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201. Variations of BRAF mutant allele percentage in melanomas

Author

Hélias-Rodzewicz, Zofia, primary, Funck-Brentano, Elisa, additional, Baudoux, Laure, additional, Jung, Chan Kwon, additional, Zimmermann, Ute, additional, Marin, Cristi, additional, Clerici, Thierry, additional, Le Gall, Catherine, additional, Peschaud, Frédérique, additional, Taly, Valérie, additional, Saiag, Philippe, additional, and Emile, Jean-François, additional

Published
2015
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203. Phase II multicentric uncontrolled national trial assessing the efficacy of nilotinib in the treatment of advanced melanomas with c-KIT mutation or amplification: Results of the pharmacodynamic study.

Author

Lesteven, Elodie, primary, Battistella, Maxime, additional, Jouary, Thomas, additional, Dalac, Sophie, additional, Dalle, Stephane, additional, Guillot, Bernard, additional, Arnault, Jean-Philippe, additional, Avril, Marie-Françoise, additional, Bedane, Christophe, additional, Bens, Guido, additional, Beylot-Barry, Marie-, additional, Grange, Florent, additional, Meyer, Nicolas, additional, Machet, Laurent, additional, Saiag, Philippe, additional, Dumaz, Nicolas, additional, Mourah, Samia, additional, and Lebbe, Celeste, additional

Published
2015
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205. Follow-up of a French national cohort of melanoma stage IV and unresectable stage III patients, MelBase.

Author

Allayous, Clara, primary, Dalle, Stephane, additional, Saiag, Philippe, additional, Dutriaux, Caroline, additional, Mortier, Laurent, additional, Dupuy, Alain, additional, Lesimple, Thierry, additional, Bahadoran, Philippe, additional, Dalac, Sophie, additional, Beylot-Barry, Marie-, additional, Maubec, Eve, additional, Stoebner, Pierre-Emmanuel, additional, Aubin, Francois, additional, Arnault, Jean-Philippe, additional, Verneuil, Laurence, additional, Dreno, Brigitte, additional, Kowal, Anita, additional, Porcher, Raphael, additional, Leccia, Marie Thérèse, additional, and Lebbe, Celeste, additional

Published
2015
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206. First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients with in transit melanoma.

Author

Le Tourneau, Christophe, primary, Dreno, Brigitte, additional, Kirova, Youlia, additional, Grob, Jean Jacques, additional, Jouary, Thomas, additional, Dutriaux, Caroline, additional, Thomas, Luc, additional, Lebbe, Celeste, additional, Mortier, Laurent, additional, Saiag, Philippe, additional, Avril, Marie-Françoise, additional, Maubec, Eve, additional, Bey, Pierre, additional, Cosset, Jean-Marc, additional, Sun, Jian-sheng, additional, Asselain, Bernard, additional, Devun, Flavien, additional, Marty, Michel E., additional, and Dutreix, Marie, additional

Published
2015
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207. Dabrafenib plus trametinib in patients with BRAFV600-mutant melanoma brain metastases (COMBI-MB): a multicentre, multicohort, open-label, phase 2 trial.

Author

Davies, Michael A, Saiag, Philippe, Robert, Caroline, Grob, Jean-Jacques, Flaherty, Keith T, Arance, Ana, Chiarion-Sileni, Vanna, Thomas, Luc, Lesimple, Thierry, Mortier, Laurent, Moschos, Stergios J, Hogg, David, Márquez-Rodas, Iván, Del Vecchio, Michele, Lebbé, Céleste, Meyer, Nicolas, Zhang, Ying, Huang, Yingjie, Mookerjee, Bijoyesh, and Long, Georgina V

