[Show abstract][Hide abstract] ABSTRACT: 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.
This prospective, observational study included patients with B-RAF mutant metastatic melanoma: 34 patients treated with vemurafenib and 9 with dabrafenib.
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.
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.
[Show abstract][Hide abstract] ABSTRACT: To evaluate the efficacy of a targeted screening for melanoma in high-risk patients following the receipt of a mailed invitation to an annual skin examination by a general practitioner (GP).
A prospective cohort study was conducted in a primary care setting in western France. A total of 3897 patients at elevated risk of melanoma (identified using the Self-Assessment of Melanoma Risk Score) consented to participate in a targeted melanoma screening project in 2011. One year later, the participants were invited by mail to consult their GP for an annual skin examination. Efficacy of the procedure was evaluated according to patient participation and the number of melanomas detected. The consultation dates and results were collected during the 12 months postreminder and were analysed using SAS. Analyses of whether participation decreased compared with that during the year of inclusion and whether populations at risk for thick melanoma showed reduced participation in the screening were performed.
Of the 3745 patients who received the mailed invitation, 61% underwent a skin examination. The participation of patients at risk for thick melanoma (any patient over 60 years of age and men over 50 years of age) was significantly greater than that of the patients in the other subgroups (72.4% vs 49.6%, p<0.001; and 66% vs 52.4%, p<0.001, respectively). The patients referred to the dermatologist after 1 year were more compliant compared with those referred during the first year (68.8% vs 59.1%, p=0.003). Six melanomas were detected within 1 year postreminder; therefore, the incidence of melanoma in the study population was 160/100 000.
This study confirms the benefits of developing a targeted screening strategy in primary care. In particular, after the annual reminder, patient participation and the diagnosis of melanoma remained high in the patients at elevated risk of thick melanomas.
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BMJ Open 07/2015; 5(7):e007471. DOI:10.1136/bmjopen-2014-007471 · 2.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To date, the term 'acne mechanica' defines different cutaneous lesions caused by mechanical injury.
To re-define the spectrum of cutaneous lesions caused by mechanical injury by determining their clinical and histological characteristics, to discuss and identify triggering and pathophysiologic elements.
Clinical, histological and pathophysiological differences of 135 published cases of acne mechanica were analysed and compared to cases provided from our clinics.
Mechanical factors cause 2 types of mainly inflammatory cutaneous lesions: one presents with inflammatory papules, open comedones or has no comedonal lesions. We propose using the term 'folliculitis mechanica'. The second type corresponds to a flare-up of acne in areas prone to the condition. These lesions present the typical clinical and histological features of acne vulgaris, comprising inflammatory and retentional lesions. Treatment may include topical products, including adjunctive care for reconstruction of the cutaneous barrier and the microbiome. Conventional acne medication should be used in cases of acne flare-up.
[Show abstract][Hide abstract] ABSTRACT: Background Nivolumab (a programmed death 1 [PD-1] checkpoint inhibitor) and ipilimumab (a cytotoxic T-lymphocyte-associated antigen 4 [CTLA-4] checkpoint inhibitor) have been shown to have complementary activity in metastatic melanoma. In this randomized, double-blind, phase 3 study, nivolumab alone or nivolumab plus ipilimumab was compared with ipilimumab alone in patients with metastatic melanoma. Methods We assigned, in a 1:1:1 ratio, 945 previously untreated patients with unresectable stage III or IV melanoma to nivolumab alone, nivolumab plus ipilimumab, or ipilimumab alone. Progression-free survival and overall survival were coprimary end points. Results regarding progression-free survival are presented here. Results The median progression-free survival was 11.5 months (95% confidence interval [CI], 8.9 to 16.7) with nivolumab plus ipilimumab, as compared with 2.9 months (95% CI, 2.8 to 3.4) with ipilimumab (hazard ratio for death or disease progression, 0.42; 99.5% CI, 0.31 to 0.57; P<0.001), and 6.9 months (95% CI, 4.3 to 9.5) with nivolumab (hazard ratio for the comparison with ipilimumab, 0.57; 99.5% CI, 0.43 to 0.76; P<0.001). In patients with tumors positive for the PD-1 ligand (PD-L1), the median progression-free survival was 14.0 months in the nivolumab-plus-ipilimumab group and in the nivolumab group, but in patients with PD-L1-negative tumors, progression-free survival was longer with the combination therapy than with nivolumab alone (11.2 months [95% CI, 8.0 to not reached] vs. 5.3 months [95% CI, 2.8 to 7.1]). Treatment-related adverse events of grade 3 or 4 occurred in 16.3% of the patients in the nivolumab group, 55.0% of those in the nivolumab-plus-ipilimumab group, and 27.3% of those in the ipilimumab group. Conclusions Among previously untreated patients with metastatic melanoma, nivolumab alone or combined with ipilimumab resulted in significantly longer progression-free survival than ipilimumab alone. In patients with PD-L1-negative tumors, the combination of PD-1 and CTLA-4 blockade was more effective than either agent alone. (Funded by Bristol-Myers Squibb; CheckMate 067 ClinicalTrials.gov number, NCT01844505 .).
New England Journal of Medicine 05/2015; 373(1). DOI:10.1056/NEJMoa1504030 · 54.42 Impact Factor
[Show abstract][Hide abstract] 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.
Cancer Immunology and Immunotherapy 04/2015; 64(7). DOI:10.1007/s00262-015-1691-7 · 3.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Extensive rhinectomy or full-thickness defects are not uncommon, in particular in the treatment of skin cancer. The present study lays out the principles of choice and creation of prostheses for nasal reconstruction. Prosthetic nasal reconstruction in France depends on a specialist prescription drawn up under the “Ocular and Facial Prostheses” rubric of the official List of Products and Procedures. National health insurance cover is 100% on condition that the prosthesis is produced by an approved prosthetist. The present study describes production stages, forms and means of fixation, and the timeline of implantation. Nasal prosthetic repair is simple, fast and functional, allowing social rehabilitation despite full respect of carcinologic margins, and without ruling out subsequent multilayer reconstruction. Benefits and drawbacks, and the factors determining repair options according to pathologic context are discussed. Nasal prostheses are an integral option in the repair of full-thickness nasal defects and total rhinectomies. The head and neck surgeon needs expertise in indications and techniques of reconstruction, so as to prescribe nasal prostheses as the context demands.
European Annals of Otorhinolaryngology, Head and Neck Diseases 12/2014; 132(2). DOI:10.1016/j.anorl.2014.02.007