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Melanoma: HELP
Articles by C. Robert
Based on 32 articles published since 2008
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Between 2008 and 2019, C. Robert wrote the following 32 articles about Melanoma.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Editorial [Treating metastatic melanoma: Risk management]. 2017

Lebbe, C / Robert, C. ·Université Paris-Diderot, Sorbonne-Paris-Cité, APHP services de dermatologie et CIC, hôpital Saint-Louis-Paris, INSERM U976, 1, avenue Claude-Vellefaux, 75010 Paris, France. Electronic address: celeste.lebbe@aphp.fr. · Département de médecine, service de dermatologie, institut Gustave-Roussy, 114, rue Édouard-Vaillant, 94800 Villejuif, France; Université Paris-Sud, 114, rue Édouard-Vaillant, 94800 Villejuif, France. ·Ann Dermatol Venereol · Pubmed #28063593.

ABSTRACT: -- No abstract --

2 Review [What's new in oncodermatology?] 2018

Robert, C. ·Chef du service de dermato-oncologie et INSERM U 981, Gustave-Roussy, université Paris-Sud, Le Kremlin-Bicêtre, France. Electronic address: Caroline.ROBERT@gustaveroussy.fr. ·Ann Dermatol Venereol · Pubmed #30583756.

ABSTRACT: This year again, several breaking news were published in our field of oncodermatology, especially in the domain of immunotherapy. Many works have reported results on predictive biomarker identification. Concerning melanoma treatment, we were disappointed by the negative results of the phase III trial evaluating the IDO1 inhibitor epacadostat + pembrolizumab versus pembrolizumab. However, many promising preliminary results involving the combinations of anti-PD1 and innate immunity activators have been published. We also have a new anti-BRAF + anti-MEK combination: encorafenib + binimetinib with a good benefit/risk ratio and a particularly favorable safety profile as compared with existing similar combinations. Major steps forward were obtained for locally advanced Merkel cell carcinoma and squamous cell carcinoma with anti-PDL-1 avelumab and anti-PD1 cemiplimab respectively.

3 Review Management of immune checkpoint blockade dysimmune toxicities: a collaborative position paper. 2016

Champiat, S / Lambotte, O / Barreau, E / Belkhir, R / Berdelou, A / Carbonnel, F / Cauquil, C / Chanson, P / Collins, M / Durrbach, A / Ederhy, S / Feuillet, S / François, H / Lazarovici, J / Le Pavec, J / De Martin, E / Mateus, C / Michot, J-M / Samuel, D / Soria, J-C / Robert, C / Eggermont, A / Marabelle, A. ·Department of Drug Development (DITEP), Gustave Roussy Inserm U981, Univ. Paris-Sud, Université Paris-Saclay, Villejuif. · Department of Internal Medicine and Clinical Immunology, Assistance Publique-Hôpitaux de Paris, Hôpital Universitaire Bicêtre, Le Kremlin Bicêtre Université Paris Sud 11, Le Kremlin-Bicêtre CEA, DSV/iMETI, Division of Immuno-Virology, IDMIT, Fontenay-aux-Roses INSERM, U1184, Center for Immunology of Viral Infections and Autoimmune Diseases, Le Kremlin-Bicêtre. · Department of Ophthalmology, Hôpital Universitaire Bicêtre, Le Kremlin Bicêtre. · Department of Rheumatology, Hôpitaux Universitaires Paris-Sud, Hôpital Bicêtre, AP-HP, Le Kremlin Bicêtre. · Department of Nuclear Medicine and Endocrine Tumors, Gustave Roussy, Univ. Paris-Sud, Université Paris-Saclay, Villejuif. · Gastroenterology Unit, Université Paris-Sud, Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Paris Sud, Le Kremlin Bicêtre. · Division of Adult Neurology, Hôpital Universitaire Bicêtre, Le Kremlin Bicêtre. · Faculty of Medicine, Université Paris-Saclay, Univ Paris-Sud, Paris-Sud, UMR-S1185, Le Kremlin Bicêtre Unit of Endocrinology and reproductive Health, Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Paris-Sud, Hôpital de Bicêtre, Le Kremlin Bicêtre Unit of Gastroenterology, Institut National de la Santé et de la Recherche Médicale U1185 (P.C.), Le Kremlin Bicêtre. · Department of Nephrology and Transplantation, Bicêtre Hospital, Paris Saclay University, INSERM 1197, Le Kremlin Bicêtre. · Department of Cardiology, Saint-Antoine Hospital, Assistance Publique-Hôpitaux de Paris, Pierre et Marie Curie University [UPMC], Paris-Sorbonne, Paris. · Department of Thoracic and cardiovascular, and transplantation cardio-pulmonary, Hôpital Marie-Lannelongue, Le Plessis-Robinson Univ. Paris-Sud, Faculté de Médecine, Université Paris-Saclay, Le Kremlin Bicêtre. · Hematology Unit, Department of Medical Oncology, Gustave Roussy, Univ. Paris-Sud, Université Paris-Saclay, Villejuif. · Department of Thoracic and cardiovascular, and transplantation cardio-pulmonary, Hôpital Marie-Lannelongue, Le Plessis-Robinson Univ. Paris-Sud, Faculté de Médecine, Université Paris-Saclay, Le Kremlin Bicêtre UMR_S 999, Univ. Paris-Sud; INSERM; Hôpital Marie Lannelongue, Le Plessis Robinson. · Centre Hépato-Biliaire, AP-HP, Hôpital Universitaire Paul Brousse Inserm U1193. · Dermatology Unit, Department of Medical Oncology, Gustave Roussy, Univ. Paris-Sud, Université Paris-Saclay, Villejuif. · Department of Drug Development (DITEP), Gustave Roussy. · Inserm U981, Univ. Paris-Sud, Université Paris-Saclay, Villejuif Dermatology Unit, Department of Medical Oncology, Gustave Roussy, Univ. Paris-Sud, Université Paris-Saclay, Villejuif. · Gustave Roussy Cancer Campus, Villejuif. · Department of Drug Development (DITEP), Gustave Roussy Gustave Roussy Cancer Campus, Villejuif Inserm 1015, Univ. Paris-Sud, Université Paris-Saclay, Villejuif, France aurelien.marabelle@gustaveroussy.fr. ·Ann Oncol · Pubmed #26715621.

ABSTRACT: Monoclonal antibodies targeted against the immune checkpoint molecules CTLA-4 and PD-1 have recently obtained approval for the treatment of metastatic melanoma and advanced/refractory non small-cell lung cancers. Therefore, their use will not be limited anymore to selected hospitals involved in clinical trials. Indeed, they will be routinely prescribed in many cancer centers across the world. Besides their efficacy profile, these immune targeted agents also generate immune-related adverse events (irAEs). This new family of dysimmune toxicities remains largely unknown to the broad oncology community. Although severe irAEs remain rare (∼10% of cases under monotherapy), they can become life-threatening if not anticipated and managed appropriately. Over the last 5 years, Gustave Roussy has accumulated a significant experience in the prescription of immune checkpoint blockade (ICB) antibodies and the management of their toxicities. Together with the collaboration of Gustave Roussy's network of organ specialists with expertise in irAEs, we propose here some practical guidelines for the oncologist to help in the clinical care of patients under ICB immunotherapy.

