Suivi prospectif par dermoscopie digitale de 42 patients traités par Vemurafenib pour mélanome métastatique

LYON1-BU Santé (693882101) / SudocSudocFranceF

Association of Immunotherapy With Overall Survival in Elderly Patients With Melanoma

International audienceIMPORTANCE Melanoma treatment has been revolutionized with the development of immune-based therapies that offer durable clinical responses in a subset of patients. Clinical outcomes after treatment by immunotherapy can be influenced by the host's immune system. The immune system is modified with age by age-related immune dysfunction. OBJECTIVE To evaluate if age influences clinical outcome and immune adverse events in patients treated by immunotherapy for metastatic melanoma. DESIGN. SETTING, AND PARTICIPANTS This was a single-center cohort analysis in patients treated with immunotherapy for metastatic melanoma between January 2007 and February 2016, in the Lyon Sud Hospital, France, A total of 92 patients with metastatic melanoma treated with ipilimumab, nivoiumab,or pembrolizumab were retrospectively analyzed. MAIN OUTCOMES AND MEASURES Overall survival, progression-free survival, and immune-related adverse events were evaluated for each treatment line according to the patients' age. RESULTS A total of 92 patients were eligible and included in this study for a total of 120 lines of treatment. Fifty-four patients were included in the cohort that was 65 years or younger (24 [44%] were female; mean [SD] age, 48.1 [12.5] years), and 38 patients were included in the cohort that was older than 65 years (12 [34%] were female; mean [SD] age, 74.8 [6.9] years). Mean follow-up duration starting at treatment initiation was 12.5 months. Patients older than 65 years treated with immunotherapy had a better mean progression-free survival (4.8 vs 3.4 months; P = .04) and overall survival (not reached vs 10.1 months; P = .009) than younger patients in univariate analysis, and after adjusting on prognosis covariates. This was particularly true with patients treated with anti-programmed cell death protein1. Common immune-related adverse effects were similar in both cohorts. CONCLUSIONSAND RELEVANCE Age might be associated with a better clinical outcome after treatment with immunotherapy in the real-life setting. In our cohort, older patients did not have more immune-related adverse events. Further studies are warranted to confirm our results and describe the underlying mechanisms involved

Brentuximab-vedotin in combination with cyclophosphamide, doxorubicin, prednisolone for the treatment of aggressive CD30-positive cutaneous T-cell lymphomas

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Diagnostic Concordance in Tertiary (Dermatologists-to-Experts) Teledermoscopy: A Final Diagnosis-Based Study on 290 Cases

International audienceBackground: Teledermoscopy (TDS) improves diagnostic accuracy and decreases the number of unnecessary consultations. Objectives: To determine the diagnostic concordance in tertiary (dermatologist-to-experts) TDS with histopathology/follow-up–based diagnosis. Methods: A descriptive retrospective cohort study including 290 requests. Results: Perfect diagnostic concordance was found in 202 (69.7%) cases and partial agreement in 29 (10%). Disagreement was found in 59 (20.3%) cases. Perfect concordance on the benign/malignant nature of the lesion was found in 227 (78.3%) cases and disagreement in 63 (21.7%). In onychology, diagnostic concordance was perfect in 43 (76.8%) cases, partial in 7 (12.5%), and there was disagreement in 6 (10.7%). Final concordance on the benign/malignant nature of the lesion was perfect in 48 (85.7%) and there was disagreement in 8 (14.3%) nail cases. For pediatric requests, diagnostic concordance was perfect in 29 (65.9%) cases, partial in 5 (11.4%), and there was disagreement in 10 (22.7%). Final concordance on the benign/malignant nature of the lesion was observed in 34 (77.3%) cases, disagreement in 10 (22.7%). Conclusions: This study confirms that tertiary TDS improves diagnostic accuracy of pigmented skin lesions. Moreover, it shows encouraging results in unusual conditions such as ungual and pediatric skin tumors. The main limitation was the retrospective nature and the “real-life” setting of our study that could have created a selection bias toward inclusion of the most difficult cases

