F. Grange

Hôpital Universitaire Robert Debré, Lutetia Parisorum, Île-de-France, France

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Publications (209)591.81 Total impact

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    ABSTRACT: La pemphigoïde bulleuse (PB) touche principalement le sujet âgé. Elle est souvent associée à des maladies neurologiques, qui représentent un facteur de risque connu de PB. L’objectif de cette étude rétrospective était de déterminer si les maladies neurologiques, notamment la démence, influençaient le pronostic vital et l’évolution de la PB.
    No preview · Article · Jan 2016 · Annales de Dermatologie et de Vénéréologie
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    ABSTRACT: BRAF inhibitors (BRAFi) elicit therapeutic responses in metastatic melanoma, but alarmingly, also induce the formation of secondary benign and malignant skin tumors. Here, we report the emergence and molecular characterization of 73 skin and extracutaneous tumors in 31 patients who underwent BRAFi therapy. The majority of patients presented with classic epidermal tumors such as verrucous papillomas, keratoacanthomas, and squamous cell carcinomas (SCC). However, 15 patients exhibited new or rapidly progressing tumors distinct from these classic subtypes, such as lymph node metastasis, new melanomas, and genital and oral mucosal SCCs. Genotyping of the tumors revealed that oncogenic RAS mutations were found in 58% of the evaluable tumor samples (38/66) and 49% of the control tumors from patients not treated with BRAFi (30/62). Notably, proximity ligation assays demonstrated that BRAF-CRAF heterodimerization was increased in fixed tumor samples from BRAFi-treated patients compared to untreated patients. Our findings reveal that BRAF-CRAF complex formation is significantly associated with BRAFi treatment and may therefore serve as a useful biomarker of BRAFi-induced cutaneous and extracutaneous tumor formation.
    No preview · Article · Jan 2016 · Cancer Research
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    ABSTRACT: Background: Sentinel lymph-node biopsy (SLNB) is a valuable tool to assess the regional lymph-node status in Merkel cell carcinoma (MCC). However, its prognostic value is still debated. This study was undertaken to assess SLNB usefulness for MCC management and to determine the impact of SLNB status on disease-free survival (DFS) and overall survival (OS) by comparing SLNB-positive v -negative patients according to demographic, clinical and treatment characteristics. Patients and methods: In this retrospective, multicenter observational study, SLNB was proposed to all patients referred for clinically N0 MCC. Treatment schedule consisted of wide-margin surgical resection of primary MCC followed by adjuvant radiation therapy (aRT) to the primary site and, for SLNB-positive patients, radical lymph-node dissection followed by regional aRT. Univariate and multivariate analyses determined factors associated with DFS and OS. Results: Among 87 patients with successful SLNB, 21 (24.1%) were SLNB-positive. Median follow-up for the entire series was 39 months; respective 3-year DFS and OS rates were 73% and 81.4%. Univariate analysis (all patients) identified SLNB-negativity as being associated with prolonged OS (P=.013) and aRT (all sites considered) was associated with longer DFS (P=.004) and OS (P=.018). Multivariate analysis (all patients) retained SLNB status and aRT (all sites considered) as being associated with improved DFS (P=.014 and P=.0008) and OS (P=.0020 and P=.0019). Moreover, for SLNB-negative patients, tumor-bed irradiation was also significantly associated with prolonged DFS (P=.006) and OS (P=.014). Conclusions: The present study demonstrates that SLNB-negativity is a strong predictor of longer DFS and OS in stage I and II MCC patients. The similar benefit for aRT on tumor-bed observed in this study has to be confirmed by a prospective study. The results advocate for SLNB being considered to all MCC patients.
    No preview · Article · Jan 2016 · Annals of Oncology
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    ABSTRACT: Background: Therapeutic monoclonal anti-CTLA-4-antibodies are associated with immune-mediated enterocolitis. The aim of this study was to provide a detailed description of this entity. Methods: We included patients with endoscopic signs of inflammation after anti-CTLA-4 infusions for cancer treatment. Other causes of enterocolitis were excluded. Clinical, biological and endoscopic data were recorded. A single pathologist reviewed endoscopic biopsies and colectomy specimens of 27 patients. Patients with and without enterocolitis after ipilimumab-treated melanoma were compared, to identify clinical factors associated with enterocolitis. Results: Thirty-nine patients with anti-CTLA-4-enterocolitis