Vincent Grégoire

The Catholic University of America, Washington, Washington, D.C., United States

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Publications (306)1216.32 Total impact

  • Marie-Aline Neveu · Vanesa Bol · Anne Bol · Vincent Gregoire · Bernard Gallez

    No preview · Article · Jan 2016 · Advances in Experimental Medicine and Biology
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    ABSTRACT: Background: The last few years, in radiotherapy there has been a growing focus on speed of treatment delivery (largely driven by economical and commercial interests). This study investigates the influence of treatment time on plan quality for helical tomotherapy (HT), using delivery times with Volumetric Modulated Arc Therapy (VMAT; Rapid Arc [RA]) as reference. Methods: In a previous study, double arc RA (Eclipse) and standard HT plans (TomoHD™) were created for five oropharyngeal cancer patients and reported according to ICRU 83 guidelines. By modifying the beam width from 2.5 to 5.0 cm, elevating the pitch and lowering the modulation factor, "TomoFast" (TF) plans were generated with treatment times equal to RA plans. To quantify the impact of TF's craniocaudal gradient, similar plans were generated on TomoEdge(TM) (TomoEdgeFast;TEF). The homogeneity index (HI), conformity index (CI), mean dose, Dnear-max (D2) and Dnear-min (D98) of the PTVs were analyzed as well as the mean dose, specific critical doses and volumes of 26 organs at risk (OARs). Data were analyzed using repeated measures ANOVA. Results: With a mean treatment time of 3.05 min (RA), 2.89 min (TF) and 2.95 min (TEF), PTVtherapeutic coverage was more homogeneous with TF (HI.07;SE.01) and TEF (HI.08;SE.01) compared to RA (HI.10;SE.01), while PTVprophylactic was most homogeneous with RA. Mean doses to parotid glands were comparable for RA, TF, TEF: 25.62, 25.34, 23.09 Gy for contralateral and 32.02, 31.96, 30.01 Gy for ipsilateral glands, respectively. OARs' mean doses varied between different approaches not favoring a particular technique. TF's higher dose to OARs at the cranial-caudal edges of the PTVs and its higher integral dose, both due to the extended cranial-caudal gradient, seems to be solved by the new TomoEdge™ software. However, all these faster techniques lose part of standard TomoHD's OAR sparing capacity CONCLUSION: It is possible to treat oropharyngeal cancer patients using HT (TF/TEF) within time-frames observed for RA maintaining comparable target coverage and sparing of OARs. This study indicates that treatment time is not technology specific, rather an operator's decision on balancing efficiency and quality.
    Full-text · Article · Dec 2015 · Radiation Oncology
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    ABSTRACT: Hydrogen sulfide (H2S) is the last gaseous transmitter identified in mammals and previous studies have reported disparate conclusions regarding the implication of H2S in cancer progression. In the present study, we hypothesized that NaHS, a fast H2S-releasing donor, might interfere with the mitochondrial respiratory chain of tumor cells, increase tumor oxygenation and potentiate the response to irradiation. Using EPR oximetry, we found a rapid increase in tumor pO2 after NaHS administration (0.1 mmol/kg) in two human tumor models (breast MDA-MB-231 and cervix SiHa), an effect that was due to a decreased oxygen consumption and an increased tumor perfusion. Tumors irradiated 15 minutes after a single NaHS administration were more sensitive to irradiation compared to those that received irradiation alone (increase in growth delay by 50%). This radiosensitization was due to the oxygen-effect as the increased growth delay was abolished when temporarily clamped tumors were irradiated. In contrast, daily NaHS injection (0.1 mmol/kg/day for 14 days) did not provide any effect on tumor growth in vivo. To understand these paradoxical data, we analyzed the impact of external factors on the cellular response to NaHS. We found that extracellular pH had a dramatic effect on the cell response to NaHS as the proliferation rate (measured in vitro by BrdU incorporation) was increased at pH=7.4, but decreased at pH=6.5. Overall, our study highlights the complex role of environmental components on the response of cancer cells to H2S and suggests a new approach for the use of H2S donors in combination with radiation therapy.
    No preview · Article · Dec 2015 · Molecular Cancer Therapeutics
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    ABSTRACT: Leukemia cells are described as a prototype of glucose-consuming cells with a high turnover rate. The role of glutamine in fueling the tricarboxylic acid cycle of leukemia cells was however recently identified confirming its status of major anaplerotic precursor in solid tumors. Here we examined whether glutamine metabolism could represent a therapeutic target in leukemia cells and whether resistance to this strategy could arise. We found that glutamine deprivation inhibited leukemia cell growth but also led to a glucose-independent adaptation maintaining cell survival. A proteomic study revealed that glutamine withdrawal induced the upregulation of phosphoglycerate dehydrogenase (PHGDH) and phosphoserine aminotransferase (PSAT), two enzymes of the serine pathway. We further documented that both exogenous and endogenous serine were critical for leukemia cell growth and contributed to cell regrowth following glutamine deprivation. Increase in oxidative stress upon inhibition of glutamine metabolism was identified as the trigger of the upregulation of PHGDH. Finally, we showed that PHGDH silencing in vitro and the use of serine-free diet in vivo inhibited leukemia cell growth, an effect further increased when glutamine metabolism was blocked. In conclusion, this study identified serine as a key pro-survival actor that needs to be handled to sensitize leukemia cells to glutamine-targeting modalities.
    Full-text · Article · Dec 2015 · Oncotarget
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    Full-text · Dataset · Nov 2015
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    Full-text · Dataset · Nov 2015
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    Full-text · Technical Report · Nov 2015