4 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).

5 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.

6 Review Small molecules and targeted therapies in distant metastatic disease. 2009

Hersey, P / Bastholt, L / Chiarion-Sileni, V / Cinat, G / Dummer, R / Eggermont, A M M / Espinosa, E / Hauschild, A / Quirt, I / Robert, C / Schadendorf, D. ·Immunology and Oncology Unit, Calvary Mater Newcastle Hospital, New South Wales, Australia. Peter.Hersey@newcastle.edu.au ·Ann Oncol · Pubmed #19617296.

ABSTRACT: Chemotherapy, biological agents or combinations of both have had little impact on survival of patients with metastatic melanoma. Advances in understanding the genetic changes associated with the development of melanoma resulted in availability of promising new agents that inhibit specific proteins up-regulated in signal cell pathways or inhibit anti-apoptotic proteins. Sorafenib, a multikinase inhibitor of the RAF/RAS/MEK pathway, elesclomol (STA-4783) and oblimersen (G3139), an antisense oligonucleotide targeting anti-apoptotic BCl-2, are in phase III clinical studies in combination with chemotherapy. Agents targeting mutant B-Raf (RAF265 and PLX4032), MEK (PD0325901, AZD6244), heat-shock protein 90 (tanespimycin), mTOR (everolimus, deforolimus, temsirolimus) and VEGFR (axitinib) showed some promise in earlier stages of clinical development. Receptor tyrosine-kinase inhibitors (imatinib, dasatinib, sunitinib) may have a role in treatment of patients with melanoma harbouring c-Kit mutations. Although often studied as single agents with disappointing results, new targeted drugs should be more thoroughly evaluated in combination therapies. The future of rational use of new targeted agents also depends on successful application of analytical techniques enabling molecular profiling of patients and leading to selection of likely therapy responders.

7 Clinical Trial Dabrafenib plus trametinib versus dabrafenib monotherapy in patients with metastatic BRAF V600E/K-mutant melanoma: long-term survival and safety analysis of a phase 3 study. 2017

Long, G V / Flaherty, K T / Stroyakovskiy, D / Gogas, H / Levchenko, E / de Braud, F / Larkin, J / Garbe, C / Jouary, T / Hauschild, A / Chiarion-Sileni, V / Lebbe, C / Mandalà, M / Millward, M / Arance, A / Bondarenko, I / Haanen, J B A G / Hansson, J / Utikal, J / Ferraresi, V / Mohr, P / Probachai, V / Schadendorf, D / Nathan, P / Robert, C / Ribas, A / Davies, M A / Lane, S R / Legos, J J / Mookerjee, B / Grob, J-J. ·Melanoma Institute Australia, The University of Sydney, and Royal North Shore and Mater Hospitals, North Sydney, Australia. · Developmental Therapeutics and Melanoma Programs, Massachusetts General Hospital Cancer Center, Boston, USA. · Moscow City Oncology Hospital #62, Moscow, Russia. · First Department of Medicine, "Laiko" General Hospital, National and Kapodistrian University of Athens, Athens, Greece. · Petrov Research Institute of Oncology, Saint Petersburg, Russia. · Dipartimento di Medicina Oncologica, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. · Royal Marsden NHS Foundation Trust, London, UK. · Department of Dermatology, University of Tübingen, Tübingen, Germany. · Service D'oncologie Médicale, Hopital Francois Mitterrand, Pau, France. · Department of Dermatology, University Hospital Schleswig-Holstein, Kiel, Germany. · Melanoma and Oesophageal Oncology Unit, Veneto Oncology Institute-IRCCS, Padova, Italy. · APHP Dermatology and CIC Departments, INSERM U976, University Paris Diderot, Paris, France. · Department of Oncology and Hematology, Papa Giovanni XXIII Hospital, Bergamo, Italy. · Medical Oncology Department, Sir Charles Gairdner Hospital, Perth, Australia. · Department of Medical Oncology, Hospital Clinic of Barcelona, Barcelona, Spain. · Dnipropetrovsk State Medical Academy, Clinical Hospital #4, Dnipropetrovsk, Ukraine. · Netherlands Cancer Institute, Amsterdam, The Netherlands. · Department of Oncology-Pathology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden. · Skin Cancer Unit, German Cancer Research Center (DKFZ) and Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karls University of Heidelberg, Mannheim and Heidelberg, Germany. · Department of Medical Oncology A, Regina Elena National Cancer Institute, Rome, Italy. · Dermatologisches Zentrum Buxtehude, Elbe Kliniken Buxtehude, Buxtehude, Germany. · Dnipropetrovsk Clinical Oncology Center of Dnipropetrovsk State Council, Dnipropetrovsk, Ukraine. · Department of Dermatology, University Hospital Essen, Essen, Germany. · German Cancer Consortium, Heidelberg, Germany. · Mount Vernon Cancer Centre, Northwood, UK. · Gustave Roussy, Département de Médecine Oncologique, Service de Dermatologie et Université Paris-Sud, Faculté de Médecine, Villejuif, France. · Department of Medicine, Hematology/Oncology, UCLA Jonsson Comprehensive Cancer Center, Los Angeles, USA. · Melanoma Medical Oncology and Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, USA. · Novartis Pharmaceuticals Corporation, East Hanover, USA. · Service de Dermatologie, Centre Hospitalo-Universitaire Timone, Aix-Marseille Université, Marseille, France. ·Ann Oncol · Pubmed #28475671.

ABSTRACT: Background: Previous analysis of COMBI-d (NCT01584648) demonstrated improved progression-free survival (PFS) and overall survival (OS) with combination dabrafenib and trametinib versus dabrafenib monotherapy in BRAF V600E/K-mutant metastatic melanoma. This study was continued to assess 3-year landmark efficacy and safety after ≥36-month follow-up for all living patients. Patients and methods: This double-blind, phase 3 study enrolled previously untreated patients with BRAF V600E/K-mutant unresectable stage IIIC or stage IV melanoma. Patients were randomized to receive dabrafenib (150 mg twice daily) plus trametinib (2 mg once daily) or dabrafenib plus placebo. The primary endpoint was PFS; secondary endpoints were OS, overall response, duration of response, safety, and pharmacokinetics. Results: Between 4 May and 30 November 2012, a total of 423 of 947 screened patients were randomly assigned to receive dabrafenib plus trametinib (n = 211) or dabrafenib monotherapy (n = 212). At data cut-off (15 February 2016), outcomes remained superior with the combination: 3-year PFS was 22% with dabrafenib plus trametinib versus 12% with monotherapy, and 3-year OS was 44% versus 32%, respectively. Twenty-five patients receiving monotherapy crossed over to combination therapy, with continued follow-up under the monotherapy arm (per intent-to-treat principle). Of combination-arm patients alive at 3 years, 58% remained on dabrafenib plus trametinib. Three-year OS with the combination reached 62% in the most favourable subgroup (normal lactate dehydrogenase and <3 organ sites with metastasis) versus only 25% in the unfavourable subgroup (elevated lactate dehydrogenase). The dabrafenib plus trametinib safety profile was consistent with previous clinical trial observations, and no new safety signals were detected with long-term use. Conclusions: These data demonstrate that durable (≥3 years) survival is achievable with dabrafenib plus trametinib in patients with BRAF V600-mutant metastatic melanoma and support long-term first-line use of the combination in this setting.

