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Many clinical studies have shown ultrasonography (US) is useful for the diagnosis of different abnormalities involving pleura; chest ultrasound (CUS) is widely used to detect pneumothorax in patients, but there is no data on its use for the follow-up of lung re-expansion after lung resection.We performed a unicentric observational study all patients between January 2018 and May 2021 undergoing lobectomy in which lung re-expansion was assessed daily with chest ultrasound (CUS) and chest radiography (CXR) until chest drainage was removed. Ultarsound clinical signs indicating a pneumothorax were: the detection of a positive lung point, absence of sliding or a consistent stratosphere sign with an absence of lung pulse, B-lines, I-lines or consolidations.Sensitivity, specificity, PPV, NPV of CUS and CXR were, respectively: 86% vs. 98% (p = 0.002); 100% vs. 100% (p = 1.0); 94% vs. 75% (p = 0.231); and 94% vs. 99% (p = 0.7).Ultrasound is a method available also to the patient's bed, an easy-to-learn technique even for inexperienced operators, therefore it is a valuable tool for checking the post-lobectomy lung expansion, reduce the use of chest radiography.Chest ultrasound, Chest radiography, Pneumothorax.L’ecografia del torace è ampiamente usata per riscontrare lo pneumotorace, ma non vi sono dati sui controlli della successiva riespansione del polmone dopo interventi di resezione. Abbiamo fatto uno studio osservazionale unicentrico della nostra casistica raccolta dal gennaio 2018 a maggio 2019 dopo lobectomia, con controllo quotidiano mediante l’ecografia toracica e radiografie del torace fino alla rimozione del drenaggio pleurico. La sensibilità, specificità, PPV, NPV dell’ecografia e della radiografia del torace sono state rispettivamente 86% vs. 98% (p = 0.002); 100% vs. 100% (p = 1.0); 100% vs. 100% (p = 1.0); 94% vs. 75% (p = 0.231); and 94% vs. 99% (p = 0.7). In coclusione l’ecografia risulta essere un metodo affidabile anche dei pazienti a letto, ed una tecnica di facile apprendimento anche per operatori poco esperti, quindi valido per i controlli dell’espansione polmonare dopo lobectomia, riducendo la necessità dell’uso delle radiografie ripetute del torace.

Additional file 4.

Additional file 1.

Additional file 1: Table S1. Main characteristics of the 6 randomized trials included in the pooled analysis. Table S2. Distribution of patients according to trial and treatment in the whole population and in landmark and out-of-landmark populations. Table S3. Patient characteristics in the whole eligible population (N = 1529) according to neutropenia. Table S4. Patient characteristics in the landmark population (N = 572) according to neutropenia. Table S5. Patient characteristics in the out-of-landmark population (N = 957) according to neutropenia. Table S6. Worst grade of neutropenia by treatment and trial in the landmark group. Figure S1. Distribution of worst grade of neutropenia over cycles in the landmark population.

Adding bevacizumab to erlotinib prolonged progression-free survival (PFS) of patients with EGFR-mutated advanced NSCLC in the Japanese JO25567 trial, but limited data were available in non-Asian patients. BEVERLY is an Italian, multicenter, randomized, phase 3 investigating the addition of bevacizumab to erlotinib as first-line treatment of advanced EGFR-mutated NSCLC.Eligible patients were randomized 1:1 to erlotinib plus bevacizumab or erlotinib alone. Investigator-assessed PFS and blinded independent centrally reviewed PFS were coprimary end points. With 80% power in detecting a 0.60 hazard ratio and two-sided α error of 0.05, 126 events of 160 patients were needed. The trial was registered as NCT02633189 and EudraCT 2015-002235-17.From April 11, 2016, to February 27, 2019, a total of 160 patients were randomized to erlotinib plus bevacizumab (80) or erlotinib alone (80). At a median follow-up of 36.3 months, median investigator-assessed PFS was 15.4 months (95% confidence interval [CI]: 12.2-18.6) with erlotinib plus bevacizumab and 9.6 months (95% CI: 8.2-10.6) with erlotinib alone (hazard ratio = 0.66, 95% CI: 0.47-0.92). Blinded independent centrally reviewed PFS analysis confirmed this result. A statistically significant interaction with treatment effect was found for smoking habit (p = 0.0323), with PFS prolongation being clinically significant only among current or previous smokers. Hypertension (grade ≥3: 24% versus 5%), skin rash (grade ≥ 3: 31% versus 14%), thromboembolic events (any grade: 11% versus 4%), and proteinuria (any grade: 23% versus 6%) were more frequent with the combination.The addition of bevacizumab to first-line erlotinib prolonged PFS in Italian patients with EGFR-mutated NSCLC; toxicity was increased with the combination but without unexpected safety issues.

