In head and neck squamous cell carcinoma (HNSCC), data from studies using checkpoint-inhibiting antibodies that target programmed death 1 (PD-1) or its ligand the programmed death ligand 1 (PD-L1) demonstrated outstanding clinical activity. Translational investigations also suggested some correlations between therapeutic response and PD-L1 expression in tumor tissue. We comprehensively summarize results that have evaluated PD-L1 expression in HNSCC. We discuss flaws and strength of current PD-1/PD-L1 detection, quantification methods and the evaluation of PD-L1 as a prognostic and theragnostic biomarker. Understanding tumor microenvironment may help understanding resistance to checkpoint inhibitors, designing clinical trials that can exploit drug combinations.

Video-assisted thoracic surgery (VATS) is usually performed using three ports. Uniportal VATS has not yet been widely developed. We report our single institution experience in uniportal VATS for the surgical management of 351 patients with pneumothorax. Between November 2009 and February 2016, we conducted a study in 351 patients treated for pneumothorax using uniportal VATS. Resection of apical bullae associated with partial pleurectomy, pleural abrasion, or talc effusion was performed. The mean age was 29.6 ± 10.1 years. Surgical indications were mainly persistence or recurrence of pneumothorax. Sixty-seven patients (19%) presented with complications. At the 30-day control, 60.1% of patients were asymptomatic; 85% of patients were satisfied with the single small scar. The recurrence rate was 3.6% at 24 ± 13 months. Uniportal VATS is feasible, safe, and reproducible in the treatment of pneumothorax. Morbidity is similar to multiport VATS. The recurrence rate is comparable with best results after multiport VATS or thoracotomy. Patients were satisfied with the single small scar.

Mammalian target of rapamycin (mTOR) regulates cellular functions by integrating intracellular signals and signals from the tumor microenvironment (TME). The PI3K-AKT-mTOR pathway is activated in 70% of head and neck squamous cell carcinoma (HNSCC) and associated with poor prognosis. This phase I-II study investigated the effect of mTOR inhibition using weekly everolimus (30 mg for dose level 1, 50 mg for dose level 2) combined with weekly induction chemotherapy (AUC2 carboplatin and 60 mg/m² paclitaxel) in treatment-naïve patients with locally advanced T3-4/N0-3 HNSCC. Patients received 9 weekly cycles before chemoradiotherapy. Objectives were safety and antitumor activity along with tissue and blood molecular biomarkers. A total of 50 patients were enrolled. Among 41 evaluable patients treated at the recommended dose of 50 mg everolimus weekly, tolerance was good and overall response rate was 75.6%, including 20 major responses (≥50% reduction in tumor size). A significant decrease in expression of p-S6K (p-value: 0.007) and Ki67 (p-value: 0.01) was observed in post-treatment tumor tissue. Pro-immunogenic cytokine release (Th1 cytokines IFN-γ, IL-2, and TNF-β) was observed in the peripheral blood. The combination of everolimus and chemotherapy in HNSCC was safe and achieved major tumor responses. This strategy favorably impacts the TME and might be combined with immunotherapeutic agents.