were included (ipilimumab n=37; tremelimumab n=2). The most frequent symptom was diarrhoea. Ten patients had extra-intestinal manifestations. Most colonoscopies showed ulcerations involving the rectum and sigmoid; 66% of patients had extensive colitis, 55% had patchy distribution, 20% had ileal inflammation. Endoscopic colonic biopsies showed acute colitis in most patients, while half of the patients had chronic duodenitis. Thirty-five patients received steroids that led to complete clinical remission in 13 patients (37%). Twelve patients required infliximab, of whom 10 responded (83%). Six patients underwent colectomy (perforation n=5; toxic megacolon n=1); one of them died postoperatively. Four patients had a persistent enterocolitis at follow-up colonoscopy. Patients with enterocolitis were more frequently prescribed NSAIDs as compared to patients without enterocolitis (31% vs 5%, p=0.003). Conclusions: Ipilimumab and tremelimumab may induce a severe and extensive form of inflammatory bowel disease. A rapid escalation to infliximab should be advocated in patients who do not respond to steroids. Patients treated with anti-CTLA-4 should be advised to avoid NSAIDs.
    No preview · Article · Jan 2016 · Journal of Crohn s and Colitis
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    ABSTRACT: Background. Lymphomatoid papulosis (LyP) is classified as an indolent cutaneous lymphoma, but outcome dramatically worsens if LyP is associated with lymphoma. The frequency of this association remains unclear in the literature. Here, we assess the frequency and risk factors of association between LyP and another lymphoma in an 11-year retrospective study conducted in 8 dermatology departments belonging to the French Study Group on Cutaneous Lymphoma (FSGCL). Patients and Methods. Patients with LyP were identified and data extracted from the FSGCL registry between 1991 and 2006. Patients were followed up to January 2014. Age, sex, number of skin lesions, histologic subtype, and genotype were recorded at baseline. Risk factors were determined using univariate and multivariate analysis. Cumulative probability of association was calculated using the Kaplan-Meier method. Results.Weobserved 52 cases of lymphomas (cutaneous, n= 38; systemic, n = 14) in 44 of 106 patients (41%). Lymphoma diagnosis was concomitant with or prior to LyP diagnosis in 31 cases and occurred during the course of LyP in 21 cases (cutaneous, n = 14; systemic, n = 7; median delay: 5 years; interquartile range: 1.5–7 years). In multivariate analysis, main prognostic factors for association between LyP and another lymphoma were older age (odds ratio [OR]: 1.05 per year; 95% confidence interval [CI]: 1.01–1.08;p=.011)and presence of a T-cell clone in LyP lesions (OR: 7.55; 95% CI: 2.18–26.18; p =.001). Conclusion. Older age and presence of a T-cell clone in LyP lesions are risk factors for associated lymphomas in patients with LyP. These findings should help to identify patients who require close management in clinical practice.
    No preview · Article · Dec 2015 · The Oncologist
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    ABSTRACT: Melanomas associated with blue nevi (MABN) or mimicking cellular blue nevi (MMCBN) represent exceptional variants of malignant cutaneous melanocytic tumors. Uveal and leptomeningeal melanomas frequently have somatic mutations of GNAQ or GNA11, which are believed to be early driver mutations. In uveal melanomas, monosomy 3, linked to the BAP1 gene, is an adverse prognostic factor. We have studied the clinical, histologic, BAP1 expression profile, and molecular data of 11 cases of MABN/MMCBN and 24 cellular blue nevi. Most of the cases of MABN/MMCBN occurred on the scalps of adult patients and presented as rapidly growing nodules, typically >1 cm, often arising at the site of a preexisting melanocytic lesion. The MABN/MMCBN were composed of dense nests of large dermal atypical melanocytes, in some cases lying adjacent to a blue nevus. Four patients developed metastatic disease, and 2 died from their disease. A GNA11 mutation was found in 8/11 cases and a GNAQ mutation in 1 case. Seven of 11 cases showed loss of nuclear BAP1 immunohistochemical (IHC) expression in the malignant component, sparing the adjacent nevus. Array comparative genomic hybridization revealed recurrent deletions of chromosomes 1p, 3p, 4q, 6q, 8p, 16q, and 17q and recurrent gains of chromosomes 6p, 8q, and 21q. The 24 cases of cellular blue nevi frequently occurred on the sacrum, had GNAQ mutations, and showed normal positive IHC staining for BAP1. These results underscore overlapping features in all blue-like malignant melanocytic tumors. Loss of BAP1 IHC expression was restricted to melanomas, including all metastatic cases.
    No preview · Article · Dec 2015 · The American journal of surgical pathology

