
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5. Optimal imaging time points considering accuracy and precision of Patlak linearization for 89Zr-immuno-PET: a simulation study
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Wijngaarden, Jessica E., Huisman, Marc C., Pouw, Johanna E. E., Menke-van der Houven van Oordt, C. Willemien, Jauw, Yvonne W. S., and Boellaard, Ronald
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- 2022
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6. Current state and upcoming opportunities for immunoPET biomarkers in lung cancer
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Slebe, Maarten, Pouw, Johanna E.E., Hashemi, Sayed M.S., Menke-van der Houven van Oordt, C. Willemien, Yaqub, Maqsood M., and Bahce, Idris
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- 2022
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7. Potential and pitfalls of 89Zr-immuno-PET to assess target status: 89Zr-trastuzumab as an example
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Huisman, Marc C., Menke-van der Houven van Oordt, C. Willemien, Zijlstra, Josée M., Hoekstra, Otto S., Boellaard, Ronald, van Dongen, Guus A. M. S., Shah, Dhaval K., and Jauw, Yvonne W. S.
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- 2021
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8. Non-specific irreversible 89Zr-mAb uptake in tumours: evidence from biopsy-proven target-negative tumours using 89Zr-immuno-PET.
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Wijngaarden, Jessica E., Jauw, Yvonne W. S., Zwezerijnen, Gerben J. C., de Wit-van der Veen, Berlinda J., Vugts, Daniëlle J., Zijlstra, Josée M., van Dongen, Guus A. M. S., Boellaard, Ronald, Menke-van der Houven van Oordt, C. Willemien, and Huisman, Marc C.
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TUMORS ,POSITRON emission tomography - Abstract
Background: Distribution of mAbs into tumour tissue may occur via different processes contributing differently to the
89 Zr-mAb uptake on PET. Target-specific binding in tumours is of main interest; however, non-specific irreversible uptake may also be present, which influences quantification. The aim was to investigate the presence of non-specific irreversible uptake in tumour tissue using Patlak linearization on89 Zr-immuno-PET data of biopsy-proven target-negative tumours. Data of two studies, including target status obtained from biopsies, were retrospectively analysed, and Patlak linearization provided the net rate of irreversible uptake (Ki ). Results: Two tumours were classified as CD20-negative and two as CD20-positive. Four tumours were classified as CEA-negative and nine as CEA-positive. Ki values of CD20-negative (0.43 µL/g/h and 0.92 µL/g/h) and CEA-negative tumours (mdn = 1.97 µL/g/h, interquartile range (IQR) = 1.50–2.39) were higher than zero. Median Ki values of target-negative tumours were lower than CD20-positive (1.87 µL/g/h and 1.90 µL/g/h) and CEA-positive tumours (mdn = 2.77 µL/g/h, IQR = 2.11–3.65). Conclusion: Biopsy-proven target-negative tumours showed irreversible uptake of89 Zr-mAbs measured in vivo using89 Zr-immuno-PET data, which suggests the presence of non-specific irreversible uptake in tumours. Consequently, for89 Zr-immuno-PET, even if the target is absent, a tumour-to-plasma ratio always increases over time. [ABSTRACT FROM AUTHOR]- Published
- 2024
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9. How to obtain the image-derived blood concentration from 89Zr-immuno-PET scans.
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Wijngaarden, Jessica E., Ahbari, Amina, Pouw, Johanna E. E., Greuter, Henri N. J. M., Bahce, Idris, Zwezerijnen, Gerben J. C., Vugts, Daniëlle J., van Dongen, Guus A. M. S., Boellaard, Ronald, Menke-van der Houven van Oordt, C. Willemien, and Huisman, Marc C.
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POSITRON emission tomography ,THORACIC aorta ,MONOCLONAL antibodies ,BLOOD sampling ,AORTA ,STANDARD operating procedure - Abstract
Background: PET scans using zirconium-89 labelled monoclonal antibodies (
89 Zr-mAbs), known as89 Zr-immuno-PET, are made to measure uptake in tumour and organ tissue. Uptake is related to the supply of89 Zr-mAbs in the blood. Measuring activity concentrations in blood, however, requires invasive blood sampling. This study aims to identify the best delineation strategy to obtain the image-derived blood concentration (IDBC) from89 Zr-immuno-PET scans. Methods: PET imaging and blood sampling of two89 Zr-mAbs were included,89 Zr-cetuximab and89 Zr-durvalumab. For seven patients receiving89 Zr-cetuximab, PET scans on 1–2 h, 2 and 6 days post-injection (p.i.) were analysed. Five patients received three injections of89 Zr-durvalumab. The scanning protocol for the first two injections consisted of PET scanning on 2, 5 and 7 days p.i. and for the third injection only on 7 days p.i. Blood samples were drawn with every PET scan and the sample-derived blood concentration (SDBC) was used as gold standard for the IDBC. According to an in-house developed standard operating procedure, the aortic arch, ascending aorta, descending aorta and left ventricle were delineated. Bland–Altman analyses were performed to assess the bias (mean difference) and variability (1.96 times the standard deviation of the differences) between IDBC and SDBC. Results: Overall, the activity concentration obtained from the IDBC was lower than from the SDBC. When comparing IDBC with SDBC, variability was smallest for the ascending aorta (20.3% and 17.0% for89 Zr-cetuximab and89 Zr-durvalumab, respectively). Variability for the other regions ranged between 17.9 and 30.8%. Bias for the ascending aorta was − 10.9% and − 11.4% for89 Zr-cetuximab and89 Zr-durvalumab, respectively. Conclusions: Image-derived blood concentrations should be obtained from delineating the ascending aorta in89 Zr-immuno-PET scans, as this results in the lowest variability with respect to sample-derived blood concentrations. [ABSTRACT FROM AUTHOR]- Published
- 2024
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10. Molecular imaging predicts lack of T-DM1 response in advanced HER2-positive breast cancer (final results of ZEPHIR trial).
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Mileva, Magdalena, de Vries, Elisabeth G. E., Guiot, Thomas, Wimana, Zéna, Deleu, Anne-Leen, Schröder, Carolien P., Lefebvre, Yolene, Paesmans, Marianne, Stroobants, Sigrid, Huizing, Manon, Aftimos, Philippe, Tol, Jolien, Van der Graaf, Winette T. A., Oyen, Wim J. G., Vugts, Danielle J., Menke-van der Houven van Oordt, C. Willemien, Brouwers, Adrienne H., Piccart-Gebhart, Martine, Flamen, Patrick, and Gebhart, Géraldine
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- 2024
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11. 89 Zr-Immuno-PET with Immune Checkpoint Inhibitors: Measuring Target Engagement in Healthy Organs.
