The EXcellenT Trial: Exercise in Extended Oncogene Addicted Lung Cancer in Active Treatment.

Introduction: The discovery of oncogenic mutations that drive the growth and progression of Non-small-cell lung cancer (NSCLC) led to the development of a range of molecular targeted therapies. Tyrosine kinase inhibitors (TKIs) improve the overall outcome of patients with oncogene addicted NSCLC, ensure a better compliance to treatment and few side effects compared to traditional chemotherapy. However, the treatment is still completely "drug-centric", in a population of patients who usually survive for a long time and desire to regain their quality of life.

A Phase 1 Drug-Drug Interaction Study Between Brigatinib and the CYP3A Substrate Midazolam in Patients With ALK-Positive or ROS1-Positive Solid Tumors.

Brigatinib is a next-generation anaplastic lymphoma kinase (ALK) inhibitor approved for the treatment of patients with ALK-positive (ALK+) non-small cell lung cancer (NSCLC). A phase 1 drug-drug interaction study was conducted to evaluate the effect of multiple-dose administration of brigatinib on the single-dose pharmacokinetics of midazolam, a sensitive cytochrome P450 3A substrate. In cycle 1, patients with ALK+ or ROS1+ solid tumors, including NSCLC, received a single 3-mg dose of midazolam as an oral solution alone on day 1 and then coadministered with brigatinib on day 21 (brigatinib 90 mg once daily on days 2-8; 180 mg once daily on days 9-28).

Pralsetinib in RET fusion-positive non-small-cell lung cancer: A real-world data (RWD) analysis from the Italian expanded access program (EAP).

Objectives: The selective RET-inhibitor pralsetinib has shown therapeutic activity in early clinical trials in patients with non-small cell lung cancer (NSCLC) harboring rearranged during transfection (RET) gene fusions. To date, the real-world efficacy of pralsetinib in this population is unknown.

Materials And Methods: A retrospective efficacy and safety analysis was performed on data from patients with RET-fusion positive NSCLC enrolled in the pralsetinib Italian expanded access program between July 2019 and October 2021.

Addition of Bevacizumab to Erlotinib as First-Line Treatment of Patients With EGFR-Mutated Advanced Nonsquamous NSCLC: The BEVERLY Multicenter Randomized Phase 3 Trial.

Introduction: 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.

Methods: Eligible patients were randomized 1:1 to erlotinib plus bevacizumab or erlotinib alone.

Compassionate Use Program of Ipilimumab and Nivolumab in Intermediate or Poor Risk Metastatic Renal Cell Carcinoma: A Large Multicenter Italian Study.

This is a retrospective analysis on the safety and activity of compassionate Ipilimumab and Nivolumab (IPI-NIVO) administered to patients with metastatic Renal Cell Carcinoma (mRCC) with intermediate or poor International Metastatic RCC Database Consortium (IMDC) score as a first-line regimen. IPI was infused at 1 mg/kg in combination with Nivolumab 3 mg/kg every three weeks for four doses, followed by maintenance Nivolumab (240 or 480 mg flat dose every two or four weeks, respectively) until disease progression or unacceptable toxicity. A total of 324 patients started IPI-NIVO at 86 Italian centers.

A tri-modal tissue-equivalent anthropomorphic phantom for PET, CT and multi-parametric MRI radiomics.

Purpose: Radiomics has emerged as an advanced image processing methodology to define quantitative imaging biomarkers for prognosis and prediction of treatment response and outcome. The development of quantitative imaging biomarkers requires careful analysis to define their accuracy, stability and reproducibility through phantom measurements. Few efforts were devoted to develop realistic anthropomorphic phantoms.

A Case Report on Gallbladder Agenesis: Not a Novelty but Still a Laparoscopic Surprise.

Gallbladder agenesis (GA) is a rare embryological anomaly that presents acute cholecystitis like-symptoms. It is often an incidental finding diagnosed during surgery. We reported a case of GA in a patient who presented with dyspepsia and acute right upper abdomen pain with ultrasonographic signs of acute lithiasic cholecystitis.

