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"Lung cancer"
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Perioperative Durvalumab for Resectable Non–Small-Cell Lung Cancer
Patients with resectable non–small-cell lung cancer had a greater response and longer event-free survival with preoperative durvalumab plus chemotherapy and adjuvant durvalumab than with chemotherapy alone.
Journal Article
The fluorspar mines of Newfoundland : their history and the epidemic of radiation lung cancer
John Martin tells the history of Newfoundland's fluorspar mines from their founding to the last shipment of fluorspar in 1990 and declaration of bankruptcy a year later. He focuses on the health hazards experienced by the miners, and how the mining companies, workers, governments, and health services came to terms with the unfolding human tragedy. He also covers such matters as the improvement of methods for dust quantification and radiation surveillance in the mines, battles for compensation, and the influence of the St Lawrence case on the development of labour law in the province.
Book
Non‐small cell lung cancer in China
In China, lung cancer is a primary cancer type with high incidence and mortality. Risk factors for lung cancer include tobacco use, family history, radiation exposure, and the presence of chronic lung diseases. Most early‐stage non‐small cell lung cancer (NSCLC) patients miss the optimal timing for treatment due to the lack of clinical presentations. Population‐based nationwide screening programs are of significant help in increasing the early detection and survival rates of NSCLC in China. The understanding of molecular carcinogenesis and the identification of oncogenic drivers dramatically facilitate the development of targeted therapy for NSCLC, thus prolonging survival in patients with positive drivers. In the exploration of immune escape mechanisms, programmed cell death protein 1 (PD‐1)/programmed death‐ligand 1 (PD‐L1) inhibitor monotherapy and PD‐1/PD‐L1 inhibitor plus chemotherapy have become a standard of care for advanced NSCLC in China. In the Chinese Society of Clinical Oncology's guidelines for NSCLC, maintenance immunotherapy is recommended for locally advanced NSCLC after chemoradiotherapy. Adjuvant immunotherapy and neoadjuvant chemoimmunotherapy will be approved for resectable NSCLC. In this review, we summarized recent advances in NSCLC in China in terms of epidemiology, biology, molecular pathology, pathogenesis, screening, diagnosis, targeted therapy, and immunotherapy.
Journal Article
Non–Small Cell Lung Cancer: Epidemiology, Screening, Diagnosis, and Treatment
Lung cancer remains the leading cause of cancer deaths in the United States. In the past decade, significant advances have been made in the science of non–small cell lung cancer (NSCLC). Screening has been introduced with the goal of early detection. The National Lung Screening Trial found a lung cancer mortality benefit of 20% and a 6.7% decrease in all-cause mortality with the use of low-dose chest computed tomography in high-risk individuals. The treatment of lung cancer has also evolved with the introduction of several lines of tyrosine kinase inhibitors in patients with EGFR, ALK, ROS1, and NTRK mutations. Similarly, immune checkpoint inhibitors (ICIs) have dramatically changed the landscape of NSCLC treatment. Furthermore, the results of new trials continue to help us understand the role of these novel agents and which patients are more likely to benefit; ICIs are now part of the first-line NSCLC treatment armamentarium as monotherapy, combined with chemotherapy, or after definite chemoradiotherapy in patients with stage III unresectable NSCLC. Expression of programmed cell death protein-ligand 1 in malignant cells has been studied as a potential biomarker for response to ICIs. However, important drawbacks exist that limit its discriminatory potential. Identification of accurate predictive biomarkers beyond programmed cell death protein-ligand 1 expression remains essential to select the most appropriate candidates for ICI therapy. Many questions remain unanswered regarding the proper sequence and combinations of these new agents; however, the field is moving rapidly, and the overall direction is optimistic.
Journal Article
The biology and management of non-small cell lung cancer
Important advancements in the treatment of non-small cell lung cancer (NSCLC) have been achieved over the past two decades, increasing our understanding of the disease biology and mechanisms of tumour progression, and advancing early detection and multimodal care. The use of small molecule tyrosine kinase inhibitors and immunotherapy has led to unprecedented survival benefits in selected patients. However, the overall cure and survival rates for NSCLC remain low, particularly in metastatic disease. Therefore, continued research into new drugs and combination therapies is required to expand the clinical benefit to a broader patient population and to improve outcomes in NSCLC.
