Patients with non-small cell lung cancer (NSCLC) develop bone metastasis (BoM) in more than 50% of cases during the course of the disease. This metastatic site can lead to the development of skeletal related events (SREs), such as severe pain, pathological fractures, spinal compression, and hypercalcemia, which reduce the patient’s quality of life. Recently, the treatment of advanced NSCLC has radically changed due to the advent of immunotherapy. Immune checkpoint inhibitors (ICI) alone or in combination with chemotherapy have become the main therapeutic strategy for advanced or metastatic NSCLC without driver gene mutations. Since survival has increased, it has become even more important to treat bone metastasis to prevent SRE. We know that the presence of bone metastasis is a negative prognostic factor. The lower efficacy of immunotherapy treatments in BoM+ patients could be induced by the presence of a particular immunosuppressive tumor and bone microenvironment. This article reviews the most important pre-clinical and clinical scientific evidence on the reasons for this lower sensitivity to immunotherapy and the need to combine bone target therapies (BTT) with immunotherapy to improve patient outcome.

Background: The Prognostic Nutritional Index (PNI) is a parameter of nutritional and inflammation status related to toxicity in cancer treatment. Since data for head and neck cancer are scanty, this study aims to investigate the association between PNI and acute and late toxicity for this malignancy. Methods: A retrospective cohort of 179 head and neck cancer patients treated with definitive radiotherapy with induction/concurrent chemotherapy was followed-up (median follow-up: 38 months) for toxicity and vital status between 2010 and 2017. PNI was calculated according to Onodera formula and low/high PNI levels were defined according to median value. Odds ratio (OR) for acute toxicity were calculated through logistic regression model; hazard ratios (HR) for late toxicity and survival were calculated through the Cox proportional hazards model. Results: median PNI was 50.0 (interquartile range: 45.5–53.5). Low PNI was associated with higher risk of weight loss > 10% during treatment (OR = 4.84, 95% CI: 1.73–13.53 for PNI < 50 versus PNI ≥ 50), which was in turn significantly associated with worse overall survival, and higher risk of late mucositis (HR = 1.84; 95% CI:1.09–3.12). PNI predicts acute weight loss >10% and late mucositis. Conclusions: PNI could help clinicians to identify patients undergoing radiotherapy who are at high risk of acute and late toxicity.

Osimertinib is currently the preferred first-line therapy in patients with non-small cell lung cancer (NSCLC) with common epidermal growth factor receptor (EGFR) mutation and the standard second-line therapy in T790M-positive patients in progression to previous EGFR tyrosine kinase inhibitor. Osimertinib is a highly effective treatment that shows a high response rate and long-lasting disease control. However, a resistance to the treatment inevitably develops among patients. Understanding the secondary mechanisms of resistance and the possible therapeutic options available is crucial to define the best management of patients in progression to osimertinib. We provide a comprehensive review of the emerging molecular resistance mechanism in EGFR-mutated NSCLC pre-treated with osimertinib and its future treatment applications.

We investigate Si/Si _0.85 Ge _0.15 fully depleted-SOI tunnel FET (TFET) devices operated in the electron-hole bilayer (EHB) mode. The application of negative bias on front gate and positive bias on back gate results in confined hole and electron layers that are expected to enable vertical band-to-band tunneling (BTBT). The idea of the EHB-TFET device is to enhance the tunneling current by expanding the BTBT generation area from the narrow lateral source/channel junction to the entire channel region. Our systematic measurements on a variety of TFETs with variable geometry and channel materials do not offer support to this attractive concept. Self-consistent simulations confirm that the vertical BTBT transitions do not produce an appreciable current in our devices, due to size-and bias-induced quantization, effective mass anisotropy, and incomplete formation of the bilayer. We examine the conditions for efficient vertical BTBT to occur and show that they cannot be met simultaneously, at least in Si or Si/SiGe devices.