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Miedema, Iris H. C., Wijngaarden, Jessica E., Pouw, Johanna E. E., Zwezerijnen, Gerben J. C., Sebus, Hylke J., Smit, Egbert, de Langen, Adrianus J., Bahce, Idris, Thiele, Andrea, Vugts, Daniëlle J., Boellaard, Ronald, Huisman, Marc C., and Menke-van der Houven van Oordt, C. Willemien
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BRAIN ,IMMUNE checkpoint inhibitors ,KIDNEYS ,RADIOISOTOPES ,ORGANS (Anatomy) ,MONOCLONAL antibodies ,IMMUNE system ,BLOOD collection ,POSITRON emission tomography ,RESEARCH funding ,SPLEEN ,BONE marrow - Abstract
Simple Summary: The uptake on a
89 Zr-immuno-PET scan is not just the result of the binding of a radiolabeled antibody with its target (i.e., target engagement) but also includes background factors such as non-specific binding (for example, catabolism of antibodies inside endothelial cells). In this study, we wanted to isolate target engagement. We used data from five previously performed89 Zr-immuno-PET studies with immune-targeting89 Zr-radiolabeled antibodies. First, via Patlak analysis, we separated reversible from irreversible uptake, and by using a baseline of target-negative organs, we further defined target-specific irreversible uptake. Second, we compared different mass doses (ratios of labeled and unlabeled antibody) and looked for saturation effects. Evidence for target engagement was based on the following two things: (1) when the target-specific irreversible uptake exceeded the baseline, and (2) when the signal showed saturation. We found target engagement for the different antibodies in several lymphoid organs, for example, in the spleen, while the brain had close to zero target engagement. We propose a new baseline for bone marrow and brain. In conclusion, we promote the use of Patlak analysis for89 Zr-immuno-PET studies, or similar simplified outcomes such as a tissue-to-blood ratio. Introduction:89 Zr-immuno-PET (positron emission tomography with zirconium-89-labeled monoclonal antibodies ([89 Zr]Zr-mAbs)) can be used to study the biodistribution of mAbs targeting the immune system. The measured uptake consists of target-specific and non-specific components, and it can be influenced by plasma availability of the tracer. To find evidence for target-specific uptake, i.e., target engagement, we studied five immune-checkpoint-targeting [89 Zr]Zr-mAbs to (1) compare the uptake with previously reported baseline values for non-specific organ uptake (ns-baseline) and (2) look for saturation effects of increasing mass doses. Method:89 Zr-immuno-PET data from five [89 Zr]Zr-mAbs, i.e., nivolumab and pembrolizumab (anti-PD-1), durvalumab (anti-PD-L1), BI 754,111 (anti-LAG-3), and ipilimumab (anti-CTLA-4), were analysed. For each mAb, 2–3 different mass doses were evaluated. PET scans and blood samples from at least two time points 24 h post injection were available. In 35 patients, brain, kidneys, liver, spleen, lungs, and bone marrow were delineated. Patlak analysis was used to account for differences in plasma activity concentration and to quantify irreversible uptake (Ki ). To identify target engagement, Ki values were compared to ns-baseline Ki values previously reported, and the effect of increasing mass doses on Ki was investigated. Results: All mAbs, except ipilimumab, showed Ki values in spleen above the ns-baseline for the lowest administered mass dose, in addition to decreasing Ki values with higher mass doses, both indicative of target engagement. For bone marrow, no ns-baseline was established previously, but a similar pattern was observed. For kidneys, most mAbs showed Ki values within the ns-baseline for both low and high mass doses. However, with high mass doses, some saturation effects were seen, suggestive of a lower ns-baseline value. Ki values were near zero in brain tissue for all mass doses of all mAbs. Conclusion: Using Patlak analysis and the established ns-baseline values, evidence for target engagement in (lymphoid) organs for several immune checkpoint inhibitors could be demonstrated. A decrease in the Ki values with increasing mass doses supports the applicability of Patlak analysis for the assessment of target engagement for PET ligands with irreversible uptake behavior. [ABSTRACT FROM AUTHOR]- Published
- 2023
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12. 89Zr-immuno-PET using the anti-LAG-3 tracer [89Zr]Zr-BI 754111: demonstrating target specific binding in NSCLC and HNSCC.
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Miedema, Iris H.C., Huisman, Marc C., Zwezerijnen, Gerben J.C., Grempler, Rolf, Pitarch, Alejandro Perez, Thiele, Andrea, Hesse, Raphael, Elgadi, Mabrouk, Peltzer, Alexander, Vugts, Danielle J., van Dongen, Guus A.M.S., de Gruijl, Tanja D., Menke-van der Houven van Oordt, C. Willemien, and Bahce, Idris
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POSITRON emission tomography ,LYMPHOCYTE transformation ,NON-small-cell lung carcinoma ,RNA sequencing ,ANTINEOPLASTIC agents ,PROGRAMMED cell death 1 receptors - Abstract
Purpose: Although lymphocyte activation gene-3 (LAG-3) directed therapies demonstrate promising clinical anti-cancer activity, only a subset of patients seems to benefit and predictive biomarkers are lacking. Here, we explored the potential use of the anti-LAG-3 antibody tracer [
89 Zr]Zr-BI 754111 as a predictive imaging biomarker and investigated its target specific uptake as well as the correlation of its tumor uptake and the tumor immune infiltration. Methods: Patients with head and neck (N = 2) or lung cancer (N = 4) were included in an imaging substudy of a phase 1 trial with BI 754091 (anti-PD-1) and BI 754111 (anti-LAG-3). After baseline tumor biopsy and [18 F]FDG-PET, patients were given 240 mg of BI 754091, followed 8 days later by administration of [89 Zr]Zr-BI 754111 (37 MBq, 4 mg). PET scans were performed 2 h, 96 h, and 144 h post-injection. To investigate target specificity, a second tracer administration was given two weeks later, this time with pre-administration of 40 (N = 3) or 600 mg (N = 3) unlabeled BI 754111, followed by PET scans at 96 h and 144 h post-injection. Tumor immune cell infiltration was assessed by immunohistochemistry and RNA sequencing. Results: Tracer uptake in tumors was clearly visible at the 4-mg mass dose (tumor-to-plasma ratio 1.63 [IQR 0.37-2.89]) and could be saturated by increasing mass doses (44 mg: 0.67 [IQR 0.50–0.85]; 604 mg: 0.56 [IQR 0.42–0.75]), demonstrating target specificity. Tumor uptake correlated to immune cell-derived RNA signatures. Conclusions: [89 Zr]Zr-BI-754111 PET imaging shows favorable technical and biological characteristics for developing a potential predictive imaging biomarker for LAG-3-directed therapies. Trial registration: ClinicalTrials.gov, NCT03780725. Registered 19 December 2018 [ABSTRACT FROM AUTHOR]- Published
- 2023
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13. Validation of simplified uptake measures against dynamic Patlak Ki for quantification of lesional 89Zr-Immuno-PET antibody uptake.
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Wijngaarden, Jessica E., Huisman, Marc C., Jauw, Yvonne W. S., van Dongen, Guus A. M. S., Greuter, Henri N. J. M., Schuit, Robert C., Cleveland, Matthew, Gootjes, Elske C., Vugts, Daniëlle J., Menke-van der Houven van Oordt, C. Willemien, and Boellaard, Ronald
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POSITRON emission tomography ,MONOCLONAL antibodies ,IMMUNOGLOBULINS - Abstract
Purpose: Positron emission tomography imaging of zirconium-89-labelled monoclonal antibodies (
89 Zr-Immuno-PET) allows for visualisation and quantification of antibody uptake in tumours in vivo. Patlak linearization provides distribution volume (VT ) and nett influx rate (Ki ) values, representing reversible and irreversible uptake, respectively. Standardised uptake value (SUV) and tumour-to-plasma/tumour-to-blood ratio (TPR/TBR) are often used, but their validity depends on the comparability of plasma kinetics and clearances. This study assesses the validity of SUV, TPR and TBR against Patlak Ki for quantifying irreversible89 Zr-Immuno-PET uptake in tumours. Methods: Ten patients received 37 MBq 10 mg89 Zr-anti-EGFR with 500 mg/m2 unlabelled mAbs. Five patients received two doses of 37 MBq89 Zr-anti-HER3: 8–24 mg for the first administration and 24 mg–30 mg/kg for the second. Seven tumours from four patients showed89 Zr-anti-EGFR uptake, and 18 tumours from five patients showed89 Zr-anti-HER3 uptake. SUVpeak, TPRpeak and TBRpeak values were obtained from one to six days p.i. Patlak linearization was applied to tumour time activity curves and plasma samples to obtain Ki . Results: For89 Zr-anti-EGFR, there was a small variability along the linear regression line between SUV (− 0.51–0.57), TPR (− 0.06‒0.11) and TBR (− 0.13‒0.16) on day 6 versus Ki . Similar doses of89 Zr-anti-HER3 showed similar variability for SUV (− 1.3‒1.0), TPR (− 1.1‒0.53) and TBR (− 1.5‒0.72) on day 5 versus Ki . However, for the second administration of89 Zr-anti-HER3 with a large variability in administered mass doses, SUV showed a larger variability (− 1.4‒2.3) along the regression line with Ki , which improved when using TPR (− 0.38–0.32) or TBR (− 0.56‒0.46). Conclusion: SUV, TPR and TBR at late time points were valid for quantifying irreversible lesional89 Zr-Immuno-PET uptake when constant mass doses were administered. However, for variable mass doses, only TPR and TBR provided reliable values for irreversible uptake, but not SUV, because SUV does not take patient and mass dose-specific plasma clearance into account. [ABSTRACT FROM AUTHOR]- Published
- 2023
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14. Potential and pitfalls of Zr-89-immuno-PET to assess target status: Zr-89-trastuzumab as an example:89Zr-trastuzumab as an example
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Huisman, Marc C., Menke-van der Houven van Oordt, C. Willemien, Zijlstra, Josée M., Hoekstra, Otto S., Boellaard, Ronald, van Dongen, Guus A.M.S., Shah, Dhaval K., Jauw, Yvonne W.S., Radiology and nuclear medicine, Amsterdam Neuroscience - Brain Imaging, Internal medicine, CCA - Imaging and biomarkers, Hematology, and AII - Cancer immunology
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Background: 89Zirconium-immuno-positron emission tomography (89Zr-immuno-PET) is used for assessment of target status to guide antibody-based therapy. We aim to determine the relation between antibody tumor uptake and target concentration to improve future study design and interpretation. Methods: The relation between tumor uptake and target concentration was predicted by mathematical modeling of 89Zr-labeled antibody disposition in the tumor. Literature values for trastuzumab kinetics were used to provide an example. Results: 89Zr-trastuzumab uptake initially increases with increasing target concentration, until it levels off to a constant value. This is determined by the total administered mass dose of trastuzumab. For a commonly used imaging dose of 50 mg 89Zr-trastuzumab, uptake can discriminate between immunohistochemistry score (IHC) 0 versus 1–2–3. Conclusion: The example for 89Zr-trastuzumab illustrates the potential to assess target expression. The pitfall of false-positive findings depends on the cut-off to define clinical target positivity (i.e., IHC 3) and the administered mass dose.