  • No preview · Article · Dec 2015 · Annales de Dermatologie et de Vénéréologie

  • No preview · Article · Dec 2015 · Annales de Dermatologie et de Vénéréologie
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    ABSTRACT: Background: Reactivation of hepatitis B or C virus can occur in patients undergoing chemotherapy. Recommendations for selective or systematic hepatitis B virus testing prior chemotherapy for solid tumors differ. The primary aim was to determine the seroprevalence of hepatitis B or C in a low endemic country. The second objective was to assess the relevance of a questionnaire on hepatitis B/C risk factors to consider a selective screening. Methods: Patients were prospectively tested for hepatitis B/C markers. HBs antigen positive patients and isolated anti-HBc positive patients with detectable viral load received antiviral preventive treatment. Patients or physicians completed the questionnaire on infection risk factors. Results: Among the 450 patients included, 388 were tested for all serological markers and had gastrointestinal (63.7 %), lung (31.2 %) and skin (4.6 %) cancers. The prevalence of subjects exposed to hepatitis B virus was 8.5 % (33/388). One patient tested positive for HBs antigen and received preventive treatment. Prevalence of subjects exposed to hepatitis C was 1.3 % (5/388). The questionnaire sensitivity was 45.5 %, 100 % and 50 % for detecting carriers of hepatitis B, C and one or the other, respectively. Conclusions: Seroprevalence of hepatitis B was low. Selective screening with the questionnaire was insufficiently sensitive. Systematic screening with serological tests prior to chemotherapy in patients with solid tumors is therefore relevant.
    Full-text · Article · Dec 2015 · BMC Cancer

