Journal of Thoracic Oncology

INTRODUCTION: We report the primary analysis from JAVELIN Lung 100, a phase 3 trial comparing avelumab (anti⁠-PD-L1) vs platinum-based doublet chemotherapy as first-line treatment for PD-L1+ advanced non-small cell lung cancer (NSCLC). METHODS: Adults with PD-L1+ (≥1% of tumor cells; PD-L1 IHC 73-10 pharmDx), EGFR/ALK-wild-type, previously untreated, stage IV NSCLC were randomized to avelumab 10 mg/kg every 2 weeks (Q2W), avelumab 10 mg/kg once weekly (QW) for 12 weeks and Q2W thereafter, or platinum-based doublet chemotherapy every 3 weeks...

BACKGROUND: Select tyrosine kinase inhibitors (TKIs) used to treat oncogene-driven lung cancers also inhibit MATE-1. When MATE-1 is blocked, creatinine is retained in the serum. Elevated creatinine levels raise the specter of drug-induced intrarenal insufficiency despite the lack of true renal injury. We conducted a systematic analysis of MATE-1 inhibitor (MATEi)-treated patients to comprehensively characterize this phenomenon. METHODS: Oncogene-driven lung cancer patients treated with a wide variety of MATEi TKIs (brigatinib, cabozantinib, capmatinib, crizotinib, entrectinib, lorlatinib, pralsetinib, selpercatinib, and tepotinib) were eligible for an analysis of renal dysfunction...

Systematic lymph node dissection has been widely accepted and turned into a standard procedure for lung cancer surgery. In recent years, the concept of "Minimal Invasive Surgery (MIS)" has greatly changed the surgical paradigm of lung cancer. Previous studies revealed that excessive dissection of lymph nodes without metastases showed uncertain clinical benefit. Meanwhile, it leads to the elevated risk of postoperative complications including chylothorax and laryngeal nerve injury. Additionally, dissection of non-metastatic lymph nodes may disturb systematic immunity, resulting in the secondary effect on primary tumor or latent metastases...

INTRODUCTION: Traditionally, relapsed small cell lung cancer (SCLC) has been classified as "sensitive" or "refractory" based on cutoff values (60 or 90 days) for the duration between the last chemotherapy and disease progression. However, these cutoff values are not derived from rigorous analytical methods, and their applicability to contemporary treatments remains uncertain. METHODS: We conducted a retrospective multicenter study on patients with extensive-stage (ES)-SCLC who underwent second-line therapy after platinum-doublet chemotherapy with or without immune checkpoint inhibitor (ICI) resistance before (pre-ICI cohort) and after (post-ICI cohort) approval of combination immunotherapy...

INTRODUCTION: Morphologic and molecular data for staging of multifocal lung squamous cell carcinomas (LSCC) are limited. In this study, whole exome sequencing (WES) was used as the gold standard to determine if multifocal LSCC represented separate primary cancers (SPLC) or intrapulmonary metastases (IPM). Genomic profiles were compared to the comprehensive morphologic assessment. METHODS: WES was performed on 20 tumor pairs of multifocal LSCC and matched normal lymph nodes using the Illumina NovaSeq6000 S4-Xp (Illumina, San Diego, CA)...

BACKGROUND: Brain metastasis, with the highest incidence in patients with lung cancer, significantly worsens prognosis and poses challenges to clinical management. To date, how brain metastasis evades immune elimination remains unknown. METHODS: Whole-exome sequencing and RNA-sequencing was performed on 30 matched brain metastasis (BM), primary lung adenocarcinoma (LP) and normal tissues. Data from TCGA primary lung adenocarcinoma (LUAD) cohort, as well as multiplex immunofluorescence (mIF), was used to support the findings of bioinformatics analysis...

INTRODUCTION: Currently, tumors with different histopathological characteristics and oncologic outcomes comprise the T3 category of the 8th edition tumor, node, and metastasis (TNM) classification for lung cancers. To better understand the T3 category, we evaluated completeness of resection and long-term survival in patients undergoing resection for T3 non-small-cell lung cancer (NSCLC). METHODS: The International Association for the Study of Lung Cancer 1999-2010 database was queried for patients with pathological T3N0M0 NSCLC who underwent lobectomy or pneumonectomy...

INTRODUCTION: The study aimed to prospectively investigate the bidirectional association between cardiovascular disease (CVD) and lung cancer, and whether this association differs across genetic risk levels. METHODS: This study prospectively followed 455,804 participants from the UK Biobank cohort who were free of lung cancer at baseline. Cox proportional hazards models were used to estimate hazard ratio (HR) for incident lung cancer according to CVD status. In parallel, similar approaches were used to assess the risk of incident CVD according to lung cancer status among 478,756 participants free of CVD at baseline...

INTRODUCTION: A tumor, node, metastasis (TNM)-based system for all types of thymic epithelial tumors (TET) was introduced in the 8th edition of the TNM classification of thoracic malignancies. The Thymic Domain of the Staging and Prognostic Factors Committee of the International Association for the Study of Lung Cancer, composed of multispecialty international experts, was charged to develop proposals for the 9th edition. This article outlines the proposed definitions for the T, the N and the M components, and their combination into stage groups...

