Prediction recurrence in stage I epidermal growth factor receptor-mutated non-small cell lung cancer using multi-modal data.

Introduction: Integrated recurrence prediction models that combine clinical, imaging, and genetic data are lacking for epidermal growth factor receptor (EGFR)-mutated stage I non-small cell lung cancer (NSCLC). We developed a recurrence prediction model for Stage I EGFR-mutated NSCLC by integrating clinical, radiological, and whole-exome sequencing (WES) data.

Methods: A total of 306 patients with Stage I EGFR-mutated NSCLC were stratified into training (n = 206) and validation (n = 100) cohorts using stratified random sampling.

Genomic Profiles of Pathogenic and Moderate-Penetrance Germline Variants Associated With Risk of Early-Onset Lung Adenocarcinoma.

Introduction: Up to 54% of all lung adenocarcinoma (LADC) cases in Asian populations occur in never-smoking women, suggesting that the impact of smoking and other environmental factors on the risk of early-onset LADC is minimal. Genetic factors may play a crucial role in disease development.

Methods: The prevalence of germline pathogenic variants (GPVs) of 454 hereditary cancer and DNA repair genes was evaluated by whole-exome and whole-genome sequencing of 348 early-onset LADC (aged ≤ 40 y) and 1425 later-onset LADC (aged ≥ 41 y) cases.

Implications of EGFR expression on EGFR signaling dependency and adaptive immunity against EGFR-mutated lung adenocarcinoma.

Background: In EGFR-mutated lung adenocarcinoma (EGFRm LUAD), EGFR mutations do not necessarily result in increased EGFR expression (EGFR-exp), which differs among patients. However, the factors influencing EGFR-exp and the impact of EGFR-exp on tumor characteristics in patients with EGFRm LUAD remain unclear.

Patients And Methods: Whole-exome and RNA sequencing were performed for patients with early- and advanced-stage EGFRm LUAD.

Key Therapeutic Agents for Thymic Carcinoma in Real-world Clinical Practice.

Background/aim: Thymic carcinoma is a rare cancer with poor prognosis in unresectable cases. Treatment efficacy of carboplatin+paclitaxel (CP), lenvatinib, S-1, and sunitinib remains uncertain, with some patients experiencing increased post-treatment liver metastasis.

Patients And Methods: We performed a retrospective analysis of patients with metastatic thymic carcinoma who received chemotherapy between 2006 and 2023 at the National Cancer Center Hospital.

Association between lorlatinib blood concentration and adverse events and clinical impact of dose modification.

Objectives: Lorlatinib, a third-generation anaplastic lymphoma kinase (ALK) inhibitor, causes distinct adverse events (AEs), including hyperlipidemia and central nervous system (CNS) disorders. Although dose modifications are recommended to manage these AEs, whether dose modifications can achieve optimal blood lorlatinib concentrations and reduce the incidence of lorlatinib-induced AEs remains unclear. Therefore, we investigated the association between lorlatinib exposure and AEs in each patient.

Multi-omics and clustering analyses reveal the mechanisms underlying unmet needs for patients with lung adenocarcinoma and identify potential therapeutic targets.

Background: The cancer genome contains several driver mutations. However, in some cases, no known drivers have been identified; these remaining areas of unmet needs, leading to limited progress in cancer therapy. Whole-genome sequencing (WGS) can identify non-coding alterations associated with the disease.

Mechanism of ERBB2 gene overexpression by the formation of super-enhancer with genomic structural abnormalities in lung adenocarcinoma without clinically actionable genetic alterations.

Background: In an extensive genomic analysis of lung adenocarcinomas (LUADs), driver mutations have been recognized as potential targets for molecular therapy. However, there remain cases where target genes are not identified. Super-enhancers and structural variants are frequently identified in several hundred loci per case.

Disease progression status during initial immune checkpoint inhibitor (ICI) affects the clinical outcome of ICI retreatment in advanced non-small cell lung cancer patients.

Background: It is still unclear whether patients with advanced non-small cell lung cancer (NSCLC), with disease progression after initial immune checkpoint inhibitor (ICI) therapy, would benefit from ICIs readministration.

Patients And Methods: We retrospectively collected data from patients with advanced NSCLC who received ICI retreatment. Depending on the disease status at the discontinuation of the initial ICI therapy, the patients were divided into two groups: with disease progression (PD group) and without disease progression (Without PD group).