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- 2021
15. Systemic Therapy for Patients with HER2-Positive Breast Cancer and Brain Metastases: A Systematic Review and Meta-Analysis.
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Werter, Inge M., Remmelzwaal, Sharon, Burchell, George L., de Gruijl, Tanja D., Konings, Inge R., van der Vliet, Hans J., and Menke-van der Houven van Oordt, C. Willemien
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THERAPEUTIC use of antimetabolites ,THERAPEUTIC use of monoclonal antibodies ,THERAPEUTIC use of antineoplastic agents ,ONLINE information services ,MEDICAL databases ,ETOPOSIDE ,META-analysis ,MEDICAL information storage & retrieval systems ,CONFIDENCE intervals ,EPIDERMAL growth factor receptors ,CANCER chemotherapy ,SYSTEMATIC reviews ,TRASTUZUMAB ,METASTASIS ,BRAIN tumors ,CANCER patients ,TREATMENT effectiveness ,PROTEIN-tyrosine kinase inhibitors ,DESCRIPTIVE statistics ,CISPLATIN ,MEDLINE ,PROGRESSION-free survival ,BEVACIZUMAB ,BREAST tumors - Abstract
Simple Summary: Patients with HER2-positive metastatic breast cancer develop brain metastases in up to 30% of cases. The aim of this systematic review and meta-analysis was to determine the effect of different systemic therapies in patients with HER2-positive metastatic breast cancer and brain metastases, acknowledging the heterogeneity and sometimes low quality of 51 included studies. Tucatinib (combined with trastuzumab and capecitabine) and trastuzumab-deruxtecan appear to constitute the most effective systemic therapy, while pyrotinib might be an option in Asian patients. Preferably, future research will comprise of randomized controlled trials, including patients with active and/or inactive brain metastases. Aim: Patients with HER2-positive (HER2+) metastatic breast cancer (mBC) develop brain metastases (BM) in up to 30% of cases. Treatment of patients with BM can consist of local treatment (surgery and/or radiotherapy) and/or systemic treatment. We undertook a systematic review and meta-analysis to determine the effect of different systemic therapies in patients with HER2+ mBC and BM. Methods: A systematic search was performed in the databases PubMed, Embase.com, Clarivate Analytics/Web of Science Core Collection and the Wiley/Cochrane Library. Eligible articles included prospective or retrospective studies reporting on the effect of systemic therapy on objective response rate (ORR) and/or median progression free survival (mPFS) in patients with HER2+ mBC and BM. The timeframe within the databases was from inception to 19 January 2022. Fixed-effects meta-analyses were used. Quality appraisal was performed using the ROBINS-I tool. Results: Fifty-one studies were included, involving 3118 patients. Most studies, which contained the largest patient numbers, but also often carried a moderate-serious risk of bias, investigated lapatinib and capecitabine (LC), trastuzumab-emtansine (T-DM1) or pyrotinib. The best quality data and/or highest ORR were described with tucatinib (combined with trastuzumab and capecitabine, TTC) and trastuzumab-deruxtecan (T-DXd). TTC demonstrated an ORR of 47.3% in patients with asymptomatic and/or active BM. T-DXd achieved a pooled ORR of 64% (95% CI 43–85%, I
2 0%) in a heavily pretreated population with asymptomatic BM (3 studies, n = 96). Conclusions: Though our meta-analysis should be interpreted with caution due to the heterogeneity of included studies and a related serious risk of bias, this review provides a comprehensive overview of all currently available systemic treatment options. T-Dxd and TTC that appear to constitute the most effective systemic therapy in patients with HER2+ mBC and BM, while pyrotinib might be an option in Asian patients. [ABSTRACT FROM AUTHOR]- Published
- 2022
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16. Optimal imaging time points considering accuracy and precision of Patlak linearization for 89Zr-immuno-PET: a simulation study.
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Wijngaarden, Jessica E., Huisman, Marc C., Pouw, Johanna E. E., Menke-van der Houven van Oordt, C. Willemien, Jauw, Yvonne W. S., and Boellaard, Ronald
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POSITRON emission tomography ,REFERENCE values ,MONOCLONAL antibodies ,BLOOD sampling - Abstract
Purpose: Zirconium-89-immuno-positron emission tomography (
89 Zr-immuno-PET) has enabled visualization of zirconium-89 labelled monoclonal antibody (89 Zr-mAb) uptake in organs and tumors in vivo. Patlak linearization of89 Zr-immuno-PET quantification data allows for separation of reversible and irreversible uptake, by combining multiple blood samples and PET images at different days. As one can obtain only a limited number of blood samples and scans per patient, choosing the optimal time points is important. Tissue activity concentration curves were simulated to evaluate the effect of imaging time points on Patlak results, considering different time points, input functions, noise levels and levels of reversible and irreversible uptake. Methods: Based on89 Zr-mAb input functions and reference values for reversible (VT ) and irreversible (Ki ) uptake from literature, multiple tissue activity curves were simulated. Three different89 Zr-mAb input functions, five time points between 24 and 192 h p.i., noise levels of 5, 10 and 15%, and three reference Ki and VT values were considered. Simulated Ki and VT were calculated (Patlak linearization) for a thousand repetitions. Accuracy and precision of Patlak linearization were evaluated by comparing simulated Ki and VT with reference values. Results: Simulations showed that Ki is always underestimated. Inclusion of time point 24 h p.i. reduced bias and variability in VT , and slightly reduced bias and variability in Ki , as compared to combinations of three later time points. After inclusion of 24 h p.i., minimal differences were found in bias and variability between different combinations of later imaging time points, despite different input functions, noise levels and reference values. Conclusion: Inclusion of a blood sample and PET scan at 24 h p.i. improves accuracy and precision of Patlak results for89 Zr-immuno-PET; the exact timing of the two later time points is not critical. [ABSTRACT FROM AUTHOR]- Published
- 2022
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17. Cost-Utility of the eHealth Application 'Oncokompas', Supporting Incurably Ill Cancer Patients to Self-Manage Their Cancer-Related Symptoms: Results of a Randomized Controlled Trial.