The Expression of Programmed Death Ligand 1 and Vimentin in Resected Non-Metastatic Non-Small-Cell Lung Cancer: Interplay and Prognostic Effects.

Programmed death ligand 1 (PD-L1) is an immune checkpoint with a role in cancer-related immune evasion. It is a target for cancer immunotherapy and its expression is detected for the use of some immune checkpoint inhibitors in advanced non-small cell lung cancer patients (NSCLC). Vimentin is a key component of the epithelial-to-mesenchymal transition phenotype.

Circulating ghrelin crosses the blood-cerebrospinal fluid barrier via growth hormone secretagogue receptor dependent and independent mechanisms.

Ghrelin is a peptide hormone mainly secreted from gastrointestinal tract that acts via the growth hormone secretagogue receptor (GHSR), which is highly expressed in the brain. Strikingly, the accessibility of ghrelin to the brain seems to be limited and restricted to few brain areas. Previous studies in mice have shown that ghrelin can access the brain via the blood-cerebrospinal fluid (CSF) barrier, an interface constituted by the choroid plexus and the hypothalamic tanycytes.

Primary Reattachment of Near-Complete Ear Amputation: A Successful Outcome.

Objectives: Traumatic amputation of the ear constitutes a great aesthetic deformity that can have a tremendous negative impact. Reports describing the survival of near-complete ear amputation using non-microsurgical replantation are scarce. We aimed to study the surgical outcome of patients with near-complete ear amputations supplied by small pedicle bridges that were treated with primary reattachment.

Antitumor activity of lurbinectedin in second-line small cell lung cancer patients who are candidates for re-challenge with the first-line treatment.

Introduction: The National Comprehensive Cancer Network guidelines recommend re-challenge with the first-line treatment for relapsed small cell lung cancer (SCLC) with chemotherapy-free interval (CTFI)≥180 days. A phase II study (NCT02454972) showed remarkable antitumor activity in SCLC patients treated with lurbinectedin 3.2 mg/m 1 -h intravenous infusion every 3 weeks as second-line therapy.

Lurbinectedin as second-line treatment for patients with small-cell lung cancer: a single-arm, open-label, phase 2 basket trial.

Background: Few options exist for treatment of patients with small-cell lung cancer (SCLC) after failure of first-line therapy. Lurbinectedin is a selective inhibitor of oncogenic transcription. In this phase 2 study, we evaluated the acti and safety of lurbinectedin in patients with SCLC after failure of platinum-based chemotherapy.

Prognostic Value of p16 Protein in Patients With Surgically Treated Non-small Cell Lung Cancer; Relationship With Ki-67 and PD-L1.

Background/aim: Non-small cell lung cancer (NSCLC) is the leading cause of cancer death. Patients eligible for surgery have better overall survival rate than patients who are not eligible. We investigated the prognostic value of p16 in patients who underwent surgery for lung cancer, in association with other factors such as PD-L1 and Ki-67.

Programmed death ligand 1 expression in early stage, resectable non-small cell lung cancer.

Introduction: For several years non-small cell lung cancer (NSCLC) has been considered non-immunogenic. Recent advances in antitumor immunity brought to the discovery of checkpoints that modulate immune response against cancer. One of them is programmed death receptor 1 (PD-1) and its ligand (PD-L1).

New options on the horizon for nononcogene addicted non-small-cell lung cancer.

The treatment of non-small-cell lung cancer (NSCLC) has historically been based on platinum doublets- and taxan-based chemotherapy in the first- and second-line therapy, respectively. Although new agents have emerged for patients with driver mutations, treatment options for nononcogene addicted NSCLC have not changed for years. However, the last 5 years have seen the approval and introduction of new biological agents, such as immune checkpoint inhibitors and antiangiogenic drugs.

Circulating programmed death ligand-1 (cPD-L1) in non-small-cell lung cancer (NSCLC).

