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Melanoma: HELP
Articles by Marie Therese Leccia
Based on 26 articles published since 2008
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Between 2008 and 2019, M. T. Leccia wrote the following 26 articles about Melanoma.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Guideline [Locoregional treatments of brain metastases for patients with metastatic cutaneous melanoma: French national guidelines]. 2014

Lubrano, V / Derrey, S / Truc, G / Mirabel, X / Thariat, J / Cupissol, D / Sassolas, B / Combemale, P / Modiano, P / Bedane, C / Dygai-Cochet, I / Lamant, L / Mourrégot, A / Rougé Bugat, M-È / Siegrist, S / Tiffet, O / Mazeau-Woynar, V / Verdoni, L / Planchamp, F / Leccia, M-T / Anonymous610807. ·Service de neurochirurgie, hôpital de Rangueil, CHU de Toulouse, 1, avenue du Professeur-Jean-Poulhès, TSA 50032, 31059 Toulouse, France. · Département de neurochirurgie, hôpital Charles-Nicolle, 1, rue de Germont, 76000 Rouen, France. · Département de radiothérapie, centre Georges-François-Leclerc, 1, rue du Professeur-Marion, BP 77980, 21079 Dijon, France. · Département de radiothérapie-curiethérapie, centre Oscar-Lambret, 3, rue Frédéric-Combemale, BP 307, 59020 Lille, France. · Pôle de radiothérapie, centre Antoine-Lacassagne, 33, avenue de Valombrose, 06189 Nice, France. · Service d'oncologie médicale, ICM, institut du cancer de Montpellier Val-d'Aurelle, 208, avenue des Apothicaires, parc Euromédecine, 34298 Montpellier, France. · Service de dermatologie, hôpital Cavale-Blanche, boulevard Tanguy-Prigent, 29609 Brest, France. · Unité onco-dermatologie, centre Léon Bérard, 28, rue Laennec, 69008 Lyon, France. · Service de dermatologie, hôpital Saint-Vincent-de-Paul, boulevard de Belfort, BP 387, 59020 Lille, France. · Service de dermatologie, hôpital Dupuytren, 2, avenue Martin-Luther-King, 87042 Limoges, France. · Service de médecine nucléaire, centre Georges-François-Leclerc, 1, rue du Professeur-Marion, BP 77980, 21079 Dijon, France. · Service d'anatomie pathologique, hôpital Purpan, place Baylac, 31059 Toulouse, France. · Service de chirurgie oncologique, ICM, institut du cancer de Montpellier Val-d'Aurelle, 208, avenue des Apothicaires, parc Euromédecine, 34298 Montpellier, France. · Cabinet médical, 59, rue de la Providence, 31500 Toulouse, France. · Cabinet médical, 3, rue Saint-Sigisbert, 57050 le Ban-Saint-Martin, France. · Service de chirurgie générale et thoracique, centre hospitalier universitaire, 42055 Saint-Étienne, France. · Direction des recommandations et de la qualité de l'expertise, Institut national du cancer, 52, avenue André-Morizet, 92513 Boulogne-Billancourt, France. · Direction des recommandations et de la qualité de l'expertise, Institut national du cancer, 52, avenue André-Morizet, 92513 Boulogne-Billancourt, France. Electronic address: recommandations@institutcancer.fr. · Clinique de dermatolo-vénéréologie, photobiologie et allergologie, pôle pluridisciplinaire de médecine, hôpital Michallon, 38043 Grenoble, France. ·Neurochirurgie · Pubmed #25241016.

ABSTRACT: INTRODUCTION: The management of metastatic cutaneous melanoma is changing, marked by innovative therapies. However, their respective use and place in the therapeutic strategy continue to be debated by healthcare professionals. OBJECTIVE: The French national cancer institute has led a national clinical practice guideline project since 2008. It has carried out a review of these modalities of treatment and established recommendations. METHODS: The clinical practice guidelines development process is based on systematic literature review and critical appraisal by experts. The recommendations are thus based on the best available evidence and expert agreement. Prior to publication, the guidelines are reviewed by independent practitioners in cancer care delivery. RESULTS: This article presents the results of bibliographic search, the conclusions of the literature and the recommendations concerning locoregional treatments of brain metastases for patients with metastatic cutaneous melanoma.

2 Guideline [Management of patients with metastatic cutaneous melanoma: French national guidelines. French National Cancer Institute]. 2014

Leccia, M-T / Planchamp, F / Sassolas, B / Combemale, P / Modiano, P / Bedane, C / Cupissol, D / Derrey, S / Dygai-Cochet, I / Lamant, L / Lubrano, V / Mirabel, X / Mourrégot, A / Rougé Bugat, M-E / Siegrist, S / Thariat, J / Tiffet, O / Truc, G / Verdoni, L / Mazeau-Woynar, V. ·Pôle pluridisciplinaire de médecine, clinique de dermatolo-vénéréologie, photobiologie et allergologie, hôpital Michallon, 38043 Grenoble, France. · Direction des recommandations et de la qualité de l'expertise, Institut national du cancer, 52, avenue André-Morizet, 92513 Boulogne-Billancourt, France. Electronic address: recommandations@institutcancer.fr. · Service de dermatologie, hôpital Cavale Blanche, boulevard Tanguy-Prigent, 29609 Brest, France. · Unité onco-dermatologie, centre Léon-Bérard, 28, rue Laennec, 69008 Lyon, France. · Service de dermatologie, hôpital Saint-Vincent-de-Paul, boulevard de Belfort, BP 387, 59020 Lille, France. · Service de dermatologie, hôpital Dupuytren, 2, avenue Martin-Luther-King, 87042 Limoges, France. · Service d'oncologie médicale, ICM, institut du cancer de Montpellier Val-d'Aurelle, parc Euromédecine, 208, avenue des Apothicaires, 34298 Montpellier, France. · Département de neurochirurgie, hôpital Charles-Nicolle, 1, rue de Germont, 76000 Rouen, France. · Service de médecine nucléaire, centre Georges-François-Leclerc, 1, rue du Professeur-Marion, BP 77980, 21079 Dijon, France. · Service d'anatomie pathologique, hôpital Purpan, place Baylac, 31059 Toulouse, France. · Service de neurochirurgie, hôpital de Rangueil, 1, avenue du Professeur-Jean-Poulhès, TSA 50032, 31059 Toulouse, France. · Département de radiothérapie-curiethérapie, centre Oscar-Lambret, 3, rue Frédéric-Combemale, BP 307, 59020 Lille, France. · Service de chirurgie oncologique, ICM, institut du cancer de Montpellier Val-d'Aurelle, parc Euromédecine, 208, avenue des Apothicaires, 34298 Montpellier, France. · Cabinet médical, 59, rue de la Providence, 31500 Toulouse, France. · Cabinet médical, 3, rue Saint-Sigisbert, 57050 Le Ban-Saint-Martin, France. · Pôle de radiothérapie, centre Antoine-Lacassagne, 33, avenue de Valombrose, 06189 Nice, France. · Service de chirurgie générale et thoracique, centre hospitalier universitaire de Saint-Étienne, 42055 Saint-Étienne, France. · Département de radiothérapie, centre Georges-François-Leclerc, 1, rue du Professeur-Marion, BP 77980, 21079 Dijon, France. · Direction des recommandations et de la qualité de l'expertise, Institut national du cancer, 52, avenue André-Morizet, 92513 Boulogne-Billancourt, France. ·Ann Dermatol Venereol · Pubmed #24507205.

ABSTRACT: BACKGROUND: Recent years have seen the emergence of new molecules for the treatment of patients with metastatic cutaneous melanoma, with significant benefits in terms of survival and the opening of new therapeutic perspectives. In addition, many techniques are currently being developed for locoregional treatment of metastatic sites. Management of metastatic melanoma is thus fast-changing and is marked by innovative therapeutic approaches. However, the availability of these new treatments has prompted debate among healthcare professionals concerning their use and their place in therapeutic strategy. AIMS: Since 2008, the French National Cancer Institute (INCa) has been leading a project to define and diffuse national clinical practice guidelines. It has performed a review of these treatment methods, which it aims to circulate, and it is seeking to develop recommendations in order to allow nationwide implementation of innovative approaches while promoting good use thereof. METHODS: The clinical practice guidelines development process is based on systematic literature review and critical appraisal by experts within a multidisciplinary working group, with feedback from specialists in cancer care delivery. The recommendations are thus based on the best available evidence and expert agreement. Prior to publication, the guidelines are reviewed by independent practitioners in cancer care delivery. RESULTS: This article presents the national recommendations for first- and second-line systemic treatment and for locoregional treatment of metastatic sites in patients presenting metastatic cutaneous melanoma.

