Navigating Therapeutic Challenges in BRAF-Mutated NSCLC: Non-V600 Mutations, Immunotherapy, and Overcoming Resistance.

Although rare in non-small cell lung cancer (NSCLC), BRAF mutations present considerable therapeutic challenges. While the use of BRAF and MEK inhibitor combinations has significantly improved survival outcomes in patients with BRAF V600E mutations, no targeted therapies are currently available for class II and III mutations, leaving the optimal treatment strategy and prognosis for these patients uncertain. Additionally, despite immunotherapy typically showing limited benefit in patients with other activating genomic alterations, it appears to deliver comparable efficacy in BRAF-mutated NSCLC, emerging as a potentially viable treatment option, particularly in patients with a history of smoking.

Targeted Therapy in Mesotheliomas: Uphill All the Way.

Mesothelioma (MM) is an aggressive and lethal disease with few therapeutic opportunities. Platinum-pemetrexed chemotherapy is the backbone of first-line treatment for MM. The introduction of immunotherapy (IO) has been the only novelty of the last decades, allowing an increase in survival compared to standard chemotherapy (CT).

Case report: First evidence of impressive efficacy of modulated dose selpercatinib in a young Caucasian with ANK3-RET fusion-positive NSCLC.

Over the past decade, molecular characterization has led to change the management of advanced non-small cell lung cancer (NSCLC) harboring driver mutations. Rearranged during transfection () gene fusions, occurring in 1% to 2% of NSCLC, have emerged as an oncogenic druggable target. Systemic targeted therapies with highly selective inhibitors (RETi), selpercatinib and pralsetinib, represent a recent clinical breakthrough.

Therapeutical Options in ROS1-Rearranged Advanced Non Small Cell Lung Cancer.

ROS proto-oncogene 1 (ROS1) rearrangements occur in 0.9-2.6% of patients with non small cell lung cancer (NSCLC), conferring sensitivity to treatment with specific tyrosine-kinase inhibitors (TKI).

Liquid Biopsy in NSCLC: An Investigation with Multiple Clinical Implications.

Tissue biopsy is essential for NSCLC diagnosis and treatment management. Over the past decades, liquid biopsy has proven to be a powerful tool in clinical oncology, isolating tumor-derived entities from the blood. Liquid biopsy permits several advantages over tissue biopsy: it is non-invasive, and it should provide a better view of tumor heterogeneity, gene alterations, and clonal evolution.

The Change in Paradigm for NSCLC Patients with EML4-ALK Translocation.

The severe prognosis linked with a lung cancer diagnosis has changed with the discovery of oncogenic molecularly driven subgroups and the use of tailored treatment. ALK-translocated advanced lung cancer is the most interesting model, having achieved the longest overall survival. Here, we report the most important paradigmatic shifts in the prognosis and treatment for this subgroup population occurred among lung cancer.

Targeted Therapy and Immunotherapy in Early-Stage Non-Small Cell Lung Cancer: Current Evidence and Ongoing Trials.

The scenario of neoadjuvant and adjuvant settings in non-small cell lung cancer (NSCLC) is rapidly evolving. As already happened for the advanced disease, also early stages have entered the era of precision medicine, with molecular analysis and Programmed death-ligand 1 (PD-L1) evaluation that by now can be considered a routine assessment. New treatment options have been recently approved, with osimertinib now part of clinical practice for Epidermal Growth Factor Receptor mutated (EGFRm) patients, and immune checkpoint inhibitors (ICIs) available after FDA approval both in the adjuvant (atezolizumab) and neoadjuvant (nivolumab) setting.

Acquired Resistance to Osimertinib in -Mutated Non-Small Cell Lung Cancer: How Do We Overcome It?

Osimertinib is currently the preferred first-line therapy in patients with non-small cell lung cancer (NSCLC) with common epidermal growth factor receptor () 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.

Bone Metastasis and Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer (NSCLC): Microenvironment and Possible Clinical Implications.

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.