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    ABSTRACT: The cholinic phenotype, characterized by elevated phosphocholine and a high production of total-choline (tCho)-containing metabolites, is a metabolic hallmark of cancer. It can be exploited for targeted therapy. Non-invasive imaging biomarkers are required to evaluate an individual's response to targeted anticancer agents that usually do not rapidly cause tumor shrinkage. Because metabolic changes can manifest at earlier stages of therapy than changes in tumor size, the aim of the current study was to evaluate (1) H-MRS and diffusion-weighted MRI (DW-MRI) as markers of tumor response to the modulation of the choline pathway in mammary tumor xenografts. Inhibition of choline kinase activity was achieved with the direct pharmacological inhibitor H-89, indirect inhibitor sorafenib and down-regulation of choline-kinase α (ChKA) expression using specific short-hairpin RNA (shRNA). While all three strategies significantly decreased tCho tumor content in vivo, only sorafenib and anti-ChKA shRNA significantly repressed tumor growth. The increase of apparent-diffusion-coefficient of water (ADCw) measured by DW-MRI, was predictive of the induced necrosis and inhibition of the tumor growth in sorafenib treated mice, while the absence of change in ADC values in H89 treated mice predicted the absence of effect in terms of tumor necrosis and tumor growth. In conclusion, (1) H-choline spectroscopy can be useful as a pharmacodynamic biomarker for choline targeted agents, while DW-MRI can be used as an early marker of effective tumor response to choline targeted therapies. DW-MRI combined to choline spectroscopy may provide a useful non-invasive marker for the early clinical assessment of tumor response to therapies targeting choline signaling. This article is protected by copyright. All rights reserved.
    No preview · Article · Nov 2015 · International Journal of Cancer
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    ABSTRACT: Early markers of treatment response may help in the management of patients by predicting the outcome of a specific therapeutic intervention. Here, we studied the potential value of diffusion-weighted MRI (DW-MRI) and 18F-fluorothymidine (18F-FLT), markers of cell death and cell proliferation respectively, to predict the response to irradiation. In addition, dose escalation and/or carbogen breathing were used to modulate the response to irradiation. The studies were performed on two hypoxic rat tumor models: rhabdomyosarcoma and 9L-glioma. The rats were imaged using MRI and PET before and two days after the treatment. In both tumor models, changes in ADC (apparent diffusion coefficient) and 18F-FLT SUV (standardized uptake value) were significantly correlated with the tumor growth delay. For both tumor models, the ADC values increased in all irradiated groups two days after the treatment while they decreased in the untreated groups. At the same time, the uptake of 18F-FLT increased in the untreated groups and decreased in all treated groups. Yet, ADC values were not sensitive enough to predict the added value of dose escalation or carbogen breathing in either model. Change in 18F-FLT uptake was able to predict the higher tumor response when using increased dose of irradiation, but not when using a carbogen breathing challenge. Our results also emphasize that the magnitude of change in 18F-FLT uptake was strongly dependent on the tumor model. Copyright © 2015 John Wiley & Sons, Ltd.
    No preview · Article · Oct 2015 · Contrast Media & Molecular Imaging
  • Vincent Grégoire · Jan A Langendijk · Sandra Nuyts
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    ABSTRACT: Over the last few decades, significant improvements have been made in the radiotherapy (RT) treatment of head and neck malignancies. The progressive introduction of intensity-modulated RT and the use of multimodality imaging for target volume and organs at risk delineation, together with the use of altered fractionation regimens and concomitant administration of chemotherapy or targeted agents, have accompanied efficacy improvements in RT. Altogether, such improvements have translated into improvement in locoregional control and overall survival probability, with a decrease in the long-term adverse effects of RT and an improvement in quality of life. Further progress in the treatment of head and neck malignancies may come from a better integration of molecular imaging to identify tumor subvolumes that may require additional radiation doses (ie, dose painting) and from treatment adaptation tracing changes in patient anatomy during treatment. Proton therapy generates even more exquisite dose distribution in some patients, thus potentially further improving patient outcomes. However, the clinical benefit of these approaches, although promising, for patients with head and neck cancer need to be demonstrated in prospective randomized studies. In this context, our article will review some of these advances, with special emphasis on target volume and organ-at-risk delineation, use of molecular imaging for tumor delineation, dose painting for dose escalation, dose adaptation throughout treatment, and potential benefit of proton therapy.
    No preview · Article · Sep 2015 · Journal of Clinical Oncology
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    ABSTRACT: AimsSlide digitalization has brought pathology to a new era, including powerful image analysis possibilities. However, while being a powerful prognostic tool, immunostaining automated analysis on digital images is still not worldwide implemented in routine clinical practice.Methods and ResultsDigitalized biopsy sections from two independent cohorts of patients, immunostained for membrane or nuclear markers, were quantified with two automated methods. The first one was based on stained cell counting through tissue segmentation while the second one relied on stained area proportion within tissue sections. Different steps of image preparation like automated tissue detection, folds exclusion, scanning magnification, were also assessed and validated. Quantification of either stained cells or stained area were found to be highly correlated for all tested markers. Both methods were also correlated to visual scoring performed by a pathologist. For an equivalent reliability, quantification of stained area is however faster and easier to fine-tune and is therefore more compatible with time constraints for prognosis.Conclusions This work provides an incentive for the implementation of automated immunostaining analysis with a stained area method in routine laboratory practice.This article is protected by copyright. All rights reserved.
    No preview · Article · Sep 2015 · Histopathology
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    ABSTRACT: The objective of this project was to define consensus guidelines for delineating organs at risk (OARs) for head and neck radiotherapy for routine daily practice and for research purposes. Consensus guidelines were formulated based on in-depth discussions of a panel of European, North American, Asian and Australian radiation oncologists. Twenty-five OARs in the head and neck region were defined with a concise description of their main anatomic boundaries. The Supplemental material provides an atlas of the consensus guidelines, projected on 1mm axial slices. The atlas can also be obtained in DICOM-RT format on request. Consensus guidelines for head and neck OAR delineation were defined, aiming to decrease interobserver variability among clinicians and radiotherapy centers. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.