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Schuit, Anouk S., Holtmaat, Karen, Coupé, Veerle M. H., Eerenstein, Simone E. J., Zijlstra, Josée M., Eeltink, Corien, Becker-Commissaris, Annemarie, van Zuylen, Lia, van Linde, Myra E., Menke-van der Houven van Oordt, C. Willemien, Sommeijer, Dirkje W., Verbeek, Nol, Bosscha, Koop, Nandoe Tewarie, Rishi, Sedee, Robert-Jan, de Bree, Remco, de Graeff, Alexander, de Vos, Filip, Cuijpers, Pim, and Verdonck-de Leeuw, Irma M.
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PALLIATIVE treatment ,CANCER patients ,QUALITY of life ,QUALITY-adjusted life years ,RANDOMIZED controlled trials - Abstract
Evidence on the cost-effectiveness of eHealth in palliative care is scarce. Oncokompas, a fully automated behavioral intervention technology, aims to support self-management in cancer patients. This study aimed to assess the cost-utility of the eHealth application Oncokompas among incurably ill cancer patients, compared to care as usual. In this randomized controlled trial, patients were randomized into the intervention group (access to Oncokompas) or the waiting-list control group (access after three months). Healthcare costs, productivity losses, and health status were measured at baseline and three months. Intervention costs were also taken into account. Non-parametric bootstrapping with 5000 replications was used to obtain 95% confidence intervals around the incremental costs and quality-adjusted life years (QALYs). A probabilistic approach was used because of the skewness of cost data. Altogether, 138 patients completed the baseline questionnaire and were randomly assigned to the intervention group (69) or the control group (69). In the base case analysis, mean total costs and mean total effects were non-significantly lower in the intervention group (−€806 and −0.01 QALYs). The probability that the intervention was more effective and less costly was 4%, whereas the probability of being less effective and less costly was 74%. Among patients with incurable cancer, Oncokompas does not impact incremental costs and seems slightly less effective in terms of QALYs, compared to care as usual. Future research on the costs of eHealth in palliative cancer care is warranted to assess the generalizability of the findings of this study. [ABSTRACT FROM AUTHOR]
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- 2022
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18. PET‐CT Imaging of Polymeric Nanoparticle Tumor Accumulation in Patients.
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Miedema, Iris H. C., Zwezerijnen, Gerben J. C., Huisman, Marc C., Doeleman, Ellen, Mathijssen, Ron H. J., Lammers, Twan, Hu, Qizhi, van Dongen, Guus A. M. S., Rijcken, Cristianne J. F., Vugts, Danielle J., and Menke‐van der Houven van Oordt, C. Willemien
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- 2022
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19. Potential and pitfalls of 89Zr-immuno-PET to assess target status: 89Zr-trastuzumab as an example.
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Huisman, Marc C., Menke-van der Houven van Oordt, C. Willemien, Zijlstra, Josée M., Hoekstra, Otto S., Boellaard, Ronald, van Dongen, Guus A. M. S., Shah, Dhaval K., and Jauw, Yvonne W. S.
- Subjects
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TRASTUZUMAB , *MONOCLONAL antibodies - Abstract
Background: 89Zirconium-immuno-positron emission tomography (89Zr-immuno-PET) is used for assessment of target status to guide antibody-based therapy. We aim to determine the relation between antibody tumor uptake and target concentration to improve future study design and interpretation. Methods: The relation between tumor uptake and target concentration was predicted by mathematical modeling of 89Zr-labeled antibody disposition in the tumor. Literature values for trastuzumab kinetics were used to provide an example. Results: 89Zr-trastuzumab uptake initially increases with increasing target concentration, until it levels off to a constant value. This is determined by the total administered mass dose of trastuzumab. For a commonly used imaging dose of 50 mg 89Zr-trastuzumab, uptake can discriminate between immunohistochemistry score (IHC) 0 versus 1–2–3. Conclusion: The example for 89Zr-trastuzumab illustrates the potential to assess target expression. The pitfall of false-positive findings depends on the cut-off to define clinical target positivity (i.e., IHC 3) and the administered mass dose. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
20. Irreversible Electroporation and Nivolumab Combined with Intratumoral Administration of a Toll-Like Receptor Ligand, as a Means of In Vivo Vaccination for Metastatic Pancreatic Ductal Adenocarcinoma (PANFIRE-III). A Phase-I Study Protocol.
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Geboers, Bart, Timmer, Florentine E. F., Ruarus, Alette H., Pouw, Johanna E. E., Schouten, Evelien A. C., Bakker, Joyce, Puijk, Robbert S., Nieuwenhuizen, Sanne, Dijkstra, Madelon, van den Tol, M. Petrousjka, de Vries, Jan J. J., Oprea-Lager, Daniela E., Menke-van der Houven van Oordt, C. Willemien, van der Vliet, Hans J., Wilmink, Johanna W., Scheffer, Hester J., de Gruijl, Tanja D., and Meijerink, Martijn R.
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PANCREATIC tumors ,ADENOCARCINOMA ,METASTASIS ,IMMUNOSUPPRESSION ,RANDOMIZED controlled trials ,ELECTROPORATION ,NIVOLUMAB ,ELECTROTHERAPEUTICS ,COMBINED modality therapy ,CANCER vaccines ,COMPUTED tomography ,TOLL-like receptors ,LIGANDS (Biochemistry) ,IMMUNOTHERAPY ,PATIENT safety ,EMISSION-computed tomography - Abstract
Simple Summary: Metastatic pancreatic ductal adenocarcinoma has a dismal prognosis, and to date no curative treatment options exist. The image guided tumor ablation technique irreversible electroporation (IRE) employs high-voltage electrical pulses through the application of several needle electrodes in and around the tumor in order to induce cell death. IRE ablation of the primary tumor has the ability to reduce pancreatic tumor induced immune suppression while allowing the expansion of tumor specific effector T cells, hereby possibly shifting the pancreatic tumor microenvironment into a more immune permissive state. The addition of immune enhancing therapies to IRE might work synergistically and could potentially induce a clinically significant treatment effect. This study protocol describes the rationale and design of the PANFIRE-III trial that aims to assess the safety of the combination of IRE with IMO-2125 (toll-like receptor 9 ligand) and/or nivolumab in patients with metastatic pancreatic ductal adenocarcinoma. Irreversible electroporation (IRE) is a novel image-guided tumor ablation technique with the ability to generate a window for the establishment of systemic antitumor immunity. IRE transiently alters the tumor's immunosuppressive microenvironment while simultaneously generating antigen release, thereby instigating an adaptive immune response. Combining IRE with immunotherapeutic drugs, i.e., electroimmunotherapy, has synergistic potential and might induce a durable antitumor response. The primary objective of this study is to assess the safety of the combination of IRE with IMO-2125 (a toll-like receptor 9 ligand) and/or nivolumab in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC). In this randomized controlled phase I clinical trial, 18 patients with mPDAC pretreated with chemotherapy will be enrolled in one of three study arms: A (control): nivolumab monotherapy; B: percutaneous IRE of the primary tumor followed by nivolumab; or C: intratumoral injection of IMO-2125 followed by percutaneous IRE of the primary tumor and nivolumab. Assessments include contrast enhanced computed tomography (ceCT),
18 F-FDG and1 8 F-BMS-986192 (PD-L1) positron emission tomography (PET)-CT, biopsies of the primary tumor and metastases, peripheral blood samples, and quality of life and pain questionnaires. There is no curative treatment option for patients with mPDAC, and palliative chemotherapy regimens only moderately improve survival. Consequently, there is an urgent need for innovative and radically different treatment approaches. Should electroimmunotherapy establish an effective and durable anti-tumor response, it may ultimately improve PDAC's dismal prognosis. [ABSTRACT FROM AUTHOR]- Published
- 2021
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21. Design, development and clinical translation of CriPec®-based core-crosslinked polymeric micelles.
