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.
Abstract Background Despite the efficacy of innovative treatments for metastatic melanoma, their high costs has led to disparities in cancer care among different European countries. We analysed the ...availability of these innovative therapies in Europe and estimated the number of patients without access to first-line recommended treatment per current guidelines of professional entities such as the European Society for Medical Oncology (ESMO), the European Organisation for Research and Treatment of Cancer (EORTC), the European Association of Dermato-Oncology (EADO), and European Dermatology Forum (EDF). Materials and methods Web-based online survey was conducted in 30 European countries with questions about the treatment schedules from 1st May 2015 to 1st May 2016: number of metastatic melanoma patients, registration and reimbursement of innovative medicines (updated data, as of 1st October 2016), percentage of patients treated and availability of clinical studies and compassionate-use programmes. Results The recommended BRAF inhibitor (BRAFi) + MEK inhibitor (MEKi) combination was both registered and fully reimbursed in 9/30 (30%) countries, and in 13/30 (43%) (all from Eastern Europe) not reimbursed. First-line immunotherapy with anti-PD1 antibodies was registered and fully reimbursed in 14/30 (47%) countries, while in 13/30 (43%) (all from Eastern Europe) not reimbursed. It was estimated that in Europe 19,600 patients with metastatic melanoma are treated, and 5238 (27%) do not have access to recommended first-line therapy. Significant correlation was found between human development index (HDI, UNDP report 2015), (r = 0.662; p < 0.001), health expenditure per capita (r = 0.695; p < 0.001) and the Mackenbach score of health policy performance (r = 0.765; p < 0.001) with the percentage of patients treated with innovative medicines and a number of reimbursed medicines. Conclusions Great discrepancy exists in metastatic melanoma treatment across Europe. It is crucial to increase the awareness of national and European policymakers, oncological societies, melanoma patients' associations and pharma industry.
This report provides a survival update at a follow-up of >5 years (5.5–6 years) for patients with advanced melanoma who previously received ipilimumab in phase II clinical trials. Safety and efficacy ...data following ipilimumab retreatment are also reported.
Patients who previously received ipilimumab 0.3, 3, or 10 mg/kg in one of six phase II trials (CA184-004, CA184-007, CA184-008, CA184-022, MDX010-08, and MDX010-15) were eligible to enroll in the companion study, CA184-025. Upon enrollment, patients initially received ipilimumab retreatment, extended maintenance therapy, or were followed for survival only. Overall survival (OS) rates were evaluated in patients from studies CA184-004, CA184-007, CA184-008, and CA184-022. Safety and best overall response during ipilimumab retreatment at 10 mg/kg were assessed in study CA184-025.
Five-year OS rates for previously treated patients who received ipilimumab induction at 0.3, 3, or 10 mg/kg were 12.3%, 12.3%–16.5%, and 15.5%–28.4%, respectively. Five-year OS rates for treatment-naive patients who received ipilimumab induction at 3 or 10 mg/kg were 26.8% and 21.4%–49.5%, respectively. Little to no change in OS was observed from year 5 up to year 6. The objective response rate among retreated patients was 23%. Grade 3/4 immune-related adverse events occurred in 25%, 5.9%, and 13.2% of retreated patients who initially received ipilimumab 0.3, 3, and 10 mg/kg, with the most common being observed in the skin (4.2%, 2.9%, 3.8%) and gastrointestinal tract (12.5%, 2.9%, 3.8%), respectively.
At a follow-up of 5–6 years, ipilimumab continues to demonstrate durable, long-term survival in a proportion of patients with advanced melanoma. In some patients, ipilimumab retreatment can re-establish disease control with a safety profile that is comparable with that observed during ipilimumab induction. Further studies are needed to determine the contribution of ipilimumab retreatment to OS.
NCT00162123.
This analysis was carried out to evaluate the long-term survival of patients with metastatic melanoma who received ipilimumab, a fully human monoclonal antibody that binds to cytotoxic T-lymphocyte ...antigen-4, in clinical trials.
Patients received ipilimumab in one of three completed phase II clinical trials (CA184-008, CA184-022, and CA184-007). Previously treated patients were enrolled in all studies, and treatment-naïve patients were also included in study CA184-007. Patients received ipilimumab at a dose of 10 mg/kg in studies CA184-008 and CA184-007, and at doses of 0.3, 3, or 10 mg/kg in study CA184-022. Ipilimumab was given every 3 weeks for four doses, and eligible patients could receive ipilimumab maintenance therapy every 12 weeks. In study CA184-022, patients could cross over to be retreated with ipilimumab at 10 mg/kg upon disease progression. Ongoing survival follow-up is conducted in a companion study, CA184-025.
