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Melanoma: HELP
Articles by Lucie Peuvrel
Based on 23 articles published since 2008
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Between 2008 and 2019, L. Peuvrel wrote the following 23 articles about Melanoma.
 
+ Citations + Abstracts
1 Guideline Guidelines of the French Society of Otorhinolaryngology (SFORL), short version. Extension assessment and principles of resection in cutaneous head and neck tumors. 2014

Anonymous4420813 / Durbec, M / Couloigner, V / Tronche, S / Albert, S / Kanitakis, J / Ltaief Boudrigua, A / Malard, O / Maubec, E / Mourrain Langlois, E / Navailles, B / Peuvrel, L / Phulpin, B / Thimonier, J-C / Disant, F / Dolivet, G. ·Service d'ORL, hôpital Édouard-Herriot, 5, place d'Arsonval, 69003 Lyon, France. Electronic address: mickael.durbec@chu-lyon.fr. · Société française d'ORL & CCF, 26, rue Lalo, 75116 Paris, France. · Service d'ORL, hôpital Bichat, AP-HP, 46, rue Henri-Huchard, 75018 Paris, France. · Service de dermatologie, hôpital Édouard-Herriot, 5, place d'Arsonval, 69003 Lyon, France. · Service de radiologie, hôpital Édouard-Herriot, 5, place d'Arsonval, 69003 Lyon, France. · Service d'ORL, Hôtel-Dieu, 1, place Alexis-Ricordeau, 44093 Nantes cedex 1, France. · Service de dermatologie, hôpital Saint-Louis, 1, avenue Claude-Vellefaux, 75010 Paris, France. · Service de radiologie, Hôtel-Dieu, 1, place Alexis-Ricordeau, 44093 Nantes cedex 1, France. · Service d'ORL, centre hospitalier de Valence, 179, avenue du Maréchal-Juin, 26000 Valence, France. · Service d'onco-dermatologie, Hôtel-Dieu, 1, place Alexis-Ricordeau, 44093 Nantes cedex 1, France. · Institut de cancérologie de Lorraine, 6, avenue de Bourgogne, 54519 Vandœuvre-lès-Nancy, France. · Service d'ORL, hôpital Édouard-Herriot, 5, place d'Arsonval, 69003 Lyon, France. · Service d'ORL, département de chirurgie oncologique, institut de cancérologie de Lorraine, 6, avenue de Bourgogne, 54519 Vandœuvre-lès-Nancy, France. ·Eur Ann Otorhinolaryngol Head Neck Dis · Pubmed #25456243.

ABSTRACT: Cutaneous head and neck tumors mainly comprise malignant melanoma, squamous cell carcinoma, trichoblastic carcinoma, Merkel cell carcinoma, adnexal carcinoma, dermatofibrosarcoma protuberans, sclerodermiform basalioma and angiosarcoma. Adapted management requires an experienced team with good knowledge of the various parameters relating to health status, histology, location and extension: risk factors for aggression, extension assessment, resection margin requirements, indications for specific procedures, such as lateral temporal bone resection, orbital exenteration, resection of the calvarium and meningeal envelopes, neck dissection and muscle resection.

2 Review Melanoma and rituximab: an incidental association? 2013

Peuvrel, L / Chiffoleau, A / Quéreux, G / Brocard, A / Saint-Jean, M / Batz, A / Jolliet, P / Dréno, B. ·Department of Dermato-Cancerology, Nantes University Hospital, INSERM U892-CNRS U6299, CIC Biothérapie INSERM 0503, Nantes, France. ·Dermatology · Pubmed #23941917.

ABSTRACT: Rituximab is an anti-CD20 monoclonal antibody increasingly used in haematology and rheumatology, but also in internal medicine and dermatology. It has a good tolerance profile without known increased risk of cancer. We report a case of nodular melanoma with a 4.8 mm Breslow thickness that appeared after 2 years of rituximab in a 45-year-old patient with non-Hodgkin lymphoma. Fifteen additional rituximab-associated melanoma cases in 13 patients have been identified in the literature and in the EudraVigilance database. These patients were treated for various indications and had melanomas, often aggressive, initially diagnosed at a metastatic stage in 31% of cases. Our work raises the question of rituximab accountability in melanoma onset in these immunosuppressed patients. A dermatological monitoring seems necessary in patients treated with rituximab, especially in case of risk factors for melanoma. In case of individual melanoma history, the benefit/risk ratio of initiating rituximab therapy should be carefully assessed.

3 Clinical Trial Adoptive T cell therapy combined with intralesional administrations of TG1042 (adenovirus expressing interferon-γ) in metastatic melanoma patients. 2015

Khammari, Amir / Nguyen, Jean-Michel / Saint-Jean, Melanie / Knol, Anne-Chantal / Pandolfino, Marie-Christine / Quereux, Gaelle / Brocard, Anabelle / Peuvrel, Lucie / Saiagh, Soraya / Bataille, Vincent / Limacher, Jean-Marc / Dreno, Brigitte. ·Dermato-Oncology Department, Nantes Hospital, 1 Place Alexis Ricordeau, 44093, Nantes Cedex 1, France. ·Cancer Immunol Immunother · Pubmed #25846669.