    Full-text · Article · Aug 2015 · Radiotherapy and Oncology
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    ABSTRACT: To develop a methodology for using FDG PET/CT in adaptive dose painting by numbers (DPBN) in head and neck squamous cell carcinoma (HNSCC) patients. Issues related to noise in PET and treatment robustness against geometric errors are addressed. Five patients with locally advanced HNSCC scheduled for chemo-radiotherapy were imaged with FDG-PET/CT at baseline and 2-3 times during radiotherapy (RT). The GTVPET was segmented with a gradient-based method. A double median filter reduces the impact of noise in the PET uptake-to-dose conversion. Filtered FDG uptake values were linearly converted into a voxel-by-voxel prescription from 70 (median uptake) to 86 Gy (highest uptake). A PTVPET was obtained by applying a dilation of 2.5 mm to the entire prescription. Seven iso-uptake thresholds led to seven sub-levels compatible with the Tomotherapy HiArt(®) Treatment Planning System. Planning aimed to deliver a median dose of 56 Gy and 70 Gy in 35 fractions on the elective and therapeutic PTVs, respectively. Plan quality was assessed with quality volume histogram (QVH). At each time point, plans were generated with a total of 3-4 plans for each patient. Deformable image registration was used for automatic contour propagation and dose summation of the 3 or 4 treatment plans (MIMvista(®)). GTVPET segmentations were performed successfully until week 2 of RT but failed in two patients at week 3. QVH analysis showed high conformity for all plans (mean VQ = 0.95 93%; mean VQ = 1.05 3.9%; mean QF 2.2%). Good OAR sparing was achieved while keeping high plan quality. Our results show that adaptive FDG-PET-based escalated dose painting in patients with locally advanced HNSCC is feasible while respecting strict dose constraints to organs at risk. Clinical studies must be conducted to evaluate toxicities and tumor response of such a strategy.
    Full-text · Article · Jun 2015 · Acta oncologica (Stockholm, Sweden)
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    ABSTRACT: The use of FDG-PET for target volume delineation has been validated by our group for patients with locally advanced head and neck squamous cell carcinoma (HNSCC) treated by concomitant chemo-radiotherapy providing a strict methodology for image acquisition and segmentation. The aims of this study were (1) to confirm these results in a multicentric setting, and (2) to evaluate the clinical outcome in a prospective series of patients treated with FDG-PET scan-based radiotherapy planning. Forty-one patients with stage III or IV HNSCC were included in this prospective multicentric study from 2007 to 2009. Before treatment, each patient underwent head and neck endoscopy, contrast enhanced CT or MRI and FDG PET scan. Patients were treated with invert or forward planning IMRT (using dose-volume constraints on PTVs and OARs). Primary tumor GTVPET were automatically delineated using a gradient based method and were registered on the planning CT. A prophylactic (50Gy) and a therapeutic (70Gy) primary tumor CTVPET were contoured using GTVPET volume along with data provided by endoscopy and pre-treatment imaging. Nodal CTV were delineated on the planning CT using internationally accepted guidelines. PTV was created by adding a security margin of 4-5mm around CTVPET (PTVPET). At the end of the inclusion period after a minimal follow-up of 2years, target volumes (GTVCT, CTVCT, PTVCT) for the primary tumors were re-delineated on the planning CT-scan using anatomic imaging only to perform a volumetric and a dosimetric comparison. Mean age of the population was 59years. Oropharynx was the most common tumor location (68%), followed by oral cavity (17%), larynx (7%) and hypopharynx (7%). GTVPET contours were significantly smaller than GTVCT contours in all cases but one (average volume 28.8ml vs 40.4ml, p<0.0001). The prophylactic primary tumor target volumes (CTV 50Gy and PTV 50Gy) based on PET scan were significantly smaller (p<0.0001) in oropharynx cases. The boost target volumes (CTV 70Gy and PTV 70Gy) contoured on PET scan were also significantly smaller than the ones contoured on CT scan in all cases (p<0.0001). The dosimetry comparison showed a significant decrease in parotid and oral cavity mean dose from the PET-based plans. After completion of chemo-radiotherapy, 5 patients had selective node dissection for suspicious lymph nodes on MRI and/or PET scan; only one had a positive pathological node. At a median follow-up of 3years, the relapse-free and overall survival rates were respectively 32% and 43%. No marginal recurrence (in the CTVCT but outside the CTVPET) was observed. This study confirms that the use of (18)FDG-PET translated into smaller GTV, CTV and PTV for the primary tumor volumes in comparison with the use of CT. PET planning also demonstrated an improvement on dosimetry by lowering dose to certain organs at risk. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    Full-text · Article · Jun 2015 · Radiotherapy and Oncology
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    ABSTRACT: We investigated the impact of oxygenation status (measured by EPR oximetry) on the uptake of (18)F-FDG (measured by PET) in two different tumor models during a carbogen breathing challenge. We observed a significant drop in (18)F-FDG uptake under carbogen breathing that suggests a rapid metabolic adaptation to the oxygen environment. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    No preview · Article · May 2015 · Radiotherapy and Oncology
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    ABSTRACT: This document describes best practice and evidence based recommendations for the use of FDG-PET/CT for the purposes of radiotherapy target volume delineation (TVD) for curative intent treatment of non-small cell lung cancer (NSCLC). These recommendations have been written by an expert advisory group, convened by the International Atomic Energy Agency (IAEA) to facilitate a Coordinated Research Project (CRP) aiming to improve the applications of PET based radiation treatment planning (RTP) in low and middle income countries. These guidelines can be applied in routine clinical practice of radiotherapy TVD, for NSCLC patients treated with concurrent chemoradiation or radiotherapy alone, where FDG is used, and where a calibrated PET camera system equipped for RTP patient positioning is available. Recommendations are provided for PET and CT image visualization and interpretation, and for tumor delineation using planning CT with and without breathing motion compensation. Copyright © 2015. Published by Elsevier Ireland Ltd.
    Full-text · Article · Apr 2015 · Radiotherapy and Oncology
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    S. Differding · E. Sterpin · J.A. Lee · V. Grégoire