8 Clinical Trial Effect of nivolumab on health-related quality of life in patients with treatment-naïve advanced melanoma: results from the phase III CheckMate 066 study. 2016

Long, G V / Atkinson, V / Ascierto, P A / Robert, C / Hassel, J C / Rutkowski, P / Savage, K J / Taylor, F / Coon, C / Gilloteau, I / Dastani, H B / Waxman, I M / Abernethy, A P. ·Melanoma Institute Australia, The University of Sydney, and Mater Hospital, Sydney, Australia georgina.long@sydney.edu.au. · Gallipoli Medical Research Foundation and Princess Alexandra Hospital, Greenslopes, Australia. · Istituto Nazionale Tumori Fondazione Pascale, Napoli, Italy. · Gustave-Roussy, Paris, France. · University Hospital Heidelberg and National Center for Tumor Diseases, Heidelberg, Germany. · Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland. · BC Cancer Agency, University of British Columbia, Vancouver, Canada. · Adelphi Values, Boston, MA, USA. · Bristol-Myers Squibb, Princeton, NJ, USA. · Duke Clinical Research Institute, Durham, NC, USA. ·Ann Oncol · Pubmed #27405322.

ABSTRACT: BACKGROUND: Nivolumab has shown significant survival benefit and a favorable safety profile compared with dacarbazine chemotherapy among treatment-naïve patients with metastatic melanoma in the CheckMate 066 phase III study. Results from the health-related quality of life (HRQoL) analyses from CheckMate 066 are presented. PATIENTS AND METHODS: HRQoL was evaluated at baseline and every 6 weeks while on treatment using the European Organisation for Research and Treatment of Care (EORTC) Core Quality of Life Questionnaire (QLQ-C30) and the EuroQoL Five Dimensions Questionnaire (EQ-5D). Via a multi-step statistical plan, data were analyzed descriptively, cross-sectionally, and longitudinally, adjusting for baseline covariates, in patients having baseline plus ≥1 post-baseline assessment. RESULTS: Baseline-adjusted completion rates for all HRQoL questionnaires across treatment arms were 65% and 70% for dacarbazine and nivolumab, respectively, and remained similar throughout treatment. The mean baseline HRQoL scores were similar for patients treated with nivolumab and dacarbazine. Baseline HRQoL levels with nivolumab were maintained over time. This exploratory analysis showed a between-arm difference in favor of nivolumab on the EQ-5D utility index and clinically meaningful EQ-5D improvements from baseline at several time points for patients receiving nivolumab. Patients treated with nivolumab did not show increased symptom burden as assessed by the EORTC QLQ-C30. No HRQoL change was noted with dacarbazine patients up to week 43, although the high attrition rate after week 13 did not allow any meaningful analyses. Patients receiving nivolumab deteriorated significantly later than those receiving dacarbazine on several EORTC QLQ-C30 scales and the EQ-5D utility index. CONCLUSIONS: In addition to prolonged survival, these exploratory HRQoL results show that nivolumab maintains baseline HRQoL levels to provide long-term quality of survival benefit, compared with dacarbazine in patients with advanced melanoma.

9 Clinical Trial A randomized, controlled phase III trial of nab-Paclitaxel versus dacarbazine in chemotherapy-naïve patients with metastatic melanoma. 2015

Hersh, E M / Del Vecchio, M / Brown, M P / Kefford, R / Loquai, C / Testori, A / Bhatia, S / Gutzmer, R / Conry, R / Haydon, A / Robert, C / Ernst, S / Homsi, J / Grob, J J / Kendra, K / Agarwala, S S / Li, M / Clawson, A / Brachmann, C / Karnoub, M / Elias, I / Renschler, M F / Hauschild, A. ·Department of Medicine, Arizona Cancer Center, Tucson, USA ehersh@azcc.arizona.edu. · Department of Medical Oncology, Fondazione IRCCS National Tumor Institute, Milan, Italy. · Cancer Clinical Trials Unit, Royal Adelaide Hospital and School of Medicine, University of Adelaide, Adelaide. · Sydney West Cancer Trials Centre/Westmead Hospital and Melanoma Institute Australia, University of Sydney, North Sydney, Australia. · Department of Dermatology, University of Mainz, Mainz, Germany. · Melanoma and Muscle Cutaneous Sarcoma Division, European Institute of Oncology, Milan, Italy. · Department of Medicine, Seattle Cancer Care Alliance, Seattle, USA. · Department of Dermatology and Oncology, Hannover Medical School, Hannover, Germany. · Division of Hematology and Oncology, University of Alabama at Birmingham, Birmingham, USA. · Department of Medical Oncology, Alfred Hospital, Melbourne, Australia. · Demartology Unit, Department of Medicine, The Gustave Roussy Cancer Institute, Villejuif, France. · Department of Medical Oncology, London Health Sciences Center-London Regional Cancer Program, London, Canada. · Department of Medical Oncology, Banner MD Anderson Cancer Center, Gilbert, USA. · Department of Dermatology, Timone Hospital, APHM and Aix-Marseille University, Marseille, France. · Department of Internal Medicine, Division of Medical Oncology, Ohio State University Comprehensive Cancer Center, Columbus. · Department of Hematology and Oncology, St Luke's Cancer Center and Temple University, Bethlehem. · Biometrics and Data Operations/Translational Medicine/Biometrics and Data Operations/Clinical Research & Development/Global Medical Affairs, Celgene Corporation, Summit, USA. · Department of Dermatology, University Medical Center Schleswig-Holstein, Kiel, Germany. ·Ann Oncol · Pubmed #26410620.

