Evaluation of immune microenvironment in non-small cell lung carcinoma after neoadjuvant immunotherapy: a case report.

Immune checkpoint inhibitors are increasingly used in neoadjuvant non-small cell lung carcinoma (NSCLC). Data regarding histologic features of the tumor microenvironment in this group of patients are limited. This study aimed to analyze the histologic features and the immune cell infiltrates within the tumor microenvironment of NSCLC after neoadjuvant immunotherapy.

TTF-1 Negativity Predicts Poor Outcomes in Advanced Non-Squamous NSCLC Also in the Immunotherapy Era: A Multicenter Cohort Study and Meta-Analysis.

Despite advances in immunotherapy, reliable biomarkers beyond PD-L1 expression are urgently needed to optimize treatment decisions in advanced non-squamous NSCLC. Thyroid Transcription Factor-1 (TTF-1), a biomarker associated with favorable prognosis in chemotherapy-treated patients, has unclear prognostic implications in the immunotherapy era. : We conducted a multicenter retrospective study involving 163 advanced non-squamous NSCLC patients treated with first-line immunotherapy or chemo-immunotherapy and an additional historical chemotherapy-only cohort (n = 37).

Screening and Identification of a Common Haplotype in the Jewish Community of Rome Reveal a Founder Effect for the c.7007G>C, p. (Arg2336Pro) Variant.

Background/objectives: Cancer risk-reducing strategies in Ashkenazi women carrying founder variants have a cost-effective effect on reducing cancer morbidity and mortality. The British and US guidelines recommend () screening among Ashkenazi Jewish people to identify high-risk individuals. status has not been investigated yet in the Jewish community of Rome.

Immunological Network Signature of Naïve Non-Oncogene-Addicted Non-Small Cell Lung Cancer Patients Treated with Anti-PD1 Therapy: A Pilot Study.

Non-small cell lung cancer (NSCLC) patients without gene driver mutations receive anti-PD1 treatments either as monotherapy or in combination with chemotherapy based on PD-L1 expression in tumor tissue. Anti-PD1 antibodies target various immune system components, perturbing the balance between immune cells and soluble factors. In this study, we identified the immune signatures of NSCLC patients associated with different clinical outcomes through network analysis.

Determinants of 5-year survival in patients with advanced NSCLC with PD-L1≥50% treated with first-line pembrolizumab outside of clinical trials: results from the Pembro-real 5Y global registry.

Background: Pembrolizumab monotherapy is an established front-line treatment for advanced non-small cell lung cancer (NSCLC) with programmed cell death-ligand 1 (PD-L1) tumor proportion score (TPS)≥50%. However, real-world data on its long-term efficacy remains sparse.

Methods: This study assessed 5-year outcomes of first-line pembrolizumab monotherapy in a large, multicenter, real-world cohort of patients with advanced NSCLC and PD-L1 TPS≥50%, referred to as Pembro-real 5Y.

Anti-PD1 therapies induce an early expansion of Ki67CD8 T cells in metastatic non-oncogene addicted NSCLC patients.

Pembrolizumab (an anti-PD1 antibody) alone or combined with chemotherapy represented the standard of care for advanced non-oncogene addicted non-small cell lung cancer (NSCLC) patients. These therapies induced early modifications of the immune response impacting the clinical outcome. Identifying early changes in the immune system was critical to directing the therapeutic choice and improving the clinical outcome.

Testicular ultrasonographic features predict future risk for bilateral testicular germ cell tumour: A long-term single centre follow-up study.

Background: Bilateral testicular germ cell tumours (B-GCT) are rare, with an incidence of 2-5%, and can be classified as synchronous (sB-GCT) or metachronous (mB-GCT). Our study aimed to identify clinical, biochemical, and radiological risk factors for mB-GCT in a cohort of patients with GCT at a single tertiary referral centre.

Methods: This retrospective case-control study included patients with GCT referred to Policlinico Umberto I-Sapienza University of Rome, from 2005 to 2023.

Circulating Cancer-Associated Macrophage-like Cells as a Blood-Based Biomarker of Response to Immune Checkpoint Inhibitors.

Evidence has been provided that circulating cancer-associated macrophage-like cell (CAM-L) numbers increase in response to chemotherapy, with an inverse trend compared to circulating tumor cells (CTCs). In the era of evolving cancer immunotherapy, whether CAM-Ls might have a potential role as predictive biomarkers of response has been unexplored. We evaluated whether a serial blood evaluation of CTC to CAM-L ratio might predict response to immune checkpoint inhibitors in a cohort of non-small-cell lung cancer patients.