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Rijcken, Cristianne J.F., De Lorenzi, Federica, Biancacci, Ilaria, Hanssen, Rob G.J.M., Thewissen, Marielle, Hu, Qizhi, Atrafi, Florence, Liskamp, Rob M.J., Mathijssen, Ron H.J., Miedema, Iris H.C., Menke - van der Houven van Oordt, C. Willemien, van Dongen, Guus A.M.S., Vugts, Danielle J., Timmers, Matt, Hennink, Wim E., and Lammers, Twan
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MICELLES , *SMALL molecules , *TARGETED drug delivery , *DRUG delivery systems , *BLOCK copolymers , *ADVANCED glycation end-products - Abstract
[Display omitted] Nanomedicines are used to improve the efficacy and safety of pharmacotherapeutic interventions. Unraveling the biological behavior of nanomedicines, including their biodistribution and target site accumulation, is essential to establish design criteria that contribute to superior performance. CriPec® technology is based on amphiphilic methoxy-poly(ethylene glycol)- b -poly[N-(2-hydroxypropyl) methacrylamide lactate] (mPEG- b -pHPMAmLac n) block copolymers, which are designed to upon self-assembly covalently entrap active pharmaceutical ingredients (API) in core-crosslinked polymeric micelles (CCPM). Key features of CCPM are a prolonged circulation time, high concentrations at pathological sites, and low levels of accumulation in the majority of healthy tissues. Proprietary hydrolysable linkers allow for tunable and sustained release of entrapped API, including hydrophobic and hydrophilic small molecules, as well as peptides and oligonucleotides. Preclinical imaging experiments provided valuable information on their tumor and tissue accumulation and distribution, as well as on uptake by cancer, healthy and immune cells. The frontrunner formulation CPC634, which refers to 65 nm-sized CCPM entrapping the chemotherapeutic drug docetaxel, showed excellent pharmacokinetic properties, safety, tumor accumulation and antitumor efficacy in multiple animal models. In the clinic, CPC634 also demonstrated favorable pharmacokinetics, good tolerability, signs of efficacy, and enhanced localization in tumor tissue as compared to conventional docetaxel. PET imaging of radiolabeled CPC634 showed quantifiable accumulation in ∼50 % of tumors and metastases in advanced-stage cancer patients, and demonstrated potential for use in a theranostic setting even when applied at a companion diagnostic dose. Altogether, the preclinical and clinical results obtained to date demonstrate that mPEG- b -pHPMAmLac n CCPM based on CriPec® technology are a potent, tunable, broadly applicable and well-tolerable platform for targeted drug delivery and improved anticancer therapy. [ABSTRACT FROM AUTHOR]
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- 2022
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22. Circulating T cell status and molecular imaging may predict clinical benefit of neoadjuvant PD-1 blockade in oral cancer.
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Wondergem NE, Miedema IHC, van de Ven R, Zwezerijnen GJC, de Graaf P, Karagozoglu KH, Hendrickx JJ, Eerenstein SEJ, Bun RJ, Mulder DC, Voortman J, Boellaard R, Windhorst AD, Hagers JP, Peferoen LAN, de Gruijl TD, Bloemena E, Brakenhoff RH, Leemans CR, and Menke-van der Houven van Oordt CW
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- Humans, Male, Female, Middle Aged, Aged, Immune Checkpoint Inhibitors therapeutic use, Immune Checkpoint Inhibitors pharmacology, Molecular Imaging methods, Nivolumab therapeutic use, Nivolumab pharmacology, T-Lymphocytes immunology, T-Lymphocytes metabolism, Programmed Cell Death 1 Receptor antagonists & inhibitors, Positron-Emission Tomography methods, Adult, Mouth Neoplasms drug therapy, Mouth Neoplasms diagnostic imaging, Mouth Neoplasms pathology, Neoadjuvant Therapy methods
- Abstract
Background: Addition of neoadjuvant immune checkpoint inhibition to standard-of-care interventions for locally advanced oral cancer could improve clinical outcome., Methods: In this study, 16 evaluable patients with stage III/IV oral cancer were treated with one dose of 480 mg nivolumab 3 weeks prior to surgery. Primary objectives were safety, feasibility, and suitability of programmed death receptor ligand-1 positron emission tomography (PD-L1 PET) as a biomarker for response. Imaging included
18 F-BMS-986192 (PD-L1) PET and18 F-fluorodeoxyglucose (FDG) PET before and after nivolumab treatment. Secondary objectives included clinical and pathological response, and immune profiling of peripheral blood mononuclear cells (PBMCs) for response prediction. Baseline tumor biopsies and postnivolumab resection specimens were evaluated by histopathology., Results: Grade III or higher adverse events were not observed and treatment was not delayed in relation to nivolumab administration and other study procedures. Six patients (38%) had a pathological response, of whom three (19%) had a major (≥90%) pathological response (MPR). Tumor PD-L1 PET uptake (quantified using standard uptake value) was not statistically different in patients with or without MPR (median 5.3 vs 3.4). All major responders showed a significantly postnivolumab decreased signal on FDG PET. PBMC immune phenotyping showed higher levels of CD8+ T cell activation in MPR patients, evidenced by higher baseline expression levels of PD-1, TIGIT, IFNγ and lower levels of PD-L1., Conclusion: Together these data support that neoadjuvant treatment of advanced-stage oral cancers with nivolumab was safe and induced an MPR in a promising 19% of patients. Response was associated with decreased FDG PET uptake as well as activation status of peripheral T cell populations., Competing Interests: Competing interests: RvdV has received research funding from Genmab BV. TDdG is scientific advisor to Immunicum, GE Health, and Lava Therapeutics, holds stock from LAVA Therapeutics and received research funding from Idera Pharmaceuticals (now Aceragen). RHB received research grants from KWF Kankerbestrijding/Dutch Cancer Society, Cancer Center Amsterdam Foundation, ZonMW and NWO, Genmab BV and the Hanarth Foundation and is on the advisory board of Nanobiotix. He has a scientific collaboration with Orfenix BV and Qialix DoT. CRL received research grants from KWF Kankerbestrijding/Dutch Cancer Society, Cancer Center Amsterdam Foudation, Genmab BV, BMS and the Hanarth Foundation and is on the advisory board of Merck & Co. CWM-vdHvO received research grants from BMS, Boeringher Ingelheim, GSK, Pfizer and AstraZeneca and consulted for GE Health Care, Novartis and EliLilly. All other authors report no competing interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)- Published
- 2024
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23. Exploring the predictive potential of programmed death ligand 1 expression in healthy organs and lymph nodes as measured by 18 F-BMS986-192 PET: pooled analysis of data from four solid tumor types.
