B Dreno

University of Nantes, Naoned, Pays de la Loire, France

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Publications (583)2167.38 Total impact

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    Journal of Translational Medicine 12/2015; 13(1):2061. DOI:10.1186/1479-5876-13-S1-O4 · 3.93 Impact Factor
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    ABSTRACT: Rarely, basal cell carcinomas (BCCs) have the potential to become extensively invasive and destructive, a phenomenon that has led to the term "locally advanced BCC" (laBCC). We identified and described the diverse settings that could be considered "locally advanced". The panel of experts included oncodermatologists, dermatological and maxillofacial surgeons, pathologists, radiotherapists and geriatricians. During a 1-day workshop session, an interactive flow/sequence of questions and inputs was debated. Discussion of nine cases permitted us to approach consensus concerning what constitutes laBCC. The expert panel retained three major components for the complete assessment of laBCC cases: factors of complexity related to the tumour itself, factors related to the operability and the technical procedure, and factors related to the patient. Competing risks of death should be precisely identified. To ensure homogeneous multidisciplinary team (MDT) decisions in different clinical settings, the panel aimed to develop a practical tool based on the three components. The grid presented is not a definitive tool, but rather, it is a method for analysing the complexity of laBCC.
    11/2015; DOI:10.1684/ejd.2015.2641
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    ABSTRACT: Background: Vemurafenib, a BRAF inhibitor, is commonly associated with skin toxicity. The impact of severe forms is unknown. Objective: To determine the rate of permanent vemurafenib discontinuation due to grade 3-4 skin toxicity, features of these toxicities, their recurrence rate after a switch to dabrafenib and their impact on overall survival. Methods: Retrospective cohort study of 131 patients treated with vemurafenib for melanoma between November 2010 and December 2014. Data on skin toxicities, the need for vemurafenib adjustment and the impact of switching to dabrafenib were collected. Regarding survival analysis, a conditional landmark analysis was performed to correct lead-time bias. Results: Among the 131 vemurafenib-treated patients, 26% developed grade 3-4 skin toxicity. Forty-four percent of them permanently discontinued their treatment, mainly due to rash and classic skin adverse reactions (Steven-Johnson syndrome, Drug Reaction with Eosinophilia and Systemic Symptoms). Conversely, photosensitivity and carcinomas rarely required treatment adjustment. Grade 3-4 rashes were associated with clinical or biological abnormalities in 94% of patients. Among the 10 patients who subsequently switched to dabrafenib, skin toxicity recurred only in one patient. Overall survival was significantly prolonged in case of severe skin toxicity emerging within the first 4 (P = 0.014) and 8 weeks (P = 0.038) on vemurafenib, with only a trend at 12 weeks (P = 0.052). Median overall survival was also prolonged in case of severe rash. Conclusion: In this study, vemurafenib was continued in 56% of patients with grade 3-4 skin toxicity, which was associated with prolonged overall survival when emerging within the first 4 and 8 weeks of treatment. While developing severe skin adverse reactions permanently contraindicates vemurafenib use, other rashes should lead to retreatment attempts with dose reduction. In case of recurrence, dabrafenib seems to be an interesting option. For other skin toxicities, including photosensitivity and cutaneous carcinoma, treatment adjustment is usually not needed.
    Journal of the European Academy of Dermatology and Venereology 11/2015; DOI:10.1111/jdv.13443 · 2.83 Impact Factor
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    ABSTRACT: Objectives: To assess the development of brain metastases under ipilimumab and identify clinical, histological or evolving criteria related to the appearance of these metastases. A retrospective study was conducted in 52 patients treated with 4 cycles of ipilimumab 3 mg/kg every 3 weeks for unresectable stage III or stage IV melanoma between January 2011 and July 2013 in a Department of Dermato-Oncology. As no data has been find in the literature, the results were compared to our other cohort of patients treated with vemurafenib during the same period. Ten patients (21.7 %) developed brain metastases under ipilimumab in a median time of 6.58 months after treatment initiation. The multivariate analysis showed a lower rate of brain metastases in patients with acral lentiginous melanoma and melanoma of unknown primary site. The median survival after diagnosis of brain metastases was of 2.5 months. There was no significant difference with vemurafenib-treated patients in terms of incidence rate of brain metastasis, time of development and survival after diagnosis of cerebral metastases. This was the first study focused on the development of brain metastases under treatment with ipilimumab 3 mg/kg. Although ipilimumab is used for the treatment of brain metastases, it paradoxically did not seem to reduce the risk of developing brain metastases.
    Journal of Neuro-Oncology 10/2015; DOI:10.1007/s11060-015-1977-9 · 3.07 Impact Factor