ABSTRACT: BACKGROUND: The efficacy and safety of nab-paclitaxel versus dacarbazine in patients with metastatic melanoma was evaluated in a phase III randomized, controlled trial. PATIENTS AND METHODS: Chemotherapy-naïve patients with stage IV melanoma received nab-paclitaxel 150 mg/m(2) on days 1, 8, and 15 every 4 weeks or dacarbazine 1000 mg/m(2) every 3 weeks. The primary end point was progression-free survival (PFS) by independent radiologic review; the secondary end point was overall survival (OS). RESULTS: A total of 529 patients were randomized to nab-paclitaxel (n = 264) or dacarbazine (n = 265). Baseline characteristics were well balanced. The majority of patients were men (66%), had an Eastern Cooperative Oncology Group status of 0 (71%), and had M1c stage disease (65%). The median PFS (primary end point) was 4.8 months with nab-paclitaxel and 2.5 months with dacarbazine [hazard ratio (HR), 0.792; 95.1% confidence interval (CI) 0.631-0.992; P = 0.044]. The median OS was 12.6 months with nab-paclitaxel and 10.5 months with dacarbazine (HR, 0.897; 95.1% CI 0.738-1.089; P = 0.271). Independently assessed overall response rate was 15% versus 11% (P = 0.239), and disease control rate (DCR) was 39% versus 27% (P = 0.004) for nab-paclitaxel versus dacarbazine, respectively. The most common grade ≥3 treatment-related adverse events were neuropathy (nab-paclitaxel, 25% versus dacarbazine, 0%; P < 0.001), and neutropenia (nab-paclitaxel, 20% versus dacarbazine, 10%; P = 0.004). There was no correlation between secreted protein acidic and rich in cysteine (SPARC) status and PFS in either treatment arm. CONCLUSIONS: nab-Paclitaxel significantly improved PFS and DCR compared with dacarbazine, with a manageable safety profile.

10 Clinical Trial Functional and symptom impact of trametinib versus chemotherapy in BRAF V600E advanced or metastatic melanoma: quality-of-life analyses of the METRIC study. 2014

Schadendorf, D / Amonkar, M M / Milhem, M / Grotzinger, K / Demidov, L V / Rutkowski, P / Garbe, C / Dummer, R / Hassel, J C / Wolter, P / Mohr, P / Trefzer, U / Lefeuvre-Plesse, C / Rutten, A / Steven, N / Ullenhag, G / Sherman, L / Wu, F S / Patel, K / Casey, M / Robert, C. ·Department of Dermatology, University Hospital Essen, Essen, Germany. ·Ann Oncol · Pubmed #24504441.

ABSTRACT: BACKGROUND: In a randomized phase III study, trametinib prolonged progression-free survival and improved overall survival versus chemotherapy in patients with BRAF V600 mutation-positive melanoma. PATIENTS AND METHODS: Patients' quality of life (QOL) was assessed at baseline and follow-up visits using the European Organisation for Research and Treatment of Cancer Core QOL questionnaire. RESULTS: In the primary efficacy population (BRAF V600E+, no brain metastases) from baseline to weeks 6 and 12, patients' global health status scores worsened by 4-5 points with chemotherapy but improved by 2-3 points with trametinib. Rapid and substantive reductions in QOL functionality (e.g. role functioning, 8-11 points at weeks 6 and 12) and symptom exacerbation (e.g. fatigue, 4-8 points; nausea and vomiting, 5 points, both at weeks 6 and 12) were observed in chemotherapy-treated patients. In contrast, trametinib-treated patients reported small improvements or slight worsening from baseline at week 12, depending on the functional dimension and symptom. The mean symptom-scale scores for chemotherapy-treated patients increased from baseline (symptoms worsened) for seven of eight symptoms at week 6 (except insomnia) and six of eight symptoms at week 12 (except dyspnea and insomnia). In contrast, at weeks 6 and 12, the mean symptom-scale scores for trametinib decreased from baseline (symptoms improved) for pain (11-12 points), insomnia (10-12 points), and appetite loss (1-5 points), whereas those for diarrhea worsened (15-16 points). Mixed-model repeated-measures analyses showed significant (P < 0.05) and/or clinically meaningful improvements (small to moderate) from baseline in favor of trametinib for global health; physical, role, and social functioning; fatigue; pain; insomnia; nausea and vomiting; constipation; dyspnea; and appetite at weeks 6 and/or 12. QOL results for the intent-to-treat population were consistent. CONCLUSIONS: This first QOL assessment for a MEK inhibitor in metastatic melanoma demonstrated that trametinib was associated with less functional impairment, smaller declines in health status, and less exacerbation of symptoms versus chemotherapy.

11 Clinical Trial Sorafenib and dacarbazine as first-line therapy for advanced melanoma: phase I and open-label phase II studies. 2011

Eisen, T / Marais, R / Affolter, A / Lorigan, P / Robert, C / Corrie, P / Ottensmeier, C / Chevreau, C / Chao, D / Nathan, P D / Jouary, T / Harries, M / Negrier, S / Montegriffo, E / Ahmad, T / Gibbens, I / James, M G / Strauss, U P / Prendergast, S / Gore, M E. ·Department of Oncology (R4), Cambridge Biomedical Research Centre, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QQ, UK. tgqe2@cam.ac.uk ·Br J Cancer · Pubmed #21750549.

ABSTRACT: METHOD: The safety of oral sorafenib up to a maximum protocol-specified dose combined with dacarbazine in patients with metastatic, histologically confirmed melanoma was investigated in a phase I dose-escalation study and the activity of the combination was explored in an open-label phase II study. RESULTS: In the phase I study, three patients were treated with sorafenib 200 mg twice daily (b.i.d.) plus 1000 mg m(-2) dacarbazine on day 1 of a 21-day cycle and 15 patients had the sorafenib dose escalated to 400 mg b.i.d. without reaching the maximum tolerated dose of the combination. In the phase II study (n=83), the overall response rate was 12% (95% CI: 6, 21): one complete and nine partial, with median response duration of 46.7 weeks. Stable disease was the best response in 37%; median duration was 13.3 weeks. Median overall survival (OS) was 37.0 weeks (95% CI: 33.9, 46.0). CONCLUSION: Oral sorafenib combined with dacarbazine had acceptable toxicity and some antineoplastic activity against metastatic melanoma.

12 Article Sentinel lymph node biopsy in cutaneous head and neck melanoma. 2018

Evrard, D / Routier, E / Mateus, C / Tomasic, G / Lombroso, J / Kolb, F / Robert, C / Moya-Plana, A. ·Head and Neck Surgery Department, Gustave Roussy Cancer Campus, Paris Sud University, Villejuif, France. evrard.diane@gmail.com. · Onco-dermatology Department, Gustave Roussy Cancer Campus, Paris Sud University, Saclay University, Villejuif, France. · Pathology Department, Gustave Roussy Cancer Campus, Paris Sud University, Villejuif, France. · Nuclear Medicine Department, Gustave Roussy Cancer Campus, Paris Sud University, Villejuif, France. · Plastic and Reconstructive Surgery Department, Gustave Roussy Cancer Campus, Paris Sud University, Villejuif, France. · Head and Neck Surgery Department, Gustave Roussy Cancer Campus, Paris Sud University, Villejuif, France. ·Eur Arch Otorhinolaryngol · Pubmed #29552728.