ABSTRACT: Tumor immune escape has recently been shown to be related to the development of an immune tolerance state of the microenvironment. Cytokines activating the immune system such as IFN-γ can be used to reverse the immune escape and thus to potentiate the efficacy of immunotherapy. A clinical study was conducted in 18 stage IIIc/IV melanoma patients treated with tumor-infiltrating lymphocytes (TILs) in combination with intratumoral TG1042 injection (adenovirus expressing IFN-γ). The primary objective was to investigate the safety of treatment. Secondary objectives were to study the clinical response and translational research. The treatment was well tolerated. Among the 13 patients evaluable for tumor response, 38.5% had an overall objective response (OOR = CR + PR) and disease control rate (DCR = CR + PR + S) of 46%. The clinical response of the 37 targeted lesions led to an OOR of 51% and a DCR of 75%. Translational research on predictive markers did not significantly differ between responder and non-responder patients. However, specifically regarding injected lesions, the clinical response correlated with CD3-/CD56+ NK cells which could be activated by TG1042. Further larger studies of this combined immunotherapy are needed to confirm our findings. Intralesional TG1042 combined with antigen-selected TILs should be discussed.

4 Article Drug reaction with eosinophilia and systemic symptoms syndrome induced by combination of vemurafenib and cobimetinib in melanoma: A series of 11 cases. 2019

Brégeon, Barbara / Bernier, Claire / Josselin, Nicolas / Peuvrel, Lucie / Le Moigne, Marie / Saint-Jean, Mélanie / Quéreux, Gaëlle. ·Service de Dermatologie, Centre Hospitalier Universitaire de Nantes, Nantes, France; Immuno-Dermatology Laboratory, Nantes University Hospital, Nantes, France; Nantes University, Nantes, France. Electronic address: barbara.bregeon@gmail.com. · Service de Dermatologie, Centre Hospitalier Universitaire de Nantes, Nantes, France. · Immuno-Dermatology Laboratory, Nantes University Hospital, Nantes, France. · Service de Dermatologie, Centre Hospitalier Universitaire de Nantes, Nantes, France; Immuno-Dermatology Laboratory, Nantes University Hospital, Nantes, France. · Service de Dermatologie, Centre Hospitalier Universitaire de Nantes, Nantes, France; Immuno-Dermatology Laboratory, Nantes University Hospital, Nantes, France; Nantes University, Nantes, France. ·J Am Acad Dermatol · Pubmed #30081108.

ABSTRACT: -- No abstract --

5 Article Positive margins after surgical excision of locoregional cutaneous melanoma metastasis and their impact on patient outcome. 2018

Bregeon, Barbara / Nguyen, Jean-Michel / Varey, Emilie / Quereux, Gaelle / Saint-Jean, Mélanie / Peuvrel, Lucie / Khammari, Amir / Dreno, Brigitte. ·Service de dermatologie, Hôtel-Dieu, CHU de Nantes, Nantes, France. · Service de dermatologie, Hôtel-Dieu, CHU de Nantes, Nantes, France, PIMESP-SEB, Saint-Jacques Hospital, Nantes, France. · Service de dermatologie, Hôtel-Dieu, CHU de Nantes, Nantes, France, Service de dermatologie, CIC 1413, CRCINA INSERM 1232, CHU de Nantes, Nantes, France. ·Eur J Dermatol · Pubmed #30378546.

ABSTRACT: For melanoma patients, surgery is a standard treatment for locoregional skin metastasis (LSM). To assess the frequency and risk factors for positive margins after excision of LSM and their impact on patient overall survival (OS) and progression-free survival (PFS). A monocentric, retrospective observational study was performed including 87 patients with LSM who had undergone surgical excision. Positive margins were found in 45% of patients after excision. After additional excision, 28% of patients still had positive margins. Interestingly, there was no difference in PFS or OS for clear margins after the first or additional excision or for margins that remained positive without additional excision. LSM size was the only identified predictive factor for positive margins. This is the first reported study investigating the frequency of, and risk factors for positive margins of cutaneous LSM, which raises the question of whether additional excision should be performed following positive margin excision.

6 Article Adoptive Cell Therapy with Tumor-Infiltrating Lymphocytes in Advanced Melanoma Patients. 2018

Saint-Jean, Mélanie / Knol, Anne-Chantal / Volteau, Christelle / Quéreux, Gaëlle / Peuvrel, Lucie / Brocard, Anabelle / Pandolfino, Marie-Christine / Saiagh, Soraya / Nguyen, Jean-Michel / Bedane, Christophe / Basset-Seguin, Nicole / Khammari, Amir / Dréno, Brigitte. ·Dermato-cancerology Department, CHU Nantes, Place Alexis Ricordeau, 44093 Nantes, France. · CIC1413, CRCINA INSERM U1232, CHU Nantes, Place Alexis Ricordeau, Nantes, France. · Research Leading Department, CHU Nantes, Place Alexis Ricordeau, 44093 Nantes, France. · Cell and Gene Therapy Unit, CHU Nantes, Place Alexis Ricordeau, 44093 Nantes, France. · SEME, CIC1413, CRCINA INSERM U1232, CHU Nantes, Place Alexis Ricordeau, Nantes, France. · Dermatology Department, University Hospital, 2 avenue Martin Luther King, 87042 Limoges Cedex, France. · Dermatology Department, Saint-Louis Hospital, 1 avenue Claude-Vellefaux, 75475 Paris Cedex 10, France. ·J Immunol Res · Pubmed #29750176.

