Jean Bourhis

University Hospital of Lausanne, Lausanne, Vaud, Switzerland

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Publications (216)1446.09 Total impact

  • [Show abstract] [Hide abstract]
    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.
    Radiotherapy and Oncology 08/2015; DOI:10.1016/j.radonc.2015.07.041 · 4.86 Impact Factor
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    ABSTRACT: Background and purpose The dose effect-effect relationship for cardiac diseases following radiotherapy suffers from uncertainties. Three dimensional coronary artery (CA) dose calculation after mediastinal Hodgkin lymphoma radiotherapy was performed, using the patient’s coronary CT angiography (CCTA), and the relationship between the coronary arteries’ radiation doses and the risk of stenosis was estimated. Materials and methods Radiotherapy simulation CT scans and CCTAs of patients treated for a mediastinal Hodgkin lymphoma were used to merge thoracic and detailed cardiovascular anatomies. Radiation treatment parameters were used to estimate CA radiation doses. Twenty-one patients without coronary stenosis (controls) were matched with twelve patients with stenosis (cases). CA segments were considered as sub-volumes of interest. Radiation doses to stenotic segments were compared with those received by normal segments (from cases and controls) using a logistic regression. Results In eleven cases out of twelve, the highest of the coronary dose distribution was on a damaged segment. Logistic regression with CA segments yielded an odds ratio associated with the risk of coronary stenosis of 1.049 per additional gray with the CA segment median dose (95% confidence interval, 1.004–1.095; p-value <0.05). Conclusion The CA segment dose significantly increased the risk of stenosis on the segment. Such personalized CA dose calculations on larger cohorts are expected to improve the understanding of the cardiovascular radiation dose–effect relationship.
    Radiotherapy and Oncology 08/2015; DOI:10.1016/j.radonc.2015.07.043 · 4.86 Impact Factor
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    ABSTRACT: Second mitochondria-derived activator of caspase (SMAC)-mimetics are a new class of targeted drugs that specifically induce apoptotic cancer cell death and block pro-survival signaling by antagonizing selected members of the inhibitor of apoptosis protein (IAP) family. The present study was designed to investigate the radiosensitizing effect and optimal sequence of administration of the novel SMAC-mimetic Debio 1143 in vitro and in vivo. Apoptosis, alteration of DNA damage repair (DDR), and tumor necrosis factor-alpha (TNF-α) signaling were examined. In vitro, Debio 1143 displayed anti-proliferative activity and enhanced intrinsic radiation sensitivity in 5/6 head and neck squamous cell carcinoma (HNSCC) cell lines in a synergistic manner. In vivo, Debio 1143 dose-dependently radio-sensitized FaDu and SQ20B xenografts, resulting in complete tumor regression in 8/10 FaDu-xenografted mice at the high dose level. At the molecular level, Debio 1143 combined with radiotherapy (RT) induced enhancement of caspase-3 activity, increase in Annexin V-positive cells and karyopyknosis, and increase in TNF-α mRNA levels. Finally, in a neutralization experiment using a TNF-α-blocking antibody and a caspase inhibitor, it was shown that the radiosensitizing effect of Debio 1143 is mediated by caspases and TNF-α. These results demonstrate that the novel SMAC-mimetic Debio 1143 is a radiosensitizing agent that is worthy of further investigation in clinical trials in combination with radiotherapy. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    Radiotherapy and Oncology 06/2015; DOI:10.1016/j.radonc.2015.05.017 · 4.86 Impact Factor
  • 12-th International Stereotactic Radiosurgery Society Congress (ISRS), June 2015, Yokohama, Japan ; Journal of Radiosurgery and SBRT, Volume 3, Supllement 1, page 42, Yokohama, Japan; 06/2015
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    ABSTRACT: A previous individual patient data meta-analysis by the Meta-Analysis of Chemotherapy in Nasopharynx Carcinoma (MAC-NPC) collaborative group to assess the addition of chemotherapy to radiotherapy showed that it improves overall survival in nasopharyngeal carcinoma. This benefit was restricted to patients receiving concomitant chemotherapy and radiotherapy. The aim of this study was to update the meta-analysis, include recent trials, and to analyse separately the benefit of concomitant plus adjuvant chemotherapy.
