A conserved pilin from uncultured gut bacterial clade TANB77 enhances cancer immunotherapy.

Immune checkpoint blockade (ICB) has become a standard anti-cancer treatment, offering durable clinical benefits. However, the limited response rate of ICB necessitates biomarkers to predict and modulate the efficacy of the therapy. The gut microbiome's influence on ICB efficacy is of particular interest due to its modifiability through various interventions.

Complete Remission of Dural-Based Leptomeningeal Metastasis in Patient With Non-Small Cell Lung Cancer by Osimertinib.

We report complete remission of dural-based leptomeningeal metastasis (LM) in an 80-year-old female patient with non-small cell lung cancer (NSCLC) by osimertinib. She was diagnosed with NSCLC (adenocarcinoma, T4N3M1a) 8 years ago. Mutation analysis of biopsied tissue revealed exon 19 deletion positive, and gefitinib was prescribed.

Blood Neurofilament Light Chain and Glial Fibrillary Acidic Protein as Promising Screening Biomarkers for Brain Metastases in Patients with Lung Cancer.

The diagnosis of brain metastases (BMs) in patients with lung cancer (LC) predominantly relies on magnetic resonance imaging (MRI), a method that is constrained by high costs and limited accessibility. This study explores the potential of serum neurofilament light chain (sNfL) and serum glial fibrillary acidic protein (sGFAP) as screening biomarkers for BMs in LC patients. We conducted a retrospective analysis of 700 LC cases at the National Cancer Center, Korea, from July 2020 to June 2022, measuring sNfL and sGFAP levels at initial LC diagnosis.

A phase 2 study of spartalizumab (PDR001) among patients with recurrent or metastatic esophageal squamous cell carcinoma (KCSG HN18-17, K-MASTER project 12).

Unlabelled: Spartalizumab (PDR001) is a humanized IgG4 monoclonal antibody targeting programmed cell death protein 1 (PD-1). We conducted a single-arm, phase 2 trial to investigate the efficacy and safety of spartalizumab in patients with refractory esophageal squamous cell carcinoma (ESCC). Patients with histologically confirmed ESCC who experienced disease progression after platinum-based chemotherapy received 300 mg of intravenous spartalizumab every three weeks until disease progression or occurrence of unacceptable toxicity.

Drug Response of Patient-Derived Lung Cancer Cells Predicts Clinical Outcomes of Targeted Therapy.

Intratumor heterogeneity leads to different responses to targeted therapies, even within patients whose tumors harbor identical driver oncogenes. This study examined clinical outcomes according to a patient-derived cell (PDC)-based drug sensitivity test in lung cancer patients treated with targeted therapies. From 487 lung cancers, 397 PDCs were established with a success rate of 82%.

Treatment Outcomes of Proton Beam Therapy for Esophageal Squamous Cell Carcinoma at a Single Institute.

Recently, proton beam therapy (PBT) has gathered attention for improving outcomes and reducing toxicities in various cancers; however, the evidence for esophageal squamous cell carcinoma (ESCC) is lacking. Our study retrospectively evaluated the outcomes of PBT for ESCC patients at a single institute. The patients treated with PBT between November 2015 and February 2022 were included in the study, excluding those with distant metastases or those that had undertaken prior treatment for esophageal cancer (EC).

Nivolumab after Induction Chemotherapy in Previously Treated Non-Small-Cell Lung Cancer Patients with Low PD-L1 Expression.

This study aimed to investigate whether cyclophosphamide (C) and adriamycin (A) induction therapy (IT) prior to nivolumab could enhance the efficacy of nivolumab in previously treated patients with non-squamous (NSQ) non-small-cell lung cancer (NSCLC) with less than 10% programmed death-ligand 1 (PD-L1) expression. Twenty-two enrolled patients received four cycles of CA-IT every 3 weeks. Nivolumab was given 360 mg every 3 weeks from the second cycle and 480 mg every 4 weeks after four cycles of CA-IT.

Tumor Microenvironment Modulation by Neoadjuvant Erlotinib Therapy and Its Clinical Impact on Operable EGFR-Mutant Non-Small Cell Lung Cancer.

Purpose: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors have greatly improved survival in EGFR-mutant (EGFRm) non-small cell lung cancer (NSCLC); however, their effects on the tumor microenvironment (TME) are unknown. We assessed the changes induced by neoadjuvant erlotinib therapy (NE) in the TME of operable EGFRm NSCLC.

