Henri Roché

Institut Universitaire de France, Lutetia Parisorum, Île-de-France, France

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Publications (83)574.18 Total impact

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    ABSTRACT: We report four patients developing a late form of papulopustular rash induced by epidermal growth factor receptor inhibitors. These patients presented an unusual presentation of acneiform rash, characterized by late development (several months after treatment commenced), localization to the limbs with sparing of the face, and association with severe pruritus and Staphylococcus aureus superinfection in all cases. These clinical symptoms may suggest a distinct mechanism from the early acne-like rash frequently observed with these targeted anticancer therapies. Clinicians should be aware of this delayed adverse event, and we suggest the term 'late acneiform toxicity of EGFR inhibitors (LATE) syndrome' to permit better characterization of this clinical picture. © 2015 British Association of Dermatologists.
    Clinical and Experimental Dermatology 05/2015; DOI:10.1111/ced.12675 · 1.23 Impact Factor
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    ABSTRACT: Inflammatory breast cancer (IBC) is a rare and aggressive disease requiring a multimodal treatment. We evaluated the benefit of adding docetaxel-5 fluorouracil (D-5FU) regimen after pre-operative dose-intense epirubicin-cyclophosphamide (EC) and loco-regional treatment in IBC patients PATIENTS AND METHODS: PEGASE 07 was a national randomized phase 3 open-label study involving 14 hospitals in France. Women with non-metastatic IBC were eligible and randomly assigned to receive either 4 cycles of dose-intense EC (E150 mg/m² and C 4000 mg/m² every 3 weeks with repeated hematopoietic stem cell support), then mastectomy with axillary lymph node dissection, and radiotherapy (Arm A) or the same treatment followed by 4 cycles of D-5FU (D 85 mg/m², day 1 and 5FU 750 mg/m²/day continuous infusion, days 1-5 every 3 weeks) administered post-radiotherapy (Arm B). Patients with hormone receptor positive tumors received hormonal therapy. Disease-free survival (DFS) was the primary endpoint. Secondary endpoints included tolerance, pathological complete response (pCR) rate, and overall survival (OS). Between January 2001 and May 2005, 174 patients were enrolled and treated (87 in each arm). Median follow-up was similar in both arms: 59.6 months (95%CI: 58.4-60.3) in arm A and 60·5 months (95%CI: 58.3-61.4) in arm B. The estimated 5-year DFS rates were not different: 55% (95%CI: 43.9-64.7) in arm A and 55·5% (95%CI: 44.3-65.3) in arm B (hazard ratio, HR =0.94 [0.61-1.48]; p=0.81). Identical results were observed for 5-year OS: 70.2% (95%CI: 59.1-78.8) in arm A and 70% (95%CI: 58.8-78.7) in arm B (HR= 0.93 [0.55-1.60]; p=0.814). Following dose-intense EC induction, in-breast and global (breast plus nodes) pCR were 28.9% and 20.1%, respectively. Estrogen receptor and pCR status were independently associated with survival. The addition of D-5FU after pre-operative dose-intense EC and standard local therapy did not improve DFS in IBC. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.