3 Guideline [Loco-regional treatments of the metastatic sites for patients with pauci-metastatic cutaneous melanoma (without brain metastasis): French national guidelines]. 2014

Sassolas, Bruno / Mourrégot, Anne / Thariat, Juliette / Tiffet, Olivier / Dygai-Cochet, Inna / Mirabel, Xavier / Truc, Gilles / Cupissol, Didier / Modiano, Philippe / Combemale, Patrick / Bedane, Christophe / Derrey, Stéphane / Lamant, Laurence / Lubrano, Vincent / Siegrist, Sophie / Rougé-Bugat, Marie-Ève / Mazeau-Woynar, Valérie / Verdoni, Laëtitia / Planchamp, François / Leccia, Marie-Thérèse. ·Hôpital Cavale Blanche, boulevard Tanguy-Prigent, 29609 Brest, France. · Institut du Cancer de Montpellier Val-d'Aurelle, parc Euromédecine, 208, avenue des Apothicaires, 34298 Montpellier, France. · Centre Antoine-Lacassagne, 33, avenue de Valombrose, 06189 Nice, France. · Centre hospitalier universitaire de Saint-Étienne, 42055 Saint-Étienne, France. · Centre Georges-François-Leclerc, 1, rue du Professeur-Marion, BP 77980, 21079 Dijon, France. · Centre Oscar-Lambret, 3, rue Frédéric-Combemale, BP 307, 59020 Lille, France. · Hôpital Saint-Vincent-de-Paul, boulevard de Belfort, BP 387, 59020 Lille, France. · Centre Léon-Bérard, 28, rue Laënnec, 69008 Lyon, France. · Hôpital Dupuytren, 2, avenue Martin-Luther-King, 87042 Limoge, France. · Hôpital Charles-Nicolle, 1, rue de Germont, 76000 Rouen, France. · Hôpital Purpan, place Baylac, 31059 Toulouse, France. · Hôpital de Rangueil, 1, avenue du Professeur-Jean-Poulhès, TSA 50032, 31059 Toulouse, France. · Cabinet médical, 3, rue Saint-Sigisbert, 57050Le Ban-Saint-Martin, France. · Cabinet médical, 59, rue de la Providence, 31500 Toulouse, France. · Institut national du cancer, 52, avenue André-Morizet, 92513 Boulogne-Billancourt, France. · Hôpital Michallon, 38043 Grenoble, France. ·Bull Cancer · Pubmed #24369290.

ABSTRACT: INTRODUCTION: The last years are marked by the emergence of new molecules for the treatment of metastatic cutaneous melanoma with a significant benefit on the survival. Besides, some techniques are in development for the loco-regional treatment of the metastatic sites, bringing new therapeutic perspectives. However, their respective use and place in the therapeutic strategy are debated by healthcare professionals. OBJECTIVE: The French National Cancer Institute leads a national clinical practice guidelines project since 2008. It realized a review of these modalities of treatment and developed recommendations. METHODS: The clinical practice guidelines development process is based on systematic literature review and critical appraisal by a multidisciplinary expert workgroup. The recommendations are thus based on the best available evidence and expert agreement. Prior to publication, the guidelines are reviewed by independent practitioners in cancer care delivery. RESULTS: This article presents recommendations for loco-regional treatments of the pulmonary, bone, cutaneous, hepatic and digestive metastatic sites for patients with pauci-metastatic cutaneous melanoma.

4 Review Plasma Circulating Tumor DNA Levels for the Monitoring of Melanoma Patients: Landscape of Available Technologies and Clinical Applications. 2017

Busser, Benoit / Lupo, Julien / Sancey, Lucie / Mouret, Stéphane / Faure, Patrice / Plumas, Joel / Chaperot, Laurence / Leccia, Marie Thérèse / Coll, Jean Luc / Hurbin, Amandine / Hainaut, Pierre / Charles, Julie. ·Biochemistry Pharmacology and Toxicology Department, Grenoble University Hospital, Grenoble, France. · Institute for Advanced Biosciences, UGA/INSERM U1209/CNRS UMR5309, Grenoble, France. · Virology Laboratory, Grenoble University Hospital, Grenoble, France. · Institut de Biologie Structurale, CEA-CNRS UMR 5075/UGA, Grenoble, France. · Dermatology Unit, Grenoble University Hospital, Grenoble, France. · UGA, Laboratory of Hypoxy Physiopathology Study, INSERM U1042, Grenoble, France. · EFS Rhone-Alpes-Auvergne, Grenoble, France. ·Biomed Res Int · Pubmed #28484715.

ABSTRACT: Melanoma is a cutaneous cancer with an increasing worldwide prevalence and high mortality due to unresectable or metastatic stages. Mutations in

5 Review [Systemic treatment of melanoma brain metastases]. 2015

Le Rhun, É / Mateus, C / Mortier, L / Dhermain, F / Guillot, B / Grob, J-J / Lebbe, C / Thomas, M / Jouary, T / Leccia, M-T / Robert, C. ·Neuro-oncologie, département de neurochirurgie, hôpital Roger-Salengro, CHRU, rue Émile-Laine, 59037 Lille cedex, France; Oncologie médicale, centre Oscar-Lambret, 3, rue Frédéric-Combemale, BP 307, 59020 Lille cedex, France; Inserm U1192, laboratoire Prism, université Lille 1, bâtiment SN3 1(er) étage, 59655 Villeneuve-d'Ascq cedex, France; Groupe de réflexion sur la prise en charge des métastases cérébrales (GRPCMaC), 13273 Marseille cedex 09, France. Electronic address: emilie.lerhun@chru-lille.fr. · Département de dermatologie, institut de cancérologie Gustave-Roussy, 114, rue Édouard-Vaillant, 94805 Villejuif cedex, France. · Département de dermatologie, centre hospitalier régional et universitaire de Lille, 2, avenue Oscar-Lambret, 59037 Lille cedex, France. · Groupe de réflexion sur la prise en charge des métastases cérébrales (GRPCMaC), 13273 Marseille cedex 09, France; Département de radiothérapie, institut de cancérologie Gustave-Roussy, 114, rue Édouard-Vaillant, 94805 Villejuif cedex, France; Réunion de concertation pluridisciplinaire de neuro-oncologie, institut de cancérologie Gustave-Roussy, 114, rue Édouard-Vaillant, 94805 Villejuif cedex, France. · Département de dermatologie, centre hospitalier universitaire, 80, avenue Augustin-Fliche, 34295 Montpellier cedex 5, France; Université Montpellier 1, 5, boulevard Henri-IV, CS 19044, 34967 Montpellier cedex 2, France. · Département de dermatologie, centre hospitalo-universitaire, AP-HM, 264, rue Saint-Pierre, 13385 Marseille cedex 05, France. · Département de dermatologie, hôpital Saint-Louis, Assistance publique-Hôpitaux de Paris, 1, avenue Claude-Vellefaux, 75010 Paris, France. · Service de dermatologie, pôle d'oncologie-radiothérapie, de dermatologie et des soins palliatifs, groupe hospitalier Saint-André, centre hospitalier universitaire de Bordeaux, 1, rue Jean-Burguet, 33075 Bordeaux, France. · Clinique de dermatologie, d'allergologie et de photobiologie, centre hospitalier Albert-Michallon, boulevard de la Chantourne, BP 217, 38043 Grenoble cedex 9, France; Inserm U832, institut A.-Bonniot, 38043 Grenoble cedex 09, France. ·Cancer Radiother · Pubmed #25656856.