Subjects
*BRAIN metastasis, *BRAF genes, *MEDICAL centers, *ANTINEOPLASTIC agents, *COMBINATION drug therapy, *TARGETED drug delivery, *PATIENTS, *AMINES, *BRAIN tumors, *CLINICAL trials, *COMPARATIVE studies, *FEVER, *HEADACHE, *HETEROCYCLIC compounds, *IMIDAZOLES, *LONGITUDINAL method, *MAGNETIC resonance imaging, *RESEARCH methodology, *MEDICAL cooperation, *MELANOMA, *GENETIC mutation, *PYRIDINE, *RESEARCH, *RESEARCH funding, *TRANSFERASES, *EVALUATION research, *STROKE volume (Cardiac output)
Abstract

Background: Dabrafenib plus trametinib improves clinical outcomes in BRAFV600-mutant metastatic melanoma without brain metastases; however, the activity of dabrafenib plus trametinib has not been studied in active melanoma brain metastases. Here, we report results from the phase 2 COMBI-MB trial. Our aim was to build on the current body of evidence of targeted therapy in melanoma brain metastases through an evaluation of dabrafenib plus trametinib in patients with BRAFV600-mutant melanoma brain metastases.Methods: This ongoing, multicentre, multicohort, open-label, phase 2 study evaluated oral dabrafenib (150 mg twice per day) plus oral trametinib (2 mg once per day) in four patient cohorts with melanoma brain metastases enrolled from 32 hospitals and institutions in Europe, North America, and Australia: (A) BRAFV600E-positive, asymptomatic melanoma brain metastases, with no previous local brain therapy, and an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; (B) BRAFV600E-positive, asymptomatic melanoma brain metastases, with previous local brain therapy, and an ECOG performance status of 0 or 1; (C) BRAFV600D/K/R-positive, asymptomatic melanoma brain metastases, with or without previous local brain therapy, and an ECOG performance status of 0 or 1; and (D) BRAFV600D/E/K/R-positive, symptomatic melanoma brain metastases, with or without previous local brain therapy, and an ECOG performance status of 0, 1, or 2. The primary endpoint was investigator-assessed intracranial response in cohort A in the all-treated-patients population. Secondary endpoints included intracranial response in cohorts B, C, and D. This study is registered with ClinicalTrials.gov, number NCT02039947.Findings: Between Feb 28, 2014, and Aug 5, 2016, 125 patients were enrolled in the study: 76 patients in cohort A; 16 patients in cohort B; 16 patients in cohort C; and 17 patients in cohort D. At the data cutoff (Nov 28, 2016) after a median follow-up of 8·5 months (IQR 5·5-14·0), 44 (58%; 95% CI 46-69) of 76 patients in cohort A achieved an intracranial response. Intracranial response by investigator assessment was also achieved in nine (56%; 95% CI 30-80) of 16 patients in cohort B, seven (44%; 20-70) of 16 patients in cohort C, and ten (59%; 33-82) of 17 patients in cohort D. The most common serious adverse events related to study treatment were pyrexia for dabrafenib (eight [6%] of 125 patients) and decreased ejection fraction (five [4%]) for trametinib. The most common grade 3 or worse adverse events, regardless of study drug relationship, were pyrexia (four [3%] of 125) and headache (three [2%]).Interpretation: Dabrafenib plus trametinib was active with a manageable safety profile in this melanoma population that was consistent with previous dabrafenib plus trametinib studies in patients with BRAFV600-mutant melanoma without brain metastases, but the median duration of response was relatively short. These results provide evidence of clinical benefit with dabrafenib plus trametinib and support the need for additional research to further improve outcomes in patients with melanoma brain metastases.Funding: Novartis. [ABSTRACT FROM AUTHOR]

Published
2017
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208. Comparing PD-L1 scores for predicting pembrolizumab efficacy in first-line treatment of unresectable cutaneous squamous cell carcinomas.