  • No preview · Article · Dec 2015 · Annales de Dermatologie et de Vénéréologie

  • No preview · Article · Dec 2015 · Annales de Dermatologie et de Vénéréologie
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    ABSTRACT: Background: In the COMBI-v trial, patients with previously untreated BRAF Val600Glu or Val600Lys mutant unresectable or metastatic melanoma who were treated with the combination of dabrafenib and trametinib had significantly longer overall and progression-free survival than those treated with vemurafenib alone. Here, we present the effects of treatments on health-related quality of life (HRQoL), an exploratory endpoint in the COMBI-v study. Methods: COMBI-v was an open-label, randomised phase 3 study in which 704 patients with metastatic melanoma with a BRAF Val600 mutation were randomly assigned (1:1) by an interactive voice response system to receive either a combination of dabrafenib (150 mg twice-daily) and trametinib (2 mg once-daily) or vemurafenib monotherapy (960 mg twice-daily) orally as first-line therapy. The primary endpoint was overall survival. In this pre-specified exploratory analysis, we prospectively assessed HRQoL in the intention-to-treat population with the European Organisation for Research and Treatment of Cancer quality of life (EORTC QLQ-C30), EuroQoL-5D (EQ-5D), and Melanoma Subscale of the Functional Assessment of Cancer Therapy-Melanoma (FACT-M), completed at baseline, during study treatment, at disease progression, and after progression. We used a mixed-model, repeated measures ANCOVA to assess differences in mean scores between groups with baseline score as covariate; all p-values are descriptive. The COMBI-v trial is registered with ClinicalTrials.gov, number NCT01597908, and is ongoing for the primary endpoint, but is not recruiting patients. Findings: From June 4, 2012, to Oct 7, 2013, 1645 patients at 193 centres worldwide were screened for eligibility, and 704 patients were randomly assigned to dabrafenib plus trametinib (n=352) or vemurafenib (n=352). Questionnaire completion rates for both groups were high (>95% at baseline, >80% at follow-up assessments, and >70% at disease progression) with similar HRQoL and symptom scores reported at baseline in both treatment groups for all questionnaires. Differences in mean scores between treatment groups were significant and clinically meaningful in favour of the combination compared with vemurafenib monotherapy for most domains across all three questionnaires during study treatment and at disease progression, including EORTC QLQ-C30 global health (7·92, 7·62, 6·86, 7·47, 5·16, 7·56, and 7·57 at weeks 8, 16, 24, 32, 40, 48, and disease progression, respectively; p<0·001 for all assessments except p=0·005 at week 40), EORTC QLQ-C30 pain (-13·20, -8·05, -8·82, -12·69, -12·46, -11·41, and -10·57 at weeks 8, 16, 24, 32, 40, 48, and disease progression, respectively; all p<0·001), EQ-5D thermometer scores (7·96, 8·05, 6·83, 11·53, 7·41, 9·08, and 10·51 at weeks 8, 16, 24, 32, 40, 48, and disease progression, respectively; p<0·001 for all assessments except p=0·006 at week 32), and FACT-M Melanoma Subscale score (3·62, 2·93, 2·45, 3·39, 2·85, 3·00, and 3·68 at weeks 8, 16, 24, 32, 40, 48, and disease progression, respectively; all p<0·001). Interpretation: From the patient's perspective, which integrates not only survival advantage but also disease-associated and adverse-event-associated symptoms, treatment with the combination of a BRAF inhibitor plus a MEK inhibitor (dabrafenib plus trametinib) adds a clear benefit over monotherapy with the BRAF inhibitor vemurafenib and supports the combination therapy as standard of care in this population. Funding: GlaxoSmithKline.
    Full-text · Article · Oct 2015 · The Lancet Oncology
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    ABSTRACT: Corresponding author. Lab dermatologie, université Reims-Champagne-Ardenne, 51100 Reims, France.
    No preview · Article · Jul 2015 · Annales de Dermatologie et de Vénéréologie
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    ABSTRACT: Monoclonal T-cell receptor (TCR) rearrangement is detected in 57% to 75% of early-stage mycosis fungoides (MF) at diagnosis. A retrospective study showed molecular residual disease (MRD) in 31% of patients in complete clinical remission (CR) after 1 year of treatment. To confirm the frequency of MRD at 1 year and to determine its prognostic value for further relapse. Patients with T1-, T2- or T4-stage MF were prospectively included in this multicenter study. At diagnosis, clinical lesions and healthy skin were biopsied. After 1 year of topical treatment, previously involved skin (PIS) of patients in CR was biopsied for histology and analysis of TCR-γ gene rearrangement. Results were compared to the clinical status each year for 4 years. We included 214 patients, 133 at T1, 78 T2, and 3 T4 stage. At diagnosis, 126/204 cases (61.8%) showed TCR clonality in lesional skin. After 1 year, 83/178 patients (46.7%) still being followed up were in CR and 13/63 (20.6%) showed MRD. At 4 years, 55/109 (50.5%) patients still being followed up were in CR and 44/109 were in T1 stage (40.4%). MRD did not affect clinical status at 4 years (CR vs. T1/T2, p=1.0, positive predictive value 36.4%, negative predictive value 67.6%). T-cell clonality at diagnosis and MRD at 1 year are not a prognostic factor of clinical status at 4 years. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    No preview · Article · Jul 2015 · British Journal of Dermatology