ABSTRACT: Melanomas have a high rate of brain metastases. Both the functional prognosis and the overall survival are poor in these patients. Until now, surgery and radiotherapy represented the two main modalities of treatment. Nevertheless, due to the improvement in the management of the extracerebral melanoma, the systemic treatment may be an option in patients with brain metastases. Immunotherapy with anti-CTLA4 (cytotoxic T-lymphocyte-associated protein 4) - ipilimumab - or BRAF (serine/threonine-protein kinase B-raf) inhibitors - vemurafenib, dabrafenib - has shown efficacy in the management of brain metastases in a- or pauci-symptomatic patients. Studies are ongoing with anti-PD1 (programmed cell death 1) and combinations of targeted therapies associating anti-RAF (raf proto-oncogene, serine/threonine kinase) and anti-MEK (mitogen-activated protein kinase kinase).

6 Review [Mechanisms of resistance to anti-BRAF treatments]. 2014

Charles, J / Martel, C / de Fraipont, F / Leccia, M-T / Robert, C / Busser, B. ·Centre de recherche Inserm/UJF U823, institut Albert-Bonniot, BP 170, 38042 Grenoble cedex 9, France; Dermatologie, CHU de Grenoble, CS 10217, 38043 Grenoble cedex 9, France. · Centre de recherche Inserm/UJF U823, institut Albert-Bonniot, BP 170, 38042 Grenoble cedex 9, France. · Unité médicale de biochimie des cancers et biothérapies, institut de biologie et pathologie, CHU de Grenoble, CS 10217, 38043 Grenoble cedex 09, France. · Inserm U981, Institut Gustave-Roussy, 114, rue Edouard-Vaillant, 94805 Villejuif-Paris-Sud, France. · Centre de recherche Inserm/UJF U823, institut Albert-Bonniot, BP 170, 38042 Grenoble cedex 9, France. Electronic address: bbusser@chu-grenoble.fr. ·Ann Dermatol Venereol · Pubmed #25442471.

ABSTRACT: CONTEXT: In patients with melanoma positive for the BRAF V600 mutation, clinical response to specific BRAF inhibitors is usually rapid and striking, with significant benefits in terms of progression-free survival and overall survival. However, resistance to treatment almost invariably arises, typically within a median timeframe of 6 months. Indeed, very few patients exhibit long-lasting response to these targeted therapies. AIMS: It is essential to better understand the mechanisms of resistance to targeted anti-BRAF therapies in order to increase both response rates and the duration of clinical response to treatment. This literature review describes the signaling pathways involving BRAF and presents recent data from clinical trials with these molecules. Furthermore, we aim to describe the main resistance mechanisms linked with targeted anti-BRAF therapies. METHODS: The keywords (resistance, BRAF, melanoma, targeted therapy, vemurafenib, and dabrafenib) were used to extract relevant articles in the Medline/Pubmed database published before 31 January 2014. DISCUSSION: Improved knowledge and understanding of the mechanisms of resistance to targeted anti-BRAF therapies should enable the development of new therapeutic strategies in order to overcome such resistance and allow more significant and sustained response rates to be achieved among melanoma patients.

7 Review Phototoxicity and photocarcinogenesis associated with voriconazole. 2011

Epaulard, O / Leccia, M-T / Blanche, S / Chosidow, O / Mamzer-Bruneel, M-F / Ravaud, P / Thiebaut, A / Villier, C / Lortholary, O. ·Service des maladies infectieuses et de médecine tropicale, CHU de Grenoble, France. OEpaulard@chu-grenoble.fr ·Med Mal Infect · Pubmed #22055586.

ABSTRACT: The antifungal voriconazole was given its marketing authorization in 2002. Several kinds of adverse effects have been reported, including acute and chronic cutaneous adverse effects, mainly due to a phototoxicity mechanism. More recently, some authors have reported that voriconazole was involved in the occurrence of multiple and often-aggressive cutaneous squamous cell carcinomas if the treatment was maintained for a long time. According to safety data in studies assessing voriconazole effectiveness, 8% of outpatients may experience phototoxic events. An overview of the different types of phototoxicity and of the concerned population was given by the 61 published case reports of photo-induced voriconazole-related skin adverse events (including 18 cases of squamous cell carcinomas). The most likely mechanisms may be phototoxicity directly related to either voriconazole or to its N-oxide main metabolite, and an interaction with retinoid metabolism; moreover, immunodeficiency may enhance the risk of skin cancer. Several issues remain to be investigated, and studies are needed concerning the phototoxicity and photocarcinogenesis of voriconazole and the prognosis of chronic non-malignant skin lesions. Voriconazole prescription must be associated with strict photoprotection; in case of a phototoxic adverse event, another azole may be recommended.

8 Clinical Trial Treatment patterns and outcomes in patients with advanced melanoma in France. 2013

Bedane, Christophe / Leccia, Marie-Thérèse / Sassolas, Bruno / Bregman, Bruno / Lebbé, Céleste / Anonymous4020762. ·Hôpital Dupuytren, CHU de Limoges , Limoges , France. ·Curr Med Res Opin · Pubmed #23808961.

ABSTRACT: BACKGROUND: Melanoma is associated with high mortality and poor response to standard chemotherapy. In order to benchmark benefits of recently introduced treatments, outcome with standard chemotherapy in everyday practice should be documented. OBJECTIVES: To document treatment pathways in patients with advanced melanoma, to compare clinical outcomes between treatment lines, and to measure associated healthcare resource utilisation in terms of hospital visits and adverse event management. METHODS: An observational, longitudinal survey of patients with unresectable stage III/IV melanoma in France evaluated 278 patients with ≥ 2 months follow-up. Data were collected retrospectively for 2-3 years following the index consultation. Treatment history was documented and outcomes determined for each treatment line. Complete and partial response rates were compared between treatment lines. Overall and progression-free survival were determined by Kaplan-Meier analysis. Health resource utilisation was documented hospitalisations, hospice stays, emergency room visits, outpatient visits and adverse event management. RESULTS: In total, 271 patients (97.5%) received first-line therapy, 161 (57.9%) second-line therapy and 85 (30.6%) third-line therapy. The most frequent first-line therapy strategies were systemic treatment alone (46.5%) or in combination with surgery (22.9%). The most frequently used chemotherapy was dacarbazine monotherapy (62.3% of chemotherapy). Median duration of first-line systemic therapy was 11.9 (IQR: 6.6-24.0) weeks. First-line therapy was discontinued in 190 patients (68.3%), principally due to disease progression (150 patients). Median overall survival was 17.1 (95% CI: 14.6-20.1) months since diagnosis, 9.5 (95% CI: 6.7-12.8) months since initiation of first-line therapy and 5.3 (95% CI: 3.7-7.2) months since initiation of second-line therapy. Median progression-free survival time was 2.8 (95% CI: 2.5-3.3) months. Ninety-six patients (40.2%) received medication to manage adverse events and 131 patients (47.1%) required hospitalisation (mean: 3.1 hospitalisations; mean duration: 27 days). STUDY LIMITATIONS: The retrospective data collection precludes ascertainment of medical information and completion of missing data. CONCLUSIONS: Existing therapies provide limited survival benefit to patients with unresectable stage III/IV melanoma. New more effective treatment options are needed.

9 Clinical Trial Adjuvant therapy with pegylated interferon alfa-2b (36 months) versus low-dose interferon alfa-2b (18 months) in melanoma patients without macrometastatic nodes: an open-label, randomised, phase 3 European Association for Dermato-Oncology (EADO) study. 2013

Grob, Jean Jacques / Jouary, Thomas / Dréno, Brigitte / Asselineau, Julien / Gutzmer, Ralf / Hauschild, Axel / Leccia, Marie Thérèse / Landthaler, Michael / Garbe, Claus / Sassolas, Bruno / Herbst, Rudolf A / Guillot, Bernard / Chene, Genevieve / Pehamberger, Hubert. ·Aix-Marseille University, CRO2, Service de Dermatologie, Hopital de Timone, 264 Rue St Pierre, 13885 Marseille CEDEX 05, Marseille, France. jean-jacques.grob@ap-hm.fr ·Eur J Cancer · Pubmed #22975216.