Author

Maubec, Eve, Boubaya, Marouane, Deschamps, Lydia, Beylot-Barry, Marie, Petrow, Peter, Scheer-Senyarich, Isabelle, Basset-Seguin, Nicole, Grob, Jean-Jacques, Dreno, Brigitte, Bloch-Queyrat, Coralie, Leccia, Marie Thérèse, Stefan, Andreea Raluca, Saiag, Philippe, Grange, Florent, Meyer, Nicolas, Dalac, Sophie, Alloux, Céline, Lopez, Isabelle, Tibi, Annick, and Lévy, Vincent

Published
2023
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209. Avelumab as second-line or later (2L+) treatment in patients (pts) with metastatic Merkel cell carcinoma (mMCC): Analysis of real-world outcomes in France using the CARADERM registry and the French national healthcare database.

Author

Blom Fily, Astrid, Mortier, Laurent, Kachaner, Isabelle, Meyer, Nicolas, Samimi, Mahtab, Luciani, Laura, Cahuzac, Capucine, Robert, Caroline, Quéreux, Gaëlle, Maubec, Eve, Maillard, Cathy, Miotti, Hakima, Aubin, François, Lenormand, Cédric, Solbes, Marie-Noelle, Joly, Pascal, van Hille, Benoît, Lebbe, Celeste, Dutriaux, Caroline, and Saiag, Philippe

Published
2023
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210. Efficacy of adjuvant therapy in patients (pts) with AJCC v8 stage IIIA cutaneous melanoma.

Author

Grover, Piyush, Li, Isabel, Kuijpers, Anke, Kreidieh, Firas Y., Williamson, Andrew, Amaral, Teresa Maria Santos, Dimitriou, Florentia, Placzke, Joanna, Olino, Kelly, Vitale, Maria Grazia, Saiag, Philippe, Gutzmer, Ralf, Allayous, Clara, Olofsson Bagge, Roger, Asher, Nethanel, Meniawy, Tarek, Lawless, Aleigha, Warburton, Lydia, Menzies, Alexander M., and Long, Georgina V.

Published
2023
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211. Genes involved in the WNT and vesicular trafficking pathways are associated with melanoma predisposition

Author

Ibarrola-Villava, Maider, primary, Kumar, Rajiv, additional, Nagore, Eduardo, additional, Benfodda, Meriem, additional, Guedj, Mickael, additional, Gazal, Steven, additional, Hu, Hui-Han, additional, Guan, Jian, additional, Rachkonda, P. Sivaramakishna, additional, Descamps, Vincent, additional, Basset-Seguin, Nicole, additional, Bensussan, Armand, additional, Bagot, Martine, additional, Saiag, Philippe, additional, Schadendorf, Dirk, additional, Martin-Gonzalez, Manuel, additional, Mayor, Matias, additional, Grandchamp, Bernard, additional, Ribas, Gloria, additional, and Nadem, Soufir, additional

Published
2014
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215. A Large French Case-Control Study Emphasizes the Role of RareMc1RVariants in Melanoma Risk

Author

Hu, Hui-Han, primary, Benfodda, Mériem, additional, Dumaz, Nicolas, additional, Gazal, Steven, additional, Descamps, Vincent, additional, Bourillon, Agnès, additional, Basset-Seguin, Nicole, additional, Riffault, Angélique, additional, Ezzedine, Khaled, additional, Bagot, Martine, additional, Bensussan, Armand, additional, Saiag, Philippe, additional, Grandchamp, Bernard, additional, and Soufir, Nadem, additional

Published
2014
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219. Detection of BRAF p.V600E Mutations in Melanomas

Author

Colomba, Emeline, primary, Hélias-Rodzewicz, Zofia, additional, Von Deimling, Andreas, additional, Marin, Cristi, additional, Terrones, Nathalie, additional, Pechaud, Dominique, additional, Surel, Sylvie, additional, Côté, Jean-François, additional, Peschaud, Frédérique, additional, Capper, David, additional, Blons, Hélène, additional, Zimmermann, Ute, additional, Clerici, Thierry, additional, Saiag, Philippe, additional, and Emile, Jean-François, additional

Published
2013
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220. PARKIN Inactivation Links Parkinson's Disease to Melanoma.