    Preview · Article · Apr 2015
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    ABSTRACT: We report on a retrospective analysis of 147 patients with early and locoregionally advanced squamous cell head and neck cancer (SCCHN) treated with helical tomotherapy (HT). Included were patients with SCCHN of the oral cavity (OC), oropharynx (OP), hypopharynx (HP), or larynx (L) consecutively treated in one radiotherapy center in 2008 and 2009. The prescribed HT dose was 60-66 Gy in the postoperative setting (group A) and 66-70 Gy when given as primary treatment (group B). HT was given alone, concurrent with systemic therapy (ST), that is, chemotherapy, biotherapy, or both, and with or without induction therapy (IT). Acute and late toxicities are reported using standard criteria; locoregional failure/progression (LRF), distant metastases (DM), and second primary tumors (SPT) were documented, and event-free survival (EFS) and overall survival (OS) were calculated from the start of HT. Group A patients received HT alone in 22 cases and HT + ST in 20 cases; group B patients received HT alone in 17 cases and HT + ST in 88 cases. Severe (grade ≥ 3) acute mucosal toxicity and swallowing problems increased with more additional ST. After a median follow-up of 44 months, grade ≥2 late toxicity after HT + ST was approximately twice that of HT alone for skin, subcutis, pharynx, and larynx. Forty percent had grade ≥2 late xerostomia, and 29% had mucosal toxicity. At 3 years, LRF/DM/SPT occurred in 7%/7%/17% and 25%/13%/5% in groups A and B, respectively, leading to a 3-year EFS/OS of 64%/74% and 56%/63% in groups A and B, respectively. The use of HT alone or in combination with ST is feasible and promising and has a low late fatality rate. However, late toxicity is nearly twice as high when ST is added to HT. ©AlphaMed Press.
    Full-text · Article · Feb 2015 · The Oncologist
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    ABSTRACT: Purpose: To assess the predictive value of hypoxia imaging by (18)F-FAZA PET in identifying tumors that may benefit from radiotherapy combined with nimorazole, a hypoxic radiosensitizer. Material and methods: Rats of two tumor models (Rhabdomyosarcoma and 9L-glioma) were divided into two treated groups: radiotherapy (RT) alone or RT plus nimorazole. (18)F-FAZA PET images were obtained to evaluate tumor hypoxia before the treatment. Treatment outcome was assessed through the tumor growth time assay, defined as the time required for tumor to grow to 1.5 times its size before irradiation. Results: For rhabdomyosarcomas, the benefit of adding nimorazole to RT was not significant when considering all tumors. When stratifying into more and less hypoxic tumors according to the median (18)F-FAZA T/B ratio, we found that the combined treatment significantly improved the response of the "more hypoxic" subgroup, while there was no significant difference in the tumor growth time between the two treatment modalities for the "less hypoxic" subgroup. For 9L-gliomas, a clear benefit was demonstrated for the group receiving RT+nimorazole. However, the individual responses within the RT+nimorazole group were highly variable and independent of the (18)F-FAZA uptake. Conclusions: (18)F-FAZA PET may be useful to guide hypoxia-directed RT using nimorazole as radiosensitizer. It identified a subgroup of more hypoxic tumors (displaying T/B ratio>2.72) that would benefit from this combined treatment. Nevertheless, the predictive power was limited to rhabdomyosarcomas and ineffective for 9L-gliomas.
    Full-text · Article · Jan 2015 · Radiotherapy and Oncology
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    Full-text · Dataset · Jan 2015