ABSTRACT: AIM: Both low-dose interferon (IFN) alfa-2b and pegylated interferon (Peg-IFN) alfa-2b have been shown to be superior to observation in the adjuvant treatment of melanoma without macrometastatic nodes, but have never been directly compared. Peg-IFN facilitates prolongation of treatment, which could provide additional benefit. This multicentre, open-label, randomised, phase 3 trial compared standard low-dose interferon IFN and prolonged treatment with Peg-IFN. PATIENTS AND METHODS: Patients with resected melanoma ≥1.5mm thick and without clinically detectable node metastases were randomised 1:1 to treatment with IFN 3 MU subcutaneously (SC) three times weekly for 18 months or Peg-IFN 100 μg SC once weekly for 36 months. Sentinel lymph node dissection (SLND) was optional. The primary endpoint was disease-free survival (DFS). Secondary endpoints included distant metastasis-free survival (DMFS), overall survival (OS) and adverse events (AEs) grade 3-4. RESULTS: Of 898 patients enrolled, 896 (443 Peg-IFN, 453 IFN) were eligible for evaluation (median follow-up 4.7 years). SLND was performed in 68.2% of patients. There were no statistical differences between the two arms for the primary outcome of DFS (hazard ratio [HR] 0.91, 95% confidence interval [CI] 0.73-1.15) or the secondary outcomes of DMFS (HR 1.02, 95% CI 0.80-1.32) and OS (HR 1.09, 95% CI 0.82-1.45). Peg-IFN was associated with higher rates of grade 3-4 AEs (47.3% versus 25.2%; p<0.0001) and discontinuations (54.3% versus 30.4%) compared with IFN. CONCLUSION: This trial did not show superiority for adjuvant Peg-IFN over conventional low-dose IFN in melanoma patients without clinically detectable nodes. ClinicalTrials.gov identifier: NCT00221702.

10 Article Real-world treatment patterns and clinical outcomes in advanced cutaneous melanoma patients in France. 2018

Sassolas, B / Leccia, M T / Godard, C / Benmahamed, L / Flinois, A / Levy-Bachelot, L / Bédane, C. ·Hôpital Morvan, CHU de Brest, Brest, France. · Hôpital Michallon, CHU de Grenoble, Grenoble, France. · MSD France, Courbevoie, France. · Kantar Health, Paris, France. · Hôpital Dupuytren, CHU de Limoges, Limoges, France. ·J Eur Acad Dermatol Venereol · Pubmed #28960564.

ABSTRACT: BACKGROUND: Since 2011, the management of advanced melanoma has radically changed with the availability of new therapies (immunotherapy and BRAF-targeted therapy) and with BRAF testing. OBJECTIVES: Following the introduction of these new therapies, the objectives of this AMEL study were to describe treatment patterns and evaluate overall survival (OS) among unresectable stage III/IV melanoma patients, in a real-life setting in France. METHODS: The AMEL study is a multicentre retrospective record review study. Thirty-three physicians working in 33 unique treatment centres participated in the study. Two hundred and sixty-four patients diagnosed between 1 January 2012 and 31 October 2012 with unresectable stage III/IV melanoma were included in the study. RESULTS: 94.7% of the patients received a first-line antitumour drug treatment, 62.5% a second-line treatment while 26.9% received a third-line treatment with no significant differences between patients with a BRAF mutation (50.4%) and BRAF wild type (47.0%). First-line treatment differs according to the BRAF status: 74.8% of patients with a BRAF mutation received a BRAF inhibitor while 79.3% of the BRAF wild-type patients were treated with conventional chemotherapy. In second line and over, the treatment patterns were more heterogeneous, depending on the BRAF mutation, the treatment received previously, the speed of progression of the disease and the availability of immunotherapy at the time the treatment was initiated. CONCLUSION: Regardless of the BRAF mutation status, the median OS of patients was 16 months (95% CI = 14-18). Compared to a similar study conducted in 2007 (MELODY), a gain of 4 months is observed. The gain seems to be higher for patients with a BRAF mutation (18 months) than for those without a BRAF mutation (14 months). The OS of patients who sequentially received both a BRAF inhibitor and ipilimumab (28 months) highlights the benefit of this treatment sequence.

11 Article The avidity of tumor-specific T cells amplified by a plasmacytoid dendritic cell-based assay can predict the clinical evolution of melanoma patients. 2018

Charles, Julie / Chaperot, Laurence / Revol, Bruno / Baudin, Marine / Mouret, Stephane / Hamon, Agnes / Leccia, Marie-Therese / Plumas, Joel / Aspord, Caroline. ·University Grenoble Alpes, Grenoble, France. · Immunobiology& Immunotherapy of Chronic Diseases, U1209, INSERM, La Tronche, France. · Dermatology, Pôle Pluridisciplinaire de Médecine, CHU Grenoble Alpes, Grenoble, France. · R&D Laboratory, Etablissement Français du Sang Rhone-Alpes, La Tronche, France. · Pharmacovigilance Department, CHU Grenoble Alpes, Grenoble, France. · Laboratoire Jean Kuntzmann, Universite Grenoble Alpes, Grenoble, France. ·Pigment Cell Melanoma Res · Pubmed #28741900.

ABSTRACT: The advent of immune checkpoint blockers and targeted therapies has changed the outcome of melanoma. However, many patients experience relapses, emphasizing the need for predictive and prognostic biomarkers. We developed a strategy based on plasmacytoid dendritic cells (pDCs) loaded with melanoma tumor antigens that allows eliciting highly efficient antitumor T-cell responses. We used it to investigate antitumor T-cell functionality in peripheral blood mononuclear cells and tumor-infiltrating lymphocytes from melanoma patients. The pDCs elicited tumor-specific T cells in different proportions and displaying diverse functional features, dependent upon the stage of the disease, but independent of the histological parameters at diagnosis. Strikingly, the avidity of the MelA-specific T cells triggered by the pDCs was found to predict patient relapse time and overall survival. Our findings highlighted unexplored aspects of antitumor T-cell responsiveness in melanoma, and revealed for the first time the structural avidity of tumor-specific T cells as a crucial feature for predicting clinical evolution.

12 Article Mucosal melanoma: clinical, histological and c-kit gene mutational profile of 86 French cases. 2017

Cinotti, E / Chevallier, J / Labeille, B / Cambazard, F / Thomas, L / Balme, B / Leccia, M T / D'Incan, M / Vercherin, P / Douchet, C / Rubegni, P / Perrot, J L. ·Department of Dermatology, University Hospital of Saint Etienne, Saint Etienne, France. · Department of Medical, Surgical and Neurological Science, Dermatology Section, University of Siena, S. Maria alle Scotte Hospital, Siena, Italy. · Dermatology Department, University Hospital of Lyon Sud, Pierre Bénite, France. · Dermatopathology Department, University Hospital of Lyon Sud, Pierre Bénite, France. · Department of Dermatology, University Hospital of Grenoble, Grenoble, France. · Dermatology Department, University Hospital of Clermont-Ferrand, Clermont-Ferrand, France. · Department of Public Health and Medical Information, University Hospital of Saint Etienne, Saint Etienne, France. · Department of Pathology, University Hospital of Saint Etienne, Saint Etienne, France. ·J Eur Acad Dermatol Venereol · Pubmed #28543798.

ABSTRACT: BACKGROUND: Mucosal melanomas are rare and highly aggressive tumours. Few studies evaluated mucosal melanomas of locations other than the head and neck region, and other than those of the Asian population. OBJECTIVES: The objective of this study was to analyse the clinical and histological features, as well as the mutational status of c-kit and b-raf gene of mucosal melanoma in any localization in a French series. METHODS: We investigated clinical (sex, age, performance status, survival, treatment of the patients and lack of pigmentation of the tumours) and histopathological features (ulceration, Breslow's index, mitotic rate), as well as the mutational status of c-kit and b-raf of 86 mucosal melanomas diagnosed in 15 years in four French University Hospitals. RESULTS: Most melanomas affected women (72%) and the genital region (46.5%). A fifth of melanomas were amelanotic. 81% of melanomas had a Breslow's index ≥1, whereas all glans melanomas, and most vulvar melanomas had a Breslow index ≤1 mm. Overall survival was 54% at 3 years; 11.6% of the 43 tested mucosal melanomas were c-kit-mutated while the 15 tested genital melanomas were not. The c-kit gene mutation did not influence the overall survival. Age ≥ 50, amelanotic type and performance status ≥1 were not poor prognostic factors in our series. CONCLUSION: This study confirmed that mucosal melanomas are rare and could be difficult to diagnose being often amelanotic and in hidden sites. Most melanomas were thick at the diagnosis, but glans and vulvar melanomas were thinner probably because of their greater visibility. The frequency of the c-kit mutation varied depending on the initial tumour site. In our series, the prognosis was poor, independently from c-kit mutations and the patient's general health and age. The presence of metastasis at diagnosis was associated with a worse prognosis indicating the importance of an early diagnosis.