ABSTRACT: PURPOSE: Sentinel lymph node biopsy (SLNB) is now a standard of care for cutaneous melanoma, but it is still controversial for cutaneous head and neck melanoma (CHNM). This study aims to confirm the feasibility, accuracy and low morbidity of SLNB in CHNM and evaluate its prognostic value. METHODS: A monocentric and retrospective study on patients with CHNM treated in our tertiary care center (Gustave Roussy) between January 2008 and December 2012 was performed. The feasibility, morbidity and prognostic value of this technique were analysed. RESULTS: One hundred and twenty-four consecutive patients were included. SLNB was realized in 97.6% of the cases. No significant post-operative morbidity was observed. Nineteen percents of patients had a positive SN while only 14.3% of complete lymph node dissections (CLND) had additional nodal metastasis. The risk of recurrence after positive SN was significantly higher (69.2 vs 30.8%, p = 0.043). The false omission rate was low with 7.1%. Overall survival and disease-free survival were better in the negative SN group (82 vs 49%, p < 0.001 and 69.3 vs 41.8%, p = 0.0131). The risk of recurrence was significantly higher in the positive SN group (p = 0.043) and when primary tumour was ulcerated (p = 0.031). Only the mitotic rate of the primary tumour was associated with SN positivity (p = 0.049). CONCLUSION: As in other sites, SLNB status is a strong prognostic factor with comparable false omission rate and no superior morbidity.

13 Article Vemurafenib in patients with BRAFV600 mutation-positive metastatic melanoma: final overall survival results of the randomized BRIM-3 study. 2017

Chapman, P B / Robert, C / Larkin, J / Haanen, J B / Ribas, A / Hogg, D / Hamid, O / Ascierto, P A / Testori, A / Lorigan, P C / Dummer, R / Sosman, J A / Flaherty, K T / Chang, I / Coleman, S / Caro, I / Hauschild, A / McArthur, G A. ·Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, USA. · Department of Medicine, Institut Gustave Roussy and Paris Sud University, Paris, France. · Department of Medicine, The Royal Marsden NHS Foundation Trust, London, UK. · Division of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands. · Department of Medicine, Hematology and Oncology, Jonsson Comprehensive Cancer Center at the University of California Los Angeles, Los Angeles, USA. · Division of Medical Oncology and Hematology, Princess Margaret Hospital and University Health Network, Toronto, Canada. · The Angeles Clinic and Research Institute, Melanoma Therapeutics, Los Angeles, USA. · Melanoma, Cancer Immunotherapy and Innovative Therapy Unit, Istituto Nazionale Tumori Fondazione G. Pascale, Naples. · Melanoma and Sarcoma, Istituto Europeo di Oncologia, Milan, Italy. · Department of Medical Oncology, University of Manchester, Manchester, UK. · Department of Dermatology, University of Zurich, Zurich, Switzerland. · Department of Hematology/Oncology, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago. · Department of Medicine, Massachusetts General Hospital, Boston. · Department of Biostatistics in Product Development, Biometrics. · Clinical Department. · Product Development, Oncology, Genentech Inc., South San Francisco, USA. · Department of Dermatology, University Hospital Schleswig-Holstein, Kiel, Germany. · Department of Oncology, Peter MacCallum Cancer Centre, East Melbourne. · Department of Oncology, University of Melbourne, Parkville, Australia. ·Ann Oncol · Pubmed #28961848.

ABSTRACT: Background: The BRIM-3 trial showed improved progression-free survival (PFS) and overall survival (OS) for vemurafenib compared with dacarbazine in treatment-naive patients with BRAFV600 mutation-positive metastatic melanoma. We present final OS data from BRIM-3. Patients and methods: Patients were randomly assigned in a 1 : 1 ratio to receive vemurafenib (960 mg twice daily) or dacarbazine (1000 mg/m2 every 3 weeks). OS and PFS were co-primary end points. OS was assessed in the intention-to-treat population, with and without censoring of data for dacarbazine patients who crossed over to vemurafenib. Results: Between 4 January 2010 and 16 December 2010, a total of 675 patients were randomized to vemurafenib (n = 337) or dacarbazine (n = 338, of whom 84 crossed over to vemurafenib). At the time of database lock (14 August 2015), median OS, censored at crossover, was significantly longer for vemurafenib than for dacarbazine {13.6 months [95% confidence interval (CI) 12.0-15.4] versus 9.7 months [95% CI 7.9-12.8; hazard ratio (HR) 0.81 [95% CI 0.67-0.98]; P = 0.03}, as was median OS without censoring at crossover [13.6 months (95% CI 12.0-15.4) versus 10.3 months (95% CI 9.1-12.8); HR 0.81 (95% CI 0.68-0.96); P = 0.01]. Kaplan-Meier estimates of OS rates for vemurafenib versus dacarbazine were 56% versus 46%, 30% versus 24%, 21% versus 19% and 17% versus 16% at 1, 2, 3 and 4 years, respectively. Overall, 173 of the 338 patients (51%) in the dacarbazine arm and 175 of the 337 (52%) of those in the vemurafenib arm received subsequent anticancer therapies, most commonly ipilimumab. Safety data were consistent with the primary analysis. Conclusions: Vemurafenib continues to be associated with improved median OS in the BRIM-3 trial after extended follow-up. OS curves converged after ≈3 years, likely as a result of crossover from dacarbazine to vemurafenib and receipt of subsequent anticancer therapies. ClinicalTrials.gov: NCT01006980.

14 Article Baseline gut microbiota predicts clinical response and colitis in metastatic melanoma patients treated with ipilimumab. 2017

Chaput, N / Lepage, P / Coutzac, C / Soularue, E / Le Roux, K / Monot, C / Boselli, L / Routier, E / Cassard, L / Collins, M / Vaysse, T / Marthey, L / Eggermont, A / Asvatourian, V / Lanoy, E / Mateus, C / Robert, C / Carbonnel, F. ·Laboratory of Immunomonitoring in Oncology, CNRS-UMS 3655 and INSERM-US23, Gustave Roussy Cancer Campus, Villejuif. · Faculty of Pharmacy, Chatenay-Malabry. · Micalis Institute, INRA, AgroParisTech, Paris. · Faculty of Medicine, University Paris-Saclay, Le Kremlin Bicêtre. · Department of Gastroenterology, Kremlin Bicêtre Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Le Kremlin Bicêtre. · Dermatology Unit, Department of Medicine, Gustave Roussy, Cancer Campus, Villejuif. · INSERM U1015, Gustave Roussy, Cancer Campus, Villejuif. · Biostatistics and Epidemiology Unit, Gustave Roussy Cancer Campus (GRCC), Villejuif. · University Paris-Saclay, Université Paris-Sud, UVSQ, CESP, INSERM, Villejuif, France. ·Ann Oncol · Pubmed #28368458.