Author

Hui-Han Hu, Kannengiesser, Caroline, Lesage, Suzanne, André, Jocelyne, Mourah, Samia, Michel, Laurence, Descamps, Vincent, Basset-Seguin, Nicole, Bagot, Martine, Bensussan, Armand, Lebbé, Céleste, Deschamps, Lydia, Saiag, Philippe, Leccia, Marie-Thérèse, Bressac-de-Paillerets, Brigitte, Tsalamlal, Amel, Kumar, Rajiv, Klebe, Stephan, Grandchamp, Bernard, and Andrieu-Abadie, Nathalie

Subjects
PROTEIN metabolism, DNA analysis, ENZYME metabolism, CELL lines, CELL physiology, ENZYMES, EPITHELIAL cells, GENES, GENETICS, MELANOMA, GENETIC mutation, PARKINSON'S disease, PROTEINS, SKIN tumors, WESTERN immunoblotting, RELATIVE medical risk, CASE-control method, SEQUENCE analysis, ODDS ratio, GENOTYPES
Abstract

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

Published
2016
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221. Genetic variation atKITlocus may predispose to melanoma

Author

Bourillon, Agnes, primary, Hu, Hui‐Han, additional, Hetet, Gilles, additional, Lacapere, Jean‐Jacques, additional, André, Jocelyne, additional, Descamps, Vincent, additional, Basset‐Seguin, Nicole, additional, Ogbah, Zighereda, additional, Puig, Susana, additional, Saiag, Philippe, additional, Bagot, Martine, additional, Bensussan, Armand, additional, Grandchamp, Bernard, additional, Dumaz, Nicolas, additional, and Soufir, Nadem, additional

Published
2012
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223. Prognostic value of BRAFV600 mutations in melanoma patients after resection of metastatic lymph nodes.

Author

Saiag, Philippe, primary, Moreau, Stephanie, additional, Aegerter, Philippe, additional, Bosset, Daphne, additional, Longvert, Christine, additional, Helias-Rodzewicz, Zofia, additional, Marin, Cristi, additional, Peschaud, Frederique, additional, Chagnon, Sophie, additional, Zimmermann, Ute, additional, Clerici, Thierry, additional, and Emile, Jean-François, additional

Published
2012
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224. Vemurafenib (V) in BRAF V600E metastatic melanoma (mM): Analysis of 507 patients (pts) enrolled in the French temporary authorization for use (ATU).

Author

Lebbe, Celeste, primary, Robert, Caroline, additional, Dreno, Brigitte, additional, Thomas, Luc, additional, Grob, Jean Jacques, additional, Meyer, Nicolas, additional, Regnier-Rosencher, Elodie, additional, Saiag, Philippe, additional, Mortier, Laurent, additional, Hospital, Valerie, additional, Duval-Modeste, Anne Benedicte, additional, Dalac-Rat, Sophie, additional, Lesimple, Thierry, additional, Guillot, Bernard, additional, Leccia, Marie Thérèse, additional, Bitoun, Laurence, additional, Bobadilla, Luz, additional, and Jouary, Thomas, additional

Published
2012
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228. Inherited variants in the MC1R gene and survival from cutaneous melanoma: a BioGenoMEL study

Author

Davies, John R., primary, Randerson‐Moor, Juliette, additional, Kukalizch, Kairen, additional, Harland, Mark, additional, Kumar, Rajiv, additional, Madhusudan, Srinivasan, additional, Nagore, Eduardo, additional, Hansson, Johan, additional, Höiom, Veronica, additional, Ghiorzo, Paola, additional, Gruis, Nelleke A., additional, Kanetsky, Peter A., additional, Wendt, Judith, additional, Pjanova, Dace, additional, Puig, Susana, additional, Saiag, Philippe, additional, Schadendorf, Dirk, additional, Soufir, Nadem, additional, Okamoto, Ichiro, additional, Affleck, Paul, additional, García‐Casado, Zaida, additional, Ogbah, Zighereda, additional, Ozola, Aija, additional, Queirolo, Paola, additional, Sucker, Antje, additional, Barrett, Jennifer H., additional, van Doorn, Remco, additional, Bishop, D. Timothy, additional, and Newton‐Bishop, Julia, additional