Journal Article
Mechanisms and management of 3rd-generation EGFR-TKI resistance in advanced non-small cell lung cancer (Review)
Targeted therapy with epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) is a standard modality of the 1st-line treatments for patients with advanced EGFR-mutated non-small cell lung cancer (NSCLC), and substantially improves their prognosis. However, EGFR T790M mutation is the primary mechanism of 1st- and 2nd-generation EGFR-TKI resistance. Osimertinib is a representative of the 3rd-generation EGFR-TKIs that target T790M mutation, and has satisfactory efficacy in the treatment of T790M-positive NSCLC with disease progression following use of 1st- or 2nd-generation EGFR-TKIs. Other 3rd-generation EGFR-TKIs, such as abivertinib, rociletinib, nazartinib, olmutinib and alflutinib, are also at various stages of development. However, the occurrence of acquired resistance is inevitable, and the mechanisms of 3rd-generation EGFR-TKI resistance are complex and incompletely understood. Genomic studies in tissue and liquid biopsies of resistant patients reveal multiple candidate pathways. The present review summarizes the recent findings in mechanisms of resistance to 3rd-generation EGFR-TKIs in advanced NSCLC, and provides possible strategies to overcome this resistance. The mechanisms of acquired resistance mainly include an altered EGFR signaling pathway (EGFR tertiary mutations and amplification), activation of aberrant bypassing pathways (hepatocyte growth factor receptor amplification, human epidermal growth factor receptor 2 amplification and aberrant insulin-like growth factor 1 receptor activation), downstream pathway activation (RAS/RAF/MEK/ERK and PI3K/AKT/mTOR) and histological/phenotypic transformations (SCLC transformation and epithelial-mesenchymal transition). The combination of targeted therapies is a promising strategy to treat osimertinib-resistant patients, and multiple clinical studies on novel combined therapies are ongoing.
Journal Article
Targeting the PI3K/Akt/mTOR pathway in non‐small cell lung cancer (NSCLC)
The traditional classification of lung cancer into small cell lung cancer and non‐small cell lung cancer (NSCLC) has been transformed with the increased understanding of the molecular alterations and genomic biomarkers that drive the development of lung cancer. Increased activation of the phosphatidylinositol 3‐kinase (PI3K)/Akt/mechanistic target of rapamycin (mTOR) pathway leads to numerous hallmarks of cancer and this pathway represents an attractive target for novel anticancer therapies. In NSCLC, the PI3K/Akt/mTOR pathway has been heavily implicated in both tumorigenesis and the progression of disease. A number of specific inhibitors of PI3K, Akt and mTOR are currently under development and in various stages of preclinical investigation and in early phase clinical trials for NSCLC. Early evidence has yielded disappointing results. Clinical trials, however, have been performed on predominantly molecularly unselected populations, and patient enrichment strategies using high‐precision predictive biomarkers in future trials will increase the likelihood of success. A greater understanding of the underlying molecular biology including epigenetic alterations is also crucial to allow for the detection of appropriate biomarkers and guide combination approaches.
Journal Article
Perioperative Pembrolizumab for Early-Stage Non–Small-Cell Lung Cancer
Patients with resectable lung cancer were assigned to neoadjuvant pembrolizumab or placebo plus chemotherapy and adjuvant pembrolizumab or placebo. Two-year event-free survival was 62.4% with pembrolizumab and 40.6% with placebo.
Journal Article
Atezolizumab for First-Line Treatment of Metastatic Nonsquamous NSCLC
The addition of atezolizumab (anti–PD-L1 antibody) to a platinum-based chemotherapy regimen improved progression-free survival among patients who had not previously received chemotherapy for metastatic NSCLC, regardless of PD-L1 expression and
EGFR
or
ALK
genomic alteration status.
Journal Article