ABSTRACT: Immunotherapy for melanoma includes adoptive cell therapy with autologous tumor-infiltrating lymphocytes (TILs). This monocenter retrospective study was undertaken to evaluate the efficacy and safety of this treatment of patients with advanced melanoma. All advanced melanoma patients treated with TILs using the same TIL expansion methodology and same treatment interleukin-2 (IL-2) regimen between 2009 and 2012 were included. After sterile intralesional excision of a cutaneous or subcutaneous metastasis, TILs were produced according to a previously described method and then infused into the patient who also received a complementary subcutaneous IL-2 regimen. Nine women and 1 man were treated for unresectable stage IIIC (

7 Article Pyoderma Gangrenosum Under Dabrafenib and Trametinib for Metastatic Melanoma. 2018

Saint-Jean, Mélanie / Le Moigne, Marie / Daguze, Justine / Bossard, Céline / Peuvrel, Lucie / Quéreux, Gaëlle / Dréno, Brigitte. ·Department of Dermatology, University of Poitiers, Poitiers, France. ·Acta Derm Venereol · Pubmed #29362816.

ABSTRACT: -- No abstract --

8 Article Blood Predictive Biomarkers for Nivolumab in Advanced Melanoma. 2018

Chasseuil, Edouard / Saint-Jean, Mélanie / Chasseuil, Hannah / Peuvrel, Lucie / Quéreux, Gaëlle / Nguyen, Jean-Michel / Gaultier, Aurélie / Varey, Emilie / Khammari, Amir / Dréno, Brigitte. ·Department of Dermatology, University of Poitiers, Poitiers, France. ·Acta Derm Venereol · Pubmed #29327065.

ABSTRACT: Nivolumab response rate is 40% in metastatic melanoma. Few studies have evaluated pre-treatment biomarkers predictive of response. The aim of this study was to identify potential peripheral blood biomarkers associated with survival in patients with advanced melanoma treated with nivolumab. All advanced melanoma cases treated with anti-programmed cell death protein 1 (anti-PD1) over a 3-year period in the Dermato-Oncology Department, Nantes, France were identified. For each case, 9 potential blood biomarkers were identified. Bivariate and multivariate analyses, adjusted for the American Joint Committee on Cancer (AJCC) classification stage, Eastern Cooperative Oncology Group (ECOG) performance status, lactate dehydrogenase (LDH) level and failure to respond to first-line therapy, were used to test the association between biomarkers and overall survival (primary outcome) or progression-free survival (secondary outcome). Increased monocyte count, leukocyte/lymphocyte ratio and neutrophil/lymphocyte ratio were significantly associated with decreased overall survival after bivariate and multivariate analyses. Increased monocyte count was also significantly associated with decreased progression-free survival. These blood variables are easily measured and could help to predict patient response before the introduction of anti-PD1 therapy.

9 Article Histopathological aspects of cutaneous erythematous-papular eruptions induced by immune checkpoint inhibitors for the treatment of metastatic melanoma. 2017

Perret, Raul E / Josselin, Nicolas / Knol, Anne-Chantal / Khammari, Amir / Cassecuel, Julie / Peuvrel, Lucie / Dreno, Brigitte / Anonymous4570896. ·Oncodermatology department, CIC, CHU, Nantes, France. · Histopathology Institute, Nantes, France. · Immunodermatology lab, CHU, Nantes, France. · U 892, INSERM, Nantes, France. ·Int J Dermatol · Pubmed #28188628.

ABSTRACT: BACKGROUND: Immune checkpoint blockade therapy (ICBT) for the treatment of melanoma has led to an important improvement of overall survival in advanced stage patients. However, secondary cutaneous maculopapular eruptions (CMPEs) are frequent and remain poorly characterized. METHODS: We performed a retrospective analysis of melanoma patients from our institution who developed CMPEs during ICBT. Clinical information was retrieved, and histopathological and immunohistochemical characterization was performed by two pathologists. For comparison, a group of biopsies from CMPE caused by anti-v-raf murine sarcoma viral oncogene homolog B1 (BRAF) therapy was analyzed. RESULTS: Eleven patients met the inclusion criteria. On clinical grounds, CMPE developed mainly on early onset of immunotherapy and were of low grade. Typical lesions included erythematous papules and macules affecting the trunk and/or extremities with associated pruritus. The histopathological patterns consisted of a superficial perivascular lymphocytic dermatitis (SPLD) with eosinophils followed by a granulomatous dermatitis. Other patterns included lichenoid, spongiotic, and a case of Grover's disease. The inflammatory infiltrate consisted of T lymphocytes (CD3 CONCLUSIONS: Our study showed the clinical features of a group of melanoma patients with CMPE for ICBT and emphasized the wide spectrum of histological findings as well as their immunohistochemical profile. Differential diagnosis can be difficult with CMPE provoked by other therapies as was seen in our comparison group of anti-BRAF-induced eruptions.

