Phase 4 Multinational Multicenter Retrospective and Prospective Real-World Study of Nivolumab in Recurrent and Metastatic Squamous Cell Carcinoma of the Head and Neck.

This study examined the real-world use of nivolumab in patients with recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). This was a multinational retrospective study (VOLUME) assessing treatment effectiveness and safety outcomes and a prospective study (VOLUME-PRO) assessing HRQoL and patient-reported symptoms. There were 447 and 51 patients in VOLUME and VOLUME-PRO, respectively. Across both studies, the median age was 64.0 years, 80.9% were male, and 52.6% were former smokers. Clinical outcomes of interest included real-world overall survival (rwOS) and real-world progression-free survival (rwPFS). The median rwOS was 9.2 months. Among patients with at least one assessment, 21.7% reported their best response as 'partial response', with 3.9% reporting 'complete response'. The median duration of response (DoR) and median rwPFS were 11.0 months and 3.9 months, respectively. At baseline, VOLUME-PRO patients reported difficulties relating to fatigue, physical and sexual functioning, dyspnea, nausea, sticky saliva, dry mouth, pain/discomfort, mobility, and financial difficulties. There were improvements in social functioning and financial difficulties throughout the study; however, no other clinically meaningful changes were noted. No new safety concerns were identified. This real-world, multinational, multicenter, retrospective and prospective study supports the effectiveness and safety of nivolumab for R/M SCCHN patients

U–Pb isotopic ages and Hf isotope composition of zircons in Variscan gabbros from central Spain: evidence of variable crustal contamination

Ion microprobe U–Pb analyses of zircons from three gabbroic intrusions from the Spanish Central System (SCS) (Talavera, La Solanilla and Navahermosa) yield Variscan ages (300 to 305 Ma) in agreement with recent studies. Only two zircon crystals from La Solanilla massif gave slightly discordant Paleoproterozoic ages (1,848 and 2,010 Ma). Hf isotope data show a relatively large variation with the juvenile end-members showing ɛHfi values as high as +3.6 to +6.9 and +1.5 to +2.9 in the Navahermosa and Talavera gabbros, respectively. These positive ɛHfi values up to +6.9 might represent the composition of the subcontinental mantle which generates these SCS gabbros. This ɛHfi range is clearly below depleted mantle values suggesting the involvement of enriched mantle components on the origin of these Variscan gabbros, and is consistent with previous whole-rock studies. The presence of zircons with negative ɛHfi values suggest variable, but significant, crustal contamination of the gabbros, mainly by mixing with coeval granite magmas. Inherited Paleoproterozoic zircons of La Solanilla gabbros have similar trace element composition (e.g. Th/U ratios), but more evolved Hf-isotope signatures than associated Variscan zircons. Similar inherited ages have been recorded in zircons from coeval Variscan granitoids from the Central Iberian Zone. Granitic rocks have Nd model ages (TDM) predominantly in the range of 1.4 to 1.6 Ga, suggesting a juvenile addition during the Proterozoic. However, Hf crustal model ages of xenocrystic Proterozoic zircons in La Solanilla gabbro indicate the presence of reworked Archean protoliths (TDM2 model ages of 3.0 to 3.2 Ga) incorporated into the hybridized mafic magma