Materials And Methods: This was a single-arm phase II trial for neoadjuvant/adjuvant erlotinib therapy in patients with stage II/IIIA EGFRm NSCLC (EGFR exon 19 deletion or L858R mutations).

Clinical utility of a plasma-based comprehensive genomic profiling test in patients with non-small cell lung cancer in Korea.

Objectives: Plasma-based comprehensive circulating cell-free DNA (cfDNA) next generation sequencing (NGS) has shown utility in advanced non-small cell lung cancer (aNSCLC). The aim of this study was to determine the feasibility of cfDNA-based NGS to identify actionable gene alterations in patients with aNSCLC.

Patients And Methods: This single-center non-interventional retrospective study evaluated Korean patients with biopsy-confirmed stage III/IV non-squamous aNSCLC.

Patient-derived cell-based pharmacogenomic assessment to unveil underlying resistance mechanisms and novel therapeutics for advanced lung cancer.

Background: A pharmacogenomic platform using patient-derived cells (PDCs) was established to identify the underlying resistance mechanisms and tailored treatment for patients with advanced or refractory lung cancer.

Methods: Drug sensitivity screening and multi-omics datasets were acquired from lung cancer PDCs (n = 102). Integrative analysis was performed to explore drug candidates according to genetic variants, gene expression, and clinical profiles.

Real World Characteristics and Clinical Outcomes of HER2-Mutant Non-Small Cell Lung Cancer Patients Detected by Next-Generation Sequencing.

Purpose: This study was conducted to investigate the clinical characteristics of patients with advanced non-small cell lung cancer (NSCLC) harboring human epidermal growth factor receptor 2 (HER2) mutations and to evaluate response to standard treatment and HER2-targeted agents.

Materials And Methods: Using tissue and/or blood next-generation sequencing, we identified 44 patients with NSCLC harboring HER2 mutations who were treated at Severance Hospital between December 2016 and February 2021. Clinical data, including patient characteristics, mutation status, incidence of metastasis for distant lesions, and response to chemotherapy, were retrospectively analyzed.

Incorporation of SKI-G-801, a Novel AXL Inhibitor, With Anti-PD-1 Plus Chemotherapy Improves Anti-Tumor Activity and Survival by Enhancing T Cell Immunity.

A recently developed treatment strategy for lung cancer that combines immune checkpoint inhibitors with chemotherapy has been applied as a standard treatment for lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), and it has improved the outcomes of chemotherapy. Maintenance treatment with anti-PD-1 antibody (aPD-1) enhances the effect of immunochemical combination therapy and improves therapeutic efficacy, which contributes toward a significant improvement in patient survival rates. The AXL receptor tyrosine kinase (AXL), which is expressed in tumor cells, plays an essential role in the resistance of cancers to chemotherapy and immunotherapy, and stimulates signaling associated with epithelial-mesenchymal transition (EMT) in metastatic cancer.

Predicting treatment outcomes using F-FDG PET biomarkers in patients with non-small-cell lung cancer receiving chemoimmunotherapy.

Background: Predictive markers for treatment response and survival outcome have not been identified in patients with advanced non-small-cell lung cancer (NSCLC) receiving chemoimmunotherapy. We aimed to evaluate whether imaging biomarkers of F-fluorodeoxyglucose (F-FDG) positron emission tomography/computed tomography (PET/CT) and routinely assessed clinico-laboratory values were associated with clinical outcomes in patients with advanced NSCLC receiving pembrolizumab plus platinum-doublet chemotherapy as a first-line treatment.

Methods: We retrospectively enrolled 52 patients with advanced NSCLC who underwent baseline F-FDG PET/CT before treatment initiation.

SKI-G-801, an AXL kinase inhibitor, blocks metastasis through inducing anti-tumor immune responses and potentiates anti-PD-1 therapy in mouse cancer models.

Objectives: AXL-mediated activation of aberrant tyrosine kinase drives various oncogenic processes and facilitates an immunosuppressive microenvironment. We evaluated the anti-tumor and anti-metastatic activities of SKI-G-801, a small-molecule inhibitor of AXL, alone and in combination with anti-PD-1 therapy.

Methods: pAXL inhibition by SKI-G-801 was performed in both human and mouse cancer cell lines.

Efficacy and safety of atezolizumab, in combination with etoposide and carboplatin regimen, in the first-line treatment of extensive-stage small-cell lung cancer: a single-center experience.