Incidence of serious adverse events caused by tyrosine kinase inhibitor treatment following immune checkpoint inhibitor therapy in advanced NSCLC patients with oncogenic driver alterations.

Background: Sequential tyrosine kinase inhibitors (TKIs) following immune checkpoint inhibitors (ICIs) increases the incidence of serious adverse events (SAEs). However, the factors and the types of TKIs that affect the incidence of SAEs remain unknown.

Methods: We retrospectively reviewed advanced non-small cell lung cancer (NSCLC) patients who received sequential TKIs following ICIs between November 2015 and April 2021.

Onco-biome in pharmacotherapy for lung cancer: a narrative review.

Background And Objective: The gut microbiota (GM) was recently recognized to play an important role in modulating systemic immune responses and is known to influence the effects or adverse events of immune checkpoint blockade (ICB) or carcinogenesis by crosstalk with regulators of cancer-related immunity, and this relationship is complex and multifactorial. Diversity in the gut microbiome and the abundance of specific bacterial species have been identified to be associated with better response and prognosis. Therefore, the purpose of the current interest in the gut microbiome is to enable modulation of the immune system in donor cancer patients by the administration of specific bacterial species and enabling their dominance.

[Cancer Therapy Targeting Fusion Genes in Lung Cancer].

Therapeutic landscape of lung cancer has undergone a dramatic shift due to the better understandings of disease biology and the identification of oncogenic driver alterations. Consequently, the new classification paradigm of non-small-cell lung cancer is further characterized by molecularly defined subsets, and making the therapeutic landscape increasingly complex. Driver gene mutations have been found in approximately 75% of Japanese non-squamous, non-small-cell lung cancers.

Correlation between body mass index and efficacy of anti-PD-1 inhibitor in patients with non-small cell lung cancer.

Background: High body mass index (BMI) has been reported to be associated with the efficacy of immune checkpoint inhibitors in patients with advanced non-small cell lung cancer (NSCLC), but the association between BMI and efficacy of anti-PD-1 inhibitors remains controversial. The present study investigated this association in patients with advanced NSCLC.

Methods: We retrospectively reviewed patients with advanced NSCLC who received PD-1 inhibitors at the National Cancer Center Hospital between January 2016 and December 2018.

Disease flare of leptomeningeal metastases without radiological and cytological findings after the discontinuation of osimertinib.

Objectives: Rapid tumor progression occurring after the discontinuation of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy is referred to as a disease flare of non-small cell lung cancer (NSCLC). The clinicopathological features of disease flares after osimertinib discontinuation remain unclear.

Results: We report a patient with EGFR-mutated NSCLC who experienced the progression of leptomeningeal metastases as a disease flare shortly after the discontinuation of osimertinib despite the absence of radiological or cytological findings.

The utility of transbronchial rebiopsy for peripheral pulmonary lesions in patients with advanced non-squamous non-small cell lung cancer.

Background: Patients treated for non-squamous (non-Sq) non-small cell lung cancer (NSCLC) often require repeat biopsies to determine the optimal subsequent treatment. However, the differences between rebiopsy and initial biopsy in terms of their diagnostic yields and their ability to test the molecular profiles using bronchoscopy with radial endobronchial ultrasound guidance in patients with advanced NSCLC remain unclear. Hence, we aimed to compare the diagnostic yields and ability for molecular analyses of rebiopsies with those of initial biopsies.

Remarkable Alteration of PD-L1 Expression after Immune Checkpoint Therapy in Patients with Non-Small-Cell Lung Cancer: Two Autopsy Case Reports.

Pembrolizumab is an immune checkpoint inhibitor (ICI), currently recommended as the first-line treatment for patients with advanced non-small-cell lung cancer (NSCLC) showing ≥50% expression of programmed death-ligand 1 (PD-L1). Previously it was reported that platinum-based chemotherapy may change PD-L1 expression in solid cancers. However, no reports addressing alteration of PD-L1 expression after ICI therapy in NSCLC are available so far.

Successful treatment with idarucizumab for diffuse alveolar hemorrhage induced by dabigatran etexilate: a case report.

We report the case of an 81-year-old man taking dabigatran etexilate (dabigatran) for chronic atrial fibrillation, who presented with acute-onset hemoptysis and hypoxia. Chest high-resolution computed tomography showed bilateral ground grass opacities. After admission, his respiratory failure progressed rapidly and bronchoalveolar lavage was performed immediately, which showed copious amounts of bloody fluid and hemosiderin-laden macrophages with Prussian blue staining.