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    Full-text · Dataset · Apr 2015
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    ABSTRACT: Background The incidence of melanoma is increasing worldwide, causing significant economic burden at community and individual levels. Ultraviolet radiation, from natural sunlight or artificial sources, is the main environmental, modifiable risk factor for melanoma.Objectives The present analysis assesses the profile of sun exposure in the French population as well as the level of awareness about ultraviolet risk and protection.Methods The survey was conducted via telephone interviews in September and October 2011. In total, 1502 respondents were questioned about their own sun exposure with the question “do you ever, even occasionally, spend time in the sun, during leisure-time, vacation or your professional occupation?” They were also asked about sun protection measures used: protective clothing, a hat or sunscreen.ResultsMore than three respondents out of four (78%) declared exposing themselves to the sun, with an average of 113 days per year. Of these, 38% did not use appropriate sun protection measures. We identified the following characteristics of individuals declaring high sun exposure: chiefly men under the age of 40, higher socio-professional levels, and adults with no children. Individuals who make a poor use of protective measures are mostly men and of low educational levels. Individuals declaring low sun exposure were chiefly: women, individuals over the age of 60, and those with no professional activity. The high sun protection population comprises mostly: women, higher socio-professional levels, with no specific age-group profile.Conclusions Analysis of the EDIFICE Melanoma survey provides information about the attitudes of the French population towards sun exposure. The most frequent contexts of sun exposure and the associated socio-demographic characteristics of the population with at-risk attitudes regarding sun exposure are identified. This deeper insight into the profile of at-risk populations will allow interventions to be more accurately targeted, thus potentially improving public health benefits.
    No preview · Article · Feb 2015 · Journal of the European Academy of Dermatology and Venereology
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    ABSTRACT: Background Melanoma incidence is increasing worldwide thus justifying information campaigns aimed at reducing ultraviolet exposure levels and promoting early diagnosis.Objectives We set out to assess awareness, knowledge and attitudes of the French population with regard to melanoma prevention and early diagnosis, following more than 15 years of nationwide information campaigns.Methods The French nationwide observational survey, EDIFICE Melanoma, was conducted after the summer (September to October 2011) through structured telephone interviews of a representative sample of 1502 individuals aged ≥18 years, using the quota method. All French regions were represented.ResultsRespondents had heard of sun-induced skin damage: 92% knew that sun increases melanoma risk. Knowledge of sun-protection measures was also good: 97% correctly cited at least one method of photoprotection (clothing 80%, sunscreens 69%) and 97% declared that sun exposure should be reduced between 12 pm and 4 pm in France. Knowledge of melanoma was encouraging: 70% of respondents could define the disease accurately and 60% knew the ABCDE rule for early diagnosis. However, self-tanning and sunbed use were considered by 25% and 13% of respondents, respectively, to provide protection from skin cancer. Although 43% of respondents (58% of high-risk respondents) declared they had consulted a doctor at least once for a suspect skin lesion, their actual behaviour was less encouraging: 30% declared never or almost never protecting their skin; 25% declared regularly checking their skin for atypical nevi; 12% declared checking the entire skin surface. Declared behaviour was better in fair-skin responders and those with a history of sunburn or skin cancer.Conclusions Awareness of melanoma, early-diagnosis procedures and preventive behaviour has improved in the general French population since 1990. However, despite the good level of information, numerous misconceptions persist. Improved information campaigns in the future may help reduce the ever-increasing incidence of melanoma in France.
    No preview · Article · Feb 2015 · Journal of the European Academy of Dermatology and Venereology
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    ABSTRACT: Background The efficiency of skin cancer prevention programmes is strongly correlated with the information dispensed, and with the level of risk awareness, of the overall population on one hand, and on the other, of specific sub-populations, according to their risk profiles.Objectives The primary objective of this analysis was to establish a correlation between individual perceptions of the risk of developing a melanoma, and the recognized intrinsic risk factors for a given individual. Secondary objectives were to assess factors that are potentially associated with acceptable, high or low perception of melanoma risk.Methods The EDIFICE Melanoma survey was conducted in 2011 via telephone interviews of a representative sample of 1502 individuals aged 18 and older in the French population.ResultsAlthough most respondents (73%) had a true estimation of their intrinsic risk for melanoma, those who did not (underestimation, 17%; overestimation, 10%) had an attitude towards environmental risk factors (sun exposure, sun protection, sunbed use) that did not compensate for this misplaced perception.Conclusions Skin cancer prevention messages need to be reinforced, new methods of evaluating understanding of the messages need to be implemented, and both need to be included into personal risk assessment.