Published
2012
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230. Assessment of tyrosinase variants and skin cancer risk in a large cohort of French subjects

Author

Hu, Hui-Han, primary, Guedj, Mickael, additional, Descamps, Vincent, additional, Jouary, Thomas, additional, Bourillon, Agnes, additional, Ezzedine, Khaled, additional, Taieb, Alain, additional, Bagot, Martine, additional, Bensussan, Armand, additional, Saiag, Philippe, additional, Grandchamp, Bernard, additional, Basset-Seguin, Nicole, additional, and Soufir, Nadem, additional

Published
2011
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234. GLI2-Mediated Melanoma Invasion and Metastasis

Author

Alexaki, Vasileia-Ismini, primary, Javelaud, Delphine, additional, Van Kempen, Leon C. L., additional, Mohammad, Khalid S., additional, Dennler, Sylviane, additional, Luciani, Flavie, additional, Hoek, Keith S., additional, Juàrez, Patricia, additional, Goydos, James S., additional, Fournier, Pierrick J., additional, Sibon, Claire, additional, Bertolotto, Corine, additional, Verrecchia, Franck, additional, Saule, Simon, additional, Delmas, Veronique, additional, Ballotti, Robert, additional, Larue, Lionel, additional, Saiag, Philippe, additional, Guise, Theresa A., additional, and Mauviel, Alain, additional

Published
2010
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236. No Correlation between the Molecular Subtype of COL1A1–PDGFB Fusion Gene and the Clinico-Histopathological Features of Dermatofibrosarcoma Protuberans

Author

Giacchero, Damien, primary, Maire, Georges, additional, Nuin, Paulo A.S., additional, Berthier, Frédéric, additional, Ebran, Nathalie, additional, Carlotti, Agnès, additional, Celerier, Philippe, additional, Coindre, Jean Michel, additional, Esteve, Eric, additional, Fraitag, Sylvie, additional, Guillot, Bernard, additional, Ranchere-Vince, Dominique, additional, Saiag, Philippe, additional, Terrier, Philippe, additional, Lacour, Jean Philippe, additional, and Pedeutour, Florence, additional

Published
2010
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237. Diagnosis and treatment of melanoma: European consensus-based interdisciplinary guideline

Author

Garbe, Claus, primary, Peris, Ketty, additional, Hauschild, Axel, additional, Saiag, Philippe, additional, Middleton, Mark, additional, Spatz, Alain, additional, Grob, Jean-Jacques, additional, Malvehy, Josep, additional, Newton-Bishop, Julia, additional, Stratigos, Alexander, additional, Pehamberger, Hubert, additional, and Eggermont, Alexander, additional

Published
2010
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238. Variants of the xeroderma pigmentosum variant gene (POLH) are associated with melanoma risk

Author

Di Lucca, Julie, primary, Guedj, Mickael, additional, Lacapère, Jean-Jacques, additional, Fargnoli, Maria Concetta, additional, Bourillon, Agnes, additional, Dieudé, Philippe, additional, Dupin, Nicolas, additional, Wolkenstein, Pierre, additional, Aegerter, Philippe, additional, Saiag, Philippe, additional, Descamps, Vincent, additional, Lebbe, Celeste, additional, Basset-Seguin, Nicole, additional, Peris, Ketty, additional, Grandchamp, Bernard, additional, and Soufir, Nadem, additional

Published
2009
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240. A Comparison of Two Regimens of Topical Corticosteroids in the Treatment of Patients with Bullous Pemphigoid: A Multicenter Randomized Study