10 Article Clinical, Genetic and Innate Immunity Characteristics of Melanoma in Organ Transplant Recipients. 2017

Brocard, Anabelle / Knol, Anne-Chantal / Bossard, Céline / Denis, Marc Guillaume / Quéreux, Gaëlle / Saint-Jean, Mélanie / Peuvrel, Lucie / Khammari, Amir / Blancho, Gilles / Dantal, Jacques / Dréno, Brigitte. ·Department of Dermatology, Nantes University Hospital, INSERM, 892, FR-44000 Nantes, France. ·Acta Derm Venereol · Pubmed #27868139.

ABSTRACT: The aims of this study were to determine the clinical and histological characteristics of melanoma in transplant recipients, the mutation profile (BRAF, NRAS and c-KIT genes), and the immune tolerance of the tumour microenvironment by immunohistochemical study of the expression of indoleamine 2,3-dioxygenase (IDO), PD1, PD-L1, CD8 and FoxP3. The study population comprised patients who had undergone a renal transplant in Nantes University Hospital who developed post-transplantation melanoma. Twenty cases of melanoma out of 4,663 transplant recipients were studied. The results differed from the usual data with respect to melanoma site: 40% were located on the face and were of the malignant lentigo type. The mutation profile was concordant with that of the immunocompetent population. IDO was expressed in all the sections tested, while CD8, FoxP3, PD1 and PD-L1 were poorly expressed. This reflected a highly immunodepressed tumour environment, raising the question of the inductive role of IDO on tumour immune tolerance in patients presenting with long-term immunodepression.

11 Article Clinical significance of BRAF mutation status in circulating tumor DNA of metastatic melanoma patients at baseline. 2016

Knol, Anne C / Vallée, Audrey / Herbreteau, Guillaume / Nguyen, Jean-Michel / Varey, Emilie / Gaultier, Aurélie / Théoleyre, Sandrine / Saint-Jean, Mélanie / Peuvrel, Lucie / Brocard, Anabelle / Quéreux, Gaëlle / Khammari, Amir / Denis, Marc G / Dréno, Brigitte. ·CRCNA, , INSERM U892, CNRS 6299, Nantes Cedex 01, France. · Laboratoire de Biochimie et Plateforme de Génétique des Cancers, CHU Hôtel-Dieu, Nantes Cedex 01, France. · SEB-PIMESP, CHU Nantes, Nantes Cedex 01, France. · Unité de Cancéro-Dermatologie-CIC biothérapie INSERM 0503, CHU Hôtel-Dieu, Nantes Cedex 01, France. · CRCNA, , INSERM U892, CNRS 6299, Nantes Cedex 01, France. brigitte.dreno@wanadoo.fr. · Unité de Cancéro-Dermatologie-CIC biothérapie INSERM 0503, CHU Hôtel-Dieu, Nantes Cedex 01, France. brigitte.dreno@wanadoo.fr. ·Exp Dermatol · Pubmed #27194447.

ABSTRACT: Circulating tumor DNA is a promising non-invasive tool for cancer monitoring. The main objective of our work was to investigate the relationship between mutant BRAF DNA in plasma and clinical response. Thirty-eight stage IV patients with a V600 mutated BRAF melanoma were included prior to any treatment. DNA was extracted from plasma and mutant DNA was detected using the amplification-refractory mutation system method. Before the beginning of any treatment, the corresponding BRAF mutation was detected in 29 of the 38 tested plasma samples (76.3% positive per cent agreement). We observed a strong correlation between the presence of circulating mutated DNA and overall survival (OS; P=.02), and with the number of metastatic sites (P=.01). The presence of circulating mutated DNA was also strongly correlated with serum LDH activity (P<.01) and S100 protein concentration (P<.01). Finally, seven patients presented discordant BRAF status in different tumor sites. In all these patients, the test performed on ctDNA was positive, suggesting that ctDNA analysis might be less sensitive to tumor heterogeneity. Altogether, these results suggest that plasmatic mutant BRAF DNA is a prognostic factor of OS, correlated with tumor burden. In addition, it represents an interesting alternative source of DNA to detect BRAF mutations before treatment.

12 Article Development of brain metastases in patients with metastatic melanoma while receiving ipilimumab. 2016

Frenard, C / Peuvrel, L / Jean, M Saint / Brocard, A / Knol, A C / Nguyen, J M / Khammari, A / Quereux, G / Dreno, B. ·Department of dermatology, Skin Cancer Unit, Nantes University Hospital, INSERM 892, 1 place Alexis Ricordeau, 44093, Nantes Cedex 1, France. · Department of dermatology, Skin Cancer Unit, Nantes University Hospital, INSERM 892, 1 place Alexis Ricordeau, 44093, Nantes Cedex 1, France. brigitte.dreno@wanadoo.fr. ·J Neurooncol · Pubmed #26511495.