ABSTRACT: Background: Ipilimumab, an immune checkpoint inhibitor targeting CTLA-4, prolongs survival in a subset of patients with metastatic melanoma (MM) but can induce immune-related adverse events, including enterocolitis. We hypothesized that baseline gut microbiota could predict ipilimumab anti-tumor response and/or intestinal toxicity. Patients and methods: Twenty-six patients with MM treated with ipilimumab were prospectively enrolled. Fecal microbiota composition was assessed using 16S rRNA gene sequencing at baseline and before each ipilimumab infusion. Patients were further clustered based on microbiota patterns. Peripheral blood lymphocytes immunophenotypes were studied in parallel. Results: A distinct baseline gut microbiota composition was associated with both clinical response and colitis. Compared with patients whose baseline microbiota was driven by Bacteroides (cluster B, n = 10), patients whose baseline microbiota was enriched with Faecalibacterium genus and other Firmicutes (cluster A, n = 12) had longer progression-free survival (P = 0.0039) and overall survival (P = 0.051). Most of the baseline colitis-associated phylotypes were related to Firmicutes (e.g. relatives of Faecalibacterium prausnitzii and Gemmiger formicilis), whereas no colitis-related phylotypes were assigned to Bacteroidetes. A low proportion of peripheral blood regulatory T cells was associated with cluster A, long-term clinical benefit and colitis. Ipilimumab led to a higher inducible T-cell COStimulator induction on CD4+ T cells and to a higher increase in serum CD25 in patients who belonged to Faecalibacterium-driven cluster A. Conclusion: Baseline gut microbiota enriched with Faecalibacterium and other Firmicutes is associated with beneficial clinical response to ipilimumab and more frequent occurrence of ipilimumab-induced colitis.

15 Article Timing of completion lymphadenectomy after positive sentinel node biopsy in patients with melanoma. 2017

Oude Ophuis, C M C / van Akkooi, A C J / Rutkowski, P / Powell, W E M / Robert, C / Testori, A / van Leeuwen, B L / Siegel, P / Eggermont, A M M / Verhoef, C / Grünhagen, D J. ·Department of Surgical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands. · Department of Surgery, The Netherlands Cancer Institute - Antoni van Leeuwenhoek, Amsterdam, The Netherlands. · Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Warsaw, Poland. · Melanoma Unit, St George's Foundation University Hospital, London, UK. · Department of Dermatology and Allergology, Cancer Institute Gustave Roussy, Villejuif, France. · Division of Dermato-Oncological Surgery, European Institute of Oncology, Milan, Italy. · Department of Surgical Oncology, Groningen University, University Medical Centre Groningen, Groningen, The Netherlands. · Department of Dermatology and Allergology, Charité - University of Medicine Berlin, Berlin, Germany. · Board of Directors, Cancer Institute Gustave Roussy, Villejuif, France. ·Br J Surg · Pubmed #28218385.

ABSTRACT: BACKGROUND: Nodal staging with sentinel node biopsy (SNB) and completion lymph node dissection (CLND) provides prognostic information to patients with melanoma and their physicians. It is not known whether the timing of CLND is associated with survival outcome and/or CLND tumour load. This study investigated whether CLND timing is associated with CLND tumour load, disease-free survival (DFS) and/or melanoma-specific survival (MSS). METHODS: A retrospective cohort of patients with SNB-positive melanoma from nine European Organisation for Research and Treatment of Cancer (EORTC) Melanoma Group centres undergoing surgery between 1993 and 2009 were examined. Patients were selected based on availability of CLND and follow-up data. The CLND interval was defined as the number of days between diagnosis and CLND. Patient and tumour characteristics were collected. Five-year DFS and MSS rates were calculated. Cox and logistic regression analysis were performed, adjusting for known prognostic/predictive indicators. RESULTS: A total of 784 patients were included in the study. Their median age was 51 (i.q.r. 40-62) years, and 418 patients (53·3 per cent) were men. Median Breslow thickness was 3·0 (i.q.r. 2·0-5·0) mm, and 148 patients (18·9 per cent) had a residual tumour load. Median CLND interval was 84 (i.q.r. 65-105) days. Five-year DFS and MSS rates were not significantly different for patients operated on with a median CLND interval of less than 84 days and those with an interval of at least 84 days (DFS: 54·2 versus 53·3 per cent respectively; MSS: 66·9 versus 65·1 per cent). In a multivariable Cox model, CLND interval was not a significant prognostic indicator. CLND interval was negatively correlated with identification of positive non-sentinel nodes, but following adjustment for known risk factors this effect was no longer found. CONCLUSION: The time interval between diagnosis of melanoma and CLND did not influence CLND tumour load, DFS or MSS.

16 Article Pregnancy and melanoma: a European-wide survey to assess current management and a critical literature overview. 2017

Ribero, S / Longo, C / Dika, E / Fortes, C / Pasquali, S / Nagore, E / Glass, D / Robert, C / Eggermont, A M / Testori, A / Quaglino, P / Nathan, P / Argenziano, G / Puig, S / Bataille, V / Anonymous10650869. ·Department of Twin Research and Genetic Epidemiology, King's College London, London, UK. · Department of Medical Sciences, University of Turin, Turin, Italy. · Dermatology and Skin Cancer Unit, Arcispedale Santa Maria Nuova IRCCS, Reggio Emilia, Italy. · Dermatology Department, University of Bologna, Bologna, Italy. · Clinical Epidemiology Unit, IDI-IRCSS-FLMM Rome, Rome, Italy. · Surgical Oncology, Veneto Institute of Oncology - IRCCS, Padova, Italy. · Department of Dermatology, Instituto Valenciano de Oncología, Valencia, Spain. · Institut de Cancérologie, Institut Gustave Roussy, Villejuif, France. · European Institute of Oncology, Milan, Italy. · Mount Vernon Cancer Center, Northwood, UK. · Dermatology Department, Federico II University of Naples, Naples, Italy. · Melanoma Unit, Dermatology Department Hospital Clinic and University of Barcelona, CIBER de Enfermedades Raras, Barcelona, Spain. · Dermatology Department, West Herts NHS Trust, Herts, UK. ·J Eur Acad Dermatol Venereol · Pubmed #27231086.

ABSTRACT: BACKGROUND: Management of melanoma during pregnancy can be extremely challenging. The reported incidence of melanoma in pregnancy ranges from 2.8 to 5.0 per 100 000 pregnancies. There are no guidelines for the management of melanoma during pregnancy. METHODS: The survey was designed to investigate the opinions of melanoma physicians on decision making in relation to pregnancy and melanoma. A clinical scenario-based survey on management of pregnancy in melanoma was distributed all over Europe via the membership of the EORTC and other European melanoma societies. RESULTS: A total of 290 questionnaires were returned with a larger participation from southern Europe. A large heterogeneity was found for the answers given in the different clinical scenarios with 50% of the answers showing discordance, especially regarding sentinel lymph node biopsy during pregnancy. Discordant answers were also found for the counselling of women about a potential delay in getting pregnant after a high-risk melanoma (35% for a 2 year wait minimum vs. 57% no waiting needed), while for thin melanomas, as expected, there was more concordance with 70% of the physicians recommending no delay. Fifteen per cent of physicians recommended an abortion in stage II melanoma during the third month of pregnancy. Twenty per cent of the responders advised against hormonal replacement therapy in melanoma patients. CONCLUSIONS: The management of melanoma during pregnancy varies widely in Europe. At present, there is a lack of consensus in Europe, which may lead to very important decisions in women with melanoma, and guidelines are needed.

