Three-year follow-up of advanced melanoma patients who received ipilimumab plus fotemustine in the Italian Network for Tumor Biotherapy (NIBIT)-M1 phase II study.

BACKGROUND: In the NIBIT-M1 study, we reported a promising activity of ipilimumab combined with fotemustine in metastatic melanoma (MM) patients with or without brain metastases. To corroborate these initial findings, we now investigated the long-term efficacy of this combination. PATIENTS AND METHODS: This analysis captured the 3-year outcome of MM patients who received ipilimumab combined with fotemustine as first- or second-line treatment. Median overall survival (OS), 3-year survival rates, immune-related (ir) progression-free survival (irPFS), brain PFS, and ir duration of response (irDOR) for the entire population and for patients with brain metastases were assessed. Clinical results were correlated with circulating CD3(+)CD4(+)ICOS(+)CD45RO(+) or CD45RA(+) T cells, neutrophil/lymphocyte (N/L) ratios, and tumorBRAF-V600 mutational status. RESULTS: Eighty-six MM patients, including 20 with asymptomatic brain metastases that had been pre-treated with radiotherapy in 7 subjects, were enrolled in the study. With a median follow-up of 39.9 months, median OS and 3-year survival rates were 12.9 months [95% confidence interval (CI) 7.1-18.7 months] and 28.5% for the whole study population, and 12.7 months (95% CI 2.7-22.7 months) and 27.8% for patients with brain metastases, respectively. Long-term ir adverse events consisting of G1 rush and pruritus occurred in 21% of patients. The absolute increase from baseline to week 12 in 'memory' but not in 'naïve' T cells identified patients with a better survival (P = 0.002). The N/L ratio correlated with a significantly better survival at early time points. BRAF status did not correlate with clinical outcome. CONCLUSIONS: Long-term analysis of the NIBIT-M1 trial continues to demonstrate efficacy of ipilimumab combined with fotemustine in MM patients. Fotemustine does not seem to impair the immunologic activity of ipilimumab. EUDRACT NUMBER: 2010-019356-50. CINICALTRIALSGOV: NCT01654692.

[Pilot study of professional exposure and hearing functionality of orchestra musicians of a national lyric theatre]. / Studio pilota dell'esposizione professionale a rumore e della funzionalità uditiva dei musicisti di una orchestra lirica nazionale.

The sound exposure of classic orchestra musicians is not well assessed in Italy even though the protectionistic law includes all the working environments, as stated in the European Directive 2003/10/EC relative to the protection of workers against noise-induced damage. Scientific data in the literature show that the musicians are exposed to high daily personal exposure levels. These levels can systematically exceed the 85 dB(A) in the case of percussionists. In this study, preliminary results are shown relative to an experimental campaign performed in a lyric National Theatre. The aim of the study was the assessment of the risk due to high sound level in the theatre musicians and their cochlear functionality. The noise levels were measured by using wearable phonometers and multichannel sound analyzers. The signals were recorded during the whole working time in the rehearsal hall and in the fossa. The cochlear functionality was monitored before and immediately after rehearsal in a sample of volunteers by means of otoacoustic emission tests. Both TEOAE and DPOAE were measured using the ILO292 portable system. The data show that OAE-based tests can effectively discriminate between different classes of exposure. A good correlation was found between the daily exposure level and the DPOAE level.