Search

Colorectal cancer is one of the most prevalent cancers nowadays. In the metastatic setting, diagnosis and treatment have relied on tumor tissue analysis. However, the different limitations of this approach have recently opened the door to the introduction of liquid biopsy in the clinical setting. Liquid biopsy provides real-time information about the tumor and its heterogeneity in a simple, non-invasive, and repeatable way. There are several analytes that can be sought: exosomes, circulating tumor cells, and circulating tumor DNA, showing promising results in the areas of early detection, minimal residual disease, prognosis, or response to treatment. Here, we review the clinical applications of liquid biopsy in advanced colorectal cancer patients, focusing on metastatic diagnosis, prognostic assessment, drug sensitivity, treatment response, and acquired resistance monitoring.

RET alterations are recognized as key oncogenic drivers in different cancer types, including non-small cell lung cancer (NSCLC). Multikinase inhibitors (MKIs) with anti-RET activities resulted in variable efficacy with significant toxicities because of low target specificity. Selective RET kinase inhibitors, such as pralsetinib and selepercatinib, demonstrated high efficacy and favorable tolerability in advanced RET-rearranged NSCLC patients, leading to their introduction in the clinical setting. Among the different approaches available for the identification of RET rearrangements, next-generation sequencing (NGS) assays present substantial advantages in terms of turnaround time and diagnostic accuracy, even if potentially limited by accessibility issues. The recent advent of novel effective targeted therapies raises several questions regarding the emergence of resistance mechanisms and the potential ways to prevent/overcome them. In this review, we discuss molecular testing and treatment strategies to manage RET fusion positive NSCLC patients with a focus on resistance mechanisms and future perspectives in this rapidly evolving scenario.

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. In recent years, increasing knowledge about the mutational profile of lung cancer, in addition to the spreading diffusion of next-generation sequencing (NGS) in different centers, have been helpful in the identification of rare variants of lung cancer. Hence, the hope is that several new drugs will be available in the near future to treat these rare lung tumors, such as in targeted therapy and immunotherapy, which are often used in clinical practice for several malignancies. The aim of this review is to summarize the current knowledge about the molecular pathology and clinical management of the most common rare adenocarcinoma subtypes in order to provide a concise and updated report that can drive clinicians’ choices in their routine practice.

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. Despite the large number of molecules tested and the numerous therapeutic failures, some targeted therapies have recently shown interesting preliminary results. In this review, we describe the main molecular pathways involved in SCLC development/progression and provide an updated summary of the targeted therapies currently under investigation in SCLC patients.

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. An anonymous questionnaire investigating the occurrence of SEs/AEs and PROs was administered to the study population 21 days after the first dose. Pearson’s chi-squared test was used to estimate the risk of experiencing SEs/AEs according to selected variables. A total of 997 patients were included in the study: 62.0% had stage IV cancer, and 68.8% were receiving an active treatment, of whom 15.9% were receiving immunotherapy. SEs/AEs were recorded in 37.1% of cases after the first dose and in 48.5% of cases after the second dose. The most common SEs were muscle pain/local rash (27.9% and 28%, after the first and second dose, respectively). Patients older than 70 years showed lower risk of SEs/AEs, while women showed a higher risk. Before receiving the vaccine, 18.2% of patients felt fearful and/or insecure about the vaccination. After the first dose, 57.5% of patients changed their feelings positively. Our data support the short-term safety of BNT162b2 in CPs, regardless of disease stage and concurrent treatments. Overall, the vaccination showed a positive impact on quality of life.

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. Results: Of 33 patients undergoing BAL and PB sampling, 21 had histologically-confirmed LC. Most cases were locally-advanced or metastatic non-small cell LC. T cell characteristics were not significantly different in t-BAL vs. cl-BAL. Compared to PB, CD8 T cells in BAL presented features of immune activation and exhaustion (high PD-1, low IFN-g production). Accordingly, regulatory CD4 T cells were also higher in BAL vs. PB. When dichotomizing T cell density in t-BAL in high and low, we found that PD-L1 expression in LC was associated with T cell density in t-BAL. T-BAL with high T cell density had higher %IFN-g+CD8 T cells and lower %T-regs. Conclusion: In BAL from advanced LC patients, T cells present features of exhaustion. T cells in t-BAL could be the best surrogate of tumor-infiltrating T cell, and future studies should evaluate T cell phenotype and density as potential biomarkers for cancer immunotherapy outcome.

Lung cancer patients have been associated with an increased risk of COVID-19 infection, pulmonary complications, and worse survival outcomes compared to the general population. The world’s leading professional organizations provided new recommendations for the diagnosis, treatment, and follow-up of lung cancer patients during the pandemic as a guide for prioritizing cancer care issues. Telemedicine was preferred for non-urgent consultations, and screening programs were temporarily suspended, leading to possible diagnostic delays along with an estimated increase in cause-specific mortality. A vaccine campaign has recently emerged as the main weapon to fight the COVID-19 pandemic, inverting this negative trend. This work aims to provide a comprehensive overview of the epidemiology and immune-pathophysiology of SARS-CoV-2 infection in cancer patients, highlighting the most relevant changes in the clinical management of lung cancer patients during the pandemic.