  • OncoImmunology 10/2015; DOI:10.1080/2162402X.2015.1104448 · 6.27 Impact Factor

  • Journal of the European Academy of Dermatology and Venereology 10/2015; DOI:10.1111/jdv.13446 · 2.83 Impact Factor
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    ABSTRACT: Background Unmet needs exist in actinic keratosis (AK) treatment. Daylight photodynamic therapy (DL-PDT) has shown good efficacy and safety results compared to conventional PDT (c-PDT) in a recent Phase III multi-centre randomised controlled trial in Australia among 100 subjects with AKs.Objectives Demonstrate non-inferior efficacy and superior safety of DL-PDT compared to c-PDT in treating multiple mild and/or moderate facial/scalp AKs.Methods Phase III, 12 week, multi-centre, randomised, investigator-blinded, controlled, intra-individual study conducted at different latitudes in Europe. AKs of adult subjects were treated once with methyl aminolevulinate (MAL) DL-PDT on one side of the face and MAL c-PDT contralaterally. Endpoints for DL-PDT concerned efficacy (non-inferiority regarding complete lesion response at week 12) and safety (superiority regarding subject's assessment of pain after treatment, on an 11-point numeric rating scale). Safety evaluation also included incidence of adverse events. Subject satisfaction was described using a questionnaire at baseline and last visit.ResultsAt week 12, the total lesion complete response rate with DL-PDT was similar (non-inferior) to c-PDT (70% vs. 74%, respectively; 95% CI [−9.5; 2.4] in PP analysis, confirmed in ITT analysis). In addition, efficacy of DL-PDT was demonstrated regardless of weather conditions (sunny or cloudy). DL-PDT was nearly painless compared to c-PDT (0.7 vs. 4.4, respectively; P < 0.001), better tolerated and resulted in higher subject satisfaction.ConclusionDL-PDT in comparison with c-PDT was as effective, better tolerated and nearly painless with high patient satisfaction, and may be considered a treatment of choice to meet needs of patients with mild or moderate facial/scalp AKs.
    Journal of the European Academy of Dermatology and Venereology 10/2015; DOI:10.1111/jdv.13228 · 2.83 Impact Factor
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    ABSTRACT: Vemurafenib is a BRAF inhibitor indicated in metastatic or unresectable melanoma in patients with BRAF mutations. Vemurafenib is frequently toxic, but the toxicity is often not serious. The third case of vemurafenib-induced drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is reported herein. The case is unusual in that the onset was early, with symptoms emerging as of day 8 of treatment. Treatment of DRESS syndrome is not currently based on precise recommendations, but systemic corticosteroid therapy is effective in serious cases. Severe toxidermias under vemurafenib are exceptional; immediate discontinuation of treatment upon diagnosis is imperative. Switching from vemurafenib to dabrafenib then seems to constitute an interesting therapeutic alternative, since its efficacy is the same but with fewer cutaneous adverse reactions. This case highlights the importance of awareness of the risk of DRESS syndrome associated with vemurafenib and monitoring for warning signs from treatment initiation.
    Dermatology 09/2015; DOI:10.1159/000439272 · 1.57 Impact Factor
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    ABSTRACT: Purpose: Whereas vismodegib is effective in the treatment of locally advanced/metastatic basal cell carcinoma, dysgeusia and weight loss are common side effects of such treatment. The main objective of this study was to monitor the nutritional status of vismodegib-treated patients. Secondary objective was to assess the incidence of dysgeusia and the benefit of early nutritional management. Methods: This prospective study included all patients who started vismodegib between October 2011 and May 2013 at Nantes University Hospital. Prior to July 2012, patients treated with vismodegib had not received any specific nutritional management (Historical cohort). Body weight and presence of dysgeusia were recorded monthly. Patients treated after July 2012 (Nutrition cohort) were evaluated by a physician of the Nutrition Support Unit and received dietary counseling at vismodegib initiation. A standardized nutritional management protocol was initiated in case of significant weight loss. Results: Forty-five patients (21 and 24 in the Nutrition and Historical cohort, respectively) were enrolled. In the Nutrition cohort, five patients (24 %) were undernourished at vismodegib initiation, and the 6-month cumulative incidence of dysgeusia was 71 %. Eight patients (38 %) and 13 patients (54 %) had a weight loss greater than 5 % in the Nutrition and Historical cohort, respectively (p = 0.3727). Conclusion: The results of this pilot study suggest the benefit of early nutritional screening. The potential benefit of nutritional support in this setting warrants further investigation.
    Supportive Care in Cancer 09/2015; DOI:10.1007/s00520-015-2932-1 · 2.36 Impact Factor