Antinuclear antibodies may predict the development of immune-related adverse events in asymptomatic patients treated with immune checkpoint inhibitors: results from a single-center cohort.

We aim at investigating the association between subclinical autoimmunity and immune-related adverse events (irAEs) in a cohort of patients treated by immune checkpoint inhibitors for solid metastatic cancer. In the context of an oncology/rheumatology outpatient clinic, we evaluated patients treated with anti-PD-1 or anti-PD-L1. Before treatment, each patient underwent a physical evaluation and a blood sample to identify the presence of a set of autoantibodies.

CD137 and regulatory T cells as independent prognostic factors of survival in advanced non-oncogene addicted NSCLC patients treated with immunotherapy as first-line.

Background: Immune checkpoint inhibitors (ICIs), administered alone or combined with chemotherapy, are the standard of care in advanced non-oncogene addicted Non-Small Cell Lung Cancer (NSCLC). Despite these treatments' success, most long-term survival benefit is restricted to approximately 20% of patients, highlighting the need to identify novel biomarkers to optimize treatment strategies. In several solid tumors, immune soluble factors, the activatory CD137 Tcells, and the immunosuppressive cell subsets Tregs and MDSCs (PMN(Lox1)-MDSC and M-MDSCs) correlated with responses to ICIs and clinical outcomes thus becoming appealing predictive and prognostic factors.

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).

Surgical and survival outcomes with perioperative or neoadjuvant immune-checkpoint inhibitors combined with platinum-based chemotherapy in resectable NSCLC: A systematic review and meta-analysis of randomised clinical trials.

The use of neoadjuvant or perioperative anti-PD(L)1 was recently tested in multiple clinical trials. We performed a systematic review and meta-analysis of randomised trials comparing neoadjuvant or perioperative chemoimmunotherapy to neoadjuvant chemotherapy in resectable NSCLC. Nine reports from 6 studies were included.

Circulating Natural Killer Cells as Prognostic Value for Non-Small-Cell Lung Cancer Patients Treated with Immune Checkpoint Inhibitors: Correlation with Sarcopenia.

Background: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of tumors. Natural killer (NK) cells can play an important role in cancer immune surveillance. The aim of this prospective observational study was to analyze peripheral blood mononuclear cells (PBMCs) in patients with advanced non-small-cell lung cancer (NSCLC) receiving ICIs in order to identify predictive factors for better survival outcomes.

Evaluation of Efficacy of ALK Inhibitors According to Body Mass Index in ALK Rearranged NSCLC Patients-A Retrospective Observational Study.

No evidence exists as to whether body mass index (BMI) impairs clinical outcomes from ALK inhibitors (ALKi) in patients with ALK-rearranged non-small cell lung cancer (NSCLC). Retrospective data of patients affected by metastatic ALK-rearranged NSCLC treated with ALKi were collected. We divided patients into "low- BMI" (≤25 kg/m) and "high- BMI" (>25 kg/m) categories and correlated them with overall survival (OS) and progression-free survival (PFS).

Type 2 Diabetes Mellitus and Efficacy Outcomes from Immune Checkpoint Blockade in Patients with Cancer.

Purpose: No evidence exists as to whether type 2 diabetes mellitus (T2DM) impairs clinical outcome from immune checkpoint inhibitors (ICI) in patients with solid tumors.

Experimental Design: In a large cohort of ICI recipients treated at 21 institutions from June 2014 to June 2020, we studied whether patients on glucose-lowering medications (GLM) for T2DM had shorter overall survival (OS) and progression-free survival (PFS). We used targeted transcriptomics in a subset of patients to explore differences in the tumor microenvironment (TME) of patients with or without diabetes.

Rheumatic Diseases Development in Patients Treated by Anti-PD1 Immune Checkpoint Inhibitors: A Single-Centre Descriptive Study.

The introduction of the so-called immune checkpoint inhibitors (ICIs) substantially changed the history of cancer therapy. On the other hand, they can induce the development of rheumatic immune-related adverse events (Rh-irAEs). In the scenario of a joint oncology/rheumatology outpatient clinic, we conducted a single-centre descriptive study to define from a laboratory, clinical and therapeutic point of view, rheumatic conditions developed during anti-PD1 treatment.

Non-small-cell lung cancer: how to manage - and -rearranged disease.