NSCLC as the Paradigm of Precision Medicine at Its Finest: The Rise of New Druggable Molecular Targets for Advanced Disease.

Standard treatment for advanced non-small cell lung cancer (NSCLC) historically consisted of systemic cytotoxic chemotherapy until the early 2000s, when precision medicine led to a revolutionary change in the therapeutic scenario. The identification of oncogenic driver mutations in EGFR, ALK and ROS1 rearrangements identified a subset of patients who largely benefit from targeted agents. However, since the proportion of patients with druggable alterations represents a minority, the discovery of new potential driver mutations is still an urgent clinical need.

Brain Metastases Management in Oncogene-Addicted Non-Small Cell Lung Cancer in the Targeted Therapies Era.

The therapeutic landscape in patients with advanced non-small-cell lung cancer harboring oncogenic biomarkers has radically changed with the development of targeted therapies. Although lung cancers are known to frequently metastasize to the brain, oncogene-driven non-small-cell lung cancer patients show a higher incidence of both brain metastases at baseline and a further risk of central nervous system progression/relapse. Recently, a new generation of targeted agents, highly active in the central nervous system, has improved the control of intracranial disease.

Acquired EGFR C797G Mutation Detected by Liquid Biopsy as Resistance Mechanism After Treatment With Osimertinib: A Case Report.

Background: Osimertinib is a third-generation EGFR-tyrosine kinase inhibitor approved for the treatment of T790M-positive non-small-cell lung cancer. More recently, osimertinib demonstrated improved disease control compared to other EGFR-TKIs. Multiple mechanisms of resistance have been described in T790M-positive patients who experienced treatment failure with osimertinib.

Chemotherapy in non-small cell lung cancer patients after prior immunotherapy: The multicenter retrospective CLARITY study.

Objectives: In the most of cases, for non-small cell lung cancer (NSCLC) patients who progressed to previous immune checkpoint inhibitors (CKI) administered as first- or as second-line therapy, chemotherapy (CT) remains the only viable options in the absence of "druggable" mutations. We aimed to explore the efficacy of salvage chemotherapy after immunotherapy (SCAI) in advanced NSCLC patients.

Materials And Methods: We designed a retrospective, multicenter study, involving 20 Italian centers, with the primary objective of describing the clinical outcome of advanced NSCLC patients treated with SCAI at the participating institutions from November 2013 to July 2019.

First-line pembrolizumab in advanced non-small cell lung cancer patients with poor performance status.

Background: Pembrolizumab is the first-line standard of care for advanced non-small cell lung cancer (NSCLC) with a PD-L1 tumour proportion score (TPS) ≥ 50%. Eastern Cooperative Oncology Group performance status (PS) 2 patients may receive pembrolizumab, despite the absence of sustaining evidence.

Patients And Methods: GOIRC-2018-01 is a multicentre, retrospective, observational study.

Can Work Engagement Be a Resource for Reducing Workaholism's Undesirable Outcomes? A Multiple Mediating Model Including Moderated Mediation Analysis.

This study aimed to explore a possible process explaining the relationship between workaholism and sleep disorders, including two mediators: work-family conflict and emotional exhaustion. Moreover, since a possible buffering role of work engagement was recently proposed against the detrimental effects of workaholism, the aim was to examine the moderating role of work engagement in the relationship between workaholism and several outcomes such as work-family conflict, emotional exhaustion, and sleep disorders. Two models were tested using conditional process analysis for testing direct and indirect effects on a sample of 395 employees: (1) a serial multiple mediation model, and (2) the same serial multiple mediation model including the moderating role of work engagement.

Therapeutic decision based on molecular detection of resistance mechanism in an ALK-rearranged lung cancer patient: a case report.

Background: The use of tyrosine kinase inhibitors (TKIs) of ALK is the therapy of choice for ALK-fusion patients. Unfortunately, all patients under this kind of treatment eventually develop acquired resistance through several well-known mechanisms, such as acquisition of a secondary mutation within the kinase domain, activation of a bypass signaling pathway, or a histological change like small-cell lung cancer transformation. At the time of progression, a tissue re-biopsy may give important molecular and morphological information regarding the mechanisms driving resistance to ALK TKIs.