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    ABSTRACT: Only a few studies have focused on the description of sexual well-being in patients with vulvar disease (VD). The aim of this study was to test the hypothesis that VD patients have an overall impaired sexual well-being that varies depending on the type of VD. An observational, prospective, single center and 1:1 matched case-control study was conducted in Nantes University Hospital (France). All new patients attending the specific consultation for VD between June 2011 and January 2013 were included. A control group was randomly selected from women who had a scheduled consultation for gynecologic follow-up. A validated French version of the Female Sexual Function Index (FSFI) was used. This self-administered questionnaire was distributed to all case and control women. VD was classified into 4 groups: inflammatory, (pre)malignant, infectious, and other VD. Descriptive statistics and multivariate mixed analyses were performed. Seventy-two VD patients and seventy-two control women completed the FSFI questionnaire. The median FSFI score was 21.1 in the VD patients versus 28.1 in the control patients. In the multivariate analysis, the FSFI score was significantly decreased by an average of 4.5 points (p=0.003) in the VD patients. On the FSFI subscores, VD had significant impacts on items related to "arousal", "pain", "lubrication", "satisfaction", and "desire". When comparing the VD groups, the total FSFI score seemed lower for (pre)malignant VD. This preliminary study showed that VD patients had an impaired sexual well-being. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    European journal of obstetrics, gynecology, and reproductive biology 08/2015; 194:106-110. DOI:10.1016/j.ejogrb.2015.08.011 · 1.70 Impact Factor
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    ABSTRACT: is missing (Short communication).
    Acta Dermato-Venereologica 08/2015; DOI:10.2340/00015555-2199 · 3.03 Impact Factor
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    ABSTRACT: New targeted melanoma therapies such as B-RAF inhibitors have shown high and promising clinical benefit but have cutaneous side-effects, including photosensitivity, which is triggered in the UVA radiation spectrum. However, visible spectrum implication has not yet been investigated. We conducted a study to determine whether visible light also contributes to the phototoxicity action spectrum of vemurafenib. The secondary end points were to determine the time to complete regression of the phototoxicity post-vemurafenib discontinuation and whether there was a significant difference between the UVA radiation immediate reactivity cut-offs, in patients treated with vemurafenib vs. those treated with dabrafenib. This prospective, observational study included patients with B-RAF mutant metastatic melanoma: 34 patients treated with vemurafenib and 9 with dabrafenib. The visible-light phototest results in patients treated with vemurafenib were all negative before and after 2 months of treatment. The UVA radiation phototests conducted 1 or 2 weeks post-vemurafenib discontinuation in 4 patients showed a normalised UVA-radiation reactivity cut-off. UVA radiation phototests after 2 months of treatment were conducted for all patients. The UVA radiation reactivity cut-off had been lowered for 30 patients (88%) on vemurafenib and 3 patients (33%) on dabrafenib. The median UVA radiation reactivity cut-off was 12 J/cm(2) for the patients on vemurafenib and 20 J/cm(2) for the patients on dabrafenib. B-RAF inhibitor phototoxicity is exclusively triggered by UVA radiation and resolves rapidly post-treatment discontinuation. A significant difference between the UVA immediate reactivity cut-offs, vemurafenib vs. dabrafenib, explains the difference in the clinical photosensitivity rates reported in the clinical trials.
    08/2015; DOI:10.1684/ejd.2015.2628
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    ABSTRACT: Objective To evaluate the efficacy of a targeted screening for melanoma in high-risk patients following the receipt of a mailed invitation to an annual skin examination by a general practitioner (GP). Methods A prospective cohort study was conducted in a primary care setting in western France. A total of 3897 patients at elevated risk of melanoma (identified using the Self-Assessment of Melanoma Risk Score) consented to participate in a targeted melanoma screening project in 2011. One year later, the participants were invited by mail to consult their GP for an annual skin examination. Efficacy of the procedure was evaluated according to patient participation and the number of melanomas detected. The consultation dates and results were collected during the 12 months postreminder and were analysed using SAS. Analyses of whether participation decreased compared with that during the year of inclusion and whether populations at risk for thick melanoma showed reduced participation in the screening were performed. Results Of the 3745 patients who received the mailed invitation, 61% underwent a skin examination. The participation of patients at risk for thick melanoma (any patient over 60 years of age and men over 50 years of age) was significantly greater than that of the patients in the other subgroups (72.4% vs 49.6%, p<0.001; and 66% vs 52.4%, p<0.001, respectively). The patients referred to the dermatologist after 1 year were more compliant compared with those referred during the first year (68.8% vs 59.1%, p=0.003). Six melanomas were detected within 1 year postreminder; therefore, the incidence of melanoma in the study population was 160/100 000. Conclusions This study confirms the benefits of developing a targeted screening strategy in primary care. In particular, after the annual reminder, patient participation and the diagnosis of melanoma remained high in the patients at elevated risk of thick melanomas. Trial registration number NCT01610531.
    BMJ Open 07/2015; 5(7):e007471. DOI:10.1136/bmjopen-2014-007471 · 2.27 Impact Factor
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    ABSTRACT: To date, the term 'acne mechanica' defines different cutaneous lesions caused by mechanical injury. To re-define the spectrum of cutaneous lesions caused by mechanical injury by determining their clinical and histological characteristics, to discuss and identify triggering and pathophysiologic elements. Clinical, histological and pathophysiological differences of 135 published cases of acne mechanica were analysed and compared to cases provided from our clinics. Mechanical factors cause 2 types of mainly inflammatory cutaneous lesions: one presents with inflammatory papules, open comedones or has no comedonal lesions. We propose using the term 'folliculitis mechanica'. The second type corresponds to a flare-up of acne in areas prone to the condition. These lesions present the typical clinical and histological features of acne vulgaris, comprising inflammatory and retentional lesions. Treatment may include topical products, including adjunctive care for reconstruction of the cutaneous barrier and the microbiome. Conventional acne medication should be used in cases of acne flare-up.
    06/2015; 25(2). DOI:10.1684/ejd.2014.2502
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  • H P M Gollnick · B Dreno ·