    The Lancet Oncology 05/2015; 16(6). DOI:10.1016/S1470-2045(15)70126-9 · 24.73 Impact Factor
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    ABSTRACT: The standard treatment of anal canal cancer (ACC) is combined chemotherapy and radiation therapy (RT), which is complex because of the shape of the target volumes and the need to minimize the irradiation of normal pelvic structures. In this study we compared the dosimetric results of helical tomotherapy (HT) plans with traditional 3D conformal RT (3DRT) plans for the treatment of ACC. Twelve patients (median age 57 years, range 38-83; F/M 8/4) treated with HT and concurrent chemotherapy for locally advanced ACC were selected. All had histologically confirmed squamous-cell carcinoma. A clinical target volume including the tumor and pelvic and inguinal lymph nodes was treated with HT to a total dose of 36 Gy in 1.8-Gy daily fractions. Then a sequential boost of 23.4 Gy in 1.8-Gy daily fractions (total dose 59.4 Gy) was delivered to the tumor and involved nodes. For all 12 patients, 3DRT plans were generated for comparison. Treatment plans were evaluated by means of standard dose-volume histograms. Dose coverage of the planning target volumes (PTVs), homogeneity index (HI), and mean doses to organs at risk (OARs) were compared. The coverage of PTV was comparable between the two treatment plans. HI was better in the HT vs. 3DRT plans (1.25 and 3.57, respectively; p<0.0001). HT plans resulted in better sparing of OARs (p<0.0001). HT showed superior target dose conformality and significant sparing of pelvic structures compared with 3DRT. Further investigation should determine if these dosimetric improvements will improve clinical outcomes regarding locoregional control, survival, and treatment-related acute and late morbidity.
    04/2015; DOI:10.5301/tj.5000269
  • Pelagia G Tsoutsou · Jean Bourhis · George Coukos
    Journal of Clinical Oncology 03/2015; 33(11). DOI:10.1200/JCO.2014.59.2808 · 18.43 Impact Factor
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    ABSTRACT: Objectives: This study investigated the effectiveness of stereotactic body radiotherapy with helical tomotherapy (T-SBRT) for treating medically inoperable primary and second-primary (SPLN) early stage non-small cell lung neoplasm and evaluated whether the movement of organising pneumonia (OP) within the irradiation field (IF) can be detected via analysis of radiological changes. Methods: Patients (n = 16) treated for 1 year (2011-2012) at our hospital by T-SBRT at a total dose of 60 Gy in five fractions were examined retrospectively. Outcome and toxicity were recorded, and were separately described for SPLN. Computed tomography scans were reviewed by a single radiologist. Results: Of 16 the patients, five (31.3%) had primary lung malignancies, 10 (62.5%) had SPLN, and one case (6.2%) had isolated mediastinal metastasis of lung neoplasm. Pathological evidence was obtained for 72.2% of all lesions. The median radiological follow-up was 11.0 months (10.5 for SPLN). For all cases, the 6- and 12-month survival rates were 100% and 77.7% (100% and 71.4%, respectively, for SPLN), and the 6- and 12-month loco-regional control rates were 100% in all cases. Two (12.5%) of 16 patients developed grade 3 late transient radiation pneumonitis following steroid therapy and one (6.2%) presented asymptomatic infiltrates comparable to OP opacities. Conclusions: T-SBRT seems to be safe and effective. Advances in knowledge: Mild OP is likely associated with radiation-induced anomalies in the IF, identification of migrating opacities can help discern relapse of radiation-induced opacities.