Publication Stats

8k Citations
1,216.32 Total Impact Points

Institutions

  • 2011-2015
    • The Catholic University of America
      Washington, Washington, D.C., United States
    • Hospital Clínic de Barcelona
      Barcino, Catalonia, Spain
    • University of Wisconsin–Madison
      • Department of Human Oncology
      Madison, Wisconsin, United States
    • Maastricht Universitair Medisch Centrum
      Maestricht, Limburg, Netherlands
  • 1999-2015
    • University Hospital Brussels
      Bruxelles, Brussels Capital, Belgium
  • 1989-2015
    • Catholic University of Louvain
      • Institute of Experimental and Clinical Research (IREC)
      Лувен-ла-Нев, Walloon, Belgium
  • 1989-2013
    • Cliniques Universitaires Saint-Luc
      • • Division of Radiation Oncology
      • • Division of Nuclear Medicine
      • • Division of Medical Oncology
      Bruxelles, Brussels Capital Region, Belgium
  • 2009
    • Queen Elizabeth Hospital
      Hong Kong, Hong Kong
  • 2008
    • Clinique Saint-Luc, Bouge
      Namen, Walloon Region, Belgium
  • 2007
    • Universität Heidelberg
      Heidelburg, Baden-Württemberg, Germany
    • Molecular Imaging Inc
      Ann Arbor, Michigan, United States
  • 2004
    • Erasmus MC
      • Daniel den Hoed Centre
      Rotterdam, South Holland, Netherlands
    • Centre Georges-François Leclerc
      Dijon, Bourgogne, France
  • 1995
    • University of Houston
      Houston, Texas, United States
  • 1993-1995
    • University of Texas MD Anderson Cancer Center
      • Department of Clinical Investigations
      Houston, Texas, United States