Background: Patients with small-cell lung cancer (SCLC) have a dismal prognosis with limited overall survival (OS) despite a high response rate to chemotherapy. Recently, immune checkpoint inhibitors, combined with chemotherapy, as the first-line treatment for extensive-stage (ES)-SCLC have shown improvement in clinical outcomes.

Patients And Methods: Real-world data from 68 Korean ES-SCLC patients, treated with atezolizumab, etoposide, and carboplatin at Yonsei Cancer Center between June 2019 and November 2020, were retrospectively analyzed to determine safety and efficacy using Cox regression analysis.

A phase II study of poziotinib in patients with recurrent and/or metastatic head and neck squamous cell carcinoma.

Background: In phase I studies, poziotinib has shown meaningful efficacy against various types of cancers. This phase 2 study aimed to investigate the efficacy and safety of poziotinib in recurrent and/or metastatic head and neck squamous cell carcinoma (R/M-HNSCC).

Methods: Overall, 49 patients were enrolled (median age, 62 years; age range, 21-78 years).

Analyses of CNS Response to Osimertinib in Patients with T790M-Positive Advanced NSCLC from ASTRIS Korean Subset, Open-Label Real-World Study.

Up to 40% of patients with epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC) may develop central nervous system (CNS) metastases throughout their disease. Moreover, the first- and second-generation EGFR-tyrosine kinase inhibitors have limited efficacy because of their poor blood-brain barrier permeability. Therefore, we conducted preplanned analyses of ASTRIS, a clinical study of the third-generation EGFR-TKI osimertinib to demonstrate its potential role in intracranial response efficacies.

Distinct Characteristics and Clinical Outcomes to Predict the Emergence of Amplification in Patients with Non-Small Cell Lung Cancer Who Developed Resistance after Treatment with Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors.

Objectives: Patients with epidermal growth factor receptor () mutant non-small cell lung cancer (NSCLC) ultimately acquire resistance to tyrosine kinase inhibitors (TKIs) during treatment. In 5-22% of these patients, resistance is mediated by aberrant mesenchymal epithelial transition factor () gene amplification. Here, we evaluated the emergence of amplification after EGFR-TKI treatment failure based on clinical parameters.

Clinical decision support algorithm based on machine learning to assess the clinical response to anti-programmed death-1 therapy in patients with non-small-cell lung cancer.

Objective: Anti-programmed death (PD)-1 therapy confers sustainable clinical benefits for patients with non-small-cell lung cancer (NSCLC), but only some patients respond to the treatment. Various clinical characteristics, including the PD-ligand 1 (PD-L1) level, are related to the anti-PD-1 response; however, none of these can independently serve as predictive biomarkers. Herein, we established a machine learning (ML)-based clinical decision support algorithm to predict the anti-PD-1 response by comprehensively combining the clinical information.

Prognostic implications of PD-L1 expression in patients with angiosarcoma.

Aim: There are limited data on the feasibility of programmed death ligand-1 (PD-L1) expression as a prognostic biomarker in metastatic angiosarcoma.

Patients & Methods: We retrospectively collected and analyzed the data on PD-L1 expression in 70 angiosarcoma patients who were diagnosed at our center between 2005 and 2019.

Results: Thirteen (19%) patients had PD-L1 expression.

Dynamic changes in circulating PD-1CD8 T lymphocytes for predicting treatment response to PD-1 blockade in patients with non-small-cell lung cancer.

Background: The predictive value of immune monitoring with circulating CD8 T lymphocytes for treatment response to programmed cell death protein 1 (PD-1) inhibitors has not been explored in non-small-cell lung cancer (NSCLC), prompting us to investigate whether dynamic changes in PD-1CD8 T lymphocytes have predictive value for durable clinical benefit (DCB) and survival after PD-1 blockade.

Methods: Patients with recurrent and/or metastatic NSCLC treated with PD-1 inhibitors were enrolled (discovery cohort; n = 94). Peripheral blood was obtained immediately before and after one cycle of treatment with PD-1 blockade.

Patient-Derived Cells to Guide Targeted Therapy for Advanced Lung Adenocarcinoma.

Adequate preclinical model and model establishment procedure are required to accelerate translational research in lung cancer. We streamlined a protocol for establishing patient-derived cells (PDC) and identified effective targeted therapies and novel resistance mechanisms using PDCs. We generated 23 PDCs from 96 malignant effusions of 77 patients with advanced lung adenocarcinoma.