Prognostic evaluation in palliative care: final results from a prospective cohort study.

Prognostic characterization in the initial assessment of patients with advanced cancer disease is an essential step to plan the most appropriate therapeutic program. Since clinical prediction of survival (CPS) may be of limited value, some authors have tried to integrate specific prognostic factors into prognostic multidimensional scores. We carried out a prospective cohort study in two palliative care units to compare the accuracy of the Palliative Prognostic (PaP) Score, the Objective Prognostic Score (OPS), and the Palliative Prognostic Index (PPI).

Defining a prognostic score based on O6-methylguanine-DNA methyltransferase cut-off methylation level determined by pyrosequencing in patients with glioblastoma multiforme.

Purpose: Epigenetic variations in the O6-methylguanine-methyltransferase gene had been widely associated with a favorable impact on survival in patients affected by glioblastoma multiforme (GBM). Aim of this study is to explore a scoring system based on the gene promoter methylation in order to predict patients' prognosis.

Methods: A series of 128 patients with GBM was retrospectively analyzed.

Use and perception of complementary and alternative medicine among cancer patients: the CAMEO-PRO study : Complementary and alternative medicine in oncology.

Background: It is estimated that about half of cancer patients use at least one form of complementary and alternative medicines (CAM) in their life but there is a strong reticence of patients in talking about CAM with their oncologist. Primary aim of this study was to inform patients about CAM, focusing on their supposed benefits, toxicities and interactions with conventional therapeutic agents. The study also explored patients' perception about CAM and ascertained the level of CAM use among cancer patients of an Italian academic hospital.

[Checkpoint inhibitors in the decision-making algorithm of advanced non-small-cell lung cancer.].

The checkpoint inhibitors opened a new era in the treatment of advanced non-small-cell lung cancer (NSCLC) initially by replacing second-line standard chemotherapy with docetaxel and subsequently by replacing platinum-based chemotherapy in the first line, albeit in patients selected for a high expression of PD-L1. The decision algorithm has therefore been radically modified for patients who do not have activating mutations. However, we are only at the beginning of a new era from which we expect in the near future the use of immunotherapy in most patients as a first line treatment in substitution or in combination with chemotherapy.

Outcomes of ALK positive lung cancer patients treated with crizotinib or second-generation ALK inhibitor: a monoinstitutional experience.

Rearrangement in the anaplastic lymphoma kinase (ALK) gene is one of the oncogenic drivers in non-small cell lung cancer (NSCLC) patients. Several ALK inhibitors (ALKis) have been developed and have demonstrated their efficacy, however the best treatment strategy for ALK positive NSCLC patients has yet to be determined. Our retrospective study has investigated the outcome of 40 ALK-rearranged NSCLC patients treated with two different sequential strategies in our Institute; a "classical group", treated with crizotinib followed by second or third generation ALKis, and the "experimental group", treated upfront with a second generation ALK inhibitor.

MGMT pyrosequencing-based cut-off methylation level and clinical outcome in patients with glioblastoma multiforme.

Aim: MGMT promoter methylation has been associated with improved survival in glioblastoma multiforme treated with temozolomide. However, there is no consensus on specific cut-off levels of methylation. The aims of the study were to explore the prognostic impact of MGMT methylation status and to analyze the role of specific cut-off values.

INTEGRATED CARE PATHWAYS IN LUNG CANCER: A QUALITY IMPROVEMENT PROJECT.

Background: Non small cell lung cancer (NSCLC) diagnosis and treatment is a highly complex process, requiring managerial skills merged with clinical knowledge and experience. Integrated care pathways (ICPs) might be a good strategy to overview and improve patient's management. The aim of this study was to review the ICPs of NSCLC patients in a University Hospital and to identify areas of quality improvement.