Hendrik Everaert

Vrije Universiteit Brussel, Bruxelles, Brussels Capital, Belgium

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Publications (140)411.43 Total impact

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    Dataset: 2627 suppl

    Full-text · Dataset · Jan 2016
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    ABSTRACT: A patient with a pleural epitheloid hemangio-endothelioma (EHE) who failed to respond to six cycles of initial chemotherapy with iphosphamide and epirubicine was treated with pazopanib in second-line. A significant subjective and objective metabolic response on F-18-fluoro-deoxyglucose positron-emission tomography-computed tomography was noted. Based on this observation, the role of vasculoendothelial growth factor receptor inhibitors such as pazopanib (or other tyrosine kinase inhibitors), in the treatment of pleural EHE should be established through prospective collaborative studies as upfront medication and in combination with chemotherapy.
    No preview · Article · Jan 2016 · Anticancer research
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    ABSTRACT: Aim: the primary aims were assessment of safety, biodistribution and dosimetry. The secondary aim was to investigate tumor targeting potential. Methods: In total, 20 female patients with primary or metastatic breast carcinoma (HER2 IHC 2+ or 3+) were included. Anti-HER2 Nanobody is labeled with (68)Ga via a NOTA derivative. Administered activities were 53-174 MBq (average 107 MBq). PET/CT scans (for dosimetry assessment) were obtained at 10, 60 and 90 min post administration. Physical evaluation and blood analysis were performed for safety evaluation. Biodistribution was analyzed for 11 organs using MIM software; dosimetry was assessed using OLINDA/EXM. Tumor targeting potential was assessed in primary and metastatic lesions. Results: No adverse reactions occurred. A fast blood clearance was observed, with only 10% of injected activity remaining in the blood at 1h post injection. Uptake was mainly seen in kidneys, liver, and intestines. The effective dose was 0.043 mSv/MBq, resulting in an average of 4.6 mSv per patient. The critical organ was the urinary bladder wall with a dose of 0.406 mGy/MBq. In patients with metastatic disease, tracer accumulation well above background was demonstrated in the majority of identified sites of disease. Primary lesions were more variable in tracer accumulation. Conclusion: (68)Ga--HER2-Nanobody PET/CT is a safe procedure with a radiation dose comparable to other routinely used PET tracers. Its biodistribution is favorable, with the highest uptake in kidneys, liver and intestines, but very low background levels in all other organs that typically house primary breast carcinoma or tumor metastasis. Tracer accumulation in HER2-positive metastases is high, compared to normal surrounding tissues, and warrants further assessment in a phase II trial.
    Full-text · Article · Oct 2015 · Journal of Nuclear Medicine
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    ABSTRACT: Tyrosine kinase signaling through the vascular endothelial growth factor receptor 2 (VEGFR2), plateletderived growth factor receptor- α (PDGFR-α) and KIT cell surface receptors mediates neo-angiogenesis and contributes to cancer cell survival in recurrent anaplastic and low-grade glioma. Thirteen patients with temozolomide-refractory recurrent anaplastic or low-grade glioma were treated with sunitinib malate, a small-molecule tyrosine kinase inhibitor of the VEGFR, PDGFR, and KIT receptors, in combination with lomustine. The most frequent grade 3 and 4 adverse events were fatigue, thrombocytopenia, neutropenia and lymphopenia. The best objective tumor response by Response Assessment in Neuro-Oncology (RANO) criteria was one complete response, one unconfirmed partial response and three cases of stable disease. The median progression-free survival was 1.8 months (95% confidence interval=1.0-2.7 months) with 6-month progression-free survival of 15% (95% confidence interval=0-35%). The median overall survival was 6.7 months (95% confidence interval=0.7-12 months). The investigated combination regimen of sunitinib and lomustine is well-tolerated but insufficiently active to warrant further investigation in an unselected population of patients with temozolomide-refractory recurrent anaplastic and lowgrade glioma.