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Miedema IHC, Pouw JEE, Kwakman A, Zwezerijnen GJC, Huisman MC, Timmer FEF, van de Ven R, de Gruijl TD, Hospers GAP, de Langen AJ, and Menke-van der Houven van Oordt CW
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- Humans, Male, Female, Neoplasms drug therapy, Neoplasms metabolism, Neoplasms diagnostic imaging, Immune Checkpoint Inhibitors therapeutic use, Immune Checkpoint Inhibitors pharmacology, Middle Aged, Aged, B7-H1 Antigen metabolism, Lymph Nodes metabolism, Lymph Nodes pathology, Lymph Nodes diagnostic imaging, Positron-Emission Tomography methods
- Abstract
Introduction: Immune checkpoint inhibitors (ICIs) can elicit anticancer immune responses, but predictive biomarkers are needed. We measured programmed death ligand 1 (PD-L1) expression in organs and lymph nodes using
18 F-BMS-986192 positron emission tomography (PET)-imaging and looked for correlations with response and immune-related adverse events., Methods: Four18 F-BMS-986192 PET studies in patients with melanoma, lung, pancreatic and oral cancer, receiving ICI treatment, were combined. Imaging data (organ standardized uptake value (SUV)mean , lymph node SUVmax ) and clinical data (response to treatment and incidence of immune-related adverse events) were extracted., Results: Baseline PD-L1 uptake in the spleen was on average higher in non-responding patients than in responders (spleen SUVmean 16.1±4.4 vs 12.5±3.4, p=0.02). This effect was strongest in lung cancer, and not observed in oral cancer. In the oral cancer cohort, benign tumor-draining lymph nodes (TDLNs) had higher PD-L1 uptake (SUVmax 3.3 IQR 2.5-3.9) compared with non-TDLNs (SUVmax 1.8, IQR 1.4-2.8 p=0.04). Furthermore, in the same cohort non-responders showed an increase in PD-L1 uptake in benign TDLNs on-treatment with ICIs (+15%), while for responders the PD-L1 uptake decreased (-11%). PD-L1 uptake did not predict immune-related adverse events, though elevated thyroid uptake on-treatment correlated with pre-existing thyroid disease or toxicity., Conclusion: PD-L1 PET uptake in the spleen is a potential negative predictor of response to ICIs. On-treatment with ICIs, PD-L1 uptake in benign TDLNs increases in non-responders, while it decreases in responders, potentially indicating a mechanism for resistance to ICIs in patients with oral cancer., Competing Interests: Competing interests: RvdV: Research funding for Institute: Genmab B.V. TDdG: Research funding for Institute: Idera Pharmaceuticals (now Aceragen); Consultancy: GE Health, LAVA Therapeutics, Mendus (all to Institute); holds stocks from LAVA Therapeutics. GAPH: Research funding for Institute: Bristol-Myers Squibb, Seerave. Consultancy/advisory relationships with Amgen, Bristol-Myers Squibb, Roche, MSD, Pfizer, Novartis, Sanofi, Pierre Fabre. AJdL: Research funding for Institute: Bristol-Myers Squibb, MSD, Boehringer Ingelheim, AstraZeneca. Non-financial support from Merck Serono, non-financial support from Roche. CWM-vdHvO: Research funding for Institute: Bristol-Myers Squibb, Boehringer Ingelheim, GSK, Pfizer; AstraZeneca. Consultancy: GE Health Care, Novartis, Eli Lilly. IHCM, JEEP, AK, GJCZ, MCH, FEFT: No competing interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)- Published
- 2024
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24. Non-specific irreversible 89 Zr-mAb uptake in tumours: evidence from biopsy-proven target-negative tumours using 89 Zr-immuno-PET.
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Wijngaarden JE, Jauw YWS, Zwezerijnen GJC, de Wit-van der Veen BJ, Vugts DJ, Zijlstra JM, van Dongen GAMS, Boellaard R, Menke-van der Houven van Oordt CW, and Huisman MC
- Abstract
Background: Distribution of mAbs into tumour tissue may occur via different processes contributing differently to the
89 Zr-mAb uptake on PET. Target-specific binding in tumours is of main interest; however, non-specific irreversible uptake may also be present, which influences quantification. The aim was to investigate the presence of non-specific irreversible uptake in tumour tissue using Patlak linearization on89 Zr-immuno-PET data of biopsy-proven target-negative tumours. Data of two studies, including target status obtained from biopsies, were retrospectively analysed, and Patlak linearization provided the net rate of irreversible uptake (Ki )., Results: Two tumours were classified as CD20-negative and two as CD20-positive. Four tumours were classified as CEA-negative and nine as CEA-positive. Ki values of CD20-negative (0.43 µL/g/h and 0.92 µL/g/h) and CEA-negative tumours (mdn = 1.97 µL/g/h, interquartile range (IQR) = 1.50-2.39) were higher than zero. Median Ki values of target-negative tumours were lower than CD20-positive (1.87 µL/g/h and 1.90 µL/g/h) and CEA-positive tumours (mdn = 2.77 µL/g/h, IQR = 2.11-3.65)., Conclusion: Biopsy-proven target-negative tumours showed irreversible uptake of89 Zr-mAbs measured in vivo using89 Zr-immuno-PET data, which suggests the presence of non-specific irreversible uptake in tumours. Consequently, for89 Zr-immuno-PET, even if the target is absent, a tumour-to-plasma ratio always increases over time., (© 2024. The Author(s).)- Published
- 2024
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25. How to obtain the image-derived blood concentration from 89 Zr-immuno-PET scans.
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Wijngaarden JE, Ahbari A, Pouw JEE, Greuter HNJM, Bahce I, Zwezerijnen GJC, Vugts DJ, van Dongen GAMS, Boellaard R, Menke-van der Houven van Oordt CW, and Huisman MC
- Abstract
Background: PET scans using zirconium-89 labelled monoclonal antibodies (
89 Zr-mAbs), known as89 Zr-immuno-PET, are made to measure uptake in tumour and organ tissue. Uptake is related to the supply of89 Zr-mAbs in the blood. Measuring activity concentrations in blood, however, requires invasive blood sampling. This study aims to identify the best delineation strategy to obtain the image-derived blood concentration (IDBC) from89 Zr-immuno-PET scans., Methods: PET imaging and blood sampling of two89 Zr-mAbs were included,89 Zr-cetuximab and89 Zr-durvalumab. For seven patients receiving89 Zr-cetuximab, PET scans on 1-2 h, 2 and 6 days post-injection (p.i.) were analysed. Five patients received three injections of89 Zr-durvalumab. The scanning protocol for the first two injections consisted of PET scanning on 2, 5 and 7 days p.i. and for the third injection only on 7 days p.i. Blood samples were drawn with every PET scan and the sample-derived blood concentration (SDBC) was used as gold standard for the IDBC. According to an in-house developed standard operating procedure, the aortic arch, ascending aorta, descending aorta and left ventricle were delineated. Bland-Altman analyses were performed to assess the bias (mean difference) and variability (1.96 times the standard deviation of the differences) between IDBC and SDBC., Results: Overall, the activity concentration obtained from the IDBC was lower than from the SDBC. When comparing IDBC with SDBC, variability was smallest for the ascending aorta (20.3% and 17.0% for89 Zr-cetuximab and89 Zr-durvalumab, respectively). Variability for the other regions ranged between 17.9 and 30.8%. Bias for the ascending aorta was - 10.9% and - 11.4% for89 Zr-cetuximab and89 Zr-durvalumab, respectively., Conclusions: Image-derived blood concentrations should be obtained from delineating the ascending aorta in89 Zr-immuno-PET scans, as this results in the lowest variability with respect to sample-derived blood concentrations., (© 2024. The Author(s).)- Published
- 2024
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26. First exploration of the on-treatment changes in tumor and organ uptake of a radiolabeled anti PD-L1 antibody during chemoradiotherapy in patients with non-small cell lung cancer using whole body PET.