Author

Joly, Pascal, primary, Roujeau, Jean-Claude, additional, Benichou, Jacques, additional, Delaporte, Emmanuel, additional, D'Incan, Michel, additional, Dreno, Brigitte, additional, Bedane, Christophe, additional, Sparsa, Agnes, additional, Gorin, Isabelle, additional, Picard, Catherine, additional, Tancrede-Bohin, Emmanuelle, additional, Sassolas, Bruno, additional, Lok, Catherine, additional, Guillaume, Jean-Claude, additional, Doutre, Marie-Sylvie, additional, Richard, Marie-Aleth, additional, Caux, Frédéric, additional, Prost, Catherine, additional, Plantin, Patrice, additional, Chosidow, Olivier, additional, Pauwels, Christine, additional, Maillard, Hervé, additional, Saiag, Philippe, additional, Descamps, Vincent, additional, Chevrant-Breton, Jacqueline, additional, Dereure, Olivier, additional, Hellot, Marie-France, additional, Esteve, Eric, additional, and Bernard, Philippe, additional

Published
2009
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242. Variants of theMATP/SLC45A2gene are protective for melanoma in the French population

Author

Guedj, Mickaël, primary, Bourillon, Agnès, additional, Combadières, Christophe, additional, Rodero, Mathieu, additional, Dieudé, Philippe, additional, Descamps, Vincent, additional, Dupin, Nicolas, additional, Wolkenstein, Pierre, additional, Aegerter, Philippe, additional, Lebbe, Céleste, additional, Basset-Seguin, Nicole, additional, Prum, Bernard, additional, Saiag, Philippe, additional, Grandchamp, Bernard, additional, and Soufir, Nadem, additional

Published
2008
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244. Melanoma susceptibility and progression: Association study between polymorphisms of the chemokine (CCL2) and chemokine receptors (CX3CR1, CCR5)

Author

Rodero, Mathieu, primary, Rodero, Pauline, additional, Descamps, Vincent, additional, Aegerter, Philippe, additional, Vitoux, Dominique, additional, Lebbe, Céleste, additional, Wolkenstein, Pierre, additional, Basset-Seguin, Nicole, additional, Dupin, Nicolas, additional, Grandchamp, Bernard, additional, Soufir, Nadem, additional, Saiag, Philippe, additional, and Combadière, Christophe, additional

Published
2007
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245. A French CDK4-positive melanoma family with a co-inherited EDNRB mutation

Author

Soufir, Nadem, primary, Ollivaud, Laurence, additional, Bertrand, Guylene, additional, Lacapère, Jean-Jacques, additional, Descamps, Vincent, additional, Vitoux, Dominique, additional, Lebbe, Céleste, additional, Wolkenstein, Pierre, additional, Dupin, Nicolas, additional, Saiag, Philippe, additional, Basset-Seguin, Nicole, additional, and Grandchamp, Bernard, additional

Published
2007
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246. Prognostic Value of 25-hydroxyvitamin D3 Levels at Diagnosis and During Follow-up in Melanoma Patients.

Author

Saiag, Philippe, Aegerter, Philippe, Vitoux, Dominique, Lebbé, Celeste, Wolkenstein, Pierre, Dupin, Nicolas, Descamps, Vincent, Aractingi, Selim, Funck-Brentano, Elisa, Autier, Philippe, Dragomir, Miruna, and Boniol, Mathieu

Subjects
*MELANOMA diagnosis, *MELANOMA treatment, *TREATMENT of skin tumors, *FORECASTING, *LONGITUDINAL method, *MASS spectrometry, *MELANOMA, *PROGNOSIS, *REGRESSION analysis, *SKIN tumors, *VITAMIN D, *TREATMENT effectiveness, *PREDICTIVE tests, *PROPORTIONAL hazards models, *KAPLAN-Meier estimator, *ODDS ratio, *DIAGNOSIS
Abstract

