Actionable non-small cell lung cancer mutation identification by comprehensive genomic profiling for clinical trial enrollment: the European Program for the ROutine testing of Patients with Advanced lung cancer (EPROPA).

Background: To reduce the gap about the relevant heterogeneity of molecular testing and cancer care across Europe, Women Against Lung Cancer in Europe (WALCE) promoted the European Program for ROutine testing of Patients with Advanced lung cancer (EPROPA) and provided a free-of-charge molecular profiling platform for non-small cell lung cancer sample characterization with the aim of increasing the detection of targetable drivers and improving patients' access to clinical trials.

Methods: From January 2021 to December 2023, 20 centres located at 5 different European countries (Greece, Slovenia, Romania, Albania and Italy) joined EPROPA, with 555 advanced NSCLC patients registered into the program. Anonymized patients' clinical-pathological data were shared through the EPROPA web platform and tissue samples were collected to the Molecular Pathology Unit of the Reference Center (University of Turin) for molecular analyses.

Segmentectomy vs. Lobectomy in stage IA non-small cell lung cancer: A systematic review and meta-analysis of perioperative and survival outcomes.

While recent randomized controlled trials (RCT) have suggested superior overall survival (OS) outcomes with segmentectomy over lobectomy, questions remain regarding the comparability of these surgical procedures for treating early-stage non-small cell lung cancer (NSCLC). This systematic review and meta-analysis aimed to synthetize existing evidence and to compare the survival outcomes observed for stage IA NSCLC following segmentectomy or lobectomy. 40 studies (38 observational, 2 RCTs) encompassing 103,926 patients were analyzed.

Extracellular vesicles miR-574-5p and miR-181a-5p as prognostic markers in NSCLC patients treated with nivolumab.

Immune checkpoint inhibitors (ICIs) have revolutionized the management of advanced non-small cell lung cancer (NSCLC), although patient survival is still unsatisfactory. Accurate predictive markers capable of personalizing the treatment of patients with NSCLC are still lacking. Circulating extracellular vesicles involved in cell-to-cell communications through miRNAs (EV-miRs) transfer are promising markers.

HER2-Altered Non-Small Cell Lung Cancer: A Journey from Current Approaches to Emerging Strategies.

For patients diagnosed with advanced HER2-altered non-small cell lung cancer (NSCLC), the current standard of care is represented by a platinum-pemetrexed-based chemotherapy, eventually in combination with immunotherapy. Different pan-HER tyrosine kinase inhibitors have been evaluated in limited phase II trials, yielding generally unsatisfactory outcomes, although certain genotypes demonstrated some clinical benefit. Conversely, antibody-drug conjugates (ADCs) targeting HER2, particularly trastuzumab-deruxtecan, have shown promising results against HER2-mutant disease, including a great intracranial activity in patients with brain metastasis.

The biomarkers ATLAS: An audit on 1100 non-small cell lung cancer from an Italian knowledge-based database.

Aims: To date, precision medicine has revolutionized the clinical management of Non-Small Cell Lung Cancer (NSCLC). International societies approved a rapidly improved mandatory testing biomarkers panel for the clinical stratification of NSCLC patients, but harmonized procedures are required to optimize the diagnostic workflow. In this context a knowledge-based database (Biomarkers ATLAS, https://biomarkersatlas.

Real-world outcomes of Italian patients with advanced non-squamous lung cancer treated with first-line pembrolizumab plus platinum-pemetrexed.

Purpose: The aim of this multi-center, retrospective/prospective cohort observational study was to evaluate outcomes in routine clinical practice of first-line chemo-immunotherapy with cis/carboplatin, pemetrexed and pembrolizumab in patients with advanced non-squamous non-small cell lung cancer (NSCLC) in 33 Italian centers.

Methods: The outcome measure was to evaluate overall survival (OS) in a real-world patient population. Secondary endpoints were: progression-free survival (PFS), objective response rate (ORR), duration of response (DoR) and incidence of treatment-related adverse events (AEs).

Sotorasib in KRASp.G12C mutated advanced NSCLC: Real-world data from the Italian expanded access program.

