Integrated molecular and clinical characterization of pulmonary large cell neuroendocrine carcinoma.

Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a rare, aggressive lung tumor marked by significant molecular heterogeneity. In a study of 590 patients across two independent cohorts, we observe comparable overall survival across treatment regimens (chemotherapy, chemoimmunotherapy, immunotherapy) without unexpected adverse events. Genomic analysis identifies distinct non-small cell lung cancer-like (NSCLC-like, KEAP1, KRAS, STK11 mutations) and SCLC-like (RB1, TP53 mutations) LCNEC subtypes, with 80% aligning with SCLC transcriptional profiles.

Molecular and immunological features associated with long-term benefits in metastatic NSCLC patients undergoing immune checkpoint blockade.

Introduction: Immunotherapy is firmly established as a treatment regimen in various solid tumors, driven by its exceptional benefits in a selected group of patients. Despite widespread adoption of immune checkpoint blockade (ICB) across diverse solid tumors, the quest for a clinically informative biomarker for long-term benefit remains unmet.

Methods: A total of 49 patients with metastatic NSCLC treated with ICB were included.

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.

Exploring the value of routinely collected data on EQ-5D-5L and other electronic patient-reported outcome measures as prognostic factors in adults with advanced non-small cell lung cancer receiving immunotherapy.

Objective: Investigate whether routinely collected electronic patient-reported outcome measures (ePROMs) add prognostic value to clinical and tumour characteristics for adults with advanced non-small cell lung cancer (NSCLC) receiving immunotherapy.

Methods And Analysis: We retrospectively analysed data from adults with advanced NSCLC commencing immunotherapy between April 2019 and June 2022. Prognostic factors were ePROMs on quality of life (EuroQoL five-dimension five-level (EQ-5D-5L); EuroQoL Visual Analogue Scale (EQ-VAS)) and symptoms (patient-reported version of the Common Terminology Criteria for Adverse Events v5.

First-line osimertinib compared to earlier generation TKIs in advanced EGFR-mutant NSCLC: A real-world survival analysis.

Objectives: This study aimed to compare the overall survival (OS) of patients with advanced EGFR-mutant NSCLC treated with first-line osimertinib versus earlier-generation EGFR tyrosine kinase inhibitors (TKIs) in a real-world setting. Secondary endpoint included OS in patients with uncommon EGFR mutations. Exploratory aim focused on the impact of TKIs sequencing strategies.

First-Line Chemo-Immunotherapy in SCLC: Outcomes of a Binational Real-World Study.

Introduction: SCLC is characterized by aggressiveness and limited treatment options, especially in extensive-stage SCLC (ES-SCLC). Immunotherapy added to the platinum-etoposide combination has recently become standard in this setting. This retrospective study aims to evaluate the real-world effectiveness of chemo-immunotherapy in patients with ES-SCLC, focusing on subpopulations excluded from clinical trials.

An international and multidisciplinary EORTC survey on resectability of stage III non-small cell lung cancer.

Introduction: The EORTC-Lung Cancer Group initiated a Delphi consensus process to establish a consensual definition of resectable stage III non-small cell lung cancer (NSCLC) for the use in clinical trials, including a systematic review, survey, and review of clinical cases. Here, the survey results are presented, aimed to identify areas of controversy.

Methods: A survey was distributed among the members of six international organizations related to lung cancer.

Design and proof of concept of a double-panel TOF-PET system.

Objective: Positron Emission Tomography (PET) is a well-known imaging technology for the diagnosis, treatment, and monitoring of several diseases. Most PET scanners use a Ring-Shaped Detector Configuration (RSDC), which helps obtain homogeneous image quality but are restricted to an invariable Field-of-View (FOV), scarce spatial resolution, and low sensitivity. Alternatively, few PET systems use Open Detector Configurations (ODC) to permit an accessible FOV adaptable to different target sizes, thus optimizing sensitivity.

Pre-existing tumor host immunity characterization in resected non-small cell lung cancer.

Introduction: Neoadjuvant and adjuvant immune checkpoint blockade (ICB) have recently become standard of care in resectable non-small cell lung cancer (NSCLC). Yet, biomarkers that inform patients who benefit from this approach remain largely unknown. Here, we interrogated the tumor immune microenvironment (TIME) in early-stage NSCLC patients that underwent up-front surgery.

Novel therapeutic strategies for recurrent SCLC.