    Annals of Oncology 05/2015; DOI:10.1093/annonc/mdv216 · 6.58 Impact Factor
  • Cancer Research 05/2015; 75(9 Supplement):P6-16-07-P6-16-07. DOI:10.1158/1538-7445.SABCS14-P6-16-07 · 9.28 Impact Factor
  • Cancer Research 05/2015; 75(9 Supplement):OT1-1-12-OT1-1-12. DOI:10.1158/1538-7445.SABCS14-OT1-1-12 · 9.28 Impact Factor
  • Cancer Research 05/2015; 75(9 Supplement):P3-05-12-P3-05-12. DOI:10.1158/1538-7445.SABCS14-P3-05-12 · 9.28 Impact Factor
  • Cancer Research 05/2015; 75(9 Supplement):P4-07-08-P4-07-08. DOI:10.1158/1538-7445.SABCS14-P4-07-08 · 9.28 Impact Factor
  • Journal of the European Academy of Dermatology and Venereology 04/2015; DOI:10.1111/jdv.13164 · 3.11 Impact Factor
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    ABSTRACT: This phase 2 randomized study evaluated trebananib (AMG 386), a peptide-Fc fusion protein that inhibits angiogenesis by neutralizing the interaction of angiopoietin-1 and -2 with Tie2, in combination with paclitaxel with or without bevacizumab in previously untreated patients with HER2-negative locally recurrent/metastatic breast cancer. Patients received paclitaxel 90 mg/m(2) once weekly (3-weeks-on/1-week-off) and were randomly assigned 1:1:1:1 to also receive blinded bevacizumab 10 mg/kg once every 2 weeks plus either trebananib 10 mg/kg once weekly (Arm A) or 3 mg/kg once weekly (Arm B), or placebo (Arm C); or open-label trebananib 10 mg/kg once a week (Arm D). Progression-free survival was the primary endpoint. In total, 228 patients were randomized. Median estimated progression-free survival for Arms A, B, C, and D was 11.3, 9.2, 12.2, and 10 months, respectively. Hazard ratios (95% CI) for Arms A, B, and D versus Arm C were 0.98 (0.61-1.59), 1.12 (0.70-1.80), and 1.28 (0.79-2.09), respectively. The objective response rate was 71% in Arm A, 51% in Arm B, 60% in Arm C, and 46% in Arm D. The incidence of grade 3/4/5 adverse events was 71/9/4%, 61/14/5%, 62/16/3%, and 52/4/7% in Arms A/B/C/D. In Arm D, median progression-free survival was 12.8 and 7.4 months for those with high and low trebananib exposure (AUCss ≥ 8.4 versus < 8.4 mg·h/mL), respectively. There was no apparent prolongation of estimated progression-free survival with the addition of trebananib to paclitaxel and bevacizumab at the doses tested. Toxicity was manageable. Exposure-response analyses support evaluation of combinations incorporating trebananib at doses > 10 mg/kg in this setting. ClinicalTrials.gov, NCT00511459. Copyright © 2015. Published by Elsevier Ltd.
    Breast (Edinburgh, Scotland) 03/2015; 24(3). DOI:10.1016/j.breast.2014.11.003 · 2.58 Impact Factor
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    ABSTRACT: Metastatic breast cancer (MBC) is an incurable disease and represents a complex therapeutic challenge for oncologists. Despite the possibility of prescribing new agents such as tailored therapy, cytotoxic chemotherapy and hormone therapy remain the major treatments for MBC. Several lines of chemotherapy can be proposed for these patients, but beyond the second-line, evidence of effectiveness is lacking and such treatment has important associated toxicity affecting quality of life (QoL). Prospective data on third-line chemotherapy is very poor. There is no recent retrospective data and it mainly includes single-centre experiences. Moreover, prognostic parameters considered in these retrospective studies are limited to clinico-pathological factors. Previous reports don't evaluate prognostic impact of circulating tumour cells (CTC) and baseline QoL. METAL3 METAstatic Line 3 is a prospective, multicentric trial designed to prospectively construct a prognostic score (including selected clinico-pathological factors, CTC and baseline QoL) to identify patients who benefit from third-line chemotherapy for MBC in terms of overall survival (training cohort). Score will then be validated with another cohort (validation cohort). The aim of this paper is to review literature data on third-line chemotherapy for MBC and to describe in detail our prospective study. We hope that this prognostic score could be used by physicians to develop new therapeutic strategies when there will be limited benefit of third-line chemotherapy; this score will also help to improve patient information on their outcome.