ABSTRACT: OBJECTIVES: To assess the development of brain metastases under ipilimumab and identify clinical, histological or evolving criteria related to the appearance of these metastases. A retrospective study was conducted in 52 patients treated with 4 cycles of ipilimumab 3 mg/kg every 3 weeks for unresectable stage III or stage IV melanoma between January 2011 and July 2013 in a Department of Dermato-Oncology. As no data has been find in the literature, the results were compared to our other cohort of patients treated with vemurafenib during the same period. Ten patients (21.7 %) developed brain metastases under ipilimumab in a median time of 6.58 months after treatment initiation. The multivariate analysis showed a lower rate of brain metastases in patients with acral lentiginous melanoma and melanoma of unknown primary site. The median survival after diagnosis of brain metastases was of 2.5 months. There was no significant difference with vemurafenib-treated patients in terms of incidence rate of brain metastasis, time of development and survival after diagnosis of cerebral metastases. This was the first study focused on the development of brain metastases under treatment with ipilimumab 3 mg/kg. Although ipilimumab is used for the treatment of brain metastases, it paradoxically did not seem to reduce the risk of developing brain metastases.

13 Article Early-Onset Vemurafenib-Induced DRESS Syndrome. 2016

Munch, Marion / Peuvrel, Lucie / Brocard, Anabelle / Saint Jean, Mélanie / Khammari, Amir / Dreno, Brigitte / Quereux, Gaelle. ·Dermatology, Inserm 892, Nantes University Hospital, Nantes, France. ·Dermatology · Pubmed #26418832.

ABSTRACT: Vemurafenib is a BRAF inhibitor indicated in metastatic or unresectable melanoma in patients with BRAF mutations. Vemurafenib is frequently toxic, but the toxicity is often not serious. The third case of vemurafenib-induced drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is reported herein. The case is unusual in that the onset was early, with symptoms emerging as of day 8 of treatment. Treatment of DRESS syndrome is not currently based on precise recommendations, but systemic corticosteroid therapy is effective in serious cases. Severe toxidermias under vemurafenib are exceptional; immediate discontinuation of treatment upon diagnosis is imperative. Switching from vemurafenib to dabrafenib then seems to constitute an interesting therapeutic alternative, since its efficacy is the same but with fewer cutaneous adverse reactions. This case highlights the importance of awareness of the risk of DRESS syndrome associated with vemurafenib and monitoring for warning signs from treatment initiation.

14 Article Phototoxicity of B-RAF inhibitors: Exclusively due to UVA radiation and rapidly regressive. 2015

Gabeff, Romain / Dutartre, Hervé / Khammari, Amir / Boisrobert, Aurélie / Nguyen, Jean-Michel / Quereux, Gaëlle / Brocard, Anabelle / Saint-Jean, Mélanie / Peuvrel, Lucie / Dreno, Brigitte. ·Clinique Dermatologique, Hôpital Hôtel-Dieu, CHU Nantes Place Alexis Ricordeau, 44093 Cedex 01 - France. ·Eur J Dermatol · Pubmed #26242321.

ABSTRACT: BACKGROUND: New targeted melanoma therapies such as B-RAF inhibitors have shown high and promising clinical benefit but have cutaneous side-effects, including photosensitivity, which is triggered in the UVA radiation spectrum. However, visible spectrum implication has not yet been investigated. We conducted a study to determine whether visible light also contributes to the phototoxicity action spectrum of vemurafenib. The secondary end points were to determine the time to complete regression of the phototoxicity post-vemurafenib discontinuation and whether there was a significant difference between the UVA radiation immediate reactivity cut-offs, in patients treated with vemurafenib vs. those treated with dabrafenib. METHOD: This prospective, observational study included patients with B-RAF mutant metastatic melanoma: 34 patients treated with vemurafenib and 9 with dabrafenib. RESULTS: The visible-light phototest results in patients treated with vemurafenib were all negative before and after 2 months of treatment. The UVA radiation phototests conducted 1 or 2 weeks post-vemurafenib discontinuation in 4 patients showed a normalised UVA-radiation reactivity cut-off. UVA radiation phototests after 2 months of treatment were conducted for all patients. The UVA radiation reactivity cut-off had been lowered for 30 patients (88%) on vemurafenib and 3 patients (33%) on dabrafenib. The median UVA radiation reactivity cut-off was 12 J/cm(2) for the patients on vemurafenib and 20 J/cm(2) for the patients on dabrafenib. CONCLUSION: B-RAF inhibitor phototoxicity is exclusively triggered by UVA radiation and resolves rapidly post-treatment discontinuation. A significant difference between the UVA immediate reactivity cut-offs, vemurafenib vs. dabrafenib, explains the difference in the clinical photosensitivity rates reported in the clinical trials.