    Journal of the European Academy of Dermatology and Venereology 06/2015; 29 Suppl 4(S4):1-2. DOI:10.1111/jdv.13182 · 2.83 Impact Factor
  • B Dréno ·
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    ABSTRACT: Acne is affecting an increasing number of adult females and so can no longer be considered as a disease of adolescence. The disease has a greater negative impact on the quality of life of adult females than their younger counterparts. Adult female acne may persist from adolescence or may have its first occurrence once adulthood has been reached. The clinical presentation and pathogenesis of adult female acne may be somewhat different to that of adolescent acne and this may require a different treatment approach. Genetic and hormonal factors are thought to play key roles in the pathogenesis of adult female acne and the disease is characterized by a chronic evolution with frequent relapses requiring long-term maintenance therapy. Fixed-dose retinoid/antimicrobial combinations may be of interest for the treatment of adult female acne given that subgroup analysis of clinical trials has indicated that they are effective against both inflammatory and non-inflammatory lesions in these patients. These treatments may also be of interest, given the chronic course of the disease in adult females, the high likelihood of the presence of antibiotic-resistant P. acnes and the poor adherence of patients to other long-term therapies. Oral hormonal treatment or isotretinoin may be required in patients with severe acne or disease that is refractory to other treatments. Additional clinical studies of acne treatments specifically conducted in adult female patients are required to increase the evidence base on which future treatment recommendations can be based. © 2015 European Academy of Dermatology and Venereology.
    Journal of the European Academy of Dermatology and Venereology 06/2015; 29 Suppl 5(S5):14-9. DOI:10.1111/jdv.13188 · 2.83 Impact Factor
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    ABSTRACT: Acne has long been understood to have a complex physiological basis involving several main factors: hormonally-stimulated sebum production, abnormal keratinization of the pilosebaceous duct, and an inflammatory immune response to Propionibacterium acnes. Recent studies at the molecular and cellular level have begun clarifying how all of these factors interact, and the role of the innate immune system is better appreciated. Inflammation has been demonstrated in all acne lesions - the preclinical microcomedo, comedones, inflammatory lesions, 'post-inflammatory' erythema or hyperpigmentation, and scarring. Inflammation localized to the pilosebaceous unit can be considered the defining feature of acne and should be addressed via multiple therapeutic pathways. Clinicians tend to think oral antibiotics should be used to 'calm' inflammatory acne, but there is good evidence showing that topical retinoids also have anti-inflammatory properties as a class effect. For best therapeutic outcomes, most patients with acne should be treated first line with a topical retinoid plus an antimicrobial agent, as has been demonstrated in thousands of patients involved in clinical trials and recommended by the Global Alliance to Improve Outcomes in Acne for more than a decade. Moving away from reliance on antibiotic therapy for acne is particularly important in an era of worsening antimicrobial resistance and worldwide calls to reduce antibiotic use. Improved understanding about the role of P. acnes and the innate immune system in acne should help clinicians in designing efficacious treatment strategies. © 2015 European Academy of Dermatology and Venereology.
    Journal of the European Academy of Dermatology and Venereology 06/2015; 29 Suppl 4(S4):3-11. DOI:10.1111/jdv.13190 · 2.83 Impact Factor
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    ABSTRACT: Background: Nivolumab (a programmed death 1 [PD-1] checkpoint inhibitor) and ipilimumab (a cytotoxic T-lymphocyte-associated antigen 4 [CTLA-4] checkpoint inhibitor) have been shown to have complementary activity in metastatic melanoma. In this randomized, double-blind, phase 3 study, nivolumab alone or nivolumab plus ipilimumab was compared with ipilimumab alone in patients with metastatic melanoma. Methods: We assigned, in a 1:1:1 ratio, 945 previously untreated patients with unresectable stage III or IV melanoma to nivolumab alone, nivolumab plus ipilimumab, or ipilimumab alone. Progression-free survival and overall survival were coprimary end points. Results regarding progression-free survival are presented here. Results: The median progression-free survival was 11.5 months (95% confidence interval [CI], 8.9 to 16.7) with nivolumab plus ipilimumab, as compared with 2.9 months (95% CI, 2.8 to 3.4) with ipilimumab (hazard ratio for death or disease progression, 0.42; 99.5% CI, 0.31 to 0.57; P<0.001), and 6.9 months (95% CI, 4.3 to 9.5) with nivolumab (hazard ratio for the comparison with ipilimumab, 0.57; 99.5% CI, 0.43 to 0.76; P<0.001). In patients with tumors positive for the PD-1 ligand (PD-L1), the median progression-free survival was 14.0 months in the nivolumab-plus-ipilimumab group and in the nivolumab group, but in patients with PD-L1-negative tumors, progression-free survival was longer with the combination therapy than with nivolumab alone (11.2 months [95% CI, 8.0 to not reached] vs. 5.3 months [95% CI, 2.8 to 7.1]). Treatment-related adverse events of grade 3 or 4 occurred in 16.3% of the patients in the nivolumab group, 55.0% of those in the nivolumab-plus-ipilimumab group, and 27.3% of those in the ipilimumab group. Conclusions: Among previously untreated patients with metastatic melanoma, nivolumab alone or combined with ipilimumab resulted in significantly longer progression-free survival than ipilimumab alone. In patients with PD-L1-negative tumors, the combination of PD-1 and CTLA-4 blockade was more effective than either agent alone. (Funded by Bristol-Myers Squibb; CheckMate 067 ClinicalTrials.gov number, NCT01844505.).
    New England Journal of Medicine 05/2015; 373(1). DOI:10.1056/NEJMoa1504030 · 55.87 Impact Factor