    Contemporary Clinical Trials 01/2015; 40. DOI:10.1016/j.cct.2014.11.005 · 1.99 Impact Factor
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    ABSTRACT: Purpose: The BEVERLY-2 single-arm phase 2 trial assessed the efficacy and safety of combining neoadjuvant chemotherapy with bevacizumab and trastuzumab for the treatment of HER2-positive inflammatory breast cancer (IBC). Here we report the results of a pre-planned survival analysis at three years of follow-up, along with the association between outcome and circulating biomarkers and pathological complete response (pCR). Experimental design: Patients received fluorouracil, epirubicin, cyclophosphamide and bevacizumab (cycles 1-4) and docetaxel, trastuzumab and bevacizumab (cycles 5-8) prior to surgery, followed by trastuzumab and bevacizumab for 30 weeks post-surgery. Circulating tumor (CTC) and endothelial cell (CEC) counts were assessed at baseline, cycle 5, pre-operative, post-operative and at one year. Results: 52 patients were included. The 3-year disease-free survival (DFS) rate was 68% and overall survival (OS) rate was 90%. pCR (centrally reviewed) was strongly associated with 3-year DFS (80% and 53% in patients with/without pCR, respectively [p=0.03]). CTC detection also independently predicted 3-year DFS (81% vs. 43% for patients with <1 vs. ≥1 CTC/7.5 mL at baseline [p=0.01]). Patients with no CTC detected at baseline and with pCR had a high 3-year DFS (95%). CEC changes during treatment had no prognostic value. Conclusions: Our study suggests that the prognosis of IBC relies on more than the achievement of pCR and highlights the role of early hematogenous tumor dissemination as assessed by CTCs. Combining these two prognostic factors isolates a subgroup of IBC with excellent survival when treated with bevacizumab and trastuzumab-containing regimens. Copyright © 2014, American Association for Cancer Research.
    Clinical Cancer Research 12/2014; 21(6). DOI:10.1158/1078-0432.CCR-14-1705 · 8.19 Impact Factor
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    ABSTRACT: Objective: This study is a longitudinal follow-up of metastatic breast cancer patients treated with ixabepilone as first-line chemotherapy, with the aim to evaluate the association between a mechanism-based neurotoxicity and the efficacy of ixabepilone. Patients and Methods: At the 2 main investigational sites of a phase II clinical trial, 50 patients previously treated with anthracycline received ixabepilone. A chart review was performed to evaluate overall survival (OS) and time to progression (TTP) and to describe the subsequent treatments. Results: The severe neurotoxicity induced by ixabepilone (38%) is correlated with a higher overall response rate to ixabepilone (79 vs. 48%; p = 0.042), a longer TTP (11.4 vs. 6.8 months; p = 0.023) and a longer OS (36.6 vs. 19.9 months; p = 0.05). After ixabepilone discontinuation, patients received a median of 4 subsequent chemotherapy lines (range 1-12). Among the 31 patients who received taxanes, neither the neurotoxicity incidence under treatment with taxanes nor the response was affected by a previous occurrence under ixabepilone treatment. Conclusion: These findings suggest that neurotoxicity development under ixabepilone treatment is a predictor of treatment outcomes as well as a favorable prognostic factor. It highlights the risk-to-benefit ratio issue of ixabepilone. We noticed the possibility to treat patients with taxanes after ixabepilone without systematic recurrent neurotoxicity. © 2014 S. Karger AG, Basel.
    Oncology 11/2014; 88(3):180-188. DOI:10.1159/000367808 · 2.61 Impact Factor
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    ABSTRACT: IntroductionTriple Negative Breast Cancers (TNBC) represent about 12% to 20% of all breast cancers (BC) and have a worse outcome compared to other BC subtypes. TNBC often show a deficiency in DNA double-strand break repair mechanisms. This is generally related to the inactivation of a repair enzymatic complex involving BRCA1 caused either by genetic mutations, epigenetic modifications or by post-transcriptional regulations.The identification of new molecular biomarkers that would allow the rapid identification of BC presenting a BRCA1 deficiency could be useful to select patients who could benefit from PARP inhibitors, alkylating agents or platinum-based chemotherapy.Methods Genomic DNA from 131 formalin-fixed paraffin-embedded (FFPE) tumors (luminal A and B, HER2+ and triple negative BC) with known BRCA1 mutation status or unscreened for BRCA1 mutation were analysed by array Comparative Genomic Hybridization (array CGH). One highly significant and recurrent gain in the 17q25.3 genomic region was analysed by fluorescent in situ hybridization (FISH). Expression of the genes of the 17q25.3 amplicon was studied using customized Taqman low density arrays and single Taqman assays (Applied Biosystems).ResultsWe identified by array CGH and confirmed by FISH a gain in the 17q25.3 genomic region in 90% of the BRCA1 mutated tumors. This chromosomal gain was present in only 28.6% of the BRCA1 non-mutated TNBC, 26.7% of the unscreened TNBC, 13.6% of the luminal B, 19.0% of the HER2+ and 0% of the luminal A breast cancers. The 17q25.3 gain was also detected in 50% of the TNBC with BRCA1 promoter methylation. Interestingly, BRCA1 promoter methylation was never detected in BRCA1 mutated BC. Gene expression analyses of the 17q25.3 sub-region showed a significant over-expression of 17 genes in BRCA1 mutated TNBC (n¿=¿15) as compared to the BRCA1 non mutated TNBC (n¿=¿13).Conclusions In this study, we have identified by array CGH and confirmed by FISH a recurrent gain in 17q25.3 significantly associated to BRCA1 mutated TNBC. Up-regulated genes in the 17q25.3 amplicon might represent potential therapeutic targets and warrant further investigation.