Therapeutic options for patients with relapsed SCLC are limited, and the prognosis in this setting remains poor. While clinical outcomes for frontline treatment have modestly improved with the introduction of immunotherapy, treatment in the second-line setting persists almost unchanged. In this review, current treatment options and recent advances in molecular biology are described.

Acquired Mechanisms of Resistance to Osimertinib-The Next Challenge.

EGFR-mutated tumors represent a significant percentage of non-small cell lung cancer. Despite the increasing use of osimertinib, a treatment that has demonstrated an outstanding clinical benefit with a tolerable toxicity profile, EGFR tumors eventually acquire mechanisms of resistance. In the last years, multiple mechanisms of resistance have been identified; however, after progressing on osimertinib, treatment options remain bleak.

Comparison of Different Methods for Defining Hyperprogressive Disease in NSCLC.

Introduction: Hyperprogressive disease (HPD) as a consequence of immune checkpoint inhibitors in NSCLC has been reported in multiple studies. However, inconsistent results in incidence and survival outcomes within studies, together with different assessment methods, have led to increasing controversy regarding the concept of HPD.

Methods: Consecutive patients treated with nivolumab (N = 42) or docetaxel (N = 37) were evaluated.

Gamma Camera Imaging with Rotating Multi-Pinhole Collimator. A Monte Carlo Feasibility Study.

In this work, we propose and analyze a new concept of gamma ray imaging that corresponds to a gamma camera with a mobile collimator, which can be used in vivo, during surgical interventions for oncological patients for localizing regions of interest such as tumors or ganglia. The benefits are a much higher sensitivity, better image quality and, consequently, a dose reduction for the patient and medical staff. This novel approach is a practical solution to the overlapping problem which is inherent to multi-pinhole gamma camera imaging and single photon emission computed tomography and which translates into artifacts and/or image truncation in the final reconstructed image.

Prognostic factors and effect on survival of immune-related adverse events in patients with non-small-cell lung cancer treated with immune checkpoint blockage.

Our aim was to describe the incidence and characteristics of immune-related adverse events (irAEs) in patients with non-small-cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICI) and to evaluate their impact on outcome. All cases of NSCLC patients treated with ICIs in the second-line setting between December 2015 and May 2018 were evaluated. Seventy patients were included.

Author Correction: High resolution and sensitivity gamma camera with active septa. A first Monte Carlo study.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Pilot performance of a dedicated prostate PET suitable for diagnosis and biopsy guidance.

Background: Prostate cancer (PCa) represents one of the most common types of cancers facing the male population. Nowadays, to confirm PCa, systematic or multiparametric MRI-targeted transrectal or transperineal biopsies of the prostate are required. However, due to the lack of an accurate imaging technique capable to precisely locate cancerous cells in the prostate, ultrasound biopsies sample random parts of the prostate and, therefore, it is possible to miss regions where those cancerous cells are present.

Simulation Study for Designing a Dedicated Cardiac TOF-PET System.

The development of dedicated positron emission tomography scanners is an active area of research, especially aiming at the improvement of lesion detection and in support of cancer treatment and management. Recently, dedicated Positron Emission Tomography (PET) systems with different configurations for specific organs have been developed for improving detection effectiveness. Open geometries are always subject to distortion and artifacts in the reconstructed images.

High resolution and sensitivity gamma camera with active septa. A first Monte Carlo study.

Gamma cameras are of great interest due to their high potential in the field of Nuclear Medicine Imaging. They allow for an early diagnosis of reduced size tumors, and also for a wide variety of preclinical studies with the aim of designing more effective treatments against cancer. In this work we propose a significantly improved multi-pinhole collimator gamma camera and perform a first Monte Carlo analysis of its characteristics.

NEMA Performance Evaluation of CareMiBrain dedicated brain PET and Comparison with the whole-body and dedicated brain PET systems.

This article presents system performance studies of the CareMiBrain dedicated brain PET according to NEMA NU 2-2012 (for whole-body PETs) and NU 4-2008 (for preclinical PETs). This scanner is based on monolithic LYSO crystals coupled to silicon photomultipliers. The results obtained for both protocols are compared with current commercial whole body PETs and dedicated brain PETs found in the literature.

MET Inhibitors in Small Cell Lung Cancer: From the Bench to the Bedside.

Small cell lung cancer (SCLC) is the most aggressive type of lung cancer. The different systemic treatment approaches attempted in the last 35 years have not improved overall survival in the advanced stage. Targeted therapies assessed in clinical trials have failed to show efficacy against SCLC.