    No preview · Article · Feb 2015 · Journal of the European Academy of Dermatology and Venereology
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    ABSTRACT: Objectives: The incidence of skin cancers, melanoma in particular, is increasing rapidly. Consequently, specific recommendations for sun-protection measures now exist. This survey set out to assess the compliance of the general population with these guidelines. Methods: The French nationwide observational survey, EDIFICE Melanoma, was conducted (28 September to 20 October 2011) through phone interviews of a representative sample of 1502 subjects aged ≥ 18 years, using the quota method. Sun-protection was defined as frequent or systematic use of clothes or sunscreen. The group of individuals who declared exposure to the sun (N = 1172) was subdivided: risk-takers (N = 442), and those who used sun protection (N = 730). Results: Risk-takers were significantly more often male (62% vs. 44%, P < 0.01), had a lower level of education (40% vs. 26%, P < 0.01), lower incomes (2587 euros vs. 2948 euros/month) and were more often smokers (42% vs. 31%, P < 0.01). In contrast, age, marital status and use of sunbeds were not significantly different between the two groups. Interestingly, risk-takers had less risk factors for melanoma. However, they were less well-informed about high-risk exposure and optimal use of sunscreen. Sun-protection measures for their children were less stringent than those of the group who used sun protection: systematic/frequent use of sunglasses (42% vs. 59%, P < 0.01), systematic use of sunscreen (77% vs. 86%, P < 0.01), and frequent renewal (69% vs. 82%, P < 0.01), high sun protection factors (SPF) (46% vs. 56%, P < 0.01), use of clothing (84% vs. 92%, P < 0.01) and hats (88% vs. 94%, P < 0.01). Conclusions: Risk-takers are characterized by a lesser understanding of sun-protection measures and behaviours. Their children benefit less from protective measures than those of people who use sun protection themselves. Improved understanding may well improve behaviours; one can therefore legitimately predict a considerable impact on parents' attitude to their own protection and that of their children.
    No preview · Article · Feb 2015 · Journal of the European Academy of Dermatology and Venereology
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    ABSTRACT: Background The prevention of melanoma can be significantly improved by targeting information directly towards the subpopulation of children and, as a means to achieve it, towards young parents.Objectives The objective of this analysis was to determine the evolution over time of the sun-protection measures adopted by parents for their young children.Methods The Edifice Melanoma survey was based on telephone interviews of a representative sample of 1502 subjects aged ≥18 years. This particular analysis focuses on 864 adults whose children are exposed to the sun for more than 10 days a year. We compared the characteristics and attitudes of two sub-groups of parents with regard to sun protection of young children: current-day behaviour of parents with children <15 years and behaviour in the past of parents whose children are now ≥15 years.ResultsPresent-day parents are more likely than those of previous generations to systematically or often use hats (96% vs. 90%, P < 0.01), protective clothes (92% vs. 84%, P < 0.01), sunscreen (89% vs. 80%, P < 0.01) and sunglasses (63% vs. 44%, P < 0.01) for their children. Systematic application of sunscreen is also more frequent today than several years ago as reported by 81% of present-day parents vs. 74% of those in the past (P < 0.05). Cream is reapplied every 2 h by 41% of present-day parents, compared to 33%, in the past (P < 0.05).Conclusions The attitude of parents towards sun protection for their children has improved over the past decade.
    No preview · Article · Feb 2015 · Journal of the European Academy of Dermatology and Venereology

Publication Stats

4k Citations
591.81 Total Impact Points

Institutions

  • 2005-2016
    • Hôpital Universitaire Robert Debré
      Lutetia Parisorum, Île-de-France, France
  • 2005-2015
    • Université de Reims Champagne-Ardenne
      • Laboratoire SiRMa
      Rheims, Champagne-Ardenne, France
  • 2005-2014
    • Centre Hospitalier Universitaire de Reims
      • Service de Dermatologie
      Rheims, Champagne-Ardenne, France
  • 2013
    • Université Blaise Pascal - Clermont-Ferrand II
      Clermont, Auvergne, France
  • 1993-2013
    • Institut de Cancérologie Gustave Roussy
      • Department of Radiotherapy
      Villejuif, Île-de-France, France
  • 2011
    • Hôpital Louis Pradel
      Lyons, Rhône-Alpes, France
  • 2010
    • Centre Hospitalier Universitaire de Bordeaux
      Burdeos, Aquitaine, France
  • 1997-2008
    • Hopitaux Civils De Colmar
      Kolmar, Alsace, France
  • 2002
    • IST Austria
      Klosterneuberg, Lower Austria, Austria
  • 2000
    • Université Victor Segalen Bordeaux 2
      Burdeos, Aquitaine, France