Background: A low 25-hydroxyvitamin D3 (25(OH)D3) serum concentration at melanoma diagnosis might be associated with worse survival. We prospectively studied the prognostic value of 25(OH)D3 at diagnosis and during follow-up.Methods: MelanCohort is a cohort of invasive melanoma patients. Serum 25(OH)D3 was measured by mass spectrometry and standardized on month of blood drawn, age, sex, and body mass index (BMI). Role of 25(OH)D3 levels and risk of relapse was analyzed in a Cox proportional hazards model adjusting for age, sex, BMI, and American Joint Committee on Cancer (AJCC) stage. All statistical tests were two-sided.Results: One thousand one hundred seventy-one patients were included. 25(OH)D3 levels at diagnosis (median = 49.0 nmol/L) were inversely correlated with prognostic factors such as AJCC stage (P < .001 Kruskal-Wallis), Breslow's thickness (P < .001 Spearman correlation), and ulceration (P < .001 Kruskal-Wallis), but not with risk of relapse. Changes in 25(OH)D3 levels during follow-up were associated with worse prognosis: With a third quartile Q3 of average change per year (-0.30 to 4.60 nmol/L/Y) used as reference, hazard ratios for the first, second, and fourth quarters were 1.94 (95% confidence interval [CI] = 1.36 to 2.76), 1.23 (95% CI = 0.85 to 1.78), and 1.61 (95% CI = 1.14 to 2.28), respectively. In sensitivity analyses, no changes were observed either by AJCC stage, number of 25(OH)D3 measures performed, or by 25(OH)D3 level at baseline. No evidence of reverse causation was identified. Analyses performed on overall survival yielded similar results.Conclusions: We show that 25(OH)D3 variation during follow-up is an independent melanoma prognostic marker, but not its level at diagnosis. Previously reported associations between low 25(OH)D3 level at diagnosis and poor prognosis seem to be due to insufficient adjustment for prognostic factors. [ABSTRACT FROM AUTHOR]

Published
2015
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247. Sentinel Node Status and Immunosuppression: Recurrence Factors in Localized Merkel Cell Carcinoma.

Author

JOUARY, Thomas, KUBICA, Emeline, DALLE, Stéphane, PAGES, Cecile, DUVAL-MODESTE, Anne-Benedicte, GUILLOT, Bernard, MANSARD, Sandrine, SAIAG, Philippe, AUBIN, François, BEDANE, Christophe, DALAC, Sophie, DOMPMARTIN, Anne, GRANEL-BROCARD, Florence, LOK, Catherine, STOEBNER, Pierre-Emmanuel, LACOUR, Jean-Philippe, LECCIA, Marie-Therese, DIALLO, Abou, EZZEDINE, Khaled, and MATEUS, Christina

Subjects
LYMPH nodes, IMMUNOSUPPRESSION, MERKEL cell carcinoma, RADIOTHERAPY, DIAGNOSIS
Abstract

The prognostic value of the sentinel lymph node in Merkel cell carcinoma (MCC) has been examined previously in heterogeneous retrospective studies. The current retrospective study included a homogeneous population of patients with a localized MCC, all staged with sentinel lymph node biopsy. Factors associated with 3-year progression-free survival were analysed using logistic regression. The sentinel lymph node was positive in 32% of patients. The recurrence rate was 26.9%. In first analyses (n = 108), gender (p = 0.0115) and the presence of immunosuppression (p = 0.0494) were the only significant independent factors. In further analyses (n = 80), excluding patients treated with regional radiotherapy, sentinel lymph node status was the only significant prognostic factor (p = 0.0281). Immunosuppression and positive sentinel lymph node are associated with a worse prognosis in patients with MCC. Nodal irradiation impacts on the prognostic value of the sentinel lymph node status. [ABSTRACT FROM AUTHOR]

Published
2015
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248. Immunohistochemistry as a potential tool for routine detection of the NRAS Q61R mutation in patients with metastatic melanoma.

