Introduction: Epidermal growth factor receptor (EGFR) mutations are key oncogenic drivers in lung adenocarcinoma (LUAD), predominantly affecting Asian, non-smoking, and female populations. While common mutations, such as exon 19 deletions and L858R, respond well to tyrosine kinase inhibitors (TKIs), uncommon EGFR mutations and compound variants exhibit variable treatment responses. This study aims to compare clinical characteristics and molecular profiles of patients with common, uncommon, and compound EGFR mutations, assessing their implications for therapy outcomes.
View Article and Find Full Text PDFBackground And Introduction: Over the last decade, treatment of patients with advanced non-small cell lung cancer (NSCLC) has become dependent on tissue and/or blood biomarkers to guide treatment decisions. Timely access to comprehensive biomarker and tumor signature information is crucial for diagnostic testing. With the rapid development and implementation of complex biomarker testing, comprehensive molecular profiling with in-depth analysis of DNA, RNA, and proteins can be easily performed.
View Article and Find Full Text PDFIntroduction: Patients with advanced ALK-positive NSCLC typically have poor response to immunotherapy; the benefit of consolidation durvalumab in patients with unresectable stage III ALK-positive NSCLC remains unclear. Herein, we compare the efficacy and safety of consolidation ALK tyrosine kinase inhibitor (TKI) versus durvalumab or observation after concurrent chemoradiation.
Methods: We conducted a retrospective study using a multicenter study of 17 institutions globally.
Introduction: Tyrosine kinase inhibitors (TKIs) are first-line treatment options for ALK-positive (ALK+) NSCLC. Factors such as variant allele frequencies (VAFs), EML4-ALK fusion variant, and concurrent TP53 mutations (TP53mt) in circulating tumor DNA (ctDNA) may affect treatment outcomes. We evaluated their effects on time to discontinuation (TTD) of first-line treatment with next-generation ALK TKIs in a real-world setting.
View Article and Find Full Text PDFThe success of checkpoint inhibitors (CPIs) for cancer has been tempered by immune-related adverse effects including colitis. CPI-induced colitis is hallmarked by expansion of resident mucosal IFNγ cytotoxic CD8 T cells, but how these arise is unclear. Here, we track CPI-bound T cells in intestinal tissue using multimodal single-cell and subcellular spatial transcriptomics (ST).
View Article and Find Full Text PDFLung diseases, including lung cancer, are rising causes of global mortality. Despite novel imaging technologies and the development of biomarker assays, the detection of lung cancer remains a significant challenge. However, the lung communicates directly with the external environment and releases aerosolized droplets during normal tidal respiration, which can be collected, stored and analzsed as exhaled breath condensate (EBC).
View Article and Find Full Text PDFBackground: Primary cardiac soft tissue sarcomas (CSTS) affect young adults, with dismal outcomes.
Objectives: The aim of this study was to investigate the clinical outcomes of patients with CSTS receiving immune checkpoint inhibitors (ICIs).
Methods: A retrospective, multi-institutional cohort study was conducted among patients with CSTS between 2015 and 2022.
Uncommon EGFR mutations represent a rare subgroup of NSCLC. Data on the efficacy of different generations of tyrosine kinase inhibitors (TKIs) in these rare mutations are scattered and limited to mostly retrospective small cohorts because these patients were usually excluded from clinical trials. This was a systematic review on the efficacy of TKIs in patients harboring uncommon EGFR mutations, defined as mutations other than exon 20 insertions mutations or T790M.
View Article and Find Full Text PDFLung cancer ranks among the most common cancers world-wide and is the first cancer-related cause of death. The classification of lung cancer has evolved tremendously over the past two decades. Today, non-small cell lung cancer (NSCLC), particularly lung adenocarcinoma, comprises a multitude of molecular oncogenic subsets that change both the prognosis and management of disease.
View Article and Find Full Text PDFIntroduction: Durvalumab improves survival when used as consolidation therapy after chemoradiation (CRT) in patients with stage III NSCLC. The optimal consolidation therapy for patients with EGFR-mutant (EGFRmut) stage III NSCLC remains unknown.
Methods: In this multi-institutional, international retrospective analysis across 24 institutions, we evaluated outcomes in patients with stage III EGFRmut NSCLC treated with concurrent CRT followed by consolidation therapy with osimertinib, durvalumab, or observation between 2015 and 2022.
Background: Lurbinectedin has emerged as a potential treatment option for relapsed small cell lung cancer (SCLC). While clinical trials have demonstrated its efficacy and safety, real-world data are limited. This study aimed to evaluate the safety and efficacy of lurbinectedin in a real-world setting, focusing on its use as a second-line agent and beyond in SCLC patients.
View Article and Find Full Text PDFAfter decades of efforts, we have recently made progress into targeting KRAS mutations in several malignancies. Known as the 'holy grail' of targeted cancer therapies, KRAS is the most frequently mutated oncogene in human malignancies. Under normal conditions, KRAS shuttles between the GDP-bound 'off' state and the GTP-bound 'on' state.
View Article and Find Full Text PDFBackground: Second and third-generation ALK inhibitors (ALKIs) have been recently approved for ALK-translocated lung cancer treatment, improving - and expanding - the first-line scenario.
Methods: In this systematic review and metanalysis, we investigated the efficacy and safety of next-generation ALKIs in untreated advanced ALK-translocated lung cancer patients, searching for randomized phase III controlled trials through databases (PubMed, EMBASE, and the Cochrane Library). Inclusion and exclusion of studies, quality assessment, data extraction, and synthesis were independently accomplished by two reviewers, with discrepancies adjudicated by a third reviewer.
Malignant pleural mesothelioma (MPM) is a rare and orphan thoracic malignancy, with a poor prognosis as the majority of patients are diagnosed with unresectable MPM, with no significant improvements in the therapeutic strategy for over a decade. However, the recent approval of immune checkpoint inhibitors (ICI) in treatment-naïve patients with unresectable MPM marks a significant step forward and hope for the treatment of this disease. In this narrative review, we discuss the biological rationale to use ICI in the treatment of MPM.
View Article and Find Full Text PDFWith the recent FDA approval of tumor mutational burden-high (TMB-H) status as a biomarker for treatment with a PD-1 inhibitor regardless of tumor type, accurate assessment of patient-specific TMB is more critical now more than ever. Using paired tumor and germline exome sequencing data from 701 patients newly diagnosed with multiple myeloma, including 575 self-reported White patients and 126 self-reported Black patients, we observed that compared to the gold standard of filtering germline variants with patient-paired germline sequencing data, TMB estimates were significantly higher in both Black and White patients when using public databases for filtering non-somatic mutations; however, TMB was more significantly inflated in Black patients compared to White patients. TMB as a biomarker for patient selection to receive immune checkpoint inhibitors (ICIs) therapy without patient-paired germline sequencing may introduce racial bias due to the under-representation of minority groups in public databases.
View Article and Find Full Text PDFDevelopment of the human intestine is not well understood. Here, we link single-cell RNA sequencing and spatial transcriptomics to characterize intestinal morphogenesis through time. We identify 101 cell states including epithelial and mesenchymal progenitor populations and programs linked to key morphogenetic milestones.
View Article and Find Full Text PDFLung cancer is the most common cancer worldwide. Approximately 18% of all deaths related to cancer are associated with lung cancer. Management of non-small cell lung cancer (NSCLC) has been changing rapidly in last few years.
View Article and Find Full Text PDFClin Gastroenterol Hepatol
November 2021