15 Article Incidence and characteristics of melanoma brain metastases developing during treatment with vemurafenib. 2014

Peuvrel, L / Saint-Jean, M / Quéreux, G / Brocard, A / Khammari, A / Knol, A C / Dréno, B. ·Department of Dermato-Cancerology, Nantes University Hospital, INSERM U892-CNRS U6299, CIC Biothérapie INSERM 0503, 1 place Alexis Ricordeau, 44000, Nantes, France. ·J Neurooncol · Pubmed #25098698.

ABSTRACT: Vemurafenib is indicated for the treatment of patients with BRAF (V600)-mutant metastatic melanoma. We studied for the first time the characteristics of brain metastases developed during treatment with vemurafenib in real-life conditions. We included all patients treated over 3 years with vemurafenib in our department for metastatic melanoma without initial brain involvement. Our primary endpoint was to assess the incidence of brain metastases in these patients. Our secondary endpoints were to identify the risk factors for metastases occurrence and their characteristics and course. In our retrospective cohort of 86 patients, 20% had developed brain metastases on average 5.3 months after vemurafenib initiation. The median follow-up was 9 months (1-26 months). Radiological examinations revealed multiple brain metastases in 41% of patients. The only risk factor for metastasis occurrence identified was a high number of metastatic sites when initiating vemurafenib (p = 0.045). Metastasis development was associated with a trend toward a decrease in overall survival from 12.8 to 8.5 months (p = 0.07) and a significant decrease in progression-free survival from 7 to 5 months (p = 0.04). Among the patients who developed brain metastases, 82% died, of whom 64% within 3 months, versus 58% of patients without brain metastases over the same period. The extra-cerebral disease was well controlled in 59% of patients during brain progression. In vemurafenib-treated melanoma patients, brain metastases are frequent and associated with a particularly poor prognosis. Because of their high frequency in patients with controlled extra-cerebral disease, brain explorations should be systematically performed during treatment.

16 Article Younger age at the time of first metastasis in BRAF-mutated compared to BRAF wild-type melanoma patients. 2014

Saint-Jean, Melanie / Quereux, Gaëlle / Nguyen, Jean-Michel / Peuvrel, Lucie / Brocard, Anabelle / Vallee, Audrey / Knol, Anne-Chantal / Khammari, Amir / Denis, Marc G / Dréno, Brigitte. ·Department of Dermato-Cancerology, University Hospital Hôtel-Dieu, Nantes, France. · PIMESP, Saint-Jacques Hospital, Nantes, France. · Department of Biochemistry, University Hospital Hôtel-Dieu, Nantes, France. · Inserm U892, CIC Biothérapie Inserm 0503, Nantes, France. ·Oncol Rep · Pubmed #24926836.

ABSTRACT: The relationship between BRAF mutations and the patient clinical profile is still under question. The objective of the present study was to correlate the BRAF mutation status in primary and metastatic melanomas with the clinicopathological profile, disease-free (DFS) and overall survival (OS). A total of 367 melanoma samples from 278 patients were screened for their BRAF status using a combination of allele-specific amplification and DNA sequencing. Two or three tissue samples from the same patient were available for 74 patients. The clinicopathological characteristics were tested for their association with the BRAF mutation using the Fisher's or Pearson's χ2 test. Log-rank tests and Cox models were used for survival analyses. BRAF mutation was found in 152 samples (41.4%). Ten of the 74 patients with several tissue samples (13.5%) had discordant BRAF mutation results. BRAF-mutated patients were significantly younger at the time of primary melanoma and first diagnosis of metastasis than BRAF wild-type patients but with no difference in DFS and OS. According to our results, a primary melanoma with BRAF mutation is not associated with a more aggressive illness.

17 Article Ipilimumab-induced autoimmune pancytopenia in a case of metastatic melanoma. 2014

du Rusquec, Pauline / Saint-Jean, Melanie / Brocard, Anabelle / Peuvrel, Lucie / Khammari, Amir / Quéreux, Gaelle / Dréno, Brigitte. ·Departments of *Dermato-Oncology †CIC Biotherapy INSERM U892, Hôtel-Dieu University Hospital, Nantes, France. ·J Immunother · Pubmed #24911795.

ABSTRACT: A 77-year-old patient treated with ipilimumab (anti-CTLA-4 antibody) for metastatic melanoma developed autoimmune pancytopenia (anemia, thrombocytopenia, and neutropenia) 8 days after the fourth infusion. This pancytopenia was resistant to high-dose oral corticosteroids (1 mg/kg) and to hematopoietic growth factors. It resolved after intravenous immunoglobulins injection. To date, only 1 case of autoimmune pancytopenia has been reported after this treatment. According to the case that we report, it seems essential to control the leukocyte count before any injection of ipilimumab.

18 Article Severe radiotherapy-induced extracutaneous toxicity under vemurafenib. 2013

Peuvrel, Lucie / Ruellan, Anne-Lise / Thillays, François / Quereux, Gaëlle / Brocard, Anabelle / Saint-Jean, Mélanie / Aumont, Maud / Drouet, Franck / Dreno, Brigitte. ·Department of Dermato-Cancerology, Nantes University Hospital, INSERM U892-CNRS U6299, CIC Biothérapie INSERM 0503, 1 place Ricordeau, 44000 Nantes, France. · Pharmacovigilance, Department of Clinical Pharmacology, Nantes University Hospital, Nantes, France. · Service de radiothérapie, ICO René Gauducheau, 44800 Saint-Herblain, France. ·Eur J Dermatol · Pubmed #24192487.

