Predictors of outcomes in advanced non-small cell lung cancer treated with pembrolizumab maintenance.

Background: Real-world first-line maintenance (1LM) treatment data are limited for advanced/metastatic non-small cell lung cancer (a/mNSCLC).

Materials And Methods: In this electronic health record-derived, deidentified database study, eligible patients (≥18 years; diagnosed with stage III/IV non-small cell lung cancer [June 1, 2017-September 30, 2021]) initiated pembrolizumab-based 1LM after 4-6 cycles of first-line (1L) platinum-based chemotherapy-pembrolizumab ± pemetrexed. Study outcomes were real-world time to next treatment or death (rwTTNTD), overall survival (rwOS), and predictors of outcomes.

Patient-Reported Outcomes for Patients With Metastatic NSCLC Treated at an Academic Medical Center, 2017-2021.

Background: Understanding the symptom burden experienced by patients with cancer can enable appropriate supportive care. Our aim was to describe patient-reported outcomes (PROs) for patients with metastatic NSCLC initiating first-line (1L) systemic therapy under usual care at a large academic center.

Methods: Patients eligible for this prospective observational study were ≥ 18 years old when initiating 1L systemic therapy for stage IV NSCLC from January 1, 2017 to December 31, 2020.

Machine-learning driven strategies for adapting immunotherapy in metastatic NSCLC.

Immune checkpoint inhibitors (ICIs), either as monotherapy (ICI-Mono) or combined with chemotherapy (ICI-Chemo), improves survival in advanced non-small cell lung cancer (NSCLC). However, prospective guidance for choosing between these options remains limited, and single-feature biomarkers like PD-L1 prove inadequate. We develop a machine learning model using clinicogenomic data from four cohorts (MD Anderson n = 750; Mayo Clinic n = 80; Dana-Farber n = 1077; Stand Up To Cancer n = 393) to predict individual benefit from adding chemotherapy.

Correction: Bronchoalveolar lavage cell percentages as diagnostic markers of immune checkpoint inhibitor pneumonitis.

[This corrects the article DOI: 10.3389/fmed.2025.

Bronchoalveolar lavage cell percentages as diagnostic markers of immune checkpoint inhibitor pneumonitis.

Introduction: Diagnostic biomarkers for immune checkpoint inhibitor pneumonitis (ICIP) are lacking. Bronchoalveolar lavage (BAL) lymphocytosis has been associated with ICIP, but studies have not evaluated BAL lymphocytosis as a diagnostic biomarker for ICIP.

Purpose: This study aimed to measure the association of BAL immune cell percentage with ICIP and test its performance as a diagnostic biomarker.

Incidence and Risk Factors for Pneumonitis Associated With Checkpoint Inhibitors in Relapsed or Refractory Lymphoma.

Introduction: Immune checkpoint inhibitors (ICI) have revolutionized relapsed/refractory lymphoma treatment but can cause severe immune-related adverse events (irAEs), including pneumonitis. The incidence and risk factors for ICI-pneumonitis in real-world lymphoma cohorts remain unreported.

Methods: We retrospectively reviewed 302 lymphoma patients treated with PD-1 inhibitors at MD Anderson (2015-2022).

Lung Cancer Risk Prediction in Patients with Persistent Pulmonary Nodules Using the Brock Model and Sybil Model.

Background/objectives: Persistent pulmonary nodules are at higher risk of developing into lung cancers. Assessing their future cancer risk is essential for successful interception. We evaluated the performance of two risk prediction models for persistent nodules in hospital-based cohorts: the Brock model, based on clinical and radiological characteristics, and the Sybil model, a novel deep learning model for lung cancer risk prediction.

PD-L1 Testing, Treatment Patterns, and Clinical Outcomes Among Patients with Metastatic NSCLC at an Academic Medical Center, 2017-2021.

Introduction: Targeted therapies and immune checkpoint inhibitors (ICIs) have revolutionized the management of metastatic non-small cell lung cancer (NSCLC) over the past decade.