13 Article PARKIN Inactivation Links Parkinson's Disease to Melanoma. 2016

Hu, Hui-Han / Kannengiesser, Caroline / Lesage, Suzanne / André, Jocelyne / Mourah, Samia / Michel, Laurence / Descamps, Vincent / Basset-Seguin, Nicole / Bagot, Martine / Bensussan, Armand / Lebbé, Céleste / Deschamps, Lydia / Saiag, Philippe / Leccia, Marie-Thérèse / Bressac-de-Paillerets, Brigitte / Tsalamlal, Amel / Kumar, Rajiv / Klebe, Stephan / Grandchamp, Bernard / Andrieu-Abadie, Nathalie / Thomas, Luc / Brice, Alexis / Dumaz, Nicolas / Soufir, Nadem. ·Affiliations of authors: INSERM, U976, Centre de Recherche sur la Peau, Hôpital Saint Louis , Paris , France (HHH, JA, SM, LM, VD, NBS, MB, AB, CL, ND, NS) · AP-HP, Hôpital Bichat Claude Bernard, Département de Génétique , Paris , France (HHH, CK, AT, BG, NS) · Université Paris Diderot, Sorbonne Paris Cité , UMRS976, Paris , France (HHH, CK, JA, LM, NBS, MB, AB, LD, AT, BG, ND, NS) · Université Paris 6, INSERM UMRS975, Centre de Recherche de l'Institut du Cerveau et de la Moelle Epinière, Hôpital Pitié-Salpêtrière, AP-HP , Paris , France (SL, AB) · INSERM, U940, Laboratoire de Pharmacologie, Hôpital Saint Louis Paris , France (SM) · AP-HP, Hôpital Bichat Claude Bernard, Service de Dermatologie , Paris , France (VD) · AP-HP, Hôpital Saint Louis, Service de Dermatologie , Paris , France (NBS, MB, CL, ND) · INSERM, CRB3, Département de Pathologie, Hôpital Bichat, AP-HP , Paris , France (LD) · AP-HP, Hôpital Ambroise Paré, Service de Dermatologie , Boulogne Billancourt , France (PS) · CHU Grenoble, Service de Dermatologie , Grenoble , France (MTL) · Gustave Roussy, Service de Génétique, Département de Biopathologie , Villejuif , France (BBdP) · Division of Molecular Genetic Epidemiology, German Cancer Research Center, Im Neuenheimer Feld 580 , Heidelberg , Germany (RK) · Department of Neurology, University Hospital of Würzburg , Würzburg , Germany (SK) · Inserm UMR1037, Centre de Recherche en Cancérologie de Toulouse , Toulouse , France (NAA) · Hôpital de l'Hôtel-Dieu, Service de Dermatologie , Lyon , France (LT) · AP-HP, Groupe Pitié-Salpêtrière, Département de Génétique, Cytogénétique et Embryologie , Paris , France (AB). ·J Natl Cancer Inst · Pubmed #26683220.

ABSTRACT: BACKGROUND: Melanoma incidence is higher in patients affected by Parkinson's disease (PD) and vice versa, but the genetic link shared by both diseases is unknown. As PARK2 is both a tumor suppressor gene and frequently mutated in young onset PD, we evaluated the role of PARK2 in melanoma predisposition and progression. METHODS: An in-depth PARK2 gene dosage analysis and sequencing was performed on 512 French case patients and 562 healthy control patients, as well as sporadic tumors and melanoma cell lines. The frequency of genetic alterations was compared between case patients and control patients using two-sided Fisher's exact tests and odds ratio (OR) calculations. We used western blotting to determine PARKIN expression in melanocytes and melanoma cell lines and transfection followed by clonogenic assays to evaluate the effect of PARKIN expression on cellular proliferation. All statistical tests were two-sided. RESULTS: Germline PARK2 mutations (including copy number variations, splicing, and putative deleterious missense mutations) were present in 25 case patients but only four control patients (OR = 3.95, 95% confidence interval = 1.34 to 15.75). Copy number variations (CNVs) and loss of heterozygosity were present in 60% and 74%, respectively, of primary tumors. PARKIN protein was expressed in melanocytes but not in most melanoma cell lines, and its expression decreased following melanocyte transformation by oncogenic NRAS. Re-expression of PARKIN in melanoma cell lines resulted in a drastic reduction of cell proliferation and inhibition of PARKIN in melanocytes stimulated their proliferation. CONCLUSION: Our results show an important role for PARK2 as a tumor suppressor both in melanoma predisposition and progression, which could explain the epidemiological association of these diseases.

14 Article [Recommendations for genetic testing and management of individuals genetically at-risk of cutaneous melanoma]. 2015

Avril, M-F / Bahadoran, P / Cabaret, O / Caron, O / de la Fouchardière, A / Demenais, F / Desjardins, L / Frébourg, T / Hammel, P / Leccia, M-T / Lesueur, F / Mahé, E / Martin, L / Maubec, E / Remenieras, A / Richard, S / Robert, C / Soufir, N / Stoppa-Lyonnet, D / Thomas, L / Vabres, P / Bressac-de Paillerets, B. ·Service de dermatologie, groupe hospitalier Cochin-Saint-Vincent-de-Paul, AP-HP, pavillon Tarnier, 89, rue d'Assas, 75006 Paris, France. · Inserm U895, service de dermatologie, hôpital Archet 2, CHU, 151, route Saint-Antoine-Ginestiere, BP 79, 06200 Nice cedex 3, France. · Service de génétique, département de biologie et pathologie médicales, Gustave-Roussy, 114, rue Édouard-Vaillant, 94805 Villejuif cedex, France. · Consultation d'oncogénétique, Gustave-Roussy, 114, rue Édouard-Vaillant, 94805 Villejuif, France. · Département de biopathologie, centre Léon-Bérard, 28, rue Laennec, 69008 Lyon, France. · Inserm, UMR946, variabilité génétique et maladies humaines, fondation Jean-Dausset, CEPH, 27, rue Juliette-Dodu, 75010 Paris, France. · Service d'ophtalmologie, institut Curie, 26, rue d'Ulm, 75231 Paris cedex 05, France. · Inserm U1079, service de génétique, CHU de Rouen, IRIB, faculté de médecine et de pharmacie, 22, boulevard Gambetta, 76183 Rouen cedex, France. · Service de gastro-entérologie-pancréatologie, hôpital Beaujon, AP-HP, 100, boulevard du Général-Leclerc, 92118 Clichy cedex, France. · Service de dermatologie, CHU Michallon, BP 217, 38043 Grenoble cedex 9, France. · Inserm U900, équipe épidémiologie génétique des cancers, institut Curie, 26, rue d'Ulm, 75248 Paris cedex 05, France. · Service de dermatologie, centre hospitalier Victor-Dupouy, 69, rue du Lieutenant-Colonel-Prud'hon, 95107 Argenteuil cedex, France. · Service de dermatologie, CHU d'Angers, université d'Angers, 4, rue Larrey, 49933 Angers cedex 9, France. · Inserm, UMR946, variabilité génétique et maladies humaines, fondation Jean-Dausset, CEPH, 27, rue Juliette-Dodu, 75010 Paris, France; Service de dermatologie, hôpital Bichat, AP-HP, 46, rue Henri-Huchard, 75018 Paris, France. · Département d'oncologie génétique, institut Paoli-Calmettes, 232, boulevard Saint-Marguerite, 13273 Marseille cedex 9, France. · Service d'urologie, hôpital Bicêtre, Centre expert national cancers rares INCa PREDIR, 78, rue du Général-Leclerc, 94275 Le Kremlin-Bicêtre cedex, France. · Service de dermatologie, Gustave-Roussy, 114, rue Édouard-Vaillant, 94805 Villejuif, France. · Inserm U976, laboratoire de génétique moléculaire, unité fonctionnelle de génétique, hôpital Xavier-Bichat-Claude-Bernard, AP-HP, Paris 7 université, 75018 Paris, France. · Inserm U830, service de génétique, département de biologie des tumeurs, institut Curie, 26, rue d'Ulm, 75231 Paris cedex 05, France. · Service de dermatologie, centre hospitalier Lyon Sud, université Lyon 1, 165, chemin du Grand-Revoyet, 69495 Pierre-Bénite cedex, France. · Service de dermatologie, CHU de Dijon, BP 77908, 21079 Dijon cedex, France. · Service de génétique, département de biologie et pathologie médicales, Gustave-Roussy, 114, rue Édouard-Vaillant, 94805 Villejuif cedex, France. Electronic address: brigitte.bressac@gustaveroussy.fr. ·Ann Dermatol Venereol · Pubmed #25600792.