    No preview · Article · Oct 2015 · Anticancer research
  • M. Meysman · H. Everaert · N. Buls · K. Nieboer · J. de Mey
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    ABSTRACT: The natural evolution of treated symptomatic pulmonary embolism shows often incomplete resolution of pulmonary thrombi. The prevalence of perfusion defects depend on the image modality used. This study directly compares V/Q SPECT with DECT. A single-center prospective observational cohort study of patients with intermediate risk PE, reassessed at the end of treatment with V/Q SPECT. Abnormal V/Q SPECT images were compared with DECT. We compared DECT en V/Q SPECT in 28 consecutive patients with persistent V/Q mismatch on V/Q SPECT, 13 men and 15 woman, mean age 60 (+17), range 23-82 year. One patient was excluded from the final analysis due to inferior quality DECT. In 18/27 (66.7%) the results were concordant between CTPA (persistent embolus visible), DECT (segmentary defects on iodine map) and V/Q SPECT (segmentary ventilation-perfusion mismatch). In 3/18 (11.1% of the total group) the partialy matched V/Q SPECT defect could be explained on DECT lung images by lung infarction. In 6/27 (22.1%) only hypoperfusion was seen on DECT iodine map. In 3/27 (11.1%) results were discordant between V/Q SPECT and DECT images. Six months after diagnosis of first or recurrent PE, residual pulmonary perfusion-defects encountered on V/Q-SPECT corresponds in the majority of patients with chronic thromboembolic disease seen on DECT. In 22.1% of patients V/Q SPECT mismatch only corresponds with hypoperfusion on iodine map DECT scan. Some (11.1%) of the chronic thromboembolic lesions seen on V/Q SPECT can not be explained by DECT results. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    No preview · Article · May 2015 · European Journal of Radiology
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    ABSTRACT: Purpose To compare using immuno-PET/CT the distribution of Zr-89-labelled rituximab without and with a preload of unlabelled rituximab to assess the impact of preloading with unlabelled rituximab on tumour targeting and radiation dose of subsequent radioimmunotherapy with Y-90-labelled rituximab in CD20+ B-cell lymphoma. Methods Five patients with CD20+ B-cell lymphoma and progressive disease were prospectively enrolled. All patients underwent three study phases: initial dosimetric phase with baseline Zr-89-rituximab PET/CT imaging without a cold preload, followed 3 weeks later by a second dosimetric phase with administration of a standard preload (250 mg/m(2)) of unlabelled rituximab followed by injection of Zr-89-rituximab, and a therapeutic phase 1 week later with administration of unlabelled rituximab followed by Y-90-rituximab. PET/CT imaging and tracer uptake by organs and lesions were assessed. Results With a cold rituximab preload, the calculated whole-body dose of Y-90-rituximab was similar (mean 0.87 mSv/MBq, range 0.82-0.99 mSv/MBq) in all patients. Without a preload, an increase in whole-body dose of 59 % and 87 % was noted in two patients with preserved circulating CD20+ B cells. This increase in radiation dose was primarily due to a 12.4-fold to 15-fold higher dose to the spleen without a preload. No significant change in whole-body dose was noted in the three other patients with B-cell depletion. Without a preload, consistently higher tumour uptake was noticed in patients with B-cell depletion. Conclusion Administration of the standard preload of unlabelled rituximab impairs radioconjugate tumour targeting in the majority of patients eligible for radioimmunotherapy, that is patients previously treated with rituximab-containing therapeutic regimens. This common practice may need to be reconsidered and further evaluated as the rationale for this high preload has its origin in the "prerituximab era".