    British Journal of Radiology 03/2015; 88(1049):20140687. DOI:10.1259/bjr.20140687 · 2.02 Impact Factor
  • Mahmut Ozsahin · Jean Bourhis
    Cancer 11/2014; 121(7). DOI:10.1002/cncr.29152 · 4.90 Impact Factor
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    ABSTRACT: To quantify the relationship between bone marrow (BM) response to radiation and radiation dose by using (18)F-labeled fluorodeoxyglucose positron emission tomography [(18)F]FDG-PET standard uptake values (SUV) and to correlate these findings with hematological toxicity (HT) in cervical cancer (CC) patients treated with chemoradiation therapy (CRT). Seventeen women with a diagnosis of CC were treated with standard doses of CRT. All patients underwent pre- and post-therapy [(18)F]FDG-PET/computed tomography (CT). Hemograms were obtained before and during treatment and 3 months after treatment and at last follow-up. Pelvic bone was autosegmented as total bone marrow (BMTOT). Active bone marrow (BMACT) was contoured based on SUV greater than the mean SUV of BMTOT. The volumes (V) of each region receiving 10, 20, 30, and 40 Gy (V10, V20, V30, and V40, respectively) were calculated. Metabolic volume histograms and voxel SUV map response graphs were created. Relative changes in SUV before and after therapy were calculated by separating SUV voxels into radiation therapy dose ranges of 5 Gy. The relationships among SUV decrease, radiation dose, and HT were investigated using multiple regression models. Mean relative pre-post-therapy SUV reductions in BMTOT and BMACT were 27% and 38%, respectively. BMACT volume was significantly reduced after treatment (from 651.5 to 231.6 cm(3), respectively; P<.0001). BMACT V30 was significantly correlated with a reduction in BMACT SUV (R(2), 0.14; P<.001). The reduction in BMACT SUV significantly correlated with reduction in white blood cells (WBCs) at 3 months post-treatment (R(2), 0.27; P=.04) and at last follow-up (R(2), 0.25; P=.04). Different dosimetric parameters of BMTOT and BMACT correlated with long-term hematological outcome. The volumes of BMTOT and BMACT that are exposed to even relatively low doses of radiation are associated with a decrease in WBC counts following CRT. The loss in proliferative BM SUV uptake translates into low WBC nadirs after treatment. These results suggest the potential of intensity modulated radiation therapy to spare BMTOT to reduce long-term hematological toxicity. Copyright © 2014 Elsevier Inc. All rights reserved.
    International journal of radiation oncology, biology, physics 10/2014; 90(5):1099-1107. DOI:10.1016/j.ijrobp.2014.08.017 · 4.18 Impact Factor
  • Acta Oncologica 10/2014; DOI:10.3109/0284186X.2014.962664 · 3.71 Impact Factor
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    ABSTRACT: Purpose To report the application of the Global Risk Analysis (GRA), an innovative proactive risk analysis method, to a radiotherapy department. Material and methods Analyses were conducted by a multidisciplinary working group with the support of a quality engineer. First, a mapping of hazardous situations was developed. For this, a double entry table was filled in, crossing the process of patient care divided into steps with a comprehensive list of pre-established hazards. The cells of the table represented interactions, which were, when relevant, considered as dangerous situations and then sorted by level of priority. For each high priority dangerous situation, scenarios were developed. Their criticality was assessed, using likelihood and severity scales, and a criticality matrix was used to allocate them into categories: acceptable (C1), tolerable (C2) and unacceptable (C3). Corrective actions were planned when relevant. Afterward, the criticality of the scenarios was reevaluated, leading to a residual risk mapping. Results The number of high priority dangerous situations to analyze was 78, for which 205 scenarios were generated: 95 C1, 98 C2, and 12 C3 scenarios. Twenty-two corrective actions were planned. Mapping of residual risk resulted in the disappearance of C3 risks, leaving 18 C2 scenarios, for which six monitoring indicators were implemented. Conclusion The implementation of the GRA appeared feasible and led to the implementation of 22 corrective actions based on scenarios, without the occurrence of any incidents.