Four-year survival rates 95% confidence interval (95% CI) for previously treated patients who received ipilimumab at 0.3, 3, or 10 mg/kg were 13.8% 6.1–22.5, 18.2% 9.5–27.6, and 19.7% 13.4–26.5 to 28.4% 13.9–44.2, respectively. In treatment-naïve patients who received ipilimumab at 10 mg/kg, 4-year survival rates were 37.7% 18.6–57.4 to 49.5% 23.8–75.4.
These results demonstrate durable survival in a significant proportion of patients with metastatic melanoma who received ipilimumab therapy.
Objective. Familial and HIV-associated lipodystrophies are associated with metabolic disorders and elevated blood pressure. Whether corticosteroid-induced lipodystrophy (CIL) is also associated with ...features of the metabolic syndrome is unknown.
Methods. We conducted a prospective study in two French tertiary centres and enrolled all consecutive patients starting long-term (≥3 months), high dosage (≥20 mg/day) systemic corticosteroid therapy. Three investigators assessed the development of CIL from standardized head and neck photographs. Arterial blood pressure and fasting blood glucose levels were assessed at baseline and then every three months until month 12. Total, HDL- and LDL-cholesterol and triglycerides were recorded at baseline, month 3 and month 12.
Results. Eighty-eight patients were enrolled (women: 75%, mean age: 57.4 ± 17.9 yrs, mean baseline dosage of prednisolone: 56 ± 15 mg/day). Sixty-four patients still received corticosteroids at month 12 (mean prednisolone dosage: 11 ± 4 mg/day). In intention-to-treat analysis, the cumulative incidence rate of CIL at months 3 and 12 was 61 ± 8% and 69 ± 9%, respectively. Baseline characteristics were similar in patients who developed CIL and patients who did not develop CIL during follow-up except with regard to baseline body mass index, which was higher in patients who develop CIL (24.3 ± 3.7 kg/m2
vs 21.4 ± 3.2 kg/m2, P= 0.02). Blood pressure was significantly higher in CIL+ patients at month 9 (135/78 mmHg vs 127/73 mmHg) and month 12 (141/81 mmHg vs 128/72 mmHg) visits. Moreover, compared with CIL− patients, CIL+ patients had significantly higher plasma concentrations of fasting blood glucose, triglycerides and total cholesterol and lower HDL-cholesterol concentration during follow-up.
Conclusions. CIL is associated with features of the metabolic syndrome and should then not be considered only as an aesthetic challenge. Further studies are required to test the relation between CIL and cardiovascular events.
The aims of the study were to assess the risk of HHV8 transmission resulting from organ transplantation, and related morbidity in liver, heart and kidney transplant recipients. Donor and recipient ...serologies were screened between January 1, 2004 and January 1, 2005 using HHV8 indirect immunofluorescence latent assay (latent IFA) and indirect immunofluorescent lytic assay (lytic IFA). Recipients negative for latent IFA with a donor positive for at least one test were sequentially monitored for HHV8 viremia and underwent serological tests over a period of 2 years. The results showed that among 2354 donors, HHV8 seroprevalence was 9.9% (lytic IFA) and 4.4% (latent IFA). A total of 454 organ recipients (281 renal, 116 liver and 57 heart) were monitored over a 2‐year period. Seroconversion was observed in 12 patients (cumulative incidence 28%) whose donor had positive latent IFA and in 36 patients (cumulative incidence 29%) whose donors were positive only for lytic IFA, without differences across types of transplants. Positive HHV8 viremia was detected in only 4 out of 89 liver transplant recipients during follow‐up and not in recipients of other types of transplant. Two liver transplant recipients and one kidney transplant recipient developed KS. In conclusion, although HHV8 transmission is a frequent event after organ transplantation, HHV8‐related morbidity is rather rare but can be life threatening. Donor screening is advisable for monitoring HHV8 seronegative liver transplant recipients.
This prospective French national cohort study shows a cumulative incidence of 28% of human herpesvirus‐8 seroconversion among organ transplant recipients at risk of contamination, without any difference regardless of the organ transplanted, together with an overall very low prevalence of positive viremia and morbidity.