ABSTRACT: Cutaneous melanoma is a multifactorial disease resulting from both environmental and genetic factors. Five susceptibility genes have been identified over the past years, comprising high-risk susceptibility genes (CDKN2A, CDK4, and BAP1 genes) and intermediate-risk susceptibility genes (MITF, and MC1R genes). The aim of this expert consensus was to define clinical contexts justifying genetic analyses, to describe the conduct of these analyses, and to propose surveillance recommendations. Given the regulatory constraints, it is recommended that dermatologists work in tandem with a geneticist. Genetic analysis may be prescribed when at least two episodes of histologically proven invasive cutaneous melanoma have been diagnosed before the age of 75 years in two 1st or 2nd degree relatives or in the same individual. The occurrence in the same individual or in a relative of invasive cutaneous melanoma with ocular melanoma, pancreatic cancer, renal cancer, mesothelioma or a central nervous system tumour are also indications for genetic testing. Management is based upon properly managed photoprotection and dermatological monitoring according to genetic status. Finally, depending on the mutated gene and the familial history, associated tumour risks require specific management (e.g. ocular melanoma, pancreatic cancer). Due to the rapid progress in genetics, these recommendations will need to be updated regularly.

15 Article [Acantholytic dermatosis in patients treated by vemurafenib: 2 cases]. 2014

Sabatier-Vincent, M / Charles, J / Pinel, N / Challende, I / Claeys, A / Leccia, M-T. ·Clinique de dermatologie et photobiologie, hôpital Nord, CHU de Grenoble, Cs 10217, boulevard de la-Chantourne-La-Tronche, 38043 Grenoble cedex 9, France. Electronic address: msabatiervincent@chu-grenoble.fr. · Clinique de dermatologie et photobiologie, hôpital Nord, CHU de Grenoble, Cs 10217, boulevard de la-Chantourne-La-Tronche, 38043 Grenoble cedex 9, France. · Département d'anatomie pathologique, CHU de Grenoble, Cs 10217, 38043 Grenoble cedex 9, France. ·Ann Dermatol Venereol · Pubmed #25442474.

ABSTRACT: BACKGROUND: Acantholytic dyskeratosis under BRAF inhibitors are dermatological diseases rarely reported to date. PATIENTS AND METHODS: We report 2 cases of acantholytic dyskeratosis, reaching the trunk and the seborrheic zones, not itchy, appeared one month after the introduction of vemurafenib. The histological analysis was typical of a "Grover-like rash" for the 2 patients. DISCUSSION: The appearance of acantholytic dyskeratosis under vemurafenib, a BRAF inhibitor, seems related with a paradoxical activation of the MAP-kinases pathway and with a growth acceleration of lesions in which RAS mutations of keratinocytes. Theses dermatoses seem also to occur with dabrafenib. CONCLUSION: The patients treated by BRAF inhibitors (vemurafenib and dabrafenib) can present acantholytic dyskeratosis. The arisen of this mild dermatosis does not question, of course, the continuation of the treatment. These cutaneous manifestations can be managed with emollients.

16 Article Imiquimod inhibits melanoma development by promoting pDC cytotoxic functions and impeding tumor vascularization. 2014

Aspord, Caroline / Tramcourt, Laetitia / Leloup, Claire / Molens, Jean-Paul / Leccia, Marie-Therese / Charles, Julie / Plumas, Joel. ·R&D Laboratory, Etablissement Français du Sang Rhône-Alpes, La Tronche, France; University Joseph Fourier, Grenoble, France; Immunobiology & Immunotherapy of Cancers, U823, INSERM, La Tronche, France. Electronic address: carolineaspord@yahoo.com. · R&D Laboratory, Etablissement Français du Sang Rhône-Alpes, La Tronche, France; University Joseph Fourier, Grenoble, France; Immunobiology & Immunotherapy of Cancers, U823, INSERM, La Tronche, France. · University Joseph Fourier, Grenoble, France; Immunobiology & Immunotherapy of Cancers, U823, INSERM, La Tronche, France; Department of Dermatology, Grenoble University Hospital, Grenoble, France. ·J Invest Dermatol · Pubmed #24751730.

ABSTRACT: Imiquimod (IMQ) is a synthetic Toll-like receptor (TLR7/8) ligand that can trigger antiviral and antitumor activities. Despite evidence of potent therapeutic effects, the clinical use of IMQ in melanoma is impeded by incomplete understanding of its mechanisms of action. Mice and humans differ in many aspects of immunity, including TLR7 expression patterns, thus impeding the use of mouse models in translating discoveries into clinical applications. In this article, we investigated the mechanisms behind IMQ effects in vivo in a human context of melanoma and immunity using an innovative melanoma-bearing humanized mouse model. In this model, IMQ strongly inhibited melanoma tumor development through prompt mobilization of plasmacytoid dendritic cells and by triggering their cytotoxic functions, and through upregulation of expression of type 1 IFN response genes. IMQ also drastically impeded tumor vascularization by inducing the downregulation of angiogenic factors vascular endothelial growth factor, angiogenin, IL-8, and fibroblast growth factor. Our results revealed the short- and long-term multifactorial effects of IMQ converging toward inhibition of melanoma development. By providing a better understanding of the mechanisms of action of IMQ in melanoma, our study opens the way for its further clinical use in the treatment of metastatic melanoma.

17 Article Plasmacytoid dendritic cells support melanoma progression by promoting Th2 and regulatory immunity through OX40L and ICOSL. 2013

Aspord, Caroline / Leccia, Marie-Therese / Charles, Julie / Plumas, Joel. ·Authors' Affiliations: Department of Dermatology, Grenoble University Hospital, Grenoble, France. ·Cancer Immunol Res · Pubmed #24778133.

ABSTRACT: Even though melanoma is considered to be one of the most immunogenic solid tumors, handling its development remains a challenge. The basis for such escape from antitumor immune control has not yet been documented. Plasmacytoid dendritic cells (pDC) are emerging as crucial but still enigmatic cells in cancer. In melanoma, the function of tumor-infiltrating pDCs remains poorly explored. We investigated the pathophysiologic role of pDCs in melanoma, both ex vivo from a large cohort of melanoma patients and in vivo in melanoma-bearing humanized mice. pDCs were found in high proportions in cutaneous melanoma and tumor-draining lymph nodes, yet associated with poor clinical outcome. We showed that pDCs migrating to the tumor microenvironment displayed particular features, subsequently promoting proinflammatory Th2 and regulatory immune profiles through OX40L and ICOSL expression. Elevated frequencies of interleukin (IL)-5-, IL-13- and IL-10-producing T cells in patients with melanoma correlated with high proportions of OX40L- and ICOSL-expressing pDCs. Strikingly TARC/CCL17, MDC/CCL22, and MMP-2 found in the melanoma microenvironment were associated with pDC accumulation, OX40L and ICOSL modulation, and/or early relapse. Thus, melanoma actively exploits pDC plasticity to promote its progression. By identifying novel insights into the mechanism of hijacking of immunity by melanoma, our study exposes potential for new therapeutic opportunities.

18 Article Identification of a novel complex BRAF mutation associated with major clinical response to vemurafenib in a patient with metastatic melanoma. 2013

Busser, Benoit / Leccia, Marie Therese / Gras-Combe, Guillaume / Bricault, Ivan / Templier, Isabelle / Claeys, Antoine / Richard, Marie Jeanne / de Fraipont, Florence / Charles, Julie. ·Institut Albert Bonniot INSERM/UJF U823, Grenoble, France. · Department of Neurosurgery, CHRU Grenoble University Hospital, Grenoble, France. · Department of Medical Imaging, CHRU Grenoble University Hospital, Grenoble, France. · Department of Dermatology, CHRU Grenoble University Hospital, Grenoble, France. · Department of Cancer Clinical Chemistry, CHRU Grenoble University Hospital, Grenoble, France. ·JAMA Dermatol · Pubmed #24108467.