Author

Ilie, Marius, Long-Mira, Elodie, Funck-Brentano, Elisa, Lassalle, Sandra, Butori, Catherine, Lespinet-Fabre, Virginie, Bordone, Olivier, Gay, Alexandre, Zahaf, Katia, Poissonnet, Gilles, Lacour, Jean-Philippe, Bahadoran, Philippe, Ballotti, Robert, Gros, Audrey, Dutriaux, Caroline, Saiag, Philippe, Merlio, Jean-Philippe, Vergier, Béatrice, Emile, Jean François, and Hofman, Véronique

Abstract

Background It can be useful to assess the NRAS mutation status in patients with metastatic melanoma because NRAS -activating mutations confer resistance to RAF inhibitors, and NRAS- mutated patients appear to be sensitive to mitogen-activated protein kinase (MEK) inhibitors. Objective We aimed to assess the diagnostic accuracy of an immunohistochemistry (IHC) approach using a novel anti-NRAS (Q61R) monoclonal antibody on formalin-fixed paraffin-embedded tissue samples from patients with metastatic melanoma. Methods We conducted a retrospective multicenter cohort study on 170 patients with metastatic melanoma. The automated IHC assay was performed using the SP174 clone, and compared with results of the molecular testing. Results Evaluation of a test cohort with knowledge of the mutation status established a specific IHC pattern for the mutation. In the independent blinded analysis of the remaining cases, the anti-NRAS (Q61R) antibody accurately identified all NRAS Q61R-mutated tumors, and demonstrated 100% sensitivity and specificity. Limitations Limitations include retrospective design and lack of multicenter interobserver reproducibility. Conclusion The NRAS (Q61R) IHC assay is reliable and specific for the evaluation of the Q61R mutation status in metastatic melanoma and may be an alternative to molecular biology in evaluation of metastatic melanoma in routine practice. [ABSTRACT FROM AUTHOR]

Published
2015
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249. Genes involved in the WNT and vesicular trafficking pathways are associated with melanoma predisposition.

Author

Ibarrola‐Villava, Maider, Kumar, Rajiv, Nagore, Eduardo, Benfodda, Meriem, Guedj, Mickael, Gazal, Steven, Hu, Hui‐Han, Guan, Jian, Rachkonda, P. Sivaramakishna, Descamps, Vincent, Basset‐Seguin, Nicole, Bensussan, Armand, Bagot, Martine, Saiag, Philippe, Schadendorf, Dirk, Martin‐Gonzalez, Manuel, Mayor, Matias, Grandchamp, Bernard, Ribas, Gloria, and Nadem, Soufir

Abstract

Multifactorial predisposition to melanoma includes genes involved in pigmentation, immunity and DNA repair. Nonetheless, missing heritability in melanoma is still important. We studied the role of 335 candidate SNPs in melanoma susceptibility by using a dedicated chip and investigating 110 genes involved in different pathways. A discovery set was comprised of 1069 melanoma patients and 925 controls from France. Data were replicated using validation phases II (1085 cases and 801 controls from Spain) and III (1808 cases and 1894 controls from Germany and a second set of Spanish samples). In addition, an exome sequencing study was performed in three high-risk French melanoma families. Nineteen SNPs in 17 genes were initially associated with melanoma in the French population. Six SNPs were replicated in phase II, including two new SNPs in the WNT3 (rs199524) and VPS41 (rs11773094) genes. The role of VPS41 and WNT3 was confirmed in a meta-analysis (3940 melanoma cases and 3620 controls) with two-side p values of 0.002, (OR = 0.86) and 4.07 × 10−10 (OR = 0.80), respectively. Exome sequencing revealed a non-synonymous VPS41 variant in one family that was shown to be strongly associated with familial melanoma (OR = 4.46, p = 0.001) in an independent sample of 178 melanoma families. WNT3 belongs to WNT pathway known to play a crucial role in melanoma, whereas VPS41 regulates vesicular trafficking and is thought to play a role in pigmentation. Our work identified two new pathways involved in melanoma predisposition. These results may be useful in the future for identifying individuals highly predisposed to melanoma. [ABSTRACT FROM AUTHOR]

Published
2015
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