Abstract Objective To describe patterns of healthcare resource utilisation and associated costs for patients with advanced melanoma in the United Kingdom (UK), Italy, and France. Methods For patients ...receiving systemic treatment, or supportive care, data describing hospitalisations, hospice care, and outpatient visits were retrieved retrospectively from advanced disease diagnosis as part of a multicountry observational study. Costs were estimated by multiplying utilisation level by unit cost. In an exploratory analysis, costs were compared between individuals who died within one year of initiating first-line treatment (short-term survivors) and those with ⩾1 year follow-up (long-term survivors). Results Hospitalisation costs were highest in France (€6262 per-person compared with €3225 in the UK and €2486 in Italy), reflecting higher rates of hospitalisation. In contrast, outpatient costs were highest in the UK (€782 per-person, compared with €115 in France and €72 in Italy), reflecting the highest rate and frequency of outpatient visits and the highest cost per visit. Hospitalisation rates were consistently higher during supportive care compared with systemic therapy. Roughly one-third of patients entered clinical trials and were not included in the analysis. In exploratory analysis, total costs were generally higher for long-term survivors, but monthly per-patient costs were generally lower for long-term survivors, consistent with a hypothesis that resource utilisation and costs do not necessarily increase proportionally with extended survival. Conclusion Total costs associated with resource utilisation for advanced melanoma patients varied across countries. Overall cost differences were due to differences in frequency and intensity of utilisation patterns and variation in unit costs of health resources.
Les inhibiteurs de checkpoint immunitaire (ICI), tels que les anticorps anti-PD-1, PD-L1 et anti-CTLA-4, sont efficaces dans de nombreux cancers. Cependant, entre 70 et 90 % des patients présentent ...des effets indésirables (EI). Le lupus érythémateux immuno-induit (LEII) est un EI rare.
L’objectif de notre étude était d’éstimer la prévalence des LEII dans une population traitée en oncodermatologie pour un mélanome métastatique et décrire les caractéristiques cliniques et biologiques des patients présentant un LEII.
Nous avons interrogé rétrospectivement la base de données Melbase afin d’estimer la prévalence de LEII dans la population de mélanome traitée par ICI dans notre centre et la base nationale de pharmacovigilance (BNPV).
Sur 330 patients traités par ICI pour un mélanome dans notre centre depuis 2013, 2 patients présentaient un LEII (0,6 %). Dans la BNPV, 11 LEII étaient enregistrés, dont 6 femmes. L’âge médian était de 65 ans 42-82, les cancers primitifs étaient des adénocarcinomes pulmonaires (5), des mélanomes (4), un cancer du sein et un cancer ovarien. Les traitements reçus étaient : nivolumab en monothérapie (4) ou associé à ipilimumab (1), pembrolizumab (3), atezolizumab (2) durvalumab (1). Le délai médian entre l’introduction des ICI et les premiers symptômes était de 3 mois 0,5-6. Huit patients sur 11 présentaient un lupus cutané isolé confirmé histologiquement, 6 étaient des femmes, 1 avait des lésions muqueuses, 5 avaient des anticorps anti-SSA. Les traitements utilisés étaient des dermocorticoïdes (8/8), du plaquenil (3/8), des corticoïdes oraux (2/8) permettant une évolution favorable. L’ICI était poursuivi ou repris chez 3 patients sans récidive. Trois patients sur 11 présentaient un lupus érythémateux systémique (LES) répondant aux critères EULAR/ACR 2019, 2 patients présentaient une atteinte articulaire avec des anticorps anti-ADN natifs, d’évolution favorable sous corticoïdes et plaquenil, un présentait des sérites et un syndrome d’Evans traité par corticoïdes et immunoglobulines intraveineuses. Chez ces 3 patients, l’immunothérapie a été interrompue sans reprise.
Les lupus induits sont des EI rares dont les inducteurs les plus incriminés sont l’hydralazine et la procaïnamide. Les LEII sont peu rapportés et de diagnostic difficile de par l’absence de critères diagnostiques établis et la présentation clinique et biologique variée. Son incidence est estimée à 0,48 % dans l’étude de Michot et al. 1, proche de celle de notre expérience (0,6 %). L’atteinte cutanée isolée semble plus fréquente que la présentation systémique avec une prédominance de forme subaiguë et d’anti SSA. Les traitements classiques du lupus sont à proposer et l’arrêt de l’immunothérapie est à discuter selon la présentation clinique.
Le LEII est un EI rare mais parfois sévère. Le diagnostic peut être difficile devant des signes cliniques et biologiques variés.
Les inhibiteurs de point de contrôle immunitaire (ICIs) ont considérablement changé ces dernières années le pronostic de nombreuses néoplasies. Ces traitements peuvent induire des toxicités graves, ...comme la myocardite, la myasthénie et la myosite. Ces dernières sont d’ailleurs souvent intriquées. Au cours de ces toxicités, les anticorps anti-récepteurs de acéthyl-choline (anti-RAch), hautement spécifiques des myasthénies hors ICIs, peuvent être positifs. Leur signification clinique ou pronostique, n’est pas claire. L’objectif de cette étude était de décrire le profil clinique et biologique des patients présentant une myosite induite par ICIs avec anti-RAch positifs et de les comparer avec ceux testés anti-RAch négatifs.