ABSTRACT: IMPORTANCE: There is an increasing interest in BRAF V600 mutations in melanomas and their associated sensitivity to vemurafenib, a BRAF inhibitor. However, physicians cannot find information in the literature about vemurafenib response for rare and/or atypical BRAF mutations. OBSERVATIONS: We describe the identification of a novel complex BRAF mutation associated with major clinical response to vemurafenib in a patient with metastatic melanoma. Using a pyrosequencing method, we determined that the tumor positive for mutated BRAF, uncovering a novel c.1799_1803delinsAT; p.V600-K601>D variant. We uncovered this atypical BRAF mutation with 2 different sequencing methods, both in the primary lesion and in 1 metastasis. The patient was immediately treated with vemurafenib as monotherapy and achieved a prolonged (5.5-month) positive response. CONCLUSIONS AND RELEVANCE: We analyzed the consequences of the BRAF V600-K601>D mutation in terms of amino acids. We referred to the published data and databases to screen chemical properties of well-known BRAF V600 mutations and other complex BRAF mutations to find common features of activated BRAF mutations. Importantly, we highlighted that both the site of the mutation and the involved amino acids are important to predict vemurafenib response. Our conclusion is that complex BRAF mutation surrounding codon 600 could also be sensitive to BRAF inhibitors.

19 Article Familial melanoma: clinical factors associated with germline CDKN2A mutations according to the number of patients affected by melanoma in a family. 2012

Maubec, Eve / Chaudru, Valérie / Mohamdi, Hamida / Blondel, Christophe / Margaritte-Jeannin, Patricia / Forget, Sébastien / Corda, Eve / Boitier, Françoise / Dalle, Stéphane / Vabres, Pierre / Perrot, Jean-Luc / Lyonnet, Dominique Stoppa / Zattara, Hélène / Mansard, Sandrine / Grange, Florent / Leccia, Marie-Thérèse / Vincent-Fetita, Lynda / Martin, Ludovic / Crickx, Béatrice / Joly, Pascal / Thomas, Luc / Anonymous6380732 / Bressac-de Paillerets, Brigitte / Avril, Marie-Françoise / Demenais, Florence. ·INSERM (Institut National de Santé et de Recherche Médicale), Genetic Variation and Human Diseases Unit (U946), Paris, France. eve.maubec@bch.aphp.fr ·J Am Acad Dermatol · Pubmed #22841127.

ABSTRACT: BACKGROUND: Features associated with an increased frequency of cyclin-dependent kinase inhibitor 2A (CDKN2A) mutations have been identified in families with 3 or more patients with cutaneous melanoma (CM). However, in families with 2 patients with CM, which represent the majority of familial melanoma, these factors have been rarely studied. OBJECTIVE: We investigated association of 3 clinical features with the presence of a CDKN2A mutation in a family by extent of CM family clustering (2 vs ≥3 patients with CM among first-degree relatives in a family). METHODS: We included 483 French families that comprised 387 families with 2 patients with CM (F2 families) and 96 families with 3 or more patients with CM (F3+ families). Three clinical factors were examined individually and in a joint analysis: median age at diagnosis younger than 50 years, and 1 or more patient in a family with multiple primary melanoma or with pancreatic cancer. RESULTS: The frequency of CDKN2A mutations was higher in F3+ families (32%) than in F2 families (13%). Although early age at melanoma diagnosis and occurrence of multiple primary melanoma in 1 or more patient were significantly associated with the risk of a CDKN2A mutation in F2 families, early age at melanoma diagnosis and occurrence of pancreatic cancer in a family were significantly associated with CDKN2A mutations in F3+ families. LIMITATIONS: The study was not population based. CONCLUSIONS: This study shows that factors associated with CDKN2A mutations differ by extent of CM family clustering. It indicates that, in France, families with 2 patients with CM are eligible for genetic testing especially when there is an early age at CM diagnosis and/or 1 or more patients with multiple primary melanoma.

20 Article HLA-A(*)0201(+) plasmacytoid dendritic cells provide a cell-based immunotherapy for melanoma patients. 2012

Aspord, Caroline / Leccia, Marie-Therese / Salameire, Dimitri / Laurin, David / Chaperot, Laurence / Charles, Julie / Plumas, Joel. ·Etablissement Français du Sang Rhone-Alpes, R&D Laboratory, La Tronche, France; University Joseph Fourier, Grenoble, France; INSERM U823, Immunobiology & Immunotherapy of Cancers, La Tronche, France. Electronic address: carolineaspord@yahoo.com. · University Joseph Fourier, Grenoble, France; INSERM U823, Immunobiology & Immunotherapy of Cancers, La Tronche, France; Department of Dermatology, Michallon Hospital, Pôle Pluridisciplinaire de Médecine, Grenoble, France. · University Joseph Fourier, Grenoble, France; INSERM U823, Immunobiology & Immunotherapy of Cancers, La Tronche, France; Anatomo-cytopathology, Michallon Hospital, Grenoble, France. · Etablissement Français du Sang Rhone-Alpes, R&D Laboratory, La Tronche, France; University Joseph Fourier, Grenoble, France; INSERM U823, Immunobiology & Immunotherapy of Cancers, La Tronche, France. · Etablissement Français du Sang Rhone-Alpes, R&D Laboratory, La Tronche, France; University Joseph Fourier, Grenoble, France; INSERM U823, Immunobiology & Immunotherapy of Cancers, La Tronche, France; University College London, Cancer Institute, London, UK. ·J Invest Dermatol · Pubmed #22696054.

ABSTRACT: Several sources of evidence suggest that tumor-specific T cells have the potential to control melanoma tumors. Current active and adoptive therapeutic approaches to elicit such T cells are either not sufficiently clinically efficient or require fastidious processes that impede their extensive clinical use. As plasmacytoid dendritic cells (pDCs) have a crucial role in triggering antitumor immunity especially in melanoma, we explored their potential as a cell-based approach for melanoma immunotherapy. An irradiated human HLA-A(*)0201(+) pDC line loaded with peptides derived from the major melanoma tumor antigens, MelA/MART-1, gp100/pmel17, tyrosinase, and MAGE-A3, was used to trigger functional multi-specific T cells ex vivo from peripheral blood mononuclear cells and tumor-infiltrating lymphocytes from stage I-IV HLA-A(*)0201(+) melanoma patients. pDCs loaded with melanoma-derived peptides promptly induced high levels of melanoma tumor-specific T cells from both sources. pDC-primed central/effector memory antitumor T cells were highly functional as indicated by the specific IFNγ secretion and membrane CD107 expression upon stimulation. Cells also exhibited strong cytotoxicity toward semi-allogeneic melanoma cells and patient-derived tumor cells. The simple design and potent efficacy of this promising approach provides a preclinical basis for the development of a pDC-based vaccine and an alternative means to produce tumor-specific T cells for adoptive cellular immunotherapy in melanoma patients.

21 Article Sentinel lymph node biopsy for melanoma is becoming a consensus: a national survey of French centres involved in melanoma care in 2008. 2012

Lourari, S / Paul, C / Gouraud, P-A / Tavitian, S / Viraben, R / Leccia, M-T / Saiag, P / Lebbe, C / Meyer, N / Anonymous4070705. ·Dermatology Department, Paul Sabatier - Toulouse III University and Hôpital Larrey, Toulouse, France. ·J Eur Acad Dermatol Venereol · Pubmed #21929549.