Publication Stats

12k Citations
2,167.38 Total Impact Points


  • 1995-2015
    • University of Nantes
      • Faculté de Médecine
      Naoned, Pays de la Loire, France
  • 1993-2015
    • Centre Hospitalier Universitaire de Nantes
      • • Service de dermatologie
      • • Service de génétique médicale
      Naoned, Pays de la Loire, France
  • 1997-2014
    • Hotel Dieu Hospital
      Kingston, Ontario, Canada
    • Centre D'Etudes Et De Recherche Sur Les Qualifications
      Marsiglia, Provence-Alpes-Côte d'Azur, France
  • 2013
    • Erasmus MC
      Rotterdam, South Holland, Netherlands
  • 2009-2013
    • Hôtel-Dieu de Paris – Hôpitaux universitaires Paris Centre
      Lutetia Parisorum, Île-de-France, France
  • 2002-2013
    • Unité Inserm U1077
      Caen, Lower Normandy, France
  • 2012
    • CHU de Lyon - Groupement Hospitalier Edouard Herriot
      Lyons, Rhône-Alpes, France
  • 1986-2012
    • French Institute of Health and Medical Research
      • Unit of Immunology, Dermatology, Oncology
      Lutetia Parisorum, Île-de-France, France
  • 2010
    • New York Presbyterian Hospital
      • Department of Dermatology
      New York, New York, United States
  • 2007
    • Université Paris-Est Créteil Val de Marne - Université Paris 12
      Créteil, Île-de-France, France
    • Centre Hospitalier Universitaire de Nancy
      Laxou, Lorraine, France
  • 2006
    • Ludwig Institute for Cancer Research
      لا هویا, California, United States
  • 2005
    • Société Française de Cardiologie
      Lutetia Parisorum, Île-de-France, France
  • 1998
    • Centre Hospitalier Universitaire de Dijon
      Dijon, Bourgogne, France
  • 1990
    • Centre Hospitalier Universitaire de Limoges
      Limages, Limousin, France