Oncogene addiction in non-small-cell lung cancer (NSCLC) has profound diagnostic and therapeutic implications. , and rearrangements are found in about 2-7%, 1-2% and 0.2% of unselected NSCLC samples, respectively; however, their frequency is markedly higher in younger and never-smoker patients with adenocarcinoma histology.

Safety and efficacy of combining afatinib and whole-brain radiation therapy in treating brain metastases from EGFR-mutated NSCLC: a case report and literature review.

Combining EGFR-tyrosine kinase inhibitors (TKIs) to whole brain radiation therapy (WBRT) has been shown to be more effective than EGFR-TKIs or WBRT alone in treating brain metastases (BMs) from EGFR-mutated Non Small-Cell Lung Cancer (NSCLC). However, despite the combination results well tolerated, EGFR-TKIs are often discontinued before WBRT, to reduce the risk of possible side effects, potentially resulting in reduced treatment efficacy and possible progression of intra- and extra-cranial disease. Afatinib, an irreversible inhibitor of EGFR-TK, has been shown to radiosensitize NSCLC in pre-clinical models and, compared to the other EGFR-TKIs, more efficiently penetrates the blood-brain barrier.

Advanced non-small-cell lung cancer: how to manage and exon 20 insertion mutation-positive disease.

exon 20 insertion mutations (Ex20ins) and 2 mutations characterize an oncogene-addicted subtype of non-small-cell lung cancer (NSCLC) typically associated with a never or light smoking history, female sex, and adenocarcinoma histology. Nevertheless, Ex20ins-mutant and 2-mutant advanced NSCLCs are still difficult to treat for various reasons. First, there is a need for sophisticated diagnostic tools (e.

Renal Function Outcomes in Metastatic Non-Small-Cell Lung Carcinoma Patients Treated with Chemotherapy or Immune Checkpoint Inhibitors: An Unexpected Scenario.

Immune checkpoint inhibitors (ICIs) and platinum-based chemotherapy (CT) are effective therapeutic agents for the palliative treatment of metastatic non-small-cell lung cancer (NSCLC); the aim of our study was to investigate the acute and chronic renal toxicities in this setting. We collected data on 292 patients who received cisplatin (35%), carboplatin-based regimens (25%), or ICI monotherapy (40%). The primary and secondary outcomes were compared to the acute kidney injury (AKI) rate and the mean estimated GFR (eGFR) decay between groups, respectively, over a mean follow-up duration of 15 weeks.

Response to immunotherapy in KRAS G12C mutated NSCLC: a single-centre retrospective observational study.

Background: Non-small cell lung cancer is the leading cause of cancer death worldwide. New strategies in molecular therapies are being explored to detect and target genetic mutations in NSCLC. Therefore, it is also important to understand the interaction between these mutations and other therapies.

Circulating CD137+ T Cells Correlate with Improved Response to Anti-PD1 Immunotherapy in Patients with Cancer.

Purpose: CD137 molecule is expressed by activated lymphocytes, and in patients with cancer identifies the tumor-reactive T cells. In solid tumors, high levels of circulating CD137+ T cells are associated with the clinical response and the disease-free status. Here, we examined the role of the CD137+ T cells in the improvement of patients' selection for immunotherapy treatment.

Impact of Sarcopenia and Inflammation on Patients with Advanced Non-Small Cell Lung Cancer (NCSCL) Treated with Immune Checkpoint Inhibitors (ICIs): A Prospective Study.

Background: Sarcopenia is a condition characterized by loss of skeletal muscle mass associated with worse clinical outcomes in cancer patients. Data on sarcopenia in patients undergoing immune checkpoint inhibitors (ICI) therapy are still limited. The aim of this prospective observational study was to investigate the relationship between sarcopenia, ICI treatment response and immunological profile, in patients with advanced non-small cell lung cancer (NSCLC).

Comparison of Two Blood-Based Genotyping Tests to Investigate the KRAS G12C Mutation in Patients with Non-Small-Cell Lung Cancer at Failure of First-Line Treatments.

Although molecular profiling at diagnosis has traditionally relied on direct sampling of neoplastic tissue, cancer clonal evolution represents a critical obstacle to use primary tissue biopsies to guide clinical decision-making at the time of progressive disease. Liquid biopsies might offer enormous advantages over tissue biopsies, tracking in real-time temporal-based tumor dynamics following each line of treatment. Here, we compared two liquid biopsy assays, specifically real-time polymerase chain reaction and next-generation sequencing, to track the KRAS G12C mutation at onset of progression from previous lines of therapy.