Background: Sotorasib showed a significant improvement of progression free survival (PFS), safety and quality of life over docetaxel in patients with KRASp.G12C-mutated advanced non-small-cell lung cancer (NSCLC) within the CodeBreak-200 study. Here we report real-world efficacy and tolerability data from NSCLC patients who received sotorasib within the Italian expanded access program (EAP).

Niraparib plus Dostarlimab in Pleural Mesothelioma or Non-Small Cell Lung Cancer Harboring HRR Mutations: Interim Results of the UNITO-001 Phase II Prospective Trial.

Purpose: Treatment of homologous recombination repair-deficient (HRD)-tumors with PARP inhibitors has the potential to further increase tumor immunogenicity, suggesting a synergistic effect with immunotherapy. Here we present the preliminary results of niraparib in combination with dostarlimab for pleural mesothelioma (PM) or non-small cell lung cancer (NSCLC) harboring HRR mutations.

Patients And Methods: UNITO-001 is a phase II, prospective, study aiming to investigate the combination of niraparib plus dostarlimab in pretreated patients with HRD and programmed death ligand-1 (PD-L1) ≥1% NSCLC and/or PM.

Exploring the Potential of Non-Coding RNAs as Liquid Biopsy Biomarkers for Lung Cancer Screening: A Literature Review.

Lung cancer represent the leading cause of cancer mortality, so several efforts have been focused on the development of a screening program. To address the issue of high overdiagnosis and false positive rates associated to LDCT-based screening, there is a need for new diagnostic biomarkers, with liquid biopsy ncRNAs detection emerging as a promising approach. In this scenario, this work provides an updated summary of the literature evidence about the role of non-coding RNAs in lung cancer screening.

Deciphering Lung Adenocarcinoma Heterogeneity: An Overview of Pathological and Clinical Features of Rare Subtypes.

Lung cancer is one of the most frequently diagnosed cancers worldwide and the leading cause of cancer-related death. The 2021 World Health Organization (WHO) classification provided a detailed and updated categorization of lung adenocarcinomas with a special focus on rare histological types, including enteric, fetal and colloid types, as well as not otherwise specified adenocarcinoma, overall accounting for about 5-10% of all cases. However, rare entities are nowadays difficult to diagnose in most centers, and evidence of optimal therapeutic management for these patients is still lacking.

The Role of Germline Mutations in Thoracic Malignancies: Between Myth and Reality.

Considering the established contribution of environmental factors to the development of thoracic malignancies, the inherited susceptibility of these tumors has rarely been explored. However, the recent introduction of next-generation sequencing-based tumor molecular profiling in the real-word setting enabled us to deeply characterize the genomic background of patients with lung cancer with or without smoking-related history, increasing the likelihood of detecting germline mutations with potential prevention and treatment implications. Pathogenic germline variants have been detected in 2% to 3% of patients with NSCLC undergoing next-generation sequencing analysis, whereas the proportion of germline mutations associated with the development of pleural mesothelioma widely varies across different studies, ranging between 5% and 10%.

Autocrine 17-β-Estradiol/Estrogen Receptor-α Loop Determines the Response to Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer.

Purpose: The response to immune checkpoint inhibitors (ICI) often differs between genders in non-small cell lung cancer (NSCLC), but metanalyses results are controversial, and no clear mechanisms are defined. We aim at clarifying the molecular circuitries explaining the differential gender-related response to anti-PD-1/anti-PD-L1 agents in NSCLC.

Experimental Design: We prospectively analyzed a cohort of patients with NSCLC treated with ICI as a first-line approach, and we identified the molecular mechanisms determining the differential efficacy of ICI in 29 NSCLC cell lines of both genders, recapitulating patients' phenotype.

Targeted Therapies in Small Cell Lung Cancer: From Old Failures to Novel Therapeutic Strategies.

The clinical management of small cell lung cancer (SCLC) treatment remains a major challenge for thoracic oncologists, with very few therapeutic advances significantly impacting patients' survival. The recent introduction of immunotherapy in the clinical setting produced a marginal benefit for a limited subset of metastatic patients, while the therapeutic scenario for relapsing extended-disease small cell lung cancers (ED-SCLCs) remains almost deserted. Recent efforts clarified the molecular features of this disease, leading to the identification of key signalling pathways which may serve as potential targets for clinical use.