Background: This study aimed at investigating feasibility of programmed death ligand-1 (PD-L1) testing in plasma samples of advanced NSCLC patients receiving first-line treatment, assessing whether circulating (c)PD-L1 levels were modified by the therapy and whether baseline cPD-L1 levels were associated with patients' clinical responses and survival outcome.

Methods: Peripheral blood samples were collected from 16 healthy volunteers and 56 newly diagnosed NSCLC patients before and at 12th week during the course of first-line therapy. The level of PD-L1 was measured in plasma samples using the human (PD-L1/CD274) ELISA kit (CUSABIO, MD, USA).

RANK rewires energy homeostasis in lung cancer cells and drives primary lung cancer.

Lung cancer is the leading cause of cancer deaths. Besides smoking, epidemiological studies have linked female sex hormones to lung cancer in women; however, the underlying mechanisms remain unclear. Here we report that the receptor activator of nuclear factor-kB (RANK), the key regulator of osteoclastogenesis, is frequently expressed in primary lung tumors, an active RANK pathway correlates with decreased survival, and pharmacologic RANK inhibition reduces tumor growth in patient-derived lung cancer xenografts.

The use of circulating biomarkers in early clinical trials in patients with cancer.

The development of targeted therapies has changed the approach to early oncological clinical trial design. Identification of patient populations most likely to derive benefit and the biologically effective dose are now as important as determination of the maximum tolerated dose. Completion of the 'pharmacological audit trail' highlights drugs most likely to progress through to license, so resources can be allocated appropriately.

Cancer Stem Cells Sensitivity Assay (STELLA) in Patients with Advanced Lung and Colorectal Cancer: A Feasibility Study.

Background: Cancer stem cells represent a population of immature tumor cells found in most solid tumors. Their peculiar features make them ideal models for studying drug resistance and sensitivity. In this study, we investigated whether cancer stem cells isolation and in vitro sensitivity assay are feasible in a clinical setting.

Clinical and comparative utility of afatinib in non-small cell lung cancer.

The first targeted agents approved for non-small cell lung cancer (NSCLC) treatment, the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib, have an impressive activity in the presence of activating mutations of the EGFR gene. However, all patients develop acquired resistance principally through secondary mutations (T790M), HER2 amplification, MET amplification, and other molecular aberrations. An attempt to overcome EGFR TKI resistance has been through the development of irreversible blockers.

Rare mutations in non-small-cell lung cancer.

In the last decade, new insights in molecular biology have changed the therapeutic landscape of non-small-cell lung cancer. Since 2004, when activating mutations of the EGFR were firstly identified, several genetic aberrations have been discovered, mainly in adenocarcinoma. EGFR mutations are a relatively frequent event in non-small-cell lung cancer, generally consisting of exon 19 deletion or exon 21 substitution.

Erlotinib in the first-line treatment of non-small-cell lung cancer.

Non-small-cell lung cancer (NSCLC) is the leading cause of cancer-related deaths. In the last decade the EGF receptor (EGFR) signaling pathway has emerged as one of the most important molecular aberrations in NSCLC. Drugs interfering with the tyrosine kinase domain of the EGFR (EGFR-TKI), such as erlotinib or gefitinib, demonstrated efficacy in patients with advanced NSCLC irrespective of therapy line and particularly in patients harboring activating mutations of the EGFR gene.

The role of anaplastic lymphoma kinase inhibitors in the treatment of advanced nonsmall cell lung cancer.

Purpose Of Review: Treatment of advanced nonsmall cell lung cancer (NSCLC) has rapidly changed over the last decade. On the basis of the progress made in cancer biology, the old-fashioned 'one size fits all' chemotherapeutic approach is shifting to a novel approach in which treatment choice is mainly based on the tumor's biological genotype. The aim of the present review is to describe the anaplastic lymphoma kinase (ALK) translocation as a prominent molecular driver aberration in NSCLC, its prognostic and predictive role, and the new available treatment options.