ABSTRACT: BACKGROUND: Vemurafenib is a BRAF inhibitor indicated for the treatment of metastatic melanoma. We report the two first cases of severe and prolonged radiotherapy-induced visceral toxicity in patients treated concomitantly with vemurafenib: a brain radionecrosis and an anorectitis. It raises the question of both the risks of this association and its benefit in melanoma. OBSERVATIONS: The first patient, a female aged 32, treated with vemurafenib for three months, presented a steroid-dependent radionecrosis after brain stereotactic radiosurgery. Symptoms persisted until her death six months later. The second patient, a male aged 64 and treated with vemurafenib for nineteen days, presented a radiation-induced anorectitis complicated by diarrhoea, anorexia and weight loss following the concomitant radiation of a primary rectal tumour. A colostomy was needed after ten months in order to improve local status and general health. CONCLUSIONS: In our patients, the radiotherapy-induced toxicity under vemurafenib was unusual in its intensity and duration, suggesting a radiosensitization phenomenon. This hypothesis is reinforced by the publication of six cases of severe radiodermatitis under vemurafenib and by in vitro data. The combination of vemurafenib and radiotherapy should thus lead to discussion of a transient cessation of vemurafenib, given the severity of the adverse events experienced. Meanwhile, further studies are needed to determine the potential benefit of this combined treatment in metastatic melanoma.

19 Article Tissue biomarkers in melanoma patients treated with TIL. 2012

Knol, Anne-Chantal / Nguyen, Jean-Michel / Pandolfino, Marie-Christine / Quéreux, Gaëlle / Brocard, Anabelle / Peuvrel, Lucie / Saint-Jean, Mélanie / Saiagh, Soraya / Khammari, Amir / Dréno, Brigitte. ·INSERM, U892, CRCNA, Nantes, France. ·PLoS One · Pubmed #23284620.

ABSTRACT: While treating stage III melanoma patients with autologous therapeutic TIL in an adjuvant setting, we previously reported a significant benefit of treatment on both progression-free survival and overall survival in patients with only one invaded lymph node (early stage III) compared to patients with more than one invaded lymph nodes (advanced stage III). In this context, in order to understand the difference of activity of TIL therapy according to the progression of the illness at stage III, the first objective of the present study was to determine potential differences in the characteristics of TIL populations obtained from an early stage III and a more advanced stage III when tumor burden is more important. The second objective was to determine possible differences in tissue expression level of several molecules involved in interactions between tumor cells and T cells between early and advanced stage III considering that the tumor microenvironment of invaded lymph nodes could become more tolerant with the progression of the disease. A total of 47 samples of melanoma invaded LN from stage IIIb (AJCC 2007) melanoma patients treated with TIL plus IL-2 were included in this study. We confirmed that both PFS and OS were significantly associated to the presence of tumor-reactive T-cells among TIL injected to the patients and that these tumor reactive T cells were more frequently observed at the early stage III. Moreover, while analyzing the expression of 17 markers on 34/47 tumor specimens using immunohistochemistry, we identified that 3 tissue markers involved in interactions between melanoma cells and T cells have a significant difference of expression between early and advanced stage III: MHC class I, adhesion molecule ICAM-1 and the co-stimulation molecule LFA-3 had a significantly weaker expression in melanoma tissue specimens from advanced stage III. In addition, the expression of the alpha chain of the IL-2 receptor (CD25) and the nuclear transcription factor Foxp3 was significantly increased in the melanoma tissue specimens from advanced stage III. Our results suggest differences in the immunological status of the tumor microenvironment between early and advanced stage III, which could explain the difference in clinical response to TIL infusion in an adjuvant setting between early and advanced stage III.

20 Article Is primary melanoma ulceration a factor of good response to adoptive immunotherapy? 2011

Peuvrel, L / Nguyen, J M / Khammari, A / Quereux, G / Brocard, A / Dreno, B. ·Nantes University Hospital Centre, Skin Cancer Unit, Alexis Ricordeau CIC biothérapie, INSERM 0305, Nantes, France. ·J Eur Acad Dermatol Venereol · Pubmed #21348897.

ABSTRACT: BACKGROUND: Primary melanoma ulceration is a factor of poor prognosis at the local and regional stage. The physiopathological mechanisms which explain its prognostic impact are still little known. However, two recent studies suggest that it could be a predictive factor of good response to a non-specific immunotherapy (interferon-alpha) and to an active immunotherapy (vaccine). OBJECTIVE: The aim of this study was to determine whether ulceration could be a factor of good prognosis in the context of an adoptive immunotherapy with tumour infiltrating lymphocytes (TIL) in stage III regional lymph node metastatic melanoma (sixth American Joint Committee on Cancer staging system) and whether it was associated with an improvement in the effectiveness of this treatment compared with the control group. METHODS: We have included all the patients treated in open prospective randomized TIL vs. control protocols in our unit from 1997 to 2009. Clinical data were derived retrospectively from patient files. Statistical analysis was performed using log-rank tests, Cox models and tests for interaction. RESULTS: A total of 144 patients were included. In the group of 80 patients treated with TIL, primary melanoma ulceration remained a pejorative factor for relapse-free and overall survival in univariate and multivariate analysis. The presence of ulceration did not change the effectiveness of TIL treatment in comparison with the control group with regards to relapse-free and overall survival. CONCLUSION: Our study demonstrates that primary melanoma ulceration does not have any impact on the response to TIL adoptive immunotherapy and thus does not confirm its positive prognostic value suggested by two other immunotherapy approaches.