    Breast cancer research: BCR 11/2014; 16(6):466. DOI:10.1186/s13058-014-0466-y · 5.88 Impact Factor
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    ABSTRACT: A selective and accurate analytical method is needed to quantify tamoxifen and its phase I metabolites in a prospective clinical protocol, for evaluation of pharmacokinetic parameters of tamoxifen and its metabolites in adjuvant treatment of breast cancer. The selectivity of the analytical method is a fundamental criteria to allow the quantification of the main active metabolites (Z)-isomers from (Z)'-isomers. An UPLC-MS/MS method was developed and validated for the quantification of (Z)-tamoxifen, (Z)-endoxifen, (E)-endoxifen, Z'-endoxifen, (Z)'-endoxifen, (Z)-4-hydroxytamoxifen, (Z)-4'-hydroxytamoxifen, N-desmethyl tamoxifen, and tamoxifen-N-oxide. The validation range was set between 0.5ng/mL and 125ng/mL for 4-hydroxytamoxifen and endoxifen isomers, and between 12.5ng/mL and 300ng/mL for tamoxifen, tamoxifen N-desmethyl and tamoxifen-N-oxide. The application to patient plasma samples was performed.
    Journal of Pharmaceutical and Biomedical Analysis 08/2014; 100C:254-261. DOI:10.1016/j.jpba.2014.07.033 · 2.83 Impact Factor
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    ABSTRACT: Background Despite high initial sensitivity to chemotherapy, triple-negative breast cancer (TNBC) is associated with a poor prognosis, highlighting the need for novel therapeutic strategies. The aim of this multicenter, randomized, open-label phase II trial was to assess the efficacy of ixabepilone as monotherapy, and the combination of ixabepilone plus cetuximab, as first-line treatment in patients with TN locally advanced non-resectable and/or metastatic breast cancer. Patients and Methods Women were randomly assigned to receive either ixabepilone (40 mg/m2) every 21 days (n = 40), or ixabepilone (40 mg/m2) every 21 days plus cetuximab (400 mg/m2 loading dose, followed by 250 mg/m2) once weekly (n = 39). The primary endpoint of the trial was to estimate the response rates of ixabepilone monotherapy and ixabepilone plus cetuximab combination therapy. Results Of 79 randomized patients, 77 were treated. Based on an intent-to-treat analysis, an objective response rate of 30% (95% confidence interval [CI], 16.6, 46.5) was observed in the monotherapy arm, and 35.9% (95% CI, 21.2, 52.8) in the combination arm. Median progression-free survival was 4.1 months in both treatment groups. Safety findings were consistent with the known individual toxicity profiles of ixabepilone and cetuximab. Skin and subcutaneous tissue disorders were more common with combination therapy, as were discontinuations due to adverse events. Conclusion Ixabepilone monotherapy and the ixabepilone and cetuximab combination demonstrated similar levels of clinical activity in first-line treatment of advanced TNBC, with a predictable safety profile. Further investigation of novel therapies for TNBC is required in order to improve patient outcomes.