    Radiotherapy and Oncology 09/2014; 112(2). DOI:10.1016/j.radonc.2014.08.037 · 4.86 Impact Factor
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    ABSTRACT: To assess the use of radiotherapy (RT) or concurrent chemoradiotherapy (CRT) following taxane-based induction chemotherapy (T-ICT) in locally advanced head and neck squamous cell carcinoma (LAHNSCC) and to evaluate the tolerability of CRT after T-ICT. From 01/2006 to 08/2012, 173 LAHNSCC patients treated as a curative intent by T-ICT, followed by definitive RT/CRT were included in this analysis. There was an 86% objective response (OR) after ICT among 154 evaluable patients. Forty-four patients received less than three cycles (25%) and 20 received only one cycle of T-ICT. The 3-year actuarial overall survival (OS) was 49% and there was no OS difference according to the type of ICT (regimen or number of cycle) or the addition of concurrent CT (cisplatin, carboplatin, or cetuximab) to RT. In multivariate analysis (MVA), clinically involved lymph node (cN+), age more than 60 years, the absence of OR after ICT, and performance status of at least 1 predicted for a decreased OS, with hazard ratios (HR) of 2.8, 2.2, 2.1, and 2, respectively. The 3-year actuarial locoregional control (LRC) and distant control (DC) rates were 52 and 73%, respectively. In MVA, the absence of OR after ICT (HR: 3.2), cN+ (HR: 3), and age more than 60 years (HR: 1.7) were prognostic for a lower LRC whereas cN+ (HR: 4.2) and carboplatin-based T-ICT (HR: 2.9) were prognostic for a lower DC. The number of cycles (≤2) received during ICT was borderline significant for DC in the MVA (P=0.08). Among patients receiving less than or equal to three cycles of ICT, higher outcomes were observed in patients who received cisplatin-based T-ICT (vs. carboplatin-based T-ICT) or subsequent CRT (vs. RT). T-ICT in our experience, followed by RT or CRT, raises several questions on the role and type of induction, and the efficacy of CRT over RT. The role of RT or CRT following induction, although feasible in these advanced patients, awaits answers from randomized trials.
    Anti-Cancer Drugs 08/2014; 25(10). DOI:10.1097/CAD.0000000000000161 · 1.89 Impact Factor
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    ABSTRACT: In vitro studies suggested that sub-millisecond pulses of radiation elicit less genomic instability than continuous, protracted irradiation at the same total dose. To determine the potential of ultrahigh dose-rate irradiation in radiotherapy, we investigated lung fibrogenesis in C57BL/6J mice exposed either to short pulses (≤500 ms) of radiation delivered at ultrahigh dose rate (≥40 Gy/s, FLASH) or to conventional dose-rate irradiation (≤0.03 Gy/s, CONV) in single doses. The growth of human HBCx-12A and HEp-2 tumor xenografts in nude mice and syngeneic TC-1 Luc(+) orthotopic lung tumors in C57BL/6J mice was monitored under similar radiation conditions. CONV (15 Gy) triggered lung fibrosis associated with activation of the TGF-β (transforming growth factor-β) cascade, whereas no complications developed after doses of FLASH below 20 Gy for more than 36 weeks after irradiation. FLASH irradiation also spared normal smooth muscle and epithelial cells from acute radiation-induced apoptosis, which could be reinduced by administration of systemic TNF-α (tumor necrosis factor-α) before irradiation. In contrast, FLASH was as efficient as CONV in the repression of tumor growth. Together, these results suggest that FLASH radiotherapy might allow complete eradication of lung tumors and reduce the occurrence and severity of early and late complications affecting normal tissue.
    Science translational medicine 07/2014; 6(245):245ra93. DOI:10.1126/scitranslmed.3008973 · 14.41 Impact Factor
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    ABSTRACT: Cancer of the nasopharynx is an uncommon malignancy in France (incidence = 0.5/year/100,000 men) but is endemic in areas like in South-East Asia. Exclusive radiation therapy used to be the standard and results in local control rates for T3-T4 tumors around 50-75 %. Intensity-modulated radiotherapy (IMRT) improves tumor coverage with a sparing of organs at risk and has to be privileged. Concurrent chemotherapy with IMRT achieved significant survival benefice with 5-year overall survival above 75 %. Concurrent radiochemotherapy with platinium is the most frequent scheme but induction and adjuvant chemotherapies are discussed to reduce distant failure: studies are currently ongoing. Follow-up aims to detect early local failures with a chance of cure and to manage long-term toxicities.