Deciphering the spectrum of cutaneous lymphomas expressing TFH markers

International audienceAbstract T-follicular helper (TFH) markers are expressed in the microenvironnement of marginal zone B-cell lymphoma (MZL), and in lymphomas arising from TFH-cells, sometimes making the differential diagnosis difficult. In the skin, the “TFH-spectrum” is poorly defined, going from primary cutaneous lymphoproliferative disorder with small/medium CD4+ T-cells (SMLPD) to cutaneous localizations of systemic angioimmunoblastic T-cell lymphoma (cAITL), and may pass through intermediate forms (primary cutaneous T-follicular helper derived lymphoma, not otherwise specified (PCTFHL,NOS)). We retrospectively analyzed 20 MZL, 13 SMLPD, 5 PCTFHL, and 11 cAITL clinically, histologically, and molecularly, to define tools to differentiate them. Characteristics that might favor the diagnosis of MZL over SMLPD are: multiple skin nodules (p < 0.001), nodular architecture (p < 0.01), residual germinal centers with follicular dendritic cell network (p < 0.001), monotypic plasma cells (p < 0.001), and few staining with PD1 (p = 0.016) or CXCL13 (p = 0.03). PCTFHL and cAITL presented as multiple (p < 0.01) lesions, in older patients (p < 0.01), with systemic symptoms and/or biological alterations (p < 0.01). Immunophenotypic loss of T-cell markers (p < 0.001), BCL6 (p = 0.023) and/or CD10 staining (p = 0.08), and a higher proliferative index (≥ 30%, p = 0.039) favoured these diagnoses over SMLPD. Pathogenic variants were observed by genomic sequencing in 47% of MZL ( TNFAIP3 (32%), EP300 (21%), NOTCH2 (16%), KMT2D (16%), CARD11 (10.5%)), 8% of SMLPD ( TET2 ), 40% of PCTFHL ( SOCS1 (20%), ARID1A (20%)) and 64% of cAITL ( TET2 (63.6%), RHOA (36.4%), NOTCH1 (9%)). This study characterizes the various clinical and histological features between cutaneous lymphomas expressing TFH markers and highlights the value of the interest of screening for genomic mutations in difficult cases

Deciphering the spectrum of cutaneous lymphomas expressing TFH markers

International audienceAbstract T-follicular helper (TFH) markers are expressed in the microenvironnement of marginal zone B-cell lymphoma (MZL), and in lymphomas arising from TFH-cells, sometimes making the differential diagnosis difficult. In the skin, the “TFH-spectrum” is poorly defined, going from primary cutaneous lymphoproliferative disorder with small/medium CD4+ T-cells (SMLPD) to cutaneous localizations of systemic angioimmunoblastic T-cell lymphoma (cAITL), and may pass through intermediate forms (primary cutaneous T-follicular helper derived lymphoma, not otherwise specified (PCTFHL,NOS)). We retrospectively analyzed 20 MZL, 13 SMLPD, 5 PCTFHL, and 11 cAITL clinically, histologically, and molecularly, to define tools to differentiate them. Characteristics that might favor the diagnosis of MZL over SMLPD are: multiple skin nodules (p < 0.001), nodular architecture (p < 0.01), residual germinal centers with follicular dendritic cell network (p < 0.001), monotypic plasma cells (p < 0.001), and few staining with PD1 (p = 0.016) or CXCL13 (p = 0.03). PCTFHL and cAITL presented as multiple (p < 0.01) lesions, in older patients (p < 0.01), with systemic symptoms and/or biological alterations (p < 0.01). Immunophenotypic loss of T-cell markers (p < 0.001), BCL6 (p = 0.023) and/or CD10 staining (p = 0.08), and a higher proliferative index (≥ 30%, p = 0.039) favoured these diagnoses over SMLPD. Pathogenic variants were observed by genomic sequencing in 47% of MZL ( TNFAIP3 (32%), EP300 (21%), NOTCH2 (16%), KMT2D (16%), CARD11 (10.5%)), 8% of SMLPD ( TET2 ), 40% of PCTFHL ( SOCS1 (20%), ARID1A (20%)) and 64% of cAITL ( TET2 (63.6%), RHOA (36.4%), NOTCH1 (9%)). This study characterizes the various clinical and histological features between cutaneous lymphomas expressing TFH markers and highlights the value of the interest of screening for genomic mutations in difficult cases

ZEB1-mediated melanoma cell plasticity enhances resistance to MAPK inhibitors

International audienceTargeted therapies with MAPK inhibitors (MAPKi) are faced with severe problems of resistance in BRAF-mutant melanoma. In parallel to the acquisition of genetic mutations, melanoma cells may also adapt to the drugs through phenotype switching. The ZEB1 transcription factor, a known inducer of EMT and invasiveness, is now considered as a genuine oncogenic factor required for tumor initiation, cancer cell plasticity, and drug resistance in carcinomas. Here, we show that high levels of ZEB1 expression are associated with inherent resistance to MAPKi in BRAFV600-mutated cell lines and tumors. ZEB1 levels are also elevated in melanoma cells with acquired resistance and in biopsies from patients relapsing while under treatment. ZEB1 overexpression is sufficient to drive the emergence of resistance to MAPKi by promoting a reversible transition toward a MITFlow/p75high stem-like and tumorigenic phenotype. ZEB1 inhibition promotes cell differentiation, prevents tumorigenic growth in vivo, sensitizes naive melanoma cells to MAPKi, and induces cell death in resistant cells. Overall, our results demonstrate that ZEB1 is a major driver of melanoma cell plasticity, driving drug adaptation and phenotypic resistance to MAPK