Methods: This single-center observational study was conducted to describe programmed death-ligand 1 (PD-L1) testing, choice of therapy, and outcomes for adult patients with stage IV NSCLC initiating first-line therapy from 2017 through 2020, with follow-up through June 2021. Patient characteristics and study assessments were described according to four histomolecular subtypes, defined by histologic characteristics and availability of standard-of-care therapies for molecular subgroups at the time of study conduct.

Longitudinal Tracking of -Rearranged NSCLC From Plasma Using Circulating Tumor RNA and Circulating Tumor DNA.

Background: Although the administration of tyrosine-kinase inhibitors in -rearranged NSCLC has revolutionized precision medicine, the detection of gene rearrangements from liquid biopsies remains challenging. RNA-based detection has revealed promising sensitivity for rearrangement detection and thus we hypothesize that a liquid biopsy assay analyzing circulating tumor RNA (ctRNA) in addition to circulating tumor DNA (ctDNA) will improve detection. Furthermore, we hypothesize that the detection of gene fusions at baseline will correlate with clinical outcomes.

Rapid Intracranial Response With Tarlatamab in Patients With Untreated Brain Metastases From SCLC-A Real-World Case Series: Case Report.

SCLC has the highest propensity for brain metastases among all malignancies. Systemic treatment for SCLC, particularly in the setting of brain metastases, is very limited. Tarlatamab, the CD3/delta-like ligand 3 bispecific T-cell engager, has changed the treatment landscape of relapsed SCLC since its Food and Drug Administration approval in May 2024.

Comparison of imaging-based single-cell resolution spatial transcriptomics profiling platforms using formalin-fixed, paraffin-embedded tumor samples.

Imaging-based spatial transcriptomics (ST) is evolving rapidly as a pivotal technology in studying the biology of tumors and their associated microenvironments. However, the strengths of the commercially available ST platforms in studying spatial biology have not been systematically evaluated using rigorously controlled experiments. In this study, we used serial 5-μm sections of formalin-fixed, paraffin-embedded surgically resected lung adenocarcinoma and pleural mesothelioma tumor samples in tissue microarrays to compare the performance of the single cell ST platforms CosMx, MERFISH, and Xenium (uni/multi-modal) platforms in reference to bulk RNA sequencing, multiplex immunofluorescence, GeoMx Digital Spatial Profiler, and hematoxylin and eosin staining data for the same samples.

Impact of Co-mutations and Transcriptional Signatures in Non-Small Cell Lung Cancer Patients Treated with Adagrasib in the KRYSTAL-1 Trial.

Purpose: KRAS inhibitors are revolutionizing the treatment of non-small cell lung cancer (NSCLC), but clinico-genomic determinants of treatment efficacy warrant continued exploration.

Experimental Design: Patients with advanced KRASG12C-mutant NSCLC treated with adagrasib [KRYSTAL-1 (NCT03785249)] were included in the analysis. Pretreatment next-generation sequencing data were collected per protocol.

Comparison of imaging-based single-cell resolution spatial transcriptomics profiling platforms using formalin-fixed, paraffin-embedded tumor samples.

Imaging-based spatial transcriptomics (ST) is evolving rapidly as a pivotal technology in studying the biology of tumors and their associated microenvironments. However, the strengths of the commercially available ST platforms in studying spatial biology have not been systematically evaluated using rigorously controlled experiments. In this study, we used serial 5-m sections of formalin-fixed, paraffin-embedded surgically resected lung adenocarcinoma and pleural mesothelioma tumor samples in tissue microarrays to compare the performance of the single cell ST platforms CosMx, MERFISH, and Xenium (uni/multi-modal) platforms in reference to bulk RNA sequencing, multiplex immunofluorescence, GeoMx Digital Spatial Profiler, and hematoxylin and eosin staining data for the same samples.

Phase II Parallel Arm Study of Sacituzumab Govitecan-Hziy in Patients With Advanced Thymoma or Thymic Carcinoma.