ABSTRACT: BACKGROUND: The role of sentinel lymph node (SLN) biopsy in melanoma care remains controversial and is not included in most guidelines for the management of melanoma in Europe. OBJECTIVE: To evaluate the practice of SLN biopsy for melanoma. METHODS: In 2008, a self-administered questionnaire was mailed to physicians in 49 hospitals in France. RESULTS: Questionnaires were returned by 34 (69.3%). A median number of 90 new cases of melanoma were treated each year per centre. SLN biopsy was performed routinely in 21 (61.7%) centres. The practice of SLN biopsy for melanoma was recommended in the local guidelines in 53% of centres. The proportion of patients reported as undergoing SLN biopsy for melanoma was significantly higher in centres with local guidelines than in centres without local guidelines (33.4 ± 21.4% vs. 13.1 ± 21.8%; P = 0.003). Where the local guidelines recommended SLN biopsy (n = 21), it was advocated in the case of Breslow thickness ≥1.0 mm (76%) and/or ulceration of the primary melanoma (38%) and/or histological regression of the primary melanoma (24%). CONCLUSION: Our study may be considered representative of SLN practice in France. Contrary to current national guidelines for melanoma care in France, SLN biopsy is routinely recommended in the majority of centres. Our study shows that the practice of SLN biopsy for melanoma is increasingly performed in patients with intermediate Breslow melanoma.

22 Article [GENiusVac, a novel antitumor vaccine strategy based on allogeneic plasmacytoid dendritic cells]. 2011

Aspord, C / Charles, J / Leccia, M-T / Laurin, D / Richard, M-J / Chaperot, L / Plumas, J. ·Inserm U823, Établissement français du sang (EFS) Rhone-Alpes, R&D Laboratory, 38701 La Tronche, France. carolineaspord@yahoo.com ·Rev Med Interne · Pubmed #21429635.

ABSTRACT: The development of effective vaccines against cancer and viruses still remains a challenge. Many immunotherapeutic strategies have been developed but without sufficient therapeutic success. Plasmacytoid dendritic cells (pDC) play a crucial role in antitumor and antiviral responses. Despite their outstanding functional properties, their therapeutic potential has not yet been worked out. We propose a new immunotherapeutic strategy based on a pDC cell line irradiated and pulsed with tumor or viral antigens. GENiusVac allows the induction of multispecific and highly functional cytotoxic cell responses directed against viral or tumor targets. We demonstrated the potential of this strategy in vitro, its therapeutic efficacy in vivo in a humanized mouse model, and its clinical relevance ex vivo from melanoma patients' cells. GENiusVac highlights pDCs as potent vector of immunotherapy and provide a way to exploit them in cell therapy to fight cancer or chronic viral infections.

23 Article A novel cancer vaccine strategy based on HLA-A*0201 matched allogeneic plasmacytoid dendritic cells. 2010

Aspord, Caroline / Charles, Julie / Leccia, Marie-Therese / Laurin, David / Richard, Marie-Jeanne / Chaperot, Laurence / Plumas, Joel. ·Etablissement Français du Sang Rhone-Alpes, R&D Laboratory, La Tronche, France. carolineaspord@yahoo.com ·PLoS One · Pubmed #20454561.

ABSTRACT: BACKGROUND: The development of effective cancer vaccines still remains a challenge. Despite the crucial role of plasmacytoid dendritic cells (pDCs) in anti-tumor responses, their therapeutic potential has not yet been worked out. We explored the relevance of HLA-A*0201 matched allogeneic pDCs as vectors for immunotherapy. METHODS AND FINDINGS: Stimulation of PBMC from HLA-A*0201(+) donors by HLA-A*0201 matched allogeneic pDCs pulsed with tumor-derived peptides triggered high levels of antigen-specific and functional cytotoxic T cell responses (up to 98% tetramer(+) CD8 T cells). The pDC vaccine demonstrated strong anti-tumor therapeutic in vivo efficacy as shown by the inhibition of tumor growth in a humanized mouse model. It also elicited highly functional tumor-specific T cells ex-vivo from PBMC and TIL of stage I-IV melanoma patients. Responses against MelA, GP100, tyrosinase and MAGE-3 antigens reached tetramer levels up to 62%, 24%, 85% and 4.3% respectively. pDC vaccine-primed T cells specifically killed patients' own autologous melanoma tumor cells. This semi-allogeneic pDC vaccine was more effective than conventional myeloid DC-based vaccines. Furthermore, the pDC vaccine design endows it with a strong potential for clinical application in cancer treatment. CONCLUSIONS: These findings highlight HLA-A*0201 matched allogeneic pDCs as potent inducers of tumor immunity and provide a promising immunotherapeutic strategy to fight cancer.

24 Article Characterization of circulating dendritic cells in melanoma: role of CCR6 in plasmacytoid dendritic cell recruitment to the tumor. 2010

Charles, Julie / Di Domizio, Jérémy / Salameire, Dimitri / Bendriss-Vermare, Nathalie / Aspord, Caroline / Muhammad, Ramzan / Lefebvre, Christine / Plumas, Joël / Leccia, Marie-Thérèse / Chaperot, Laurence. ·INSERM U823, Centre de Recherche Albert Bonniot, Immunobiologie et Immunothérapie des Cancers, Université Joseph Fourier, R&D Laboratory, EFS Rhônes-Alpes, 29 Avenue Maquis du Gresivaudan, La Tronche, France. ·J Invest Dermatol · Pubmed #20220766.

ABSTRACT: Dendritic cells (DCs) are central cells in the development of antitumor immune responses, but the number and function of these cells can be altered in various cancers. Whether these cells are affected during the development of melanoma is not known. We investigated the presence, phenotype, and functionality of circulating myeloid DCs (MDCs) and plasmacytoid DCs (PDCs) in newly diagnosed melanoma patients, compared to controls. The frequencies of PDCs and MDCs were equivalent in melanoma patients as compared with normal subjects. Both circulating DC subsets were immature, but on ex vivo stimulation with R848 they efficiently upregulated their expression of costimulatory molecules. We found that circulating DCs from melanoma patients and controls displayed similar pattern of expression of the chemokine receptors CXCR3, CXCR4, CCR7, and CCR10. Strikingly, PDCs from melanoma patients expressed higher levels of CCR6 than control PDCs, and were able to migrate toward CCL20. Further data showed that CCR6-expressing PDCs were present in melanoma primary lesions, and that CCL20 was produced in melanoma tumors. These results suggest that PDCs and MDCs are functional in melanoma patients at the time of diagnosis, and that CCL20 may participate to their recruitment from the blood to the tumor.

25 Article Management and outcome of metastatic melanoma during pregnancy. 2010

Pagès, C / Robert, C / Thomas, L / Maubec, E / Sassolas, B / Granel-Brocard, F / Chevreau, C / De Raucourt, S / Leccia, M-T / Fichet, D / Khammari, A / Boitier, F / Stoebner, P-E / Dalac, S / Celerier, P / Aubin, F / Viguier, M. ·Service de Dermatologie, Université Paris VII, Hôpital Saint-Louis, INSERM U697, 1 Avenue Claude-Vellefaux, 75475 Paris Cedex 10, France. ·Br J Dermatol · Pubmed #19804595.

ABSTRACT: BACKGROUND: Although metastatic melanoma occurrence during pregnancy challenges the physician in several ways, only a few studies have been published. OBJECTIVES: Our aim was to investigate therapeutic management together with maternal and fetal outcomes in pregnant women with advanced melanoma. METHODS: A French national retrospective study was conducted in 34 departments of Dermatology or Oncology. All patients with American Joint Committee on Cancer (AJCC) stage III/IV melanoma diagnosed during pregnancy were included. Data regarding melanoma history, pregnancy, treatment, delivery, maternal and infant outcomes were collected. RESULTS: Twenty-two women were included: 10 AJCC stage III and 12 stage IV. Abortion was performed in three patients. Therapeutic abstention during pregnancy was observed in three cases, 14 patients underwent surgery, four patients received chemotherapy and one patient was treated with brain radiotherapy alone. The median gestational age was 36 weeks amenorrhoea. Neither neonatal metastases nor deformities were observed. Placenta metastases were found in one case. Among 18 newborns, 17 are currently alive (median follow up, 17 months); one died of sudden infant death. The 2-year maternal survival rates were 56% (stage III) and 17% (stage IV). CONCLUSIONS: Faced with metastatic melanoma, a majority of women chose to continue with pregnancy, giving birth, based on our samples, to healthy, frequently premature infants. Except during the first trimester of pregnancy, conventional melanoma treatment was applied. No serious side effect was reported, except one case of miscarriage after surgery. Mortality rates do not suggest a worsened prognosis due to pregnancy but larger prospective controlled studies are necessary to assess this specific point.

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