Real-world retrospective study of KRAS mutations in advanced non-small cell lung cancer in the era of immunotherapy.

Background: KRAS mutation-positive (KRAS-positive), advanced nonsmall-cell lung cancer (NSCLC) is characterized by a poor prognosis. KRAS mutations are extremely heterogeneous from a biologic point of view, and real-world data by mutation subtype in the era of immunotherapy are still incomplete.

Methods: The objective of this study was to retrospectively analyze all consecutive patients with advanced/metastatic, KRAS-positive NSCLC who were diagnosed at a single academic institution since the advent of immunotherapy.

Rare thoracic cancers: a comprehensive overview of diagnosis and management of small cell lung cancer, malignant pleural mesothelioma and thymic epithelial tumours.

Despite the progress in outcomes seen with immunotherapy in various malignancies, including nonsmall cell lung cancer, the benefits are less in small cell lung cancer, malignant pleural mesothelioma and thymic epithelial tumours. New effective treatment options are needed, guided more in-depth insights into the pathophysiology of these rare malignancies. This review comprehensively presents an overview of the clinical presentation, diagnostic tools, staging systems, pathophysiology and treatment options for these rare thoracic cancers.

Short-Term Safety and Psychosocial Impact of the BNT162b2 mRNA COVID-19 Vaccine in Cancer Patients-An Italian Single-Center Experience.

Safety data regarding BNT162b2 in cancer patients (CPs) are scarce. Herein we report the side effects (SEs), the adverse events (AEs), and the patient-reported outcomes (PROs) following BNT162b2 administration in CPs treated at the San Luigi Gonzaga University Hospital. All CPs who agreed to participate in our vaccination campaign received BNT162b2 and were included in the descriptive analysis.

RET-MAP: An International Multicenter Study on Clinicobiologic Features and Treatment Response in Patients With Lung Cancer Harboring a RET Fusion.

Introduction: Nearly 1% to 2% of NSCLCs harbor RET fusions. Characterization of this rare population is still incomplete.

Methods: This retrospective multicenter study included patients with any-stage RET positive (RET+) NSCLC from 31 cancer centers.

Treatment response and safety of immunotherapy for advanced non-small cell lung cancer with comorbid chronic obstructive pulmonary disease: a retrospective cohort study.

Background: Immunotherapy has provided a novel therapeutic option for lung cancer but studies involving patients with advanced non-small cell lung cancer (NSCLC) coupled with various degrees of comorbid chronic obstructive pulmonary disease (COPD) are limited. Thus, we performed a retrospective cohort study to optimize the use of immunotherapy in this special population.

Methods: We enrolled a total of 99 patients with advanced (stage IIIB/C-IV) NSCLC with comorbid COPD who had received immune checkpoint inhibitors (ICIs) according to the inclusion and exclusion criteria.

Targeting KRASp.G12C Mutation in Advanced Non-Small Cell Lung Cancer: a New Era Has Begun.

KRASp.G12C mutation occurs in 12% of newly diagnosed advanced NSCLC and has recently emerged as a positive predictive biomarker for the selection of advanced NSCLC patients who may respond to novel KRASp.G12C inhibitors.

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.

Comparing T Cell Subsets in Broncho-Alveolar Lavage (BAL) and Peripheral Blood in Patients with Advanced Lung Cancer.

Background: Lung cancer (LC) tissue for immunological characterization is often scarce. We explored and compared T cell characteristics between broncho-alveolar lavage from tumor affected (t-BAL) and contralateral lung (cl-BAL), with matched peripheral blood (PB).

Methods: BAL and PB were collected during bronchoscopy for diagnostic and/or therapeutic purposes in patients with monolateral primary lesion.

Alectinib for the treatment of pretreated RET-rearranged advanced NSCLC: Results of the ETOP ALERT-lung trial.

Background: Alectinib, a highly selective next generation ALK-inhibitor, has exhibited potent anti-tumour activity in RET-rearranged NSCLC in the preclinical stage.

Methods: ALERT-lung is a single-arm, phase II trial evaluating the activity of alectinib for the treatment of pretreated RET-rearranged advanced NSCLC. Alectinib was administered orally, 600 mg, twice per day until progression, refusal or unacceptable toxicity (treatment could continue beyond progression, if patient was deriving clinical benefit).