17 Article The interval between primary melanoma excision and sentinel node biopsy is not associated with survival in sentinel node positive patients - An EORTC Melanoma Group study. 2016

Oude Ophuis, C M C / Verhoef, C / Rutkowski, P / Powell, B W E M / van der Hage, J A / van Leeuwen, P A M / Voit, C A / Testori, A / Robert, C / Hoekstra, H J / Grünhagen, D J / Eggermont, A M M / van Akkooi, A C J. ·Department of Surgical Oncology, Erasmus MC Cancer Institute, Groene Hilledijk 301, 3075 EA Rotterdam, The Netherlands. Electronic address: c.oudeophuis@erasmusmc.nl. · Department of Surgical Oncology, Erasmus MC Cancer Institute, Groene Hilledijk 301, 3075 EA Rotterdam, The Netherlands. Electronic address: c.verhoef@erasmusmc.nl. · Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, ul. W.K. Roentgena 5, 02-781 Warsaw, Poland. Electronic address: rutkowskip@coi.waw.pl. · Melanoma Unit, St. George's Foundation University Hospital, Blakshaw Road, Tooting, London SW17 0QT, United Kingdom. Electronic address: bpowell@sgul.ac.uk. · Department of Surgery, The Netherlands Cancer Institute - Antoni van Leeuwenhoek, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands. Electronic address: j.vd.hage@nki.nl. · Department of Surgical Oncology, Vrije Universiteit Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands. Electronic address: pam.vleeuwen@vumc.nl. · Department of Dermatology, Charité, University of Medicine Berlin, Charitéplatz 1, 10117 Berlin, Germany. · Division of Dermato Oncological Surgery, European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy. Electronic address: alessandro.testori@ieo.it. · Department of Dermatology, Cancer Institute Gustave Roussy, 114 rue Édouard-Vaillant, 94805 Villejuif, France. Electronic address: caroline.robert@igr.fr. · Department of Surgical Oncology, Groningen University, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands. Electronic address: h.j.hoekstra@umcg.nl. · Department of Surgical Oncology, Erasmus MC Cancer Institute, Groene Hilledijk 301, 3075 EA Rotterdam, The Netherlands. Electronic address: d.grunhagen@erasmusmc.nl. · Cancer Institute Gustave Roussy, 114 rue Édouard-Vaillant, 94805 Villejuif, France. Electronic address: alexander.eggermont@igr.fr. · Department of Surgery, The Netherlands Cancer Institute - Antoni van Leeuwenhoek, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands. Electronic address: a.v.akkooi@nki.nl. ·Eur J Surg Oncol · Pubmed #27266406.

ABSTRACT: BACKGROUND: Worldwide, sentinel node biopsy (SNB) is the recommended staging procedure for stage I/II melanoma. Most melanoma guidelines recommend re-excision plus SNB as soon as possible after primary excision. To date, there is no evidence to support this timeframe. AIM: To determine melanoma specific survival (MSS) for time intervals between excisional biopsy and SNB in SNB positive patients. METHODS: Between 1993 and 2008, 1080 patients were diagnosed with a positive SNB in nine Melanoma Group centers. We selected 1015 patients (94%) with known excisional biopsy date. Time interval was calculated from primary excision until SNB. Kaplan-Meier estimated MSS was calculated for different cutoff values. Multivariable analysis was performed to correct for known prognostic factors. RESULTS: Median age was 51 years (Inter Quartile Range (IQR) 40-62 years), 535 (53%) were men, 603 (59%) primary tumors were located on extremities. Median Breslow thickness was 3.00 mm (IQR 1.90-4.80 mm), 442 (44%) were ulcerated. Median follow-up was 36 months (IQR 20-62 months). Median time interval was 47 days (IQR 32-63 days). Median Breslow thickness was equal for both <47 days and ≥47 days interval: 3.00 mm (1.90-5.00 mm) vs 3.00 mm (1.90-4.43 mm) (p = 0.402). Sentinel node tumor burden was significantly higher in patients operated ≥47 days (p = 0.005). Univariate survival was not significantly different for median time interval. Multivariable analysis confirmed that time interval was no independent prognostic factor for MSS. CONCLUSIONS: Time interval from primary melanoma excision until SNB was no prognostic factor for MSS in this SNB positive cohort. This information can be used to counsel patients.

18 Article Cancer Immunotherapy with Anti-CTLA-4 Monoclonal Antibodies Induces an Inflammatory Bowel Disease. 2016

Marthey, L / Mateus, C / Mussini, C / Nachury, M / Nancey, S / Grange, F / Zallot, C / Peyrin-Biroulet, L / Rahier, J F / Bourdier de Beauregard, M / Mortier, L / Coutzac, C / Soularue, E / Lanoy, E / Kapel, N / Planchard, D / Chaput, N / Robert, C / Carbonnel, F. ·Department of Gastroenterology, Kremlin Bicêtre Hospital, Assistance publique-Hôpitaux de Paris (AP-HP), Paris Sud University, Le Kremlin Bicêtre, France Department of Gastroenterology, Antoine Béclère Hospital, Assistance publique-Hôpitaux de Paris (AP-HP), Paris Sud University, Clamart, France. · Dermatology Unit, Department of Medical Oncology, Gustave Roussy, Paris Sud University, Villejuif, F-94805, France. · Department of Pathology, Kremlin Bicêtre Hospital, Assistance publique-Hôpitaux de Paris (AP-HP), Paris Sud University, Le Kremlin Bicêtre, France. · Department of Gastroenterology, Claude Huriez Hospital, Lille, France. · Department of Gastroenterology, Lyon Sud Hospital, Hospices Civils de Lyon, Pierre-Benite, France. · Department of Dermatology, Robert Debré Hospital, Reims, France. · Department of Gastroenterology, Nancy Hospital, Inserm U954, Lorraine University, Vandoeuvre Les Nancy, France. · Department of Hepato-Gastroenterology, CHU Dinant Godinne UCL Namur, Yvoir, Belgium. · Department of Gastroenterology, Jean Minjoz Hospital, Besançon, France. · Department of Dermatology, Claude Huriez Hospital, Lille, France. · Laboratoire d'Immunomonitoring en Oncologie, Gustave Roussy, Villejuif, F-94805, France. · Department of Gastroenterology, Kremlin Bicêtre Hospital, Assistance publique-Hôpitaux de Paris (AP-HP), Paris Sud University, Le Kremlin Bicêtre, France. · Biostatistics and Epidemiology Unit, Gustave-Roussy, Villejuif, France Inserm Unit U1018, CESP, Paris Sud University, Paris-Saclay University, Villejuif, France. · Department of Functional Coprology, Pitié Salpêtrière Hospital, Assistance publique-Hôpitaux de Paris (AP-HP), Paris, France. · Pneumology Unit, Department of Medical Oncology, Gustave Roussy, Villejuif, F-94805, France. · Laboratoire d'Immunomonitoring en Oncologie, Gustave Roussy, Villejuif, F-94805, France CNRS, UMS 3655, Villejuif, F-94805, France INSERM, US23, Villejuif, F-94805, France. · Department of Gastroenterology, Kremlin Bicêtre Hospital, Assistance publique-Hôpitaux de Paris (AP-HP), Paris Sud University, Le Kremlin Bicêtre, France fcarbonnel7@gmail.com. ·J Crohns Colitis · Pubmed #26783344.