    Bulletin du cancer 05/2014; 101(5):445-454. DOI:10.1684/bdc.2014.1964 · 0.64 Impact Factor
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    ABSTRACT: Squamous cell carcinomas of larynx and hypopharynx can be treated by surgery and/or radiotherapy according to tumor size. For small tumors, the results are similar. For locally advanced tumors, the surgical approach is mutilating and requires a total (pharyngo)laryngectomy. Exclusive chemoradiotherapy has shown its interest at the cost of late sequelae. In order to reduce these effects and mutilation, induction chemotherapy with cisplatin, docetaxel and 5FU for organ preservation becomes the standard treatment but there are no solid studies comparing this approach with the exclusive chemoradiotherapy. And it is not possible to conclude as to the superiority of a scheme in terms of overall survival. When chemotherapy is chosen, the modalities of any potentiation of radiation have not been yet established.
    Bulletin du cancer 05/2014; 101(5):438-444. DOI:10.1684/bdc.2014.1945 · 0.64 Impact Factor
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    ABSTRACT: The aim of radiotherapy is to deliver enough radiation to the tumor in order to achieve maximum tumour control in the irradiated volume with as few serious complications as possible with an irradiation dose as low as possible to normal tissue. The quality of radiotherapy is essential for optimal treatment and quality control is to reduce the bias in clinical trials avoiding possible major deviations. The assurance and quality control programs have been developed in large european (EORTC, GORTEC) and american cooperative groups (RTOG) of radiation oncology since the 1980s. We insist here on the importance of quality assurance in radiotherapy and the current status in this domain and the criteria for quality control especially for current clinical trials within GORTEC are discussed here.
    Bulletin du cancer 05/2014; 101(5):481-485. DOI:10.1684/bdc.2014.1924 · 0.64 Impact Factor
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    ABSTRACT: The goal of the present work was to compare outcomes of definitive concurrent cisplatin-based chemoradiotherapy (CRT) with cetuximab-based bioradiotherapy (BRT) in locally advanced head-and-neck squamous cell carcinoma (HNSCC). Between 2006 and 2012, 265 patients with locally advanced HNSCC were treated at our institution with CRT (n = 194; 73 %) with three cycles of cisplatin (100 mg/m(2), every 3 weeks) or BRT (n = 71; 27 %) with weekly cetuximab. Patients receiving BRT had more pre-existing conditions (Charlson index ≥ 2) than the CRT group (p = 0.005). Median follow-up was 29 months. In all, 56 % of patients treated with CRT received the planned three cycles (92 % at least two cycles) and 79 % patients treated with BRT received six cycles or more. The 2-year actuarial overall survival (OS) and progression-free survival (PFS) were 72 % and 61 %, respectively. In the multivariate analysis (MVA), T4 stage, N2-3 stage, smoking status (current smoker as compared with never smoker), and non-oropharyngeal locations predicted for OS, whereas BRT association with OS was of borderline significance (p = 0.054). The 2-year actuarial locoregional control (LRC) and distant control (DC) rates were 73 and 79 %, respectively. CRT was independently associated with an improved LRC (2-year LRC: 76 % for CRT vs. 61 % for BRT) and DC (2-year LRC: 81 % for CRT vs. 68 % for BRT) in comparison with BRT (p < 0.001 and p = 0.01 in the MVA). Subgroup analyses showed that T4 patients benefited significantly from CRT (vs. BRT) in LRC, while T1-3 did not. BRT patients had more G3-4 skin complications (p < 0.001) and CRT patients had higher rates of feeding tube placement (p = 0.006) and G3-4 gastrointestinal toxicities (p < 0.001). This retrospective analysis showed a better LRC in locally advanced HNSCC treated by cisplatin-based CRT than cetuximab-based BRT, and a nonsignificant trend towards an improved OS.