21 Article Impact of a campaign to train general practitioners in screening for melanoma. 2009

Peuvrel, Lucie / Quereux, Gaëlle / Jumbou, Olivier / Sassolas, Bruno / Lequeux, Yves / Dreno, Brigitte. ·Réseau Mélanome Ouest, Dermatological Clinic, Nantes University Hospital Center, Nantes, France. ·Eur J Cancer Prev · Pubmed #19491609.

ABSTRACT: Melanoma is a serious cancer whose incidence is growing. At this time, its prognosis is dependent on the Breslow index and therefore on early screening. The objective of the study was to evaluate the impact of a campaign to train general practitioners based, in particular, on learning the ABCDE rule. The training, performed by Réseau Mélanome Ouest, involved 210 general practitioners from the Pays de la Loire (Loire region) in France. Eight identical 2-h sessions were held between 2004 and 2006, conducted by a hospital dermatologist, a dermatologist in private practice, and a general practitioner as a moderator. The training was evaluated in two stages, with a self-administered questionnaire followed by a telephone survey. Thirty-six percent of the doctors stated that they had detected melanomas since the training over a median period of 27 months (2-39 months); 15% sent in the corresponding pathological anatomy reports on 37 confirmed melanomas from 30 doctors. The Breslow index scores of the melanomas detected ranged from 0.16 to 4 mm. Therefore, our training promoted the screening of a large number of melanomas, most of them with a low Breslow index. As a result, after a short prior training, the ABCDE rule clearly seems to be a valuable tool. Dermatologists retain an important role both in the diagnostic confirmation of melanomas and in the training of general practitioners.

22 Minor BRAF mutations might be more common than supposed in vulvar melanomas. 2018

Wylomanski, Sophie / Denis, Marc G / Théoleyre, Sandrine / Bouquin, Réjane / Vallée, Audrey / Knol, Anne-Chantal / Saint-Jean, Mélanie / Peuvrel, Lucie / Dréno, Brigitte / Quéreux, Gaëlle. ·Department of Obstetrics and Gynecology, Nantes University Hospital, Nantes, France. · INSERM U 1232, Nantes, France. · Department of Biochemistry, Nantes University Hospital, Nantes, France. · Immuno-Dermatology Laboratory, Nantes University Hospital, Nantes, France. · Department of Dermatology, Nantes University Hospital, Nantes, France. · INSERM CIC 1413, Clinical Investigation Center, Nantes University Hospital, Nantes, France. ·Exp Dermatol · Pubmed #29178146.

ABSTRACT: Data on BRAF, NRAS and KIT mutations are scarce in patients with vulvo-vaginal melanomas and are associated with important therapeutic issues. We investigated their prevalence in a cohort of patients with female lower genital tract melanomas between 2003 and 2017. Of the 22 patients, 5 (22.7%) harboured a BRAF mutation, which was much higher than the rate of 5% reported in the literature. One patient, who was tested negative on the primary melanoma, had a NRAS mutation in a cutaneous metastasis. Our data provide a rationale for prospective and repeated mutations testing in female lower genital tract melanomas.

23 Minor Is a single BRAF wild-type test sufficient to exclude melanoma patients from vemurafenib therapy? 2014

Saint-Jean, Mélanie / Quéreux, Gaëlle / Nguyen, Jean-Michel / Peuvrel, Lucie / Brocard, Anabelle / Vallée, Audrey / Knol, Anne-Chantal / Khammari, Amir / Denis, Marc G / Dréno, Brigitte. ·Department of Dermato-Cancerology, University Hospital Hôtel-Dieu, Nantes, France; Inserm U892, CIC Biothérapie Inserm 0503, Nantes, France. · PIMESP, Saint-Jacques Hospital, Nantes, France. · Department of Biochemistry, University Hospital Hôtel-Dieu, Nantes, France. · Inserm U892, CIC Biothérapie Inserm 0503, Nantes, France; Immuno-Dermatology Laboratory, University Hospital Hôtel-Dieu, Nantes, France. · Department of Dermato-Cancerology, University Hospital Hôtel-Dieu, Nantes, France; Inserm U892, CIC Biothérapie Inserm 0503, Nantes, France; Immuno-Dermatology Laboratory, University Hospital Hôtel-Dieu, Nantes, France. Electronic address: brigitte.dreno@wanadoo.fr. ·J Invest Dermatol · Pubmed #24025553.

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