INTRODUCTION: A lymph node map is the pillar on which accurate assignment and documentation of nodal classification stands. The International Thymic Malignancy Interest Group created the first map for thymic epithelial malignancies in conjunction with the 8th edition of the tumor, node and metastasis (TNM) classification, representing the first official TNM classification of thymic epithelial malignancies. The map was based on clinical experience and published studies, but was largely empiric because of limited available data...

NRG1 gene fusions are clinically actionable alterations identified in non-small cell lung cancer (NSCLC) and other tumors. Previous studies have demonstrated that NRG1 fusions signal through HER2/HER3 but thus far strategies targeting HER3 specifically or HER2/HER3 signaling have demonstrated modest activity in NSCLC patients bearing NRG1 fusions. Although NRG1 fusion proteins can bind HER4 in addition to HER3, the contribution of HER4 and other HER family members in NRG1 fusion-positive cancers isn't fully understood...

INTRODUCTION: Approximately 10% of mutations in the epidermal growth factor receptor (EGFR) gene in non-small cell lung cancer (NSCLC) are in-frame insertions in exon 20 (X20ins). These tumors usually do not respond to conventional EGFR-tyrosine kinase inhibitors (TKIs). Several novel EGFR-TKIs active for X20ins are in clinical development, including mobocertinib, which was recently approved by the US FDA. However, acquired resistance during treatment with these TKIs still occurs as in the case of EGFR-TKIs of earlier generations...

INTRODUCTION: A tumor, node, metastases (TNM)-based stage classification system of thymic epithelial tumors was adopted for the 8th edition of the stage classification of malignant tumors. The Thymic Domain of the Staging and Prognostics Factor Committee of the International Association for the Study of Lung Cancer developed a new database with the purpose to make proposals for the 9th edition stage classification system. This article outlines the proposed definitions for the T categories for the 9th Ed...

INTRODUCTION: Lazertinib is a third-generation central nervous system-penetrant tyrosine kinase inhibitor targeting mutant EGFR in NSCLC. Lazertinib exhibited improved efficacy versus gefitinib in the LASER301 study; this subset analysis compared lazertinib with gefitinib among Asian patients. METHODS: The phase 3 LASER301 study evaluated lazertinib efficacy and safety in treatment-naive patients with EGFR-mutated (exon 19 deletion or L858R) locally advanced or metastatic NSCLC...

INTRODUCTION: Bintrafusp alfa, a first-in-class bifunctional fusion protein composed of the extracellular domain of TGF-βRII (a TGF-β "trap") fused to a human immunoglobulin G1 monoclonal antibody blocking programmed death-ligand 1 (PD-L1), has exhibited clinical activity in a phase 1 expansion cohort of patients with PD-L1-high advanced NSCLC. METHODS: This adaptive phase 3 trial (NCT03631706) compared the efficacy and safety of bintrafusp alfa versus pembrolizumab as first-line treatment in patients with PD-L1-high advanced NSCLC...

BACKGROUND: With global adoption of CT lung cancer screening, there is increasing interest to use artificial intelligence (AI) deep learning methods to improve the clinical management process. To enable AI research using an open source, cloud-based, globally distributed, screening CT imaging dataset and computational environment that are compliant with the most stringent international privacy regulations that also protects the intellectual properties of researchers, the International Association of the Study of Lung Cancer (IASLC) sponsored development of the Early Lung Imaging Confederation (ELIC) resource in 2018...

INTRODUCTION: This open-label, phase 3 trial (ALTA-3; NCT03596866) compared efficacy and safety of brigatinib versus alectinib for ALK+ NSCLC after disease progression on crizotinib. METHODS: Patients with advanced ALK+ NSCLC that progressed on crizotinib were randomized 1:1 to brigatinib 180 mg once daily (7-d lead-in, 90 mg) or alectinib 600 mg twice daily, aiming to test superiority. The primary end point was blinded independent review committee-assessed progression-free survival (PFS)...

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For much of the last two decades, the treatment options for patients with stage III non-small cell lung cancer (NSCLC) was mostly stagnant. In the past five years, ongoing innovations have dovetailed alongside advances in biomarker testing, novel therapeutics, precision surgery and radiotherapy, all of which are leading to an increase in more personalized option for the treatment. This review paper will focus on several completed and ongoing initiatives involving treatment of stage III NSCLC patients. First, it will tackle the progress made in curative treatment of unresectable stage III NSCLC, starting with PACIFIC, and branching out into topics such as concurrent immunotherapy and chemoradiation, intensification of consolidative immunotherapy, dual immunotherapy consolidation, as well as a reflection on those sub-populations that may not benefit from consolidative immunotherapy...

INTRODUCTION: Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) have shown promising activity against advanced ALK-rearranged non-small cell lung cancer (NSCLC). However, co-occurring genetic alterations, such as CDKN2/B or TP53, may negatively affect the efficacy of targeted therapies. PATIENTS AND METHODS: From December 2017 to December 2022, this study cohort analyzed Next-Generation Sequencing data of 116 patients with metastatic ALK-rearranged NSCLC from five Latin-American cancer centers...