Étude monocentrique rétrospective menée entre 2018 et 2021. Tous les patients anti-RAch positifs étant des hommes, il était décidé de n’inclure que les patients masculins anti-RAch négatifs de notre cohorte. Le diagnostic de myosite était retenu d’après les données histologiques musculaires (10/12 cas) ou devant l’association myalgies+augmentation CPK+EMG et imagerie musculaire positifs. Comme signes clinique évocateurs de myasthénie on retenait la présence d’au moins un signe parmi dysphonie, dysphagie, diplopie et/ou ptosis. Une myocardite était définie et classée en certaine, probable ou possible, selon des critères cliniques, biologiques et morphologiques en vigueur (Bonaca MP, 2019). Les anti-RAch et les anti-Musk étaient systématiquement recherchés par méthode ELISA.
12 hommes étaient inclus. L’âge au moment du diagnostic était de 73 ans (50-87). Les traitements par ICIs instaurés étaient : Nivolumab seul (n=4), Nivolumab +Ipilimumab (n=3), Pembrolizumab (n=3), Cemiplimab (n=1) et Avelumab (n=1), pour mélanome (n=9), carcinome épidermoide cutané (n=1), carcinome rénal (n=1) et carcinome de Merkel (n=1). Le nombre médian de cure à la constatation de la toxicité était de 1 cure (1-3) avec un délai médian 3 semaines (2-6). Les anti-RAch étaient positifs chez 5/12 patients, les anti-Musk toujours négatifs. Groupe anti-RAch positifs : d’après nos critères, 3/5 patients présentaient des signes cliniques évocateurs de myasthénie. Aucune fatigabilité n’était notifiée, un décrément n’était retrouvé à l’électromyogramme que dans 1/5 cas. À noter que les anti-RAch étaient présents dans le sérum de 2/2 patients testés avant l’instauration du traitement par ICIs. Comparaison des groupes anti-RAch positifs vs anti-RAch négatifs : aucune différence significative n’était retrouvée en terme de sévérité de l’atteinte musculaire (testing MRC médian 4 (3-5) vs 5 (3-5)), d’atteinte axiale ou diaphragmatique (2 cas vs 2), d’augmentation des CPK (7N vs 8N, p=0,87). Les signes évocateurs de myasthénie étaient en fréquence similaire : dysphonie (2 cas vs 2), dysphagie (2 cas vs 3), diplopie (2 cas vs 1) ou ptosis (0 cas vs 3). Bien que plus fréquente dans le groupe anti-RAch positifs (3 cas vs 1) la survenue d’une myocardite probable ou certaine était similaire (p=0,22). De même, le recours à une unité de soins intensif était plus fréquente dans le groupe anti-RAch positifs (4 cas vs 1), sans que l’effectif ne permette de conclure (p=0,07). La prise en charge thérapeutique était similaire dans les deux groupes. Les ICI ont été arrêtés ou suspendus chez tous les patients. Selon la gravité initiale, les patients recevaient tous des corticoïdes, en bolus intra-veineux (n=5) même lorsque les anti-RAch revenait positifs a posteriori (n=3). 2 patients avec anti-RAch positifs recevaient initialement l’adjonction d’un immunomodulateur (Abatacept ou IVIg), comme un patient avec anti-RAch négatifs (IVIg). La durée de traitement par corticoïdes (suivi médian 255jours, 60-800) était similaire dans les deux groupes : 3 mois vs 3 (2-7). Deux patients récemment pris en charge étaient en rémission partielle à 1 mois, alors que la corticothérapie orale était en déroissance.
La positivité des anti-Rach n’est pas rare au cours des myosites induites par les ICIs, ce qui doit inciter à les rechercher systématiquement. Ils ne semblent pas associés à un profil clinico-biologique ou pronostique particulier, notamment en terme de signes cliniques évocateurs de myasthénie. Toutefois d’autres études comparatives sont nécessaires afin de mieux cerner le profil clinique de ces patients, notamment en terme de sévérité globale, et d’assurer une prise en charge et un suivi ciblé. La recherche des autres anticorps rencontrés au cours des myasthénies, notamment ceux qui ne sont pas recherchés en routine comme les anti-LRP4 mériterait d’être systématique à des fins nosologiques rigoureuses. Certaines données de la littérature (Mammen AL, 2019) et le fait que les anti-RAch étaient positifs dans le sérum de 2/2 patients testés avant le traitement par ICIs, suggèrent la possibilité d’un rôle de ces anticorps dans la genèse de ces myosites induites par les ICIs.
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