    Strahlentherapie und Onkologie 03/2014; 190(9). DOI:10.1007/s00066-014-0626-0 · 2.73 Impact Factor
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    ABSTRACT: We retrospectively reviewed the long-term outcome and late side effects of endometrial cancer (EC) patients treated with different techniques of postoperative radiotherapy (PORT). Between 1999 and 2012, 237 patients with EC were treated with PORT. Two-dimensional external beam radiotherapy (2D-EBRT) was used in 69 patients (30 %), three-dimensional EBRT (3D-EBRT) in 51 (21 %), and intensity-modulated RT (IMRT) with helical Tomotherapy in 47 (20 %). All patients received a vaginal brachytherapy (VB) boost. Seventy patients (29 %) received VB alone. After a median of 68 months (range, 6-154) of follow-up, overall survival was 75 % [95 % confidence interval (CI), 69-81], disease-free survival was 72 % (95% CI, 66-78), cancer-specific survival was 85 % (95 % CI, 80-89), and locoregional control was 86 % (95 % CI, 81-91). The 5-year estimates of grade 3 or more toxicity and second cancer rates were 0 and 7 % (95 % CI, 1-13) for VB alone, 6 % (95 % CI, 1-11) and 0 % for IMRT + VB, 9 % (95 % CI, 1-17) and 5 % (95 % CI, 1-9) for 3D-EBRT + VB, and 22 % (95 % CI, 12-32) and 12 % (95 % CI, 4-20) for 2D-EBRT + VB (P = 0.002 and P = 0.01), respectively. Pelvic EBRT should be tailored to patients with high-risk EC because the severe late toxicity observed might outweigh the benefits. When EBRT is prescribed for EC, IMRT should be considered, because it was associated with a significant reduction of severe late side effects.
    Annals of Surgical Oncology 03/2014; 21(7). DOI:10.1245/s10434-014-3622-9 · 3.94 Impact Factor
  • Journal of Clinical Oncology 12/2013; 32(3). DOI:10.1200/JCO.2013.53.5997 · 18.43 Impact Factor

Publication Stats

8k Citations
1,446.09 Total Impact Points

Institutions

  • 2014–2015
    • University Hospital of Lausanne
      Lausanne, Vaud, Switzerland
    • Groupe Oncologie Radiothérapie Tête et Cou, GORTEC
      Lutetia Parisorum, Île-de-France, France
    • University of Lausanne
      • Centre hospitalier universitaire vaudois (CHUV)
      Lausanne, Vaud, Switzerland
  • 1995–2014
    • Institut de Cancérologie Gustave Roussy
      • Department of Radiotherapy
      Île-de-France, France
    • Centre Hospitalier Universitaire de Dijon
      Dijon, Bourgogne, France
  • 2009–2012
    • Université Paris-Sud 11
      Orsay, Île-de-France, France
  • 2011
    • Centre Henri Becquerel
      Rouen, Haute-Normandie, France
  • 2003–2009
    • Institut de Radioprotection et de Sûreté Nucléaire (IRSN)
      Fontenay, Île-de-France, France
    • Centre Jean Perrin
      Clermont, Auvergne, France
  • 2008
    • Άγιος Σάββας Αντικαρκινικό Νοσοκομείο
      Athínai, Attica, Greece
  • 2006
    • Eawag: Das Wasserforschungs-Institut des ETH-Bereichs
      Duebendorf, Zurich, Switzerland
  • 2005
    • Université Paris 13 Nord
      Île-de-France, France
    • The University of Manchester
      Manchester, England, United Kingdom
  • 1992–1994
    • Memorial Sloan-Kettering Cancer Center
      • • Department of Pediatrics
      • • Bone Marrow Transplant Service
      New York City, NY, United States
  • 1989
    • French National Centre for Scientific Research
      Lutetia Parisorum, Île-de-France, France