    Full-text · Article · Mar 2015 · European journal of nuclear medicine and molecular imaging
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    ABSTRACT: INTRODUCTION: VEGF/VEGFR targeted therapy for recurrent glioblastoma (rGB) normalizes tumour vasculature and restores the blood-brain barrier (BBB), resulting in decreased contrast enhancement and reduced peritumoral oedema. MRI-T2/FLAIR images are useful to document non-contrast-enhancing tumor progression, but its specificity is limited. Since the uptake of Fluoroethyltyrosine in GB reflects tumor metabolism and not BBB-integrity, the extent of (18)F-fluoroethyltyrosine (FET) uptake, as assessed by positron emission tomography (PET), may be of value in assessing the tumor response to treatment with small molecule VEGFR-inhibitors such as axitinib., MATERIAL AND METHODS: We evaluated patients with rGB treated with axitinib with MRI and FET-PET (static images acquired 45 min. after tracer administration) at baseline. In patients demonstrating a response on MRI (using RANO criteria), FET-PET was repeated. For 18F-FET PET, reduction of the metabolically active volume (Sum of tumour associated pixels with target-to-normal brain ratio of ≥1.5) was considered as a metabolic response to treatment. RESULTS: 15 patients treated with axitinib were evaluated with MRI and FET-PET. On MRI, 2 pts had CR and 4 PR. All responses on MRI were also characterized by a decrease in FET-active tumor volume. The extent of reduction of metabolically active volume did not correlated with the extent of tumor regression on Gd- MRI: the 2 patients with CR on MRI had a 65% and 43% decrease on FET-PET, respectively, whereas the decrease on FET-PET ranged between 26 and 100% in the patients with PR on MRI. A trend was observed between a higher baseline FET-active tumor volume and an increased progression-free survival (PFS) and overall survival (OS). A greater reduction of the metabolically active volume did correlate with longer PFS and OS (logrank p > 0,001 and p < 0,025, respectively). CONCLUSION: In patients with rGB treated with the VEGFR-inhibitor axitinib, baseline FET-PET has prognostic value. Response evaluation based on FET-PET is complementary to MRI based assessment and may prove superior in predicting survival on treatment with axitinib. Our preliminary findings deserve further evaluation in a larger series.
    Full-text · Article · Sep 2014 · Neuro-Oncology
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    ABSTRACT: INTRODUCTION: Glioblastoma (GB) associated neo-angiogenesis is mediated by vascular endothelial growth factor receptor (VEGFR) signal transduction. Axitinib is an oral small molecule tyrosine kinase inhibitor with high affinity and specificity for the VEGF-receptors, approved for the treatment of metastatic renal cell carcinoma. METHODS: Axitinib (5 mg BID starting dose) vs. best alternative choice of therapy was studied in an open label, randomized, phase II clinical trial in patients (pts) with recurrent GB. Six-month progression-free survival (6mPFS) was the primary endpoint using Fleming's single-stage procedure. RESULTS: Between Sep 2011 and Oct 2013, 44 pts who failed surgery, RT and temozolomide were randomized 1:1 at 3 sites. Median age 54y (range 20-79), 33M/11F, WHO-PS 0/1/2/3: 6, 26, 11, and 1 pt. In the control arm 20 pts received bevacizumab and 2 pts received lomustine at standard doses. Axitinib (n = 22) was generally well tolerated. Most common axitinib related AEs consisted of dysphonia (3x G2), fatigue (6x G2, 2x G3), hypertension (5x G2), oral hyperesthesia (7x G2, 1x G3), diarrhea (2x G2, 2x G3), and hypothyroidism (3x G2). In 4 pts axitinib dosing was interrupted and subsequently dose reduced because of toxicity; in 4 other pts axitinib was dose escalated to 7 or 10 mg BID (2 pts each). The confirmed best overall tumor response rate by RANO criteria was 28% in the axitinib arm (2 CR / 4 PR) vs. 23% in the control arm (1 CR / 4 PR). Five additional pts in the axitinib-arm and 1 additional patient in the control-arm had an unconfirmed respons, and respectively 5 and 7 patients had a SD; 1pt in each arm was not evaluable for tumor response. Corticosteroids could be stopped in 4/12 and tapered in an additional 5/12 pts in the axitinib arm. At baseline all pts had an increased uptake on 18F-FET PET and a magnetic resonance spectroscopy (MRS) signal pattern showing an increased level of choline (Cho) and a decreased level of N-acetylaspartate (NAA) at the site of rGB. A decrease (-26 to -100%) of SUVmax/background on 18F-FET PET was documented in 6/7 pts on axitinib at the time of response on MRI. MRS-spectra obtained at the time of response and progression are currently being analysed. After a median follow-up of 10.5 mths, the 6mPFS for axitinib was 22% (95% CI 5-40) vs. 19% (95% CI 2-36) for the control arm. Median PFS and OS were respectively 2.9 vs. 2.6 mths, and 10.3 vs. 7.4 mths for pts treated in the axitinib vs. control arm. CONCLUSIONS: Axitinib has single-agent activity and manageable toxicity in pts with recurrent GB. The survival on the axitinib arm was comparable to that on the contemporary control arm. Tumor response on MRI is accompanied by decreased uptake of tracer on 18F-FET PET scan. Response characteristics in MRS are currently under evaluation. Further evaluation of axitinib for recurrent GB is warranted.