The azygos system is the most important pathway for decompression of the superior vena cava (SVC) when a blood flow obstruction to the right atrium is present. Thoracic and mediastinal malignancies, mainly lung cancers, are responsible for 60%-85% of superior vena cava syndrome (SVCS) cases. An uncommon origin of SVCS is primary malignant mediastinal germ cell tumor (PMMGCT) which represent 1%-4% of all mediastinal tumors and can be divided into two broad groups: seminomas and nonseminomatous germ cell tumors (NSGCTs). Primary mediastinal seminomas clinical presentation is often nonspecific, even if the majority of patients present with superior vena cava involvement. Here, we present the radiologic features of asymptomatic azygos system overflow in a patient with primary mediastinal seminoma.

Cancer immunotherapy has produced an unprecedented durable response rate, thus shifting from traditional doublet chemotherapy to immunotherapy-based treatments with and without chemotherapy as the first line strategies for advanced non-small cell lung cancer patients without a molecular driver. However, the majority of patients do not benefit from the treatment or may relapse after a period of response. As few treatment options are available after failure of cancer immunotherapy, including the combination of chemotherapy and anti-angiogenic drugs, a better understanding of the mechanisms limiting cancer immunotherapy may be of help in the definition of the best second line. Whereas only retrospective data support an immunotherapy rechallenge approach, new combination strategies including immunotherapy and cell-signaling inhibitors or double immunotherapy represent the newest and most promising strategy to overcome primary or acquired resistance to first line immunotherapy.

Background Pioglitazone, a synthetic peroxisome proliferator activated receptor (PPAR-γ) ligand, is known as an antidiabetic drug included in the thiazolidinediones (TZDs) class. It regulates the lipid and glucose cell metabolism and recently a role in the inhibition of numerous cancer cell processes has been described. Methods In our work we investigate the anti-tumor effects of pioglitazone in in vitro models of non small cell lung cancer (NSCLC) and also, we generated ex-vivo three-dimensional (3D) cultures from human lung adenocarcinoma (ADK) as a model to test drug efficacy observed in vitro. The inhibitory effect of pioglitazone on cell proliferation, apoptosis and cell invasion in a panel of human NSCLC cell lines was evaluated by multiple assays. Results Pioglitazone reduced proliferative and invasive abilities with an IC50 ranging between 5 and 10 μM and induced apoptosis of NSCLC cells. mRNA microarray expression profiling showed a down regulation of MAPK, Myc and Ras genes after treatment with pioglitazone; altered gene expression was confirmed by protein analysis in a dose-related reduction of survivin and phosphorylated proteins levels of MAPK pathway. Interestingly mRNA microarray analysis showed also that pioglitazone affects TGFβ pathway, which is important in the epithelial-to-mesenchimal transition (EMT) process, by down-regulating TGFβR1 and SMAD3 mRNA expression. In addition, extracellular acidification rate (ECAR) and a proportional reduction of markers of altered glucose metabolism in treated cells demonstrated also cell bioenergetics modulation by pioglitazone. Conclusions Data indicate that PPAR-γ agonists represent an attractive treatment tool and by suppression of cell growth (in vitro and ex vivo models) and of invasion via blockade of MAPK cascade and TGFβ/SMADs signaling, respectively, and its role in cancer bioenergetics and metabolism indicate that PPAR-γ agonists represent an attractive treatment tool for NSCLC.