ABSTRACT: BACKGROUND: Therapeutic monoclonal anti-cytotoxic T-lymphocyte-associated antigen 4 (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 from 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 and 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 (83%) responded. 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 compared with patients without enterocolitis (31 vs 5%, p = 0.003). CONCLUSIONS: Ipilimumab and tremelimumab may induce a severe and extensive form of inflammatory bowel disease. 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.

19 Article Melanoma risk-takers: fathers and sons. 2015

Eisinger, F / Morère, J-F / Pivot, X / Grange, F / Lhomel, C / Mortier, L / Robert, C / Saiag, P / Sassolas, B / Viguier, J. ·Paoli-Calmettes Institute, Inserm umr 599, Marseille, France. ·J Eur Acad Dermatol Venereol · Pubmed #25639932.

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.

20 Article Personal vs. intrinsic melanoma risk awareness: results of the EDIFICE Melanoma survey. 2015

Robert, C / Lebbe, C / Ricard, S / Saiag, P / Grange, F / Mortier, L / Lhomel, C / Sassolas, B. ·Department of Dermatology, Institut Gustave Roussy, Villejuif, France. ·J Eur Acad Dermatol Venereol · Pubmed #25639931.

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. RESULTS: Although 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.

21 Article Prevalence of sunbed use, and characteristics and knowledge of sunbed users: results from the French population-based Edifice Melanoma survey. 2015

Grange, F / Mortier, L / Crine, A / Robert, C / Sassolas, B / Lebbe, C / Lhomel, C / Saiag, P. ·Department of Dermatology, Robert Debré University Hospital, Reims, France. ·J Eur Acad Dermatol Venereol · Pubmed #25639930.

ABSTRACT: BACKGROUND: In addition to natural sunlight, indoor tanning has emerged as a common source of ultraviolet (UV) radiation associated with an increased risk of melanoma. It is classified as a class I human carcinogen by the World Health Organization. OBJECTIVES: This analysis presents data on the prevalence of sunbed use in France, on factors associated with sunbed use, and on risk factors, attitude and awareness of risk among sunbed users and non-users. METHODS: Edifice Melanoma, a nationwide observational survey, was conducted in France via telephone interviews among a representative sample of 1502 subjects aged ≥18 years, using the quota method. Sunbed users were defined as individuals who reported having used a sunbed at least once in their lifetime. Logistical regressions were conducted in order to identify which factors differentiate the population of sunbed users from that of non-users. RESULTS: One in ten respondents was a sunbed user and three out of four declared having used tanning facilities for over one year. In multivariate analysis, factors significantly associated with the sunbed-user group were female gender (OR = 3.897 [2.573-5.903], P < 0.001), a higher socio-professional category (OR = 2.227 [1.542-3.217]; P < 0.001), fair hair (OR = 1.583 [1.025-2.447], P = 0.039), fair skin (OR = 1.879 [1.086-3.253]; P = 0.024), freckles (OR = 1.570 [1.071-2.302]; P = 0.021) and a history of smoking (OR = 2.383 [1.633-3.476]; P < 0.001). In a second multivariate model, the fact of having a large number of melanoma risk factors was strongly associated with sunbed use (P = 0.001). Sunbed users were more likely to be informed of the role of sun exposure in reducing the skin's regenerative capacity (OR = 2.181 [1.319-3.607]; P = 0.002) but were nevertheless more likely to consider that a tan makes a person look more attractive (OR = 2.309 [1.312-4.064]; P = 0.004) and protects the skin (OR = 2.490 [1.532-4.046]; P < 0.001); they were also more frequently exposed to natural sunlight (OR = 2.214 [1.196-4.102]; P = 0.011). CONCLUSIONS: Compared to non-users, sunbed users cumulate risk factors for melanoma. Knowledge, attitudes and intentions of individuals are critical targets for public education programmes. However, awareness campaigns focusing on sunbed use, and more generally on skin cancer, should also take social and cultural norms into account.

22 Article Comparison of sun protection modalities in parents and children. 2015

Mortier, L / Lepesant, P / Saiag, P / Robert, C / Sassolas, B / Grange, F / Lhomel, C / Lebbe, C. ·Department of Dermatology, Hôpital Claude Huriez, Lille, France. ·J Eur Acad Dermatol Venereol · Pubmed #25639928.

ABSTRACT: BACKGROUND: Routine sun protection is recommended to prevent skin cancer. The aims of the present analysis were to assess and compare modalities of sun protection in parents and their children. METHODS: EDIFICE Melanoma is a French nationwide observational survey. It was conducted through phone interviews among a representative sample of 1502 individuals aged ≥18 years, using the method of quotas. The survey took place shortly after the summer, from 28 September to 20 October 2011. RESULTS: Of the 1502 subjects interviewed, 1067 reported sun exposure (SE) at least 10 days per year, 748 were parents and 319 had no children. Sun protection measures seemed adequate in both the 'parents' and 'non-parents' groups: 74% used clothing and 43% used sunscreen, which was reapplied regularly in 57% of cases. Sun protection measures used by SE parents for SE children were superior, both qualitatively and quantitatively, to those used for themselves, i.e., 50% of parents reported using clothing, sunglasses and hats for their children vs. 23% for themselves. In 87% of cases, parents reported regular re-application of sunscreen for their children vs. 44% for themselves. The sunscreen SPF (Sun Protection Factor) was significantly lower for parents than for their children. CONCLUSIONS: Sun protection awareness appears to be globally satisfactory in the French population, with no difference between adults who are parents and those who are not. From both qualitative and quantitative standpoints, French parents use sun protective measures more efficiently for their children than for themselves.

23 Article EDIFICE Melanoma survey: knowledge and attitudes on melanoma prevention and diagnosis. 2015

Saiag, P / Sassolas, B / Mortier, L / Grange, F / Robert, C / Lhomel, C / Lebbé, C. ·Department of Dermatology, Hôpital Ambroise Paré, Boulogne-Billancourt, France. ·J Eur Acad Dermatol Venereol · Pubmed #25639927.

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. RESULTS: Respondents 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.

24 Article Sun exposure profile in the French population. Results of the EDIFICE Melanoma survey. 2015

Sassolas, B / Grange, F / Touboul, C / Lebbe, C / Saiag, P / Mortier, L / Lhomel, C / Robert, C. ·Department of Internal medicine and Respiratory Diseases, Hôpital Cavale Blanche, Brest, France. ·J Eur Acad Dermatol Venereol · Pubmed #25639926.

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. RESULTS: More 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.

25 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.

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