    Full-text · Article · Sep 2014 · Neuro-Oncology
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    ABSTRACT: Purpose: To assess a classification scheme for predicting local tumor progression (LTP) after radiofrequency (RF) ablation of liver metastases, using predefined patterns on contrast-enhanced computed tomography (CT) and positron emission tomography (PET) combined with CT (PET/CT) acquired 24 hours after RF ablation. Materials and methods: There were 45 metastases in 20 patients treated. After 24 hours, imaging of the ablation zones was performed with contrast-enhanced PET/CT. Three independent radiologists prospectively assessed contrast-enhanced CT and combined PET/CT images to identify three patterns: pattern I, no tissue enhancement or fluorodeoxyglucose uptake between the ablation zone and the liver parenchyma; pattern II, a rimlike pattern; and pattern III, a peripheral nodule. PET/CT images obtained after 8-10 weeks were evaluated for LTP. The patterns were analyzed for their sensitivity, specificity, positive predictive value, and negative predictive value for predicting LTP. Results: Pattern I was most frequently observed (81% for contrast-enhanced CT and 61% for PET/CT) as well as for ablation zones that showed LTP (52% and 37%, respectively). Conversely, pattern II was observed for tumors that were completely ablated (6% and 29%, respectively). Patterns II and III together had the highest sensitivity for predicting LTP (48% and 63%, respectively); pattern III had the highest specificity (94% and 95%, respectively). For nodular patterns, test characteristics were better for PET/CT compared with contrast-enhanced CT, but the difference was not significant. Nodular patterns > 1 cm achieved high positive predictive value (both 100%). Conclusions: Inflammation and hyperemia can hinder interpretation on imaging 24 hours after RF ablation, especially on PET/CT. Nodular patterns around the ablation zone on early contrast-enhanced CT and PET/CT have a high predictive value for LTP and should be taken into account for disease management.
    No preview · Article · Jun 2014 · Journal of vascular and interventional radiology: JVIR
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    ABSTRACT: Purpose To assess a classification scheme for predicting local tumor progression (LTP) after radiofrequency (RF) ablation of liver metastases, using predefined patterns on contrast-enhanced computed tomography (CT) and positron emission tomography (PET) combined with CT (PET/CT) acquired 24 hours after RF ablation. Materials and Methods There were 45 metastases in 20 patients treated. After 24 hours, imaging of the ablation zones was performed with contrast-enhanced PET/CT. Three independent radiologists prospectively assessed contrast-enhanced CT and combined PET/CT images to identify three patterns: pattern I, no tissue enhancement or fluorodeoxyglucose uptake between the ablation zone and the liver parenchyma; pattern II, a rimlike pattern; and pattern III, a peripheral nodule. PET/CT images obtained after 8–10 weeks were evaluated for LTP. The patterns were analyzed for their sensitivity, specificity, positive predictive value, and negative predictive value for predicting LTP. Results Pattern I was most frequently observed (81% for contrast-enhanced CT and 61% for PET/CT) as well as for ablation zones that showed LTP (52% and 37%, respectively). Conversely, pattern II was observed for tumors that were completely ablated (6% and 29%, respectively). Patterns II and III together had the highest sensitivity for predicting LTP (48% and 63%, respectively); pattern III had the highest specificity (94% and 95%, respectively). For nodular patterns, test characteristics were better for PET/CT compared with contrast-enhanced CT, but the difference was not significant. Nodular patterns > 1 cm achieved high positive predictive value (both 100%). Conclusions Inflammation and hyperemia can hinder interpretation on imaging 24 hours after RF ablation, especially on PET/CT. Nodular patterns around the ablation zone on early contrast-enhanced CT and PET/CT have a high predictive value for LTP and should be taken into account for disease management.
    No preview · Article · Jan 2014
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    Full-text · Dataset · Oct 2013
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    Full-text · Dataset · May 2013
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    Full-text · Dataset · May 2013
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    Full-text · Dataset · May 2013