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Pouw JEE, Hashemi SMS, Huisman MC, Wijngaarden JE, Slebe M, Oprea-Lager DE, Zwezerijnen GJC, Vugts D, Ulas EB, de Gruijl TD, Radonic T, Senan S, Menke-van der Houven van Oordt CW, and Bahce I
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- Humans, B7-H1 Antigen metabolism, Positron-Emission Tomography methods, Chemoradiotherapy, Carcinoma, Non-Small-Cell Lung diagnostic imaging, Carcinoma, Non-Small-Cell Lung drug therapy, Lung Neoplasms drug therapy
- Abstract
Background: In patients with locally advanced unresectable non-small cell lung cancer (NSCLC), durvalumab, an anti-programmed cell death ligand-1 (PD-L1) antibody, has shown improved overall survival when used as consolidation therapy following concurrent chemoradiotherapy (CRT). However, it is unclear whether CRT itself upregulates PD-L1 expression. Therefore, this study aimed to explore the changes in the uptake of the anti PD-L1 antibody [
89 Zr]Zr-durvalumab in tumors and healthy organs during CRT in patients with NSCLC., Methods: Patients with NSCLC scheduled to undergo CRT were scanned 7±1 days after administration of 37±1 MBq [89 Zr]Zr-durvalumab at baseline, 1-week on-treatment and 1 week after finishing 6 weeks of CRT. First, [89 Zr]Zr-durvalumab uptake was visually assessed in a low dose cohort with a mass dose of 2 mg durvalumab (0.13% of therapeutic dose) and subsequently, quantification was done in a high dose cohort with a mass dose of 22.5 mg durvalumab (1.5% of therapeutic dose). Tracer pharmacokinetics between injections were compared using venous blood samples drawn in the 22.5 mg cohort. Visual assessment included suspected lesion detectability. Positron emission tomography (PET) uptake in tumoral and healthy tissues was quantified using tumor to plasma ratio (TPR) and organ to plasma ratio, respectively., Results: In the 2 mg dose cohort, 88% of the 17 identified tumor lesions were positive at baseline, compared with 69% (9/13) for the 22.5 mg cohort. Although the absolute plasma concentrations between patients varied, the intrapatient variability was low. The ten quantitatively assessed lesions in the 22.5 mg cohort had a median TPR at baseline of 1.3 (IQR 0.7-1.5), on-treatment of 1.0 (IQR 0.7-1.4) and at the end of treatment of 0.7 (IQR 0.6-0.7). On-treatment, an increased uptake in bone marrow was seen in three out of five patients together with a decreased uptake in the spleen in four out of five patients., Conclusions: This study successfully imaged patients with NSCLC with [89 Zr]Zr-durvalumab PET before and during CRT. Our data did not show any increase in [89 Zr]Zr-durvalumab uptake in the tumor 1-week on-treatment and at the end of treatment. The changes observed in bone marrow and spleen may be due to an CRT-induced effect on immune cells., Trial Registration Number: EudraCT number: 2019-004284-51., Competing Interests: Competing interests: SMSH is on the advisory board and/or received institutional research support from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Janssen, GlaxoSmithKline, Merck Sharp & Dohme, Novartis, Roche and Takeda. DV received institutional research support from Bristol-Myers Squibb, Daiichi Sankyo, GlaxoSmithKline, Boehringer Ingelheim, Roche and Aplagon. SS is on the advisory board of AstraZeneca, receives institutional research support and a speakers fee from AstraZeneca. SS is on the advisory board of Bristol-Myers Squibb and receives institutional research support from Bristol-Myers Squibb. CWM-vdHvO is advisor for GEHealthcare and Eli Lilly and received institutional research support from GlaxoSmithKline, Boehringer Ingelheim, AstraZeneca, G1 Therapeutics and Bristol-Myers Squibb., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)- Published
- 2024
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27. [18F]FDG and [18F]FES PET/CT Imaging as a Biomarker for Therapy Effect in Patients with Metastatic ER+ Breast Cancer Undergoing Treatment with Rintodestrant.
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Iqbal R, Yaqub M, Bektas HO, Oprea-Lager DE, de Vries EGE, Glaudemans AWJM, Aftimos P, Gebhart G, Beelen AP, Schuit RC, Windhorst AD, Boellaard R, and Menke-van der Houven van Oordt CW
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- Humans, Female, Fluorodeoxyglucose F18 therapeutic use, Positron Emission Tomography Computed Tomography methods, Receptors, Estrogen genetics, Receptors, Estrogen metabolism, Estradiol therapeutic use, Estrogen Antagonists therapeutic use, Molecular Imaging, Biomarkers, Breast Neoplasms diagnostic imaging, Breast Neoplasms drug therapy, Breast Neoplasms genetics
- Abstract
Purpose: PET with 16α-[18F]-fluoro-17β-estradiol ([18F]FES) allows assessment of whole body estrogen receptor (ER) expression. The aim of this study was to investigate [18F]-fluorodeoxyglucose ([18F]FDG) and [18F]FES PET/CT imaging for response prediction and monitoring of drug activity in patients with metastatic ER-positive breast cancer undergoing treatment with the selective estrogen receptor downregulator (SERD) rintodestrant., Experimental Design: In this trial (NCT03455270), PET/CT imaging was performed at baseline ([18F]FDG and [18F]FES), during treatment and at time of progression (only [18F]FES). Visual, quantitative, and mutational analysis was performed to derive a heterogeneity score (HS) and assess tracer uptake in lesions, in relation to the mutation profile. The primary outcome was progression-free survival (PFS)., Results: The HS and PFS in the entire group did not correlate (n = 16, Spearman's rho, P = 0.06), but patients with a low HS (< 25.0%, n = 4) had a PFS of > 5 months whereas patients with no [18F]FES uptake (HS 100.0%, n = 3) had a PFS of < 2 months. [18F]FES uptake was not affected by estrogen receptor 1 (ESR1) mutations. On-treatment [18F]FES PET/CT scans showed no [18F]FES uptake in any of the baseline [18F]FES-positive lesions. At progression, [18F]FES uptake remained blocked in patients scanned ≤ 1-2 half-lives of rintodestrant whereas it restored in patients scanned ≥ 5 days after end of treatment., Conclusions: Absence of ER expression on [18F]FES PET is a predictor for no response to rintodestrant. [18F]FES uptake during treatment and at time of progression is useful to monitor the (reversible) effect of therapy and continued mode of action of SERDs. See related commentary by Linden and Mankoff, p. 2015., (©2023 American Association for Cancer Research.)
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- 2023
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28. [89Zr]Zr-DFO-girentuximab and [18F]FDG PET/CT to Predict Watchful Waiting Duration in Patients with Metastatic Clear-cell Renal Cell Carcinoma.
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Verhoeff SR, Oosting SF, Elias SG, van Es SC, Gerritse SL, Angus L, Heskamp S, Desar IME, Menke-van der Houven van Oordt CW, van der Veldt AAM, Arens AIJ, Brouwers AH, Eisses B, Mulders PFA, Hoekstra OS, Zwezerijnen GJC, van der Graaf WTA, Aarntzen EHJG, Oyen WJG, and van Herpen CML
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- Humans, Positron Emission Tomography Computed Tomography, Fluorodeoxyglucose F18 therapeutic use, Radioisotopes therapeutic use, Zirconium, Watchful Waiting, Prognosis, Radiopharmaceuticals therapeutic use, Carcinoma, Renal Cell diagnostic imaging, Carcinoma, Renal Cell therapy
- Abstract
Purpose: Watchful waiting (WW) can be considered for patients with metastatic clear-cell renal cell carcinoma (mccRCC) with good or intermediate prognosis, especially those with <2 International Metastatic RCC Database Consortium criteria and ≤2 metastatic sites [referred to as watch and wait ("W&W") criteria]. The IMaging PAtients for Cancer drug SelecTion-Renal Cell Carcinoma study objective was to assess the predictive value of [18F]FDG PET/CT and [89Zr]Zr-DFO-girentuximab PET/CT for WW duration in patients with mccRCC., Experimental Design: Between February 2015 and March 2018, 48 patients were enrolled, including 40 evaluable patients with good (n = 14) and intermediate (n = 26) prognosis. Baseline contrast-enhanced CT, [18F]FDG and [89Zr]Zr-DFO-girentuximab PET/CT were performed. Primary endpoint was the time to disease progression warranting systemic treatment. Maximum standardized uptake values (SUVmax) were measured using lesions on CT images coregistered to PET/CT. High and low uptake groups were defined on the basis of median geometric mean SUVmax of RECIST-measurable lesions across patients., Results: The median WW time was 16.1 months [95% confidence interval (CI): 9.0-31.7]. The median WW period was shorter in patients with high [18F]FDG tumor uptake than those with low uptake (9.0 vs. 36.2 months; HR, 5.6; 95% CI: 2.4-14.7; P < 0.001). Patients with high [89Zr]Zr-DFO-girentuximab tumor uptake had a median WW period of 9.3 versus 21.3 months with low uptake (HR, 1.7; 95% CI: 0.9-3.3; P = 0.13). Patients with "W&W criteria" had a longer median WW period of 21.3 compared with patients without: 9.3 months (HR, 1.9; 95% CI: 0.9-3.9; Pone-sided = 0.034). Adding [18F]FDG uptake to the "W&W criteria" improved the prediction of WW duration (P < 0.001); whereas [89Zr]Zr-DFO-girentuximab did not (P = 0.53)., Conclusions: In patients with good- or intermediate-risk mccRCC, low [18F]FDG uptake is associated with prolonged WW. This study shows the predictive value of the "W&W criteria" for WW duration and shows the potential of [18F]FDG-PET/CT to further improve this., (©2022 The Authors; Published by the American Association for Cancer Research.)