    Clinical Breast Cancer 08/2014; 15(1). DOI:10.1016/j.clbc.2014.07.007 · 2.63 Impact Factor
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    ABSTRACT: Treatment of HER2-positive metastatic breast cancer with ado-trastuzumab emtansine (T-DM1), a novel antibody-drug conjugate, has resulted in both improved progression-free and overall survival. Recognition and treatment of diverse adverse events related to T-DM1 is critical for safety and tolerability. The most frequent adverse events with T-DM1 include fatigue, diarrhea, anemia, elevated transaminases, and mild-to-moderate hemorrhagic events, which are thought to be related to induced thrombocytopenia. Here, we present five case series of cutaneous and mucosal telangiectasias, definitely related to T-DM1. The development of telangiectasias represents a newly recognized adverse effect of T-DM1. We provide description and timing of the telangiectasias and review the mechanisms that may explain the formation of these vascular lesions in association with T-DM1. Further, we describe associated bleeding events and propose that induced telangiectasias could represent an additional cause of T-DM1-associated hemorrhage.
    Breast Cancer Research and Treatment 06/2014; 146(2). DOI:10.1007/s10549-014-3001-z · 4.20 Impact Factor
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    ABSTRACT: To examine the association between baseline body mass index (BMI), and disease-free survival (DFS) and overall survival (OS) in a large French early-stage breast cancer population included in the UNICANCER Programme d'Action Concerté Sein-01 (PACS01) and PACS04 phase III randomised trials. After a median follow-up of 5.9years, this report analyses 4996 patients with node-positive breast cancer, and randomly assigned to adjuvant anthracycline-based chemotherapy combined or not with taxanes. Univariate analyses were used to study the effects of well known prognostic factors and BMI on DFS and OS. BMI was obtained at baseline, before chemotherapy initiation, and obesity was defined as a BMI⩾30kg/m(2). Cox proportional hazards regression models were secondly used to assess the influence of BMI after adjusting for other factors. Exhaustive analysis of the dose intensity delivered was also studied for comparison between obese and non-obese patients. Obese patients initially present with more advanced disease at diagnosis compared to non-obese patients. By univariate analysis, obesity was moderately associated with poorer DFS (hazard ratio (HR)=1.18 [1.01-1.39] P=0.04), but mostly with poorer OS (HR=1.38 [1.13-1.69] P=0.002). Delivered dose intensity of anthracyclines and taxanes was not significantly different between obese and non-obese patients. After adjustment for disease characteristics, BMI had no influence either on DFS or OS. This report suggests that in a French population, obesity has no impact on breast cancer prognosis when modern adjuvant chemotherapy, at the appropriate dose intensity, is delivered.
    European journal of cancer (Oxford, England: 1990) 12/2013; 50(3). DOI:10.1016/j.ejca.2013.11.013 · 4.82 Impact Factor
  • Annales de Dermatologie et de Vénéréologie 12/2013; 140(12):S525-S526. DOI:10.1016/j.annder.2013.09.372 · 0.67 Impact Factor
  • Henri Roché
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    ABSTRACT: The natural history of breast diseases has changed overtime and successive therapeutic strategies have been adapted accordingly. Recently, biological findings on geno- and phenotypic characteristics of tumor cells offer new basis for the development of treatments that target homogenous and various subtypes of breast cancer. Unfortunately, traditional clinical research tools are not in phase with rapid changes in both biological knowledge of the disease and new targeted agents. New methodological approaches are urgently needed to validate such changes and improvements in prognosis.