Background: Thymic epithelial tumors (TETs), including thymoma and thymic carcinoma, are rare thoracic tumors of the anterior mediastinum. For those with advanced disease, platinum-based chemotherapy is used as first-line treatment. However, there is no standard regimen established for TET at progression after initial therapy, and treatment options for advanced/recurrent TETs are limited.

High peripheral T cell diversity is associated with lower risk of toxicity and superior response to dual immune checkpoint inhibitor therapy in patients with metastatic NSCLC.

Introduction: Despite significant successes, immune checkpoint blockade fails to achieve clinical responses in a significant proportion of patients, predictive markers for responses are imperfect and immune-related adverse events (irAEs) are unpredictable. We used T-cell receptor (TCR) sequencing to systematically analyze prospectively collected patient blood samples from a randomized clinical trial of dual immune checkpoint inhibitor therapy to evaluate changes in the T-cell repertoire and their association with response and irAEs.

Methods: Patients with immunotherapy-naïve metastatic non-small cell lung cancer (NSCLC) were treated with ipilimumab and nivolumab according to trial protocol (LONESTAR, NCT03391869).

Safety and Tolerability of Letetresgene Autoleucel (GSK3377794): Pilot Studies in Patients with Advanced Non-Small Cell Lung Cancer.

Purpose: The study aims to evaluate the safety, tolerability, and antitumor response of letetresgene autoleucel (lete-cel), genetically modified autologous T cells expressing a T-cell receptor specific for New York esophageal squamous cell carcinoma 1 (NY-ESO-1)/LAGE-1a shared epitope, alone or in combination with pembrolizumab, in HLA-A*02-positive (HLA-A*02:01, HLA-A*02:05, and/or HLA-A*02:06) patients with NY-ESO-1- and/or LAGE-1a-positive non-small cell lung cancer.

Patients And Methods: Study 208749 was a single-arm study of lete-cel alone. Study 208471 was a multiarm study of lete-cel alone or in combination with pembrolizumab in patients with advanced or recurrent non-small cell lung cancer.

Updates in Drug-Related Pneumonitis Due to Targeted Oncologic Therapies.

An increasing number of newer targeted oncologic therapies approved for clinical use can cause drug-related pneumonitis. Drug-related pneumonitis can be difficult to diagnose and requires a high index of suspicion. This review serves as an update to a prior review in this journal about pneumonitis with precision oncology therapies.

The Effect of PD-1/PD-L1 Inhibitor and Statin Combination Therapy on Overall Survival and Gastrointestinal Toxicity.

Objectives: Immune checkpoint inhibitors (ICIs), such as programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors, have been approved to treat a variety of cancers. Recently, studies have suggested that ICIs and statins are synergistic. However, the addition of statins to ICI therapy may increase the risk of gastrointestinal immune-related adverse events (irAEs).

Impact of select actionable genomic alterations on efficacy of neoadjuvant immunotherapy in resectable non-small cell lung cancer.

Background: Neoadjuvant immune checkpoint inhibitors (ICIs) have improved survival outcomes compared with chemotherapy in resectable non-small cell lung cancer (NSCLC). However, the impact of actionable genomic alterations (AGAs) on the efficacy of neoadjuvant ICIs remains unclear. We report the influence of AGAs on treatment failure (TF) in patients with resectable NSCLC treated with neoadjuvant ICIs.

Long-Term Clinical, Radiological, and Mortality Outcomes Following Pneumonitis in Nonsmall Cell Lung Cancer Patients Receiving Immune Checkpoint Inhibitors: A Retrospective Analysis.

Aims: Despite known short-term mortality risk of immune checkpoint inhibitor (ICI) pneumonitis, its impact on 1-year mortality, long-term pulmonary function, symptom persistence, and radiological resolution remains unclear.

Methods: We retrospectively analyzed 71 nonsmall cell lung cancer (NSCLC) patients treated with anti-PD(L)1 monoclonal antibodies between 2018-2021, who developed pneumonitis. Clinical and demographic covariates were collected from electronic medical record.