Melanoma and intellectual disability: do prognostic factors at diagnosis differ from general population?

BACKGROUND: Few melanoma cases are reported in individuals with intellectual disability (ID), and prognostic factors at diagnosis are unknown in this population. This work was designed to investigate whether prognostic factors at diagnostic are different in patients with ID compared with a general population. METHODS: Melanoma cases retrieved from Hérault's Tumour Registry (HTR) from 1995 to 2015 were cross-referenced against a list of adult patients with ID, living in Hérault. Major prognostic factors were compared with those in non-ID melanoma patients included in HTR and in patients followed by Montpellier University Hospital and included in the Réseau pour la Recherche et l'Investigation Clinique sur le Mélanome (RIC-Mel) database. RESULTS: Ten melanoma cases in individuals with ID were identified and compared with 3804 non-ID melanoma cases in HTR and 1024 non-ID melanoma cases included in RIC-Mel. Mean Breslow thickness at diagnosis was 4.6 mm in melanoma cases among those with ID versus 1.89 mm in HTR (P = 0.109) and 2.36 mm in RIC-Mel (P = 0.156). Stage at diagnosis was superior to stage IIB in 42.9% of ID cases versus 11.4% of non-ID cases in HTR (P < 0.05) and 8.5% in RIC-Mel (P < 0.05). CONCLUSIONS: Melanomas in patients with ID had less favourable prognostic factors at diagnosis, including higher Breslow thickness and more advanced stage, than melanomas in non-ID patients. These adverse prognostic factors indicate a later diagnosis in this population, leading to a poorer prognosis. This work underlines the need to improve melanoma screening among individuals with ID.

Profile of vemurafenib-induced severe skin toxicities.

BACKGROUND: Vemurafenib, a BRAF inhibitor, is commonly associated with skin toxicity. The impact of severe forms is unknown. OBJECTIVE: To determine the rate of permanent vemurafenib discontinuation due to grade 3-4 skin toxicity, features of these toxicities, their recurrence rate after a switch to dabrafenib and their impact on overall survival. METHODS: Retrospective cohort study of 131 patients treated with vemurafenib for melanoma between November 2010 and December 2014. Data on skin toxicities, the need for vemurafenib adjustment and the impact of switching to dabrafenib were collected. Regarding survival analysis, a conditional landmark analysis was performed to correct lead-time bias. RESULTS: Among the 131 vemurafenib-treated patients, 26% developed grade 3-4 skin toxicity. Forty-four percent of them permanently discontinued their treatment, mainly due to rash and classic skin adverse reactions (Steven-Johnson syndrome, Drug Reaction with Eosinophilia and Systemic Symptoms). Conversely, photosensitivity and carcinomas rarely required treatment adjustment. Grade 3-4 rashes were associated with clinical or biological abnormalities in 94% of patients. Among the 10 patients who subsequently switched to dabrafenib, skin toxicity recurred only in one patient. Overall survival was significantly prolonged in case of severe skin toxicity emerging within the first 4 (P = 0.014) and 8 weeks (P = 0.038) on vemurafenib, with only a trend at 12 weeks (P = 0.052). Median overall survival was also prolonged in case of severe rash. CONCLUSION: In this study, vemurafenib was continued in 56% of patients with grade 3-4 skin toxicity, which was associated with prolonged overall survival when emerging within the first 4 and 8 weeks of treatment. While developing severe skin adverse reactions permanently contraindicates vemurafenib use, other rashes should lead to retreatment attempts with dose reduction. In case of recurrence, dabrafenib seems to be an interesting option. For other skin toxicities, including photosensitivity and cutaneous carcinoma, treatment adjustment is usually not needed.

Reliability of routine disc susceptibility testing by the British Society for Antimicrobial Chemotherapy (BSAC) method.

OBJECTIVES: To ascertain the agreement between MICs determined at a central laboratory, and susceptible, intermediate and resistant categorizations based on zone diameters recorded at diagnostic laboratories using the BSAC standardized method. METHODS: Standardized disc susceptibility tests were performed at sentinel laboratories in three surveys, with MIC tests performed on the collected isolates at a reference laboratory. The organisms comprised over 3300 Enterobacteriaceae, Acinetobacter spp., pseudomonads, staphylococci and enterococci, with over 29 000 antibiotic/organism tests in total. RESULTS: More than 90% of the antibiotic/organism combinations classed as susceptible by disc tests in the sentinel laboratories were confirmed by MIC testing. Disagreements were more frequent where disc tests indicated resistance, with half of the piperacillin/tazobactam resistance and one-third of the cephalosporin resistance found in Enterobacteriaceae by disc tests not being confirmed, and with three-quarters of teicoplanin resistance in enterococci not confirmed. None of the few apparent cases of meropenem resistance in Enterobacteriaceae or linezolid, quinupristin/dalfopristin or vancomycin resistance in staphylococci were confirmed by MIC testing. When disagreements were found between disc- and MIC-based categorization, MICs were commonly, although not invariably, one to three doubling dilutions above or below the breakpoint. However, many of the disagreements where MICs were three or more dilutions from the breakpoint were not seen when disc tests were repeated in the central laboratory. CONCLUSIONS: The BSAC disc method seems adequate for confirming susceptibility to guide therapy and to monitor resistance trends. Nevertheless, there must be concern about the over-estimation of many resistances, and frequent zone:MIC disagreements for isolates with borderline susceptibility.