    Bulletin du cancer 09/2013; 100(9). DOI:10.1684/bdc.2013.1805 · 0.64 Impact Factor
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    ABSTRACT: Sorafenib is an oral multikinase inhibitor with antiangiogenic/antiproliferative activity. A randomized phase 2b screening trial in human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer demonstrated a significant improvement in progression-free survival (PFS) when sorafenib was added to capecitabine versus placebo (median 6.4 versus 4.1 months; hazard ratio = 0.58; P = 0.001). Most drug-related adverse events were Grade 1/2 in severity with the exception of Grade 3 hand-foot skin reaction/syndrome (44% versus 14%, respectively). These results suggest a role for the combination of sorafenib and capecitabine in breast cancer and supported a phase 3 confirmatory trial. Here we describe RESILIENCE - a multinational, double-blind, randomized, placebo-controlled, phase 3 trial - assessing the addition of sorafenib to first- or second-line capecitabine in advanced HER2-negative breast cancer.Methods/design: Eligibility criteria include >=18 years of age, <=1 prior chemotherapy regimen for metastatic disease, and resistant to/failed taxane and anthracycline or no indication for further anthracycline. Prior treatment with a vascular endothelial growth factor inhibitor is not allowed. Patients with significant cardiovascular disease or active brain metastases are not eligible. Patients are stratified by hormone receptor status, geographic region, and prior metastatic chemotherapy status and randomized (1:1) to capecitabine (1000 mg/m2 orally twice daily (BID), days 1 to 14 of 21) in combination with sorafenib (orally BID, days 1 to 21, total dose 600 mg/day) or matching placebo. Capecitabine and sorafenib/placebo doses can be escalated to 1250 mg/m2 BID and 400 mg BID, respectively, as tolerated, or reduced to manage toxicity. Dose re-escalation after a reduction is allowed for sorafenib/placebo but not for capecitabine. This dosing algorithm was designed to mitigate dermatologic and other toxicity, in addition to detailed guidelines for prophylactic and symptomatic treatment. Radiographic assessment is every 6 weeks for 36 weeks, and every 9 weeks thereafter. The primary endpoint is PFS by blinded independent central review (Response Evaluation Criteria in Solid Tumors 1.1 criteria). Secondary endpoints include overall survival, time to progression, overall response rate, duration of response, and safety. Enrollment began in November 2010 with a target of approximately 519 patients. RESILIENCE will provide definitive PFS data for the combination of sorafenib and capecitabine in advanced HER2-negative breast cancer and better characterize the benefit-to-risk profile.Trial registration: Clinicaltrials.gov, NCT01234337.
    Trials 07/2013; 14(1):228. DOI:10.1186/1745-6215-14-228 · 2.12 Impact Factor
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    ABSTRACT: Although young age at diagnosis is an independent prognostic factor of poor survival; no specific recommendation are provided concerning the timing and modalities of follow-up for this population. These patients are followed similarly to older women during post-therapeutic surveillance. The objective of this study is to examine patterns of recurrence in a large series of positive lymph node breast cancer women aged 35 years or below and treated within adjuvant chemotherapy trials. Data of 200 patients (≤ 35 years) included in three UNICANCER adjuvant trials for node positive breast cancer were used. Competing risks methodology was used to identify prognostic factors associated with time to first failure according to type of event. After a median follow-up of 52.4 months, 84 pts had disease related events (17 loco-regional, five contralateral, and 62 distant metastasis). Variables associated with an increased rate of first event were the number of involved lymph nodes and the type of surgery. In univariate analysis, prognostic factors associated with high potential curative recurrence were number of positive lymph nodes and vascular invasion. Only number of positive lymph node remained significant in multivariate analysis. Concerning distant metastasis, only the number of lymph node involved was associated to an increased risk of metastasis. Using the number of positive nodes as important prognostic factors, it should be possible to identify patients at a higher risk of loco-regional relapse or contralateral breast cancer, in order to propose more individualized follow-up.
    Bulletin du cancer 07/2013; DOI:10.1684/bdc.2013.1791 · 0.64 Impact Factor

Publication Stats

2k Citations
574.18 Total Impact Points

Institutions

  • 2015
    • Institut Universitaire de France
      Lutetia Parisorum, Île-de-France, France
  • 2002–2015
    • Institut Claudius Regaud
      Tolosa de Llenguadoc, Midi-Pyrénées, France
  • 2004–2014
    • Paul Sabatier University - Toulouse III
      Tolosa de Llenguadoc, Midi-Pyrénées, France
  • 2012
    • Institut de France
      Lutetia Parisorum, Île-de-France, France
    • Massachusetts General Hospital
      Boston, Massachusetts, United States
  • 2004–2009
    • Centre Jean Perrin
      Clermont, Auvergne, France
  • 2007
    • Cornell University
      Итак, New York, United States
    • Centre François Baclesse
      Caen, Lower Normandy, France
  • 2005
    • French Institute of Health and Medical Research
      Lutetia Parisorum, Île-de-France, France
    • Centre Léon Bérard
      Lyons, Rhône-Alpes, France