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- 2023
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29. Evaluating new treatments for anaplastic thyroid cancer.
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Coca-Pelaz A, Rodrigo JP, Lopez F, Shah JP, Silver CE, Al Ghuzlan A, Menke-van der Houven van Oordt CW, Smallridge RC, Shaha AR, Angelos P, Mendenhall WM, Piazza C, Olsen KD, Corry J, Tufano RP, Sanabria A, Nuyts S, Nathan CA, Vander Poorten V, Dias FL, Suarez C, Saba NF, de Graaf P, Williams MD, Rinaldo A, and Ferlito A
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- Humans, Quality of Life, Prognosis, Precision Medicine, Proto-Oncogene Proteins B-raf genetics, Mutation, Thyroid Carcinoma, Anaplastic drug therapy, Thyroid Carcinoma, Anaplastic genetics, Thyroid Carcinoma, Anaplastic pathology, Thyroid Neoplasms drug therapy, Thyroid Neoplasms genetics, Thyroid Neoplasms pathology
- Abstract
Introduction: Anaplastic thyroid cancer (ATC) is one of the most lethal diseases known to humans with a median survival of 5 months. The American Thyroid Association (ATA) recently published guidelines for the treatment of this dreadful thyroid malignancy., Areas Covered: This review presents the current therapeutic landscape of this challenging disease. We also present the results from trials published over the last five years and summarize currently active clinical trials., Expert Opinion: Recent attempts to improve the prognosis of these tumors are moving toward personalized medicine, basing the treatment decision on the specific genetic profile of the individual tumor. The positive results of dabrafenib and trametinib for ATC harboring the BRAF V600E mutation have provided a useful treatment option. For the other genetic profiles, different drugs are available and can be used to individualize the treatment, likely using drug combinations. Combinations of drugs act on different molecular pathways and achieve inhibition at separate areas. With new targeted therapies, average survival has improved considerably and death from local disease progression or airway compromise is less likely with improvement in quality of life. Unfortunately, the results remain poor in terms of survival.
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- 2022
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30. Praluzatamab Ravtansine, a CD166-Targeting Antibody-Drug Conjugate, in Patients with Advanced Solid Tumors: An Open-Label Phase I/II Trial.
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Boni V, Fidler MJ, Arkenau HT, Spira A, Meric-Bernstam F, Uboha N, Sanborn RE, Sweis RF, LoRusso P, Nagasaka M, Garcia-Corbacho J, Jalal S, Harding JJ, Kim SK, Miedema IHC, Vugts DJ, Huisman MC, Zwezerijnen GJC, van Dongen GAMS, Menke van der Houven van Oordt CW, Wang S, Dang T, Zein IA, Vasiljeva O, Lyman SK, Paton V, Hannah A, and Liu JF
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- Female, Humans, Tumor Microenvironment, Antineoplastic Agents therapeutic use, Breast Neoplasms drug therapy, Immunoconjugates adverse effects, Maytansine therapeutic use, Neoplasms pathology
- Abstract
Purpose: Praluzatamab ravtansine (CX-2009) is a conditionally activated Probody drug conjugate (PDC) comprising an anti-CD166 mAb conjugated to DM4, with a protease-cleavable linker and a peptide mask that limits target engagement in normal tissue and circulation. The tumor microenvironment is enriched for proteases capable of cleaving the linker, thereby releasing the mask, allowing for localized binding of CX-2009 to CD166. CX-2009 was evaluated in a phase I/II clinical trial for patients with advanced solid tumors., Patients and Methods: Eligible patients had metastatic cancer receiving ≥2 prior treatments. CX-2009 was administered at escalating doses every 3 weeks (0.25-10 mg/kg) or every 2 weeks (4-6 mg/kg). Primary objective was to determine the safety profile and recommended phase II dose (RP2D)., Results: Of 99 patients enrolled, the most prevalent subtype was breast cancer (n = 45). Median number of prior therapies was 5 (range, 1-19). Dose-limiting toxicities were observed at 8 mg/kg every 3 weeks and 6 mg/kg every 2 weeks. On the basis of tolerability, the RP2D was 7 mg/kg every 3 weeks. Tumor regressions were observed at doses ≥4 mg/kg. In the hormone receptor-positive/HER2-nonamplified breast cancer subset (n = 22), 2 patients (9%) had confirmed partial responses, and 10 patients (45%) had stable disease. Imaging with zirconium-labeled CX-2009 confirmed uptake in tumor lesions and shielding of major organs. Activated, unmasked CX-2009 was measurable in 18 of 22 posttreatment biopsies., Conclusions: CD166 is a novel, ubiquitously expressed target. CX-2009 is the first conditionally activated antibody-drug conjugate to CD166 to demonstrate both translational and clinical activity in a variety of tumor types., (©2022 The Authors; Published by the American Association for Cancer Research.)
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- 2022
- Full Text
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31. Efficacy of the eHealth application Oncokompas, facilitating incurably ill cancer patients to self-manage their palliative care needs: A randomized controlled trial.
- Author
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Schuit AS, Holtmaat K, Lissenberg-Witte BI, Eerenstein SEJ, Zijlstra JM, Eeltink C, Becker-Commissaris A, van Zuylen L, van Linde ME, Menke-van der Houven van Oordt CW, Sommeijer DW, Verbeek N, Bosscha K, Tewarie RN, Sedee RJ, de Bree R, de Graeff A, de Vos F, Cuijpers P, and Verdonck-de Leeuw IM
- Abstract
Background: Many patients with incurable cancer have symptoms affecting their health-related quality of life. The eHealth application 'Oncokompas' supports patients to take an active role in managing their palliative care needs, to reduce symptoms and improve health-related quality of life (HRQOL). This randomized controlled trial was conducted to determine the efficacy of Oncokompas compared to care as usual among incurably ill cancer patients with a life expectancy of more than three months., Methods: Patients were recruited in six hospitals in the Netherlands. Eligible patients were randomly assigned to the intervention (direct access to Oncokompas) or the control group (access to Oncokompas after three months). The primary outcome measure was patient activation (i.e., patients' knowledge, skills and confidence for self-management). Secondary outcomes were general self-efficacy and HRQOL. Measures were assessed at baseline, two weeks after randomization, and three months after the baseline measurement. Linear mixed models were used to compare longitudinal changes between both groups from baseline to the three-month follow-up., Findings: In total, 219 patients were eligible of which 138 patients completed the baseline questionnaire (response rate 63%), and were randomized to the intervention (69) or control group (69). There were no significant differences between the intervention and control group over time in patient activation (estimated difference in change T0-T2; 1·8 (90% CI: -1·0 to 4·7)), neither in general self-efficacy and HRQOL. Of the patients in the intervention group who activated their account, 74% used Oncokompas as intended. The course of patient activation, general self-efficacy, and HRQOL was not significantly different between patients who used Oncokompas as intended versus those who did not., Interpretation: Among incurably ill cancer patients with a life expectancy of more than three months and recruited in the hospital setting, Oncokompas did not significantly improve patient activation, self-efficacy, or HRQOL., Funding: ZonMw, Netherlands Organization for Health Research and Development (844001105)., Competing Interests: IVdL reports grants from the Netherlands Organization for Health Research and Development (ZonMw), the Dutch Cancer Society (KWF Kankerbestrijding), Bristol Myers Squibb, Danone Ecofund/Nutricia. ABC reports grants from Roche. FdV reports grants from Foundation STOPbraintumors.org and AbbVIe, BMS, Novartis, EORTC, Vaximm and BioClin Therapeutics. FdV reports participation on a DSMB during the conduct of this study, and leaderships or fiduciary roles in other boards and commissions. All other authors declare no competing interests., (© 2022 The Author(s).)
- Published
- 2022
- Full Text
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