An overactivation of hepatocyte growth factor (HGF)/mesenchymal-epithelial transition factor (MET) axis promotes tumorigenesis and tumor progression in various cancer types. Research data recently evidenced that HGF/MET signaling is also involved also in the immune response, mainly modulating dendritic cells functions. In general, the pathway seems to play an immunosuppressive role, thus hypothesizing that it could constitute a mechanism of primary and acquired resistance to cancer immunotherapy. Recently, some approaches are being developed, including drug design and cell therapy to combine MET and programmed cell death receptor-1 (PD-1)/programmed cell death receptor-ligand 1 (PD-L1) inhibition. This approach could represent a new weapon in cancer therapy in the future.

Anaplastic lymphoma kinase (ALK) gene activation is involved in the carcinogenesis process of several human cancers such as anaplastic large cell lymphoma, lung cancer, inflammatory myofibroblastic tumors and neuroblastoma, as a consequence of fusion with other oncogenes (NPM, EML4, TIM, etc) or gene amplification, mutation or protein overexpression. ALK is a transmembrane tyrosine kinase receptor that, upon ligand binding to its extracellular domain, undergoes dimerization and subsequent autophosphorylation of the intracellular kinase domain. When activated in cancer it represents a target for specific inhibitors, such as crizotinib, ceritinib, alectinib etc. which use has demonstrated significant effectiveness in ALK-positive patients, in particular ALK-positive non- small cell lung cancer. Several mechanisms of resistance to these inhibitors have been described and new strategies are underway to overcome the limitations of current ALK inhibitors.

Our previous works demonstrated the ability of metformin to revert resistance to gefitinib, a selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, in non-small-cell lung cancer (NSCLC) EGFR/LKB1 wild-type (WT) cell lines. However, the optimal dose of metformin to be used in non-diabetic patients still remains to be defined. The phase I-II trial METformin in Advanced Lung cancer (METAL) was designed to identify the maximum tolerated dose and to evaluate safety and activity of metformin combined with erlotinib in second-line treatment of patients with stage IV NSCLC, whose tumours harbour the WT EGFR gene. Purpose Our previous works demonstrated the ability of metformin to revert resistance to gefitinib, a selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, in non-small-cell lung cancer (NSCLC) EGFR/LKB1 wild-type (WT) cell lines. However, the optimal dose of metformin to be used in non-diabetic patients still remains to be defined. The phase I-II trial METformin in Advanced Lung cancer (METAL) was designed to identify the maximum tolerated dose and to evaluate safety and activity of metformin combined with erlotinib in second-line treatment of patients with stage IV NSCLC, whose tumours harbour the WT EGFR gene.Patients and methods We report results from the safety run-in part designed to detect acute toxicities, to study pharmacokinetics and to identify the recommended phase II dose (RPD) to be used for the following phase of the study. In the run-in phase, metformin treatment was administered according to a dose escalation scheme and, subsequently, combined with erlotinib.Results Twelve patients were enrolled. Common adverse events were diarrhoea, decreased appetite, abdominal pain, vomiting and skin toxicity, mostly reversible with symptomatic medical treatment. Dose-limiting toxicities were vomiting and diarrhoea registered in the initial cohort receiving metformin 2000 mg plus erlotinib at 150 mg die, which was declared the maximum administered dose. Only one of nine patients treated at the next lower dose of 1500 mg of metformin plus erlotinib at 150 mg experienced G3 gastrointestinal toxicity. Metformin plasma-concentration profile confirmed the trend already observed in nondiabetic population. Glycemic profiles showed stability of the blood glucose level within the physiological range for non-diabetic subjects. At a follow-up of 30 weeks, six (50%) patients experienced a disease control (5 SD and 1 partial response).Conclusions The RP2D of metformin dose was defined at 1500 mg/day to be combined with erlotinib 150 mg.