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BACKGROUND: Rhinological procedures demand a high degree of technical expertise and anatomical knowledge. Because of limited surgical opportunities, ethical considerations and the complexity of these procedures, simulation-based training has become increasingly important. This review aimed to evaluate the effectiveness of simulation models used in rhinology training. METHODS: Searches were conducted on PubMed, Embase, Cochrane and Google Scholar for studies conducted between July 2012 and July 2022. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis ('PRISMA') protocol defined a final list of articles. Each validated study was assigned a level of evidence and a level of recommendation based on the Oxford Centre of Evidence-Based Medicine classification. RESULTS: Following exclusions, 42 articles were identified which encompassed six types of simulation models and 26 studies evaluated validity. The rhinological skills assessed included endoscopic sinus surgery (n = 28), skull base/cerebrospinal fluid leak repair (n = 14), management of epistaxis and/or sphenopalatine artery ligation (n = 8), and septoplasty and septorhinoplasty (n = 6). All studies reported the beneficial impact of their simulation models on trainee development. CONCLUSION: Simulation training in rhinology is a valuable adjunct to traditional surgical education. Although evidence is of moderate quality, the findings highlight the importance of simulation-based training in rhinology training.
RESUMEN
PURPOSE: Coblockade of lymphocyte activation gene-3 (LAG-3) and PD-1 receptors could provide significant clinical benefit for patients with advanced melanoma. Fianlimab and cemiplimab are high-affinity, human, hinge-stabilized IgG4 monoclonal antibodies, targeting LAG-3 and PD-1, respectively. We report results from a first-in-human phase-I study of fianlimab and cemiplimab safety and efficacy in various malignancies including advanced melanoma. METHODS: Patients with advanced melanoma were eligible for enrollment into four cohorts: three for patients without and one for patients with previous anti-PD-1 therapy in the advanced disease setting. Patients were treated with fianlimab 1,600 mg and cemiplimab 350 mg intravenously once every 3 weeks for up to 51 weeks, with an optional additional 51 weeks if clinically indicated. The primary end point was objective response rate (ORR) per RECIST 1.1 criteria. RESULTS: ORRs were 63% for patients with anti-PD-1-naïve melanoma (cohort-6; n = 40; median follow-up 20.8 months), 63% for patients with systemic treatment-naïve melanoma (cohort-15; n = 40; 11.5 months), and 56% for patients with previous neo/adjuvant treatment melanoma (cohort-16; n = 18, 9.7 months). At a median follow-up of 12.6 months for the combined cohorts (6 + 15 + 16), the ORR was 61.2% and the median progression-free survival (mPFS) 13.3 months (95% CI, 7.5 to not estimated [NE]). In patients (n = 13) with previous anti-PD-1 adjuvant therapy, ORR was 61.5% and mPFS 12 months (95% CI, 1.4 to NE). ORR in patients with previous anti-PD-1 therapy for advanced disease (n = 15) was 13.3% and mPFS 1.5 months (95% CI, 1.3 to 7.7). Treatment-emergent and treatment-related adverse events ≥grade 3 (G3) were observed in 44% and 22% of patients, respectively. Except for increased incidence of adrenal insufficiency (12%-G1-4, 4%-G3-4), no new safety signals were recorded. CONCLUSION: The current results show a promising benefit-risk profile of fianlimab/cemiplimab combination for patients with advanced melanoma, including those with previous anti-PD-1 therapy in the adjuvant, but not advanced, setting.